Conference Coverage

The benefits of doxycycline postexposure prophylaxis (Doxy PEP) in preventing the transmission of sexually transmitted infections (STIs) in men and transgender women do not appear to extend to cisgender women, who have disproportionately high rates of infection in many regions.

“This was the first trial to evaluate doxycycline PEP for cisgender women,” said first author Jenell Stewart, DO, of the University of Minnesota, Minneapolis, in discussing the findings at a press conference at the Conference on Retroviruses & Opportunistic Infections.

“Unfortunately, our primary outcome was not statistically significant – we did not see a reduction in STIs among cisgender women, which is in stark contrast to [reported effects] among cisgender men and transgender women,” she said.

The findings are from a study of 449 nonpregnant cisgender women (mean age, 24 years) in Kenya who had been taking daily oral HIV preexposure prophylaxis (PrEP) for a median of about 7 months.

The women were randomly assigned to receive either Doxy PEP 200 mg, to be taken within 72 hours of sex (n = 224), or standard care, which included quarterly screening and treatment of STIs (n = 225).

Of the women, 36.7% reported transactional sex at enrollment; their baseline prevalence of STIs was 17.9%, including 14.1% with chlamydia, 3.8% gonorrhea, and 0.4% syphilis. There were no differences between the study groups.

In surveys, 78% of the women reported adherence to the use of Doxy PEP; they took the prophylaxis at least as many days as they had sex.

Nevertheless, there was no significant difference in the incidence of STIs, reported over 1 year, at quarterly visits that included genital STI testing, between groups, with 50 patients in the Doxy PEP group and 59 in the standard screening group developing STIs (relative risk, 0.88; P = .51).

Of the infections, 85 were chlamydia, including 35 in the Doxy PEP group and 50 with standard of care, while 31 were gonorrhea, including 19 in the Doxy PEP group and 12 with standard of care; 8 had both infections, and there was 1 syphilis infection.

The results were consistent across subanalyses of patients grouped according to STI, who became pregnant (n = 80), or sorted by other factors including age, contraceptive use, transactional sex, and STI at baseline.

None of the women developed HIV, and there were no serious events associated with the Doxy PEP treatment.
 

Cisgender women bear ‘highest burden’ of STIs

The findings are disappointing in light of the higher rates of STIs among cisgender women, with the Centers for Disease Control and Prevention reporting that women also disproportionately bear the long-term consequences of STIs.

“For example, each year, untreated sexually transmitted diseases cause infertility in at least 20,000 women in the United States, and a pregnant woman is highly likely to pass syphilis unto her unborn baby if left untested or untreated,” the CDC reports.

The STI rates are particularly high for women taking HIV PrEP in regions like East Africa, where rates of STIs among cisgender women in many cases are higher than rates for men taking PrEP in high income countries, Dr. Stewart said.

Previous studies of Doxy PEP in men and transgender women taking HIV PrEP, including new research presented at CROI, have shown highly encouraging reductions in STIs, at rates of up to approximately 80% for chlamydia and syphilis.
 

Adherence, anatomy, resistance

The key theories for the lack of a prevention of infections in cisgender women surround the issues of resistances, as well as anatomy and adherence, said Dr. Stewart.

In terms of bacterial resistances, while initial testing in a limited number of samples the study found no evidence of markers of resistance for chlamydia, all of the gonorrhea samples did show tetracycline-resistant N gonorrhea at baseline and follow-up in both groups.

Regarding anatomic differences, doxycycline may not prevent STIs in endocervical tissue among cisgender women, Dr. Stewart noted. Women are known to be at higher risk of infection because the lining of the vagina is thinner than the skin of the penis, allowing for easier penetration of bacteria and viruses.

The study was designed to optimize adherence to Doxy PEP. Measures included monitoring with weekly text message surveys, in which the women reported a high rate of adherence.

The overall retention rate in the study was high; as many as 97% of the quarterly follow-up visits were completed, including 95% in the Doxy PEP group and 98% of the standard care group. The response rate for the weekly surveys was 81%.

Of note, women reported the use of the treatment to be “imperfect,” suggesting social problems, such as biases toward the use of the prophylaxis.

The results underscore the need for ongoing efforts to make sure no groups of patients are left behind as interventions advance, Dr. Stewart said.

“The burden of STIs on cisgender women is large and growing,” she concluded. “STI prevention interventions are needed.”

Commenting on the study, Renee A. Heffron, PhD, MPH, said the findings “are somewhat surprising because results from trials in other populations have been positive.

“But cisgender women are exposed through the cervix, and this tissue is different from rectal or urethral tissue,” Dr. Heffron, a professor at the department of medicine and director of the Center for AIDS Research at the University of Alabama, Birmingham, told this news organization.

Further findings from the research should help shed light on key issues of adherence and drug concentration levels in cervical tissue, she added.

“For cisgender women, these data are the first and the beginning of understanding whether this is a viable strategy,” Dr. Heffron said.

“We have more to learn to better understand the results from the trial main outcomes, and if there are tweaks to this strategy that would improve efficacy.”

The authors and Dr. Heffron have disclosed no relevant financial relationships.

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

The benefits of doxycycline postexposure prophylaxis (Doxy PEP) in preventing the transmission of sexually transmitted infections (STIs) in men and transgender women do not appear to extend to cisgender women, who have disproportionately high rates of infection in many regions.

“This was the first trial to evaluate doxycycline PEP for cisgender women,” said first author Jenell Stewart, DO, of the University of Minnesota, Minneapolis, in discussing the findings at a press conference at the Conference on Retroviruses & Opportunistic Infections.

“Unfortunately, our primary outcome was not statistically significant – we did not see a reduction in STIs among cisgender women, which is in stark contrast to [reported effects] among cisgender men and transgender women,” she said.

The findings are from a study of 449 nonpregnant cisgender women (mean age, 24 years) in Kenya who had been taking daily oral HIV preexposure prophylaxis (PrEP) for a median of about 7 months.

The women were randomly assigned to receive either Doxy PEP 200 mg, to be taken within 72 hours of sex (n = 224), or standard care, which included quarterly screening and treatment of STIs (n = 225).

Of the women, 36.7% reported transactional sex at enrollment; their baseline prevalence of STIs was 17.9%, including 14.1% with chlamydia, 3.8% gonorrhea, and 0.4% syphilis. There were no differences between the study groups.

In surveys, 78% of the women reported adherence to the use of Doxy PEP; they took the prophylaxis at least as many days as they had sex.

Nevertheless, there was no significant difference in the incidence of STIs, reported over 1 year, at quarterly visits that included genital STI testing, between groups, with 50 patients in the Doxy PEP group and 59 in the standard screening group developing STIs (relative risk, 0.88; P = .51).

Of the infections, 85 were chlamydia, including 35 in the Doxy PEP group and 50 with standard of care, while 31 were gonorrhea, including 19 in the Doxy PEP group and 12 with standard of care; 8 had both infections, and there was 1 syphilis infection.

The results were consistent across subanalyses of patients grouped according to STI, who became pregnant (n = 80), or sorted by other factors including age, contraceptive use, transactional sex, and STI at baseline.

None of the women developed HIV, and there were no serious events associated with the Doxy PEP treatment.
 

Cisgender women bear ‘highest burden’ of STIs

The findings are disappointing in light of the higher rates of STIs among cisgender women, with the Centers for Disease Control and Prevention reporting that women also disproportionately bear the long-term consequences of STIs.

“For example, each year, untreated sexually transmitted diseases cause infertility in at least 20,000 women in the United States, and a pregnant woman is highly likely to pass syphilis unto her unborn baby if left untested or untreated,” the CDC reports.

The STI rates are particularly high for women taking HIV PrEP in regions like East Africa, where rates of STIs among cisgender women in many cases are higher than rates for men taking PrEP in high income countries, Dr. Stewart said.

Previous studies of Doxy PEP in men and transgender women taking HIV PrEP, including new research presented at CROI, have shown highly encouraging reductions in STIs, at rates of up to approximately 80% for chlamydia and syphilis.
 

Adherence, anatomy, resistance

The key theories for the lack of a prevention of infections in cisgender women surround the issues of resistances, as well as anatomy and adherence, said Dr. Stewart.

In terms of bacterial resistances, while initial testing in a limited number of samples the study found no evidence of markers of resistance for chlamydia, all of the gonorrhea samples did show tetracycline-resistant N gonorrhea at baseline and follow-up in both groups.

Regarding anatomic differences, doxycycline may not prevent STIs in endocervical tissue among cisgender women, Dr. Stewart noted. Women are known to be at higher risk of infection because the lining of the vagina is thinner than the skin of the penis, allowing for easier penetration of bacteria and viruses.

The study was designed to optimize adherence to Doxy PEP. Measures included monitoring with weekly text message surveys, in which the women reported a high rate of adherence.

The overall retention rate in the study was high; as many as 97% of the quarterly follow-up visits were completed, including 95% in the Doxy PEP group and 98% of the standard care group. The response rate for the weekly surveys was 81%.

Of note, women reported the use of the treatment to be “imperfect,” suggesting social problems, such as biases toward the use of the prophylaxis.

The results underscore the need for ongoing efforts to make sure no groups of patients are left behind as interventions advance, Dr. Stewart said.

“The burden of STIs on cisgender women is large and growing,” she concluded. “STI prevention interventions are needed.”

Commenting on the study, Renee A. Heffron, PhD, MPH, said the findings “are somewhat surprising because results from trials in other populations have been positive.

“But cisgender women are exposed through the cervix, and this tissue is different from rectal or urethral tissue,” Dr. Heffron, a professor at the department of medicine and director of the Center for AIDS Research at the University of Alabama, Birmingham, told this news organization.

Further findings from the research should help shed light on key issues of adherence and drug concentration levels in cervical tissue, she added.

“For cisgender women, these data are the first and the beginning of understanding whether this is a viable strategy,” Dr. Heffron said.

“We have more to learn to better understand the results from the trial main outcomes, and if there are tweaks to this strategy that would improve efficacy.”

The authors and Dr. Heffron have disclosed no relevant financial relationships.

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

The benefits of doxycycline postexposure prophylaxis (Doxy PEP) in preventing the transmission of sexually transmitted infections (STIs) in men and transgender women do not appear to extend to cisgender women, who have disproportionately high rates of infection in many regions.

“This was the first trial to evaluate doxycycline PEP for cisgender women,” said first author Jenell Stewart, DO, of the University of Minnesota, Minneapolis, in discussing the findings at a press conference at the Conference on Retroviruses & Opportunistic Infections.

“Unfortunately, our primary outcome was not statistically significant – we did not see a reduction in STIs among cisgender women, which is in stark contrast to [reported effects] among cisgender men and transgender women,” she said.

The findings are from a study of 449 nonpregnant cisgender women (mean age, 24 years) in Kenya who had been taking daily oral HIV preexposure prophylaxis (PrEP) for a median of about 7 months.

The women were randomly assigned to receive either Doxy PEP 200 mg, to be taken within 72 hours of sex (n = 224), or standard care, which included quarterly screening and treatment of STIs (n = 225).

Of the women, 36.7% reported transactional sex at enrollment; their baseline prevalence of STIs was 17.9%, including 14.1% with chlamydia, 3.8% gonorrhea, and 0.4% syphilis. There were no differences between the study groups.

In surveys, 78% of the women reported adherence to the use of Doxy PEP; they took the prophylaxis at least as many days as they had sex.

Nevertheless, there was no significant difference in the incidence of STIs, reported over 1 year, at quarterly visits that included genital STI testing, between groups, with 50 patients in the Doxy PEP group and 59 in the standard screening group developing STIs (relative risk, 0.88; P = .51).

Of the infections, 85 were chlamydia, including 35 in the Doxy PEP group and 50 with standard of care, while 31 were gonorrhea, including 19 in the Doxy PEP group and 12 with standard of care; 8 had both infections, and there was 1 syphilis infection.

The results were consistent across subanalyses of patients grouped according to STI, who became pregnant (n = 80), or sorted by other factors including age, contraceptive use, transactional sex, and STI at baseline.

None of the women developed HIV, and there were no serious events associated with the Doxy PEP treatment.
 

Cisgender women bear ‘highest burden’ of STIs

The findings are disappointing in light of the higher rates of STIs among cisgender women, with the Centers for Disease Control and Prevention reporting that women also disproportionately bear the long-term consequences of STIs.

“For example, each year, untreated sexually transmitted diseases cause infertility in at least 20,000 women in the United States, and a pregnant woman is highly likely to pass syphilis unto her unborn baby if left untested or untreated,” the CDC reports.

The STI rates are particularly high for women taking HIV PrEP in regions like East Africa, where rates of STIs among cisgender women in many cases are higher than rates for men taking PrEP in high income countries, Dr. Stewart said.

Previous studies of Doxy PEP in men and transgender women taking HIV PrEP, including new research presented at CROI, have shown highly encouraging reductions in STIs, at rates of up to approximately 80% for chlamydia and syphilis.
 

Adherence, anatomy, resistance

The key theories for the lack of a prevention of infections in cisgender women surround the issues of resistances, as well as anatomy and adherence, said Dr. Stewart.

In terms of bacterial resistances, while initial testing in a limited number of samples the study found no evidence of markers of resistance for chlamydia, all of the gonorrhea samples did show tetracycline-resistant N gonorrhea at baseline and follow-up in both groups.

Regarding anatomic differences, doxycycline may not prevent STIs in endocervical tissue among cisgender women, Dr. Stewart noted. Women are known to be at higher risk of infection because the lining of the vagina is thinner than the skin of the penis, allowing for easier penetration of bacteria and viruses.

The study was designed to optimize adherence to Doxy PEP. Measures included monitoring with weekly text message surveys, in which the women reported a high rate of adherence.

The overall retention rate in the study was high; as many as 97% of the quarterly follow-up visits were completed, including 95% in the Doxy PEP group and 98% of the standard care group. The response rate for the weekly surveys was 81%.

Of note, women reported the use of the treatment to be “imperfect,” suggesting social problems, such as biases toward the use of the prophylaxis.

The results underscore the need for ongoing efforts to make sure no groups of patients are left behind as interventions advance, Dr. Stewart said.

“The burden of STIs on cisgender women is large and growing,” she concluded. “STI prevention interventions are needed.”

Commenting on the study, Renee A. Heffron, PhD, MPH, said the findings “are somewhat surprising because results from trials in other populations have been positive.

“But cisgender women are exposed through the cervix, and this tissue is different from rectal or urethral tissue,” Dr. Heffron, a professor at the department of medicine and director of the Center for AIDS Research at the University of Alabama, Birmingham, told this news organization.

Further findings from the research should help shed light on key issues of adherence and drug concentration levels in cervical tissue, she added.

“For cisgender women, these data are the first and the beginning of understanding whether this is a viable strategy,” Dr. Heffron said.

“We have more to learn to better understand the results from the trial main outcomes, and if there are tweaks to this strategy that would improve efficacy.”

The authors and Dr. Heffron have disclosed no relevant financial relationships.

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

HONOLULU – In the clinical experience of April W. Armstrong, MD, MPH, topical therapies typically don’t work well for nail psoriasis, so she sometimes resorts to intralesional injections combined with systemic therapy.

One might think of intralesional injections “as a torture method from the medieval days,” she said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!, but intramatricial corticosteroid injections have been performed for many years as a treatment for nail psoriasis, typically with triamcinolone acetonide.

Doug Brunk/MDedge News

According to Dr. Armstrong, professor of dermatology and associate dean of clinical research at the University of Southern California, Los Angeles, nail matrix psoriasis can present as pitting, leukonychia, red macules in the lunula, crumbling, or trachyonychia. Nail bed psoriasis can present as splinter hemorrhages and onycholysis, hyperkeratosis and splinter hemorrhages, salmon patch or oil spot dyschromia, or onycholysis and salmon patch dyschromia.

