SAN FRANCISCO – Efficacy and safety of a novel oral chemotherapy in patients with heavily pretreated metastatic gastric cancer are largely unaffected by prior gastrectomy, suggests a preplanned subgroup analysis of the global phase 3 randomized controlled TAGS trial. Results were reported at the 2019 GI Cancers Symposium.

Susan London/MDEdge News

“The standard of care for early-stage gastric cancer is surgery, which is the only potentially curative treatment,” noted lead investigator David H. Ilson, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York. “Forty percent of patients with metastatic disease have had a history of previous gastrectomy.”

The TAGS trial assessed efficacy of combined trifluridine and tipiracil (Lonsurf) among 507 patients with metastatic gastric or gastroesophageal junction cancer who had received at least two prior chemotherapy regimens. (This combination chemotherapy is currently approved in the United States as later-line therapy for metastatic colorectal cancer.)

Compared with placebo, trifluridine/tipiracil prolonged overall survival by 2.6 months in the subgroup who had previously undergone gastrectomy, a benefit slightly greater than the 2.1 months previously reported for the entire trial population (Lancet Oncol. 2018;19:1437-48). And although the gastrectomy subgroup experienced more grade 3 or 4 adverse events, they were not more likely to stop treatment because of toxicity.

“The data from this analysis reinforce the benefit for trifluridine/tipiracil as prolonging survival versus placebo, and this is regardless of prior gastrectomy,” Dr. Ilson summarized. “Hematologic adverse events, such as neutropenia and leukopenia, may have been somewhat more frequent among the trifluridine/tipiracil–treated patients with gastrectomy than in the overall population, but this did not result in more treatment discontinuations. Exposure to the drug was similar between patients with gastrectomy and those in the overall population.”

“Trifluridine/tipiracil is an effective treatment option with a manageable toxicity profile for patients with metastatic gastric cancer, regardless of prior gastrectomy status,” he concluded.
 

Still fit for treatment

The disconnect between toxicity and treatment discontinuation seen in the TAGS trial is not new, according to invited discussant Martine Extermann, MD, PhD, leader of the Senior Adult Oncology Program at the Moffitt Cancer Center in Tampa. Previous data among geriatric cancer patients have similarly shown that, despite substantial chemotherapy toxicity, by and large, there are only modest effects on health-related quality of life, performance status, and instrumental activities of daily living, she noted.

“The CTCAE [Common Terminology Criteria for Adverse Events] toxicity differences do not always translate into functional impact and treatment cessation. So this is only part of the picture. It’s a convenient part. It’s easily measurable. It’s well acknowledged as a measurement of side effects. But it does not tell the whole story. Quality of life and functional status add to the picture,” Dr. Extermann elaborated. “What the TAGS study is telling us is, despite a gastrectomy, these patients can be treated as a third-line treatment population for gastric cancer, which is not necessarily obvious to every oncologist.”

At the same time, she added that it would be helpful to have nutritional data on the study patients – and on all patients in similar trials, for that matter – because nutritional status is one of the components of the CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) score used to predict chemotherapy toxicity in older adults.

“I would support that [trifluridine/tipiracil] is an effective third-line chemotherapy in gastric cancer patients with or without prior gastrectomy, and this can be given safely,” Dr. Extermann concluded.
 

Study details

Patients in TAGS were randomized 2:1 to trifluridine/tipiracil (formerly TAS-102) or placebo, each added to best supportive care. (Trifluridine is a novel oral thymidine analogue, and tipiracil prevents trifluridine degradation.) Overall, 44% had undergone gastrectomy before entering the trial.

In the entire trial population, overall survival was 5.7 months with trifluridine/tipiracil and 3.6 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.56-0.85; P = .0006), as previously reported.

Among the subgroup who had undergone prior gastrectomy, overall survival was 6.0 months with trifluridine/tipiracil and 3.4 months with placebo (HR, 0.57; 95% CI, 0.41-0.79), Dr. Ilson reported at the symposium, which is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. The combination also netted better progression-free survival (2.2 vs. 1.8 months; HR, 0.48; 95% CI, 0.35-0.65). “These data mirror the data seen in the overall treatment population,” he commented.

In a multivariate analysis including all prespecified factors, prior gastrectomy was neither prognostic nor predictive. Moreover, the treatment effect size remained the same after adjustment for potential prognostic factors.

Exposure to trifluridine/tipiracil was similar for the gastrectomy subgroup and the entire trial population in terms of relative dose intensity, median number of cycles, and treatment duration.

The rate of grade 3 or 4 treatment-related adverse events with trifluridine/tipiracil in the gastrectomy subgroup, 64%, was higher than that in the entire trial population, 53%, but the rate of discontinuation because of any-grade adverse events was similar, at 10% and 13%, respectively.

The difference in grade 3 or 4 adverse events between the gastrectomy subgroup and the entire trial population was mainly driven by higher rates of neutropenia (44% vs. 34%) and leukopenia (14% vs. 9%) in the former.

Dr. Ilson disclosed that he has a consulting role with Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Merck, Pieris, Roche/Genentech, and Taiho and that he receives research support from Taiho. The study was funded by Taiho Oncology and Taiho Pharmaceutical.

SOURCE: Ilson DH et al. 2019 GI Cancers Symposium, Abstract 3.

SAN FRANCISCO – Efficacy and safety of a novel oral chemotherapy in patients with heavily pretreated metastatic gastric cancer are largely unaffected by prior gastrectomy, suggests a preplanned subgroup analysis of the global phase 3 randomized controlled TAGS trial. Results were reported at the 2019 GI Cancers Symposium.

Susan London/MDEdge News

“The standard of care for early-stage gastric cancer is surgery, which is the only potentially curative treatment,” noted lead investigator David H. Ilson, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York. “Forty percent of patients with metastatic disease have had a history of previous gastrectomy.”

The TAGS trial assessed efficacy of combined trifluridine and tipiracil (Lonsurf) among 507 patients with metastatic gastric or gastroesophageal junction cancer who had received at least two prior chemotherapy regimens. (This combination chemotherapy is currently approved in the United States as later-line therapy for metastatic colorectal cancer.)

Compared with placebo, trifluridine/tipiracil prolonged overall survival by 2.6 months in the subgroup who had previously undergone gastrectomy, a benefit slightly greater than the 2.1 months previously reported for the entire trial population (Lancet Oncol. 2018;19:1437-48). And although the gastrectomy subgroup experienced more grade 3 or 4 adverse events, they were not more likely to stop treatment because of toxicity.

“The data from this analysis reinforce the benefit for trifluridine/tipiracil as prolonging survival versus placebo, and this is regardless of prior gastrectomy,” Dr. Ilson summarized. “Hematologic adverse events, such as neutropenia and leukopenia, may have been somewhat more frequent among the trifluridine/tipiracil–treated patients with gastrectomy than in the overall population, but this did not result in more treatment discontinuations. Exposure to the drug was similar between patients with gastrectomy and those in the overall population.”

“Trifluridine/tipiracil is an effective treatment option with a manageable toxicity profile for patients with metastatic gastric cancer, regardless of prior gastrectomy status,” he concluded.
 

Still fit for treatment

The disconnect between toxicity and treatment discontinuation seen in the TAGS trial is not new, according to invited discussant Martine Extermann, MD, PhD, leader of the Senior Adult Oncology Program at the Moffitt Cancer Center in Tampa. Previous data among geriatric cancer patients have similarly shown that, despite substantial chemotherapy toxicity, by and large, there are only modest effects on health-related quality of life, performance status, and instrumental activities of daily living, she noted.

“The CTCAE [Common Terminology Criteria for Adverse Events] toxicity differences do not always translate into functional impact and treatment cessation. So this is only part of the picture. It’s a convenient part. It’s easily measurable. It’s well acknowledged as a measurement of side effects. But it does not tell the whole story. Quality of life and functional status add to the picture,” Dr. Extermann elaborated. “What the TAGS study is telling us is, despite a gastrectomy, these patients can be treated as a third-line treatment population for gastric cancer, which is not necessarily obvious to every oncologist.”

At the same time, she added that it would be helpful to have nutritional data on the study patients – and on all patients in similar trials, for that matter – because nutritional status is one of the components of the CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) score used to predict chemotherapy toxicity in older adults.

“I would support that [trifluridine/tipiracil] is an effective third-line chemotherapy in gastric cancer patients with or without prior gastrectomy, and this can be given safely,” Dr. Extermann concluded.
 

Study details

Patients in TAGS were randomized 2:1 to trifluridine/tipiracil (formerly TAS-102) or placebo, each added to best supportive care. (Trifluridine is a novel oral thymidine analogue, and tipiracil prevents trifluridine degradation.) Overall, 44% had undergone gastrectomy before entering the trial.

In the entire trial population, overall survival was 5.7 months with trifluridine/tipiracil and 3.6 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.56-0.85; P = .0006), as previously reported.

Among the subgroup who had undergone prior gastrectomy, overall survival was 6.0 months with trifluridine/tipiracil and 3.4 months with placebo (HR, 0.57; 95% CI, 0.41-0.79), Dr. Ilson reported at the symposium, which is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. The combination also netted better progression-free survival (2.2 vs. 1.8 months; HR, 0.48; 95% CI, 0.35-0.65). “These data mirror the data seen in the overall treatment population,” he commented.

In a multivariate analysis including all prespecified factors, prior gastrectomy was neither prognostic nor predictive. Moreover, the treatment effect size remained the same after adjustment for potential prognostic factors.

Exposure to trifluridine/tipiracil was similar for the gastrectomy subgroup and the entire trial population in terms of relative dose intensity, median number of cycles, and treatment duration.

The rate of grade 3 or 4 treatment-related adverse events with trifluridine/tipiracil in the gastrectomy subgroup, 64%, was higher than that in the entire trial population, 53%, but the rate of discontinuation because of any-grade adverse events was similar, at 10% and 13%, respectively.

The difference in grade 3 or 4 adverse events between the gastrectomy subgroup and the entire trial population was mainly driven by higher rates of neutropenia (44% vs. 34%) and leukopenia (14% vs. 9%) in the former.

Dr. Ilson disclosed that he has a consulting role with Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Merck, Pieris, Roche/Genentech, and Taiho and that he receives research support from Taiho. The study was funded by Taiho Oncology and Taiho Pharmaceutical.

SOURCE: Ilson DH et al. 2019 GI Cancers Symposium, Abstract 3.

SAN FRANCISCO – Efficacy and safety of a novel oral chemotherapy in patients with heavily pretreated metastatic gastric cancer are largely unaffected by prior gastrectomy, suggests a preplanned subgroup analysis of the global phase 3 randomized controlled TAGS trial. Results were reported at the 2019 GI Cancers Symposium.

Susan London/MDEdge News

“The standard of care for early-stage gastric cancer is surgery, which is the only potentially curative treatment,” noted lead investigator David H. Ilson, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York. “Forty percent of patients with metastatic disease have had a history of previous gastrectomy.”

