Aripiprazole lauroxil (AL) and paliperidone palmitate (PP) are effective and well tolerated for initiating treatment of schizophrenia in the hospital and for continuing outpatient treatment, results of a phase 3, double-blind trial show.

A total of 200 patients completed the study, 99 of whom received aripiprazole lauroxil (Aristada Initio) and 101 of whom received paliperidone palmitate (Invega Sustenna). The baseline Positive and Negative Syndrome scale (PANSS) total score for those who received aripiprazole lauroxil was 94.1 and 94.6 for those who received paliperidone palmitate, Peter J. Weiden, MD, of Alkermes, and his associates reported in the Journal of Clinical Psychiatry.

After 4 weeks of treatment, patients who received aripiprazole lauroxil saw a mean PANSS score reduction of 17.4 points; after 9 weeks the reduction was 19.8 points and was 23.3 points after 25 weeks. For patients who received paliperidone palmitate the reduction in PANSS score was 20.1 points at week 4, 22.5 points at week 9, and 21.7 points at week 25. The most common adverse events in both groups were injection-site pain (17.2% and 24.8%, respectively), increased weight (9.1% and 16.8%, respectively), and akathisia (9.1% and 10.9%, respectively).

“Acutely symptomatic patients with schizophrenia on a 2-month dose regimen of AL with the 1-day initiation regimen demonstrated safety and efficacy consistent with that seen in prior AL studies. ... The inclusion of PP provided an active control with known safety and efficacy that can also be rapidly initiated. Both regimens can be effectively used in patients with schizophrenia through the often challenging transition from acute hospitalization to outpatient continuation treatment, the investigators concluded.

The study was sponsored by Alkermes, manufacturer of Aristada Initio. Invega Sustenna is produced by Janssen Pharmaceuticals. The investigators reported being employed by, owning stock/options in, or receiving research support from Alkermes; two investigators reported receiving research support from numerous other companies.

lfranki@mdedge.com

SOURCE: Weiden PJ et al. J Clin Psychiatry. 2020 May 19. doi: 10.4088/JCP.19m13207.

Aripiprazole lauroxil (AL) and paliperidone palmitate (PP) are effective and well tolerated for initiating treatment of schizophrenia in the hospital and for continuing outpatient treatment, results of a phase 3, double-blind trial show.

A total of 200 patients completed the study, 99 of whom received aripiprazole lauroxil (Aristada Initio) and 101 of whom received paliperidone palmitate (Invega Sustenna). The baseline Positive and Negative Syndrome scale (PANSS) total score for those who received aripiprazole lauroxil was 94.1 and 94.6 for those who received paliperidone palmitate, Peter J. Weiden, MD, of Alkermes, and his associates reported in the Journal of Clinical Psychiatry.

After 4 weeks of treatment, patients who received aripiprazole lauroxil saw a mean PANSS score reduction of 17.4 points; after 9 weeks the reduction was 19.8 points and was 23.3 points after 25 weeks. For patients who received paliperidone palmitate the reduction in PANSS score was 20.1 points at week 4, 22.5 points at week 9, and 21.7 points at week 25. The most common adverse events in both groups were injection-site pain (17.2% and 24.8%, respectively), increased weight (9.1% and 16.8%, respectively), and akathisia (9.1% and 10.9%, respectively).

“Acutely symptomatic patients with schizophrenia on a 2-month dose regimen of AL with the 1-day initiation regimen demonstrated safety and efficacy consistent with that seen in prior AL studies. ... The inclusion of PP provided an active control with known safety and efficacy that can also be rapidly initiated. Both regimens can be effectively used in patients with schizophrenia through the often challenging transition from acute hospitalization to outpatient continuation treatment, the investigators concluded.

The study was sponsored by Alkermes, manufacturer of Aristada Initio. Invega Sustenna is produced by Janssen Pharmaceuticals. The investigators reported being employed by, owning stock/options in, or receiving research support from Alkermes; two investigators reported receiving research support from numerous other companies.

lfranki@mdedge.com

SOURCE: Weiden PJ et al. J Clin Psychiatry. 2020 May 19. doi: 10.4088/JCP.19m13207.

Aripiprazole lauroxil (AL) and paliperidone palmitate (PP) are effective and well tolerated for initiating treatment of schizophrenia in the hospital and for continuing outpatient treatment, results of a phase 3, double-blind trial show.

A total of 200 patients completed the study, 99 of whom received aripiprazole lauroxil (Aristada Initio) and 101 of whom received paliperidone palmitate (Invega Sustenna). The baseline Positive and Negative Syndrome scale (PANSS) total score for those who received aripiprazole lauroxil was 94.1 and 94.6 for those who received paliperidone palmitate, Peter J. Weiden, MD, of Alkermes, and his associates reported in the Journal of Clinical Psychiatry.

After 4 weeks of treatment, patients who received aripiprazole lauroxil saw a mean PANSS score reduction of 17.4 points; after 9 weeks the reduction was 19.8 points and was 23.3 points after 25 weeks. For patients who received paliperidone palmitate the reduction in PANSS score was 20.1 points at week 4, 22.5 points at week 9, and 21.7 points at week 25. The most common adverse events in both groups were injection-site pain (17.2% and 24.8%, respectively), increased weight (9.1% and 16.8%, respectively), and akathisia (9.1% and 10.9%, respectively).

“Acutely symptomatic patients with schizophrenia on a 2-month dose regimen of AL with the 1-day initiation regimen demonstrated safety and efficacy consistent with that seen in prior AL studies. ... The inclusion of PP provided an active control with known safety and efficacy that can also be rapidly initiated. Both regimens can be effectively used in patients with schizophrenia through the often challenging transition from acute hospitalization to outpatient continuation treatment, the investigators concluded.

The study was sponsored by Alkermes, manufacturer of Aristada Initio. Invega Sustenna is produced by Janssen Pharmaceuticals. The investigators reported being employed by, owning stock/options in, or receiving research support from Alkermes; two investigators reported receiving research support from numerous other companies.

lfranki@mdedge.com

SOURCE: Weiden PJ et al. J Clin Psychiatry. 2020 May 19. doi: 10.4088/JCP.19m13207.

Here are the stories our MDedge editors across specialties think you need to know about today:

Patients returning slowly to primary care

Patients are beginning to return for outpatient visits. These visits dropped 60% from prepandemic levels in early April, but have rebounded to about 30% less than baseline, on average, according to data from the Commonwealth Fund, Harvard University, and Phreesia. For primary care in particular, practices are seeing 25% fewer visits than they did in early March. But even with visits rebounding, primary care faces financial challenges. “Primary care practices are in dire straits, and their ability to treat patients is under threat,” said Melinda Abrams, MS, senior vice president of delivery system reform and international innovations for the Commonwealth Fund. “In the long term, an investment in primary care will ensure we have primary care, because we are concerned about its collapse.” READ MORE.
 

Are the eyes at risk from COVID-19?

Recently, Joseph Fair, PhD, an NBC News contributor, suggested that he may have become ill with COVID-19 because of a lack of eye protection on an airplane. From his hospital bed in New Orleans, he told the network that he had flown on a crowded plane where flight attendants weren’t wearing masks. He wore a mask and gloves, but no eye protection. “My best guess,” he told the interviewer, “was that it came through the eye route.” But experts still aren’t sure if infection through the eyes is possible. “I don’t think we can answer that question with 100% confidence at this time,” said H. Nida Sen, MD, director of the uveitis clinic at the National Eye Institute in Bethesda, Md., and a clinical investigator who is studying the effects of COVID-19 on the eye. But, she says, “I think it is biologically plausible.” READ MORE.

Social distancing shows harm in older adults

As physical distancing continues to be necessary to maintain the health of older adults during the COVID-19 pandemic, experts are raising the alarm about the harms of also being socially distant. Studies of previous quarantine periods as well as preliminary findings during the COVID-19 pandemic demonstrate an inverse relationship between social isolation measures and cognitive functioning in the elderly, according to Myrra Vernooij-Dassen, PhD, of Radboud University in Nigmegen, the Netherlands, and chair of INTERDEM, a pan-European network of dementia researchers. “A striking finding is that lack of social interaction is associated with incident dementia. Conversely, epidemiologic data indicate that a socially integrated lifestyle had a favorable influence on cognitive functioning and could even delay onset of dementia,” she said. READ MORE.

Americans are split on COVID-19 vaccination

As researchers race to produce a safe and effective vaccine against SARS-CoV-2, about half of Americans report they would get the vaccine if it were available. A recent poll, conducted by the AP-NORC Center for Public Affairs Research, found that 31% of respondents weren’t sure if they’d get a vaccine, and 20% said they’d refuse to get one. The poll was conducted May 14-18 and released May 27. Among respondents who said they don’t plan to get vaccinated, 70% said they’re concerned about side effects. Another 42% are worried about getting the coronavirus from the vaccine. READ MORE.

Biologic approved for atopic dermatitis

The Food and Drug Administration approved dupilumab for children aged 6-11 years with moderate to severe atopic dermatitis. This is the first biologic approved for atopic dermatitis in this age group. The new indication is for children whose disease is not adequately controlled with topical prescription therapies. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Patients returning slowly to primary care

Patients are beginning to return for outpatient visits. These visits dropped 60% from prepandemic levels in early April, but have rebounded to about 30% less than baseline, on average, according to data from the Commonwealth Fund, Harvard University, and Phreesia. For primary care in particular, practices are seeing 25% fewer visits than they did in early March. But even with visits rebounding, primary care faces financial challenges. “Primary care practices are in dire straits, and their ability to treat patients is under threat,” said Melinda Abrams, MS, senior vice president of delivery system reform and international innovations for the Commonwealth Fund. “In the long term, an investment in primary care will ensure we have primary care, because we are concerned about its collapse.” READ MORE.
 

Are the eyes at risk from COVID-19?

Recently, Joseph Fair, PhD, an NBC News contributor, suggested that he may have become ill with COVID-19 because of a lack of eye protection on an airplane. From his hospital bed in New Orleans, he told the network that he had flown on a crowded plane where flight attendants weren’t wearing masks. He wore a mask and gloves, but no eye protection. “My best guess,” he told the interviewer, “was that it came through the eye route.” But experts still aren’t sure if infection through the eyes is possible. “I don’t think we can answer that question with 100% confidence at this time,” said H. Nida Sen, MD, director of the uveitis clinic at the National Eye Institute in Bethesda, Md., and a clinical investigator who is studying the effects of COVID-19 on the eye. But, she says, “I think it is biologically plausible.” READ MORE.

Social distancing shows harm in older adults

As physical distancing continues to be necessary to maintain the health of older adults during the COVID-19 pandemic, experts are raising the alarm about the harms of also being socially distant. Studies of previous quarantine periods as well as preliminary findings during the COVID-19 pandemic demonstrate an inverse relationship between social isolation measures and cognitive functioning in the elderly, according to Myrra Vernooij-Dassen, PhD, of Radboud University in Nigmegen, the Netherlands, and chair of INTERDEM, a pan-European network of dementia researchers. “A striking finding is that lack of social interaction is associated with incident dementia. Conversely, epidemiologic data indicate that a socially integrated lifestyle had a favorable influence on cognitive functioning and could even delay onset of dementia,” she said. READ MORE.

Americans are split on COVID-19 vaccination

As researchers race to produce a safe and effective vaccine against SARS-CoV-2, about half of Americans report they would get the vaccine if it were available. A recent poll, conducted by the AP-NORC Center for Public Affairs Research, found that 31% of respondents weren’t sure if they’d get a vaccine, and 20% said they’d refuse to get one. The poll was conducted May 14-18 and released May 27. Among respondents who said they don’t plan to get vaccinated, 70% said they’re concerned about side effects. Another 42% are worried about getting the coronavirus from the vaccine. READ MORE.

Biologic approved for atopic dermatitis

The Food and Drug Administration approved dupilumab for children aged 6-11 years with moderate to severe atopic dermatitis. This is the first biologic approved for atopic dermatitis in this age group. The new indication is for children whose disease is not adequately controlled with topical prescription therapies. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Patients returning slowly to primary care

Patients are beginning to return for outpatient visits. These visits dropped 60% from prepandemic levels in early April, but have rebounded to about 30% less than baseline, on average, according to data from the Commonwealth Fund, Harvard University, and Phreesia. For primary care in particular, practices are seeing 25% fewer visits than they did in early March. But even with visits rebounding, primary care faces financial challenges. “Primary care practices are in dire straits, and their ability to treat patients is under threat,” said Melinda Abrams, MS, senior vice president of delivery system reform and international innovations for the Commonwealth Fund. “In the long term, an investment in primary care will ensure we have primary care, because we are concerned about its collapse.” READ MORE.
 

Are the eyes at risk from COVID-19?

Recently, Joseph Fair, PhD, an NBC News contributor, suggested that he may have become ill with COVID-19 because of a lack of eye protection on an airplane. From his hospital bed in New Orleans, he told the network that he had flown on a crowded plane where flight attendants weren’t wearing masks. He wore a mask and gloves, but no eye protection. “My best guess,” he told the interviewer, “was that it came through the eye route.” But experts still aren’t sure if infection through the eyes is possible. “I don’t think we can answer that question with 100% confidence at this time,” said H. Nida Sen, MD, director of the uveitis clinic at the National Eye Institute in Bethesda, Md., and a clinical investigator who is studying the effects of COVID-19 on the eye. But, she says, “I think it is biologically plausible.” READ MORE.

Social distancing shows harm in older adults

As physical distancing continues to be necessary to maintain the health of older adults during the COVID-19 pandemic, experts are raising the alarm about the harms of also being socially distant. Studies of previous quarantine periods as well as preliminary findings during the COVID-19 pandemic demonstrate an inverse relationship between social isolation measures and cognitive functioning in the elderly, according to Myrra Vernooij-Dassen, PhD, of Radboud University in Nigmegen, the Netherlands, and chair of INTERDEM, a pan-European network of dementia researchers. “A striking finding is that lack of social interaction is associated with incident dementia. Conversely, epidemiologic data indicate that a socially integrated lifestyle had a favorable influence on cognitive functioning and could even delay onset of dementia,” she said. READ MORE.

Americans are split on COVID-19 vaccination

As researchers race to produce a safe and effective vaccine against SARS-CoV-2, about half of Americans report they would get the vaccine if it were available. A recent poll, conducted by the AP-NORC Center for Public Affairs Research, found that 31% of respondents weren’t sure if they’d get a vaccine, and 20% said they’d refuse to get one. The poll was conducted May 14-18 and released May 27. Among respondents who said they don’t plan to get vaccinated, 70% said they’re concerned about side effects. Another 42% are worried about getting the coronavirus from the vaccine. READ MORE.