In a German cross-sectional study of patients with psoriasis, nails were one of the body sites that have the greatest impact on quality of life – especially those in younger age groups.

While topical treatments are generally considered first for limited disease involving special areas such as the nails, systemic therapy is warranted in patients with moderate-to-severe involvement of specific sites or in those refractory to topical therapy, Dr. Armstrong said.

In 2018, Indian researchers published results from an open-label study of 17 patients, with nail psoriasis, comparing three treatments . Patients were assigned to three groups of 30 nails each and treated with intramatricial injections of triamcinolone acetonide (10 mg/mL), methotrexate (25 mg/mL), and cyclosporine (50 mg/mL), respectively. Each nail was treated with two injections at 6-week intervals and graded at 24 weeks using the Nail Psoriasis Severity Index (NAPSI). In the triamcinolone acetonide and methotrexate groups, 50% of treated nails showed a greater than 75% improvement at 24 weeks, compared with 33% of those in the cyclosporine group. The most side effects occurred in the nails treated with cyclosporine.

When Dr. Armstrong performs intramatricial injections, she uses triamcinolone acetonide at 10 mg/mL. However, she said, “my favorite way of treating severe nail psoriasis is with biologics.”

In an early study of patients with moderate to severe psoriasis treated with the tumor necrosis factor blocker adalimumab 80 mg subcutaneously at week 0, followed by 40 mg subcutaneously every other week from weeks 1 to 15, a post hoc analysis on the effects on nail psoriasis showed a 10-point decrease in the median NAPSI score through week 16 – from 21 to 11 .

In VOYAGE 2, which compared the interleukin-23 blocker guselkumab and adalimumab in patients with moderate to severe psoriasis, the mean percent improvement from baseline in the NAPSI score was similar in patients treated with adalimumab or guselkumab at week 16 (39.6% vs. 46.9%, respectively) and at week 24 (55% vs. 53.7%).

In another study of patients with nail psoriasis, researchers evaluated the efficacy of the IL-17A antagonist secukinumab 150 mg, 300 mg, or placebo at weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter for 2.5 years. At 2.5 years, the mean reduction in NAPSI score was 63.6% in the secukinumab 150 mg group and 73.3% in the secukinumab 300 mg group.

“I do have to tell my patients what to expect, because the nails grow out slowly, but over time we do see this increase in efficacy,” Dr. Armstrong said.

Studies of another IL-17A antagonist, ixekizumab, have yielded positive results as well, she noted. In 2021, Taiwanese researchers published a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis. They drew from 39 studies involving 15,673 patients with nail psoriasis and found that the oral Janus kinase inhibitor tofacitinib and ixekizumab had the best efficacy for treating nail psoriasis in 10-16 weeks and 24-26 weeks, respectively.

“They found that overall, the biologics have a good effect on nail psoriasis and that the treatment effects are overall quite similar,” Dr. Armstrong said.

Dr. Armstrong disclosed that she is a consultant or adviser for numerous pharmaceutical companies. She has also received research funding from Bristol-Myers Squibb, Dermavant, Dermira, Leo, Lilly, Pfizer, and UCB Pharma.

HONOLULU – In the clinical experience of April W. Armstrong, MD, MPH, topical therapies typically don’t work well for nail psoriasis, so she sometimes resorts to intralesional injections combined with systemic therapy.

One might think of intralesional injections “as a torture method from the medieval days,” she said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!, but intramatricial corticosteroid injections have been performed for many years as a treatment for nail psoriasis, typically with triamcinolone acetonide.

Doug Brunk/MDedge News

According to Dr. Armstrong, professor of dermatology and associate dean of clinical research at the University of Southern California, Los Angeles, nail matrix psoriasis can present as pitting, leukonychia, red macules in the lunula, crumbling, or trachyonychia. Nail bed psoriasis can present as splinter hemorrhages and onycholysis, hyperkeratosis and splinter hemorrhages, salmon patch or oil spot dyschromia, or onycholysis and salmon patch dyschromia.

In a German cross-sectional study of patients with psoriasis, nails were one of the body sites that have the greatest impact on quality of life – especially those in younger age groups.

While topical treatments are generally considered first for limited disease involving special areas such as the nails, systemic therapy is warranted in patients with moderate-to-severe involvement of specific sites or in those refractory to topical therapy, Dr. Armstrong said.

In 2018, Indian researchers published results from an open-label study of 17 patients, with nail psoriasis, comparing three treatments . Patients were assigned to three groups of 30 nails each and treated with intramatricial injections of triamcinolone acetonide (10 mg/mL), methotrexate (25 mg/mL), and cyclosporine (50 mg/mL), respectively. Each nail was treated with two injections at 6-week intervals and graded at 24 weeks using the Nail Psoriasis Severity Index (NAPSI). In the triamcinolone acetonide and methotrexate groups, 50% of treated nails showed a greater than 75% improvement at 24 weeks, compared with 33% of those in the cyclosporine group. The most side effects occurred in the nails treated with cyclosporine.

When Dr. Armstrong performs intramatricial injections, she uses triamcinolone acetonide at 10 mg/mL. However, she said, “my favorite way of treating severe nail psoriasis is with biologics.”

In an early study of patients with moderate to severe psoriasis treated with the tumor necrosis factor blocker adalimumab 80 mg subcutaneously at week 0, followed by 40 mg subcutaneously every other week from weeks 1 to 15, a post hoc analysis on the effects on nail psoriasis showed a 10-point decrease in the median NAPSI score through week 16 – from 21 to 11 .

In VOYAGE 2, which compared the interleukin-23 blocker guselkumab and adalimumab in patients with moderate to severe psoriasis, the mean percent improvement from baseline in the NAPSI score was similar in patients treated with adalimumab or guselkumab at week 16 (39.6% vs. 46.9%, respectively) and at week 24 (55% vs. 53.7%).

In another study of patients with nail psoriasis, researchers evaluated the efficacy of the IL-17A antagonist secukinumab 150 mg, 300 mg, or placebo at weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter for 2.5 years. At 2.5 years, the mean reduction in NAPSI score was 63.6% in the secukinumab 150 mg group and 73.3% in the secukinumab 300 mg group.

“I do have to tell my patients what to expect, because the nails grow out slowly, but over time we do see this increase in efficacy,” Dr. Armstrong said.

Studies of another IL-17A antagonist, ixekizumab, have yielded positive results as well, she noted. In 2021, Taiwanese researchers published a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis. They drew from 39 studies involving 15,673 patients with nail psoriasis and found that the oral Janus kinase inhibitor tofacitinib and ixekizumab had the best efficacy for treating nail psoriasis in 10-16 weeks and 24-26 weeks, respectively.

“They found that overall, the biologics have a good effect on nail psoriasis and that the treatment effects are overall quite similar,” Dr. Armstrong said.

Dr. Armstrong disclosed that she is a consultant or adviser for numerous pharmaceutical companies. She has also received research funding from Bristol-Myers Squibb, Dermavant, Dermira, Leo, Lilly, Pfizer, and UCB Pharma.

HONOLULU – In the clinical experience of April W. Armstrong, MD, MPH, topical therapies typically don’t work well for nail psoriasis, so she sometimes resorts to intralesional injections combined with systemic therapy.

One might think of intralesional injections “as a torture method from the medieval days,” she said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!, but intramatricial corticosteroid injections have been performed for many years as a treatment for nail psoriasis, typically with triamcinolone acetonide.

Doug Brunk/MDedge News

According to Dr. Armstrong, professor of dermatology and associate dean of clinical research at the University of Southern California, Los Angeles, nail matrix psoriasis can present as pitting, leukonychia, red macules in the lunula, crumbling, or trachyonychia. Nail bed psoriasis can present as splinter hemorrhages and onycholysis, hyperkeratosis and splinter hemorrhages, salmon patch or oil spot dyschromia, or onycholysis and salmon patch dyschromia.

In a German cross-sectional study of patients with psoriasis, nails were one of the body sites that have the greatest impact on quality of life – especially those in younger age groups.

While topical treatments are generally considered first for limited disease involving special areas such as the nails, systemic therapy is warranted in patients with moderate-to-severe involvement of specific sites or in those refractory to topical therapy, Dr. Armstrong said.

In 2018, Indian researchers published results from an open-label study of 17 patients, with nail psoriasis, comparing three treatments . Patients were assigned to three groups of 30 nails each and treated with intramatricial injections of triamcinolone acetonide (10 mg/mL), methotrexate (25 mg/mL), and cyclosporine (50 mg/mL), respectively. Each nail was treated with two injections at 6-week intervals and graded at 24 weeks using the Nail Psoriasis Severity Index (NAPSI). In the triamcinolone acetonide and methotrexate groups, 50% of treated nails showed a greater than 75% improvement at 24 weeks, compared with 33% of those in the cyclosporine group. The most side effects occurred in the nails treated with cyclosporine.

When Dr. Armstrong performs intramatricial injections, she uses triamcinolone acetonide at 10 mg/mL. However, she said, “my favorite way of treating severe nail psoriasis is with biologics.”

In an early study of patients with moderate to severe psoriasis treated with the tumor necrosis factor blocker adalimumab 80 mg subcutaneously at week 0, followed by 40 mg subcutaneously every other week from weeks 1 to 15, a post hoc analysis on the effects on nail psoriasis showed a 10-point decrease in the median NAPSI score through week 16 – from 21 to 11 .

In VOYAGE 2, which compared the interleukin-23 blocker guselkumab and adalimumab in patients with moderate to severe psoriasis, the mean percent improvement from baseline in the NAPSI score was similar in patients treated with adalimumab or guselkumab at week 16 (39.6% vs. 46.9%, respectively) and at week 24 (55% vs. 53.7%).

In another study of patients with nail psoriasis, researchers evaluated the efficacy of the IL-17A antagonist secukinumab 150 mg, 300 mg, or placebo at weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter for 2.5 years. At 2.5 years, the mean reduction in NAPSI score was 63.6% in the secukinumab 150 mg group and 73.3% in the secukinumab 300 mg group.

“I do have to tell my patients what to expect, because the nails grow out slowly, but over time we do see this increase in efficacy,” Dr. Armstrong said.

Studies of another IL-17A antagonist, ixekizumab, have yielded positive results as well, she noted. In 2021, Taiwanese researchers published a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis. They drew from 39 studies involving 15,673 patients with nail psoriasis and found that the oral Janus kinase inhibitor tofacitinib and ixekizumab had the best efficacy for treating nail psoriasis in 10-16 weeks and 24-26 weeks, respectively.

“They found that overall, the biologics have a good effect on nail psoriasis and that the treatment effects are overall quite similar,” Dr. Armstrong said.

Dr. Armstrong disclosed that she is a consultant or adviser for numerous pharmaceutical companies. She has also received research funding from Bristol-Myers Squibb, Dermavant, Dermira, Leo, Lilly, Pfizer, and UCB Pharma.

Prone positioning significantly reduced the need for intubation among nonintubated adults with COVID-19, as indicated by data from a new meta-analysis of more than 2,000 individuals.

The use of prone positioning for nonintubated patients (so-called “awake prone positioning”) has been common since the early days of the COVID-19 pandemic. Prone positioning is more comfortable for patients, and it entails no additional cost. Also, awake prone positioning is less labor intensive than prone positioning for intubated patients, said Jie Li, PhD, in a presentation at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

However, data on the specific benefits of prone positioning are lacking and contradictory, said Dr. Li, a respiratory care specialist at Rush University, Chicago.

Dr. Li and colleagues from a multinational research group found that outcomes were improved for patients who were treated with awake prone positioning – notably, fewer treatment failures at day 28 – but a pair of subsequent studies by other researchers showed contradictory outcomes.

For more definitive evidence, Dr. Li and colleagues conducted a systematic review and meta-analysis of 11 randomized, controlled trials and one unpublished study of awake prone positioning for patients with COVID-19. The studies were published between Jan. 1, 2020, and July 1, 2022, and included a total of 2,886 adult patients.

The primary outcome was the reported cumulative risk of intubation among nonintubated COVID-19 patients. Secondary outcomes included mortality, the need for escalating respiratory support, length of hospital length of stay, ICU admission, and adverse events.

Overall, awake prone positioning significantly reduced the intubation risk among nonintubated patients compared to standard care (risk ratio, 0.85).

A further subgroup analysis showed a significant reduction in risk for intubation among patients supported by high-flow nasal cannula or noninvasive ventilation (RR, 0.83).

However, no additional reduction in intubation risk occurred among patients who received conventional oxygen therapy (RR, 1.02).

Mortality rates were similar for patients who underwent awake prone positioning and those who underwent supine positioning (RR, 0.96), as was the need for additional respiratory support (RR, 1.03). The length of hospital stay, ICU admission, and adverse events were similar between the patients who underwent prone positioning and those who underwent supine positioning.

The findings were limited by several factors. There was a potential for confounding by disease severity, which may have increased the use of respiratory support devices, Li said in her presentation.

“Another factor we should not ignore is the daily duration of prone positioning,” said Dr. Li. More research is needed to identify which factors play the greatest roles in treatment success.

The current study was important in that it evaluated the current evidence of awake prone positioning, “particularly to identify the patients who benefit most from this treatment, in order to guide clinical practice,” Dr. Li said in an interview.

“Since early in the pandemic, awake prone positioning has been broadly utilized to treat patients with COVID-19,” she said. “In 2021, we published a multinational randomized controlled trial with over 1,100 patients enrolled and reported lower treatment failure. However, no significant differences of treatment failure were reported in several subsequent multicenter randomized, controlled trials published after our study.”

Dr. Li said she was not surprised by the findings, which reflect those of her team’s previously published meta-analysis. “The increased number of patients helps confirm our previous finding, even with the inclusion of several recently published randomized controlled trials,” she said.

For clinicians, “the current evidence supports the use of awake prone positioning for patients with COVID-19, particularly those who require advanced respiratory support from high-flow nasal cannula or noninvasive ventilation,” Dr. Li said.

The study received no outside funding. Dr. Li has relationships with AARC, Heyer, Aeorgen, the Rice Foundation, and Fisher & Paykel Healthcare.

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

Prone positioning significantly reduced the need for intubation among nonintubated adults with COVID-19, as indicated by data from a new meta-analysis of more than 2,000 individuals.

The use of prone positioning for nonintubated patients (so-called “awake prone positioning”) has been common since the early days of the COVID-19 pandemic. Prone positioning is more comfortable for patients, and it entails no additional cost. Also, awake prone positioning is less labor intensive than prone positioning for intubated patients, said Jie Li, PhD, in a presentation at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

However, data on the specific benefits of prone positioning are lacking and contradictory, said Dr. Li, a respiratory care specialist at Rush University, Chicago.

Dr. Li and colleagues from a multinational research group found that outcomes were improved for patients who were treated with awake prone positioning – notably, fewer treatment failures at day 28 – but a pair of subsequent studies by other researchers showed contradictory outcomes.

For more definitive evidence, Dr. Li and colleagues conducted a systematic review and meta-analysis of 11 randomized, controlled trials and one unpublished study of awake prone positioning for patients with COVID-19. The studies were published between Jan. 1, 2020, and July 1, 2022, and included a total of 2,886 adult patients.

The primary outcome was the reported cumulative risk of intubation among nonintubated COVID-19 patients. Secondary outcomes included mortality, the need for escalating respiratory support, length of hospital length of stay, ICU admission, and adverse events.

Overall, awake prone positioning significantly reduced the intubation risk among nonintubated patients compared to standard care (risk ratio, 0.85).

A further subgroup analysis showed a significant reduction in risk for intubation among patients supported by high-flow nasal cannula or noninvasive ventilation (RR, 0.83).