The TAGS trial assessed efficacy of combined trifluridine and tipiracil (Lonsurf) among 507 patients with metastatic gastric or gastroesophageal junction cancer who had received at least two prior chemotherapy regimens. (This combination chemotherapy is currently approved in the United States as later-line therapy for metastatic colorectal cancer.)

Compared with placebo, trifluridine/tipiracil prolonged overall survival by 2.6 months in the subgroup who had previously undergone gastrectomy, a benefit slightly greater than the 2.1 months previously reported for the entire trial population (Lancet Oncol. 2018;19:1437-48). And although the gastrectomy subgroup experienced more grade 3 or 4 adverse events, they were not more likely to stop treatment because of toxicity.

“The data from this analysis reinforce the benefit for trifluridine/tipiracil as prolonging survival versus placebo, and this is regardless of prior gastrectomy,” Dr. Ilson summarized. “Hematologic adverse events, such as neutropenia and leukopenia, may have been somewhat more frequent among the trifluridine/tipiracil–treated patients with gastrectomy than in the overall population, but this did not result in more treatment discontinuations. Exposure to the drug was similar between patients with gastrectomy and those in the overall population.”

“Trifluridine/tipiracil is an effective treatment option with a manageable toxicity profile for patients with metastatic gastric cancer, regardless of prior gastrectomy status,” he concluded.
 

Still fit for treatment

The disconnect between toxicity and treatment discontinuation seen in the TAGS trial is not new, according to invited discussant Martine Extermann, MD, PhD, leader of the Senior Adult Oncology Program at the Moffitt Cancer Center in Tampa. Previous data among geriatric cancer patients have similarly shown that, despite substantial chemotherapy toxicity, by and large, there are only modest effects on health-related quality of life, performance status, and instrumental activities of daily living, she noted.

“The CTCAE [Common Terminology Criteria for Adverse Events] toxicity differences do not always translate into functional impact and treatment cessation. So this is only part of the picture. It’s a convenient part. It’s easily measurable. It’s well acknowledged as a measurement of side effects. But it does not tell the whole story. Quality of life and functional status add to the picture,” Dr. Extermann elaborated. “What the TAGS study is telling us is, despite a gastrectomy, these patients can be treated as a third-line treatment population for gastric cancer, which is not necessarily obvious to every oncologist.”

At the same time, she added that it would be helpful to have nutritional data on the study patients – and on all patients in similar trials, for that matter – because nutritional status is one of the components of the CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) score used to predict chemotherapy toxicity in older adults.

“I would support that [trifluridine/tipiracil] is an effective third-line chemotherapy in gastric cancer patients with or without prior gastrectomy, and this can be given safely,” Dr. Extermann concluded.
 

Study details

Patients in TAGS were randomized 2:1 to trifluridine/tipiracil (formerly TAS-102) or placebo, each added to best supportive care. (Trifluridine is a novel oral thymidine analogue, and tipiracil prevents trifluridine degradation.) Overall, 44% had undergone gastrectomy before entering the trial.

In the entire trial population, overall survival was 5.7 months with trifluridine/tipiracil and 3.6 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.56-0.85; P = .0006), as previously reported.

Among the subgroup who had undergone prior gastrectomy, overall survival was 6.0 months with trifluridine/tipiracil and 3.4 months with placebo (HR, 0.57; 95% CI, 0.41-0.79), Dr. Ilson reported at the symposium, which is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. The combination also netted better progression-free survival (2.2 vs. 1.8 months; HR, 0.48; 95% CI, 0.35-0.65). “These data mirror the data seen in the overall treatment population,” he commented.

In a multivariate analysis including all prespecified factors, prior gastrectomy was neither prognostic nor predictive. Moreover, the treatment effect size remained the same after adjustment for potential prognostic factors.

Exposure to trifluridine/tipiracil was similar for the gastrectomy subgroup and the entire trial population in terms of relative dose intensity, median number of cycles, and treatment duration.

The rate of grade 3 or 4 treatment-related adverse events with trifluridine/tipiracil in the gastrectomy subgroup, 64%, was higher than that in the entire trial population, 53%, but the rate of discontinuation because of any-grade adverse events was similar, at 10% and 13%, respectively.

The difference in grade 3 or 4 adverse events between the gastrectomy subgroup and the entire trial population was mainly driven by higher rates of neutropenia (44% vs. 34%) and leukopenia (14% vs. 9%) in the former.

Dr. Ilson disclosed that he has a consulting role with Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Merck, Pieris, Roche/Genentech, and Taiho and that he receives research support from Taiho. The study was funded by Taiho Oncology and Taiho Pharmaceutical.

SOURCE: Ilson DH et al. 2019 GI Cancers Symposium, Abstract 3.

The Food and Drug Administration has granted fast track designation to IPH4102 for the treatment of adults with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies.

IPH4102 is an anti-KIR3DL2 antibody being developed by Innate Pharma as a treatment for T-cell lymphomas.

The FDA’s fast track program is designed to expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs.

The fast track designation for IPH4102 is based on preliminary results from a phase 1 study (NCT02593045) of patients with advanced cutaneous T-cell lymphoma.

Data on 35 Sézary patients in this trial were presented at the 2018 annual meeting of the American Society of Hematology (Blood. 2018;132:684). The patients had a median age of 70 (range, 31-90), and they had received a median of 2 (range, 1-9) prior systemic therapies.


As of Oct. 15, 2018, the overall response rate was 42.9%, with 2 complete responses and 13 partial responses. The median duration of response was 13.8 months, and the median progression-free survival was 11.7 months.

Treatment-related adverse events (AEs) included asthenia (n = 5), lymphopenia (n = 5), fatigue (n = 3), pyrexia (n = 3), arthralgia (n = 2), and diarrhea (n = 1). The only grade 3/4 treatment-related AE was lymphopenia (n = 2).

Four patients experienced six grade 3 or higher AEs that were possibly related to treatment—grade 5 hepatitis (n = 1), grade 4 sepsis (n = 1), grade 3 lymphopenia (n = 3), and grade 3 hypotension (n = 1).

Based on these results, Innate Pharma is planning a phase 2 trial of IPH4102, which is expected to begin in the first half of this year.

jensmith@mdedge.com

The Food and Drug Administration has granted fast track designation to IPH4102 for the treatment of adults with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies.

IPH4102 is an anti-KIR3DL2 antibody being developed by Innate Pharma as a treatment for T-cell lymphomas.

The FDA’s fast track program is designed to expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs.

The fast track designation for IPH4102 is based on preliminary results from a phase 1 study (NCT02593045) of patients with advanced cutaneous T-cell lymphoma.

Data on 35 Sézary patients in this trial were presented at the 2018 annual meeting of the American Society of Hematology (Blood. 2018;132:684). The patients had a median age of 70 (range, 31-90), and they had received a median of 2 (range, 1-9) prior systemic therapies.


As of Oct. 15, 2018, the overall response rate was 42.9%, with 2 complete responses and 13 partial responses. The median duration of response was 13.8 months, and the median progression-free survival was 11.7 months.

Treatment-related adverse events (AEs) included asthenia (n = 5), lymphopenia (n = 5), fatigue (n = 3), pyrexia (n = 3), arthralgia (n = 2), and diarrhea (n = 1). The only grade 3/4 treatment-related AE was lymphopenia (n = 2).

Four patients experienced six grade 3 or higher AEs that were possibly related to treatment—grade 5 hepatitis (n = 1), grade 4 sepsis (n = 1), grade 3 lymphopenia (n = 3), and grade 3 hypotension (n = 1).

Based on these results, Innate Pharma is planning a phase 2 trial of IPH4102, which is expected to begin in the first half of this year.

jensmith@mdedge.com

The Food and Drug Administration has granted fast track designation to IPH4102 for the treatment of adults with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies.

IPH4102 is an anti-KIR3DL2 antibody being developed by Innate Pharma as a treatment for T-cell lymphomas.

The FDA’s fast track program is designed to expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs.

The fast track designation for IPH4102 is based on preliminary results from a phase 1 study (NCT02593045) of patients with advanced cutaneous T-cell lymphoma.

Data on 35 Sézary patients in this trial were presented at the 2018 annual meeting of the American Society of Hematology (Blood. 2018;132:684). The patients had a median age of 70 (range, 31-90), and they had received a median of 2 (range, 1-9) prior systemic therapies.


As of Oct. 15, 2018, the overall response rate was 42.9%, with 2 complete responses and 13 partial responses. The median duration of response was 13.8 months, and the median progression-free survival was 11.7 months.

Treatment-related adverse events (AEs) included asthenia (n = 5), lymphopenia (n = 5), fatigue (n = 3), pyrexia (n = 3), arthralgia (n = 2), and diarrhea (n = 1). The only grade 3/4 treatment-related AE was lymphopenia (n = 2).

Four patients experienced six grade 3 or higher AEs that were possibly related to treatment—grade 5 hepatitis (n = 1), grade 4 sepsis (n = 1), grade 3 lymphopenia (n = 3), and grade 3 hypotension (n = 1).

Based on these results, Innate Pharma is planning a phase 2 trial of IPH4102, which is expected to begin in the first half of this year.

jensmith@mdedge.com

Many adults spend a large part of their time at work—making the workplace an important but underused location for suicide prevention, say CDC researchers who analyzed data on 22,053 suicides in 17 states. The US suicide rate among working adults (aged 16-64 years) rose 34% between 2000 and 2016, from 12.9 to 17.3 per 100,000.

Suicide rates rose in many occupational groups between 2012 and 2015, but identifying the specific role that occupational factors might play in suicide risk is complicated, the researchers say: Both work (eg, little job control and job insecurity) and nonwork (eg, relationship conflict) factors are associated with psychological distress and suicide. And factors such as access to lethal means while on the job play a part as well.

The major occupational group with the highest male suicide rate was Construction and Extraction (from 43.6% in 2012 to 53.2% in 2015. The Arts, Design, Entertainment, Sports, and Media groups had the highest female suicide rate (15.6%, up from 11.7%).

Health Care Support, which ranked twelfth on the 2015 list, actually saw a drop in the numbers of male suicides (19.5/100,000 in 2015, vs 22.1 in 2012). But among women, the numbers rose 31%: from 8.4 per 100,000 to 11.0, making that category third among females. 

With a 13% drop (from 10.3 to 9.0), Health Care Practitioners and Technical (female) moved from fourth to sixth place. For men, the category ranked eighth, with a rate change of 23%, from 20.8 to 25.6 suicide deaths per 100,000.

The researchers say better understanding of how suicides are distributed by occupational group might help inform prevention programs and policies. The CDC recommends a comprehensive approach, including strategies such as:

• Enhancing social connectedness;
• Strengthening state or local economic supports;
• Implementing practices that encourage help-seeking and reduce stigma;
• Providing referrals to mental health and other services; and
• Reducing access to lethal means among people at risk

The CDC also encourages decision makers, such as employers, to create a response plan, should someone in their organization commit suicide.