Biologic approved for atopic dermatitis

The Food and Drug Administration approved dupilumab for children aged 6-11 years with moderate to severe atopic dermatitis. This is the first biologic approved for atopic dermatitis in this age group. The new indication is for children whose disease is not adequately controlled with topical prescription therapies. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

The current standard frontline therapy for advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer includes a combination of surgical cytoreduction and at least six cycles of platinum-based chemotherapy. While this achieves a complete clinical response (“remission”) in most, 85% of patients will recur and eventually succumb to the disease. This suggests that treatments are good at inducing remission, but poor at eradicating the disease altogether. This has motivated the consideration of maintenance therapy: extended treatment beyond completion of chemotherapy during the period of time when patients are clinically disease free.

Maintenance therapy is an appealing concept for clinicians who desperately want to “hold” their patients in a disease-free state for longer periods. It is also a profitable way to administer therapy as there is more compensation to the pharmaceutical industry from chronic, long-term drug administration rather than episodic treatment courses. However, the following question must be asked: Is this extended therapy worthwhile for all patients, and is it good value?

In the past 12 months, three major industry-sponsored clinical trials have been published (PRIMA, PAOLA-1, and VELIA)which suggest a benefit for all patients with advanced epithelial ovarian cancer in receiving prolonged poly (ADP-ribose) polymerase inhibitor (PARPi) therapy after primary chemotherapy.^1-3 This has resulted in Food and Drug Administration approval for some of these agents as maintenance therapy. Despite differences in the drugs tested and the timing of therapy, these studies observed that treatment of advanced ovarian cancer with the addition of a PARPi during and/or after carboplatin and paclitaxel chemotherapy for up to an additional 3 years resulted in a longer progression-free survival (PFS) of approximately 6 months. PFS is defined as the time to measurable recurrence or death. However, this positive effect was not equally distributed across the whole population; rather, it appeared to be created by a substantial response in a smaller subgroup.

PARP inhibitor therapies such as olaparib, niraparib, veliparib, and rucaparib target a family of enzymes that repair DNA and stabilize the human genome through the repair of single-stranded DNA breaks. Inhibiting these enzymes facilitates the accumulation of single-stranded breaks, allowing the development of double-strand breaks, which in turn cannot be repaired if the cell has deficient homologous recombination (HRD) such as through a germline or somatic BRCA mutation, or alternative relevant mutation that confers a similar effect. The opportunistic pairing of a drug interaction with a pathway specific to the cancer is an example of a targeted therapy.

In order to improve the value of cancer drug therapy, there has been emphasis by cooperative research groups, such as the Gynecologic Oncology Group, to study the efficacy of targeted therapies, such as PARPi, in patients identified by biomarkers such as tumors that possess germline or somatic HRD in whom they are most likely to work. This approach makes good common sense and promises to deliver a large magnitude of clinical benefit in a smaller focused population. Therefore, even if drug costs are high, the treatment may still have value. Consistent with that principle, the recently published VELIA, PRIMA, and PAOLA-1 trials all showed impressive benefit in PFS (on average 11-12 months) for the subgroup of patients with HRD. However, these studies were designed and funded by the pharmaceutical industry, and abandoned the principle of biomarker-driven targeted therapy. They did not limit their studies to the HRD-positive population most likely to benefit, but instead included and reported on the impact on all-comers (patients with both HRD and HR-proficient tumors). Subsequently their final conclusions could be extrapolated to the general population of ovarian cancer patients, and in doing so, a larger share of the marketplace.

Only 30% of the general population of ovarian, fallopian tube and primary peritoneal cancer patients carry a germline or somatic BRCA mutation and less than half carry this or alternative mutations which confer HRD. The remaining majority are HR-proficient tumors. However, the three study populations in the aforementioned trials were enriched for HRD tumors with 50%-60% subjects carrying germline or somatic HRD. Therefore, it is likely that the observed benefits in the “intent-to-treat” group were larger than what a clinician would observe in their patient population. Additionally, the large (11-12 month) gains in the HRD-positive group may have been so significant that they compensated for the subtle impact in the HR-proficient population (less than 3 months), resulting in an average total effect that, while being statistically significant for “all comers,” was actually only clinically significant for the HRD group. The positive impact for HRD tumors effectively boosted the results for the group as a whole.

The use of PFS as a primary endpoint raises another significant concern with the design of these PARPi maintenance trials. Much has been written about the importance of PFS as an endpoint for ovarian cancer because of confounding effects of subsequent therapy and to minimize the costs and duration of clinical trials.⁴ PFS is a quicker, less expensive endpoint to capture than overall survival. It usually correlates with overall survival, but typically only when there is a large magnitude of benefit in PFS. These arguments are fair when considering episodic drug therapies in the setting of measurable, active disease. However, maintenance therapy is given during a period of what patients think of as remission. Remission is valued by patients because it is a gateway to cure, and also because it is a time devoid of symptoms of disease, toxicity (therapeutic and financial), and the burden of frequent medical visits and interventions. While PFS is a measure of the length of remission, it is not a measure of cure. We should ask: What does it mean to a patient if she has a longer remission but needs to be on drug therapy (with its associated burdens and toxicities) in order to maintain that remission? We know that an increase in PFS with maintenance therapy does not always result in a commensurate increase in survival. One does not always precede the other. An example of this is the use of maintenance bevacizumab following upfront chemotherapy which improves PFS by 4 months, but is not associated with an increase in survival.⁵

When considering the value and ethics of maintenance therapy, it should be associated with a proven survival benefit or an improvement in quality of life. With respect to PARPi maintenance, we lack the data regarding the former, and have contrary evidence regarding the latter. In these three trials, PARPi maintenance was associated with significantly more toxicity than placebo including the commonly observed nausea and fatigue. Most of us would not like to be on a drug therapy for 3 years that made us feel nauseated or fatigued if it didn’t also increase our chance of cure or a longer life. While the significant PFS benefit of maintenance PARPi that is consistently observed in HRD-positive ovarian cancers suggests there will also likely be a clinically significant improvement in survival and cure in that specific subpopulation, this is less likely true for the majority of women with HR-proficient ovarian cancers. Time will tell this story, but as yet, we don’t know.

The use of maintenance PARPi therapy during and/or after primary cytotoxic chemotherapy for advanced epithelial ovarian, primary peritoneal, and fallopian tube cancer is associated with a substantial benefit in time to recurrence in a population with HRD tumors and a small benefit among the majority who don’t. However, it comes at the cost of toxicity at a time when patients would otherwise be free of disease and treatment. I propose that, until a survival benefit for all women has been observed, we should consider a targeted and biomarker-driven approach to maintenance PARPi prescription, favoring prescription for those with germline or somatic HRD mutations.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no relevant financial disclosures. Email Dr. Rossi at obnews@mdedge.com.

References

1. González-Martín A et al. N Engl J Med. 2019 Dec 19;381(25):2391-402.

2. Ray-Coquard I et al. N Engl J Med. 2019 Dec 19;381(25):2416-28.

3. Coleman RL et al. N Engl J Med. 2019 Dec 19;381(25):2403-15.

4. Herzog TJ et al. Gynecol Oncol. 2014 Jan;132(1):8-17.

5. Tewari KS et al. J Clin Oncol. 2019 Sep 10;37(26):2317-28.

The current standard frontline therapy for advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer includes a combination of surgical cytoreduction and at least six cycles of platinum-based chemotherapy. While this achieves a complete clinical response (“remission”) in most, 85% of patients will recur and eventually succumb to the disease. This suggests that treatments are good at inducing remission, but poor at eradicating the disease altogether. This has motivated the consideration of maintenance therapy: extended treatment beyond completion of chemotherapy during the period of time when patients are clinically disease free.

Maintenance therapy is an appealing concept for clinicians who desperately want to “hold” their patients in a disease-free state for longer periods. It is also a profitable way to administer therapy as there is more compensation to the pharmaceutical industry from chronic, long-term drug administration rather than episodic treatment courses. However, the following question must be asked: Is this extended therapy worthwhile for all patients, and is it good value?

In the past 12 months, three major industry-sponsored clinical trials have been published (PRIMA, PAOLA-1, and VELIA)which suggest a benefit for all patients with advanced epithelial ovarian cancer in receiving prolonged poly (ADP-ribose) polymerase inhibitor (PARPi) therapy after primary chemotherapy.^1-3 This has resulted in Food and Drug Administration approval for some of these agents as maintenance therapy. Despite differences in the drugs tested and the timing of therapy, these studies observed that treatment of advanced ovarian cancer with the addition of a PARPi during and/or after carboplatin and paclitaxel chemotherapy for up to an additional 3 years resulted in a longer progression-free survival (PFS) of approximately 6 months. PFS is defined as the time to measurable recurrence or death. However, this positive effect was not equally distributed across the whole population; rather, it appeared to be created by a substantial response in a smaller subgroup.

PARP inhibitor therapies such as olaparib, niraparib, veliparib, and rucaparib target a family of enzymes that repair DNA and stabilize the human genome through the repair of single-stranded DNA breaks. Inhibiting these enzymes facilitates the accumulation of single-stranded breaks, allowing the development of double-strand breaks, which in turn cannot be repaired if the cell has deficient homologous recombination (HRD) such as through a germline or somatic BRCA mutation, or alternative relevant mutation that confers a similar effect. The opportunistic pairing of a drug interaction with a pathway specific to the cancer is an example of a targeted therapy.

In order to improve the value of cancer drug therapy, there has been emphasis by cooperative research groups, such as the Gynecologic Oncology Group, to study the efficacy of targeted therapies, such as PARPi, in patients identified by biomarkers such as tumors that possess germline or somatic HRD in whom they are most likely to work. This approach makes good common sense and promises to deliver a large magnitude of clinical benefit in a smaller focused population. Therefore, even if drug costs are high, the treatment may still have value. Consistent with that principle, the recently published VELIA, PRIMA, and PAOLA-1 trials all showed impressive benefit in PFS (on average 11-12 months) for the subgroup of patients with HRD. However, these studies were designed and funded by the pharmaceutical industry, and abandoned the principle of biomarker-driven targeted therapy. They did not limit their studies to the HRD-positive population most likely to benefit, but instead included and reported on the impact on all-comers (patients with both HRD and HR-proficient tumors). Subsequently their final conclusions could be extrapolated to the general population of ovarian cancer patients, and in doing so, a larger share of the marketplace.

Only 30% of the general population of ovarian, fallopian tube and primary peritoneal cancer patients carry a germline or somatic BRCA mutation and less than half carry this or alternative mutations which confer HRD. The remaining majority are HR-proficient tumors. However, the three study populations in the aforementioned trials were enriched for HRD tumors with 50%-60% subjects carrying germline or somatic HRD. Therefore, it is likely that the observed benefits in the “intent-to-treat” group were larger than what a clinician would observe in their patient population. Additionally, the large (11-12 month) gains in the HRD-positive group may have been so significant that they compensated for the subtle impact in the HR-proficient population (less than 3 months), resulting in an average total effect that, while being statistically significant for “all comers,” was actually only clinically significant for the HRD group. The positive impact for HRD tumors effectively boosted the results for the group as a whole.

The use of PFS as a primary endpoint raises another significant concern with the design of these PARPi maintenance trials. Much has been written about the importance of PFS as an endpoint for ovarian cancer because of confounding effects of subsequent therapy and to minimize the costs and duration of clinical trials.⁴ PFS is a quicker, less expensive endpoint to capture than overall survival. It usually correlates with overall survival, but typically only when there is a large magnitude of benefit in PFS. These arguments are fair when considering episodic drug therapies in the setting of measurable, active disease. However, maintenance therapy is given during a period of what patients think of as remission. Remission is valued by patients because it is a gateway to cure, and also because it is a time devoid of symptoms of disease, toxicity (therapeutic and financial), and the burden of frequent medical visits and interventions. While PFS is a measure of the length of remission, it is not a measure of cure. We should ask: What does it mean to a patient if she has a longer remission but needs to be on drug therapy (with its associated burdens and toxicities) in order to maintain that remission? We know that an increase in PFS with maintenance therapy does not always result in a commensurate increase in survival. One does not always precede the other. An example of this is the use of maintenance bevacizumab following upfront chemotherapy which improves PFS by 4 months, but is not associated with an increase in survival.⁵

When considering the value and ethics of maintenance therapy, it should be associated with a proven survival benefit or an improvement in quality of life. With respect to PARPi maintenance, we lack the data regarding the former, and have contrary evidence regarding the latter. In these three trials, PARPi maintenance was associated with significantly more toxicity than placebo including the commonly observed nausea and fatigue. Most of us would not like to be on a drug therapy for 3 years that made us feel nauseated or fatigued if it didn’t also increase our chance of cure or a longer life. While the significant PFS benefit of maintenance PARPi that is consistently observed in HRD-positive ovarian cancers suggests there will also likely be a clinically significant improvement in survival and cure in that specific subpopulation, this is less likely true for the majority of women with HR-proficient ovarian cancers. Time will tell this story, but as yet, we don’t know.

The use of maintenance PARPi therapy during and/or after primary cytotoxic chemotherapy for advanced epithelial ovarian, primary peritoneal, and fallopian tube cancer is associated with a substantial benefit in time to recurrence in a population with HRD tumors and a small benefit among the majority who don’t. However, it comes at the cost of toxicity at a time when patients would otherwise be free of disease and treatment. I propose that, until a survival benefit for all women has been observed, we should consider a targeted and biomarker-driven approach to maintenance PARPi prescription, favoring prescription for those with germline or somatic HRD mutations.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no relevant financial disclosures. Email Dr. Rossi at obnews@mdedge.com.

References

1. González-Martín A et al. N Engl J Med. 2019 Dec 19;381(25):2391-402.

2. Ray-Coquard I et al. N Engl J Med. 2019 Dec 19;381(25):2416-28.

3. Coleman RL et al. N Engl J Med. 2019 Dec 19;381(25):2403-15.

4. Herzog TJ et al. Gynecol Oncol. 2014 Jan;132(1):8-17.

5. Tewari KS et al. J Clin Oncol. 2019 Sep 10;37(26):2317-28.

The current standard frontline therapy for advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer includes a combination of surgical cytoreduction and at least six cycles of platinum-based chemotherapy. While this achieves a complete clinical response (“remission”) in most, 85% of patients will recur and eventually succumb to the disease. This suggests that treatments are good at inducing remission, but poor at eradicating the disease altogether. This has motivated the consideration of maintenance therapy: extended treatment beyond completion of chemotherapy during the period of time when patients are clinically disease free.

Maintenance therapy is an appealing concept for clinicians who desperately want to “hold” their patients in a disease-free state for longer periods. It is also a profitable way to administer therapy as there is more compensation to the pharmaceutical industry from chronic, long-term drug administration rather than episodic treatment courses. However, the following question must be asked: Is this extended therapy worthwhile for all patients, and is it good value?

