Study Overview

Objective. To evaluate the efficacy of cabazitaxel compared to androgen-signaling–targeted inhibitors (ASTIs) in patients with metastatic castration-resistant prostate cancer who have received docetaxel and have progressed within 12 months of treatment with either abiraterone or enzalutamide.

Design. The CARD trial was an international, randomized, open-label phase 3 trial conducted across 13 European countries.

Setting and participants. Eligible patients were 18 years of age or older; had metastatic castration-resistant prostate cancer previously treated with docetaxel; and had disease progression during 12 months of treatment with abiraterone or enzalutamide. All patients had histologically proven prostate cancer, castrate levels of serum testosterone, and disease progression, defined by at least 2 new bone lesions or rising prostate-specific antigen (PSA) level. A total of 255 patients underwent randomization between November 2015 and November 2018, with 129 assigned to receive cabazitaxel and 126 patients assigned to receive an ASTI, 58 of whom received abiraterone and 66 of whom received enzalutamide. Patients who had received an ASTI in the setting of castrate-sensitive metastatic prostate cancer were included.

Intervention. Patients were randomized in a 1:1 fashion to receive either cabazitaxel or abiraterone or enzalutamide. Patients receiving cabazitaxel 25 mg/m² intravenously every 3 weeks also received oral prednisone daily and primary prophylactic granulocyte-colony stimulating factor. Patients assigned to receive an ASTI received abiraterone 1000 mg orally daily with prednisone 5 mg twice daily or enzalutamide 160 mg daily. Patients in the ASTI group who had progressed on abiraterone were assigned to enzalutamide, and alternatively, those on enzalutamide were assigned to abiraterone. Patients were treated until 1 of the following occurred: imaging-based disease progression, unacceptable toxicity, or advancing to an alternative therapy.

Main outcome measures. The primary endpoint was imaging-based progression-free survival, which was defined as the time from randomization until objective tumor progression, progression of bone lesions, or death. The secondary endpoints were overall survival, progression-free survival, PSA response, tumor and pain responses, a new symptomatic skeletal event, and safety.

Results. The median follow-up was 9.2 months. Imaging-based disease progression or death from any cause occurred in 95 (73.6%) participants in the cabazitaxel group, as compared to 101 (80.2%) who were assigned to receive an ASTI. The median imaging-based progression-free survival was 8.0 months in the cabazitaxel group and 3.7 months in the abiraterone/enzalutamide group. The median duration of treatment was longer in those receiving cabazitaxel (22 vs 12.5 weeks). The primary reason for treatment discontinuation was disease progression (in 43.7% of patients receiving cabazitaxel and 71% receiving an ASTI) or an adverse event (19.8% and 8.9%, respectively).

The trial’s secondary endpoints demonstrated improved outcomes in the cabazitaxel group compared to the abiraterone/enzalutamide group. There were 70 deaths (54.2%) in the cabazitaxel group and 83 (65.9%) in the ASTI group. Both the median overall survival (13.6 months in the cabazitaxel group and 11 months in the ASTI group) and the median progression-free survival (4.4 months and 2.7 months, respectively) were improved in those who received cabazitaxel. There was a 50% or greater reduction in the PSA level from baseline in 35.7% of the cabazitaxel group and 13.5% of the ASTI group.

Regarding the safety of the agents, the incidence of adverse events was similar in each group (38.9% in the cabazitaxel group and 38.7% in the ASTI group). Treatment discontinuation occurred more frequently in the cabazitaxel group (19.8%) compared to the ASTI group (8.9%). Adverse events of grade 3 or higher occurred more frequently with cabazitaxel; these were asthenia (4% vs 2.4%), diarrhea (3.2% vs 0), peripheral neuropathy (3.2% vs 0 patients), and febrile neutropenia (3.2% vs 0 patients).

Conclusion. Patients who had disease progression within 12 months on an ASTI and had previously been treated for metastatic castration-resistant prostate cancer with docetaxel had longer imaging-based progression-free survival and overall survival when treated with cabazitaxel compared to those treated with an alternative ASTI. Other clinical outcomes, including overall survival and progression-free survival, were also improved in the cabazitaxel group.

Commentary

Four ASTIs are approved for therapy in men with advanced prostate cancer. The next line of therapy following progression on an ASTI, whether to consider second-line androgen targeted inhibitors or proceed to taxane-based chemotherapy, has been unclear. The current CARD trial sought to answer this question and provides evidence that cabazitaxel is the next line of therapy for these patients. The trial’s primary endpoint, imaging-based disease progression, was reported in 73.6% of those who received cabazitaxel and in 80.2% of those who received abiraterone or enzalutamide. Patients treated with cabazitaxel had a longer imaging-based progression-free survival (8.0 months vs 3.7 months) and a longer duration of treatment (22 vs 12.5 weeks).

Because there is clinical evidence of cross-resistance between different ASTIs, the value of sequential therapy has been unclear. Emergence of androgen-receptor splice variant 7 (AR-V7) mutational status in circulating tumor cells is associated with poor outcomes with secondary androgen-signaling inhibitor therapy, and may be an indicator of resistance to subsequent androgen-signaling inhibitors.^1,2 In the PROPHECY trial, the response rates to subsequent androgen targeted therapy in patients with AR-V7 mutations ranged from 30% to 40%.³ Understanding how AR-V7 mutational status may impact such outcomes will certainly help define whether a subgroup exists in whom use of second-line androgen signaling inhibitors may be considered.

The patients enrolled in the current study appear to represent a subgroup of patients with biologically aggressive disease or with inherent resistance to ASTIs. The patients included in this study progressed within 1 year of androgen targeted therapy, which is representative of a more aggressive population of patients who may be hormone insensitive and derive more benefit from chemotherapy. Initial androgen deprivation therapy was given for 13.7 and 12.6 months to the cabazitaxel and enzalutamide/abiraterone arms, respectively, prior to developing castrate-resistant prostate cancer. Patients enrolled in this study also previously received docetaxel, deselecting those who are taxane-resistant and therefore may be less likely to respond to additional taxane-based therapy. Detection of AR-V7 splice variant expression in circulating tumor cells, consideration of biomarker data, and sensitivity to taxanes may help guide decisions regarding the use of sequential androgen-targeted agents; however, there has been no clear data to guide such an approach. It is also important to consider that, because this is a European study, the approved dose given in this trial was 25 mg/m². The PROSELICA trial previously demonstrated noninferiority of 20 mg/m² compared with 25 mg/m², with fewer adverse events, which is the dose now utilized in the United States.⁴

The adverse events of grade 3 or greater occurring in the cabazitaxel group should be discussed with patients, including fatigue, diarrhea, peripheral neuropathy, and febrile neutropenia.

The data from the CARD trial provide guidance regarding therapy sequencing in those with advanced prostate cancer after progression on first-line androgen targeted inhibitors and docetaxel; however, further work is needed to understand the universal application of this data in this cohort.

Applications in Clinical Practice

Patients with metastatic castration-resistant prostate cancer who have received docetaxel and progressed on an androgen-signaling inhibitor within 12 months should be considered for cabazitaxel over an alternative androgen-signaling inhibitor. This decision should be based on several factors, including AR-V7 mutational status, duration of androgen deprivation therapy, and hormone and taxane sensitivity in the past. Future studies are likely to incorporate genomic biomarkers rather than clinical criteria alone to make treatment decisions.

–Britni Souther, DO, and Daniel Isaac, DO, MS, Michigan State University, East Lansing, MI

Study Overview

Objective. To evaluate the efficacy of cabazitaxel compared to androgen-signaling–targeted inhibitors (ASTIs) in patients with metastatic castration-resistant prostate cancer who have received docetaxel and have progressed within 12 months of treatment with either abiraterone or enzalutamide.

Design. The CARD trial was an international, randomized, open-label phase 3 trial conducted across 13 European countries.

Setting and participants. Eligible patients were 18 years of age or older; had metastatic castration-resistant prostate cancer previously treated with docetaxel; and had disease progression during 12 months of treatment with abiraterone or enzalutamide. All patients had histologically proven prostate cancer, castrate levels of serum testosterone, and disease progression, defined by at least 2 new bone lesions or rising prostate-specific antigen (PSA) level. A total of 255 patients underwent randomization between November 2015 and November 2018, with 129 assigned to receive cabazitaxel and 126 patients assigned to receive an ASTI, 58 of whom received abiraterone and 66 of whom received enzalutamide. Patients who had received an ASTI in the setting of castrate-sensitive metastatic prostate cancer were included.

Intervention. Patients were randomized in a 1:1 fashion to receive either cabazitaxel or abiraterone or enzalutamide. Patients receiving cabazitaxel 25 mg/m² intravenously every 3 weeks also received oral prednisone daily and primary prophylactic granulocyte-colony stimulating factor. Patients assigned to receive an ASTI received abiraterone 1000 mg orally daily with prednisone 5 mg twice daily or enzalutamide 160 mg daily. Patients in the ASTI group who had progressed on abiraterone were assigned to enzalutamide, and alternatively, those on enzalutamide were assigned to abiraterone. Patients were treated until 1 of the following occurred: imaging-based disease progression, unacceptable toxicity, or advancing to an alternative therapy.

Main outcome measures. The primary endpoint was imaging-based progression-free survival, which was defined as the time from randomization until objective tumor progression, progression of bone lesions, or death. The secondary endpoints were overall survival, progression-free survival, PSA response, tumor and pain responses, a new symptomatic skeletal event, and safety.

Results. The median follow-up was 9.2 months. Imaging-based disease progression or death from any cause occurred in 95 (73.6%) participants in the cabazitaxel group, as compared to 101 (80.2%) who were assigned to receive an ASTI. The median imaging-based progression-free survival was 8.0 months in the cabazitaxel group and 3.7 months in the abiraterone/enzalutamide group. The median duration of treatment was longer in those receiving cabazitaxel (22 vs 12.5 weeks). The primary reason for treatment discontinuation was disease progression (in 43.7% of patients receiving cabazitaxel and 71% receiving an ASTI) or an adverse event (19.8% and 8.9%, respectively).

The trial’s secondary endpoints demonstrated improved outcomes in the cabazitaxel group compared to the abiraterone/enzalutamide group. There were 70 deaths (54.2%) in the cabazitaxel group and 83 (65.9%) in the ASTI group. Both the median overall survival (13.6 months in the cabazitaxel group and 11 months in the ASTI group) and the median progression-free survival (4.4 months and 2.7 months, respectively) were improved in those who received cabazitaxel. There was a 50% or greater reduction in the PSA level from baseline in 35.7% of the cabazitaxel group and 13.5% of the ASTI group.

Regarding the safety of the agents, the incidence of adverse events was similar in each group (38.9% in the cabazitaxel group and 38.7% in the ASTI group). Treatment discontinuation occurred more frequently in the cabazitaxel group (19.8%) compared to the ASTI group (8.9%). Adverse events of grade 3 or higher occurred more frequently with cabazitaxel; these were asthenia (4% vs 2.4%), diarrhea (3.2% vs 0), peripheral neuropathy (3.2% vs 0 patients), and febrile neutropenia (3.2% vs 0 patients).

Conclusion. Patients who had disease progression within 12 months on an ASTI and had previously been treated for metastatic castration-resistant prostate cancer with docetaxel had longer imaging-based progression-free survival and overall survival when treated with cabazitaxel compared to those treated with an alternative ASTI. Other clinical outcomes, including overall survival and progression-free survival, were also improved in the cabazitaxel group.

Commentary

Four ASTIs are approved for therapy in men with advanced prostate cancer. The next line of therapy following progression on an ASTI, whether to consider second-line androgen targeted inhibitors or proceed to taxane-based chemotherapy, has been unclear. The current CARD trial sought to answer this question and provides evidence that cabazitaxel is the next line of therapy for these patients. The trial’s primary endpoint, imaging-based disease progression, was reported in 73.6% of those who received cabazitaxel and in 80.2% of those who received abiraterone or enzalutamide. Patients treated with cabazitaxel had a longer imaging-based progression-free survival (8.0 months vs 3.7 months) and a longer duration of treatment (22 vs 12.5 weeks).