However, no additional reduction in intubation risk occurred among patients who received conventional oxygen therapy (RR, 1.02).

Mortality rates were similar for patients who underwent awake prone positioning and those who underwent supine positioning (RR, 0.96), as was the need for additional respiratory support (RR, 1.03). The length of hospital stay, ICU admission, and adverse events were similar between the patients who underwent prone positioning and those who underwent supine positioning.

The findings were limited by several factors. There was a potential for confounding by disease severity, which may have increased the use of respiratory support devices, Li said in her presentation.

“Another factor we should not ignore is the daily duration of prone positioning,” said Dr. Li. More research is needed to identify which factors play the greatest roles in treatment success.

The current study was important in that it evaluated the current evidence of awake prone positioning, “particularly to identify the patients who benefit most from this treatment, in order to guide clinical practice,” Dr. Li said in an interview.

“Since early in the pandemic, awake prone positioning has been broadly utilized to treat patients with COVID-19,” she said. “In 2021, we published a multinational randomized controlled trial with over 1,100 patients enrolled and reported lower treatment failure. However, no significant differences of treatment failure were reported in several subsequent multicenter randomized, controlled trials published after our study.”

Dr. Li said she was not surprised by the findings, which reflect those of her team’s previously published meta-analysis. “The increased number of patients helps confirm our previous finding, even with the inclusion of several recently published randomized controlled trials,” she said.

For clinicians, “the current evidence supports the use of awake prone positioning for patients with COVID-19, particularly those who require advanced respiratory support from high-flow nasal cannula or noninvasive ventilation,” Dr. Li said.

The study received no outside funding. Dr. Li has relationships with AARC, Heyer, Aeorgen, the Rice Foundation, and Fisher & Paykel Healthcare.

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

Prone positioning significantly reduced the need for intubation among nonintubated adults with COVID-19, as indicated by data from a new meta-analysis of more than 2,000 individuals.

The use of prone positioning for nonintubated patients (so-called “awake prone positioning”) has been common since the early days of the COVID-19 pandemic. Prone positioning is more comfortable for patients, and it entails no additional cost. Also, awake prone positioning is less labor intensive than prone positioning for intubated patients, said Jie Li, PhD, in a presentation at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

However, data on the specific benefits of prone positioning are lacking and contradictory, said Dr. Li, a respiratory care specialist at Rush University, Chicago.

Dr. Li and colleagues from a multinational research group found that outcomes were improved for patients who were treated with awake prone positioning – notably, fewer treatment failures at day 28 – but a pair of subsequent studies by other researchers showed contradictory outcomes.

For more definitive evidence, Dr. Li and colleagues conducted a systematic review and meta-analysis of 11 randomized, controlled trials and one unpublished study of awake prone positioning for patients with COVID-19. The studies were published between Jan. 1, 2020, and July 1, 2022, and included a total of 2,886 adult patients.

The primary outcome was the reported cumulative risk of intubation among nonintubated COVID-19 patients. Secondary outcomes included mortality, the need for escalating respiratory support, length of hospital length of stay, ICU admission, and adverse events.

Overall, awake prone positioning significantly reduced the intubation risk among nonintubated patients compared to standard care (risk ratio, 0.85).

A further subgroup analysis showed a significant reduction in risk for intubation among patients supported by high-flow nasal cannula or noninvasive ventilation (RR, 0.83).

However, no additional reduction in intubation risk occurred among patients who received conventional oxygen therapy (RR, 1.02).

Mortality rates were similar for patients who underwent awake prone positioning and those who underwent supine positioning (RR, 0.96), as was the need for additional respiratory support (RR, 1.03). The length of hospital stay, ICU admission, and adverse events were similar between the patients who underwent prone positioning and those who underwent supine positioning.

The findings were limited by several factors. There was a potential for confounding by disease severity, which may have increased the use of respiratory support devices, Li said in her presentation.

“Another factor we should not ignore is the daily duration of prone positioning,” said Dr. Li. More research is needed to identify which factors play the greatest roles in treatment success.

The current study was important in that it evaluated the current evidence of awake prone positioning, “particularly to identify the patients who benefit most from this treatment, in order to guide clinical practice,” Dr. Li said in an interview.

“Since early in the pandemic, awake prone positioning has been broadly utilized to treat patients with COVID-19,” she said. “In 2021, we published a multinational randomized controlled trial with over 1,100 patients enrolled and reported lower treatment failure. However, no significant differences of treatment failure were reported in several subsequent multicenter randomized, controlled trials published after our study.”

Dr. Li said she was not surprised by the findings, which reflect those of her team’s previously published meta-analysis. “The increased number of patients helps confirm our previous finding, even with the inclusion of several recently published randomized controlled trials,” she said.

For clinicians, “the current evidence supports the use of awake prone positioning for patients with COVID-19, particularly those who require advanced respiratory support from high-flow nasal cannula or noninvasive ventilation,” Dr. Li said.

The study received no outside funding. Dr. Li has relationships with AARC, Heyer, Aeorgen, the Rice Foundation, and Fisher & Paykel Healthcare.

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

The latest guideline for perioperative management of antirheumatic medication in patients undergoing total hip (THA) and total knee arthroplasty (TKA) offers recommendations based on the latest evidence, but many of those recommendations are based on a low level of evidence, according to a speaker at the 2023 Rheumatology Winter Clinical Symposium.

Martin Bergman, MD, clinical professor of medicine at Drexel University, Philadelphia, said the development of the American College of Rheumatology/American Association of Hip and Knee Surgeons guideline was necessary because there was a lack of consensus on when to stop treatments prior to patients with rheumatologic disease undergoing THA and TKA, and when it was appropriate to restart those treatments.

“We all were having the same problem, and I think everybody recognized that just stopping medicines forever didn’t make sense, but maybe continuing medicines also didn’t make sense,” Dr. Bergman said.

While the 2017 ACR/AAHKS perioperative management guideline contained good recommendations, the “explosion” of new medications in rheumatology made it necessary to update the guideline with the latest data on new medications such as immunosuppressants.
 

2022 guideline recommendations

In the 2022 guideline, which covers disease-modifying treatments taken by patients with rheumatoid arthritis, spondyloarthritis, and psoriatic arthritis, the authors reaffirmed their recommendations to continue methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, and apremilast through total joint arthroplasty.

Where the 2022 guideline differs from the 2017 guideline is in which biologics are covered and under what circumstances they should be withheld and restarted around surgery. The 2022 guideline includes recommendations for abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, guselkumab, infliximab, ixekizumab, rituximab, secukinumab, tocilizumab, and ustekinumab. Each biologic has its own recommended stop and restart times based around the dosing interval and respective method of administration. Dr. Bergman said a general rule with biologics under the new guideline is that the timing of surgery should occur approximately 1 week after the first missed dose of the medication. The only biologic that does not follow this pattern is rituximab, where surgery should be planned for 1 month after the last missed dose.

Dr. Bergman noted that how the guidelines handle interval dosing with infliximab may present a problem. The guideline provides recommendations for patients receiving infliximab every 4 weeks, every 6 weeks, and every 8 weeks. However, Dr. Bergman said this can create a scenario where a patient receiving infliximab at a dose of 3 mg/kg every 8 weeks has surgery at 9 weeks, a patient receiving 5 mg/kg every 6 weeks has surgery at 7 weeks, and a patient receiving 10 mg/kg every 4 weeks has surgery at 5 weeks. “There is some intellectual problem with it,” he said.

Another change from the 2017 guideline is how long to wait for surgery after stopping Janus kinase inhibitors. While the 2017 guideline recommended withholding JAK inhibitors 7 days before surgery, the 2022 guideline lowered that waiting period to 3 days, Dr. Bergman explained.

Concerning use of steroids around THA and TKA surgery, “the days of stress steroid dosing are done,” Dr. Bergman said. “You don’t have to stress dose them. You just follow them, and you keep them on their steroid dose.”

The new guideline recommends restarting therapy once the wound is healed and there is no physical evidence of infection at approximately 2 weeks. “There’s no data to support this,” he said, and his concern is that patients who have stopped a tumor necrosis factor inhibitor may flare if they don’t restart their medication.

While the guideline also covered recommendations for systemic lupus erythematosus, they are “very similar” to the recommendations for inflammatory arthritis, Dr. Bergman noted. “If you have somebody who is not very sick, you stop the medications,” he said, “but try to stop anything else about a week before the surgery. If they’re sick, you basically have to keep them on their medications.”
 

Caveats in guideline

The recommendations in the 2022 guideline come with a number of caveats, Dr. Bergman noted. For instance, the authors acknowledged limitations in the guideline regarding providing recommendations for only THA and TKA, the “paucity of evidence” around direct infection risk resulting from medications in the perioperative period for THA and TKA, the nonseparation of biologics when assessing infection risk, and the use of dosing interval as a metric for stopping the drug without considering the drug’s half-life.

A “crucial caveat,” Dr. Bergman said, was that the guideline focused on infection risk based on a statement from a panel of patients prior to the development of the 2017 guideline, which “stated very clearly any risk of infection, while rare, was more significant to them than the possibility of postoperative flares, despite flares being reported in over 60% of patients after surgery.

“For the patients, the paramount question was infection, infection, infection, infection. That’s all they cared about, and that is the basis behind a lot of the decision-making here,” Dr. Bergman said.

Another caveat came from a communication Dr. Bergman received from one of the panel members. The panel member noted there were no conclusions or recommendations provided in the guideline for how to manage perioperative flares, such as restarting a corticosteroid or biologic agent. “There was a lot of discussion about what to do with steroids if patients flare, or what to do with [other] medications if they flare, and they just couldn’t come to a consensus,” Dr. Bergman said. “It’s just not discussed.”

Dr. Bergman said he is “somewhat critical” of the ACR/AAHKS guideline, but noted it is an “ambitious project” given the lack of evidence for the recommendations. “The alternative was stop the medications forever and having people really flare, or at least try to get some semblance of rationality behind what we’re going to do,” he said.
 

Response from attendees

Jack Cush, MD, a rheumatologist based in Dallas and executive editor of RheumNow.com, took issue with the new recommendations surrounding stopping infliximab. When giving a patient infliximab every 8 weeks at 3 mg/kg, “you’re giving [it] at the nadir of the drug,” he said.

Rather than drug half-life, “it’s about inflammation,” he emphasized. “Inflammation is dominant in causing infection. It drives risk more than anything. The worst thing you can do is wash someone out.

“If you’re going beyond 8 weeks on infliximab, you’re getting closer to washing them out,” he pointed out. “I think it’s a really bad idea.”

Allan Gibofsky, MD, JD, professor of medicine at Weill Cornell Medicine and codirector of the Clinic for Inflammatory Arthritis and Biologic Therapy at Hospital for Special Surgery, both in New York, explained that the guideline is not standard of care, which would be subject to malpractice if not implemented properly.

“When you have guidelines, you follow them unless there are clinical situations which would necessitate another approach to the patient,” he said. “Professional institutions and associations will never put forth rules, they will put forth guidelines so you have the opportunity to deviate from them when the appropriate clinical situation dictates.”

Dr. Bergman reported being a speaker and consultant for AbbVie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, Pfizer, and Regeneron; he holds stock in Johnson & Johnson and Merck.

The latest guideline for perioperative management of antirheumatic medication in patients undergoing total hip (THA) and total knee arthroplasty (TKA) offers recommendations based on the latest evidence, but many of those recommendations are based on a low level of evidence, according to a speaker at the 2023 Rheumatology Winter Clinical Symposium.

Martin Bergman, MD, clinical professor of medicine at Drexel University, Philadelphia, said the development of the American College of Rheumatology/American Association of Hip and Knee Surgeons guideline was necessary because there was a lack of consensus on when to stop treatments prior to patients with rheumatologic disease undergoing THA and TKA, and when it was appropriate to restart those treatments.

“We all were having the same problem, and I think everybody recognized that just stopping medicines forever didn’t make sense, but maybe continuing medicines also didn’t make sense,” Dr. Bergman said.

While the 2017 ACR/AAHKS perioperative management guideline contained good recommendations, the “explosion” of new medications in rheumatology made it necessary to update the guideline with the latest data on new medications such as immunosuppressants.
 

2022 guideline recommendations

In the 2022 guideline, which covers disease-modifying treatments taken by patients with rheumatoid arthritis, spondyloarthritis, and psoriatic arthritis, the authors reaffirmed their recommendations to continue methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, and apremilast through total joint arthroplasty.

Where the 2022 guideline differs from the 2017 guideline is in which biologics are covered and under what circumstances they should be withheld and restarted around surgery. The 2022 guideline includes recommendations for abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, guselkumab, infliximab, ixekizumab, rituximab, secukinumab, tocilizumab, and ustekinumab. Each biologic has its own recommended stop and restart times based around the dosing interval and respective method of administration. Dr. Bergman said a general rule with biologics under the new guideline is that the timing of surgery should occur approximately 1 week after the first missed dose of the medication. The only biologic that does not follow this pattern is rituximab, where surgery should be planned for 1 month after the last missed dose.

Dr. Bergman noted that how the guidelines handle interval dosing with infliximab may present a problem. The guideline provides recommendations for patients receiving infliximab every 4 weeks, every 6 weeks, and every 8 weeks. However, Dr. Bergman said this can create a scenario where a patient receiving infliximab at a dose of 3 mg/kg every 8 weeks has surgery at 9 weeks, a patient receiving 5 mg/kg every 6 weeks has surgery at 7 weeks, and a patient receiving 10 mg/kg every 4 weeks has surgery at 5 weeks. “There is some intellectual problem with it,” he said.

Another change from the 2017 guideline is how long to wait for surgery after stopping Janus kinase inhibitors. While the 2017 guideline recommended withholding JAK inhibitors 7 days before surgery, the 2022 guideline lowered that waiting period to 3 days, Dr. Bergman explained.

Concerning use of steroids around THA and TKA surgery, “the days of stress steroid dosing are done,” Dr. Bergman said. “You don’t have to stress dose them. You just follow them, and you keep them on their steroid dose.”

The new guideline recommends restarting therapy once the wound is healed and there is no physical evidence of infection at approximately 2 weeks. “There’s no data to support this,” he said, and his concern is that patients who have stopped a tumor necrosis factor inhibitor may flare if they don’t restart their medication.

While the guideline also covered recommendations for systemic lupus erythematosus, they are “very similar” to the recommendations for inflammatory arthritis, Dr. Bergman noted. “If you have somebody who is not very sick, you stop the medications,” he said, “but try to stop anything else about a week before the surgery. If they’re sick, you basically have to keep them on their medications.”
 

Caveats in guideline

The recommendations in the 2022 guideline come with a number of caveats, Dr. Bergman noted. For instance, the authors acknowledged limitations in the guideline regarding providing recommendations for only THA and TKA, the “paucity of evidence” around direct infection risk resulting from medications in the perioperative period for THA and TKA, the nonseparation of biologics when assessing infection risk, and the use of dosing interval as a metric for stopping the drug without considering the drug’s half-life.

A “crucial caveat,” Dr. Bergman said, was that the guideline focused on infection risk based on a statement from a panel of patients prior to the development of the 2017 guideline, which “stated very clearly any risk of infection, while rare, was more significant to them than the possibility of postoperative flares, despite flares being reported in over 60% of patients after surgery.

“For the patients, the paramount question was infection, infection, infection, infection. That’s all they cared about, and that is the basis behind a lot of the decision-making here,” Dr. Bergman said.

Another caveat came from a communication Dr. Bergman received from one of the panel members. The panel member noted there were no conclusions or recommendations provided in the guideline for how to manage perioperative flares, such as restarting a corticosteroid or biologic agent. “There was a lot of discussion about what to do with steroids if patients flare, or what to do with [other] medications if they flare, and they just couldn’t come to a consensus,” Dr. Bergman said. “It’s just not discussed.”