In the past 12 months, three major industry-sponsored clinical trials have been published (PRIMA, PAOLA-1, and VELIA)which suggest a benefit for all patients with advanced epithelial ovarian cancer in receiving prolonged poly (ADP-ribose) polymerase inhibitor (PARPi) therapy after primary chemotherapy.^1-3 This has resulted in Food and Drug Administration approval for some of these agents as maintenance therapy. Despite differences in the drugs tested and the timing of therapy, these studies observed that treatment of advanced ovarian cancer with the addition of a PARPi during and/or after carboplatin and paclitaxel chemotherapy for up to an additional 3 years resulted in a longer progression-free survival (PFS) of approximately 6 months. PFS is defined as the time to measurable recurrence or death. However, this positive effect was not equally distributed across the whole population; rather, it appeared to be created by a substantial response in a smaller subgroup.

PARP inhibitor therapies such as olaparib, niraparib, veliparib, and rucaparib target a family of enzymes that repair DNA and stabilize the human genome through the repair of single-stranded DNA breaks. Inhibiting these enzymes facilitates the accumulation of single-stranded breaks, allowing the development of double-strand breaks, which in turn cannot be repaired if the cell has deficient homologous recombination (HRD) such as through a germline or somatic BRCA mutation, or alternative relevant mutation that confers a similar effect. The opportunistic pairing of a drug interaction with a pathway specific to the cancer is an example of a targeted therapy.

In order to improve the value of cancer drug therapy, there has been emphasis by cooperative research groups, such as the Gynecologic Oncology Group, to study the efficacy of targeted therapies, such as PARPi, in patients identified by biomarkers such as tumors that possess germline or somatic HRD in whom they are most likely to work. This approach makes good common sense and promises to deliver a large magnitude of clinical benefit in a smaller focused population. Therefore, even if drug costs are high, the treatment may still have value. Consistent with that principle, the recently published VELIA, PRIMA, and PAOLA-1 trials all showed impressive benefit in PFS (on average 11-12 months) for the subgroup of patients with HRD. However, these studies were designed and funded by the pharmaceutical industry, and abandoned the principle of biomarker-driven targeted therapy. They did not limit their studies to the HRD-positive population most likely to benefit, but instead included and reported on the impact on all-comers (patients with both HRD and HR-proficient tumors). Subsequently their final conclusions could be extrapolated to the general population of ovarian cancer patients, and in doing so, a larger share of the marketplace.

Only 30% of the general population of ovarian, fallopian tube and primary peritoneal cancer patients carry a germline or somatic BRCA mutation and less than half carry this or alternative mutations which confer HRD. The remaining majority are HR-proficient tumors. However, the three study populations in the aforementioned trials were enriched for HRD tumors with 50%-60% subjects carrying germline or somatic HRD. Therefore, it is likely that the observed benefits in the “intent-to-treat” group were larger than what a clinician would observe in their patient population. Additionally, the large (11-12 month) gains in the HRD-positive group may have been so significant that they compensated for the subtle impact in the HR-proficient population (less than 3 months), resulting in an average total effect that, while being statistically significant for “all comers,” was actually only clinically significant for the HRD group. The positive impact for HRD tumors effectively boosted the results for the group as a whole.

The use of PFS as a primary endpoint raises another significant concern with the design of these PARPi maintenance trials. Much has been written about the importance of PFS as an endpoint for ovarian cancer because of confounding effects of subsequent therapy and to minimize the costs and duration of clinical trials.⁴ PFS is a quicker, less expensive endpoint to capture than overall survival. It usually correlates with overall survival, but typically only when there is a large magnitude of benefit in PFS. These arguments are fair when considering episodic drug therapies in the setting of measurable, active disease. However, maintenance therapy is given during a period of what patients think of as remission. Remission is valued by patients because it is a gateway to cure, and also because it is a time devoid of symptoms of disease, toxicity (therapeutic and financial), and the burden of frequent medical visits and interventions. While PFS is a measure of the length of remission, it is not a measure of cure. We should ask: What does it mean to a patient if she has a longer remission but needs to be on drug therapy (with its associated burdens and toxicities) in order to maintain that remission? We know that an increase in PFS with maintenance therapy does not always result in a commensurate increase in survival. One does not always precede the other. An example of this is the use of maintenance bevacizumab following upfront chemotherapy which improves PFS by 4 months, but is not associated with an increase in survival.⁵

When considering the value and ethics of maintenance therapy, it should be associated with a proven survival benefit or an improvement in quality of life. With respect to PARPi maintenance, we lack the data regarding the former, and have contrary evidence regarding the latter. In these three trials, PARPi maintenance was associated with significantly more toxicity than placebo including the commonly observed nausea and fatigue. Most of us would not like to be on a drug therapy for 3 years that made us feel nauseated or fatigued if it didn’t also increase our chance of cure or a longer life. While the significant PFS benefit of maintenance PARPi that is consistently observed in HRD-positive ovarian cancers suggests there will also likely be a clinically significant improvement in survival and cure in that specific subpopulation, this is less likely true for the majority of women with HR-proficient ovarian cancers. Time will tell this story, but as yet, we don’t know.

The use of maintenance PARPi therapy during and/or after primary cytotoxic chemotherapy for advanced epithelial ovarian, primary peritoneal, and fallopian tube cancer is associated with a substantial benefit in time to recurrence in a population with HRD tumors and a small benefit among the majority who don’t. However, it comes at the cost of toxicity at a time when patients would otherwise be free of disease and treatment. I propose that, until a survival benefit for all women has been observed, we should consider a targeted and biomarker-driven approach to maintenance PARPi prescription, favoring prescription for those with germline or somatic HRD mutations.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no relevant financial disclosures. Email Dr. Rossi at obnews@mdedge.com.

References

1. González-Martín A et al. N Engl J Med. 2019 Dec 19;381(25):2391-402.

2. Ray-Coquard I et al. N Engl J Med. 2019 Dec 19;381(25):2416-28.

3. Coleman RL et al. N Engl J Med. 2019 Dec 19;381(25):2403-15.

4. Herzog TJ et al. Gynecol Oncol. 2014 Jan;132(1):8-17.

5. Tewari KS et al. J Clin Oncol. 2019 Sep 10;37(26):2317-28.

The Food and Drug Administration has approved brigatinib (Alunbrig) to treat adults with ALK-positive metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The FDA also approved the Vysis ALK Break Apart FISH Probe Kit as a companion diagnostic for brigatinib.

Brigatinib and the companion diagnostic were both evaluated in the ALTA 1L trial (NCT02737501). The trial enrolled adults with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy. Patients had to have an ALK rearrangement based on a local standard of care test.

Clinical samples from trial participants were retrospectively tested with the Vysis ALK Break Apart FISH Probe Kit. Of the 275 patients enrolled in the trial, 239 were ALK positive according to the test. Results were negative for 20 patients and unavailable for 16 patients.

Patients were randomized to receive brigatinib at 180 mg once daily with a 7-day lead-in at 90 mg once daily (n = 137) or crizotinib at 250 mg twice daily (n = 138).

The estimated median progression-free survival was 24 months in the brigatinib arm and 11 months in the crizotinib arm (hazard ratio, 0.49; P < .0001). The overall response rate was 74% in the brigatinib arm and 62% in the crizotinib arm.

The most common adverse events in the brigatinib arm, occurring in at least 20% of patients, were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, abdominal pain, pruritus, back pain, and dyspnea.

Serious adverse events occurred in 33% of patients in the brigatinib arm, and fatal adverse events included in 2.9%. The fatal events were pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).

For more details on the ALTA 1L trial, see the full prescribing information for brigatinib.

The approval of brigatinib was granted to ARIAD Pharmaceuticals. The approval of the Vysis ALK Break Apart FISH Probe Kit was granted to Abbott Molecular.

The Food and Drug Administration has approved brigatinib (Alunbrig) to treat adults with ALK-positive metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The FDA also approved the Vysis ALK Break Apart FISH Probe Kit as a companion diagnostic for brigatinib.

Brigatinib and the companion diagnostic were both evaluated in the ALTA 1L trial (NCT02737501). The trial enrolled adults with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy. Patients had to have an ALK rearrangement based on a local standard of care test.

Clinical samples from trial participants were retrospectively tested with the Vysis ALK Break Apart FISH Probe Kit. Of the 275 patients enrolled in the trial, 239 were ALK positive according to the test. Results were negative for 20 patients and unavailable for 16 patients.

Patients were randomized to receive brigatinib at 180 mg once daily with a 7-day lead-in at 90 mg once daily (n = 137) or crizotinib at 250 mg twice daily (n = 138).

The estimated median progression-free survival was 24 months in the brigatinib arm and 11 months in the crizotinib arm (hazard ratio, 0.49; P < .0001). The overall response rate was 74% in the brigatinib arm and 62% in the crizotinib arm.

The most common adverse events in the brigatinib arm, occurring in at least 20% of patients, were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, abdominal pain, pruritus, back pain, and dyspnea.

Serious adverse events occurred in 33% of patients in the brigatinib arm, and fatal adverse events included in 2.9%. The fatal events were pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).

For more details on the ALTA 1L trial, see the full prescribing information for brigatinib.

The approval of brigatinib was granted to ARIAD Pharmaceuticals. The approval of the Vysis ALK Break Apart FISH Probe Kit was granted to Abbott Molecular.

The Food and Drug Administration has approved brigatinib (Alunbrig) to treat adults with ALK-positive metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The FDA also approved the Vysis ALK Break Apart FISH Probe Kit as a companion diagnostic for brigatinib.

Brigatinib and the companion diagnostic were both evaluated in the ALTA 1L trial (NCT02737501). The trial enrolled adults with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy. Patients had to have an ALK rearrangement based on a local standard of care test.

Clinical samples from trial participants were retrospectively tested with the Vysis ALK Break Apart FISH Probe Kit. Of the 275 patients enrolled in the trial, 239 were ALK positive according to the test. Results were negative for 20 patients and unavailable for 16 patients.

Patients were randomized to receive brigatinib at 180 mg once daily with a 7-day lead-in at 90 mg once daily (n = 137) or crizotinib at 250 mg twice daily (n = 138).

The estimated median progression-free survival was 24 months in the brigatinib arm and 11 months in the crizotinib arm (hazard ratio, 0.49; P < .0001). The overall response rate was 74% in the brigatinib arm and 62% in the crizotinib arm.

The most common adverse events in the brigatinib arm, occurring in at least 20% of patients, were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, abdominal pain, pruritus, back pain, and dyspnea.

Serious adverse events occurred in 33% of patients in the brigatinib arm, and fatal adverse events included in 2.9%. The fatal events were pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).

For more details on the ALTA 1L trial, see the full prescribing information for brigatinib.

The approval of brigatinib was granted to ARIAD Pharmaceuticals. The approval of the Vysis ALK Break Apart FISH Probe Kit was granted to Abbott Molecular.

The calcitonin gene-related peptide monoclonal antibody galcanezumab (Emgality, Lilly) compared favorably to placebo for reducing the number of average monthly migraine days in a new study of people with treatment-resistant migraine headaches. “The patients included in our study had previously tried multiple migraine preventive treatments that didn’t work for them. These patients are left with limited treatment options to help with the debilitating pain of migraine,” said lead author Holland C. Detke, PhD, senior clinical research advisor at Eli Lilly and Company Biomedicines.

Participants who took the drug experienced “a rapid reduction in migraine days starting as early as month 1, and continuing through the 6 months of the study,” Dr. Detke said.

The treatment group reported an average 4.0 fewer monthly migraine days at 3 months, for example, compared with a baseline of 13.4 days, whereas the placebo group decreased an average 1.29 days from a similar baseline of 13.0 migraine days.

Dr. Detke presented these and other results of the open-label phase of the CONQUER phase 3 trial online as part of the 2020 American Academy of Neurology Science Highlights.

The investigators enrolled 462 adults with episodic or chronic migraine. All participants previously failed two to four migraine treatments because of insufficient efficacy or issues around tolerability or safety. At month 0, 232 people were randomly assigned to galcanezumab and another 230 to placebo injections. At 3 months, 449 participants received a galcanezumab injection as part of the open-label treatment phase.

Participants were an average 48 years old, approximately 86% were women, and 82% were white. At baseline, mean Migraine Specific Quality of Life Role Function Restrictive (MSQ RFR) domain score was 45, “indicating significant impairment in functioning,” Dr. Detke said. At the same time, mean Migraine Disability Assessment Test (MIDAS) total score was 51, “indicating quite severe disability.”
 

Significant outcomes

The decrease in migraine days at 3 months – 4.0 days with treatment versus 1.29 with placebo – was statistically significant (P < .0001). During the open-label phase, participants who switched from placebo “essentially catch up to where the previously treated people were,” Dr. Detke said. At 6 months, the decrease in average monthly headache days was 5.60 in the initial galcanezumab group versus 5.24 in the initial placebo group.

Significant differences at 3 months versus baseline were observed in participants who received galcanezumab when investigators assessed reduction in 50% or more, 75% or more, or 100% of mean monthly migraine days. No such significant decreases were seen in the placebo group.

Treatment-emergent adverse events reported in the open-label phase included nasopharyngitis in 4.2%, injection site pain in 3.8%, and injection site erythema in 2.7%. Five participants discontinued during the open-label phase because of adverse events.

The results of the study suggest galcanezumab “should be considered as a treatment option for patients who have not had success with previous treatments,” Dr. Detke said.
 

Multiple strengths of study

“It is encouraging that galcanezumab works in patients who have failed prior reduction strategies,” A. Laine Green, MD, a neurologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., said when asked to comment.

This study did not look at patients who have failed more than four previous reduction strategies, he added. “Clinically we see many of these patients. To be fair, no one has studied this group using the monoclonal antibodies.”

Dr. Green noted several strengths of the study. The groups were similar, there were few dropouts during the open-label extension, and there were no unexpected side effects or adverse events. “Those who got placebo caught up to those who received active treatment in the double-blind phase,” he said. “It is also nice to see patient reported outcomes improved as headaches improve. This adds consistency to the results.”

One caveat, Dr. Green noted, is “with open-label extensions, there is always the potential for bias because patients know what treatment they are receiving.”

Overall [the study] gives hope that patients who have failed previous reduction strategies may respond to the newer monoclonal antibodies.”
 

Aligns with previous findings

The results are “the same as any other long-term extension study of a drug for migraine,” Stephen Silberstein, MD, said when asked to comment. “The longer one takes it, the better you get.”

The research also confirms that if you switch patients taking placebo to an active treatment, they get better, added Dr. Silberstein, director of the Headache Center at Jefferson Health in Philadelphia.

Because they are injections, agents such as galcanezumab, other monoclonal antibodies, and botulinum toxin offer better compliance for headache compared with small molecule medications that require daily oral dosing, he added.