Many adults spend a large part of their time at work—making the workplace an important but underused location for suicide prevention, say CDC researchers who analyzed data on 22,053 suicides in 17 states. The US suicide rate among working adults (aged 16-64 years) rose 34% between 2000 and 2016, from 12.9 to 17.3 per 100,000.

Suicide rates rose in many occupational groups between 2012 and 2015, but identifying the specific role that occupational factors might play in suicide risk is complicated, the researchers say: Both work (eg, little job control and job insecurity) and nonwork (eg, relationship conflict) factors are associated with psychological distress and suicide. And factors such as access to lethal means while on the job play a part as well.

The major occupational group with the highest male suicide rate was Construction and Extraction (from 43.6% in 2012 to 53.2% in 2015. The Arts, Design, Entertainment, Sports, and Media groups had the highest female suicide rate (15.6%, up from 11.7%).

Health Care Support, which ranked twelfth on the 2015 list, actually saw a drop in the numbers of male suicides (19.5/100,000 in 2015, vs 22.1 in 2012). But among women, the numbers rose 31%: from 8.4 per 100,000 to 11.0, making that category third among females. 

With a 13% drop (from 10.3 to 9.0), Health Care Practitioners and Technical (female) moved from fourth to sixth place. For men, the category ranked eighth, with a rate change of 23%, from 20.8 to 25.6 suicide deaths per 100,000.

The researchers say better understanding of how suicides are distributed by occupational group might help inform prevention programs and policies. The CDC recommends a comprehensive approach, including strategies such as:

• Enhancing social connectedness;
• Strengthening state or local economic supports;
• Implementing practices that encourage help-seeking and reduce stigma;
• Providing referrals to mental health and other services; and
• Reducing access to lethal means among people at risk

The CDC also encourages decision makers, such as employers, to create a response plan, should someone in their organization commit suicide.

Many adults spend a large part of their time at work—making the workplace an important but underused location for suicide prevention, say CDC researchers who analyzed data on 22,053 suicides in 17 states. The US suicide rate among working adults (aged 16-64 years) rose 34% between 2000 and 2016, from 12.9 to 17.3 per 100,000.

Suicide rates rose in many occupational groups between 2012 and 2015, but identifying the specific role that occupational factors might play in suicide risk is complicated, the researchers say: Both work (eg, little job control and job insecurity) and nonwork (eg, relationship conflict) factors are associated with psychological distress and suicide. And factors such as access to lethal means while on the job play a part as well.

The major occupational group with the highest male suicide rate was Construction and Extraction (from 43.6% in 2012 to 53.2% in 2015. The Arts, Design, Entertainment, Sports, and Media groups had the highest female suicide rate (15.6%, up from 11.7%).

Health Care Support, which ranked twelfth on the 2015 list, actually saw a drop in the numbers of male suicides (19.5/100,000 in 2015, vs 22.1 in 2012). But among women, the numbers rose 31%: from 8.4 per 100,000 to 11.0, making that category third among females. 

With a 13% drop (from 10.3 to 9.0), Health Care Practitioners and Technical (female) moved from fourth to sixth place. For men, the category ranked eighth, with a rate change of 23%, from 20.8 to 25.6 suicide deaths per 100,000.

The researchers say better understanding of how suicides are distributed by occupational group might help inform prevention programs and policies. The CDC recommends a comprehensive approach, including strategies such as:

• Enhancing social connectedness;
• Strengthening state or local economic supports;
• Implementing practices that encourage help-seeking and reduce stigma;
• Providing referrals to mental health and other services; and
• Reducing access to lethal means among people at risk

The CDC also encourages decision makers, such as employers, to create a response plan, should someone in their organization commit suicide.

The balance between medical research and the pharmaceutical world has always been unsettling. The recent spate of articles in the press reporting the large payments by industry to a number of highly paid medical staff of the Memorial Sloan Kettering Cancer Institute in New York has raised again the continuing issue around that relationship.

When large sums of money are paid to medical leaders for serving on advisory boards, it is reasonable to question whom are they representing: industry or medical science. These relationships are not limited to cancer hospitals and can be presumed to pertain to cardiology and other specialties. One need only look at the disclosure statements of contemporary published articles to become aware of the entanglement of science and industry.

There is little question that both industry and science need to interact to focus direct resources to appropriate targets. No one is better able to do that than well informed scientists working in their disease fields. Industry needs scientific input and scientists need the financial resources of industry. I have been able to see that relationship play out to achieve major impacts on heart disease. But corporate decisions also can be driven by market forces and not altruism. Drug and device research has been redirected or stopped as a result of decisions made by sales forces. At other times, drugs that have great potential in the laboratory have been shelved because of a lack of scientific leadership.


So where is the moral and ethical balance? Published disclosures by authors is not much more than a catharsis in the process where action is required. Medical advisory boards are critical for successful drug and device development. That exchange is crucial to move medical science forward, but the large sums of money raise appropriate questions of what is driving the discussion.

At a more grass roots level, the financial role of investigators and hospitals in clinical trials has raised some concern. Traditionally, the institution and investigators have been reimbursed for their time and expense for recruiting and following patients. Patients, of course, are not reimbursed in clinical trials but are placed at considerable risk of an uncertain result. The reimbursements for marginal expenses seem to be appropriate. More recently, payments to physicians and hospitals have been made at current fee schedules for the implantation of a variety of new devices such as pacemakers and valves. In addition, both physicians and hospitals have invested in the financial success of these clinical trials clouding over their altruistic goals. It has been an incentive for recruiting patients for trials and has been a source of considerable revenue both for the physicians and the institution, without informing the patients of their financial relationship to industry. The image of the patient being placed at risk for the success of a clinical trial of a device by doctors and hospitals seeking financial gain is more than a little disturbing.

There is a lot of money sloshing around in the health care world that has the potential to lead to ethical uncertainty. It is the physician’s responsibility to build up ethical barriers to prevent us from slipping into that morass.

Dr. Goldstein is professor of medicine at Wayne State University and the division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit.

The balance between medical research and the pharmaceutical world has always been unsettling. The recent spate of articles in the press reporting the large payments by industry to a number of highly paid medical staff of the Memorial Sloan Kettering Cancer Institute in New York has raised again the continuing issue around that relationship.

When large sums of money are paid to medical leaders for serving on advisory boards, it is reasonable to question whom are they representing: industry or medical science. These relationships are not limited to cancer hospitals and can be presumed to pertain to cardiology and other specialties. One need only look at the disclosure statements of contemporary published articles to become aware of the entanglement of science and industry.

There is little question that both industry and science need to interact to focus direct resources to appropriate targets. No one is better able to do that than well informed scientists working in their disease fields. Industry needs scientific input and scientists need the financial resources of industry. I have been able to see that relationship play out to achieve major impacts on heart disease. But corporate decisions also can be driven by market forces and not altruism. Drug and device research has been redirected or stopped as a result of decisions made by sales forces. At other times, drugs that have great potential in the laboratory have been shelved because of a lack of scientific leadership.


So where is the moral and ethical balance? Published disclosures by authors is not much more than a catharsis in the process where action is required. Medical advisory boards are critical for successful drug and device development. That exchange is crucial to move medical science forward, but the large sums of money raise appropriate questions of what is driving the discussion.

At a more grass roots level, the financial role of investigators and hospitals in clinical trials has raised some concern. Traditionally, the institution and investigators have been reimbursed for their time and expense for recruiting and following patients. Patients, of course, are not reimbursed in clinical trials but are placed at considerable risk of an uncertain result. The reimbursements for marginal expenses seem to be appropriate. More recently, payments to physicians and hospitals have been made at current fee schedules for the implantation of a variety of new devices such as pacemakers and valves. In addition, both physicians and hospitals have invested in the financial success of these clinical trials clouding over their altruistic goals. It has been an incentive for recruiting patients for trials and has been a source of considerable revenue both for the physicians and the institution, without informing the patients of their financial relationship to industry. The image of the patient being placed at risk for the success of a clinical trial of a device by doctors and hospitals seeking financial gain is more than a little disturbing.

There is a lot of money sloshing around in the health care world that has the potential to lead to ethical uncertainty. It is the physician’s responsibility to build up ethical barriers to prevent us from slipping into that morass.

Dr. Goldstein is professor of medicine at Wayne State University and the division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit.

The balance between medical research and the pharmaceutical world has always been unsettling. The recent spate of articles in the press reporting the large payments by industry to a number of highly paid medical staff of the Memorial Sloan Kettering Cancer Institute in New York has raised again the continuing issue around that relationship.

When large sums of money are paid to medical leaders for serving on advisory boards, it is reasonable to question whom are they representing: industry or medical science. These relationships are not limited to cancer hospitals and can be presumed to pertain to cardiology and other specialties. One need only look at the disclosure statements of contemporary published articles to become aware of the entanglement of science and industry.

There is little question that both industry and science need to interact to focus direct resources to appropriate targets. No one is better able to do that than well informed scientists working in their disease fields. Industry needs scientific input and scientists need the financial resources of industry. I have been able to see that relationship play out to achieve major impacts on heart disease. But corporate decisions also can be driven by market forces and not altruism. Drug and device research has been redirected or stopped as a result of decisions made by sales forces. At other times, drugs that have great potential in the laboratory have been shelved because of a lack of scientific leadership.


So where is the moral and ethical balance? Published disclosures by authors is not much more than a catharsis in the process where action is required. Medical advisory boards are critical for successful drug and device development. That exchange is crucial to move medical science forward, but the large sums of money raise appropriate questions of what is driving the discussion.

At a more grass roots level, the financial role of investigators and hospitals in clinical trials has raised some concern. Traditionally, the institution and investigators have been reimbursed for their time and expense for recruiting and following patients. Patients, of course, are not reimbursed in clinical trials but are placed at considerable risk of an uncertain result. The reimbursements for marginal expenses seem to be appropriate. More recently, payments to physicians and hospitals have been made at current fee schedules for the implantation of a variety of new devices such as pacemakers and valves. In addition, both physicians and hospitals have invested in the financial success of these clinical trials clouding over their altruistic goals. It has been an incentive for recruiting patients for trials and has been a source of considerable revenue both for the physicians and the institution, without informing the patients of their financial relationship to industry. The image of the patient being placed at risk for the success of a clinical trial of a device by doctors and hospitals seeking financial gain is more than a little disturbing.

There is a lot of money sloshing around in the health care world that has the potential to lead to ethical uncertainty. It is the physician’s responsibility to build up ethical barriers to prevent us from slipping into that morass.

Dr. Goldstein is professor of medicine at Wayne State University and the division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit.

Jonathan Meyer, MD, notes that TD has been the bane of the psychiatrist’s existence for the better part of a half century. In this Masterclass edition from the 2018 AACP Encore meeting in Las Vegas, Dr. Meyer talks about this movement disorder and analyzes how psychiatrists should approach treatment today.