Dr. Bergman said he is “somewhat critical” of the ACR/AAHKS guideline, but noted it is an “ambitious project” given the lack of evidence for the recommendations. “The alternative was stop the medications forever and having people really flare, or at least try to get some semblance of rationality behind what we’re going to do,” he said.
 

Response from attendees

Jack Cush, MD, a rheumatologist based in Dallas and executive editor of RheumNow.com, took issue with the new recommendations surrounding stopping infliximab. When giving a patient infliximab every 8 weeks at 3 mg/kg, “you’re giving [it] at the nadir of the drug,” he said.

Rather than drug half-life, “it’s about inflammation,” he emphasized. “Inflammation is dominant in causing infection. It drives risk more than anything. The worst thing you can do is wash someone out.

“If you’re going beyond 8 weeks on infliximab, you’re getting closer to washing them out,” he pointed out. “I think it’s a really bad idea.”

Allan Gibofsky, MD, JD, professor of medicine at Weill Cornell Medicine and codirector of the Clinic for Inflammatory Arthritis and Biologic Therapy at Hospital for Special Surgery, both in New York, explained that the guideline is not standard of care, which would be subject to malpractice if not implemented properly.

“When you have guidelines, you follow them unless there are clinical situations which would necessitate another approach to the patient,” he said. “Professional institutions and associations will never put forth rules, they will put forth guidelines so you have the opportunity to deviate from them when the appropriate clinical situation dictates.”

Dr. Bergman reported being a speaker and consultant for AbbVie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, Pfizer, and Regeneron; he holds stock in Johnson & Johnson and Merck.

The latest guideline for perioperative management of antirheumatic medication in patients undergoing total hip (THA) and total knee arthroplasty (TKA) offers recommendations based on the latest evidence, but many of those recommendations are based on a low level of evidence, according to a speaker at the 2023 Rheumatology Winter Clinical Symposium.

Martin Bergman, MD, clinical professor of medicine at Drexel University, Philadelphia, said the development of the American College of Rheumatology/American Association of Hip and Knee Surgeons guideline was necessary because there was a lack of consensus on when to stop treatments prior to patients with rheumatologic disease undergoing THA and TKA, and when it was appropriate to restart those treatments.

“We all were having the same problem, and I think everybody recognized that just stopping medicines forever didn’t make sense, but maybe continuing medicines also didn’t make sense,” Dr. Bergman said.

While the 2017 ACR/AAHKS perioperative management guideline contained good recommendations, the “explosion” of new medications in rheumatology made it necessary to update the guideline with the latest data on new medications such as immunosuppressants.
 

2022 guideline recommendations

In the 2022 guideline, which covers disease-modifying treatments taken by patients with rheumatoid arthritis, spondyloarthritis, and psoriatic arthritis, the authors reaffirmed their recommendations to continue methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, and apremilast through total joint arthroplasty.

Where the 2022 guideline differs from the 2017 guideline is in which biologics are covered and under what circumstances they should be withheld and restarted around surgery. The 2022 guideline includes recommendations for abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, guselkumab, infliximab, ixekizumab, rituximab, secukinumab, tocilizumab, and ustekinumab. Each biologic has its own recommended stop and restart times based around the dosing interval and respective method of administration. Dr. Bergman said a general rule with biologics under the new guideline is that the timing of surgery should occur approximately 1 week after the first missed dose of the medication. The only biologic that does not follow this pattern is rituximab, where surgery should be planned for 1 month after the last missed dose.

Dr. Bergman noted that how the guidelines handle interval dosing with infliximab may present a problem. The guideline provides recommendations for patients receiving infliximab every 4 weeks, every 6 weeks, and every 8 weeks. However, Dr. Bergman said this can create a scenario where a patient receiving infliximab at a dose of 3 mg/kg every 8 weeks has surgery at 9 weeks, a patient receiving 5 mg/kg every 6 weeks has surgery at 7 weeks, and a patient receiving 10 mg/kg every 4 weeks has surgery at 5 weeks. “There is some intellectual problem with it,” he said.

Another change from the 2017 guideline is how long to wait for surgery after stopping Janus kinase inhibitors. While the 2017 guideline recommended withholding JAK inhibitors 7 days before surgery, the 2022 guideline lowered that waiting period to 3 days, Dr. Bergman explained.

Concerning use of steroids around THA and TKA surgery, “the days of stress steroid dosing are done,” Dr. Bergman said. “You don’t have to stress dose them. You just follow them, and you keep them on their steroid dose.”

The new guideline recommends restarting therapy once the wound is healed and there is no physical evidence of infection at approximately 2 weeks. “There’s no data to support this,” he said, and his concern is that patients who have stopped a tumor necrosis factor inhibitor may flare if they don’t restart their medication.

While the guideline also covered recommendations for systemic lupus erythematosus, they are “very similar” to the recommendations for inflammatory arthritis, Dr. Bergman noted. “If you have somebody who is not very sick, you stop the medications,” he said, “but try to stop anything else about a week before the surgery. If they’re sick, you basically have to keep them on their medications.”
 

Caveats in guideline

The recommendations in the 2022 guideline come with a number of caveats, Dr. Bergman noted. For instance, the authors acknowledged limitations in the guideline regarding providing recommendations for only THA and TKA, the “paucity of evidence” around direct infection risk resulting from medications in the perioperative period for THA and TKA, the nonseparation of biologics when assessing infection risk, and the use of dosing interval as a metric for stopping the drug without considering the drug’s half-life.

A “crucial caveat,” Dr. Bergman said, was that the guideline focused on infection risk based on a statement from a panel of patients prior to the development of the 2017 guideline, which “stated very clearly any risk of infection, while rare, was more significant to them than the possibility of postoperative flares, despite flares being reported in over 60% of patients after surgery.

“For the patients, the paramount question was infection, infection, infection, infection. That’s all they cared about, and that is the basis behind a lot of the decision-making here,” Dr. Bergman said.

Another caveat came from a communication Dr. Bergman received from one of the panel members. The panel member noted there were no conclusions or recommendations provided in the guideline for how to manage perioperative flares, such as restarting a corticosteroid or biologic agent. “There was a lot of discussion about what to do with steroids if patients flare, or what to do with [other] medications if they flare, and they just couldn’t come to a consensus,” Dr. Bergman said. “It’s just not discussed.”

Dr. Bergman said he is “somewhat critical” of the ACR/AAHKS guideline, but noted it is an “ambitious project” given the lack of evidence for the recommendations. “The alternative was stop the medications forever and having people really flare, or at least try to get some semblance of rationality behind what we’re going to do,” he said.
 

Response from attendees

Jack Cush, MD, a rheumatologist based in Dallas and executive editor of RheumNow.com, took issue with the new recommendations surrounding stopping infliximab. When giving a patient infliximab every 8 weeks at 3 mg/kg, “you’re giving [it] at the nadir of the drug,” he said.

Rather than drug half-life, “it’s about inflammation,” he emphasized. “Inflammation is dominant in causing infection. It drives risk more than anything. The worst thing you can do is wash someone out.

“If you’re going beyond 8 weeks on infliximab, you’re getting closer to washing them out,” he pointed out. “I think it’s a really bad idea.”

Allan Gibofsky, MD, JD, professor of medicine at Weill Cornell Medicine and codirector of the Clinic for Inflammatory Arthritis and Biologic Therapy at Hospital for Special Surgery, both in New York, explained that the guideline is not standard of care, which would be subject to malpractice if not implemented properly.

“When you have guidelines, you follow them unless there are clinical situations which would necessitate another approach to the patient,” he said. “Professional institutions and associations will never put forth rules, they will put forth guidelines so you have the opportunity to deviate from them when the appropriate clinical situation dictates.”

Dr. Bergman reported being a speaker and consultant for AbbVie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, Pfizer, and Regeneron; he holds stock in Johnson & Johnson and Merck.

To address the growing workforce shortage in rheumatology, medical educators will have to adapt and learn how to train a new generation of rheumatologists, according to a speaker at the 2023 Rheumatology Winter Clinical Symposium.

Anisha B. Dua, MD, an associate professor of rheumatology at Northwestern University, Chicago, told attendees she is “heavily invested in the training of our future rheumatologists” and strives to help them “operate at the top of the level across the spectrum.”

M. Alexander Otto

“They’re carrying forward our field,” Dr. Dua said. “We need to propagate our field and we need them to go out and serve and continue to make rheumatology awesome.”

The American College of Rheumatology’s 2015 workforce study estimates that by 2030, there will be a shortage of more than 4,000 rheumatologists in the United States.

Rheumatology may have inadvertently created the problem through rheumatologists diagnosing disease earlier and prescribing better treatments, with patients subsequently living longer with disease, she noted. Compounding the problem is an increasing number of rheumatologists looking to retire over the next decade and the continued need for care in rural areas where there are few practicing rheumatologists.
 

Interest in rheumatology is increasing

The good news is there is increasing interest in the field. “This has really shifted, I would say, from about 10 years ago when I was looking at fellowships,” Dr. Dua said. “It’s not really an interest problem. But the issue is that the training programs and slots don’t necessarily exist to fill the gap of the people who are leaving the field.”

The key to bringing more people into rheumatology is to understand how Millennials and Generation Z differ from generations that came before them. In general, members of Generation Z “tend to prefer an à la carte approach to education” with hands-on experiences, and they prefer customized feedback that is actionable, Dr. Dua explained.

“As a medical educator, there are different demands, and these are changing over time, so we have to figure out how we can best serve them and educate them,” she said.

This also means connecting with younger generations on social media. A research letter published in JAMA Network Open in 2021 found a minority of 650 physicians across 14 specialties had a presence on social media platforms, with 44.9% of physicians surveyed present on LinkedIn, 23.4% on Facebook, 18.6% of on Twitter, and 14.9% on ResearchGate. “There is a lot of room to grow, and this is where some of our future teaching is headed,” Dr. Dua said.
 

Future of rheumatology education

Does this mean rheumatologists should start dancing in TikTok videos? Maybe not, but Dr. Dua noted there are ways to bring understanding, recall, comprehension, and behavioral change through active learning, spaced learning, case-based modules, podcasts, videos, and other educational strategies.

“We need to find ways to engage our learners and connect with them and teach them,” she said.

Rheumatologists are already bringing innovation to the education space with initiatives like educational podcasts, remote learning developed during the COVID-19 pandemic, development of rheumatology Objective Structured Clinical Examinations using challenging patient scenarios, and other virtual learning opportunities. “We really have been forced to push the envelope,” Dr. Dua said.

“The future of medical education is here. It’s exciting. Embrace it,” she said.
 

Training nurse practitioners and physician assistants?

Commenting on the shortage of rheumatologists, Philip J. Mease, MD, clinical professor at the University of Washington and director of rheumatology research at Swedish Medical Center, both in Seattle, said one answer to the problem may be training more nurse practitioners (NPs) and physician assistants (PAs) to bridge the gap.

“Some are suggesting that part of the answer to the deficiency of rheumatologists will be having two NPs or PAs to every single rheumatologist that there is out there,” he said. “I work with three, and the issue of ... getting access to them when they are in school to demonstrate how sexy rheumatology is, is something that is deficient, way deficient.” Rheumatologists should be putting themselves out there with preceptorships and lectures to recruit more NPs and PAs to rheumatology, he explained. “That’s a 24/7 process.”

Dr. Dua, who is cochair of the E-Learning Subcommittee within the ACR Workforce Solutions Steering Committee, said the subcomittee’s focus has been connecting with primary care doctors, pediatricians, NPs, and PAs to “expand who can provide some rheumatologic care.”

Lindsay Orme, MD, a family medicine doctor from Caldwell, Idaho, shared her experience serving as faculty for a family medicine residency program, training family medicine doctors in rural areas.

“Our curriculum hasn’t had a section for what trainees are expected to learn in rheumatology. When I did the same program years ago in Idaho, it was very well defined: What I should know how to do without consulting a cardiologist, what I should know how to do without consulting an obstetrician, what I should be able to manage in terms of [chronic kidney disease] before referring to nephrology,” she explained. “No one ever taught me what I could manage in rheumatology.

“I do think we need to find some defined areas that we’re more comfortable teaching primary care doctors to manage because there is no one – there are no rheumatologists in Boise or any of the surrounding towns that accept Medicaid patients now. They are all expected to go 250 miles away,” she said.

“That’s a major, major problem,” Dr. Dua acknowledged. “Really, for me, the goal is to develop resources that you can tap into to be able to at least figure out where things stand, and at least bide time until they can get in with that rheumatologist 250 miles away and make sure that you’re getting the training, or feel comfortable with whatever it is you’re forced to manage from a rheumatologic sense.”
 

More engagement, more adaptation

Roy M. Fleischmann, MD, clinical professor of medicine at the University of Texas and codirector of the Metroplex Clinical Research Center, both in Dallas, said one thing he’s noticed over the years is that, as time spent in the hospital has decreased, the time residents and fellows spend with practitioners in front of patients has also decreased. “It just isn’t there, and that’s where you really learn,” he said.

“You are 100% correct the two generations are different. What I think is important in life is very different than what the fellows think is different in life at this point, and how much work I’m willing to put in or how much work they’re willing to put in, in the same way, is very different,” he explained. “What they want to spend their time on, I don’t, and vice versa. We do have to adapt, but I do think that they need more time in front of patients with very experienced physicians.”

Jack Cush, MD, a rheumatologist based in Dallas and executive editor of RheumNow.com, said if education is to move forward, “it’s got to change dramatically.”

“The competencies aren’t always knowledge,” he said. “Knowledge has now been replaced by everything at your fingertips. I don’t need to know all the formulas and everything right now.”

Engagement should be the “main statistic that we need to be striving for,” Dr. Cush explained. “Engagement as the measure of ... education’s value, I think, is where it has to go.”

Dr. Dua reported being a consultant and serving on an advisory board for Sanofi, Novartis, AbbVie, and Chemocentryx/Amgen.

To address the growing workforce shortage in rheumatology, medical educators will have to adapt and learn how to train a new generation of rheumatologists, according to a speaker at the 2023 Rheumatology Winter Clinical Symposium.

Anisha B. Dua, MD, an associate professor of rheumatology at Northwestern University, Chicago, told attendees she is “heavily invested in the training of our future rheumatologists” and strives to help them “operate at the top of the level across the spectrum.”

M. Alexander Otto

“They’re carrying forward our field,” Dr. Dua said. “We need to propagate our field and we need them to go out and serve and continue to make rheumatology awesome.”

The American College of Rheumatology’s 2015 workforce study estimates that by 2030, there will be a shortage of more than 4,000 rheumatologists in the United States.

Rheumatology may have inadvertently created the problem through rheumatologists diagnosing disease earlier and prescribing better treatments, with patients subsequently living longer with disease, she noted. Compounding the problem is an increasing number of rheumatologists looking to retire over the next decade and the continued need for care in rural areas where there are few practicing rheumatologists.
 

Interest in rheumatology is increasing

The good news is there is increasing interest in the field. “This has really shifted, I would say, from about 10 years ago when I was looking at fellowships,” Dr. Dua said. “It’s not really an interest problem. But the issue is that the training programs and slots don’t necessarily exist to fill the gap of the people who are leaving the field.”

The key to bringing more people into rheumatology is to understand how Millennials and Generation Z differ from generations that came before them. In general, members of Generation Z “tend to prefer an à la carte approach to education” with hands-on experiences, and they prefer customized feedback that is actionable, Dr. Dua explained.

“As a medical educator, there are different demands, and these are changing over time, so we have to figure out how we can best serve them and educate them,” she said.