Eli Lilly and Company funded the study. Dr. Holland Detke is a Lilly employee. Dr. Green collaborated with Lilly on a poster for the AHS scientific meeting on a similar topic but did not receive compensation. Up until August 2019, he served as a consultant for Lilly, Novartis, Teva and Allergan. Dr. Green is also a member of the Medscape and American Headache Society Migraine Steering Committee. Dr. Silberstein is a member of the advisory board and consultant for Lilly.

Source: Detke HC et al. AAN 2020. Abstract 43625.

The calcitonin gene-related peptide monoclonal antibody galcanezumab (Emgality, Lilly) compared favorably to placebo for reducing the number of average monthly migraine days in a new study of people with treatment-resistant migraine headaches. “The patients included in our study had previously tried multiple migraine preventive treatments that didn’t work for them. These patients are left with limited treatment options to help with the debilitating pain of migraine,” said lead author Holland C. Detke, PhD, senior clinical research advisor at Eli Lilly and Company Biomedicines.

Participants who took the drug experienced “a rapid reduction in migraine days starting as early as month 1, and continuing through the 6 months of the study,” Dr. Detke said.

The treatment group reported an average 4.0 fewer monthly migraine days at 3 months, for example, compared with a baseline of 13.4 days, whereas the placebo group decreased an average 1.29 days from a similar baseline of 13.0 migraine days.

Dr. Detke presented these and other results of the open-label phase of the CONQUER phase 3 trial online as part of the 2020 American Academy of Neurology Science Highlights.

The investigators enrolled 462 adults with episodic or chronic migraine. All participants previously failed two to four migraine treatments because of insufficient efficacy or issues around tolerability or safety. At month 0, 232 people were randomly assigned to galcanezumab and another 230 to placebo injections. At 3 months, 449 participants received a galcanezumab injection as part of the open-label treatment phase.

Participants were an average 48 years old, approximately 86% were women, and 82% were white. At baseline, mean Migraine Specific Quality of Life Role Function Restrictive (MSQ RFR) domain score was 45, “indicating significant impairment in functioning,” Dr. Detke said. At the same time, mean Migraine Disability Assessment Test (MIDAS) total score was 51, “indicating quite severe disability.”
 

Significant outcomes

The decrease in migraine days at 3 months – 4.0 days with treatment versus 1.29 with placebo – was statistically significant (P < .0001). During the open-label phase, participants who switched from placebo “essentially catch up to where the previously treated people were,” Dr. Detke said. At 6 months, the decrease in average monthly headache days was 5.60 in the initial galcanezumab group versus 5.24 in the initial placebo group.

Significant differences at 3 months versus baseline were observed in participants who received galcanezumab when investigators assessed reduction in 50% or more, 75% or more, or 100% of mean monthly migraine days. No such significant decreases were seen in the placebo group.

Treatment-emergent adverse events reported in the open-label phase included nasopharyngitis in 4.2%, injection site pain in 3.8%, and injection site erythema in 2.7%. Five participants discontinued during the open-label phase because of adverse events.

The results of the study suggest galcanezumab “should be considered as a treatment option for patients who have not had success with previous treatments,” Dr. Detke said.
 

Multiple strengths of study

“It is encouraging that galcanezumab works in patients who have failed prior reduction strategies,” A. Laine Green, MD, a neurologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., said when asked to comment.

This study did not look at patients who have failed more than four previous reduction strategies, he added. “Clinically we see many of these patients. To be fair, no one has studied this group using the monoclonal antibodies.”

Dr. Green noted several strengths of the study. The groups were similar, there were few dropouts during the open-label extension, and there were no unexpected side effects or adverse events. “Those who got placebo caught up to those who received active treatment in the double-blind phase,” he said. “It is also nice to see patient reported outcomes improved as headaches improve. This adds consistency to the results.”

One caveat, Dr. Green noted, is “with open-label extensions, there is always the potential for bias because patients know what treatment they are receiving.”

Overall [the study] gives hope that patients who have failed previous reduction strategies may respond to the newer monoclonal antibodies.”
 

Aligns with previous findings

The results are “the same as any other long-term extension study of a drug for migraine,” Stephen Silberstein, MD, said when asked to comment. “The longer one takes it, the better you get.”

The research also confirms that if you switch patients taking placebo to an active treatment, they get better, added Dr. Silberstein, director of the Headache Center at Jefferson Health in Philadelphia.

Because they are injections, agents such as galcanezumab, other monoclonal antibodies, and botulinum toxin offer better compliance for headache compared with small molecule medications that require daily oral dosing, he added.

Eli Lilly and Company funded the study. Dr. Holland Detke is a Lilly employee. Dr. Green collaborated with Lilly on a poster for the AHS scientific meeting on a similar topic but did not receive compensation. Up until August 2019, he served as a consultant for Lilly, Novartis, Teva and Allergan. Dr. Green is also a member of the Medscape and American Headache Society Migraine Steering Committee. Dr. Silberstein is a member of the advisory board and consultant for Lilly.

Source: Detke HC et al. AAN 2020. Abstract 43625.

The calcitonin gene-related peptide monoclonal antibody galcanezumab (Emgality, Lilly) compared favorably to placebo for reducing the number of average monthly migraine days in a new study of people with treatment-resistant migraine headaches. “The patients included in our study had previously tried multiple migraine preventive treatments that didn’t work for them. These patients are left with limited treatment options to help with the debilitating pain of migraine,” said lead author Holland C. Detke, PhD, senior clinical research advisor at Eli Lilly and Company Biomedicines.

Participants who took the drug experienced “a rapid reduction in migraine days starting as early as month 1, and continuing through the 6 months of the study,” Dr. Detke said.

The treatment group reported an average 4.0 fewer monthly migraine days at 3 months, for example, compared with a baseline of 13.4 days, whereas the placebo group decreased an average 1.29 days from a similar baseline of 13.0 migraine days.

Dr. Detke presented these and other results of the open-label phase of the CONQUER phase 3 trial online as part of the 2020 American Academy of Neurology Science Highlights.

The investigators enrolled 462 adults with episodic or chronic migraine. All participants previously failed two to four migraine treatments because of insufficient efficacy or issues around tolerability or safety. At month 0, 232 people were randomly assigned to galcanezumab and another 230 to placebo injections. At 3 months, 449 participants received a galcanezumab injection as part of the open-label treatment phase.

Participants were an average 48 years old, approximately 86% were women, and 82% were white. At baseline, mean Migraine Specific Quality of Life Role Function Restrictive (MSQ RFR) domain score was 45, “indicating significant impairment in functioning,” Dr. Detke said. At the same time, mean Migraine Disability Assessment Test (MIDAS) total score was 51, “indicating quite severe disability.”
 

Significant outcomes

The decrease in migraine days at 3 months – 4.0 days with treatment versus 1.29 with placebo – was statistically significant (P < .0001). During the open-label phase, participants who switched from placebo “essentially catch up to where the previously treated people were,” Dr. Detke said. At 6 months, the decrease in average monthly headache days was 5.60 in the initial galcanezumab group versus 5.24 in the initial placebo group.

Significant differences at 3 months versus baseline were observed in participants who received galcanezumab when investigators assessed reduction in 50% or more, 75% or more, or 100% of mean monthly migraine days. No such significant decreases were seen in the placebo group.

Treatment-emergent adverse events reported in the open-label phase included nasopharyngitis in 4.2%, injection site pain in 3.8%, and injection site erythema in 2.7%. Five participants discontinued during the open-label phase because of adverse events.

The results of the study suggest galcanezumab “should be considered as a treatment option for patients who have not had success with previous treatments,” Dr. Detke said.
 

Multiple strengths of study

“It is encouraging that galcanezumab works in patients who have failed prior reduction strategies,” A. Laine Green, MD, a neurologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., said when asked to comment.

This study did not look at patients who have failed more than four previous reduction strategies, he added. “Clinically we see many of these patients. To be fair, no one has studied this group using the monoclonal antibodies.”

Dr. Green noted several strengths of the study. The groups were similar, there were few dropouts during the open-label extension, and there were no unexpected side effects or adverse events. “Those who got placebo caught up to those who received active treatment in the double-blind phase,” he said. “It is also nice to see patient reported outcomes improved as headaches improve. This adds consistency to the results.”

One caveat, Dr. Green noted, is “with open-label extensions, there is always the potential for bias because patients know what treatment they are receiving.”

Overall [the study] gives hope that patients who have failed previous reduction strategies may respond to the newer monoclonal antibodies.”
 

Aligns with previous findings

The results are “the same as any other long-term extension study of a drug for migraine,” Stephen Silberstein, MD, said when asked to comment. “The longer one takes it, the better you get.”

The research also confirms that if you switch patients taking placebo to an active treatment, they get better, added Dr. Silberstein, director of the Headache Center at Jefferson Health in Philadelphia.

Because they are injections, agents such as galcanezumab, other monoclonal antibodies, and botulinum toxin offer better compliance for headache compared with small molecule medications that require daily oral dosing, he added.

Eli Lilly and Company funded the study. Dr. Holland Detke is a Lilly employee. Dr. Green collaborated with Lilly on a poster for the AHS scientific meeting on a similar topic but did not receive compensation. Up until August 2019, he served as a consultant for Lilly, Novartis, Teva and Allergan. Dr. Green is also a member of the Medscape and American Headache Society Migraine Steering Committee. Dr. Silberstein is a member of the advisory board and consultant for Lilly.

Source: Detke HC et al. AAN 2020. Abstract 43625.

Pediatric dermatologists overwhelmingly say that the COVID-19 pandemic has affected how they prescribe and monitor immunosuppressive medications for inflammatory skin diseases, according to a task force survey designed to offer guidance to specialists and nonspecialists faced with tough choices about risks.

Some 87% reported that they were reducing the frequency of lab monitoring for some medications, while more than half said they had reached out to patients and their families to discuss the implications of continuing or stopping a drug.

Virtually all – 97% – said that the COVID-19 crisis had affected their decision to initiate immunosuppressive medications, with 84% saying the decision depended on a patient’s risk factors for contracting COVID-19 infection, and also the potential consequences of infection while treated, compared with the risks of not optimally treating the skin condition.

To develop a consensus-based guidance for clinicians, published online April 22 in Pediatric Dermatology, Kelly Cordoro, MD, professor of dermatology at the University of California, San Francisco, assembled a task force of pediatric dermatologists at academic institutions (the Pediatric Dermatology COVID-19 Response Task Force). Together with Sean Reynolds, MD, a pediatric dermatology fellow at UCSF and colleagues, they issued a survey to the 37 members of the task force with questions on how the pandemic has affected their prescribing decisions and certain therapies specifically. All the recipients responded.

The dermatologists were asked about conventional systemic and biologic medications. Most felt confident in continuing biologics, with 78% saying they would keep patients with no signs of COVID-19 exposure or infection on tumor necrosis factor (TNF) inhibitors. More than 90% of respondents said they would continue patients on dupilumab, as well as anti–interleukin (IL)–17, anti–IL-12/23, and anti–IL-23 therapies.

Responses varied more on approaches to the nonbiologic treatments. Fewer than half (46%) said they would continue patients without apparent COVID-19 exposure on systemic steroids, with another 46% saying it depended on the clinical context.

For other systemic therapies, respondents were more likely to want to continue their patients with no signs or symptoms of COVID-19 on methotrexate and apremilast (78% and 83%, respectively) than others (mycophenolate mofetil, azathioprine, cyclosporine, and JAK inhibitors), which saw between 50% and 60% support in the survey.

Patients on any immunosuppressive medications with likely exposure to COVID-19 or who test positive for the virus should be temporarily taken off their medications, the majority concurred. Exceptions were for systemic steroids, which must be tapered. And a significant minority of the dermatologists said that they would continue apremilast or dupilumab (24% and 16%, respectively) in the event of a confirmed COVID-19 infection.

In an interview, Dr. Cordoro commented that, even in normal times, most systemic or biological immunosuppressive treatments are used off-label by pediatric dermatologists. “There’s no way this could have been an evidence-based document, as we didn’t have the data to drive this. Many of the medications have been tested in children but not necessarily for dermatologic indications; some are chemotherapy agents or drugs used in rheumatologic diseases.”

The COVID-19 pandemic complicated an already difficult decision-making process, she said.

The researchers cautioned against attempting to make decisions about medications based on data on other infections from clinical trials. “Infection data from standard infections that were identified and watched for in clinical trials really still has no bearing on COVID-19 because it’s such a different virus,” Dr. Cordoro said.

And while some immunosuppressive medications could potentially attenuate a SARS-CoV-2–induced cytokine storm, “we certainly don’t assume this is necessarily going to help.”

The authors advised that physicians anxious about initiating an immunosuppressive treatment should take into consideration whether early intervention could “prevent permanent physical impairment or disfigurement” in diseases such as erythrodermic pustular psoriasis or rapidly progressive linear morphea.

Other diseases, such as atopic dermatitis, “may be acceptably, though not optimally, managed with topical and other home-based therapeutic options” during the pandemic, they wrote.

Dr. Cordoro commented that, given how fast new findings are emerging from the pandemic, the guidance on medications could change. “We will know so much more 3 months from now,” she said. And while there are no formal plans to reissue the survey, “we’re maintaining communication and will have some kind of follow up” with the academic dermatologists.

“If we recognize any signals that are counter to what we say in this work we will immediately let people know,” she said.

The researchers received no outside funding for their study. Of the study’s 24 coauthors, nine disclosed financial relationships with industry.

SOURCE: Add the first auSOURCE: Reynolds et al. Pediatr Dermatol. 2020. doi: 10.1111/pde.14202.

Pediatric dermatologists overwhelmingly say that the COVID-19 pandemic has affected how they prescribe and monitor immunosuppressive medications for inflammatory skin diseases, according to a task force survey designed to offer guidance to specialists and nonspecialists faced with tough choices about risks.

Some 87% reported that they were reducing the frequency of lab monitoring for some medications, while more than half said they had reached out to patients and their families to discuss the implications of continuing or stopping a drug.

Virtually all – 97% – said that the COVID-19 crisis had affected their decision to initiate immunosuppressive medications, with 84% saying the decision depended on a patient’s risk factors for contracting COVID-19 infection, and also the potential consequences of infection while treated, compared with the risks of not optimally treating the skin condition.

To develop a consensus-based guidance for clinicians, published online April 22 in Pediatric Dermatology, Kelly Cordoro, MD, professor of dermatology at the University of California, San Francisco, assembled a task force of pediatric dermatologists at academic institutions (the Pediatric Dermatology COVID-19 Response Task Force). Together with Sean Reynolds, MD, a pediatric dermatology fellow at UCSF and colleagues, they issued a survey to the 37 members of the task force with questions on how the pandemic has affected their prescribing decisions and certain therapies specifically. All the recipients responded.