Because there is clinical evidence of cross-resistance between different ASTIs, the value of sequential therapy has been unclear. Emergence of androgen-receptor splice variant 7 (AR-V7) mutational status in circulating tumor cells is associated with poor outcomes with secondary androgen-signaling inhibitor therapy, and may be an indicator of resistance to subsequent androgen-signaling inhibitors.^1,2 In the PROPHECY trial, the response rates to subsequent androgen targeted therapy in patients with AR-V7 mutations ranged from 30% to 40%.³ Understanding how AR-V7 mutational status may impact such outcomes will certainly help define whether a subgroup exists in whom use of second-line androgen signaling inhibitors may be considered.

The patients enrolled in the current study appear to represent a subgroup of patients with biologically aggressive disease or with inherent resistance to ASTIs. The patients included in this study progressed within 1 year of androgen targeted therapy, which is representative of a more aggressive population of patients who may be hormone insensitive and derive more benefit from chemotherapy. Initial androgen deprivation therapy was given for 13.7 and 12.6 months to the cabazitaxel and enzalutamide/abiraterone arms, respectively, prior to developing castrate-resistant prostate cancer. Patients enrolled in this study also previously received docetaxel, deselecting those who are taxane-resistant and therefore may be less likely to respond to additional taxane-based therapy. Detection of AR-V7 splice variant expression in circulating tumor cells, consideration of biomarker data, and sensitivity to taxanes may help guide decisions regarding the use of sequential androgen-targeted agents; however, there has been no clear data to guide such an approach. It is also important to consider that, because this is a European study, the approved dose given in this trial was 25 mg/m². The PROSELICA trial previously demonstrated noninferiority of 20 mg/m² compared with 25 mg/m², with fewer adverse events, which is the dose now utilized in the United States.⁴

The adverse events of grade 3 or greater occurring in the cabazitaxel group should be discussed with patients, including fatigue, diarrhea, peripheral neuropathy, and febrile neutropenia.

The data from the CARD trial provide guidance regarding therapy sequencing in those with advanced prostate cancer after progression on first-line androgen targeted inhibitors and docetaxel; however, further work is needed to understand the universal application of this data in this cohort.

Applications in Clinical Practice

Patients with metastatic castration-resistant prostate cancer who have received docetaxel and progressed on an androgen-signaling inhibitor within 12 months should be considered for cabazitaxel over an alternative androgen-signaling inhibitor. This decision should be based on several factors, including AR-V7 mutational status, duration of androgen deprivation therapy, and hormone and taxane sensitivity in the past. Future studies are likely to incorporate genomic biomarkers rather than clinical criteria alone to make treatment decisions.

–Britni Souther, DO, and Daniel Isaac, DO, MS, Michigan State University, East Lansing, MI

Study Overview

Objective. To evaluate the efficacy of cabazitaxel compared to androgen-signaling–targeted inhibitors (ASTIs) in patients with metastatic castration-resistant prostate cancer who have received docetaxel and have progressed within 12 months of treatment with either abiraterone or enzalutamide.

Design. The CARD trial was an international, randomized, open-label phase 3 trial conducted across 13 European countries.

Setting and participants. Eligible patients were 18 years of age or older; had metastatic castration-resistant prostate cancer previously treated with docetaxel; and had disease progression during 12 months of treatment with abiraterone or enzalutamide. All patients had histologically proven prostate cancer, castrate levels of serum testosterone, and disease progression, defined by at least 2 new bone lesions or rising prostate-specific antigen (PSA) level. A total of 255 patients underwent randomization between November 2015 and November 2018, with 129 assigned to receive cabazitaxel and 126 patients assigned to receive an ASTI, 58 of whom received abiraterone and 66 of whom received enzalutamide. Patients who had received an ASTI in the setting of castrate-sensitive metastatic prostate cancer were included.

Intervention. Patients were randomized in a 1:1 fashion to receive either cabazitaxel or abiraterone or enzalutamide. Patients receiving cabazitaxel 25 mg/m² intravenously every 3 weeks also received oral prednisone daily and primary prophylactic granulocyte-colony stimulating factor. Patients assigned to receive an ASTI received abiraterone 1000 mg orally daily with prednisone 5 mg twice daily or enzalutamide 160 mg daily. Patients in the ASTI group who had progressed on abiraterone were assigned to enzalutamide, and alternatively, those on enzalutamide were assigned to abiraterone. Patients were treated until 1 of the following occurred: imaging-based disease progression, unacceptable toxicity, or advancing to an alternative therapy.

Main outcome measures. The primary endpoint was imaging-based progression-free survival, which was defined as the time from randomization until objective tumor progression, progression of bone lesions, or death. The secondary endpoints were overall survival, progression-free survival, PSA response, tumor and pain responses, a new symptomatic skeletal event, and safety.

Results. The median follow-up was 9.2 months. Imaging-based disease progression or death from any cause occurred in 95 (73.6%) participants in the cabazitaxel group, as compared to 101 (80.2%) who were assigned to receive an ASTI. The median imaging-based progression-free survival was 8.0 months in the cabazitaxel group and 3.7 months in the abiraterone/enzalutamide group. The median duration of treatment was longer in those receiving cabazitaxel (22 vs 12.5 weeks). The primary reason for treatment discontinuation was disease progression (in 43.7% of patients receiving cabazitaxel and 71% receiving an ASTI) or an adverse event (19.8% and 8.9%, respectively).

The trial’s secondary endpoints demonstrated improved outcomes in the cabazitaxel group compared to the abiraterone/enzalutamide group. There were 70 deaths (54.2%) in the cabazitaxel group and 83 (65.9%) in the ASTI group. Both the median overall survival (13.6 months in the cabazitaxel group and 11 months in the ASTI group) and the median progression-free survival (4.4 months and 2.7 months, respectively) were improved in those who received cabazitaxel. There was a 50% or greater reduction in the PSA level from baseline in 35.7% of the cabazitaxel group and 13.5% of the ASTI group.

Regarding the safety of the agents, the incidence of adverse events was similar in each group (38.9% in the cabazitaxel group and 38.7% in the ASTI group). Treatment discontinuation occurred more frequently in the cabazitaxel group (19.8%) compared to the ASTI group (8.9%). Adverse events of grade 3 or higher occurred more frequently with cabazitaxel; these were asthenia (4% vs 2.4%), diarrhea (3.2% vs 0), peripheral neuropathy (3.2% vs 0 patients), and febrile neutropenia (3.2% vs 0 patients).

Conclusion. Patients who had disease progression within 12 months on an ASTI and had previously been treated for metastatic castration-resistant prostate cancer with docetaxel had longer imaging-based progression-free survival and overall survival when treated with cabazitaxel compared to those treated with an alternative ASTI. Other clinical outcomes, including overall survival and progression-free survival, were also improved in the cabazitaxel group.

Commentary

Four ASTIs are approved for therapy in men with advanced prostate cancer. The next line of therapy following progression on an ASTI, whether to consider second-line androgen targeted inhibitors or proceed to taxane-based chemotherapy, has been unclear. The current CARD trial sought to answer this question and provides evidence that cabazitaxel is the next line of therapy for these patients. The trial’s primary endpoint, imaging-based disease progression, was reported in 73.6% of those who received cabazitaxel and in 80.2% of those who received abiraterone or enzalutamide. Patients treated with cabazitaxel had a longer imaging-based progression-free survival (8.0 months vs 3.7 months) and a longer duration of treatment (22 vs 12.5 weeks).

Because there is clinical evidence of cross-resistance between different ASTIs, the value of sequential therapy has been unclear. Emergence of androgen-receptor splice variant 7 (AR-V7) mutational status in circulating tumor cells is associated with poor outcomes with secondary androgen-signaling inhibitor therapy, and may be an indicator of resistance to subsequent androgen-signaling inhibitors.^1,2 In the PROPHECY trial, the response rates to subsequent androgen targeted therapy in patients with AR-V7 mutations ranged from 30% to 40%.³ Understanding how AR-V7 mutational status may impact such outcomes will certainly help define whether a subgroup exists in whom use of second-line androgen signaling inhibitors may be considered.

The patients enrolled in the current study appear to represent a subgroup of patients with biologically aggressive disease or with inherent resistance to ASTIs. The patients included in this study progressed within 1 year of androgen targeted therapy, which is representative of a more aggressive population of patients who may be hormone insensitive and derive more benefit from chemotherapy. Initial androgen deprivation therapy was given for 13.7 and 12.6 months to the cabazitaxel and enzalutamide/abiraterone arms, respectively, prior to developing castrate-resistant prostate cancer. Patients enrolled in this study also previously received docetaxel, deselecting those who are taxane-resistant and therefore may be less likely to respond to additional taxane-based therapy. Detection of AR-V7 splice variant expression in circulating tumor cells, consideration of biomarker data, and sensitivity to taxanes may help guide decisions regarding the use of sequential androgen-targeted agents; however, there has been no clear data to guide such an approach. It is also important to consider that, because this is a European study, the approved dose given in this trial was 25 mg/m². The PROSELICA trial previously demonstrated noninferiority of 20 mg/m² compared with 25 mg/m², with fewer adverse events, which is the dose now utilized in the United States.⁴

The adverse events of grade 3 or greater occurring in the cabazitaxel group should be discussed with patients, including fatigue, diarrhea, peripheral neuropathy, and febrile neutropenia.

The data from the CARD trial provide guidance regarding therapy sequencing in those with advanced prostate cancer after progression on first-line androgen targeted inhibitors and docetaxel; however, further work is needed to understand the universal application of this data in this cohort.

Applications in Clinical Practice

Patients with metastatic castration-resistant prostate cancer who have received docetaxel and progressed on an androgen-signaling inhibitor within 12 months should be considered for cabazitaxel over an alternative androgen-signaling inhibitor. This decision should be based on several factors, including AR-V7 mutational status, duration of androgen deprivation therapy, and hormone and taxane sensitivity in the past. Future studies are likely to incorporate genomic biomarkers rather than clinical criteria alone to make treatment decisions.

–Britni Souther, DO, and Daniel Isaac, DO, MS, Michigan State University, East Lansing, MI

Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.

The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.

Now rheumatologists are trying to reassure patients with lupus or other rheumatic diseases who take the antimalarials that they will be available and are relatively easy for manufacturers to produce.

In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.

Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity. 
 

Questions about hydroxychloroquine shortage

Q: What is the current situation with hydroxychloroquine in your practice?

A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.

Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
 

Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?

A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.

Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.

Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.

The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.

Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
 

Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?

A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.

Q: Are there pharmacy restrictions on prescription amounts?

A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
 

Colchicine COVID-19 trial underway

Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too. 

Q: What is the general availability of colchicine and its susceptibility to shortage?

A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.

The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.

Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
 

Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?

A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.

The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.

While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.

Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.

The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.

Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.

So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.

Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.

jevans@mdedge.com

This article was reformatted on 3/30/2020 for clarity. 

Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.

The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.

Now rheumatologists are trying to reassure patients with lupus or other rheumatic diseases who take the antimalarials that they will be available and are relatively easy for manufacturers to produce.

In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.

Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity. 
 

Questions about hydroxychloroquine shortage

Q: What is the current situation with hydroxychloroquine in your practice?

A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.

Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
 

Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?

A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.

Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.

Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.

The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.

Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
 

Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?

A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.

Q: Are there pharmacy restrictions on prescription amounts?

A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
 

Colchicine COVID-19 trial underway

Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too. 

Q: What is the general availability of colchicine and its susceptibility to shortage?

A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.

The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.

Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
 

Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?

A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.

The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.

While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.

Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.

The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.

Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.

So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.

Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.

jevans@mdedge.com

This article was reformatted on 3/30/2020 for clarity. 

Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.

The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.

Now rheumatologists are trying to reassure patients with lupus or other rheumatic diseases who take the antimalarials that they will be available and are relatively easy for manufacturers to produce.

In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.

Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity. 
 

Questions about hydroxychloroquine shortage

Q: What is the current situation with hydroxychloroquine in your practice?

A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.

Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
 

Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?

A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.

Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.

Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.

The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.

Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
 

Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?

A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.

Q: Are there pharmacy restrictions on prescription amounts?