This also means connecting with younger generations on social media. A research letter published in JAMA Network Open in 2021 found a minority of 650 physicians across 14 specialties had a presence on social media platforms, with 44.9% of physicians surveyed present on LinkedIn, 23.4% on Facebook, 18.6% of on Twitter, and 14.9% on ResearchGate. “There is a lot of room to grow, and this is where some of our future teaching is headed,” Dr. Dua said.
 

Future of rheumatology education

Does this mean rheumatologists should start dancing in TikTok videos? Maybe not, but Dr. Dua noted there are ways to bring understanding, recall, comprehension, and behavioral change through active learning, spaced learning, case-based modules, podcasts, videos, and other educational strategies.

“We need to find ways to engage our learners and connect with them and teach them,” she said.

Rheumatologists are already bringing innovation to the education space with initiatives like educational podcasts, remote learning developed during the COVID-19 pandemic, development of rheumatology Objective Structured Clinical Examinations using challenging patient scenarios, and other virtual learning opportunities. “We really have been forced to push the envelope,” Dr. Dua said.

“The future of medical education is here. It’s exciting. Embrace it,” she said.
 

Training nurse practitioners and physician assistants?

Commenting on the shortage of rheumatologists, Philip J. Mease, MD, clinical professor at the University of Washington and director of rheumatology research at Swedish Medical Center, both in Seattle, said one answer to the problem may be training more nurse practitioners (NPs) and physician assistants (PAs) to bridge the gap.

“Some are suggesting that part of the answer to the deficiency of rheumatologists will be having two NPs or PAs to every single rheumatologist that there is out there,” he said. “I work with three, and the issue of ... getting access to them when they are in school to demonstrate how sexy rheumatology is, is something that is deficient, way deficient.” Rheumatologists should be putting themselves out there with preceptorships and lectures to recruit more NPs and PAs to rheumatology, he explained. “That’s a 24/7 process.”

Dr. Dua, who is cochair of the E-Learning Subcommittee within the ACR Workforce Solutions Steering Committee, said the subcomittee’s focus has been connecting with primary care doctors, pediatricians, NPs, and PAs to “expand who can provide some rheumatologic care.”

Lindsay Orme, MD, a family medicine doctor from Caldwell, Idaho, shared her experience serving as faculty for a family medicine residency program, training family medicine doctors in rural areas.

“Our curriculum hasn’t had a section for what trainees are expected to learn in rheumatology. When I did the same program years ago in Idaho, it was very well defined: What I should know how to do without consulting a cardiologist, what I should know how to do without consulting an obstetrician, what I should be able to manage in terms of [chronic kidney disease] before referring to nephrology,” she explained. “No one ever taught me what I could manage in rheumatology.

“I do think we need to find some defined areas that we’re more comfortable teaching primary care doctors to manage because there is no one – there are no rheumatologists in Boise or any of the surrounding towns that accept Medicaid patients now. They are all expected to go 250 miles away,” she said.

“That’s a major, major problem,” Dr. Dua acknowledged. “Really, for me, the goal is to develop resources that you can tap into to be able to at least figure out where things stand, and at least bide time until they can get in with that rheumatologist 250 miles away and make sure that you’re getting the training, or feel comfortable with whatever it is you’re forced to manage from a rheumatologic sense.”
 

More engagement, more adaptation

Roy M. Fleischmann, MD, clinical professor of medicine at the University of Texas and codirector of the Metroplex Clinical Research Center, both in Dallas, said one thing he’s noticed over the years is that, as time spent in the hospital has decreased, the time residents and fellows spend with practitioners in front of patients has also decreased. “It just isn’t there, and that’s where you really learn,” he said.

“You are 100% correct the two generations are different. What I think is important in life is very different than what the fellows think is different in life at this point, and how much work I’m willing to put in or how much work they’re willing to put in, in the same way, is very different,” he explained. “What they want to spend their time on, I don’t, and vice versa. We do have to adapt, but I do think that they need more time in front of patients with very experienced physicians.”

Jack Cush, MD, a rheumatologist based in Dallas and executive editor of RheumNow.com, said if education is to move forward, “it’s got to change dramatically.”

“The competencies aren’t always knowledge,” he said. “Knowledge has now been replaced by everything at your fingertips. I don’t need to know all the formulas and everything right now.”

Engagement should be the “main statistic that we need to be striving for,” Dr. Cush explained. “Engagement as the measure of ... education’s value, I think, is where it has to go.”

Dr. Dua reported being a consultant and serving on an advisory board for Sanofi, Novartis, AbbVie, and Chemocentryx/Amgen.

To address the growing workforce shortage in rheumatology, medical educators will have to adapt and learn how to train a new generation of rheumatologists, according to a speaker at the 2023 Rheumatology Winter Clinical Symposium.

Anisha B. Dua, MD, an associate professor of rheumatology at Northwestern University, Chicago, told attendees she is “heavily invested in the training of our future rheumatologists” and strives to help them “operate at the top of the level across the spectrum.”

M. Alexander Otto

“They’re carrying forward our field,” Dr. Dua said. “We need to propagate our field and we need them to go out and serve and continue to make rheumatology awesome.”

The American College of Rheumatology’s 2015 workforce study estimates that by 2030, there will be a shortage of more than 4,000 rheumatologists in the United States.

Rheumatology may have inadvertently created the problem through rheumatologists diagnosing disease earlier and prescribing better treatments, with patients subsequently living longer with disease, she noted. Compounding the problem is an increasing number of rheumatologists looking to retire over the next decade and the continued need for care in rural areas where there are few practicing rheumatologists.
 

Interest in rheumatology is increasing

The good news is there is increasing interest in the field. “This has really shifted, I would say, from about 10 years ago when I was looking at fellowships,” Dr. Dua said. “It’s not really an interest problem. But the issue is that the training programs and slots don’t necessarily exist to fill the gap of the people who are leaving the field.”

The key to bringing more people into rheumatology is to understand how Millennials and Generation Z differ from generations that came before them. In general, members of Generation Z “tend to prefer an à la carte approach to education” with hands-on experiences, and they prefer customized feedback that is actionable, Dr. Dua explained.

“As a medical educator, there are different demands, and these are changing over time, so we have to figure out how we can best serve them and educate them,” she said.

This also means connecting with younger generations on social media. A research letter published in JAMA Network Open in 2021 found a minority of 650 physicians across 14 specialties had a presence on social media platforms, with 44.9% of physicians surveyed present on LinkedIn, 23.4% on Facebook, 18.6% of on Twitter, and 14.9% on ResearchGate. “There is a lot of room to grow, and this is where some of our future teaching is headed,” Dr. Dua said.
 

Future of rheumatology education

Does this mean rheumatologists should start dancing in TikTok videos? Maybe not, but Dr. Dua noted there are ways to bring understanding, recall, comprehension, and behavioral change through active learning, spaced learning, case-based modules, podcasts, videos, and other educational strategies.

“We need to find ways to engage our learners and connect with them and teach them,” she said.

Rheumatologists are already bringing innovation to the education space with initiatives like educational podcasts, remote learning developed during the COVID-19 pandemic, development of rheumatology Objective Structured Clinical Examinations using challenging patient scenarios, and other virtual learning opportunities. “We really have been forced to push the envelope,” Dr. Dua said.

“The future of medical education is here. It’s exciting. Embrace it,” she said.
 

Training nurse practitioners and physician assistants?

Commenting on the shortage of rheumatologists, Philip J. Mease, MD, clinical professor at the University of Washington and director of rheumatology research at Swedish Medical Center, both in Seattle, said one answer to the problem may be training more nurse practitioners (NPs) and physician assistants (PAs) to bridge the gap.

“Some are suggesting that part of the answer to the deficiency of rheumatologists will be having two NPs or PAs to every single rheumatologist that there is out there,” he said. “I work with three, and the issue of ... getting access to them when they are in school to demonstrate how sexy rheumatology is, is something that is deficient, way deficient.” Rheumatologists should be putting themselves out there with preceptorships and lectures to recruit more NPs and PAs to rheumatology, he explained. “That’s a 24/7 process.”

Dr. Dua, who is cochair of the E-Learning Subcommittee within the ACR Workforce Solutions Steering Committee, said the subcomittee’s focus has been connecting with primary care doctors, pediatricians, NPs, and PAs to “expand who can provide some rheumatologic care.”

Lindsay Orme, MD, a family medicine doctor from Caldwell, Idaho, shared her experience serving as faculty for a family medicine residency program, training family medicine doctors in rural areas.

“Our curriculum hasn’t had a section for what trainees are expected to learn in rheumatology. When I did the same program years ago in Idaho, it was very well defined: What I should know how to do without consulting a cardiologist, what I should know how to do without consulting an obstetrician, what I should be able to manage in terms of [chronic kidney disease] before referring to nephrology,” she explained. “No one ever taught me what I could manage in rheumatology.

“I do think we need to find some defined areas that we’re more comfortable teaching primary care doctors to manage because there is no one – there are no rheumatologists in Boise or any of the surrounding towns that accept Medicaid patients now. They are all expected to go 250 miles away,” she said.

“That’s a major, major problem,” Dr. Dua acknowledged. “Really, for me, the goal is to develop resources that you can tap into to be able to at least figure out where things stand, and at least bide time until they can get in with that rheumatologist 250 miles away and make sure that you’re getting the training, or feel comfortable with whatever it is you’re forced to manage from a rheumatologic sense.”
 

More engagement, more adaptation

Roy M. Fleischmann, MD, clinical professor of medicine at the University of Texas and codirector of the Metroplex Clinical Research Center, both in Dallas, said one thing he’s noticed over the years is that, as time spent in the hospital has decreased, the time residents and fellows spend with practitioners in front of patients has also decreased. “It just isn’t there, and that’s where you really learn,” he said.

“You are 100% correct the two generations are different. What I think is important in life is very different than what the fellows think is different in life at this point, and how much work I’m willing to put in or how much work they’re willing to put in, in the same way, is very different,” he explained. “What they want to spend their time on, I don’t, and vice versa. We do have to adapt, but I do think that they need more time in front of patients with very experienced physicians.”

Jack Cush, MD, a rheumatologist based in Dallas and executive editor of RheumNow.com, said if education is to move forward, “it’s got to change dramatically.”

“The competencies aren’t always knowledge,” he said. “Knowledge has now been replaced by everything at your fingertips. I don’t need to know all the formulas and everything right now.”

Engagement should be the “main statistic that we need to be striving for,” Dr. Cush explained. “Engagement as the measure of ... education’s value, I think, is where it has to go.”

Dr. Dua reported being a consultant and serving on an advisory board for Sanofi, Novartis, AbbVie, and Chemocentryx/Amgen.

Intermittent catheterization every 6 hours in postpartum women with urinary retention may be a better strategy than extended catheterization over 24 hours, a new prospective, randomized, controlled study suggests.

Patients who were catheterized every 6 hours took significantly less time to reach full relief than those who were catheterized for at least 24 hours (mean 10.2 ± 11.8 hours vs. 26.5 ± 9.0 hours, P < .001, respectively), Israeli researchers found. Their research was released at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

“There was no difference in hospital stay or in the rate of positive urine culture after catheter removal,” said ob.gyn. Dana Vitner, MD, of Rambam Health Care Campus in Haifa, Israel, in a presentation at the conference. “Our conclusion is that intermittent catheterization for postpartum urinary retention results in shorter time to resolution with a higher satisfaction rate and no additional complications.”

The true incidence of postpartum urinary retention is unclear, and estimates vary widely, said ob.gyn. and surgeon Lisa Hickman, MD, of the Ohio State University, Columbus, in an interview. “This is likely because many cases of covert urinary retention – when postpartum women are able to urinate but have incomplete emptying – go undiagnosed unless you are screening for it.”

According to Dr. Hickman, risk factors for postpartum urinary retention include operative vaginal births, having an epidural, obstetric anal sphincter injury, episiotomy, large newborns, first-time births, and prolonged induction of labor. Most cases resolve within 72 hours, she said, but they can lead to rare complications such as bladder injury.

For the new study, researchers defined urinary retention at the bladder holding least 150 mL more than 6 hours after vaginal delivery or removal of an in-dwelling catheter after cesarean delivery. “The treatment is catheterization,” Dr. Vitner said. “However, there is no standard protocol.”

From 2020 to 2022, researchers randomly assigned 73 women to the intermittent catheterization group and 74 to continuous catheterization. The average ages in the groups were 27.7 and 29.1 years, respectively (P = .11) and other characteristics such as body mass index, parity, infant birth weight, and mode of delivery were similar.

Most women in the intermittent catheterization group needed just one catheterization to reach resolution (75.3%); 93.2% had resolution after two, and 95.9% reached it after three. All resolved their urinary retention by 48 hours.

In the continuous catheterization group, 90.5% reached resolution at 24 hours, 97.3% at 48 hours, and 100% at 72 hours. Birth satisfaction scores were higher in the intermittent catheterization group (P < .001).

Dr. Hickman, who did not take part in the study, said the findings are helpful. Randomized, controlled trials are “important to get a better understanding of the natural history of this condition and ways to improve how we manage it clinically,” she said. Should intermittent catheterization become routine? “You need to have the staffing and the resources in order to do that, such as a bladder scanner and intermittent catheterization supplies,” Dr. Hickman said. “It can be time-intensive to continue to follow the patients to make sure they are voiding normally. And there may be many hospitals in the country that just don’t have the resources to do this, especially with all the current workforce issues.”

She added that some patients may not want the intermittent approach: “It can be uncomfortable for patients. They’ve just delivered a baby, they are likely experiencing discomfort from their delivery, and their anatomy can be distorted,” she said. “Some patients may say, ‘I would prefer you not insert a catheter into my bladder every few hours.’ They may just want to rest after having a baby.”

The best approach is to let patients make an informed choice, Dr. Hickman said. She recommended that clinicians say something like, “Because of your delivery, you are not able to empty your bladder all the way. This is typically a self-limited problem, meaning that it will likely resolve within a few days. But in the meantime, we need to let your bladder rest so that it can have time to start functioning on its own.” And then, she said, explain the catheterization options.

Dr. Vitner and Dr. Hickman have no disclosures.
 

Intermittent catheterization every 6 hours in postpartum women with urinary retention may be a better strategy than extended catheterization over 24 hours, a new prospective, randomized, controlled study suggests.

Patients who were catheterized every 6 hours took significantly less time to reach full relief than those who were catheterized for at least 24 hours (mean 10.2 ± 11.8 hours vs. 26.5 ± 9.0 hours, P < .001, respectively), Israeli researchers found. Their research was released at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

“There was no difference in hospital stay or in the rate of positive urine culture after catheter removal,” said ob.gyn. Dana Vitner, MD, of Rambam Health Care Campus in Haifa, Israel, in a presentation at the conference. “Our conclusion is that intermittent catheterization for postpartum urinary retention results in shorter time to resolution with a higher satisfaction rate and no additional complications.”

The true incidence of postpartum urinary retention is unclear, and estimates vary widely, said ob.gyn. and surgeon Lisa Hickman, MD, of the Ohio State University, Columbus, in an interview. “This is likely because many cases of covert urinary retention – when postpartum women are able to urinate but have incomplete emptying – go undiagnosed unless you are screening for it.”

According to Dr. Hickman, risk factors for postpartum urinary retention include operative vaginal births, having an epidural, obstetric anal sphincter injury, episiotomy, large newborns, first-time births, and prolonged induction of labor. Most cases resolve within 72 hours, she said, but they can lead to rare complications such as bladder injury.

For the new study, researchers defined urinary retention at the bladder holding least 150 mL more than 6 hours after vaginal delivery or removal of an in-dwelling catheter after cesarean delivery. “The treatment is catheterization,” Dr. Vitner said. “However, there is no standard protocol.”