The dermatologists were asked about conventional systemic and biologic medications. Most felt confident in continuing biologics, with 78% saying they would keep patients with no signs of COVID-19 exposure or infection on tumor necrosis factor (TNF) inhibitors. More than 90% of respondents said they would continue patients on dupilumab, as well as anti–interleukin (IL)–17, anti–IL-12/23, and anti–IL-23 therapies.

Responses varied more on approaches to the nonbiologic treatments. Fewer than half (46%) said they would continue patients without apparent COVID-19 exposure on systemic steroids, with another 46% saying it depended on the clinical context.

For other systemic therapies, respondents were more likely to want to continue their patients with no signs or symptoms of COVID-19 on methotrexate and apremilast (78% and 83%, respectively) than others (mycophenolate mofetil, azathioprine, cyclosporine, and JAK inhibitors), which saw between 50% and 60% support in the survey.

Patients on any immunosuppressive medications with likely exposure to COVID-19 or who test positive for the virus should be temporarily taken off their medications, the majority concurred. Exceptions were for systemic steroids, which must be tapered. And a significant minority of the dermatologists said that they would continue apremilast or dupilumab (24% and 16%, respectively) in the event of a confirmed COVID-19 infection.

In an interview, Dr. Cordoro commented that, even in normal times, most systemic or biological immunosuppressive treatments are used off-label by pediatric dermatologists. “There’s no way this could have been an evidence-based document, as we didn’t have the data to drive this. Many of the medications have been tested in children but not necessarily for dermatologic indications; some are chemotherapy agents or drugs used in rheumatologic diseases.”

The COVID-19 pandemic complicated an already difficult decision-making process, she said.

The researchers cautioned against attempting to make decisions about medications based on data on other infections from clinical trials. “Infection data from standard infections that were identified and watched for in clinical trials really still has no bearing on COVID-19 because it’s such a different virus,” Dr. Cordoro said.

And while some immunosuppressive medications could potentially attenuate a SARS-CoV-2–induced cytokine storm, “we certainly don’t assume this is necessarily going to help.”

The authors advised that physicians anxious about initiating an immunosuppressive treatment should take into consideration whether early intervention could “prevent permanent physical impairment or disfigurement” in diseases such as erythrodermic pustular psoriasis or rapidly progressive linear morphea.

Other diseases, such as atopic dermatitis, “may be acceptably, though not optimally, managed with topical and other home-based therapeutic options” during the pandemic, they wrote.

Dr. Cordoro commented that, given how fast new findings are emerging from the pandemic, the guidance on medications could change. “We will know so much more 3 months from now,” she said. And while there are no formal plans to reissue the survey, “we’re maintaining communication and will have some kind of follow up” with the academic dermatologists.

“If we recognize any signals that are counter to what we say in this work we will immediately let people know,” she said.

The researchers received no outside funding for their study. Of the study’s 24 coauthors, nine disclosed financial relationships with industry.

SOURCE: Add the first auSOURCE: Reynolds et al. Pediatr Dermatol. 2020. doi: 10.1111/pde.14202.

Pediatric dermatologists overwhelmingly say that the COVID-19 pandemic has affected how they prescribe and monitor immunosuppressive medications for inflammatory skin diseases, according to a task force survey designed to offer guidance to specialists and nonspecialists faced with tough choices about risks.

Some 87% reported that they were reducing the frequency of lab monitoring for some medications, while more than half said they had reached out to patients and their families to discuss the implications of continuing or stopping a drug.

Virtually all – 97% – said that the COVID-19 crisis had affected their decision to initiate immunosuppressive medications, with 84% saying the decision depended on a patient’s risk factors for contracting COVID-19 infection, and also the potential consequences of infection while treated, compared with the risks of not optimally treating the skin condition.

To develop a consensus-based guidance for clinicians, published online April 22 in Pediatric Dermatology, Kelly Cordoro, MD, professor of dermatology at the University of California, San Francisco, assembled a task force of pediatric dermatologists at academic institutions (the Pediatric Dermatology COVID-19 Response Task Force). Together with Sean Reynolds, MD, a pediatric dermatology fellow at UCSF and colleagues, they issued a survey to the 37 members of the task force with questions on how the pandemic has affected their prescribing decisions and certain therapies specifically. All the recipients responded.

The dermatologists were asked about conventional systemic and biologic medications. Most felt confident in continuing biologics, with 78% saying they would keep patients with no signs of COVID-19 exposure or infection on tumor necrosis factor (TNF) inhibitors. More than 90% of respondents said they would continue patients on dupilumab, as well as anti–interleukin (IL)–17, anti–IL-12/23, and anti–IL-23 therapies.

Responses varied more on approaches to the nonbiologic treatments. Fewer than half (46%) said they would continue patients without apparent COVID-19 exposure on systemic steroids, with another 46% saying it depended on the clinical context.

For other systemic therapies, respondents were more likely to want to continue their patients with no signs or symptoms of COVID-19 on methotrexate and apremilast (78% and 83%, respectively) than others (mycophenolate mofetil, azathioprine, cyclosporine, and JAK inhibitors), which saw between 50% and 60% support in the survey.

Patients on any immunosuppressive medications with likely exposure to COVID-19 or who test positive for the virus should be temporarily taken off their medications, the majority concurred. Exceptions were for systemic steroids, which must be tapered. And a significant minority of the dermatologists said that they would continue apremilast or dupilumab (24% and 16%, respectively) in the event of a confirmed COVID-19 infection.

In an interview, Dr. Cordoro commented that, even in normal times, most systemic or biological immunosuppressive treatments are used off-label by pediatric dermatologists. “There’s no way this could have been an evidence-based document, as we didn’t have the data to drive this. Many of the medications have been tested in children but not necessarily for dermatologic indications; some are chemotherapy agents or drugs used in rheumatologic diseases.”

The COVID-19 pandemic complicated an already difficult decision-making process, she said.

The researchers cautioned against attempting to make decisions about medications based on data on other infections from clinical trials. “Infection data from standard infections that were identified and watched for in clinical trials really still has no bearing on COVID-19 because it’s such a different virus,” Dr. Cordoro said.

And while some immunosuppressive medications could potentially attenuate a SARS-CoV-2–induced cytokine storm, “we certainly don’t assume this is necessarily going to help.”

The authors advised that physicians anxious about initiating an immunosuppressive treatment should take into consideration whether early intervention could “prevent permanent physical impairment or disfigurement” in diseases such as erythrodermic pustular psoriasis or rapidly progressive linear morphea.

Other diseases, such as atopic dermatitis, “may be acceptably, though not optimally, managed with topical and other home-based therapeutic options” during the pandemic, they wrote.

Dr. Cordoro commented that, given how fast new findings are emerging from the pandemic, the guidance on medications could change. “We will know so much more 3 months from now,” she said. And while there are no formal plans to reissue the survey, “we’re maintaining communication and will have some kind of follow up” with the academic dermatologists.

“If we recognize any signals that are counter to what we say in this work we will immediately let people know,” she said.

The researchers received no outside funding for their study. Of the study’s 24 coauthors, nine disclosed financial relationships with industry.

SOURCE: Add the first auSOURCE: Reynolds et al. Pediatr Dermatol. 2020. doi: 10.1111/pde.14202.

Hyperkalemia is the most common adverse event associated with spironolactone use in women, but is uncommon in women aged 45 years or younger, according to new research.

Spironolactone, which is approved to treat heart failure, hypertension, edema, and primary hyperaldosteronism, has antagonistic effects on progesterone and androgen receptors and has been used as an off-label treatment for acne in women. “Numerous guidelines have recommended its off-label use for acne therapy to avoid antibiotic resistance and potential side effects,” wrote Yu Wang of Stony Brook (N.Y.) University and Shari R. Lipner MD, PhD, of Weill Cornell Medicine, New York. Their report is in the International Journal of Women’s Dermatology.

In a retrospective study, the investigators analyzed 7,920 adverse events with spironolactone reported by women of all ages between Jan. 1, 1969, and Dec. 30, 2018, to the Food and Drug Administration’s Adverse Event Reporting System database, for all indications. The most common adverse event was hyperkalemia, reported in 16.1%, followed by kidney injury (15.2%) and drug interactions (9%). Of the 1,272 cases of hyperkalemia reported, 25 occurred in women aged 45 years or younger; 59.3% occurred in women aged 65-85 years.

While spironolactone prescribing information was not available, the investigators compared yearly reports of adverse events with annual public interest in spironolactone using the Google Trends search term spironolactone and annual scholarly mentions of spironolactone in the Altmetric database. There was a strong correlation between the number of cases reported to the FDA and the Google Trends search (Spearman coefficient, 0.94; P less than .001) and to the Altmetric database (Spearman coefficient, 0.64; P less than .01).

Noting that hyperkalemia is “exceptionally uncommon” in women aged 45 years and younger, the investigators concluded that “in the absence of risk factors for hyperkalemia or reduced renal function, potassium laboratory monitoring is unnecessary in younger females taking spironolactone.” Because the incidence increases with age, “interval laboratory monitoring is recommended for females older than 45 years old,” they noted.

Limitations of the study, they noted, include the retrospective design and no available data before 1969. “In addition, since the [FDA Adverse Event Reporting System] data does not differentiate whether spironolactone was prescribed for heart failure, hypertension, edema, primary hyperaldosteronism, or for acne,” the study could not control for these or other confounding comorbidities or associated therapies.

“For future studies, it is important to analyze drug interactions more carefully to determine which other medications may potentiate the risk for hyperkalemia in patients taking spironolactone. It is also important to quantitate overall U.S. prescription data to better understand the relative frequency of these adverse effects reported to the FDA,” they wrote.

The investigators reported that they had no conflicts of interest; the study had no funding.

lfranki@mdedge.com

SOURCE: Wang Y, Lipner SR. Int J Womens Dermatol. 2020 May 18. doi: 10.1016/j.ijwd.2020.05.002.

Hyperkalemia is the most common adverse event associated with spironolactone use in women, but is uncommon in women aged 45 years or younger, according to new research.

Spironolactone, which is approved to treat heart failure, hypertension, edema, and primary hyperaldosteronism, has antagonistic effects on progesterone and androgen receptors and has been used as an off-label treatment for acne in women. “Numerous guidelines have recommended its off-label use for acne therapy to avoid antibiotic resistance and potential side effects,” wrote Yu Wang of Stony Brook (N.Y.) University and Shari R. Lipner MD, PhD, of Weill Cornell Medicine, New York. Their report is in the International Journal of Women’s Dermatology.

In a retrospective study, the investigators analyzed 7,920 adverse events with spironolactone reported by women of all ages between Jan. 1, 1969, and Dec. 30, 2018, to the Food and Drug Administration’s Adverse Event Reporting System database, for all indications. The most common adverse event was hyperkalemia, reported in 16.1%, followed by kidney injury (15.2%) and drug interactions (9%). Of the 1,272 cases of hyperkalemia reported, 25 occurred in women aged 45 years or younger; 59.3% occurred in women aged 65-85 years.

While spironolactone prescribing information was not available, the investigators compared yearly reports of adverse events with annual public interest in spironolactone using the Google Trends search term spironolactone and annual scholarly mentions of spironolactone in the Altmetric database. There was a strong correlation between the number of cases reported to the FDA and the Google Trends search (Spearman coefficient, 0.94; P less than .001) and to the Altmetric database (Spearman coefficient, 0.64; P less than .01).

Noting that hyperkalemia is “exceptionally uncommon” in women aged 45 years and younger, the investigators concluded that “in the absence of risk factors for hyperkalemia or reduced renal function, potassium laboratory monitoring is unnecessary in younger females taking spironolactone.” Because the incidence increases with age, “interval laboratory monitoring is recommended for females older than 45 years old,” they noted.

Limitations of the study, they noted, include the retrospective design and no available data before 1969. “In addition, since the [FDA Adverse Event Reporting System] data does not differentiate whether spironolactone was prescribed for heart failure, hypertension, edema, primary hyperaldosteronism, or for acne,” the study could not control for these or other confounding comorbidities or associated therapies.

“For future studies, it is important to analyze drug interactions more carefully to determine which other medications may potentiate the risk for hyperkalemia in patients taking spironolactone. It is also important to quantitate overall U.S. prescription data to better understand the relative frequency of these adverse effects reported to the FDA,” they wrote.

The investigators reported that they had no conflicts of interest; the study had no funding.

lfranki@mdedge.com

SOURCE: Wang Y, Lipner SR. Int J Womens Dermatol. 2020 May 18. doi: 10.1016/j.ijwd.2020.05.002.

Hyperkalemia is the most common adverse event associated with spironolactone use in women, but is uncommon in women aged 45 years or younger, according to new research.

Spironolactone, which is approved to treat heart failure, hypertension, edema, and primary hyperaldosteronism, has antagonistic effects on progesterone and androgen receptors and has been used as an off-label treatment for acne in women. “Numerous guidelines have recommended its off-label use for acne therapy to avoid antibiotic resistance and potential side effects,” wrote Yu Wang of Stony Brook (N.Y.) University and Shari R. Lipner MD, PhD, of Weill Cornell Medicine, New York. Their report is in the International Journal of Women’s Dermatology.

In a retrospective study, the investigators analyzed 7,920 adverse events with spironolactone reported by women of all ages between Jan. 1, 1969, and Dec. 30, 2018, to the Food and Drug Administration’s Adverse Event Reporting System database, for all indications. The most common adverse event was hyperkalemia, reported in 16.1%, followed by kidney injury (15.2%) and drug interactions (9%). Of the 1,272 cases of hyperkalemia reported, 25 occurred in women aged 45 years or younger; 59.3% occurred in women aged 65-85 years.

While spironolactone prescribing information was not available, the investigators compared yearly reports of adverse events with annual public interest in spironolactone using the Google Trends search term spironolactone and annual scholarly mentions of spironolactone in the Altmetric database. There was a strong correlation between the number of cases reported to the FDA and the Google Trends search (Spearman coefficient, 0.94; P less than .001) and to the Altmetric database (Spearman coefficient, 0.64; P less than .01).

Noting that hyperkalemia is “exceptionally uncommon” in women aged 45 years and younger, the investigators concluded that “in the absence of risk factors for hyperkalemia or reduced renal function, potassium laboratory monitoring is unnecessary in younger females taking spironolactone.” Because the incidence increases with age, “interval laboratory monitoring is recommended for females older than 45 years old,” they noted.

Limitations of the study, they noted, include the retrospective design and no available data before 1969. “In addition, since the [FDA Adverse Event Reporting System] data does not differentiate whether spironolactone was prescribed for heart failure, hypertension, edema, primary hyperaldosteronism, or for acne,” the study could not control for these or other confounding comorbidities or associated therapies.