Amazon
Apple Podcasts
Google Podcasts
Spotify


 

Jonathan Meyer, MD, notes that TD has been the bane of the psychiatrist’s existence for the better part of a half century. In this Masterclass edition from the 2018 AACP Encore meeting in Las Vegas, Dr. Meyer talks about this movement disorder and analyzes how psychiatrists should approach treatment today.

Amazon
Apple Podcasts
Google Podcasts
Spotify


 

Jonathan Meyer, MD, notes that TD has been the bane of the psychiatrist’s existence for the better part of a half century. In this Masterclass edition from the 2018 AACP Encore meeting in Las Vegas, Dr. Meyer talks about this movement disorder and analyzes how psychiatrists should approach treatment today.

Amazon
Apple Podcasts
Google Podcasts
Spotify


 

Physicians who are also mothers have a higher risk of burnout as well as mood and anxiety disorders if they are also caring for someone with an illness or disability at home. Also today, what one neurologist refuses to accept in his office, flu activity increases after 2 weeks of declines, and when sweaty palms are really primary hyperhidrosis.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Physicians who are also mothers have a higher risk of burnout as well as mood and anxiety disorders if they are also caring for someone with an illness or disability at home. Also today, what one neurologist refuses to accept in his office, flu activity increases after 2 weeks of declines, and when sweaty palms are really primary hyperhidrosis.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Physicians who are also mothers have a higher risk of burnout as well as mood and anxiety disorders if they are also caring for someone with an illness or disability at home. Also today, what one neurologist refuses to accept in his office, flu activity increases after 2 weeks of declines, and when sweaty palms are really primary hyperhidrosis.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

SAN DIEGO – A small study of infants with severe hemophilia A revealed that there are four distinct patient subgroups based on their unique antibody signatures.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

Bagirath Gangadharan, PhD, and his colleagues reported the results of HIPS, the Hemophilia Inhibitor Previously Untreated Patient Study, in a poster at the annual meeting of the American Society of Hematology.

The findings included data on 23 infants who had a baseline Factor VIII coagulant activity of less than 0.01 IU/mL at enrollment in the study. All patients received a single type of recombinant FVIII replacement therapy (Advate by Baxalta) with the dose, frequency, and regimen at the discretion of the treating physician.

Patients with prior exposure to clotting factor concentrates or blood products, another clinically significant chronic disease, and those participating in another investigational drug study were excluded.

The researchers discovered that patients fell into four distinct subgroups based on their antibody characteristics after 50 days’ exposure to FVIII infusions:

• Subgroup one, which included seven patients, had no detectable FVIII-specific antibodies and no FVIII inhibitors.
• Subgroup two – also made up of seven patients – had FVIII-specific IgG1, no detectable IgG class–switched antibodies, and no FVIII inhibitors.
• The third subgroup included just two patients. These patients had FVIII-specific IgG1, no detectable IgG class–switched antibodies, but low-titer FVIII inhibitors.
• The final subgroup, which had seven patients, had FVIII-specific IgG1, high-affinity IgG class–switched antibodies (IgG3, IgG4, and IgG2), and FVIII inhibitors.

The researchers concluded that high-affinity FVIII-specific class-switched antibodies precede clinical FVIII inhibitor detection, adding to the evidence of their “potential role as suitable predictive biomarkers for inhibitor development.”

The study is funded by Baxalta, a part of Shire. Dr. Gangadharan is employed by Shire and other authors reported financial disclosures related to the study sponsor.

mschneider@mdedge.com

SOURCE: Gangadharan B et al. ASH 2018, Poster 3774.

SAN DIEGO – A small study of infants with severe hemophilia A revealed that there are four distinct patient subgroups based on their unique antibody signatures.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

Bagirath Gangadharan, PhD, and his colleagues reported the results of HIPS, the Hemophilia Inhibitor Previously Untreated Patient Study, in a poster at the annual meeting of the American Society of Hematology.

The findings included data on 23 infants who had a baseline Factor VIII coagulant activity of less than 0.01 IU/mL at enrollment in the study. All patients received a single type of recombinant FVIII replacement therapy (Advate by Baxalta) with the dose, frequency, and regimen at the discretion of the treating physician.

Patients with prior exposure to clotting factor concentrates or blood products, another clinically significant chronic disease, and those participating in another investigational drug study were excluded.

The researchers discovered that patients fell into four distinct subgroups based on their antibody characteristics after 50 days’ exposure to FVIII infusions:

• Subgroup one, which included seven patients, had no detectable FVIII-specific antibodies and no FVIII inhibitors.
• Subgroup two – also made up of seven patients – had FVIII-specific IgG1, no detectable IgG class–switched antibodies, and no FVIII inhibitors.
• The third subgroup included just two patients. These patients had FVIII-specific IgG1, no detectable IgG class–switched antibodies, but low-titer FVIII inhibitors.
• The final subgroup, which had seven patients, had FVIII-specific IgG1, high-affinity IgG class–switched antibodies (IgG3, IgG4, and IgG2), and FVIII inhibitors.

The researchers concluded that high-affinity FVIII-specific class-switched antibodies precede clinical FVIII inhibitor detection, adding to the evidence of their “potential role as suitable predictive biomarkers for inhibitor development.”

The study is funded by Baxalta, a part of Shire. Dr. Gangadharan is employed by Shire and other authors reported financial disclosures related to the study sponsor.

mschneider@mdedge.com

SOURCE: Gangadharan B et al. ASH 2018, Poster 3774.

SAN DIEGO – A small study of infants with severe hemophilia A revealed that there are four distinct patient subgroups based on their unique antibody signatures.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

Bagirath Gangadharan, PhD, and his colleagues reported the results of HIPS, the Hemophilia Inhibitor Previously Untreated Patient Study, in a poster at the annual meeting of the American Society of Hematology.

The findings included data on 23 infants who had a baseline Factor VIII coagulant activity of less than 0.01 IU/mL at enrollment in the study. All patients received a single type of recombinant FVIII replacement therapy (Advate by Baxalta) with the dose, frequency, and regimen at the discretion of the treating physician.

Patients with prior exposure to clotting factor concentrates or blood products, another clinically significant chronic disease, and those participating in another investigational drug study were excluded.

The researchers discovered that patients fell into four distinct subgroups based on their antibody characteristics after 50 days’ exposure to FVIII infusions:

• Subgroup one, which included seven patients, had no detectable FVIII-specific antibodies and no FVIII inhibitors.
• Subgroup two – also made up of seven patients – had FVIII-specific IgG1, no detectable IgG class–switched antibodies, and no FVIII inhibitors.
• The third subgroup included just two patients. These patients had FVIII-specific IgG1, no detectable IgG class–switched antibodies, but low-titer FVIII inhibitors.
• The final subgroup, which had seven patients, had FVIII-specific IgG1, high-affinity IgG class–switched antibodies (IgG3, IgG4, and IgG2), and FVIII inhibitors.

The researchers concluded that high-affinity FVIII-specific class-switched antibodies precede clinical FVIII inhibitor detection, adding to the evidence of their “potential role as suitable predictive biomarkers for inhibitor development.”

The study is funded by Baxalta, a part of Shire. Dr. Gangadharan is employed by Shire and other authors reported financial disclosures related to the study sponsor.

mschneider@mdedge.com

SOURCE: Gangadharan B et al. ASH 2018, Poster 3774.

Recent findings, new classification criteria and treatment guidelines, and concerted efforts by various organizations to provide educational resources are among a number of factors improving the outlook for patients with primary Sjögren’s syndrome, according to Judith James, MD, PhD.

Additionally, the number of studies of primary Sjögren’s syndrome (pSS) is increasing, albeit slowly, and ongoing studies of biologics are showing promise, Dr. James said during a clinical update at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
 

Classification criteria

The ACR in conjunction with the European League Against Rheumatism (EULAR) published new criteria for pSS classification in 2016 based on the available evidence and expert consensus. Inclusion criteria include daily, persistent, troublesome dry eyes for more than 3 months, recurrent sensation of sand or gravel in the eyes, use of tear substitutes more than three times each day, frequent drinking of liquids to aid in swallowing dry food, or at least one EULAR Sjögren’s syndrome disease activity index (ESSDAI) domain with a positive item. Exclusion criteria include prior head and neck radiation treatment, polymerase chain reaction–confirmed active hepatitis C infection, AIDS, sarcoidosis, amyloidosis, graft-versus-host disease, or IgG4-related disease, said Dr. James, professor and chair of the arthritis and clinical immunology research program at the University of Oklahoma, Oklahoma City (Arthritis Rheumatol. Jan 2017;69[1]:35-45).

• A score of 4 or higher in patients who meet the inclusion criteria and do not have any of the exclusion criteria leads to classification with pSS, based on the following findings:
• Labial salivary gland with focal lymphocytic sialadenitis and focus score of at least 1 foci/4 mm² (weight/score = 3).
• Anti-SSA/Ro-positivity (weight/score = 3).
• Ocular Staining Score of at least 5, or van Bijsterveld score of at least 4, in at least one eye (weight/score = 1).
• Schirmer’s test of no more than 5 mm/5 min in at least one eye (weight/score = 1).
• Unstimulated whole saliva flow rate of no more than 0.1 mL/min (weight/score = 1).

Clinical pearls for detection and management

In Dr. James’ experience, the three symptoms (taken together) with the highest predictive value for diagnosing pSS are dry mouth, sore mouth/tongue, and dry eyes. About 25% of Sjögren’s patients may have no detectable salivary flow, she said.

Dry, cracked skin that can lead to secondary infections is another common issue affecting about 55% of patients.

“So we always have to talk to our Sjögren’s patients about skin,” she said. “We also have recurrent sinusitis, chronic cough, dyspepsia, constipation, and other symptoms.”

Concurrent autoimmune diseases are another concern in Sjögren’s patients, she said. One to particularly keep in mind, in addition to lupus and rheumatoid arthritis, is autoimmune thyroid disease.

Data suggest that up to 45% of Sjögren’s patients have thyroid dysfunction, and if you look at just those with autoimmune thyroiditis, their risk of Sjögren’s is increased 10-fold vs. those without autoimmune thyroiditis, she said.

Other conditions to keep in mind when it comes to diagnosing and managing patients, as has been shown in numerous studies over the years, include Raynaud’s phenomenon, which affects at least 13% of patients, and subclinical muscle inflammation, which affects more than 50% of patients, Dr. James said.

“Depression ... as well as anxiety, is quite common in Sjögren’s patients, and fatigue is profound,” she added, noting that fatigue is “the No. 1 issue” for many patients.

Another area of particular concern in Sjögren’s is the increased risk of lymphoma, she said.

Studies show varying rates of lymphoma in Sjögren’s, with one suggesting a 44-fold increased risk, but this is likely only among those at very high risk. Other studies suggest the increase is risk overall is in the range of 4- to 10-fold, she said.