From 2020 to 2022, researchers randomly assigned 73 women to the intermittent catheterization group and 74 to continuous catheterization. The average ages in the groups were 27.7 and 29.1 years, respectively (P = .11) and other characteristics such as body mass index, parity, infant birth weight, and mode of delivery were similar.

Most women in the intermittent catheterization group needed just one catheterization to reach resolution (75.3%); 93.2% had resolution after two, and 95.9% reached it after three. All resolved their urinary retention by 48 hours.

In the continuous catheterization group, 90.5% reached resolution at 24 hours, 97.3% at 48 hours, and 100% at 72 hours. Birth satisfaction scores were higher in the intermittent catheterization group (P < .001).

Dr. Hickman, who did not take part in the study, said the findings are helpful. Randomized, controlled trials are “important to get a better understanding of the natural history of this condition and ways to improve how we manage it clinically,” she said. Should intermittent catheterization become routine? “You need to have the staffing and the resources in order to do that, such as a bladder scanner and intermittent catheterization supplies,” Dr. Hickman said. “It can be time-intensive to continue to follow the patients to make sure they are voiding normally. And there may be many hospitals in the country that just don’t have the resources to do this, especially with all the current workforce issues.”

She added that some patients may not want the intermittent approach: “It can be uncomfortable for patients. They’ve just delivered a baby, they are likely experiencing discomfort from their delivery, and their anatomy can be distorted,” she said. “Some patients may say, ‘I would prefer you not insert a catheter into my bladder every few hours.’ They may just want to rest after having a baby.”

The best approach is to let patients make an informed choice, Dr. Hickman said. She recommended that clinicians say something like, “Because of your delivery, you are not able to empty your bladder all the way. This is typically a self-limited problem, meaning that it will likely resolve within a few days. But in the meantime, we need to let your bladder rest so that it can have time to start functioning on its own.” And then, she said, explain the catheterization options.

Dr. Vitner and Dr. Hickman have no disclosures.
 

Intermittent catheterization every 6 hours in postpartum women with urinary retention may be a better strategy than extended catheterization over 24 hours, a new prospective, randomized, controlled study suggests.

Patients who were catheterized every 6 hours took significantly less time to reach full relief than those who were catheterized for at least 24 hours (mean 10.2 ± 11.8 hours vs. 26.5 ± 9.0 hours, P < .001, respectively), Israeli researchers found. Their research was released at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

“There was no difference in hospital stay or in the rate of positive urine culture after catheter removal,” said ob.gyn. Dana Vitner, MD, of Rambam Health Care Campus in Haifa, Israel, in a presentation at the conference. “Our conclusion is that intermittent catheterization for postpartum urinary retention results in shorter time to resolution with a higher satisfaction rate and no additional complications.”

The true incidence of postpartum urinary retention is unclear, and estimates vary widely, said ob.gyn. and surgeon Lisa Hickman, MD, of the Ohio State University, Columbus, in an interview. “This is likely because many cases of covert urinary retention – when postpartum women are able to urinate but have incomplete emptying – go undiagnosed unless you are screening for it.”

According to Dr. Hickman, risk factors for postpartum urinary retention include operative vaginal births, having an epidural, obstetric anal sphincter injury, episiotomy, large newborns, first-time births, and prolonged induction of labor. Most cases resolve within 72 hours, she said, but they can lead to rare complications such as bladder injury.

For the new study, researchers defined urinary retention at the bladder holding least 150 mL more than 6 hours after vaginal delivery or removal of an in-dwelling catheter after cesarean delivery. “The treatment is catheterization,” Dr. Vitner said. “However, there is no standard protocol.”

From 2020 to 2022, researchers randomly assigned 73 women to the intermittent catheterization group and 74 to continuous catheterization. The average ages in the groups were 27.7 and 29.1 years, respectively (P = .11) and other characteristics such as body mass index, parity, infant birth weight, and mode of delivery were similar.

Most women in the intermittent catheterization group needed just one catheterization to reach resolution (75.3%); 93.2% had resolution after two, and 95.9% reached it after three. All resolved their urinary retention by 48 hours.

In the continuous catheterization group, 90.5% reached resolution at 24 hours, 97.3% at 48 hours, and 100% at 72 hours. Birth satisfaction scores were higher in the intermittent catheterization group (P < .001).

Dr. Hickman, who did not take part in the study, said the findings are helpful. Randomized, controlled trials are “important to get a better understanding of the natural history of this condition and ways to improve how we manage it clinically,” she said. Should intermittent catheterization become routine? “You need to have the staffing and the resources in order to do that, such as a bladder scanner and intermittent catheterization supplies,” Dr. Hickman said. “It can be time-intensive to continue to follow the patients to make sure they are voiding normally. And there may be many hospitals in the country that just don’t have the resources to do this, especially with all the current workforce issues.”

She added that some patients may not want the intermittent approach: “It can be uncomfortable for patients. They’ve just delivered a baby, they are likely experiencing discomfort from their delivery, and their anatomy can be distorted,” she said. “Some patients may say, ‘I would prefer you not insert a catheter into my bladder every few hours.’ They may just want to rest after having a baby.”

The best approach is to let patients make an informed choice, Dr. Hickman said. She recommended that clinicians say something like, “Because of your delivery, you are not able to empty your bladder all the way. This is typically a self-limited problem, meaning that it will likely resolve within a few days. But in the meantime, we need to let your bladder rest so that it can have time to start functioning on its own.” And then, she said, explain the catheterization options.

Dr. Vitner and Dr. Hickman have no disclosures.
 

The latest study to show high efficacy of doxycycline post-exposure prophylaxis (Doxy PEP) in preventing sexually transmitted infections among men who have sex with men (MSM) adds a new twist, showing – for the first time – reductions in gonorrhea among those receiving the meningococcal B vaccine.

“Among men who have sex with men on HIV PrEP, doxycycline PEP significantly reduced the incidence of chlamydia and syphilis and also had a significant impact on the incidence of gonorrhea,” said first author Jean-Michel Molina, MD, PhD, in presenting the findings at the Conference on Retroviruses and Opportunistic Infections.

In addition, “two doses of the meningococcal B vaccine reduced the incidence of a first episode of gonorrhea by roughly 50% among men who have sex with men,” said Dr. Molina, a professor of infectious diseases at the University of Paris, and head of the Infectious Diseases Department at the Saint-Louis and Lariboisière Hospitals, Paris.

Whereas the advent of PrEP has been associated with significant reductions in HIV transmission, rates of STIs have conversely been on the rise among MSM, specifically among those receiving PrEP.

Post-exposure prophylaxis with Doxy PEP has been shown to reduce the incidence of chlamydia and syphilis by approximately 70%; however, effects on prevention of gonorrhea have been less clear.

Meningococcal B vaccination has, meanwhile, shown intriguing reductions of gonorrhea incidence of as much as 26%-46% in some observational studies.

Therefore, Dr. Molina and colleagues decided to further investigate Doxy PEP as well as the meningococcal B vaccine in prevention of STIs.

For the ANRS 174 DOXYVAC trial, they enrolled 546 MSM in the open-label, multicenter study between January 2021 and July 2022.

The men were randomly assigned to one of 4 groups: doxycycline postexposure prophylaxis (Doxy PEP: 200 mg; n = 332), no Doxy PEP (n = 170), two shots of meningococcal B vaccine (4CMenB vaccine; n = 257), or no 4CMenB vaccine (n = 245).

All participants were assigned to their groups within 72 hours of condomless sex.

The men, who had a median age of 39, had a median time of PrEP use of 42 months, a history of an STI in the past year, and their median number of sexual partners in the past 3 months was 10.

Their characteristics were well-balanced across the treatment groups. After discontinuations of 54 patients across the groups, the final analysis included 502 participants.

With a median follow-up of 9 months, the intent-to-treat analysis showed 13 subjects had a first episode of chlamydia or syphilis in the Doxy PEP group, versus 49 subjects infected in the no Doxy PEP arm, for an incidence of 5.6 versus 35.4 per 100 person-years, respectively (adjusted hazard ratio, 0.16; P < .0001).

Infection specifically with chlamydia occurred among 21 men with no Doxy PEP versus 5 receiving Dox PEP (19.3 vs. 2.1 per 100 person-years, respectively; HR, 0.11; P < .0001).

And infection with syphilis occurred in 18 men receiving no Doxy PEP versus 8 receiving the treatment (16.3 vs. 3.4 per 100 person-years, respectively; HR, 0.21; P < .001).

The corresponding rates for gonorrhea infection were an incidence 41.3 versus 20.5 per 100 person-years, in the no Doxy PEP versus Doxy PEP arms, respectively (adjusted HR, 0.49; P = .001), and 29.4 versus 16.8 per 100 person-years for Mycoplasma genitalium infection (aHR, 0.55; P = .015).

Throughout the study, about 80% of patients in the Doxy PEP group reported using the prophylaxis treatment after their most recent sexual intercourse, with subjects reporting taking a median of seven pills per month.

In the vaccine/no vaccine comparisons, 32 subjects in the no meningococcal vaccine group were infected with a first gonorrhea infection, compared with 17 in the vaccine group, representing an incidence of 19.7 versus 9.8 per 100 person-years, respectively (adjusted HR, 0.49; P = .016), which Dr. Molina called “highly significant.”

An analysis of the cumulative incidence of gonorrhea infection with the meningococcal vaccine showed rates in the no vaccine versus vaccine groups of 30.4 versus 20.1 per 100 person-years, respectively; however, statistical significance was not reached (aHR, 0.66; P = .052).

Importantly, there were no significant interactions in the results between those receiving Doxy PEP or the 4CMenB vaccine group, and there were no significant differences in drug-related serious adverse events between the groups.

Dr. Molina noted that the meningococcal B vaccine is known to contain key antigens that are shared between meningitis and gonorrhea, which could explain the benefits.

Although chlamydia and syphilis thus far appear to remain susceptible to Doxy PEP, resistances with gonorrhea remain a concern, hence the ability of the vaccine to provide some protection could be an added bonus.

“We know that [gonorrhea] is able to very quickly develop resistances to any antibiotics, so that was why we wanted to look beyond the antibiotic prophylaxis,” said Dr. Molina.

Among questions to explore looking ahead is the potential longevity of protection with the vaccine.

“We don’t know at this point how long the protection with the vaccine could last, or if [people] may need booster injections, for instance, but the literature suggests benefits for at least a year,” Dr. Molina said. “We are still monitoring the patients in the study to see what happens.”

He added that combination of the interventions may be of benefit.

“In the future, we think we may need to combine these approaches if we want to meet the WHO/UNAIDS targets to reduce the incidence of HIV and STIs by 90% by 2030.”

Commenting on the study, CROI vice-chair Landon Myer, MD, PhD, noted that “gonorrhea develops resistance quickly and can be hard to treat or prophylaxis, so the vaccine finding, which was hinted at by previous observational data, is really important.”

He agrees that “the duration of protective efficacy – a big thing in vaccines – is unknown.”

“Still, this is really significant,” Dr. Myer stressed. “An efficacious vaccine against a stubborn sexually transmitted infection.”

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

The latest study to show high efficacy of doxycycline post-exposure prophylaxis (Doxy PEP) in preventing sexually transmitted infections among men who have sex with men (MSM) adds a new twist, showing – for the first time – reductions in gonorrhea among those receiving the meningococcal B vaccine.

“Among men who have sex with men on HIV PrEP, doxycycline PEP significantly reduced the incidence of chlamydia and syphilis and also had a significant impact on the incidence of gonorrhea,” said first author Jean-Michel Molina, MD, PhD, in presenting the findings at the Conference on Retroviruses and Opportunistic Infections.

In addition, “two doses of the meningococcal B vaccine reduced the incidence of a first episode of gonorrhea by roughly 50% among men who have sex with men,” said Dr. Molina, a professor of infectious diseases at the University of Paris, and head of the Infectious Diseases Department at the Saint-Louis and Lariboisière Hospitals, Paris.

Whereas the advent of PrEP has been associated with significant reductions in HIV transmission, rates of STIs have conversely been on the rise among MSM, specifically among those receiving PrEP.

Post-exposure prophylaxis with Doxy PEP has been shown to reduce the incidence of chlamydia and syphilis by approximately 70%; however, effects on prevention of gonorrhea have been less clear.

Meningococcal B vaccination has, meanwhile, shown intriguing reductions of gonorrhea incidence of as much as 26%-46% in some observational studies.

Therefore, Dr. Molina and colleagues decided to further investigate Doxy PEP as well as the meningococcal B vaccine in prevention of STIs.

For the ANRS 174 DOXYVAC trial, they enrolled 546 MSM in the open-label, multicenter study between January 2021 and July 2022.

The men were randomly assigned to one of 4 groups: doxycycline postexposure prophylaxis (Doxy PEP: 200 mg; n = 332), no Doxy PEP (n = 170), two shots of meningococcal B vaccine (4CMenB vaccine; n = 257), or no 4CMenB vaccine (n = 245).

All participants were assigned to their groups within 72 hours of condomless sex.

The men, who had a median age of 39, had a median time of PrEP use of 42 months, a history of an STI in the past year, and their median number of sexual partners in the past 3 months was 10.

Their characteristics were well-balanced across the treatment groups. After discontinuations of 54 patients across the groups, the final analysis included 502 participants.

With a median follow-up of 9 months, the intent-to-treat analysis showed 13 subjects had a first episode of chlamydia or syphilis in the Doxy PEP group, versus 49 subjects infected in the no Doxy PEP arm, for an incidence of 5.6 versus 35.4 per 100 person-years, respectively (adjusted hazard ratio, 0.16; P < .0001).

Infection specifically with chlamydia occurred among 21 men with no Doxy PEP versus 5 receiving Dox PEP (19.3 vs. 2.1 per 100 person-years, respectively; HR, 0.11; P < .0001).

And infection with syphilis occurred in 18 men receiving no Doxy PEP versus 8 receiving the treatment (16.3 vs. 3.4 per 100 person-years, respectively; HR, 0.21; P < .001).

The corresponding rates for gonorrhea infection were an incidence 41.3 versus 20.5 per 100 person-years, in the no Doxy PEP versus Doxy PEP arms, respectively (adjusted HR, 0.49; P = .001), and 29.4 versus 16.8 per 100 person-years for Mycoplasma genitalium infection (aHR, 0.55; P = .015).

Throughout the study, about 80% of patients in the Doxy PEP group reported using the prophylaxis treatment after their most recent sexual intercourse, with subjects reporting taking a median of seven pills per month.

In the vaccine/no vaccine comparisons, 32 subjects in the no meningococcal vaccine group were infected with a first gonorrhea infection, compared with 17 in the vaccine group, representing an incidence of 19.7 versus 9.8 per 100 person-years, respectively (adjusted HR, 0.49; P = .016), which Dr. Molina called “highly significant.”

An analysis of the cumulative incidence of gonorrhea infection with the meningococcal vaccine showed rates in the no vaccine versus vaccine groups of 30.4 versus 20.1 per 100 person-years, respectively; however, statistical significance was not reached (aHR, 0.66; P = .052).

Importantly, there were no significant interactions in the results between those receiving Doxy PEP or the 4CMenB vaccine group, and there were no significant differences in drug-related serious adverse events between the groups.

Dr. Molina noted that the meningococcal B vaccine is known to contain key antigens that are shared between meningitis and gonorrhea, which could explain the benefits.

Although chlamydia and syphilis thus far appear to remain susceptible to Doxy PEP, resistances with gonorrhea remain a concern, hence the ability of the vaccine to provide some protection could be an added bonus.

“We know that [gonorrhea] is able to very quickly develop resistances to any antibiotics, so that was why we wanted to look beyond the antibiotic prophylaxis,” said Dr. Molina.