A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
 

Colchicine COVID-19 trial underway

Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too. 

Q: What is the general availability of colchicine and its susceptibility to shortage?

A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.

The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.

Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
 

Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?

A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.

The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.

While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.

Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.

The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.

Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.

So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.

Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.

jevans@mdedge.com

This article was reformatted on 3/30/2020 for clarity. 

Despite highly effective antiretroviral therapy, HIV still shortens life expectancy by 9 years and healthy life expectancy free of comorbidities 16 years, according to a review of HIV patients and matched controls at Kaiser Permanente facilities in California and the mid-Atlantic states during 2000-2016.

M. Alexander Otto/MDedge News

The good news is that starting antiretroviral therapy (ART) when CD4 counts are 500 cells/mm³ or higher closes the mortality gap. People who do so can expect to live into their mid-80s, the same as people without HIV, and the years they can expect to be free of diabetes and cancer is catching up to uninfected people, although the gap for other comorbidities hasn’t changed and the overall comorbidity gap remains 16 years, according to the report, which was presented at the Conference on Retroviruses & Opportunistic Infections

“We were excited about finding no difference in lifespan for people starting ART with high CD4 counts, but we were surprised by how wide the gap was for the number of comorbidity free years. Greater attention to comorbidity prevention is needed,” said study lead Julia Marcus, PhD, an infectious disease epidemiologist and assistant professor of population medicine at Harvard Medical School, Boston.

The team estimated the average number of total and comorbidity-free years of life remaining at age 21 for 39,000 people with HIV who were matched 1:10 with 387,767 uninfected adults by sex, race/ethnicity, year, and medical center.

Overall, adults with HIV could expect to live until they were 77 years old, versus 86 years for people without HIV, during 2014-2016. It’s a large improvement over the 22 year gap during 2000-2003, when the numbers were 59 versus 81 years, respectively, Dr. Marcus reported at the virtual meeting, which was scheduled to be in Boston, but held online this year because of concerns about spreading the COVID-19 virus.

But the overall comorbidity gap didn’t budge during 2000-2016. People with HIV during 2014-2016 could expect to be comorbidity free until age 36 years, versus 52 years for the general population, the same 16-year difference during 2000-2003, when the numbers were age 32 versus age 48 years.

During 2014-2016, liver disease came 24 years sooner with HIV, and chronic kidney disease 17 years, chronic lung disease 16 years, cancer 9 years, and diabetes and cancer both 8 years sooner. Early ART didn’t narrow the gap for most comorbidities. Dr. Marcus didn’t address the reasons for the differences, except to note that “smoking rates were definitely higher among people with HIV.”

The results weren’t broken down by sex, but the majority of subjects, 88%, were men. The mean age was 41 years, and about half were white, with most of the rest either black or Hispanic. Transmission was among men who have sex with men in 70% of the cases, heterosexual sex in 20%, and IV drug accounted for the rest. Almost a third of the subjects started ART with CD4 counts at or above 500 cells/mm³.

Dr. Marcus said the results are likely generalizable to most insured people with HIV, but also that comorbidity screening might be higher in the HIV population, which could have affected the results.

The work was funded by the National Institutes of Health. Dr. Marcus is an adviser for Gilead.

aotto@mdedge.com

SOURCE: Marcus JL et al. CROI 2020. Abstract 151.

Despite highly effective antiretroviral therapy, HIV still shortens life expectancy by 9 years and healthy life expectancy free of comorbidities 16 years, according to a review of HIV patients and matched controls at Kaiser Permanente facilities in California and the mid-Atlantic states during 2000-2016.

M. Alexander Otto/MDedge News

The good news is that starting antiretroviral therapy (ART) when CD4 counts are 500 cells/mm³ or higher closes the mortality gap. People who do so can expect to live into their mid-80s, the same as people without HIV, and the years they can expect to be free of diabetes and cancer is catching up to uninfected people, although the gap for other comorbidities hasn’t changed and the overall comorbidity gap remains 16 years, according to the report, which was presented at the Conference on Retroviruses & Opportunistic Infections

“We were excited about finding no difference in lifespan for people starting ART with high CD4 counts, but we were surprised by how wide the gap was for the number of comorbidity free years. Greater attention to comorbidity prevention is needed,” said study lead Julia Marcus, PhD, an infectious disease epidemiologist and assistant professor of population medicine at Harvard Medical School, Boston.

The team estimated the average number of total and comorbidity-free years of life remaining at age 21 for 39,000 people with HIV who were matched 1:10 with 387,767 uninfected adults by sex, race/ethnicity, year, and medical center.

Overall, adults with HIV could expect to live until they were 77 years old, versus 86 years for people without HIV, during 2014-2016. It’s a large improvement over the 22 year gap during 2000-2003, when the numbers were 59 versus 81 years, respectively, Dr. Marcus reported at the virtual meeting, which was scheduled to be in Boston, but held online this year because of concerns about spreading the COVID-19 virus.

But the overall comorbidity gap didn’t budge during 2000-2016. People with HIV during 2014-2016 could expect to be comorbidity free until age 36 years, versus 52 years for the general population, the same 16-year difference during 2000-2003, when the numbers were age 32 versus age 48 years.

During 2014-2016, liver disease came 24 years sooner with HIV, and chronic kidney disease 17 years, chronic lung disease 16 years, cancer 9 years, and diabetes and cancer both 8 years sooner. Early ART didn’t narrow the gap for most comorbidities. Dr. Marcus didn’t address the reasons for the differences, except to note that “smoking rates were definitely higher among people with HIV.”

The results weren’t broken down by sex, but the majority of subjects, 88%, were men. The mean age was 41 years, and about half were white, with most of the rest either black or Hispanic. Transmission was among men who have sex with men in 70% of the cases, heterosexual sex in 20%, and IV drug accounted for the rest. Almost a third of the subjects started ART with CD4 counts at or above 500 cells/mm³.

Dr. Marcus said the results are likely generalizable to most insured people with HIV, but also that comorbidity screening might be higher in the HIV population, which could have affected the results.

The work was funded by the National Institutes of Health. Dr. Marcus is an adviser for Gilead.

aotto@mdedge.com

SOURCE: Marcus JL et al. CROI 2020. Abstract 151.

Despite highly effective antiretroviral therapy, HIV still shortens life expectancy by 9 years and healthy life expectancy free of comorbidities 16 years, according to a review of HIV patients and matched controls at Kaiser Permanente facilities in California and the mid-Atlantic states during 2000-2016.

M. Alexander Otto/MDedge News

The good news is that starting antiretroviral therapy (ART) when CD4 counts are 500 cells/mm³ or higher closes the mortality gap. People who do so can expect to live into their mid-80s, the same as people without HIV, and the years they can expect to be free of diabetes and cancer is catching up to uninfected people, although the gap for other comorbidities hasn’t changed and the overall comorbidity gap remains 16 years, according to the report, which was presented at the Conference on Retroviruses & Opportunistic Infections

“We were excited about finding no difference in lifespan for people starting ART with high CD4 counts, but we were surprised by how wide the gap was for the number of comorbidity free years. Greater attention to comorbidity prevention is needed,” said study lead Julia Marcus, PhD, an infectious disease epidemiologist and assistant professor of population medicine at Harvard Medical School, Boston.

The team estimated the average number of total and comorbidity-free years of life remaining at age 21 for 39,000 people with HIV who were matched 1:10 with 387,767 uninfected adults by sex, race/ethnicity, year, and medical center.

Overall, adults with HIV could expect to live until they were 77 years old, versus 86 years for people without HIV, during 2014-2016. It’s a large improvement over the 22 year gap during 2000-2003, when the numbers were 59 versus 81 years, respectively, Dr. Marcus reported at the virtual meeting, which was scheduled to be in Boston, but held online this year because of concerns about spreading the COVID-19 virus.

But the overall comorbidity gap didn’t budge during 2000-2016. People with HIV during 2014-2016 could expect to be comorbidity free until age 36 years, versus 52 years for the general population, the same 16-year difference during 2000-2003, when the numbers were age 32 versus age 48 years.

During 2014-2016, liver disease came 24 years sooner with HIV, and chronic kidney disease 17 years, chronic lung disease 16 years, cancer 9 years, and diabetes and cancer both 8 years sooner. Early ART didn’t narrow the gap for most comorbidities. Dr. Marcus didn’t address the reasons for the differences, except to note that “smoking rates were definitely higher among people with HIV.”

The results weren’t broken down by sex, but the majority of subjects, 88%, were men. The mean age was 41 years, and about half were white, with most of the rest either black or Hispanic. Transmission was among men who have sex with men in 70% of the cases, heterosexual sex in 20%, and IV drug accounted for the rest. Almost a third of the subjects started ART with CD4 counts at or above 500 cells/mm³.

Dr. Marcus said the results are likely generalizable to most insured people with HIV, but also that comorbidity screening might be higher in the HIV population, which could have affected the results.

The work was funded by the National Institutes of Health. Dr. Marcus is an adviser for Gilead.

aotto@mdedge.com

SOURCE: Marcus JL et al. CROI 2020. Abstract 151.

Physicians were concerned about the safety of their loved ones and themselves and pessimistic about how those outside of the medical community will respond to the pandemic, according to a survey.

One positive finding from the physicians who participated in this survey March 19-20 was that the availability of COVID-19 test kits has more than doubled since late February.

Reported access to test kits went from 31% in the first wave of a series of surveys (Jan. 31–Feb. 4), down to 20% in the second (Feb. 26-27), and then jumped to 67% by the third wave (March 19-20), InCrowd reported March 26.

Views on several other COVID-related topics were negative among the majority of responding physicians – all of whom had or were currently treating 20 or more patients with flu-like symptoms at the time of the survey.

“Their frustrations and concerns about their ability to protect themselves while meeting upcoming patient care levels has increased significantly in the last 3 months,” Daniel S. Fitzgerald, CEO and president of InCrowd, said in a written statement.

In the third wave, 78% of respondents were “concerned for the safety of loved ones due to my exposure as a physician to COVID-19” and only 16% believed that their facility was “staffed adequately to treat the influx of patients anticipated in the next 30 days,” InCrowd said.

One primary care physician from California elaborated on the issue of safety equipment: “First, [the CDC] said we need N95 masks and other masks would not protect us. As those are running out then they said just use regular surgical masks. Now they are saying use bandannas and scarves! It’s like they don’t care about the safety of the people who will be treating the ill! We don’t want to bring it home to our families!”

“Overall, morale appears low, with few optimistic about the efficacy of public-private collaboration (21%), their own safety given current PPE [personal protective equipment] supply (13%), and the U.S.’s ability to ‘flatten the curve’ (12%),” InCrowd noted in the report.

The first two waves each had 150 respondents, but the number increased to 263 for wave 3, with similar proportions – about 50% emergency medicine or critical care specialists, 25% pediatricians, and 25% primary care physicians – in all three.

rfranki@mdedge.com

Physicians were concerned about the safety of their loved ones and themselves and pessimistic about how those outside of the medical community will respond to the pandemic, according to a survey.

One positive finding from the physicians who participated in this survey March 19-20 was that the availability of COVID-19 test kits has more than doubled since late February.

Reported access to test kits went from 31% in the first wave of a series of surveys (Jan. 31–Feb. 4), down to 20% in the second (Feb. 26-27), and then jumped to 67% by the third wave (March 19-20), InCrowd reported March 26.

Views on several other COVID-related topics were negative among the majority of responding physicians – all of whom had or were currently treating 20 or more patients with flu-like symptoms at the time of the survey.

“Their frustrations and concerns about their ability to protect themselves while meeting upcoming patient care levels has increased significantly in the last 3 months,” Daniel S. Fitzgerald, CEO and president of InCrowd, said in a written statement.

In the third wave, 78% of respondents were “concerned for the safety of loved ones due to my exposure as a physician to COVID-19” and only 16% believed that their facility was “staffed adequately to treat the influx of patients anticipated in the next 30 days,” InCrowd said.