Mortality in Sjögren’s patients

A 2015 study by Soledad Retamozo et al. showed that the presence of cryoglobulinemic vasculitis (CV) at diagnosis is associated with increased mortality risk.

Of 515 consecutive pSS patients with a mean follow-up of 110 months, 65 (12%) had cryoglobulins detected, and 21 of those (32%) fulfilled CV criteria. The patients with cryoglobulins had higher cumulative mean disease activity, 45 (9%) developed B-cell lymphoma, and 33 (6%) died (Arthritis Rheumatol. 2015;67[suppl 10]. Abstract 628).

Additionally, both CV-positive and CV-negative patients had higher risk of B-cell lymphoma, but the risk was greatest in the CV-positive group (hazard ratios, 7.47 and 2.56, respectively), and the CV-positive patients had a higher risk of death (HR, 11.68).

“This actually has changed practice in our Sjögren’s clinic because we didn’t used to do cryos on everybody unless they had leukocytoclastic vasculitis, because they also have a higher risk of death,” Dr. James said.

Systemic activity also predicts pSS mortality, according to findings published in 2016 by Pilar Brito-Zerón et al. Of 1,045 patients who were part of the Spanish Group of Autoimmune Disease-SS Study Group and who were followed for a mean of 117 months, mortality was 11%. Survival was 96% at 5 years, 90% at 10 years, 81% at 20 years, and 60% at 30 years (Ann Rheum Dis. 2016;75:348-55).

Baseline factors associated with increased mortality on multivariate analysis included male gender, cryoglobulins, and low complement levels; the strongest model for death included high activity in at least one ESSDAI domain, baseline ESSDAI of at least 14, more than one laboratory predictive marker such as lymphopenia, anti-La, monoclonal gammopathy, low C3, low C4, and/or cryoglobulins.
 

Predicting progression to pSS

Progress has also been made with respect to predicting progression to pSS among patients who present with some related symptoms but don’t meet Sjögren’s criteria, Dr. James noted.

A 2017 study by Caroline Shiboski et al. looked at 771 patients from the Sjögren’s International Collaborative Clinical Alliance (SICCA) registry who had previously had objective measures of salivary hypofunction, dry eyes, focal lymphocytic sialadenitis or anti-Ro/anti-La. When these patients were recalled 2-3 years after their baseline evaluation, 28 (9%) of 308 patients who did not meet pSS criteria at baseline had then progressed to pSS (Arthritis Care Res. 2017;70[2]:284-94).

Those with baseline hypergammaglobulinemia were four times more likely to progress, and those with baseline low complement levels were six times more likely to progress.

Many patients will present with symptoms, but won’t ever develop Sjögren’s, but the subset of patients with these baseline characteristics may be at greater risk, she said.
 

Autoantibodies and pathogenesis

Up to 90% of pSS patients will have one or more of anti-Ro, anti-La, or rheumatoid factor, and many will have a positive antinuclear antibody (ANA) level of at least 1:320, Dr. James said, adding that anti-Ro and anti-La are linked with earlier disease onset, increased disease severity, longer disease duration, and extraglandular involvement.

Ro52, a target of Sjögren’s autoantibodies, may also confer more severe disease, and autoantibodies to muscarinic acetylcholine receptors appear to contribute to pathogenesis in Sjögren’s patients “above and beyond what we see with lymphocytic infiltrates and other things that are happening in the salivary gland,” she said.

Other exciting progress with respect to disease pathogenesis includes an increased focus on genetics and genetic predisposition beyond human leukocyte antigen associations.

Mutations in genes that overlap with Sjögren’s and lupus or Sjögren’s and RA, such as IRF5, Blk, and STAT4 appear to contribute to Sjögren’s syndrome development.

“And then there’s also some new genetics looking at Sjögren’s-specific genes, and these may help us as we think about new targetable pathways in this disorder,” she said.

Genomics and gene-environment interactions, such as interactions with viral infections or “other things that lead to molecular mimicry that get the disease process started,” are also getting increased attention; gene-expression profiling has shown overlap between Sjögren’s and lupus (shared genetics, autoantibodies, and similarly strong interferon signatures, for example), which isn’t surprising.

“But we’re also seeing NF-kB [NF-kappa B] activation, antigen presentation, and migration pathways that are being found in Sjögren’s that aren’t necessarily the ones that we see in lupus,” she added.
 

Clinical practice guidelines

A number of practice guidelines addressing various symptoms and issues associated with pSS have been released in the last few years, including several from EULAR, the United States, Brazil, and the United Kingdom, are summarized and reviewed in a recent paper by Vasco Romão et al. (RMD Open. 2018;4:e000789. doi: 10.1136/rmdopen-2018-000789).

The British Society of Rheumatology guideline, which came out about a year ago, has particularly practical guidance on the management of dryness and systemic disease, she said (Rheumatology. 2017;56[10]:1643-7).

The increasing focus on pSS research has important implications both for trial design and patient care, especially in light of the new classification criteria, practice guidelines, and educational resources provided by organizations such as the Sjögren’s Syndrome Foundation (including videos, health care provider information, and downloadable brochures and resource sheets) and the European Research Network’s ReCONNET Disease Info Toolbox for Sjögren’s, Dr. James concluded.

Dr. James reported having no disclosures.

sworcester@mdedge.com

Recent findings, new classification criteria and treatment guidelines, and concerted efforts by various organizations to provide educational resources are among a number of factors improving the outlook for patients with primary Sjögren’s syndrome, according to Judith James, MD, PhD.

Additionally, the number of studies of primary Sjögren’s syndrome (pSS) is increasing, albeit slowly, and ongoing studies of biologics are showing promise, Dr. James said during a clinical update at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
 

Classification criteria

The ACR in conjunction with the European League Against Rheumatism (EULAR) published new criteria for pSS classification in 2016 based on the available evidence and expert consensus. Inclusion criteria include daily, persistent, troublesome dry eyes for more than 3 months, recurrent sensation of sand or gravel in the eyes, use of tear substitutes more than three times each day, frequent drinking of liquids to aid in swallowing dry food, or at least one EULAR Sjögren’s syndrome disease activity index (ESSDAI) domain with a positive item. Exclusion criteria include prior head and neck radiation treatment, polymerase chain reaction–confirmed active hepatitis C infection, AIDS, sarcoidosis, amyloidosis, graft-versus-host disease, or IgG4-related disease, said Dr. James, professor and chair of the arthritis and clinical immunology research program at the University of Oklahoma, Oklahoma City (Arthritis Rheumatol. Jan 2017;69[1]:35-45).

• A score of 4 or higher in patients who meet the inclusion criteria and do not have any of the exclusion criteria leads to classification with pSS, based on the following findings:
• Labial salivary gland with focal lymphocytic sialadenitis and focus score of at least 1 foci/4 mm² (weight/score = 3).
• Anti-SSA/Ro-positivity (weight/score = 3).
• Ocular Staining Score of at least 5, or van Bijsterveld score of at least 4, in at least one eye (weight/score = 1).
• Schirmer’s test of no more than 5 mm/5 min in at least one eye (weight/score = 1).
• Unstimulated whole saliva flow rate of no more than 0.1 mL/min (weight/score = 1).

Clinical pearls for detection and management

In Dr. James’ experience, the three symptoms (taken together) with the highest predictive value for diagnosing pSS are dry mouth, sore mouth/tongue, and dry eyes. About 25% of Sjögren’s patients may have no detectable salivary flow, she said.

Dry, cracked skin that can lead to secondary infections is another common issue affecting about 55% of patients.

“So we always have to talk to our Sjögren’s patients about skin,” she said. “We also have recurrent sinusitis, chronic cough, dyspepsia, constipation, and other symptoms.”

Concurrent autoimmune diseases are another concern in Sjögren’s patients, she said. One to particularly keep in mind, in addition to lupus and rheumatoid arthritis, is autoimmune thyroid disease.

Data suggest that up to 45% of Sjögren’s patients have thyroid dysfunction, and if you look at just those with autoimmune thyroiditis, their risk of Sjögren’s is increased 10-fold vs. those without autoimmune thyroiditis, she said.

Other conditions to keep in mind when it comes to diagnosing and managing patients, as has been shown in numerous studies over the years, include Raynaud’s phenomenon, which affects at least 13% of patients, and subclinical muscle inflammation, which affects more than 50% of patients, Dr. James said.

“Depression ... as well as anxiety, is quite common in Sjögren’s patients, and fatigue is profound,” she added, noting that fatigue is “the No. 1 issue” for many patients.

Another area of particular concern in Sjögren’s is the increased risk of lymphoma, she said.

Studies show varying rates of lymphoma in Sjögren’s, with one suggesting a 44-fold increased risk, but this is likely only among those at very high risk. Other studies suggest the increase is risk overall is in the range of 4- to 10-fold, she said.

Mortality in Sjögren’s patients

A 2015 study by Soledad Retamozo et al. showed that the presence of cryoglobulinemic vasculitis (CV) at diagnosis is associated with increased mortality risk.

Of 515 consecutive pSS patients with a mean follow-up of 110 months, 65 (12%) had cryoglobulins detected, and 21 of those (32%) fulfilled CV criteria. The patients with cryoglobulins had higher cumulative mean disease activity, 45 (9%) developed B-cell lymphoma, and 33 (6%) died (Arthritis Rheumatol. 2015;67[suppl 10]. Abstract 628).

Additionally, both CV-positive and CV-negative patients had higher risk of B-cell lymphoma, but the risk was greatest in the CV-positive group (hazard ratios, 7.47 and 2.56, respectively), and the CV-positive patients had a higher risk of death (HR, 11.68).

“This actually has changed practice in our Sjögren’s clinic because we didn’t used to do cryos on everybody unless they had leukocytoclastic vasculitis, because they also have a higher risk of death,” Dr. James said.

Systemic activity also predicts pSS mortality, according to findings published in 2016 by Pilar Brito-Zerón et al. Of 1,045 patients who were part of the Spanish Group of Autoimmune Disease-SS Study Group and who were followed for a mean of 117 months, mortality was 11%. Survival was 96% at 5 years, 90% at 10 years, 81% at 20 years, and 60% at 30 years (Ann Rheum Dis. 2016;75:348-55).

Baseline factors associated with increased mortality on multivariate analysis included male gender, cryoglobulins, and low complement levels; the strongest model for death included high activity in at least one ESSDAI domain, baseline ESSDAI of at least 14, more than one laboratory predictive marker such as lymphopenia, anti-La, monoclonal gammopathy, low C3, low C4, and/or cryoglobulins.
 

Predicting progression to pSS

Progress has also been made with respect to predicting progression to pSS among patients who present with some related symptoms but don’t meet Sjögren’s criteria, Dr. James noted.