Among questions to explore looking ahead is the potential longevity of protection with the vaccine.

“We don’t know at this point how long the protection with the vaccine could last, or if [people] may need booster injections, for instance, but the literature suggests benefits for at least a year,” Dr. Molina said. “We are still monitoring the patients in the study to see what happens.”

He added that combination of the interventions may be of benefit.

“In the future, we think we may need to combine these approaches if we want to meet the WHO/UNAIDS targets to reduce the incidence of HIV and STIs by 90% by 2030.”

Commenting on the study, CROI vice-chair Landon Myer, MD, PhD, noted that “gonorrhea develops resistance quickly and can be hard to treat or prophylaxis, so the vaccine finding, which was hinted at by previous observational data, is really important.”

He agrees that “the duration of protective efficacy – a big thing in vaccines – is unknown.”

“Still, this is really significant,” Dr. Myer stressed. “An efficacious vaccine against a stubborn sexually transmitted infection.”

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

The latest study to show high efficacy of doxycycline post-exposure prophylaxis (Doxy PEP) in preventing sexually transmitted infections among men who have sex with men (MSM) adds a new twist, showing – for the first time – reductions in gonorrhea among those receiving the meningococcal B vaccine.

“Among men who have sex with men on HIV PrEP, doxycycline PEP significantly reduced the incidence of chlamydia and syphilis and also had a significant impact on the incidence of gonorrhea,” said first author Jean-Michel Molina, MD, PhD, in presenting the findings at the Conference on Retroviruses and Opportunistic Infections.

In addition, “two doses of the meningococcal B vaccine reduced the incidence of a first episode of gonorrhea by roughly 50% among men who have sex with men,” said Dr. Molina, a professor of infectious diseases at the University of Paris, and head of the Infectious Diseases Department at the Saint-Louis and Lariboisière Hospitals, Paris.

Whereas the advent of PrEP has been associated with significant reductions in HIV transmission, rates of STIs have conversely been on the rise among MSM, specifically among those receiving PrEP.

Post-exposure prophylaxis with Doxy PEP has been shown to reduce the incidence of chlamydia and syphilis by approximately 70%; however, effects on prevention of gonorrhea have been less clear.

Meningococcal B vaccination has, meanwhile, shown intriguing reductions of gonorrhea incidence of as much as 26%-46% in some observational studies.

Therefore, Dr. Molina and colleagues decided to further investigate Doxy PEP as well as the meningococcal B vaccine in prevention of STIs.

For the ANRS 174 DOXYVAC trial, they enrolled 546 MSM in the open-label, multicenter study between January 2021 and July 2022.

The men were randomly assigned to one of 4 groups: doxycycline postexposure prophylaxis (Doxy PEP: 200 mg; n = 332), no Doxy PEP (n = 170), two shots of meningococcal B vaccine (4CMenB vaccine; n = 257), or no 4CMenB vaccine (n = 245).

All participants were assigned to their groups within 72 hours of condomless sex.

The men, who had a median age of 39, had a median time of PrEP use of 42 months, a history of an STI in the past year, and their median number of sexual partners in the past 3 months was 10.

Their characteristics were well-balanced across the treatment groups. After discontinuations of 54 patients across the groups, the final analysis included 502 participants.

With a median follow-up of 9 months, the intent-to-treat analysis showed 13 subjects had a first episode of chlamydia or syphilis in the Doxy PEP group, versus 49 subjects infected in the no Doxy PEP arm, for an incidence of 5.6 versus 35.4 per 100 person-years, respectively (adjusted hazard ratio, 0.16; P < .0001).

Infection specifically with chlamydia occurred among 21 men with no Doxy PEP versus 5 receiving Dox PEP (19.3 vs. 2.1 per 100 person-years, respectively; HR, 0.11; P < .0001).

And infection with syphilis occurred in 18 men receiving no Doxy PEP versus 8 receiving the treatment (16.3 vs. 3.4 per 100 person-years, respectively; HR, 0.21; P < .001).

The corresponding rates for gonorrhea infection were an incidence 41.3 versus 20.5 per 100 person-years, in the no Doxy PEP versus Doxy PEP arms, respectively (adjusted HR, 0.49; P = .001), and 29.4 versus 16.8 per 100 person-years for Mycoplasma genitalium infection (aHR, 0.55; P = .015).

Throughout the study, about 80% of patients in the Doxy PEP group reported using the prophylaxis treatment after their most recent sexual intercourse, with subjects reporting taking a median of seven pills per month.

In the vaccine/no vaccine comparisons, 32 subjects in the no meningococcal vaccine group were infected with a first gonorrhea infection, compared with 17 in the vaccine group, representing an incidence of 19.7 versus 9.8 per 100 person-years, respectively (adjusted HR, 0.49; P = .016), which Dr. Molina called “highly significant.”

An analysis of the cumulative incidence of gonorrhea infection with the meningococcal vaccine showed rates in the no vaccine versus vaccine groups of 30.4 versus 20.1 per 100 person-years, respectively; however, statistical significance was not reached (aHR, 0.66; P = .052).

Importantly, there were no significant interactions in the results between those receiving Doxy PEP or the 4CMenB vaccine group, and there were no significant differences in drug-related serious adverse events between the groups.

Dr. Molina noted that the meningococcal B vaccine is known to contain key antigens that are shared between meningitis and gonorrhea, which could explain the benefits.

Although chlamydia and syphilis thus far appear to remain susceptible to Doxy PEP, resistances with gonorrhea remain a concern, hence the ability of the vaccine to provide some protection could be an added bonus.

“We know that [gonorrhea] is able to very quickly develop resistances to any antibiotics, so that was why we wanted to look beyond the antibiotic prophylaxis,” said Dr. Molina.

Among questions to explore looking ahead is the potential longevity of protection with the vaccine.

“We don’t know at this point how long the protection with the vaccine could last, or if [people] may need booster injections, for instance, but the literature suggests benefits for at least a year,” Dr. Molina said. “We are still monitoring the patients in the study to see what happens.”

He added that combination of the interventions may be of benefit.

“In the future, we think we may need to combine these approaches if we want to meet the WHO/UNAIDS targets to reduce the incidence of HIV and STIs by 90% by 2030.”

Commenting on the study, CROI vice-chair Landon Myer, MD, PhD, noted that “gonorrhea develops resistance quickly and can be hard to treat or prophylaxis, so the vaccine finding, which was hinted at by previous observational data, is really important.”

He agrees that “the duration of protective efficacy – a big thing in vaccines – is unknown.”

“Still, this is really significant,” Dr. Myer stressed. “An efficacious vaccine against a stubborn sexually transmitted infection.”

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

SAN FRANCISCO – Adding the poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib (Talzenna, Pfizer) to treatment with the androgen pathway inhibitor enzalutamide (Xtandi, Astellas, Pfizer) significantly improved progression-free survival (PFS) in comparison with enzalutamide alone for patients with metastatic, castration-resistant prostate cancer (mCRPC) in the TALAPRO-2 trial.

As determined on the basis of imaging, PFS was 37% better for talazoparib plus enzalutamide than for enzalutamide monotherapy. Combination therapy proved superior regardless of homologous recombination repair (HRR) pathway status, noted the authors.

“Not only did the combination therapy delay disease progression, it also significantly delayed progression of PSA [prostate-specific antigen] readings and the time until chemotherapy was needed compared to the control group,” said lead study author Neeraj Agarwal, MD, professor of medicine and director of the genitourinary oncology program at the Huntsman Cancer Institute, University of Utah, Salt Lake City.

“This is important because advanced prostate cancer can be associated with pain, fractures, suffering, and death. The current standard of care treatments were approved almost a decade ago, leaving a huge, unmet need for novel drugs in this setting,” he said.

The new results could pave the way for a prostate cancer indication for talazoparib; the company has said that it will submit these data to regulatory authorities. At present, the drug is approved only for use in BRCA+ breast cancer, an indication that was approved in 2018.

The findings were presented at the 2023 ASCO Genitourinary Cancers Symposium.

Overall, talazoparib plus enzalutamide resulted in a statistically significant and clinically meaningful improvement in PFS over placebo plus enzalutamide. “Results from the primary analysis of the TALAPRO-2 trial support the use of talazoparib plus enzalutamide as a first-line treatment in patients with mCRPC regardless of HRR gene alteration status,” Dr. Agarwal and colleagues concluded.

However, one expert disagreed with the authors’ conclusion regarding HHR pathway status. On the basis of imaging, PFS was 54% better in HHR-deficient patients in the combination therapy group. It was 30% better for patients with HHR-nondeficient tumors or tumors without known HHR status based on imaging and 34% better based on tumor tissue testing.

“There was a huge magnitude in benefit based on HHR, and I think HRR status matters,” commented Elena Castro, MD, PhD, Instituto de Investigación Biomédica de Málaga (Spain), who served as the invited discussant.

“We need to understand the benefit of ARPi [androgen receptor pathway inhibition] and PARP inhibitors better,” she said. “The balance between side effects and benefit depends on HRR status.”

Dr. Castro also noted that the treatment landscape has changed. ARPi is now a standard of care for metastatic prostate cancer, both for hormone-sensitive and castration-resistant disease. “So the question is, does the addition of a PARP inhibitor induce responses after progression to an ARPi in HHR-nondeficient tumors?”
 

Study details

In the TALAPRO-2 trial, Dr. Agarwal and colleagues randomly assigned 805 patients to receive either talazoparib 0.5 mg or placebo. All patients in the cohort received enzalutamide 160 mg daily.

Participants had mCRPC and were unselected for genetic alterations in DNA damage repair pathways directly or indirectly involved with HRR. They were aged 36-91 years (median age, 71). The cohort was enrolled from 25 countries, including the United States, Canada, Europe, South America, and countries in the Asia-Pacific region.

The men were stratified on the basis of prior use of abiraterone or docetaxel for castration-sensitive prostate cancer and HRR gene alteration status. The study’s primary endpoint was imaging-based PFS (ibPFS) by blinded independent central review (BICR).

Overall, median ibPFS by BICR was significantly improved in the combination group in comparison with the patients who received placebo; it was not reached versus 21.9 months (hazard ratio, 0.63; P < .001). It was also significantly improved among the HRR-deficient subgroup (HR, 0.46; P < .001) as well as in the HRR-nondeficient or unknown (HR, 0.70; P = .004) and HRR-nondeficient patients by tumor tissue testing (HR, 0.66; P = .009).

Talazoparib plus enzalutamide was also favored with regard to other endpoints. Dr. Agarwal noted that, while overall survival data are as yet immature, objective response rates, PSA response of at least 50%, and time to PSA progression and use of subsequent cytotoxic chemotherapy and antineoplastic therapy significantly favored the talazoparib group.

The objective response rate was 61.7% versus 43.9% (P = .005), with 37.5% versus 18.2% complete responses.

“The higher rates of complete response suggest a cooperative effect of talazoparib plus enzalutamide treatment,” he explained.
 

High rate of adverse events

The rate of treatment-emergent adverse events was higher among patients who received talazoparib plus enzalutamide; 71.9% of the patients who received talazoparib plus enzalutamide experienced grade 3-4 TEAEs versus 40.6%. The most common grade 3 or greater TEAEs in the talazoparib group were anemia, low neutrophil counts, and low platelet counts. Hypertension, anemia, and fatigue were the most common in the placebo group. Talazoparib was discontinued in 19.1% of patients because of TEAEs. Enzalutamide was discontinued in 10.8% of patients in the combination group versus 11.0% in the placebo group.

Dr. Agarwal pointed out that there were TEAEs of special interest for talazoparib. “Myelodysplastic syndrome was reported in one patient during the safety reporting period, and acute myeloid leukemia was reported in one patient during the follow-up period,” he said.

Additionally, pulmonary embolism was reported in 10 (2.5%) patients (grade 3 in 9 patients) in the talazoparib arm and in 3 (0.7%) patients (all grade 3) in the placebo arm.
 

Results less relevant

Commenting on the study, Matthew Zibelman, MD, associate professor, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that these results represent an “intriguing finding for men with mCRPC, particularly in conjunction with the previously reported PROPEL study results.

“However, given that many patients receive an androgen receptor inhibitor now for metastatic castration-sensitive prostate cancer, these results are less relevant to current practice,” Dr. Zibelman said.

“Demonstration of an overall survival benefit of the combination would be optimal to change standard of care vs potential sequential therapy.”

The study was sponsored by Pfizer, manufacturer of enzalutamide and talazoparib. Dr. Agarwal has relationships with numerous pharmaceutical companies. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis and Pfizer, and Roche. Dr. Zibelman has relationships with Bristol-Myers Squibb, Exelixis, Pfizer, Jannsen, EMD Serono, and Blue Earth.

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

SAN FRANCISCO – Adding the poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib (Talzenna, Pfizer) to treatment with the androgen pathway inhibitor enzalutamide (Xtandi, Astellas, Pfizer) significantly improved progression-free survival (PFS) in comparison with enzalutamide alone for patients with metastatic, castration-resistant prostate cancer (mCRPC) in the TALAPRO-2 trial.

As determined on the basis of imaging, PFS was 37% better for talazoparib plus enzalutamide than for enzalutamide monotherapy. Combination therapy proved superior regardless of homologous recombination repair (HRR) pathway status, noted the authors.

“Not only did the combination therapy delay disease progression, it also significantly delayed progression of PSA [prostate-specific antigen] readings and the time until chemotherapy was needed compared to the control group,” said lead study author Neeraj Agarwal, MD, professor of medicine and director of the genitourinary oncology program at the Huntsman Cancer Institute, University of Utah, Salt Lake City.

“This is important because advanced prostate cancer can be associated with pain, fractures, suffering, and death. The current standard of care treatments were approved almost a decade ago, leaving a huge, unmet need for novel drugs in this setting,” he said.

The new results could pave the way for a prostate cancer indication for talazoparib; the company has said that it will submit these data to regulatory authorities. At present, the drug is approved only for use in BRCA+ breast cancer, an indication that was approved in 2018.

The findings were presented at the 2023 ASCO Genitourinary Cancers Symposium.

Overall, talazoparib plus enzalutamide resulted in a statistically significant and clinically meaningful improvement in PFS over placebo plus enzalutamide. “Results from the primary analysis of the TALAPRO-2 trial support the use of talazoparib plus enzalutamide as a first-line treatment in patients with mCRPC regardless of HRR gene alteration status,” Dr. Agarwal and colleagues concluded.

However, one expert disagreed with the authors’ conclusion regarding HHR pathway status. On the basis of imaging, PFS was 54% better in HHR-deficient patients in the combination therapy group. It was 30% better for patients with HHR-nondeficient tumors or tumors without known HHR status based on imaging and 34% better based on tumor tissue testing.

“There was a huge magnitude in benefit based on HHR, and I think HRR status matters,” commented Elena Castro, MD, PhD, Instituto de Investigación Biomédica de Málaga (Spain), who served as the invited discussant.

“We need to understand the benefit of ARPi [androgen receptor pathway inhibition] and PARP inhibitors better,” she said. “The balance between side effects and benefit depends on HRR status.”

Dr. Castro also noted that the treatment landscape has changed. ARPi is now a standard of care for metastatic prostate cancer, both for hormone-sensitive and castration-resistant disease. “So the question is, does the addition of a PARP inhibitor induce responses after progression to an ARPi in HHR-nondeficient tumors?”
 

Study details

In the TALAPRO-2 trial, Dr. Agarwal and colleagues randomly assigned 805 patients to receive either talazoparib 0.5 mg or placebo. All patients in the cohort received enzalutamide 160 mg daily.