One primary care physician from California elaborated on the issue of safety equipment: “First, [the CDC] said we need N95 masks and other masks would not protect us. As those are running out then they said just use regular surgical masks. Now they are saying use bandannas and scarves! It’s like they don’t care about the safety of the people who will be treating the ill! We don’t want to bring it home to our families!”

“Overall, morale appears low, with few optimistic about the efficacy of public-private collaboration (21%), their own safety given current PPE [personal protective equipment] supply (13%), and the U.S.’s ability to ‘flatten the curve’ (12%),” InCrowd noted in the report.

The first two waves each had 150 respondents, but the number increased to 263 for wave 3, with similar proportions – about 50% emergency medicine or critical care specialists, 25% pediatricians, and 25% primary care physicians – in all three.

rfranki@mdedge.com

Physicians were concerned about the safety of their loved ones and themselves and pessimistic about how those outside of the medical community will respond to the pandemic, according to a survey.

One positive finding from the physicians who participated in this survey March 19-20 was that the availability of COVID-19 test kits has more than doubled since late February.

Reported access to test kits went from 31% in the first wave of a series of surveys (Jan. 31–Feb. 4), down to 20% in the second (Feb. 26-27), and then jumped to 67% by the third wave (March 19-20), InCrowd reported March 26.

Views on several other COVID-related topics were negative among the majority of responding physicians – all of whom had or were currently treating 20 or more patients with flu-like symptoms at the time of the survey.

“Their frustrations and concerns about their ability to protect themselves while meeting upcoming patient care levels has increased significantly in the last 3 months,” Daniel S. Fitzgerald, CEO and president of InCrowd, said in a written statement.

In the third wave, 78% of respondents were “concerned for the safety of loved ones due to my exposure as a physician to COVID-19” and only 16% believed that their facility was “staffed adequately to treat the influx of patients anticipated in the next 30 days,” InCrowd said.

One primary care physician from California elaborated on the issue of safety equipment: “First, [the CDC] said we need N95 masks and other masks would not protect us. As those are running out then they said just use regular surgical masks. Now they are saying use bandannas and scarves! It’s like they don’t care about the safety of the people who will be treating the ill! We don’t want to bring it home to our families!”

“Overall, morale appears low, with few optimistic about the efficacy of public-private collaboration (21%), their own safety given current PPE [personal protective equipment] supply (13%), and the U.S.’s ability to ‘flatten the curve’ (12%),” InCrowd noted in the report.

The first two waves each had 150 respondents, but the number increased to 263 for wave 3, with similar proportions – about 50% emergency medicine or critical care specialists, 25% pediatricians, and 25% primary care physicians – in all three.

rfranki@mdedge.com

Reports from pediatric endocrinologists in COVID-19 hot spots globally indicate that children, adolescents, and young adults with diabetes have so far not shown a different disease pattern with the virus compared to children and younger people who do not have diabetes.

Indeed, colleagues in Wuhan, China, and Italy “state they have not had cases of COVID-19 in children, adolescents, or young adults less than 25 years of age with diabetes who required hospitalization, to date [as of March 24]” according to a new statement from the International Society for Pediatric and Adolescent Diabetes (ISPAD), which currently has about 1,300 members around the globe and has instituted a discussion forum about the topic of treating children with both diabetes and COVID-19.

“We find these reports [from colleagues around the world], though anecdotal, to be reassuring,” it notes. However, there are real worries regarding other potentially dangerous effects. ISPAD has expressed concern, for example, that the COVID-19 pandemic will prevent youngsters with existing diabetes who are having diabetic emergencies from seeking hospital care.

Chinese physicians have reported to ISPAD a number of cases of delayed hospital admissions for diabetic ketoacidosis (DKA) in children with known type 1 diabetes because hospital services were closed for non–COVID-19 care.

Andrea Scaramuzza, MD, a pediatric endocrinologist at Ospedale Maggiore di Cremona, Italy, has similarly reported multiple cases of patients presenting to emergency services there with severe DKA.

“These experiences reinforce the importance of continued attentiveness to standard diabetes care to avoid the need for hospitalization and emergency or urgent care visits,” says ISPAD, under the strapline: “Keep calm and mind your diabetes care.”

But it nevertheless stresses that these resources should be used “if needed.”
 

Worries that new-onset diabetes will be missed during COVID-19

Dr. Scaramuzza said in an interview that there also are concerns regarding delays in diagnoses of new cases of type 1 diabetes “due to the fear families have to go to the emergency department because of COVID-19.”

Indeed, in Italy, a few patients have arrived with very serious DKA, he said. Dr. Scaramuzza noted a colleague from Naples, Dario Iafusco, MD, and colleagues have made a video to keep awareness high regarding new-onset diabetes.

“This coronavirus pandemic can be defeated if you stay at home, but if you know of a child who has excessive thirst, frequent urination, or who starts vomiting,” seek health care advice immediately. “This child could have [type 1] diabetes. Prevent severe DKA, or worse, death,” Dr. Iafusco of the Regional Centre of Paediatric Diabetology G.Stoppoloni Via S. Andrea delle Dame, Naples, said in the video.

Physicians from China have similar observations, reporting to ISPAD several cases of delayed admissions of newly diagnosed type 1 diabetes because hospital services were closed for non–COVID-19 care.
 

Keep calm and mind your diabetes care; physicians use telemedicine

Meanwhile, last week ISPAD issued guidance for young people with diabetes and their carers about what to do if COVID-19 infection is suspected.

Most advice is the same as for the general public because reports of COVID-19 infection suggest it is much less severe in children and adolescents, and the summary currently serves “as reassurance that youth with diabetes are not more affected by COVID-19 than peers,” it adds.

“Our approach to treating a child with diabetes would be to follow the ISPAD sick-day guidelines, which provide generalized diabetes management in any flu-like illness. We wouldn’t do anything very different right now,” one of the authors, Jamie Wood, MD, associate professor of clinical pediatrics at Case Western Reserve University, Cleveland, said in an interview.

“Any illness makes diabetes more difficult to manage and can increase the risk of DKA,” she emphasized.

“We would reinforce frequent monitoring of blood glucose and ketone levels, to never stop insulin – in fact, when most people are ill, the body is stressed and requires more insulin – and to stay hydrated and treat the underlying symptoms.”

And make sure to “treat the fever,” she stressed. “When patients with type 1 diabetes get fever, they have a tendency to make more ketones, so we recommend aggressive control of fever.”

ISPAD recommends young people aim to keep blood glucose levels between 4 and 10 mmol/L (72-180 mg/dL) and blood ketones below 0.6 mmol/L (10.8 mg/dL) during illness and to never stop insulin.

Guidance is provided on when to seek urgent specialist advice with possible referral to emergency care, for example, in cases in which the patient has DKA symptoms, such as persistent and/or worsened fruity breath odor or vomiting.

Dr. Scaramuzza said in an interview that, in Italy, he and his colleagues have increased their use of telemedicine to keep monitoring their patients with diabetes even from a distance and that it was working very well.

“Technology – such as downloading [records from] insulin pumps, continuous glucose monitoring systems, and the possibility to use Skype or other platforms – really helps,” he noted.

“There has been a rapid increase in telehealth as a way to continue to care for youth with diabetes and decrease risk for infection,” said ISPAD.

“Communication between patients, families, and health care teams is vitally important. Methods to do so that avoid visits to clinics or hospitals can provide needed diabetes advice and reduce risk for COVID-19 transmission.”

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

Reports from pediatric endocrinologists in COVID-19 hot spots globally indicate that children, adolescents, and young adults with diabetes have so far not shown a different disease pattern with the virus compared to children and younger people who do not have diabetes.

Indeed, colleagues in Wuhan, China, and Italy “state they have not had cases of COVID-19 in children, adolescents, or young adults less than 25 years of age with diabetes who required hospitalization, to date [as of March 24]” according to a new statement from the International Society for Pediatric and Adolescent Diabetes (ISPAD), which currently has about 1,300 members around the globe and has instituted a discussion forum about the topic of treating children with both diabetes and COVID-19.

“We find these reports [from colleagues around the world], though anecdotal, to be reassuring,” it notes. However, there are real worries regarding other potentially dangerous effects. ISPAD has expressed concern, for example, that the COVID-19 pandemic will prevent youngsters with existing diabetes who are having diabetic emergencies from seeking hospital care.

Chinese physicians have reported to ISPAD a number of cases of delayed hospital admissions for diabetic ketoacidosis (DKA) in children with known type 1 diabetes because hospital services were closed for non–COVID-19 care.

Andrea Scaramuzza, MD, a pediatric endocrinologist at Ospedale Maggiore di Cremona, Italy, has similarly reported multiple cases of patients presenting to emergency services there with severe DKA.

“These experiences reinforce the importance of continued attentiveness to standard diabetes care to avoid the need for hospitalization and emergency or urgent care visits,” says ISPAD, under the strapline: “Keep calm and mind your diabetes care.”

But it nevertheless stresses that these resources should be used “if needed.”
 

Worries that new-onset diabetes will be missed during COVID-19

Dr. Scaramuzza said in an interview that there also are concerns regarding delays in diagnoses of new cases of type 1 diabetes “due to the fear families have to go to the emergency department because of COVID-19.”

Indeed, in Italy, a few patients have arrived with very serious DKA, he said. Dr. Scaramuzza noted a colleague from Naples, Dario Iafusco, MD, and colleagues have made a video to keep awareness high regarding new-onset diabetes.

“This coronavirus pandemic can be defeated if you stay at home, but if you know of a child who has excessive thirst, frequent urination, or who starts vomiting,” seek health care advice immediately. “This child could have [type 1] diabetes. Prevent severe DKA, or worse, death,” Dr. Iafusco of the Regional Centre of Paediatric Diabetology G.Stoppoloni Via S. Andrea delle Dame, Naples, said in the video.

Physicians from China have similar observations, reporting to ISPAD several cases of delayed admissions of newly diagnosed type 1 diabetes because hospital services were closed for non–COVID-19 care.
 

Keep calm and mind your diabetes care; physicians use telemedicine

Meanwhile, last week ISPAD issued guidance for young people with diabetes and their carers about what to do if COVID-19 infection is suspected.

Most advice is the same as for the general public because reports of COVID-19 infection suggest it is much less severe in children and adolescents, and the summary currently serves “as reassurance that youth with diabetes are not more affected by COVID-19 than peers,” it adds.

“Our approach to treating a child with diabetes would be to follow the ISPAD sick-day guidelines, which provide generalized diabetes management in any flu-like illness. We wouldn’t do anything very different right now,” one of the authors, Jamie Wood, MD, associate professor of clinical pediatrics at Case Western Reserve University, Cleveland, said in an interview.

“Any illness makes diabetes more difficult to manage and can increase the risk of DKA,” she emphasized.

“We would reinforce frequent monitoring of blood glucose and ketone levels, to never stop insulin – in fact, when most people are ill, the body is stressed and requires more insulin – and to stay hydrated and treat the underlying symptoms.”

And make sure to “treat the fever,” she stressed. “When patients with type 1 diabetes get fever, they have a tendency to make more ketones, so we recommend aggressive control of fever.”

ISPAD recommends young people aim to keep blood glucose levels between 4 and 10 mmol/L (72-180 mg/dL) and blood ketones below 0.6 mmol/L (10.8 mg/dL) during illness and to never stop insulin.

Guidance is provided on when to seek urgent specialist advice with possible referral to emergency care, for example, in cases in which the patient has DKA symptoms, such as persistent and/or worsened fruity breath odor or vomiting.

Dr. Scaramuzza said in an interview that, in Italy, he and his colleagues have increased their use of telemedicine to keep monitoring their patients with diabetes even from a distance and that it was working very well.

“Technology – such as downloading [records from] insulin pumps, continuous glucose monitoring systems, and the possibility to use Skype or other platforms – really helps,” he noted.

“There has been a rapid increase in telehealth as a way to continue to care for youth with diabetes and decrease risk for infection,” said ISPAD.

“Communication between patients, families, and health care teams is vitally important. Methods to do so that avoid visits to clinics or hospitals can provide needed diabetes advice and reduce risk for COVID-19 transmission.”