A 2017 study by Caroline Shiboski et al. looked at 771 patients from the Sjögren’s International Collaborative Clinical Alliance (SICCA) registry who had previously had objective measures of salivary hypofunction, dry eyes, focal lymphocytic sialadenitis or anti-Ro/anti-La. When these patients were recalled 2-3 years after their baseline evaluation, 28 (9%) of 308 patients who did not meet pSS criteria at baseline had then progressed to pSS (Arthritis Care Res. 2017;70[2]:284-94).

Those with baseline hypergammaglobulinemia were four times more likely to progress, and those with baseline low complement levels were six times more likely to progress.

Many patients will present with symptoms, but won’t ever develop Sjögren’s, but the subset of patients with these baseline characteristics may be at greater risk, she said.
 

Autoantibodies and pathogenesis

Up to 90% of pSS patients will have one or more of anti-Ro, anti-La, or rheumatoid factor, and many will have a positive antinuclear antibody (ANA) level of at least 1:320, Dr. James said, adding that anti-Ro and anti-La are linked with earlier disease onset, increased disease severity, longer disease duration, and extraglandular involvement.

Ro52, a target of Sjögren’s autoantibodies, may also confer more severe disease, and autoantibodies to muscarinic acetylcholine receptors appear to contribute to pathogenesis in Sjögren’s patients “above and beyond what we see with lymphocytic infiltrates and other things that are happening in the salivary gland,” she said.

Other exciting progress with respect to disease pathogenesis includes an increased focus on genetics and genetic predisposition beyond human leukocyte antigen associations.

Mutations in genes that overlap with Sjögren’s and lupus or Sjögren’s and RA, such as IRF5, Blk, and STAT4 appear to contribute to Sjögren’s syndrome development.

“And then there’s also some new genetics looking at Sjögren’s-specific genes, and these may help us as we think about new targetable pathways in this disorder,” she said.

Genomics and gene-environment interactions, such as interactions with viral infections or “other things that lead to molecular mimicry that get the disease process started,” are also getting increased attention; gene-expression profiling has shown overlap between Sjögren’s and lupus (shared genetics, autoantibodies, and similarly strong interferon signatures, for example), which isn’t surprising.

“But we’re also seeing NF-kB [NF-kappa B] activation, antigen presentation, and migration pathways that are being found in Sjögren’s that aren’t necessarily the ones that we see in lupus,” she added.
 

Clinical practice guidelines

A number of practice guidelines addressing various symptoms and issues associated with pSS have been released in the last few years, including several from EULAR, the United States, Brazil, and the United Kingdom, are summarized and reviewed in a recent paper by Vasco Romão et al. (RMD Open. 2018;4:e000789. doi: 10.1136/rmdopen-2018-000789).

The British Society of Rheumatology guideline, which came out about a year ago, has particularly practical guidance on the management of dryness and systemic disease, she said (Rheumatology. 2017;56[10]:1643-7).

The increasing focus on pSS research has important implications both for trial design and patient care, especially in light of the new classification criteria, practice guidelines, and educational resources provided by organizations such as the Sjögren’s Syndrome Foundation (including videos, health care provider information, and downloadable brochures and resource sheets) and the European Research Network’s ReCONNET Disease Info Toolbox for Sjögren’s, Dr. James concluded.

Dr. James reported having no disclosures.

sworcester@mdedge.com

Recent findings, new classification criteria and treatment guidelines, and concerted efforts by various organizations to provide educational resources are among a number of factors improving the outlook for patients with primary Sjögren’s syndrome, according to Judith James, MD, PhD.

Additionally, the number of studies of primary Sjögren’s syndrome (pSS) is increasing, albeit slowly, and ongoing studies of biologics are showing promise, Dr. James said during a clinical update at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
 

Classification criteria

The ACR in conjunction with the European League Against Rheumatism (EULAR) published new criteria for pSS classification in 2016 based on the available evidence and expert consensus. Inclusion criteria include daily, persistent, troublesome dry eyes for more than 3 months, recurrent sensation of sand or gravel in the eyes, use of tear substitutes more than three times each day, frequent drinking of liquids to aid in swallowing dry food, or at least one EULAR Sjögren’s syndrome disease activity index (ESSDAI) domain with a positive item. Exclusion criteria include prior head and neck radiation treatment, polymerase chain reaction–confirmed active hepatitis C infection, AIDS, sarcoidosis, amyloidosis, graft-versus-host disease, or IgG4-related disease, said Dr. James, professor and chair of the arthritis and clinical immunology research program at the University of Oklahoma, Oklahoma City (Arthritis Rheumatol. Jan 2017;69[1]:35-45).

• A score of 4 or higher in patients who meet the inclusion criteria and do not have any of the exclusion criteria leads to classification with pSS, based on the following findings:
• Labial salivary gland with focal lymphocytic sialadenitis and focus score of at least 1 foci/4 mm² (weight/score = 3).
• Anti-SSA/Ro-positivity (weight/score = 3).
• Ocular Staining Score of at least 5, or van Bijsterveld score of at least 4, in at least one eye (weight/score = 1).
• Schirmer’s test of no more than 5 mm/5 min in at least one eye (weight/score = 1).
• Unstimulated whole saliva flow rate of no more than 0.1 mL/min (weight/score = 1).

Clinical pearls for detection and management

In Dr. James’ experience, the three symptoms (taken together) with the highest predictive value for diagnosing pSS are dry mouth, sore mouth/tongue, and dry eyes. About 25% of Sjögren’s patients may have no detectable salivary flow, she said.

Dry, cracked skin that can lead to secondary infections is another common issue affecting about 55% of patients.

“So we always have to talk to our Sjögren’s patients about skin,” she said. “We also have recurrent sinusitis, chronic cough, dyspepsia, constipation, and other symptoms.”

Concurrent autoimmune diseases are another concern in Sjögren’s patients, she said. One to particularly keep in mind, in addition to lupus and rheumatoid arthritis, is autoimmune thyroid disease.

Data suggest that up to 45% of Sjögren’s patients have thyroid dysfunction, and if you look at just those with autoimmune thyroiditis, their risk of Sjögren’s is increased 10-fold vs. those without autoimmune thyroiditis, she said.

Other conditions to keep in mind when it comes to diagnosing and managing patients, as has been shown in numerous studies over the years, include Raynaud’s phenomenon, which affects at least 13% of patients, and subclinical muscle inflammation, which affects more than 50% of patients, Dr. James said.

“Depression ... as well as anxiety, is quite common in Sjögren’s patients, and fatigue is profound,” she added, noting that fatigue is “the No. 1 issue” for many patients.

Another area of particular concern in Sjögren’s is the increased risk of lymphoma, she said.

Studies show varying rates of lymphoma in Sjögren’s, with one suggesting a 44-fold increased risk, but this is likely only among those at very high risk. Other studies suggest the increase is risk overall is in the range of 4- to 10-fold, she said.

Mortality in Sjögren’s patients

A 2015 study by Soledad Retamozo et al. showed that the presence of cryoglobulinemic vasculitis (CV) at diagnosis is associated with increased mortality risk.

Of 515 consecutive pSS patients with a mean follow-up of 110 months, 65 (12%) had cryoglobulins detected, and 21 of those (32%) fulfilled CV criteria. The patients with cryoglobulins had higher cumulative mean disease activity, 45 (9%) developed B-cell lymphoma, and 33 (6%) died (Arthritis Rheumatol. 2015;67[suppl 10]. Abstract 628).

Additionally, both CV-positive and CV-negative patients had higher risk of B-cell lymphoma, but the risk was greatest in the CV-positive group (hazard ratios, 7.47 and 2.56, respectively), and the CV-positive patients had a higher risk of death (HR, 11.68).

“This actually has changed practice in our Sjögren’s clinic because we didn’t used to do cryos on everybody unless they had leukocytoclastic vasculitis, because they also have a higher risk of death,” Dr. James said.

Systemic activity also predicts pSS mortality, according to findings published in 2016 by Pilar Brito-Zerón et al. Of 1,045 patients who were part of the Spanish Group of Autoimmune Disease-SS Study Group and who were followed for a mean of 117 months, mortality was 11%. Survival was 96% at 5 years, 90% at 10 years, 81% at 20 years, and 60% at 30 years (Ann Rheum Dis. 2016;75:348-55).

Baseline factors associated with increased mortality on multivariate analysis included male gender, cryoglobulins, and low complement levels; the strongest model for death included high activity in at least one ESSDAI domain, baseline ESSDAI of at least 14, more than one laboratory predictive marker such as lymphopenia, anti-La, monoclonal gammopathy, low C3, low C4, and/or cryoglobulins.
 

Predicting progression to pSS

Progress has also been made with respect to predicting progression to pSS among patients who present with some related symptoms but don’t meet Sjögren’s criteria, Dr. James noted.

A 2017 study by Caroline Shiboski et al. looked at 771 patients from the Sjögren’s International Collaborative Clinical Alliance (SICCA) registry who had previously had objective measures of salivary hypofunction, dry eyes, focal lymphocytic sialadenitis or anti-Ro/anti-La. When these patients were recalled 2-3 years after their baseline evaluation, 28 (9%) of 308 patients who did not meet pSS criteria at baseline had then progressed to pSS (Arthritis Care Res. 2017;70[2]:284-94).

Those with baseline hypergammaglobulinemia were four times more likely to progress, and those with baseline low complement levels were six times more likely to progress.

Many patients will present with symptoms, but won’t ever develop Sjögren’s, but the subset of patients with these baseline characteristics may be at greater risk, she said.
 

Autoantibodies and pathogenesis

Up to 90% of pSS patients will have one or more of anti-Ro, anti-La, or rheumatoid factor, and many will have a positive antinuclear antibody (ANA) level of at least 1:320, Dr. James said, adding that anti-Ro and anti-La are linked with earlier disease onset, increased disease severity, longer disease duration, and extraglandular involvement.

Ro52, a target of Sjögren’s autoantibodies, may also confer more severe disease, and autoantibodies to muscarinic acetylcholine receptors appear to contribute to pathogenesis in Sjögren’s patients “above and beyond what we see with lymphocytic infiltrates and other things that are happening in the salivary gland,” she said.

Other exciting progress with respect to disease pathogenesis includes an increased focus on genetics and genetic predisposition beyond human leukocyte antigen associations.

Mutations in genes that overlap with Sjögren’s and lupus or Sjögren’s and RA, such as IRF5, Blk, and STAT4 appear to contribute to Sjögren’s syndrome development.

“And then there’s also some new genetics looking at Sjögren’s-specific genes, and these may help us as we think about new targetable pathways in this disorder,” she said.

Genomics and gene-environment interactions, such as interactions with viral infections or “other things that lead to molecular mimicry that get the disease process started,” are also getting increased attention; gene-expression profiling has shown overlap between Sjögren’s and lupus (shared genetics, autoantibodies, and similarly strong interferon signatures, for example), which isn’t surprising.

“But we’re also seeing NF-kB [NF-kappa B] activation, antigen presentation, and migration pathways that are being found in Sjögren’s that aren’t necessarily the ones that we see in lupus,” she added.
 