“For future studies, it is important to analyze drug interactions more carefully to determine which other medications may potentiate the risk for hyperkalemia in patients taking spironolactone. It is also important to quantitate overall U.S. prescription data to better understand the relative frequency of these adverse effects reported to the FDA,” they wrote.

The investigators reported that they had no conflicts of interest; the study had no funding.

lfranki@mdedge.com

SOURCE: Wang Y, Lipner SR. Int J Womens Dermatol. 2020 May 18. doi: 10.1016/j.ijwd.2020.05.002.

After more than 8 months of development, Crayola is ready to release a set of specially formulated crayons that are “designed to mirror and represent over 40 global skin tones across the world.”

Crayola

“With the world growing more diverse than ever before, Crayola hopes our new Colors of the World crayons will increase representation and foster a greater sense of belonging and acceptance,” CEO Rich Wuerthele said in a written statement.

Crayola

The company partnered with a cosmetic industry foundation-color expert to create “colors that step down from light to deep shades across rose, almond, and golden undertones, resulting in a 24 global shade palette that authentically reflects the full spectrum of human complexions,” according to Crayola’s statement. The 24- and 32-count Colors of the World packs will start reaching stores in July. The pack of 32 crayons includes the 24 skin colors along with 4 hair and 4 eye colors.

rfranki@mdedge.com

After more than 8 months of development, Crayola is ready to release a set of specially formulated crayons that are “designed to mirror and represent over 40 global skin tones across the world.”

Crayola

“With the world growing more diverse than ever before, Crayola hopes our new Colors of the World crayons will increase representation and foster a greater sense of belonging and acceptance,” CEO Rich Wuerthele said in a written statement.

Crayola

The company partnered with a cosmetic industry foundation-color expert to create “colors that step down from light to deep shades across rose, almond, and golden undertones, resulting in a 24 global shade palette that authentically reflects the full spectrum of human complexions,” according to Crayola’s statement. The 24- and 32-count Colors of the World packs will start reaching stores in July. The pack of 32 crayons includes the 24 skin colors along with 4 hair and 4 eye colors.

rfranki@mdedge.com

After more than 8 months of development, Crayola is ready to release a set of specially formulated crayons that are “designed to mirror and represent over 40 global skin tones across the world.”

Crayola

“With the world growing more diverse than ever before, Crayola hopes our new Colors of the World crayons will increase representation and foster a greater sense of belonging and acceptance,” CEO Rich Wuerthele said in a written statement.

Crayola

The company partnered with a cosmetic industry foundation-color expert to create “colors that step down from light to deep shades across rose, almond, and golden undertones, resulting in a 24 global shade palette that authentically reflects the full spectrum of human complexions,” according to Crayola’s statement. The 24- and 32-count Colors of the World packs will start reaching stores in July. The pack of 32 crayons includes the 24 skin colors along with 4 hair and 4 eye colors.

rfranki@mdedge.com

About half of Americans say they would get a COVID-19 vaccine if one is available, according to the Associated Press.

The poll, conducted by the AP-NORC Center for Public Affairs Research, also found that 31% said they weren’t sure if they’d get a vaccine, and 20% said they’d refuse to get one. The poll was conducted May 14-18 and released May 27.

A massive national and international effort is underway to develop a vaccine for the coronavirus. According to the poll, 20% of Americans believe a vaccine will be available before the end of 2020. Another 61% think it will arrive in 2021, and 17% say it will take longer.

“It’s always better to under-promise and over-deliver,” William Schaffner, MD, an infectious disease specialist at Vanderbilt University Medical Center, told the AP.

Americans over age 60 were more likely to say they’ll get a coronavirus vaccine when it’s available. Those who worry that they or someone in their household could become infected with the virus were also more likely to say they’ll get a vaccine. However, Black Americans were more likely than were Hispanic or white responders to say that they don’t plan to get a vaccine.

Among those who plan to get a vaccine, 93% said they want to protect themselves, and 88% said they want to protect their family. About 72% said “life won’t go back to normal until most people are vaccinated,” and 33% said they have a chronic health condition such as asthma or diabetes and believe it’s important to receive a vaccine.

Among those who don’t plan to get a vaccine, 70% said they’re concerned about side effects. Another 42% are worried about getting the coronavirus from the vaccine. Others say they’re not concerned about getting seriously ill from the coronavirus, they don’t think vaccines work well, the COVID-19 outbreak isn’t serious, or they don’t like needles.

The National Institutes of Health says that safety is the top priority and is creating a plan to test the vaccine in thousands of people for safety and efficacy in coming months, according to the AP.

“I would not want people to think that we’re cutting corners because that would be a big mistake,” NIH director Francis Collins, MD, told AP earlier this month. “I think this is an effort to try to achieve efficiencies but not to sacrifice rigor.”

This article first appeared on WebMD.com.

About half of Americans say they would get a COVID-19 vaccine if one is available, according to the Associated Press.

The poll, conducted by the AP-NORC Center for Public Affairs Research, also found that 31% said they weren’t sure if they’d get a vaccine, and 20% said they’d refuse to get one. The poll was conducted May 14-18 and released May 27.

A massive national and international effort is underway to develop a vaccine for the coronavirus. According to the poll, 20% of Americans believe a vaccine will be available before the end of 2020. Another 61% think it will arrive in 2021, and 17% say it will take longer.

“It’s always better to under-promise and over-deliver,” William Schaffner, MD, an infectious disease specialist at Vanderbilt University Medical Center, told the AP.

Americans over age 60 were more likely to say they’ll get a coronavirus vaccine when it’s available. Those who worry that they or someone in their household could become infected with the virus were also more likely to say they’ll get a vaccine. However, Black Americans were more likely than were Hispanic or white responders to say that they don’t plan to get a vaccine.

Among those who plan to get a vaccine, 93% said they want to protect themselves, and 88% said they want to protect their family. About 72% said “life won’t go back to normal until most people are vaccinated,” and 33% said they have a chronic health condition such as asthma or diabetes and believe it’s important to receive a vaccine.

Among those who don’t plan to get a vaccine, 70% said they’re concerned about side effects. Another 42% are worried about getting the coronavirus from the vaccine. Others say they’re not concerned about getting seriously ill from the coronavirus, they don’t think vaccines work well, the COVID-19 outbreak isn’t serious, or they don’t like needles.

The National Institutes of Health says that safety is the top priority and is creating a plan to test the vaccine in thousands of people for safety and efficacy in coming months, according to the AP.

“I would not want people to think that we’re cutting corners because that would be a big mistake,” NIH director Francis Collins, MD, told AP earlier this month. “I think this is an effort to try to achieve efficiencies but not to sacrifice rigor.”

This article first appeared on WebMD.com.

About half of Americans say they would get a COVID-19 vaccine if one is available, according to the Associated Press.

The poll, conducted by the AP-NORC Center for Public Affairs Research, also found that 31% said they weren’t sure if they’d get a vaccine, and 20% said they’d refuse to get one. The poll was conducted May 14-18 and released May 27.

A massive national and international effort is underway to develop a vaccine for the coronavirus. According to the poll, 20% of Americans believe a vaccine will be available before the end of 2020. Another 61% think it will arrive in 2021, and 17% say it will take longer.

“It’s always better to under-promise and over-deliver,” William Schaffner, MD, an infectious disease specialist at Vanderbilt University Medical Center, told the AP.

Americans over age 60 were more likely to say they’ll get a coronavirus vaccine when it’s available. Those who worry that they or someone in their household could become infected with the virus were also more likely to say they’ll get a vaccine. However, Black Americans were more likely than were Hispanic or white responders to say that they don’t plan to get a vaccine.

Among those who plan to get a vaccine, 93% said they want to protect themselves, and 88% said they want to protect their family. About 72% said “life won’t go back to normal until most people are vaccinated,” and 33% said they have a chronic health condition such as asthma or diabetes and believe it’s important to receive a vaccine.

Among those who don’t plan to get a vaccine, 70% said they’re concerned about side effects. Another 42% are worried about getting the coronavirus from the vaccine. Others say they’re not concerned about getting seriously ill from the coronavirus, they don’t think vaccines work well, the COVID-19 outbreak isn’t serious, or they don’t like needles.

The National Institutes of Health says that safety is the top priority and is creating a plan to test the vaccine in thousands of people for safety and efficacy in coming months, according to the AP.

“I would not want people to think that we’re cutting corners because that would be a big mistake,” NIH director Francis Collins, MD, told AP earlier this month. “I think this is an effort to try to achieve efficiencies but not to sacrifice rigor.”

This article first appeared on WebMD.com.

Roger R., MD, a primary care physician from Philadelphia, set up a telemedicine appointment with a 24-year-old female patient who was experiencing headaches and was worried she might have COVID-19.

Photodisc/Thinkstock

During the televisit, Dr. R. noticed that “Tonya” (not her real name) had a purplish bruise under her right eye. When asked how she got the bruise, Tonya said she had bumped into a dresser. The physician suspected abuse. He then heard a man’s voice in the background and thought it might belong to the abuser. “Is this a good time for you to talk?” he asked Tonya.

Tonya hesitated.

“When might be a better time?”

Tonya suggested an alternate time, and the physician called her then. During the visit, she shared that her fiancé, a car salesman who was also sheltering at home, was punching her.

“He always had a bad temper. Once he shoved me, but he’s never hit me before. And when he was upset, we used to go out to eat and he calmed down. Now, we’re stuck inside, we can’t even get away from each other to go to work, and he’s getting scary,” she told the doctor.

The physician asked if she would like to be connected with a domestic violence counselor. When Tonya agreed, he called Jessica DuBois Palardy, a licensed social worker and the program supervisor at STOP Intimate Partner Violence, a Philadelphia-based collaborative project of the Children’s Hospital of Philadelphia and the Lutheran Settlement House’s Bilingual Domestic Violence Program.
 

A ‘horrifying’ trend

Tonya’s story is not unique. A United Nations report shows that there has been a “horrifying global surge in domestic violence” linked to “lockdowns imposed by the governments responding to the COVID-19 pandemic.” The United States is no exception – 2,345 calls were placed to the National Domestic Violence Hotline during March 16–April 6, 2020.

Carole Warshaw, MD, director of the National Center on Domestic Violence, Trauma, and Mental Health in Chicago, said, “We know that intimate partner violence is increasing among people sheltering at home, and that abuse has become more severe.”

Even in nonabusive situations, being confined together at close quarters, often amid family stress and financial hardship, can be wearing, and tempers can flare. In an abusive relationship, “the main contributor to violence during shelter-in-place restrictions is that the isolation gives abusers more opportunities for controlling their partners, who have fewer options for accessing safety and support,” Dr. Warshaw said.

It is critical to “approach every clinical encounter knowing that domestic violence may be at play,” she emphasized.
 

Physicians might be the most important lifeline

Physicians are already facing myriad COVID-19–related challenges, and having another concern to keep in mind may be daunting.

“We’re in uncharted territory and we’re all trying to figure out how to navigate this time, how to practice medicine via phone and video conferences, and how to deal with the financial repercussions of the pandemic – not to mention concern for the health of our families,” said Peter F. Cronholm, MD, associate professor of family medicine and community health at the Hospital of the University of Pennsylvania, Philadelphia. “So maintaining vigilance is often difficult. Nevertheless, it’s important not to let this critical issue fall to the wayside.”

Marcella Nyachogo, MSW, a licensed social worker and assistant director of the Bilingual Domestic Violence Program, noted that physicians and other health care providers “may be the only people the patient interacts with, since the abuser may cut the survivor off from family and friends. And because the survivor isn’t leaving the house, he or she doesn’t have an opportunity to interact with coworkers or others – which makes health care providers the most important lifeline.”
 

COVID-19 as a weapon of abuse

Carey Watson, MD, regional medical director of the Family Violence Prevention Program at Kaiser Permanente in northern California, points to a disturbing trend in COVID-19–related abuse.

“Unfortunately, I’m hearing more and more accounts of how the illness itself can be one more weapon in the abuser’s arsenal,” she said.

Experts say that increasingly, abusers are claiming that their partner, who is employed in an “essential” job outside the home, is carrying the virus, and they are using this as a means of control and manipulation.

This is especially true of abusive partners of health care providers, Dr. Watson noted. She recounted the story of a divorced nurse whose husband did not allow her to have contact with their children, allegedly out of concern that she might have COVID-19, and would threaten her with a gun when she protested.

“It is important to keep this abusive tactic in mind, not only when dealing with patients but also with fellow physicians and health care professionals, and check in to see if everything is okay – especially if they seem particularly stressed out or distant,” Dr. Watson recommended.

Trust your clinical gut

How can you tell if your patients might be experiencing abuse when you’re not seeing them in person?

Pay attention to subtle signals and “trust your clinical gut when something doesn’t feel right,” Ms. Nyachogo advised.

If a patient’s demeanor is jittery or anxious or if someone next to him or her is answering all the questions or interrupting the visit, these could be red flags.

Dr. Cronholm added that telemedicine visits offer a “rare window into a patient’s home life that would not be available in an office visit.” For example, a house in disarray, the presence of broken objects, or the presence of another person hovering in the background suggests the need for further exploration.

The starting point of screening and intervention is to recognize that any domestic violence situation is potentially explosive. “The main thing for all providers to keep in mind is ‘first, do no harm,’ ” Ms. Nyachogo emphasized.

“Our agency has been working for years with medical professionals in how to screen and connect folks with help most effectively and safely, and – although the specific situations posed by COVID are new – the overall approach is the same, which is to proceed with caution in how you approach the subject and how you make referrals,” she said.

Begin by asking if it is a convenient time to talk.

“This question takes the onus off the patient, who may not know how to communicate that she has no privacy or is in the middle of an argument,” explained Elsa Swenson, program manager of Home Free community program, which serves individuals experiencing domestic violence. The program is part of Minnesota-based Missions Inc. Programs, which serves those experiencing domestic abuse and chemical dependency.

If the patient indicates that it isn’t a convenient time to talk, find out when would be a better time. “This might be difficult for busy physicians and may not be what they’re accustomed to when calling a patient at home, but the patient’s circumstances are unknown to you, so it’s essential to organize around their ability to talk,” Ms. Swenson noted.
 

‘Are you alone?’

Another important piece of information is whether the patient has privacy – which can be tricky if the abuser is standing right there.

“You don’t want to tip the abuser off to your concerns, so you need to frame the question in a neutral way,” Dr. Watson advised.

For example, you might say that HIPAA laws require that you conduct the consultation with no one else present, and find out if there is a location in the house where the patient can have privacy.

It might be easier to talk on the phone than via video, suggests Florence Remes, a New Jersey–based licensed social worker who specializes in domestic violence. Going into another room and playing music or turning on the television might make it less obvious that a call is taking place, and the abuser would be less likely to overhear the caller’s conversation.