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

Reports from pediatric endocrinologists in COVID-19 hot spots globally indicate that children, adolescents, and young adults with diabetes have so far not shown a different disease pattern with the virus compared to children and younger people who do not have diabetes.

Indeed, colleagues in Wuhan, China, and Italy “state they have not had cases of COVID-19 in children, adolescents, or young adults less than 25 years of age with diabetes who required hospitalization, to date [as of March 24]” according to a new statement from the International Society for Pediatric and Adolescent Diabetes (ISPAD), which currently has about 1,300 members around the globe and has instituted a discussion forum about the topic of treating children with both diabetes and COVID-19.

“We find these reports [from colleagues around the world], though anecdotal, to be reassuring,” it notes. However, there are real worries regarding other potentially dangerous effects. ISPAD has expressed concern, for example, that the COVID-19 pandemic will prevent youngsters with existing diabetes who are having diabetic emergencies from seeking hospital care.

Chinese physicians have reported to ISPAD a number of cases of delayed hospital admissions for diabetic ketoacidosis (DKA) in children with known type 1 diabetes because hospital services were closed for non–COVID-19 care.

Andrea Scaramuzza, MD, a pediatric endocrinologist at Ospedale Maggiore di Cremona, Italy, has similarly reported multiple cases of patients presenting to emergency services there with severe DKA.

“These experiences reinforce the importance of continued attentiveness to standard diabetes care to avoid the need for hospitalization and emergency or urgent care visits,” says ISPAD, under the strapline: “Keep calm and mind your diabetes care.”

But it nevertheless stresses that these resources should be used “if needed.”
 

Worries that new-onset diabetes will be missed during COVID-19

Dr. Scaramuzza said in an interview that there also are concerns regarding delays in diagnoses of new cases of type 1 diabetes “due to the fear families have to go to the emergency department because of COVID-19.”

Indeed, in Italy, a few patients have arrived with very serious DKA, he said. Dr. Scaramuzza noted a colleague from Naples, Dario Iafusco, MD, and colleagues have made a video to keep awareness high regarding new-onset diabetes.

“This coronavirus pandemic can be defeated if you stay at home, but if you know of a child who has excessive thirst, frequent urination, or who starts vomiting,” seek health care advice immediately. “This child could have [type 1] diabetes. Prevent severe DKA, or worse, death,” Dr. Iafusco of the Regional Centre of Paediatric Diabetology G.Stoppoloni Via S. Andrea delle Dame, Naples, said in the video.

Physicians from China have similar observations, reporting to ISPAD several cases of delayed admissions of newly diagnosed type 1 diabetes because hospital services were closed for non–COVID-19 care.
 

Keep calm and mind your diabetes care; physicians use telemedicine

Meanwhile, last week ISPAD issued guidance for young people with diabetes and their carers about what to do if COVID-19 infection is suspected.

Most advice is the same as for the general public because reports of COVID-19 infection suggest it is much less severe in children and adolescents, and the summary currently serves “as reassurance that youth with diabetes are not more affected by COVID-19 than peers,” it adds.

“Our approach to treating a child with diabetes would be to follow the ISPAD sick-day guidelines, which provide generalized diabetes management in any flu-like illness. We wouldn’t do anything very different right now,” one of the authors, Jamie Wood, MD, associate professor of clinical pediatrics at Case Western Reserve University, Cleveland, said in an interview.

“Any illness makes diabetes more difficult to manage and can increase the risk of DKA,” she emphasized.

“We would reinforce frequent monitoring of blood glucose and ketone levels, to never stop insulin – in fact, when most people are ill, the body is stressed and requires more insulin – and to stay hydrated and treat the underlying symptoms.”

And make sure to “treat the fever,” she stressed. “When patients with type 1 diabetes get fever, they have a tendency to make more ketones, so we recommend aggressive control of fever.”

ISPAD recommends young people aim to keep blood glucose levels between 4 and 10 mmol/L (72-180 mg/dL) and blood ketones below 0.6 mmol/L (10.8 mg/dL) during illness and to never stop insulin.

Guidance is provided on when to seek urgent specialist advice with possible referral to emergency care, for example, in cases in which the patient has DKA symptoms, such as persistent and/or worsened fruity breath odor or vomiting.

Dr. Scaramuzza said in an interview that, in Italy, he and his colleagues have increased their use of telemedicine to keep monitoring their patients with diabetes even from a distance and that it was working very well.

“Technology – such as downloading [records from] insulin pumps, continuous glucose monitoring systems, and the possibility to use Skype or other platforms – really helps,” he noted.

“There has been a rapid increase in telehealth as a way to continue to care for youth with diabetes and decrease risk for infection,” said ISPAD.

“Communication between patients, families, and health care teams is vitally important. Methods to do so that avoid visits to clinics or hospitals can provide needed diabetes advice and reduce risk for COVID-19 transmission.”

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

At the end of 6 months of low-dose pomalidomide (Pomalyst), more than half of men who have sex with men had partial or complete clearance of long-standing, grade 3 anal lesions from human papillomavirus, irrespective of HIV status; the number increased to almost two-thirds when they were checked at 12 months, according to a 26-subject study said in video presentation of his research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.

“Therapy induced durable and continuous clearance of anal HSIL [high-grade squamous intraepithelial lesions]. Further study in HPV-associated premalignancy is warranted to follow up this small, single arm study,” said study lead Mark Polizzotto, MD, PhD, head of the therapeutic and vaccine research program at the Kirby Institute in Sydney.

HPV anal lesions, and subsequent HSIL and progression to anal cancer, are prevalent among men who have sex with men. The risk increases with chronic lesions and concomitant HIV infection.

Pomalidomide is potentially a less painful alternative to options such as freezing and laser ablation, and it may have a lower rate of recurrence, but it’s expensive. Copays range upward from $5,000 for a month supply, according to GoodRx. Celgene, the maker of the drug, offers financial assistance.

Pomalidomide is a derivative of thalidomide that’s approved for multiple myeloma and also has shown effect against a viral lesion associated with HIV, Kaposi sarcoma. The drug is a T-cell activator, and since T-cell activation also is key to spontaneous anal HSIL clearance, Dr. Polizzotto and team wanted to take a look to see if it could help, he said.

The men in the study were at high risk for progression to anal cancer. With a median lesion duration of more than 3 years, and at least one case out past 7 years, spontaneous clearance wasn’t in the cards. The lesions were all grade 3 HSIL, which means severe dysplasia, and more than half of the subjects had HPV genotype 16, and the rest had other risky genotypes. Ten subjects also had HIV, which also increases the risk of anal cancer.

Pomalidomide was given in back-to-back cycles for 6 months, each consisting of 2 mg orally for 3 weeks, then 1 week off, along with a thrombolytic, usually aspirin, given the black box warning of blood clots. The dose was half the 5-mg cycle for Kaposi’s.

The overall response rate – complete clearance or a partial clearance of at least a 50% on high-resolution anoscopy – was 50% at 6 months (12/24), including four complete responses (4/15, 27%) in subjects without HIV, as well as four in the HIV group (4/9, 44%).

On follow-up at month 12, “we saw something we did not expect. Strikingly, with no additional therapy in the interim, we saw a deepening of response in a number of subjects.” The overall response rate climbed to 63% (15/24), including 33% complete response in the HIV-free group (5/15) and HIV-positive group (3/9).

Some did lose their response in the interim, however, and the study team is working to figure out if it was do to a recurrence or a new infection.

A general pattern of immune activation on treatment, including increased systemic CD4+ T-cell responses to HPV during therapy, supported the investigator’s hunch of an immunologic mechanism of action, Dr. Polizzotto said.

There were four instances of grade 3 neutropenia over eight treatment cycles, and one possibly related angina attack, but other than that, adverse reactions were generally mild and self-limited, mostly to grade 1 or 2 neutropenia, constipation, fatigue, and rash, with no idiosyncratic reactions in the HIV group or loss of viral suppression, and no discontinuations because of side effects.

The men in the study were aged 40-50 years, with a median age of 54 years; all but one were white. The median lesion involved a quarter of the anal ring, but sometimes more than half.

The work was funded by the Cancer Institute of New South Wales, the Australian National Health and Medical Research Council, and Celgene. Dr. Polizzotto disclosed patents with Celgene and research funding from the company.

aotto@mdedge.com

SOURCE: Polizzotto M et al. CROI 2020. Abstract 70

At the end of 6 months of low-dose pomalidomide (Pomalyst), more than half of men who have sex with men had partial or complete clearance of long-standing, grade 3 anal lesions from human papillomavirus, irrespective of HIV status; the number increased to almost two-thirds when they were checked at 12 months, according to a 26-subject study said in video presentation of his research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.

“Therapy induced durable and continuous clearance of anal HSIL [high-grade squamous intraepithelial lesions]. Further study in HPV-associated premalignancy is warranted to follow up this small, single arm study,” said study lead Mark Polizzotto, MD, PhD, head of the therapeutic and vaccine research program at the Kirby Institute in Sydney.

HPV anal lesions, and subsequent HSIL and progression to anal cancer, are prevalent among men who have sex with men. The risk increases with chronic lesions and concomitant HIV infection.

Pomalidomide is potentially a less painful alternative to options such as freezing and laser ablation, and it may have a lower rate of recurrence, but it’s expensive. Copays range upward from $5,000 for a month supply, according to GoodRx. Celgene, the maker of the drug, offers financial assistance.

Pomalidomide is a derivative of thalidomide that’s approved for multiple myeloma and also has shown effect against a viral lesion associated with HIV, Kaposi sarcoma. The drug is a T-cell activator, and since T-cell activation also is key to spontaneous anal HSIL clearance, Dr. Polizzotto and team wanted to take a look to see if it could help, he said.

The men in the study were at high risk for progression to anal cancer. With a median lesion duration of more than 3 years, and at least one case out past 7 years, spontaneous clearance wasn’t in the cards. The lesions were all grade 3 HSIL, which means severe dysplasia, and more than half of the subjects had HPV genotype 16, and the rest had other risky genotypes. Ten subjects also had HIV, which also increases the risk of anal cancer.

Pomalidomide was given in back-to-back cycles for 6 months, each consisting of 2 mg orally for 3 weeks, then 1 week off, along with a thrombolytic, usually aspirin, given the black box warning of blood clots. The dose was half the 5-mg cycle for Kaposi’s.

The overall response rate – complete clearance or a partial clearance of at least a 50% on high-resolution anoscopy – was 50% at 6 months (12/24), including four complete responses (4/15, 27%) in subjects without HIV, as well as four in the HIV group (4/9, 44%).

On follow-up at month 12, “we saw something we did not expect. Strikingly, with no additional therapy in the interim, we saw a deepening of response in a number of subjects.” The overall response rate climbed to 63% (15/24), including 33% complete response in the HIV-free group (5/15) and HIV-positive group (3/9).

Some did lose their response in the interim, however, and the study team is working to figure out if it was do to a recurrence or a new infection.

A general pattern of immune activation on treatment, including increased systemic CD4+ T-cell responses to HPV during therapy, supported the investigator’s hunch of an immunologic mechanism of action, Dr. Polizzotto said.

There were four instances of grade 3 neutropenia over eight treatment cycles, and one possibly related angina attack, but other than that, adverse reactions were generally mild and self-limited, mostly to grade 1 or 2 neutropenia, constipation, fatigue, and rash, with no idiosyncratic reactions in the HIV group or loss of viral suppression, and no discontinuations because of side effects.

The men in the study were aged 40-50 years, with a median age of 54 years; all but one were white. The median lesion involved a quarter of the anal ring, but sometimes more than half.

The work was funded by the Cancer Institute of New South Wales, the Australian National Health and Medical Research Council, and Celgene. Dr. Polizzotto disclosed patents with Celgene and research funding from the company.

aotto@mdedge.com

SOURCE: Polizzotto M et al. CROI 2020. Abstract 70

At the end of 6 months of low-dose pomalidomide (Pomalyst), more than half of men who have sex with men had partial or complete clearance of long-standing, grade 3 anal lesions from human papillomavirus, irrespective of HIV status; the number increased to almost two-thirds when they were checked at 12 months, according to a 26-subject study said in video presentation of his research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.