Clinical practice guidelines

A number of practice guidelines addressing various symptoms and issues associated with pSS have been released in the last few years, including several from EULAR, the United States, Brazil, and the United Kingdom, are summarized and reviewed in a recent paper by Vasco Romão et al. (RMD Open. 2018;4:e000789. doi: 10.1136/rmdopen-2018-000789).

The British Society of Rheumatology guideline, which came out about a year ago, has particularly practical guidance on the management of dryness and systemic disease, she said (Rheumatology. 2017;56[10]:1643-7).

The increasing focus on pSS research has important implications both for trial design and patient care, especially in light of the new classification criteria, practice guidelines, and educational resources provided by organizations such as the Sjögren’s Syndrome Foundation (including videos, health care provider information, and downloadable brochures and resource sheets) and the European Research Network’s ReCONNET Disease Info Toolbox for Sjögren’s, Dr. James concluded.

Dr. James reported having no disclosures.

sworcester@mdedge.com

GRAND CAYMAN, CAYMAN ISLANDS – Guselkumab bested secukinumab in a 48-week-long study of plaque psoriasis, with 84.5% of patients on the interleukin (IL)-23 blocker hitting at least a 90% improvement in their Psoriasis Area Severity Index (PASI), compared with 70% of those taking secukinumab, which blocks IL-17.

The difference in the PASI 90 response, the primary endpoint, was guselkumab’s largest effect over the comparator in the phase 3 trial, which also had six secondary endpoints. The drug was numerically, but not significantly, better than secukinumab in the PASI 75 response at weeks 12 and 48 (84.6% for guselkumab at both time points vs. 80.2% for secukinumab at both time points). This finding on the primary secondary endpoint knocked the P values of the other five into “nominally significant” ranges. But the responses were still good enough for researchers to tag guselkumab as noninferior to its competitor, Jeffrey M. Sobell, MD, said at the meeting provided by Global Academy for Medical Education.

The difference also speaks to the difference in the drugs’ onset of action and its peak efficacy, said Dr. Sobell, of the department of dermatology at Tufts University, Boston.

“In both groups, the PASI 90 increased similarly in the first month,” to about 20%, he commented. “But at week 12 and after, it was consistently higher in guselkumab, peaking around week 28. Secukinumab peaked around weeks 16 to 20 and then slowly declined.”

Despite not being statistically significant, the other secondary efficacy endpoints were certainly enough to pique the audience’s attention. At week 48, guselkumab topped secukinumab in both PASI 100 (58.2% vs. 48.4%, respectively) and Investigator’s Global Assessment (IGA) scores of 0 (62.2% vs. 50.4%) and 0-1 (85% vs. 74.9%).

ECLIPSE randomized 1,048 patients with moderate to severe plaque psoriasis to 100-mg subcutaneous guselkumab at weeks 0, 4, and 12, followed by dosing every 8 weeks, or to 300-mg subcutaneous secukinumab administered by two subcutaneous injections of 150 mg at weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks. The primary endpoint of the study was the proportion of patients achieving a PASI 90 response at week 48. Secondary endpoints were assessed at weeks 12 and 48, with safety monitoring through week 56.

The mean baseline Body Surface Area score was 24, and the mean PASI score was 20. Patients had already been treated with phototherapy (51.8%), nonbiologic systemic medications (53.7%), and biologics (29%). About 37% were naive to both nonbiologics and biologics.

Both drugs were well tolerated, with no unanticipated adverse events. Through week 44, the discontinuation rates were 5% for guselkumab and 9% for secukinumab. Adverse events were common in both arms (77.9% and 81.6%, respectively). Serious adverse events occurred in 6.2% and 7.2%, respectively. These included serious infections in six patients taking guselkumab and five taking secukinumab. Superficial Candida infections occurred in 2% of the guselkumab group and 5.7% of the secukinumab group; Tinea infections occurred in 1.7% and 4.5%, respectively.

The session was sponsored by Janssen, the manufacturer of guselkumab (Tremfya). Dr. Sobell is a consultant for Janssen and also disclosed relationships with AbbVie, Amgen, Celgene, Eli Lilly, Merck, Novartis, Regeneron, and Sun Pharma. Secukinumab is marketed as Cosentyx.

Global Academy and this news organization are owned by the same parent company.

This article was updated 2/1/19.

msullivan@mdege.com

GRAND CAYMAN, CAYMAN ISLANDS – Guselkumab bested secukinumab in a 48-week-long study of plaque psoriasis, with 84.5% of patients on the interleukin (IL)-23 blocker hitting at least a 90% improvement in their Psoriasis Area Severity Index (PASI), compared with 70% of those taking secukinumab, which blocks IL-17.

The difference in the PASI 90 response, the primary endpoint, was guselkumab’s largest effect over the comparator in the phase 3 trial, which also had six secondary endpoints. The drug was numerically, but not significantly, better than secukinumab in the PASI 75 response at weeks 12 and 48 (84.6% for guselkumab at both time points vs. 80.2% for secukinumab at both time points). This finding on the primary secondary endpoint knocked the P values of the other five into “nominally significant” ranges. But the responses were still good enough for researchers to tag guselkumab as noninferior to its competitor, Jeffrey M. Sobell, MD, said at the meeting provided by Global Academy for Medical Education.

The difference also speaks to the difference in the drugs’ onset of action and its peak efficacy, said Dr. Sobell, of the department of dermatology at Tufts University, Boston.

“In both groups, the PASI 90 increased similarly in the first month,” to about 20%, he commented. “But at week 12 and after, it was consistently higher in guselkumab, peaking around week 28. Secukinumab peaked around weeks 16 to 20 and then slowly declined.”

Despite not being statistically significant, the other secondary efficacy endpoints were certainly enough to pique the audience’s attention. At week 48, guselkumab topped secukinumab in both PASI 100 (58.2% vs. 48.4%, respectively) and Investigator’s Global Assessment (IGA) scores of 0 (62.2% vs. 50.4%) and 0-1 (85% vs. 74.9%).

ECLIPSE randomized 1,048 patients with moderate to severe plaque psoriasis to 100-mg subcutaneous guselkumab at weeks 0, 4, and 12, followed by dosing every 8 weeks, or to 300-mg subcutaneous secukinumab administered by two subcutaneous injections of 150 mg at weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks. The primary endpoint of the study was the proportion of patients achieving a PASI 90 response at week 48. Secondary endpoints were assessed at weeks 12 and 48, with safety monitoring through week 56.

The mean baseline Body Surface Area score was 24, and the mean PASI score was 20. Patients had already been treated with phototherapy (51.8%), nonbiologic systemic medications (53.7%), and biologics (29%). About 37% were naive to both nonbiologics and biologics.

Both drugs were well tolerated, with no unanticipated adverse events. Through week 44, the discontinuation rates were 5% for guselkumab and 9% for secukinumab. Adverse events were common in both arms (77.9% and 81.6%, respectively). Serious adverse events occurred in 6.2% and 7.2%, respectively. These included serious infections in six patients taking guselkumab and five taking secukinumab. Superficial Candida infections occurred in 2% of the guselkumab group and 5.7% of the secukinumab group; Tinea infections occurred in 1.7% and 4.5%, respectively.

The session was sponsored by Janssen, the manufacturer of guselkumab (Tremfya). Dr. Sobell is a consultant for Janssen and also disclosed relationships with AbbVie, Amgen, Celgene, Eli Lilly, Merck, Novartis, Regeneron, and Sun Pharma. Secukinumab is marketed as Cosentyx.

Global Academy and this news organization are owned by the same parent company.

This article was updated 2/1/19.

msullivan@mdege.com

GRAND CAYMAN, CAYMAN ISLANDS – Guselkumab bested secukinumab in a 48-week-long study of plaque psoriasis, with 84.5% of patients on the interleukin (IL)-23 blocker hitting at least a 90% improvement in their Psoriasis Area Severity Index (PASI), compared with 70% of those taking secukinumab, which blocks IL-17.

The difference in the PASI 90 response, the primary endpoint, was guselkumab’s largest effect over the comparator in the phase 3 trial, which also had six secondary endpoints. The drug was numerically, but not significantly, better than secukinumab in the PASI 75 response at weeks 12 and 48 (84.6% for guselkumab at both time points vs. 80.2% for secukinumab at both time points). This finding on the primary secondary endpoint knocked the P values of the other five into “nominally significant” ranges. But the responses were still good enough for researchers to tag guselkumab as noninferior to its competitor, Jeffrey M. Sobell, MD, said at the meeting provided by Global Academy for Medical Education.

The difference also speaks to the difference in the drugs’ onset of action and its peak efficacy, said Dr. Sobell, of the department of dermatology at Tufts University, Boston.

“In both groups, the PASI 90 increased similarly in the first month,” to about 20%, he commented. “But at week 12 and after, it was consistently higher in guselkumab, peaking around week 28. Secukinumab peaked around weeks 16 to 20 and then slowly declined.”

Despite not being statistically significant, the other secondary efficacy endpoints were certainly enough to pique the audience’s attention. At week 48, guselkumab topped secukinumab in both PASI 100 (58.2% vs. 48.4%, respectively) and Investigator’s Global Assessment (IGA) scores of 0 (62.2% vs. 50.4%) and 0-1 (85% vs. 74.9%).

ECLIPSE randomized 1,048 patients with moderate to severe plaque psoriasis to 100-mg subcutaneous guselkumab at weeks 0, 4, and 12, followed by dosing every 8 weeks, or to 300-mg subcutaneous secukinumab administered by two subcutaneous injections of 150 mg at weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks. The primary endpoint of the study was the proportion of patients achieving a PASI 90 response at week 48. Secondary endpoints were assessed at weeks 12 and 48, with safety monitoring through week 56.

The mean baseline Body Surface Area score was 24, and the mean PASI score was 20. Patients had already been treated with phototherapy (51.8%), nonbiologic systemic medications (53.7%), and biologics (29%). About 37% were naive to both nonbiologics and biologics.

Both drugs were well tolerated, with no unanticipated adverse events. Through week 44, the discontinuation rates were 5% for guselkumab and 9% for secukinumab. Adverse events were common in both arms (77.9% and 81.6%, respectively). Serious adverse events occurred in 6.2% and 7.2%, respectively. These included serious infections in six patients taking guselkumab and five taking secukinumab. Superficial Candida infections occurred in 2% of the guselkumab group and 5.7% of the secukinumab group; Tinea infections occurred in 1.7% and 4.5%, respectively.

The session was sponsored by Janssen, the manufacturer of guselkumab (Tremfya). Dr. Sobell is a consultant for Janssen and also disclosed relationships with AbbVie, Amgen, Celgene, Eli Lilly, Merck, Novartis, Regeneron, and Sun Pharma. Secukinumab is marketed as Cosentyx.

Global Academy and this news organization are owned by the same parent company.