Dr. Watson suggested that questions about abuse might be included with other questions and asked in a simple yes/no format. “I’d like to ask you some standard questions I’m asking everyone during the pandemic. Do you have a cough or fever? Do you have any other physical symptoms? Do you have access to hand sanitizer? How is your sleep? Are you experiencing stress? Do you feel safe at home?”

The abuser, if present, will only hear the patient’s “yes” or “no” without knowing the question. If the patient indicates that she is being abused but is unable to talk, a later time can be arranged to further explore the issue.
 

Technology is a double-edged sword

Modern technologies have been a great boon to patients and physicians during this time of social distancing, allowing ongoing contact and health care when it would not otherwise have been possible. On the other hand, technology is fraught with potential dangers that can jeopardize the patient’s safety and compromise privacy.

Ms. Remes recounted the story of “Susan,” a client with whom she had been conducting teletherapy visits using an approved HIPAA-compliant telemedicine forum. Susan was working from home because of shelter-in-place restrictions. Her husband had been abusive, and Susan was concerned he might be “sabotaging” the household’s WiFi to isolate her from outside sources of support.

At the recommendation of Ms. Remes, Susan continued sessions either via phone calls or by using the WhatsApp program on her cellphone. Many of the requirements governing HIPAA privacy regulations have been temporarily relaxed, and clinicians can use non–encrypted forms of transmission, such as FaceTime, WhatsApp, or Skype, if no other platform is available.

But even cellphones have risks, Dr. Warshaw noted. The patient’s abuser might track texts or look at call logs – especially on unsecured platforms. It’s advisable to ask patients about who has access to their phone and computer and discuss ways to increase security.
 

Follow the patient’s lead

Proceed slowly and start with nonthreatening questions, Ms. Palardy advised. “I notice you have some injuries; can you tell me how you got them? Did someone hurt you? What does your relationship look like when you argue? Is there anything that makes you feel uncomfortable or unsafe?”

Emphasizing that you are asking these questions because of care and concern is reassuring and helps patients to feel they are not alone, Ms. Nyachogo pointed out.

“As your doctor, I’m worried about your health and (if relevant) your children’s safety. I can help connect you with counseling and support, legal resources, and a shelter, and everything is free and confidential. Would you be interested?” she said.

If the client acknowledges abuse, “follow their lead, but don’t push too hard,” Ms. Nyachogo warned.

“It is the client’s choice whether or not to take action,” she noted. “I’ve met survivors who said that it wasn’t until a doctor or nurse expressed concern about bruises that it even occurred to them that they were being abused. Some lied to the doctor about how they got hurt – but the question planted a seed, even though it might have taken years to follow up on the referral,” she said.
 

What if the patient doesn’t want to get help?

If a patient is not ready to seek help, you can create a home-safety plan. This might include setting follow-up times. If you don’t hear from him or her, you should then call the police. Or you might create a “code word,” such as “apple pie.” If the patient uses that word during a session, you know her life is in danger, Ms. Remes suggested.

Providing written information about how to get help is important but can be problematic if the abuser finds it.

Ms. Nyachogo recommends e-mailing follow-up materials that cover a variety of topics, such as keeping safe during the COVID-19 pandemic, relaxation, healthy eating, getting exercise while homebound, activities for children, and suggestions for hotlines and other resources if one is feeling suicidal or unsafe.

“If you present these as your ‘standard’ follow-up materials, the abuser is less likely to become suspicious,” Ms. Nyachogo noted.
 

Resources are available during COVID-19

All of the experts emphasize that resources for victims of domestic violence remain available during the COVID-19 pandemic, although some shelters may be operating at reduced capacity. Some agencies are finding alternatives to group shelters, such as hotels or Airbnb, which carry less risk of catching COVID-19.

Referring a patient to domestic violence resources is a delicate process. “You don’t want referring the patient for help to further endanger their life,” Ms. Nyachogo said.

The more you can take the burden off the patient, the better. If she is interested in getting help, you can call a domestic violence counselor or advocate while she is on the phone.

“This type of ‘warm handoff’ is what Tonya’s physician did,” Ms. Palardy recounted.

A warm handoff requires that physicians be familiar with domestic violence resources, Dr. Warshaw emphasized.

“Don’t wait until you are working with someone who needs help to find out where to refer them. Take the time to proactively research local agencies specializing in domestic violence and have their phone numbers on hand, so you can offer resources immediately if the person is interested,” she advised. The National Domestic Violence Hotline can also assist with safety planning and access to local resources.
 

‘Thinking on your feet’ critical for physicians

Addressing domestic violence during this unprecedented time requires “thinking on your feet” about novel forms of detection and intervention, Dr. Watson said. This involves a combination of clinical acumen, creativity, and finely honed intuition.

Ms. Nyachogo added, “Keeping an eye on domestic violence can feel like an extra burden, but don’t forget that it is lifesaving work.”
 

Resources

National Domestic Violence Hotline

• 800-799-SAFE (7233)
• The patient can also text LOVEIS to 22522.

National Center on Domestic Violence, Trauma, and Mental Health

• Provides resources for health care, mental health, and substance use treatment and recovery support providers on responding to domestic violence and other trauma.
• Provides resources for professionals and patients regarding access to substance use and mental health care during the COVID-1 pandemic.
• Provides support for parents, caregivers, and children during the pandemic.
• Provides resources for advocates serving families affected by domestic violence.

U.S. Department of Justice

• A state-by-state guide to local resources

Children’s Hospital of Philadelphia Research Institute

STOP Intimate Partner Violence (IPV)
 

New Jersey Coalition for Domestic Violence

American Bar Association COVID-19 resources for communities

Crisis Text Line

• Text HOME to 741741.

National Network to End Domestic Violence (NNEDV) COVID-19 Technology Safety

A version of this article originally appeared on Medscape.com.

Roger R., MD, a primary care physician from Philadelphia, set up a telemedicine appointment with a 24-year-old female patient who was experiencing headaches and was worried she might have COVID-19.

Photodisc/Thinkstock

During the televisit, Dr. R. noticed that “Tonya” (not her real name) had a purplish bruise under her right eye. When asked how she got the bruise, Tonya said she had bumped into a dresser. The physician suspected abuse. He then heard a man’s voice in the background and thought it might belong to the abuser. “Is this a good time for you to talk?” he asked Tonya.

Tonya hesitated.

“When might be a better time?”

Tonya suggested an alternate time, and the physician called her then. During the visit, she shared that her fiancé, a car salesman who was also sheltering at home, was punching her.

“He always had a bad temper. Once he shoved me, but he’s never hit me before. And when he was upset, we used to go out to eat and he calmed down. Now, we’re stuck inside, we can’t even get away from each other to go to work, and he’s getting scary,” she told the doctor.

The physician asked if she would like to be connected with a domestic violence counselor. When Tonya agreed, he called Jessica DuBois Palardy, a licensed social worker and the program supervisor at STOP Intimate Partner Violence, a Philadelphia-based collaborative project of the Children’s Hospital of Philadelphia and the Lutheran Settlement House’s Bilingual Domestic Violence Program.
 

A ‘horrifying’ trend

Tonya’s story is not unique. A United Nations report shows that there has been a “horrifying global surge in domestic violence” linked to “lockdowns imposed by the governments responding to the COVID-19 pandemic.” The United States is no exception – 2,345 calls were placed to the National Domestic Violence Hotline during March 16–April 6, 2020.

Carole Warshaw, MD, director of the National Center on Domestic Violence, Trauma, and Mental Health in Chicago, said, “We know that intimate partner violence is increasing among people sheltering at home, and that abuse has become more severe.”

Even in nonabusive situations, being confined together at close quarters, often amid family stress and financial hardship, can be wearing, and tempers can flare. In an abusive relationship, “the main contributor to violence during shelter-in-place restrictions is that the isolation gives abusers more opportunities for controlling their partners, who have fewer options for accessing safety and support,” Dr. Warshaw said.

It is critical to “approach every clinical encounter knowing that domestic violence may be at play,” she emphasized.
 

Physicians might be the most important lifeline

Physicians are already facing myriad COVID-19–related challenges, and having another concern to keep in mind may be daunting.

“We’re in uncharted territory and we’re all trying to figure out how to navigate this time, how to practice medicine via phone and video conferences, and how to deal with the financial repercussions of the pandemic – not to mention concern for the health of our families,” said Peter F. Cronholm, MD, associate professor of family medicine and community health at the Hospital of the University of Pennsylvania, Philadelphia. “So maintaining vigilance is often difficult. Nevertheless, it’s important not to let this critical issue fall to the wayside.”

Marcella Nyachogo, MSW, a licensed social worker and assistant director of the Bilingual Domestic Violence Program, noted that physicians and other health care providers “may be the only people the patient interacts with, since the abuser may cut the survivor off from family and friends. And because the survivor isn’t leaving the house, he or she doesn’t have an opportunity to interact with coworkers or others – which makes health care providers the most important lifeline.”
 

COVID-19 as a weapon of abuse

Carey Watson, MD, regional medical director of the Family Violence Prevention Program at Kaiser Permanente in northern California, points to a disturbing trend in COVID-19–related abuse.

“Unfortunately, I’m hearing more and more accounts of how the illness itself can be one more weapon in the abuser’s arsenal,” she said.

Experts say that increasingly, abusers are claiming that their partner, who is employed in an “essential” job outside the home, is carrying the virus, and they are using this as a means of control and manipulation.

This is especially true of abusive partners of health care providers, Dr. Watson noted. She recounted the story of a divorced nurse whose husband did not allow her to have contact with their children, allegedly out of concern that she might have COVID-19, and would threaten her with a gun when she protested.

“It is important to keep this abusive tactic in mind, not only when dealing with patients but also with fellow physicians and health care professionals, and check in to see if everything is okay – especially if they seem particularly stressed out or distant,” Dr. Watson recommended.

Trust your clinical gut

How can you tell if your patients might be experiencing abuse when you’re not seeing them in person?

Pay attention to subtle signals and “trust your clinical gut when something doesn’t feel right,” Ms. Nyachogo advised.

If a patient’s demeanor is jittery or anxious or if someone next to him or her is answering all the questions or interrupting the visit, these could be red flags.

Dr. Cronholm added that telemedicine visits offer a “rare window into a patient’s home life that would not be available in an office visit.” For example, a house in disarray, the presence of broken objects, or the presence of another person hovering in the background suggests the need for further exploration.

The starting point of screening and intervention is to recognize that any domestic violence situation is potentially explosive. “The main thing for all providers to keep in mind is ‘first, do no harm,’ ” Ms. Nyachogo emphasized.

“Our agency has been working for years with medical professionals in how to screen and connect folks with help most effectively and safely, and – although the specific situations posed by COVID are new – the overall approach is the same, which is to proceed with caution in how you approach the subject and how you make referrals,” she said.

Begin by asking if it is a convenient time to talk.

“This question takes the onus off the patient, who may not know how to communicate that she has no privacy or is in the middle of an argument,” explained Elsa Swenson, program manager of Home Free community program, which serves individuals experiencing domestic violence. The program is part of Minnesota-based Missions Inc. Programs, which serves those experiencing domestic abuse and chemical dependency.

If the patient indicates that it isn’t a convenient time to talk, find out when would be a better time. “This might be difficult for busy physicians and may not be what they’re accustomed to when calling a patient at home, but the patient’s circumstances are unknown to you, so it’s essential to organize around their ability to talk,” Ms. Swenson noted.
 

‘Are you alone?’

Another important piece of information is whether the patient has privacy – which can be tricky if the abuser is standing right there.

“You don’t want to tip the abuser off to your concerns, so you need to frame the question in a neutral way,” Dr. Watson advised.

For example, you might say that HIPAA laws require that you conduct the consultation with no one else present, and find out if there is a location in the house where the patient can have privacy.

It might be easier to talk on the phone than via video, suggests Florence Remes, a New Jersey–based licensed social worker who specializes in domestic violence. Going into another room and playing music or turning on the television might make it less obvious that a call is taking place, and the abuser would be less likely to overhear the caller’s conversation.

Dr. Watson suggested that questions about abuse might be included with other questions and asked in a simple yes/no format. “I’d like to ask you some standard questions I’m asking everyone during the pandemic. Do you have a cough or fever? Do you have any other physical symptoms? Do you have access to hand sanitizer? How is your sleep? Are you experiencing stress? Do you feel safe at home?”

The abuser, if present, will only hear the patient’s “yes” or “no” without knowing the question. If the patient indicates that she is being abused but is unable to talk, a later time can be arranged to further explore the issue.
 

Technology is a double-edged sword

Modern technologies have been a great boon to patients and physicians during this time of social distancing, allowing ongoing contact and health care when it would not otherwise have been possible. On the other hand, technology is fraught with potential dangers that can jeopardize the patient’s safety and compromise privacy.

Ms. Remes recounted the story of “Susan,” a client with whom she had been conducting teletherapy visits using an approved HIPAA-compliant telemedicine forum. Susan was working from home because of shelter-in-place restrictions. Her husband had been abusive, and Susan was concerned he might be “sabotaging” the household’s WiFi to isolate her from outside sources of support.

At the recommendation of Ms. Remes, Susan continued sessions either via phone calls or by using the WhatsApp program on her cellphone. Many of the requirements governing HIPAA privacy regulations have been temporarily relaxed, and clinicians can use non–encrypted forms of transmission, such as FaceTime, WhatsApp, or Skype, if no other platform is available.

But even cellphones have risks, Dr. Warshaw noted. The patient’s abuser might track texts or look at call logs – especially on unsecured platforms. It’s advisable to ask patients about who has access to their phone and computer and discuss ways to increase security.
 

Follow the patient’s lead

Proceed slowly and start with nonthreatening questions, Ms. Palardy advised. “I notice you have some injuries; can you tell me how you got them? Did someone hurt you? What does your relationship look like when you argue? Is there anything that makes you feel uncomfortable or unsafe?”

Emphasizing that you are asking these questions because of care and concern is reassuring and helps patients to feel they are not alone, Ms. Nyachogo pointed out.

“As your doctor, I’m worried about your health and (if relevant) your children’s safety. I can help connect you with counseling and support, legal resources, and a shelter, and everything is free and confidential. Would you be interested?” she said.

If the client acknowledges abuse, “follow their lead, but don’t push too hard,” Ms. Nyachogo warned.

“It is the client’s choice whether or not to take action,” she noted. “I’ve met survivors who said that it wasn’t until a doctor or nurse expressed concern about bruises that it even occurred to them that they were being abused. Some lied to the doctor about how they got hurt – but the question planted a seed, even though it might have taken years to follow up on the referral,” she said.
 

What if the patient doesn’t want to get help?

If a patient is not ready to seek help, you can create a home-safety plan. This might include setting follow-up times. If you don’t hear from him or her, you should then call the police. Or you might create a “code word,” such as “apple pie.” If the patient uses that word during a session, you know her life is in danger, Ms. Remes suggested.