“Therapy induced durable and continuous clearance of anal HSIL [high-grade squamous intraepithelial lesions]. Further study in HPV-associated premalignancy is warranted to follow up this small, single arm study,” said study lead Mark Polizzotto, MD, PhD, head of the therapeutic and vaccine research program at the Kirby Institute in Sydney.

HPV anal lesions, and subsequent HSIL and progression to anal cancer, are prevalent among men who have sex with men. The risk increases with chronic lesions and concomitant HIV infection.

Pomalidomide is potentially a less painful alternative to options such as freezing and laser ablation, and it may have a lower rate of recurrence, but it’s expensive. Copays range upward from $5,000 for a month supply, according to GoodRx. Celgene, the maker of the drug, offers financial assistance.

Pomalidomide is a derivative of thalidomide that’s approved for multiple myeloma and also has shown effect against a viral lesion associated with HIV, Kaposi sarcoma. The drug is a T-cell activator, and since T-cell activation also is key to spontaneous anal HSIL clearance, Dr. Polizzotto and team wanted to take a look to see if it could help, he said.

The men in the study were at high risk for progression to anal cancer. With a median lesion duration of more than 3 years, and at least one case out past 7 years, spontaneous clearance wasn’t in the cards. The lesions were all grade 3 HSIL, which means severe dysplasia, and more than half of the subjects had HPV genotype 16, and the rest had other risky genotypes. Ten subjects also had HIV, which also increases the risk of anal cancer.

Pomalidomide was given in back-to-back cycles for 6 months, each consisting of 2 mg orally for 3 weeks, then 1 week off, along with a thrombolytic, usually aspirin, given the black box warning of blood clots. The dose was half the 5-mg cycle for Kaposi’s.

The overall response rate – complete clearance or a partial clearance of at least a 50% on high-resolution anoscopy – was 50% at 6 months (12/24), including four complete responses (4/15, 27%) in subjects without HIV, as well as four in the HIV group (4/9, 44%).

On follow-up at month 12, “we saw something we did not expect. Strikingly, with no additional therapy in the interim, we saw a deepening of response in a number of subjects.” The overall response rate climbed to 63% (15/24), including 33% complete response in the HIV-free group (5/15) and HIV-positive group (3/9).

Some did lose their response in the interim, however, and the study team is working to figure out if it was do to a recurrence or a new infection.

A general pattern of immune activation on treatment, including increased systemic CD4+ T-cell responses to HPV during therapy, supported the investigator’s hunch of an immunologic mechanism of action, Dr. Polizzotto said.

There were four instances of grade 3 neutropenia over eight treatment cycles, and one possibly related angina attack, but other than that, adverse reactions were generally mild and self-limited, mostly to grade 1 or 2 neutropenia, constipation, fatigue, and rash, with no idiosyncratic reactions in the HIV group or loss of viral suppression, and no discontinuations because of side effects.

The men in the study were aged 40-50 years, with a median age of 54 years; all but one were white. The median lesion involved a quarter of the anal ring, but sometimes more than half.

The work was funded by the Cancer Institute of New South Wales, the Australian National Health and Medical Research Council, and Celgene. Dr. Polizzotto disclosed patents with Celgene and research funding from the company.

aotto@mdedge.com

SOURCE: Polizzotto M et al. CROI 2020. Abstract 70

Increased visceral fat predicts both the presence of hepatic fibrosis in HIV patients with nonalcoholic fatty liver disease and also its progression, according to a report at the Conference on Retroviruses & Opportunistic Infections.

Among 58 people with NAFLD and well-controlled HIV, mostly men, a “striking 43% had evidence of fibrosis” on liver biopsy, a quarter with severe stage 3 fibrosis. Visceral fat content on MRI predicted fibrosis (284 cm² among fibrotic patients vs. 212 cm² among nonfibrotic patients, P = .005), but body mass index (BMI), waist circumference, subcutaneous fat, and hepatic fat content did not, said investigators led by Lindsay Fourman, MD, an attending physician at the Neuroendocrine & Pituitary Tumor Clinical Center at Massachusetts General Hospital, Boston.

Among 24 subjects with a second liver biopsy a year later, 38% had fibrosis progression, more than half from no fibrosis at baseline. Baseline visceral fat (306 cm² among progressors versus 212 cm², P = .04) again predicted progression, after adjustment for baseline BMI, hepatic fat content, and NAFLD activity score.

For every 25 cm² rise in baseline visceral fat, the team found a 40% increased odds of fibrosis progression (P = .03). Body mass index was stable among subjects, so progression was not related to sudden weight gain. Dr. Fourman noted that people with HIV can have normal BMIs, but still significant accumulation of visceral fat.

The mean rate of progression was 0.2 stages per year. “To put this into perspective, the rate of fibrosis progression among NAFLD in the general population has been quoted to be about 0.03 stages per year.” Among HIV patients, it’s “more than sixfold higher,” she said in a video presentation of her research at the meeting, which was presented online this year. CROI organizers chose to hold a virtual meeting due to concerns about the spread of COVID-19.

Overall, visceral adiposity is “a novel clinical predictor of accelerated” progression in people with HIV. “Therapies to reduce visceral fat may be particularly effective in HIV-associated NAFLD,” she said.

The findings come from a trial of one such therapy, the growth hormone releasing hormone analogue tesamorelin (Egrifta). It’s approved for reduction of excess abdominal fat in HIV patients with lipodystrophy. Dr. Fourman and her colleagues recently reported a more than 30% reduction in liver fat, versus placebo, among HIV patients with NAFLD after a year of treatment, and a lower rate of fibrosis progression at 10.5% versus 37.5% (Lancet HIV. 2019 Dec;6[12]:e821-30).

In their follow-up study reported at the meeting, people with fibrosis at baseline also had higher NAFLD activity scores (3.6 points vs. 2.0 points; P < .0001), as well as higher ALT (41 U/L vs. 23 U/L, P = .002) and AST levels (44 U/L vs. 24 U/L; P = .0003).

Baseline BMI, liver fat content, NAFLD activity score, liver enzymes, waist circumference, CD4 count, and HIV duration, a median of 16 years in the study, did not predict progression, but activity scores, hemoglobin A_1C, and C-reactive protein increased as fibrosis progressed.

“We really can’t speak from our own data” if HIV regimens might have had a role in progression. Sixty-two percent of the subjects were on integrase inhibitors, and integrase inhibitors are associated with weight gain, but their effect on visceral weight gain is unclear, plus BMIs were stable. Also, there was no difference in HIV regimens among the more than 100 people screened for the study between those with NAFDL and those without.

The subjects were 54 years old, on average. The average liver fat content at baseline was about 14%, and average baseline BMI just over 30 kg/m². In addition to the 62% on integrase inhibitors, 40% were on nonnucleoside reverse transcriptase inhibitors, and 24% were on protease inhibitors.

The work was funded by the National Institutes of Health. Dr. Fourman is a paid consultant to Theratechnologies, maker of tesamorelin.

aotto@mdedge.com

SOURCE: Fourman LT et al. CROI 2020, Abstract 128

Increased visceral fat predicts both the presence of hepatic fibrosis in HIV patients with nonalcoholic fatty liver disease and also its progression, according to a report at the Conference on Retroviruses & Opportunistic Infections.

Among 58 people with NAFLD and well-controlled HIV, mostly men, a “striking 43% had evidence of fibrosis” on liver biopsy, a quarter with severe stage 3 fibrosis. Visceral fat content on MRI predicted fibrosis (284 cm² among fibrotic patients vs. 212 cm² among nonfibrotic patients, P = .005), but body mass index (BMI), waist circumference, subcutaneous fat, and hepatic fat content did not, said investigators led by Lindsay Fourman, MD, an attending physician at the Neuroendocrine & Pituitary Tumor Clinical Center at Massachusetts General Hospital, Boston.

Among 24 subjects with a second liver biopsy a year later, 38% had fibrosis progression, more than half from no fibrosis at baseline. Baseline visceral fat (306 cm² among progressors versus 212 cm², P = .04) again predicted progression, after adjustment for baseline BMI, hepatic fat content, and NAFLD activity score.

For every 25 cm² rise in baseline visceral fat, the team found a 40% increased odds of fibrosis progression (P = .03). Body mass index was stable among subjects, so progression was not related to sudden weight gain. Dr. Fourman noted that people with HIV can have normal BMIs, but still significant accumulation of visceral fat.

The mean rate of progression was 0.2 stages per year. “To put this into perspective, the rate of fibrosis progression among NAFLD in the general population has been quoted to be about 0.03 stages per year.” Among HIV patients, it’s “more than sixfold higher,” she said in a video presentation of her research at the meeting, which was presented online this year. CROI organizers chose to hold a virtual meeting due to concerns about the spread of COVID-19.

Overall, visceral adiposity is “a novel clinical predictor of accelerated” progression in people with HIV. “Therapies to reduce visceral fat may be particularly effective in HIV-associated NAFLD,” she said.

The findings come from a trial of one such therapy, the growth hormone releasing hormone analogue tesamorelin (Egrifta). It’s approved for reduction of excess abdominal fat in HIV patients with lipodystrophy. Dr. Fourman and her colleagues recently reported a more than 30% reduction in liver fat, versus placebo, among HIV patients with NAFLD after a year of treatment, and a lower rate of fibrosis progression at 10.5% versus 37.5% (Lancet HIV. 2019 Dec;6[12]:e821-30).

In their follow-up study reported at the meeting, people with fibrosis at baseline also had higher NAFLD activity scores (3.6 points vs. 2.0 points; P < .0001), as well as higher ALT (41 U/L vs. 23 U/L, P = .002) and AST levels (44 U/L vs. 24 U/L; P = .0003).

Baseline BMI, liver fat content, NAFLD activity score, liver enzymes, waist circumference, CD4 count, and HIV duration, a median of 16 years in the study, did not predict progression, but activity scores, hemoglobin A_1C, and C-reactive protein increased as fibrosis progressed.

“We really can’t speak from our own data” if HIV regimens might have had a role in progression. Sixty-two percent of the subjects were on integrase inhibitors, and integrase inhibitors are associated with weight gain, but their effect on visceral weight gain is unclear, plus BMIs were stable. Also, there was no difference in HIV regimens among the more than 100 people screened for the study between those with NAFDL and those without.

The subjects were 54 years old, on average. The average liver fat content at baseline was about 14%, and average baseline BMI just over 30 kg/m². In addition to the 62% on integrase inhibitors, 40% were on nonnucleoside reverse transcriptase inhibitors, and 24% were on protease inhibitors.

The work was funded by the National Institutes of Health. Dr. Fourman is a paid consultant to Theratechnologies, maker of tesamorelin.

aotto@mdedge.com

SOURCE: Fourman LT et al. CROI 2020, Abstract 128

Increased visceral fat predicts both the presence of hepatic fibrosis in HIV patients with nonalcoholic fatty liver disease and also its progression, according to a report at the Conference on Retroviruses & Opportunistic Infections.

Among 58 people with NAFLD and well-controlled HIV, mostly men, a “striking 43% had evidence of fibrosis” on liver biopsy, a quarter with severe stage 3 fibrosis. Visceral fat content on MRI predicted fibrosis (284 cm² among fibrotic patients vs. 212 cm² among nonfibrotic patients, P = .005), but body mass index (BMI), waist circumference, subcutaneous fat, and hepatic fat content did not, said investigators led by Lindsay Fourman, MD, an attending physician at the Neuroendocrine & Pituitary Tumor Clinical Center at Massachusetts General Hospital, Boston.

Among 24 subjects with a second liver biopsy a year later, 38% had fibrosis progression, more than half from no fibrosis at baseline. Baseline visceral fat (306 cm² among progressors versus 212 cm², P = .04) again predicted progression, after adjustment for baseline BMI, hepatic fat content, and NAFLD activity score.

For every 25 cm² rise in baseline visceral fat, the team found a 40% increased odds of fibrosis progression (P = .03). Body mass index was stable among subjects, so progression was not related to sudden weight gain. Dr. Fourman noted that people with HIV can have normal BMIs, but still significant accumulation of visceral fat.