This article was updated 2/1/19.

msullivan@mdege.com

BROOKLYN, N.Y. – Intervening effectively for children and adolescents at suicide risk involves watching for triggers such as personal loss, sleep disturbances, or interpersonal conflict, an expert said at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

It is important to distinguish the distal risks, which are factors known to increase suicidal ideation, and proximal risk factors, which predict attempts, according to Tina R. Goldstein, PhD, associate professor of psychiatry and psychology at the University of Pittsburgh. “We know that the optimal targets for preventing suicidal behavior are proximal,” Dr. Goldstein said. Treatment of distal risks, such as depression or substance use, is a foundation for risk management, but suicidal events are driven by acute crises that appear to require individualized intervention.

Dr. Goldstein said she had just “one sad slide” to summarize drug treatments aimed at controlling suicidal behavior. That slide included citations for studies associating neuroleptics and antidepressants with a reduction in aggressive or impulsive behavior in children. The only study associating a drug with a reduction in suicide attempts was performed with lithium in adults.

However, intensive cognitive and dialectical behavior interventions involving the family have been shown to reduce suicide attempts in randomized controlled trials, said Dr. Goldstein, who also is affiliated with the university’s Child and Adolescent Bipolar Spectrum Services Research Program. Those trials underscore the messages that personalizing therapy is essential, as are addressing specific triggers and helping patients develop defenses against suicidal thoughts.

Dr. Goldstein described a recently published, National Institutes of Health–funded study that focused on suicide reduction. The study was conducted in adolescents who were being discharged from a brief hospitalization for acute suicidal ideation or a suicide attempt (J Adolesc Health. 2018 Nov. 8. doi: 10.1016/j.jadohealth.2018.09.015). “We know that there is this really high-risk period after discharge from the hospital for which we could potentially do things better,” said Dr. Goldstein, whose center was involved in the study.

The tested intervention, called As Safe As Possible (ASAP), involved “front-loading some coping skills and giving [the patients] a good safety plan even before they are discharged,” Dr. Goldstein said. For risk management after discharge, the adolescents were provided with a smartphone app called BRITE that contained the safety plan as well as a summary of personalized coping skills, including reminders that the patients themselves had provided for reasons for living. The app was augmented as appropriate with favorite songs, photos of the patients’ pet, or other customized aids to provide support during the typical delay between the time of discharge and the next step in care.

In 6 months of follow-up, the rate of suicide attempts was 8.7% of those enrolled in the intensive outpatient program, compared with 27.3% (P = .08) for those who received treatment as usual. Dr. Goldstein called this trend promising, particularly in the context of other favorable results, including a significantly longer (P = .03) time to a suicide attempt in the ASAP group.

In patients at imminent risk of a suicide attempt, it is logical to assume that treatment must be personalized to the issues behind increased suicidal ideation. However, a study published by Dr. Goldstein and her associates several years ago suggested that evidence of deteriorating mental health can signal a need for intensification of suicide risk management (Arch Gen Psychiatry. 2012;69:1113-22). In one part of that study, risk factors for suicide were evaluated in the 8 weeks before a suicide attempt in 413 children with bipolar disorder. During that time, depression scores increased as did substance use, but, surprisingly, so did use of mental health services.

“The way we have come to think of these data is that the kids, their parents, and their providers were recognizing that things were getting worse and they needed more services,” Dr. Goldstein said. “The bad news is that the services we were giving them were not particularly effective.”

Those data underscore some of the challenges facing clinicians who treat pediatric patients with mental illness. “Our field has not yet developed ... gold standard treatments for preventing suicidal behavior in kids with mood disorder,” Dr. Goldstein said. However, she thinks that some progress has been made and that some of the personalized approaches are demonstrating efficacy – particularly in children and adolescents who exhibit signs of imminent risk.

BROOKLYN, N.Y. – Intervening effectively for children and adolescents at suicide risk involves watching for triggers such as personal loss, sleep disturbances, or interpersonal conflict, an expert said at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

It is important to distinguish the distal risks, which are factors known to increase suicidal ideation, and proximal risk factors, which predict attempts, according to Tina R. Goldstein, PhD, associate professor of psychiatry and psychology at the University of Pittsburgh. “We know that the optimal targets for preventing suicidal behavior are proximal,” Dr. Goldstein said. Treatment of distal risks, such as depression or substance use, is a foundation for risk management, but suicidal events are driven by acute crises that appear to require individualized intervention.

Dr. Goldstein said she had just “one sad slide” to summarize drug treatments aimed at controlling suicidal behavior. That slide included citations for studies associating neuroleptics and antidepressants with a reduction in aggressive or impulsive behavior in children. The only study associating a drug with a reduction in suicide attempts was performed with lithium in adults.

However, intensive cognitive and dialectical behavior interventions involving the family have been shown to reduce suicide attempts in randomized controlled trials, said Dr. Goldstein, who also is affiliated with the university’s Child and Adolescent Bipolar Spectrum Services Research Program. Those trials underscore the messages that personalizing therapy is essential, as are addressing specific triggers and helping patients develop defenses against suicidal thoughts.

Dr. Goldstein described a recently published, National Institutes of Health–funded study that focused on suicide reduction. The study was conducted in adolescents who were being discharged from a brief hospitalization for acute suicidal ideation or a suicide attempt (J Adolesc Health. 2018 Nov. 8. doi: 10.1016/j.jadohealth.2018.09.015). “We know that there is this really high-risk period after discharge from the hospital for which we could potentially do things better,” said Dr. Goldstein, whose center was involved in the study.

The tested intervention, called As Safe As Possible (ASAP), involved “front-loading some coping skills and giving [the patients] a good safety plan even before they are discharged,” Dr. Goldstein said. For risk management after discharge, the adolescents were provided with a smartphone app called BRITE that contained the safety plan as well as a summary of personalized coping skills, including reminders that the patients themselves had provided for reasons for living. The app was augmented as appropriate with favorite songs, photos of the patients’ pet, or other customized aids to provide support during the typical delay between the time of discharge and the next step in care.

In 6 months of follow-up, the rate of suicide attempts was 8.7% of those enrolled in the intensive outpatient program, compared with 27.3% (P = .08) for those who received treatment as usual. Dr. Goldstein called this trend promising, particularly in the context of other favorable results, including a significantly longer (P = .03) time to a suicide attempt in the ASAP group.

In patients at imminent risk of a suicide attempt, it is logical to assume that treatment must be personalized to the issues behind increased suicidal ideation. However, a study published by Dr. Goldstein and her associates several years ago suggested that evidence of deteriorating mental health can signal a need for intensification of suicide risk management (Arch Gen Psychiatry. 2012;69:1113-22). In one part of that study, risk factors for suicide were evaluated in the 8 weeks before a suicide attempt in 413 children with bipolar disorder. During that time, depression scores increased as did substance use, but, surprisingly, so did use of mental health services.

“The way we have come to think of these data is that the kids, their parents, and their providers were recognizing that things were getting worse and they needed more services,” Dr. Goldstein said. “The bad news is that the services we were giving them were not particularly effective.”

Those data underscore some of the challenges facing clinicians who treat pediatric patients with mental illness. “Our field has not yet developed ... gold standard treatments for preventing suicidal behavior in kids with mood disorder,” Dr. Goldstein said. However, she thinks that some progress has been made and that some of the personalized approaches are demonstrating efficacy – particularly in children and adolescents who exhibit signs of imminent risk.

BROOKLYN, N.Y. – Intervening effectively for children and adolescents at suicide risk involves watching for triggers such as personal loss, sleep disturbances, or interpersonal conflict, an expert said at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

It is important to distinguish the distal risks, which are factors known to increase suicidal ideation, and proximal risk factors, which predict attempts, according to Tina R. Goldstein, PhD, associate professor of psychiatry and psychology at the University of Pittsburgh. “We know that the optimal targets for preventing suicidal behavior are proximal,” Dr. Goldstein said. Treatment of distal risks, such as depression or substance use, is a foundation for risk management, but suicidal events are driven by acute crises that appear to require individualized intervention.

Dr. Goldstein said she had just “one sad slide” to summarize drug treatments aimed at controlling suicidal behavior. That slide included citations for studies associating neuroleptics and antidepressants with a reduction in aggressive or impulsive behavior in children. The only study associating a drug with a reduction in suicide attempts was performed with lithium in adults.

However, intensive cognitive and dialectical behavior interventions involving the family have been shown to reduce suicide attempts in randomized controlled trials, said Dr. Goldstein, who also is affiliated with the university’s Child and Adolescent Bipolar Spectrum Services Research Program. Those trials underscore the messages that personalizing therapy is essential, as are addressing specific triggers and helping patients develop defenses against suicidal thoughts.

Dr. Goldstein described a recently published, National Institutes of Health–funded study that focused on suicide reduction. The study was conducted in adolescents who were being discharged from a brief hospitalization for acute suicidal ideation or a suicide attempt (J Adolesc Health. 2018 Nov. 8. doi: 10.1016/j.jadohealth.2018.09.015). “We know that there is this really high-risk period after discharge from the hospital for which we could potentially do things better,” said Dr. Goldstein, whose center was involved in the study.

The tested intervention, called As Safe As Possible (ASAP), involved “front-loading some coping skills and giving [the patients] a good safety plan even before they are discharged,” Dr. Goldstein said. For risk management after discharge, the adolescents were provided with a smartphone app called BRITE that contained the safety plan as well as a summary of personalized coping skills, including reminders that the patients themselves had provided for reasons for living. The app was augmented as appropriate with favorite songs, photos of the patients’ pet, or other customized aids to provide support during the typical delay between the time of discharge and the next step in care.

In 6 months of follow-up, the rate of suicide attempts was 8.7% of those enrolled in the intensive outpatient program, compared with 27.3% (P = .08) for those who received treatment as usual. Dr. Goldstein called this trend promising, particularly in the context of other favorable results, including a significantly longer (P = .03) time to a suicide attempt in the ASAP group.

In patients at imminent risk of a suicide attempt, it is logical to assume that treatment must be personalized to the issues behind increased suicidal ideation. However, a study published by Dr. Goldstein and her associates several years ago suggested that evidence of deteriorating mental health can signal a need for intensification of suicide risk management (Arch Gen Psychiatry. 2012;69:1113-22). In one part of that study, risk factors for suicide were evaluated in the 8 weeks before a suicide attempt in 413 children with bipolar disorder. During that time, depression scores increased as did substance use, but, surprisingly, so did use of mental health services.

“The way we have come to think of these data is that the kids, their parents, and their providers were recognizing that things were getting worse and they needed more services,” Dr. Goldstein said. “The bad news is that the services we were giving them were not particularly effective.”

Those data underscore some of the challenges facing clinicians who treat pediatric patients with mental illness. “Our field has not yet developed ... gold standard treatments for preventing suicidal behavior in kids with mood disorder,” Dr. Goldstein said. However, she thinks that some progress has been made and that some of the personalized approaches are demonstrating efficacy – particularly in children and adolescents who exhibit signs of imminent risk.