Providing written information about how to get help is important but can be problematic if the abuser finds it.

Ms. Nyachogo recommends e-mailing follow-up materials that cover a variety of topics, such as keeping safe during the COVID-19 pandemic, relaxation, healthy eating, getting exercise while homebound, activities for children, and suggestions for hotlines and other resources if one is feeling suicidal or unsafe.

“If you present these as your ‘standard’ follow-up materials, the abuser is less likely to become suspicious,” Ms. Nyachogo noted.
 

Resources are available during COVID-19

All of the experts emphasize that resources for victims of domestic violence remain available during the COVID-19 pandemic, although some shelters may be operating at reduced capacity. Some agencies are finding alternatives to group shelters, such as hotels or Airbnb, which carry less risk of catching COVID-19.

Referring a patient to domestic violence resources is a delicate process. “You don’t want referring the patient for help to further endanger their life,” Ms. Nyachogo said.

The more you can take the burden off the patient, the better. If she is interested in getting help, you can call a domestic violence counselor or advocate while she is on the phone.

“This type of ‘warm handoff’ is what Tonya’s physician did,” Ms. Palardy recounted.

A warm handoff requires that physicians be familiar with domestic violence resources, Dr. Warshaw emphasized.

“Don’t wait until you are working with someone who needs help to find out where to refer them. Take the time to proactively research local agencies specializing in domestic violence and have their phone numbers on hand, so you can offer resources immediately if the person is interested,” she advised. The National Domestic Violence Hotline can also assist with safety planning and access to local resources.
 

‘Thinking on your feet’ critical for physicians

Addressing domestic violence during this unprecedented time requires “thinking on your feet” about novel forms of detection and intervention, Dr. Watson said. This involves a combination of clinical acumen, creativity, and finely honed intuition.

Ms. Nyachogo added, “Keeping an eye on domestic violence can feel like an extra burden, but don’t forget that it is lifesaving work.”
 

Resources

National Domestic Violence Hotline

• 800-799-SAFE (7233)
• The patient can also text LOVEIS to 22522.

National Center on Domestic Violence, Trauma, and Mental Health

• Provides resources for health care, mental health, and substance use treatment and recovery support providers on responding to domestic violence and other trauma.
• Provides resources for professionals and patients regarding access to substance use and mental health care during the COVID-1 pandemic.
• Provides support for parents, caregivers, and children during the pandemic.
• Provides resources for advocates serving families affected by domestic violence.

U.S. Department of Justice

• A state-by-state guide to local resources

Children’s Hospital of Philadelphia Research Institute

STOP Intimate Partner Violence (IPV)
 

New Jersey Coalition for Domestic Violence

American Bar Association COVID-19 resources for communities

Crisis Text Line

• Text HOME to 741741.

National Network to End Domestic Violence (NNEDV) COVID-19 Technology Safety

A version of this article originally appeared on Medscape.com.

Roger R., MD, a primary care physician from Philadelphia, set up a telemedicine appointment with a 24-year-old female patient who was experiencing headaches and was worried she might have COVID-19.

Photodisc/Thinkstock

During the televisit, Dr. R. noticed that “Tonya” (not her real name) had a purplish bruise under her right eye. When asked how she got the bruise, Tonya said she had bumped into a dresser. The physician suspected abuse. He then heard a man’s voice in the background and thought it might belong to the abuser. “Is this a good time for you to talk?” he asked Tonya.

Tonya hesitated.

“When might be a better time?”

Tonya suggested an alternate time, and the physician called her then. During the visit, she shared that her fiancé, a car salesman who was also sheltering at home, was punching her.

“He always had a bad temper. Once he shoved me, but he’s never hit me before. And when he was upset, we used to go out to eat and he calmed down. Now, we’re stuck inside, we can’t even get away from each other to go to work, and he’s getting scary,” she told the doctor.

The physician asked if she would like to be connected with a domestic violence counselor. When Tonya agreed, he called Jessica DuBois Palardy, a licensed social worker and the program supervisor at STOP Intimate Partner Violence, a Philadelphia-based collaborative project of the Children’s Hospital of Philadelphia and the Lutheran Settlement House’s Bilingual Domestic Violence Program.
 

A ‘horrifying’ trend

Tonya’s story is not unique. A United Nations report shows that there has been a “horrifying global surge in domestic violence” linked to “lockdowns imposed by the governments responding to the COVID-19 pandemic.” The United States is no exception – 2,345 calls were placed to the National Domestic Violence Hotline during March 16–April 6, 2020.

Carole Warshaw, MD, director of the National Center on Domestic Violence, Trauma, and Mental Health in Chicago, said, “We know that intimate partner violence is increasing among people sheltering at home, and that abuse has become more severe.”

Even in nonabusive situations, being confined together at close quarters, often amid family stress and financial hardship, can be wearing, and tempers can flare. In an abusive relationship, “the main contributor to violence during shelter-in-place restrictions is that the isolation gives abusers more opportunities for controlling their partners, who have fewer options for accessing safety and support,” Dr. Warshaw said.

It is critical to “approach every clinical encounter knowing that domestic violence may be at play,” she emphasized.
 

Physicians might be the most important lifeline

Physicians are already facing myriad COVID-19–related challenges, and having another concern to keep in mind may be daunting.

“We’re in uncharted territory and we’re all trying to figure out how to navigate this time, how to practice medicine via phone and video conferences, and how to deal with the financial repercussions of the pandemic – not to mention concern for the health of our families,” said Peter F. Cronholm, MD, associate professor of family medicine and community health at the Hospital of the University of Pennsylvania, Philadelphia. “So maintaining vigilance is often difficult. Nevertheless, it’s important not to let this critical issue fall to the wayside.”

Marcella Nyachogo, MSW, a licensed social worker and assistant director of the Bilingual Domestic Violence Program, noted that physicians and other health care providers “may be the only people the patient interacts with, since the abuser may cut the survivor off from family and friends. And because the survivor isn’t leaving the house, he or she doesn’t have an opportunity to interact with coworkers or others – which makes health care providers the most important lifeline.”
 

COVID-19 as a weapon of abuse

Carey Watson, MD, regional medical director of the Family Violence Prevention Program at Kaiser Permanente in northern California, points to a disturbing trend in COVID-19–related abuse.

“Unfortunately, I’m hearing more and more accounts of how the illness itself can be one more weapon in the abuser’s arsenal,” she said.

Experts say that increasingly, abusers are claiming that their partner, who is employed in an “essential” job outside the home, is carrying the virus, and they are using this as a means of control and manipulation.

This is especially true of abusive partners of health care providers, Dr. Watson noted. She recounted the story of a divorced nurse whose husband did not allow her to have contact with their children, allegedly out of concern that she might have COVID-19, and would threaten her with a gun when she protested.

“It is important to keep this abusive tactic in mind, not only when dealing with patients but also with fellow physicians and health care professionals, and check in to see if everything is okay – especially if they seem particularly stressed out or distant,” Dr. Watson recommended.

Trust your clinical gut

How can you tell if your patients might be experiencing abuse when you’re not seeing them in person?

Pay attention to subtle signals and “trust your clinical gut when something doesn’t feel right,” Ms. Nyachogo advised.

If a patient’s demeanor is jittery or anxious or if someone next to him or her is answering all the questions or interrupting the visit, these could be red flags.

Dr. Cronholm added that telemedicine visits offer a “rare window into a patient’s home life that would not be available in an office visit.” For example, a house in disarray, the presence of broken objects, or the presence of another person hovering in the background suggests the need for further exploration.

The starting point of screening and intervention is to recognize that any domestic violence situation is potentially explosive. “The main thing for all providers to keep in mind is ‘first, do no harm,’ ” Ms. Nyachogo emphasized.

“Our agency has been working for years with medical professionals in how to screen and connect folks with help most effectively and safely, and – although the specific situations posed by COVID are new – the overall approach is the same, which is to proceed with caution in how you approach the subject and how you make referrals,” she said.

Begin by asking if it is a convenient time to talk.

“This question takes the onus off the patient, who may not know how to communicate that she has no privacy or is in the middle of an argument,” explained Elsa Swenson, program manager of Home Free community program, which serves individuals experiencing domestic violence. The program is part of Minnesota-based Missions Inc. Programs, which serves those experiencing domestic abuse and chemical dependency.

If the patient indicates that it isn’t a convenient time to talk, find out when would be a better time. “This might be difficult for busy physicians and may not be what they’re accustomed to when calling a patient at home, but the patient’s circumstances are unknown to you, so it’s essential to organize around their ability to talk,” Ms. Swenson noted.
 

‘Are you alone?’

Another important piece of information is whether the patient has privacy – which can be tricky if the abuser is standing right there.

“You don’t want to tip the abuser off to your concerns, so you need to frame the question in a neutral way,” Dr. Watson advised.

For example, you might say that HIPAA laws require that you conduct the consultation with no one else present, and find out if there is a location in the house where the patient can have privacy.

It might be easier to talk on the phone than via video, suggests Florence Remes, a New Jersey–based licensed social worker who specializes in domestic violence. Going into another room and playing music or turning on the television might make it less obvious that a call is taking place, and the abuser would be less likely to overhear the caller’s conversation.

Dr. Watson suggested that questions about abuse might be included with other questions and asked in a simple yes/no format. “I’d like to ask you some standard questions I’m asking everyone during the pandemic. Do you have a cough or fever? Do you have any other physical symptoms? Do you have access to hand sanitizer? How is your sleep? Are you experiencing stress? Do you feel safe at home?”

The abuser, if present, will only hear the patient’s “yes” or “no” without knowing the question. If the patient indicates that she is being abused but is unable to talk, a later time can be arranged to further explore the issue.
 

Technology is a double-edged sword

Modern technologies have been a great boon to patients and physicians during this time of social distancing, allowing ongoing contact and health care when it would not otherwise have been possible. On the other hand, technology is fraught with potential dangers that can jeopardize the patient’s safety and compromise privacy.

Ms. Remes recounted the story of “Susan,” a client with whom she had been conducting teletherapy visits using an approved HIPAA-compliant telemedicine forum. Susan was working from home because of shelter-in-place restrictions. Her husband had been abusive, and Susan was concerned he might be “sabotaging” the household’s WiFi to isolate her from outside sources of support.

At the recommendation of Ms. Remes, Susan continued sessions either via phone calls or by using the WhatsApp program on her cellphone. Many of the requirements governing HIPAA privacy regulations have been temporarily relaxed, and clinicians can use non–encrypted forms of transmission, such as FaceTime, WhatsApp, or Skype, if no other platform is available.

But even cellphones have risks, Dr. Warshaw noted. The patient’s abuser might track texts or look at call logs – especially on unsecured platforms. It’s advisable to ask patients about who has access to their phone and computer and discuss ways to increase security.
 

Follow the patient’s lead

Proceed slowly and start with nonthreatening questions, Ms. Palardy advised. “I notice you have some injuries; can you tell me how you got them? Did someone hurt you? What does your relationship look like when you argue? Is there anything that makes you feel uncomfortable or unsafe?”

Emphasizing that you are asking these questions because of care and concern is reassuring and helps patients to feel they are not alone, Ms. Nyachogo pointed out.

“As your doctor, I’m worried about your health and (if relevant) your children’s safety. I can help connect you with counseling and support, legal resources, and a shelter, and everything is free and confidential. Would you be interested?” she said.

If the client acknowledges abuse, “follow their lead, but don’t push too hard,” Ms. Nyachogo warned.

“It is the client’s choice whether or not to take action,” she noted. “I’ve met survivors who said that it wasn’t until a doctor or nurse expressed concern about bruises that it even occurred to them that they were being abused. Some lied to the doctor about how they got hurt – but the question planted a seed, even though it might have taken years to follow up on the referral,” she said.
 

What if the patient doesn’t want to get help?

If a patient is not ready to seek help, you can create a home-safety plan. This might include setting follow-up times. If you don’t hear from him or her, you should then call the police. Or you might create a “code word,” such as “apple pie.” If the patient uses that word during a session, you know her life is in danger, Ms. Remes suggested.

Providing written information about how to get help is important but can be problematic if the abuser finds it.

Ms. Nyachogo recommends e-mailing follow-up materials that cover a variety of topics, such as keeping safe during the COVID-19 pandemic, relaxation, healthy eating, getting exercise while homebound, activities for children, and suggestions for hotlines and other resources if one is feeling suicidal or unsafe.

“If you present these as your ‘standard’ follow-up materials, the abuser is less likely to become suspicious,” Ms. Nyachogo noted.
 

Resources are available during COVID-19

All of the experts emphasize that resources for victims of domestic violence remain available during the COVID-19 pandemic, although some shelters may be operating at reduced capacity. Some agencies are finding alternatives to group shelters, such as hotels or Airbnb, which carry less risk of catching COVID-19.

Referring a patient to domestic violence resources is a delicate process. “You don’t want referring the patient for help to further endanger their life,” Ms. Nyachogo said.

The more you can take the burden off the patient, the better. If she is interested in getting help, you can call a domestic violence counselor or advocate while she is on the phone.

“This type of ‘warm handoff’ is what Tonya’s physician did,” Ms. Palardy recounted.

A warm handoff requires that physicians be familiar with domestic violence resources, Dr. Warshaw emphasized.

“Don’t wait until you are working with someone who needs help to find out where to refer them. Take the time to proactively research local agencies specializing in domestic violence and have their phone numbers on hand, so you can offer resources immediately if the person is interested,” she advised. The National Domestic Violence Hotline can also assist with safety planning and access to local resources.
 

‘Thinking on your feet’ critical for physicians

Addressing domestic violence during this unprecedented time requires “thinking on your feet” about novel forms of detection and intervention, Dr. Watson said. This involves a combination of clinical acumen, creativity, and finely honed intuition.

Ms. Nyachogo added, “Keeping an eye on domestic violence can feel like an extra burden, but don’t forget that it is lifesaving work.”
 

Resources

National Domestic Violence Hotline

• 800-799-SAFE (7233)
• The patient can also text LOVEIS to 22522.

National Center on Domestic Violence, Trauma, and Mental Health

• Provides resources for health care, mental health, and substance use treatment and recovery support providers on responding to domestic violence and other trauma.
• Provides resources for professionals and patients regarding access to substance use and mental health care during the COVID-1 pandemic.
• Provides support for parents, caregivers, and children during the pandemic.
• Provides resources for advocates serving families affected by domestic violence.

U.S. Department of Justice

• A state-by-state guide to local resources

Children’s Hospital of Philadelphia Research Institute

STOP Intimate Partner Violence (IPV)
 

New Jersey Coalition for Domestic Violence

American Bar Association COVID-19 resources for communities

Crisis Text Line

• Text HOME to 741741.

National Network to End Domestic Violence (NNEDV) COVID-19 Technology Safety

A version of this article originally appeared on Medscape.com.