The mean rate of progression was 0.2 stages per year. “To put this into perspective, the rate of fibrosis progression among NAFLD in the general population has been quoted to be about 0.03 stages per year.” Among HIV patients, it’s “more than sixfold higher,” she said in a video presentation of her research at the meeting, which was presented online this year. CROI organizers chose to hold a virtual meeting due to concerns about the spread of COVID-19.

Overall, visceral adiposity is “a novel clinical predictor of accelerated” progression in people with HIV. “Therapies to reduce visceral fat may be particularly effective in HIV-associated NAFLD,” she said.

The findings come from a trial of one such therapy, the growth hormone releasing hormone analogue tesamorelin (Egrifta). It’s approved for reduction of excess abdominal fat in HIV patients with lipodystrophy. Dr. Fourman and her colleagues recently reported a more than 30% reduction in liver fat, versus placebo, among HIV patients with NAFLD after a year of treatment, and a lower rate of fibrosis progression at 10.5% versus 37.5% (Lancet HIV. 2019 Dec;6[12]:e821-30).

In their follow-up study reported at the meeting, people with fibrosis at baseline also had higher NAFLD activity scores (3.6 points vs. 2.0 points; P < .0001), as well as higher ALT (41 U/L vs. 23 U/L, P = .002) and AST levels (44 U/L vs. 24 U/L; P = .0003).

Baseline BMI, liver fat content, NAFLD activity score, liver enzymes, waist circumference, CD4 count, and HIV duration, a median of 16 years in the study, did not predict progression, but activity scores, hemoglobin A_1C, and C-reactive protein increased as fibrosis progressed.

“We really can’t speak from our own data” if HIV regimens might have had a role in progression. Sixty-two percent of the subjects were on integrase inhibitors, and integrase inhibitors are associated with weight gain, but their effect on visceral weight gain is unclear, plus BMIs were stable. Also, there was no difference in HIV regimens among the more than 100 people screened for the study between those with NAFDL and those without.

The subjects were 54 years old, on average. The average liver fat content at baseline was about 14%, and average baseline BMI just over 30 kg/m². In addition to the 62% on integrase inhibitors, 40% were on nonnucleoside reverse transcriptase inhibitors, and 24% were on protease inhibitors.

The work was funded by the National Institutes of Health. Dr. Fourman is a paid consultant to Theratechnologies, maker of tesamorelin.

aotto@mdedge.com

SOURCE: Fourman LT et al. CROI 2020, Abstract 128

Fecal microbiota transplantation (FMT) appears safe and effective for treating recurrent Clostridioides difficile infection in patients with inflammatory bowel disease (IBD), according to an ongoing prospective trial.

Most patients were cured of C. difficile after one fecal transplant, reported Jessica Allegretti, MD, associate director of the Crohn’s and Colitis Center at Brigham and Women’s Hospital in Boston.

“[For patients without IBD], fecal microbiota transplantation has been shown to be very effective for the treatment of recurrent C. diff,” Dr. Allegretti said at the annual Gut Microbiota for Health World Summit.

But similar data for patients with IBD are scarce, and this knowledge gap has high clinical relevance, Dr. Allegretti said. She noted that C. difficile infections are eight times more common among patients with IBD, and risk of recurrence is increased 4.5-fold.

According to Dr. Allegretti, three small clinical trials have tested FMT for treating recurrent C. difficile infections in patients with IBD.

“[These studies were] somewhat prospective, but [data] mainly retrospectively collected, as they relied heavily on chart review for the assessment of IBD disease activity,” she said at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility..

Across the trials, C. difficile infection cure rates were comparable with non-IBD cohorts; but disease flare rates ranged from 17.9% to 54%, which raised concern that FMT may trigger inflammation.

To investigate further, Dr. Allegretti and her colleagues designed a prospective trial that is set to enroll 50 patients with IBD. Among 37 patients treated to date, a slight majority were women (56.8%), about one-third had Crohn’s disease (37.8%), and two-thirds had ulcerative colitis (62.2%). The average baseline calprotectin level, which measures inflammation in the intestines, was 1,804.8 microg/g of feces, which is far above the upper limit of 50 microg/g.

“This is a very inflamed patient population,” Dr. Allegretti said.

Out of these 37 patients, 34 (92%) were cured of C. difficile infection after only one fecal transplant, and the remaining three patients were cured after a second FMT.

“They all did very well,” Dr. Allegretti said.

Concerning IBD clinical scores, all patients with Crohn’s disease either had unchanged or improved disease. Among those with ulcerative colitis, almost all had unchanged or improved disease, except for one patient who had a de novo flare.

Early microbiome analyses showed patients had increased alpha diversity and richness after FMT that was sustained through week 12. Because only three patients had recurrence, numbers were too small to generate predictive data based on relative abundance.

Dr. Allegretti continued her presentation with a review of FMT for IBD in general.

“For Crohn’s disease, the role [of microbiome manipulation] seems a bit more clear,” Dr. Allegretti said, considering multiple effective treatments that alter gut flora, such as antibiotics.

In contrast, the role for microbiome manipulation in treating ulcerative colitis “has remained a bit unclear,” she said. Although some probiotics appear effective for treating mild disease, other microbiome-altering treatments, such as diversion of fecal stream, antibiotics, and bowel rest, have fallen short.

Still, pooled data from four randomized clinical trials showed that FMT led to remission in 28% of patients with ulcerative colitis, compared with 9% who receive placebo.

“You may be thinking that seems a bit underwhelming compared to the 90% or so cure rate we get for C. diff trials,” Dr. Allegretti said. “However, if you look at our other biologic trials in IBD, 28% puts FMT on par with our other IBD therapies.”

According to Dr. Allegretti, at least three stool-based, FMT-like therapeutics are poised to become commercially available in the next few years for the treatment of C. difficile infection, including broad- and narrow-spectrum enema bags and oral capsules.

“I certainly think we will start to see off-label usage in our IBD patients, and we will start to have an easier and more systemic way of utilizing these microbiome-based therapies,” Dr. Allegretti said. “They will be coming to market, and when they do, whether or not we are allowed to still do traditional FMT in its current form remains unseen. The FDA may not allow us to do that in the future when we have an FDA-approved product.”Dr. Allegretti disclosed relationships with Merck, Openbiome, Finch Therapeutics, and others.

aotto@mdedge.com

Fecal microbiota transplantation (FMT) appears safe and effective for treating recurrent Clostridioides difficile infection in patients with inflammatory bowel disease (IBD), according to an ongoing prospective trial.

Most patients were cured of C. difficile after one fecal transplant, reported Jessica Allegretti, MD, associate director of the Crohn’s and Colitis Center at Brigham and Women’s Hospital in Boston.

“[For patients without IBD], fecal microbiota transplantation has been shown to be very effective for the treatment of recurrent C. diff,” Dr. Allegretti said at the annual Gut Microbiota for Health World Summit.

But similar data for patients with IBD are scarce, and this knowledge gap has high clinical relevance, Dr. Allegretti said. She noted that C. difficile infections are eight times more common among patients with IBD, and risk of recurrence is increased 4.5-fold.

According to Dr. Allegretti, three small clinical trials have tested FMT for treating recurrent C. difficile infections in patients with IBD.

“[These studies were] somewhat prospective, but [data] mainly retrospectively collected, as they relied heavily on chart review for the assessment of IBD disease activity,” she said at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility..

Across the trials, C. difficile infection cure rates were comparable with non-IBD cohorts; but disease flare rates ranged from 17.9% to 54%, which raised concern that FMT may trigger inflammation.

To investigate further, Dr. Allegretti and her colleagues designed a prospective trial that is set to enroll 50 patients with IBD. Among 37 patients treated to date, a slight majority were women (56.8%), about one-third had Crohn’s disease (37.8%), and two-thirds had ulcerative colitis (62.2%). The average baseline calprotectin level, which measures inflammation in the intestines, was 1,804.8 microg/g of feces, which is far above the upper limit of 50 microg/g.

“This is a very inflamed patient population,” Dr. Allegretti said.

Out of these 37 patients, 34 (92%) were cured of C. difficile infection after only one fecal transplant, and the remaining three patients were cured after a second FMT.

“They all did very well,” Dr. Allegretti said.

Concerning IBD clinical scores, all patients with Crohn’s disease either had unchanged or improved disease. Among those with ulcerative colitis, almost all had unchanged or improved disease, except for one patient who had a de novo flare.

Early microbiome analyses showed patients had increased alpha diversity and richness after FMT that was sustained through week 12. Because only three patients had recurrence, numbers were too small to generate predictive data based on relative abundance.

Dr. Allegretti continued her presentation with a review of FMT for IBD in general.

“For Crohn’s disease, the role [of microbiome manipulation] seems a bit more clear,” Dr. Allegretti said, considering multiple effective treatments that alter gut flora, such as antibiotics.

In contrast, the role for microbiome manipulation in treating ulcerative colitis “has remained a bit unclear,” she said. Although some probiotics appear effective for treating mild disease, other microbiome-altering treatments, such as diversion of fecal stream, antibiotics, and bowel rest, have fallen short.

Still, pooled data from four randomized clinical trials showed that FMT led to remission in 28% of patients with ulcerative colitis, compared with 9% who receive placebo.

“You may be thinking that seems a bit underwhelming compared to the 90% or so cure rate we get for C. diff trials,” Dr. Allegretti said. “However, if you look at our other biologic trials in IBD, 28% puts FMT on par with our other IBD therapies.”

According to Dr. Allegretti, at least three stool-based, FMT-like therapeutics are poised to become commercially available in the next few years for the treatment of C. difficile infection, including broad- and narrow-spectrum enema bags and oral capsules.

“I certainly think we will start to see off-label usage in our IBD patients, and we will start to have an easier and more systemic way of utilizing these microbiome-based therapies,” Dr. Allegretti said. “They will be coming to market, and when they do, whether or not we are allowed to still do traditional FMT in its current form remains unseen. The FDA may not allow us to do that in the future when we have an FDA-approved product.”Dr. Allegretti disclosed relationships with Merck, Openbiome, Finch Therapeutics, and others.

aotto@mdedge.com

Fecal microbiota transplantation (FMT) appears safe and effective for treating recurrent Clostridioides difficile infection in patients with inflammatory bowel disease (IBD), according to an ongoing prospective trial.

Most patients were cured of C. difficile after one fecal transplant, reported Jessica Allegretti, MD, associate director of the Crohn’s and Colitis Center at Brigham and Women’s Hospital in Boston.

“[For patients without IBD], fecal microbiota transplantation has been shown to be very effective for the treatment of recurrent C. diff,” Dr. Allegretti said at the annual Gut Microbiota for Health World Summit.

But similar data for patients with IBD are scarce, and this knowledge gap has high clinical relevance, Dr. Allegretti said. She noted that C. difficile infections are eight times more common among patients with IBD, and risk of recurrence is increased 4.5-fold.

According to Dr. Allegretti, three small clinical trials have tested FMT for treating recurrent C. difficile infections in patients with IBD.

“[These studies were] somewhat prospective, but [data] mainly retrospectively collected, as they relied heavily on chart review for the assessment of IBD disease activity,” she said at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility..

Across the trials, C. difficile infection cure rates were comparable with non-IBD cohorts; but disease flare rates ranged from 17.9% to 54%, which raised concern that FMT may trigger inflammation.

To investigate further, Dr. Allegretti and her colleagues designed a prospective trial that is set to enroll 50 patients with IBD. Among 37 patients treated to date, a slight majority were women (56.8%), about one-third had Crohn’s disease (37.8%), and two-thirds had ulcerative colitis (62.2%). The average baseline calprotectin level, which measures inflammation in the intestines, was 1,804.8 microg/g of feces, which is far above the upper limit of 50 microg/g.

“This is a very inflamed patient population,” Dr. Allegretti said.

Out of these 37 patients, 34 (92%) were cured of C. difficile infection after only one fecal transplant, and the remaining three patients were cured after a second FMT.

“They all did very well,” Dr. Allegretti said.

Concerning IBD clinical scores, all patients with Crohn’s disease either had unchanged or improved disease. Among those with ulcerative colitis, almost all had unchanged or improved disease, except for one patient who had a de novo flare.

Early microbiome analyses showed patients had increased alpha diversity and richness after FMT that was sustained through week 12. Because only three patients had recurrence, numbers were too small to generate predictive data based on relative abundance.

Dr. Allegretti continued her presentation with a review of FMT for IBD in general.

“For Crohn’s disease, the role [of microbiome manipulation] seems a bit more clear,” Dr. Allegretti said, considering multiple effective treatments that alter gut flora, such as antibiotics.

In contrast, the role for microbiome manipulation in treating ulcerative colitis “has remained a bit unclear,” she said. Although some probiotics appear effective for treating mild disease, other microbiome-altering treatments, such as diversion of fecal stream, antibiotics, and bowel rest, have fallen short.

Still, pooled data from four randomized clinical trials showed that FMT led to remission in 28% of patients with ulcerative colitis, compared with 9% who receive placebo.

“You may be thinking that seems a bit underwhelming compared to the 90% or so cure rate we get for C. diff trials,” Dr. Allegretti said. “However, if you look at our other biologic trials in IBD, 28% puts FMT on par with our other IBD therapies.”

According to Dr. Allegretti, at least three stool-based, FMT-like therapeutics are poised to become commercially available in the next few years for the treatment of C. difficile infection, including broad- and narrow-spectrum enema bags and oral capsules.

“I certainly think we will start to see off-label usage in our IBD patients, and we will start to have an easier and more systemic way of utilizing these microbiome-based therapies,” Dr. Allegretti said. “They will be coming to market, and when they do, whether or not we are allowed to still do traditional FMT in its current form remains unseen. The FDA may not allow us to do that in the future when we have an FDA-approved product.”Dr. Allegretti disclosed relationships with Merck, Openbiome, Finch Therapeutics, and others.

aotto@mdedge.com

Annual opioid prescriptions for American aged 65 years and older are more than double the amount received by adults under age 65, according to the Agency for Healthcare Quality and Research.

Elderly adults with chronic and acute pain obtained an average of 774 morphine milligram equivalents (MMEs) of prescription opioids annually during 2015-2016 from outpatient clinicians, compared with 376 MMEs a year for nonelderly adults, said Asako S. Moriya, PhD, and G. Edward Miller, PhD, of the AHRQ.

Narrowing the age groups shows that opioid MMEs increased with age, starting at 49 MMEs for 18- to 26-year-olds and rising to a high of 856 MMEs in the 65- to 74-year-old group, before dropping off in the oldest adults, the investigators said in a Medical Expenditure Panel Survey (MEPS) research findings report.

The analysis included “all opioid medications that are commonly used to treat pain” and excluded respiratory agents, antitussives, and drugs used for medication-assisted treatment, they noted. The MEPS data cover prescriptions purchased or obtained in outpatient settings but not those administered in inpatient settings or in clinics or physician offices.

rfranki@mdedge.com

Annual opioid prescriptions for American aged 65 years and older are more than double the amount received by adults under age 65, according to the Agency for Healthcare Quality and Research.

Elderly adults with chronic and acute pain obtained an average of 774 morphine milligram equivalents (MMEs) of prescription opioids annually during 2015-2016 from outpatient clinicians, compared with 376 MMEs a year for nonelderly adults, said Asako S. Moriya, PhD, and G. Edward Miller, PhD, of the AHRQ.

Narrowing the age groups shows that opioid MMEs increased with age, starting at 49 MMEs for 18- to 26-year-olds and rising to a high of 856 MMEs in the 65- to 74-year-old group, before dropping off in the oldest adults, the investigators said in a Medical Expenditure Panel Survey (MEPS) research findings report.

The analysis included “all opioid medications that are commonly used to treat pain” and excluded respiratory agents, antitussives, and drugs used for medication-assisted treatment, they noted. The MEPS data cover prescriptions purchased or obtained in outpatient settings but not those administered in inpatient settings or in clinics or physician offices.

rfranki@mdedge.com

Annual opioid prescriptions for American aged 65 years and older are more than double the amount received by adults under age 65, according to the Agency for Healthcare Quality and Research.

Elderly adults with chronic and acute pain obtained an average of 774 morphine milligram equivalents (MMEs) of prescription opioids annually during 2015-2016 from outpatient clinicians, compared with 376 MMEs a year for nonelderly adults, said Asako S. Moriya, PhD, and G. Edward Miller, PhD, of the AHRQ.

Narrowing the age groups shows that opioid MMEs increased with age, starting at 49 MMEs for 18- to 26-year-olds and rising to a high of 856 MMEs in the 65- to 74-year-old group, before dropping off in the oldest adults, the investigators said in a Medical Expenditure Panel Survey (MEPS) research findings report.

The analysis included “all opioid medications that are commonly used to treat pain” and excluded respiratory agents, antitussives, and drugs used for medication-assisted treatment, they noted. The MEPS data cover prescriptions purchased or obtained in outpatient settings but not those administered in inpatient settings or in clinics or physician offices.

rfranki@mdedge.com

A pair of focus groups explored the experience of transgender patients with HIV prevention, finding many were discouraged by experiences of care that was not culturally competent and affirming.

The findings, including other important themes, were published in Pediatrics.

The pair of online asynchronous focus groups, conducted by Holly B. Fontenot, PhD, RN/NP, of the Fenway Institute in Boston, and colleagues, sought input from 30 transgender participants from across the United States. Eleven were aged 13-18 years, and 19 were aged 18-24 years, with an average age of 19. Most (70%) were white, and the remainder were African American (7%), Asian American (3%), multiracial (17%), and other (3%); 10% identified as Hispanic. Participants were given multiple options for reporting gender identity; 27% reported identifying as transgender males, 17% reported identifying as transgender females, and the rest identified with other terms, including 27% using one or more terms.

The quantitative analysis found four common themes, which the study explored in depth: “barriers to self-efficacy in sexual decision making; safety concerns, fear, and other challenges in forming romantic and/or sexual relationships; need for support and education; and desire for affirmative and culturally competent experiences and interactions.”

Based on their findings, the authors suggested ways of improving transgender youth experiences:

• Increasing provider knowledge and skills in providing affirming care through transgender health education programs.
• Addressing the barriers, such as stigma and lack of accessibility.
• Expanding sexual health education to be more inclusive regarding gender identities, sexual orientations, and definitions of sex.

Providers also need to include information on sexually transmitted infection and HIV prevention, including “discussion of safer sexual behaviors, negotiation and consent, sexual and physical assault, condoms, lubrication, STI and HIV testing, human papillomavirus vaccination, and PrEP [preexposure prophylaxis]” the authors emphasized.

Dr. Fontenot and associates determined that this study’s findings were consistent with what’s known about adult transgender patients, but this study provides more context regarding transgender youth experiences.

“It is important to elicit transgender youth experiences and perspectives related to HIV risk and preventive services,” they concluded. “This study provided a greater understanding of barriers to and facilitators of youth obtaining HIV preventive services and sexual health education.”

Limitations of the study included that non–English speaking participants were excluded, and that participants were predominantly white, non-Hispanic, and assigned female sex at birth.

This study was funded by the Centers for Disease Control and Prevention and NORC at The University of Chicago. The authors had no relevant financial disclosures.

cpalmer@mdedge.com

SOURCE: Fontenot HB et al., Pediatrics. 2020. doi: 10.1542/peds.2019-2204.

A pair of focus groups explored the experience of transgender patients with HIV prevention, finding many were discouraged by experiences of care that was not culturally competent and affirming.

The findings, including other important themes, were published in Pediatrics.

The pair of online asynchronous focus groups, conducted by Holly B. Fontenot, PhD, RN/NP, of the Fenway Institute in Boston, and colleagues, sought input from 30 transgender participants from across the United States. Eleven were aged 13-18 years, and 19 were aged 18-24 years, with an average age of 19. Most (70%) were white, and the remainder were African American (7%), Asian American (3%), multiracial (17%), and other (3%); 10% identified as Hispanic. Participants were given multiple options for reporting gender identity; 27% reported identifying as transgender males, 17% reported identifying as transgender females, and the rest identified with other terms, including 27% using one or more terms.

The quantitative analysis found four common themes, which the study explored in depth: “barriers to self-efficacy in sexual decision making; safety concerns, fear, and other challenges in forming romantic and/or sexual relationships; need for support and education; and desire for affirmative and culturally competent experiences and interactions.”

Based on their findings, the authors suggested ways of improving transgender youth experiences:

• Increasing provider knowledge and skills in providing affirming care through transgender health education programs.
• Addressing the barriers, such as stigma and lack of accessibility.
• Expanding sexual health education to be more inclusive regarding gender identities, sexual orientations, and definitions of sex.

Providers also need to include information on sexually transmitted infection and HIV prevention, including “discussion of safer sexual behaviors, negotiation and consent, sexual and physical assault, condoms, lubrication, STI and HIV testing, human papillomavirus vaccination, and PrEP [preexposure prophylaxis]” the authors emphasized.

Dr. Fontenot and associates determined that this study’s findings were consistent with what’s known about adult transgender patients, but this study provides more context regarding transgender youth experiences.

“It is important to elicit transgender youth experiences and perspectives related to HIV risk and preventive services,” they concluded. “This study provided a greater understanding of barriers to and facilitators of youth obtaining HIV preventive services and sexual health education.”

Limitations of the study included that non–English speaking participants were excluded, and that participants were predominantly white, non-Hispanic, and assigned female sex at birth.

This study was funded by the Centers for Disease Control and Prevention and NORC at The University of Chicago. The authors had no relevant financial disclosures.

cpalmer@mdedge.com

SOURCE: Fontenot HB et al., Pediatrics. 2020. doi: 10.1542/peds.2019-2204.

A pair of focus groups explored the experience of transgender patients with HIV prevention, finding many were discouraged by experiences of care that was not culturally competent and affirming.

The findings, including other important themes, were published in Pediatrics.

The pair of online asynchronous focus groups, conducted by Holly B. Fontenot, PhD, RN/NP, of the Fenway Institute in Boston, and colleagues, sought input from 30 transgender participants from across the United States. Eleven were aged 13-18 years, and 19 were aged 18-24 years, with an average age of 19. Most (70%) were white, and the remainder were African American (7%), Asian American (3%), multiracial (17%), and other (3%); 10% identified as Hispanic. Participants were given multiple options for reporting gender identity; 27% reported identifying as transgender males, 17% reported identifying as transgender females, and the rest identified with other terms, including 27% using one or more terms.

The quantitative analysis found four common themes, which the study explored in depth: “barriers to self-efficacy in sexual decision making; safety concerns, fear, and other challenges in forming romantic and/or sexual relationships; need for support and education; and desire for affirmative and culturally competent experiences and interactions.”

Based on their findings, the authors suggested ways of improving transgender youth experiences:

• Increasing provider knowledge and skills in providing affirming care through transgender health education programs.
• Addressing the barriers, such as stigma and lack of accessibility.
• Expanding sexual health education to be more inclusive regarding gender identities, sexual orientations, and definitions of sex.

Providers also need to include information on sexually transmitted infection and HIV prevention, including “discussion of safer sexual behaviors, negotiation and consent, sexual and physical assault, condoms, lubrication, STI and HIV testing, human papillomavirus vaccination, and PrEP [preexposure prophylaxis]” the authors emphasized.

Dr. Fontenot and associates determined that this study’s findings were consistent with what’s known about adult transgender patients, but this study provides more context regarding transgender youth experiences.

“It is important to elicit transgender youth experiences and perspectives related to HIV risk and preventive services,” they concluded. “This study provided a greater understanding of barriers to and facilitators of youth obtaining HIV preventive services and sexual health education.”

Limitations of the study included that non–English speaking participants were excluded, and that participants were predominantly white, non-Hispanic, and assigned female sex at birth.

This study was funded by the Centers for Disease Control and Prevention and NORC at The University of Chicago. The authors had no relevant financial disclosures.

cpalmer@mdedge.com

SOURCE: Fontenot HB et al., Pediatrics. 2020. doi: 10.1542/peds.2019-2204.