Participants had mCRPC and were unselected for genetic alterations in DNA damage repair pathways directly or indirectly involved with HRR. They were aged 36-91 years (median age, 71). The cohort was enrolled from 25 countries, including the United States, Canada, Europe, South America, and countries in the Asia-Pacific region.

The men were stratified on the basis of prior use of abiraterone or docetaxel for castration-sensitive prostate cancer and HRR gene alteration status. The study’s primary endpoint was imaging-based PFS (ibPFS) by blinded independent central review (BICR).

Overall, median ibPFS by BICR was significantly improved in the combination group in comparison with the patients who received placebo; it was not reached versus 21.9 months (hazard ratio, 0.63; P < .001). It was also significantly improved among the HRR-deficient subgroup (HR, 0.46; P < .001) as well as in the HRR-nondeficient or unknown (HR, 0.70; P = .004) and HRR-nondeficient patients by tumor tissue testing (HR, 0.66; P = .009).

Talazoparib plus enzalutamide was also favored with regard to other endpoints. Dr. Agarwal noted that, while overall survival data are as yet immature, objective response rates, PSA response of at least 50%, and time to PSA progression and use of subsequent cytotoxic chemotherapy and antineoplastic therapy significantly favored the talazoparib group.

The objective response rate was 61.7% versus 43.9% (P = .005), with 37.5% versus 18.2% complete responses.

“The higher rates of complete response suggest a cooperative effect of talazoparib plus enzalutamide treatment,” he explained.
 

High rate of adverse events

The rate of treatment-emergent adverse events was higher among patients who received talazoparib plus enzalutamide; 71.9% of the patients who received talazoparib plus enzalutamide experienced grade 3-4 TEAEs versus 40.6%. The most common grade 3 or greater TEAEs in the talazoparib group were anemia, low neutrophil counts, and low platelet counts. Hypertension, anemia, and fatigue were the most common in the placebo group. Talazoparib was discontinued in 19.1% of patients because of TEAEs. Enzalutamide was discontinued in 10.8% of patients in the combination group versus 11.0% in the placebo group.

Dr. Agarwal pointed out that there were TEAEs of special interest for talazoparib. “Myelodysplastic syndrome was reported in one patient during the safety reporting period, and acute myeloid leukemia was reported in one patient during the follow-up period,” he said.

Additionally, pulmonary embolism was reported in 10 (2.5%) patients (grade 3 in 9 patients) in the talazoparib arm and in 3 (0.7%) patients (all grade 3) in the placebo arm.
 

Results less relevant

Commenting on the study, Matthew Zibelman, MD, associate professor, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that these results represent an “intriguing finding for men with mCRPC, particularly in conjunction with the previously reported PROPEL study results.

“However, given that many patients receive an androgen receptor inhibitor now for metastatic castration-sensitive prostate cancer, these results are less relevant to current practice,” Dr. Zibelman said.

“Demonstration of an overall survival benefit of the combination would be optimal to change standard of care vs potential sequential therapy.”

The study was sponsored by Pfizer, manufacturer of enzalutamide and talazoparib. Dr. Agarwal has relationships with numerous pharmaceutical companies. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis and Pfizer, and Roche. Dr. Zibelman has relationships with Bristol-Myers Squibb, Exelixis, Pfizer, Jannsen, EMD Serono, and Blue Earth.

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

SAN FRANCISCO – Adding the poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib (Talzenna, Pfizer) to treatment with the androgen pathway inhibitor enzalutamide (Xtandi, Astellas, Pfizer) significantly improved progression-free survival (PFS) in comparison with enzalutamide alone for patients with metastatic, castration-resistant prostate cancer (mCRPC) in the TALAPRO-2 trial.

As determined on the basis of imaging, PFS was 37% better for talazoparib plus enzalutamide than for enzalutamide monotherapy. Combination therapy proved superior regardless of homologous recombination repair (HRR) pathway status, noted the authors.

“Not only did the combination therapy delay disease progression, it also significantly delayed progression of PSA [prostate-specific antigen] readings and the time until chemotherapy was needed compared to the control group,” said lead study author Neeraj Agarwal, MD, professor of medicine and director of the genitourinary oncology program at the Huntsman Cancer Institute, University of Utah, Salt Lake City.

“This is important because advanced prostate cancer can be associated with pain, fractures, suffering, and death. The current standard of care treatments were approved almost a decade ago, leaving a huge, unmet need for novel drugs in this setting,” he said.

The new results could pave the way for a prostate cancer indication for talazoparib; the company has said that it will submit these data to regulatory authorities. At present, the drug is approved only for use in BRCA+ breast cancer, an indication that was approved in 2018.

The findings were presented at the 2023 ASCO Genitourinary Cancers Symposium.

Overall, talazoparib plus enzalutamide resulted in a statistically significant and clinically meaningful improvement in PFS over placebo plus enzalutamide. “Results from the primary analysis of the TALAPRO-2 trial support the use of talazoparib plus enzalutamide as a first-line treatment in patients with mCRPC regardless of HRR gene alteration status,” Dr. Agarwal and colleagues concluded.

However, one expert disagreed with the authors’ conclusion regarding HHR pathway status. On the basis of imaging, PFS was 54% better in HHR-deficient patients in the combination therapy group. It was 30% better for patients with HHR-nondeficient tumors or tumors without known HHR status based on imaging and 34% better based on tumor tissue testing.

“There was a huge magnitude in benefit based on HHR, and I think HRR status matters,” commented Elena Castro, MD, PhD, Instituto de Investigación Biomédica de Málaga (Spain), who served as the invited discussant.

“We need to understand the benefit of ARPi [androgen receptor pathway inhibition] and PARP inhibitors better,” she said. “The balance between side effects and benefit depends on HRR status.”

Dr. Castro also noted that the treatment landscape has changed. ARPi is now a standard of care for metastatic prostate cancer, both for hormone-sensitive and castration-resistant disease. “So the question is, does the addition of a PARP inhibitor induce responses after progression to an ARPi in HHR-nondeficient tumors?”
 

Study details

In the TALAPRO-2 trial, Dr. Agarwal and colleagues randomly assigned 805 patients to receive either talazoparib 0.5 mg or placebo. All patients in the cohort received enzalutamide 160 mg daily.

Participants had mCRPC and were unselected for genetic alterations in DNA damage repair pathways directly or indirectly involved with HRR. They were aged 36-91 years (median age, 71). The cohort was enrolled from 25 countries, including the United States, Canada, Europe, South America, and countries in the Asia-Pacific region.

The men were stratified on the basis of prior use of abiraterone or docetaxel for castration-sensitive prostate cancer and HRR gene alteration status. The study’s primary endpoint was imaging-based PFS (ibPFS) by blinded independent central review (BICR).

Overall, median ibPFS by BICR was significantly improved in the combination group in comparison with the patients who received placebo; it was not reached versus 21.9 months (hazard ratio, 0.63; P < .001). It was also significantly improved among the HRR-deficient subgroup (HR, 0.46; P < .001) as well as in the HRR-nondeficient or unknown (HR, 0.70; P = .004) and HRR-nondeficient patients by tumor tissue testing (HR, 0.66; P = .009).

Talazoparib plus enzalutamide was also favored with regard to other endpoints. Dr. Agarwal noted that, while overall survival data are as yet immature, objective response rates, PSA response of at least 50%, and time to PSA progression and use of subsequent cytotoxic chemotherapy and antineoplastic therapy significantly favored the talazoparib group.

The objective response rate was 61.7% versus 43.9% (P = .005), with 37.5% versus 18.2% complete responses.

“The higher rates of complete response suggest a cooperative effect of talazoparib plus enzalutamide treatment,” he explained.
 

High rate of adverse events

The rate of treatment-emergent adverse events was higher among patients who received talazoparib plus enzalutamide; 71.9% of the patients who received talazoparib plus enzalutamide experienced grade 3-4 TEAEs versus 40.6%. The most common grade 3 or greater TEAEs in the talazoparib group were anemia, low neutrophil counts, and low platelet counts. Hypertension, anemia, and fatigue were the most common in the placebo group. Talazoparib was discontinued in 19.1% of patients because of TEAEs. Enzalutamide was discontinued in 10.8% of patients in the combination group versus 11.0% in the placebo group.

Dr. Agarwal pointed out that there were TEAEs of special interest for talazoparib. “Myelodysplastic syndrome was reported in one patient during the safety reporting period, and acute myeloid leukemia was reported in one patient during the follow-up period,” he said.

Additionally, pulmonary embolism was reported in 10 (2.5%) patients (grade 3 in 9 patients) in the talazoparib arm and in 3 (0.7%) patients (all grade 3) in the placebo arm.
 

Results less relevant

Commenting on the study, Matthew Zibelman, MD, associate professor, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that these results represent an “intriguing finding for men with mCRPC, particularly in conjunction with the previously reported PROPEL study results.

“However, given that many patients receive an androgen receptor inhibitor now for metastatic castration-sensitive prostate cancer, these results are less relevant to current practice,” Dr. Zibelman said.

“Demonstration of an overall survival benefit of the combination would be optimal to change standard of care vs potential sequential therapy.”

The study was sponsored by Pfizer, manufacturer of enzalutamide and talazoparib. Dr. Agarwal has relationships with numerous pharmaceutical companies. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis and Pfizer, and Roche. Dr. Zibelman has relationships with Bristol-Myers Squibb, Exelixis, Pfizer, Jannsen, EMD Serono, and Blue Earth.

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

SAN FRANCISCO – New findings lend further support to adjuvant nivolumab (Opdivo) as a standard of care for patients with metastatic urothelial cancer.

Extended follow-up data from the phase 3 CheckMate 274 trial continue to show that, compared with placebo, nivolumab improves disease-free survival, nonurothelial tract recurrence-free survival (NUTRFS), and distant metastasis-free survival (DMFS) in patients with high-risk, muscle-invasive urothelial cancer after undergoing radical surgery.

The benefit was observed in both in the intent-to-treat population (ITT) and in the subset of patients with programmed death–ligand 1 (PD-L1) expression of at least 1%.

“In the ITT population, median disease-free survival with nivolumab was doubled compared to placebo,” said lead author Matthew Galsky, MD, director of genitourinary medical oncology and codirector of the Center of Excellence for Bladder Cancer at Tisch Cancer Institute, New York. “For the patients with high PD-L1 expression, the median disease-free survival with nivolumab reached 52.6 months, more than six times that of the placebo arm.

“These results further support adjuvant nivolumab as a standard of care in high-risk muscle-invasive urothelial cancer after resection,” he concluded.

Dr. Galsky presented the findings at the 2023 ASCO Genitourinary Cancers Symposium.

Practice changing

The earlier results of this study have already led to an approval from the Food and Drug Administration. In August 2021, nivolumab became the first adjuvant immunotherapy for use in patients with urothelial carcinoma at high risk for recurrence after radical resection

“This is a practice-changing study,” said Scot Niglio, MD, medical oncologist, New York University Perlmutter Cancer Center, who was approached for an independent comment.

“For decades, there were limited to zero treatment options in the postsurgical setting for urothelial cancer patients with a high recurrence risk,” he said.

The standard of care for muscle-invasive urothelial carcinoma is surgery, which may include neoadjuvant cisplatin-based chemotherapy, but most patients will experience disease recurrence, he explained.

“When urothelial cancer recurs outside the urinary tract, the prognosis quickly changes from curable to incurable,” he said, “making this area of research paramount.”

Dr. Niglio emphasized that these updated results show continued benefit from nivolumab on disease-free survival, as well as nonurothelial tract recurrence-free survival and distant metastasis-free survival, supporting its use as standard of care therapy.

“Even though the overall survival data is still maturing, the current data remains promising,” he said. “Patients with urothelial cancer meeting the criteria for high risk now have a treatment option to mitigate the potential of distant recurrence.”

In his own practice, Dr. Niglio added that he will “continue to discuss adjuvant nivolumab as a potential treatment option with all patients who are eligible based on this study.”
 

Met all endpoints

The Checkmate 274 trial involved 353 patients (of whom 140 patients had PD-L1 ≥ 1%) randomly assigned to take nivolumab 240 mg every 2 weeks and 356 patients (with 142 patients with PD-L1 ≥ 1%) randomized to placebo. All patients had pathologic evidence of urothelial cancer at high risk of recurrence and Eastern Cooperative Oncology Group performance status (ECOG PS) of1 or less.

Previous results, at a median follow-up of about 20 months, show that the study met its primary endpoint, showing significant prolongation of disease-free survival in the intention-to-treat population, with nivolumab at 21 months versus placebo at 10.9 months (hazard ratio, 0.70; P < .001).

When the analysis considered only patients with tumors expressing PD-L1 of at least 1%, the median disease-free survival was even higher (not reached vs. 10.8 months; HR, 0.53; P < .001).

Nivolumab was also superior to placebo for NUTRFS, in both in the entire ITT population and in the subset with PD-L1–positive tumors.

The latest results come from a median follow-up of 36.1 months. The median disease-free survival was 22 months with nivolumab, compared with 10.9 months with placebo in ITT patients and 52.6 months on nivolumab versus 8.4 months in patients with PD-L1 of at least 1%.

Nivolumab was superior to placebo for secondary and exploratory endpoints, NUTRFS (ITT: HR, 0.72 and PD-L1 ≥ 1%: HR, 0.53) and DMFS (ITT: HR, 0.74; PD-L1 ≥ 1%: HR, 0.58). However, overall survival data remained immature and will be assessed as a future data cutoff, Dr. Galsky explained.

The updated analysis also included another exploratory endpoint, progression-free survival 2 (PFS2), defined as time from randomization to disease progression after subsequent next-line systemic therapy, start of second subsequent next-line systemic therapy, or death.

Median PFS2 was 61.2 months for all-patients who received nivolumab versus 47.1 months with placebo (HR, 0.79). In the PD-L1 of 1% or greater subgroup, median PFS2 was not reached with nivolumab versus 39.4 months with placebo (HR, 0.54).

Grade 3-4 treatment-related adverse events occurred in 18.2% and 7.2% of patients (nivolumab vs. placebo), and this was consistent with the primary analysis. “No new safety signals were identified,” said Dr. Galsky.

The CheckMate 274 trial was funded by Bristol-Myers Squibb, manufacturer of nivolumab. Dr. Galsky reported relationships with numerous pharmaceutical companies.

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

SAN FRANCISCO – New findings lend further support to adjuvant nivolumab (Opdivo) as a standard of care for patients with metastatic urothelial cancer.

Extended follow-up data from the phase 3 CheckMate 274 trial continue to show that, compared with placebo, nivolumab improves disease-free survival, nonurothelial tract recurrence-free survival (NUTRFS), and distant metastasis-free survival (DMFS) in patients with high-risk, muscle-invasive urothelial cancer after undergoing radical surgery.

The benefit was observed in both in the intent-to-treat population (ITT) and in the subset of patients with programmed death–ligand 1 (PD-L1) expression of at least 1%.

“In the ITT population, median disease-free survival with nivolumab was doubled compared to placebo,” said lead author Matthew Galsky, MD, director of genitourinary medical oncology and codirector of the Center of Excellence for Bladder Cancer at Tisch Cancer Institute, New York. “For the patients with high PD-L1 expression, the median disease-free survival with nivolumab reached 52.6 months, more than six times that of the placebo arm.

“These results further support adjuvant nivolumab as a standard of care in high-risk muscle-invasive urothelial cancer after resection,” he concluded.

Dr. Galsky presented the findings at the 2023 ASCO Genitourinary Cancers Symposium.

Practice changing

The earlier results of this study have already led to an approval from the Food and Drug Administration. In August 2021, nivolumab became the first adjuvant immunotherapy for use in patients with urothelial carcinoma at high risk for recurrence after radical resection

“This is a practice-changing study,” said Scot Niglio, MD, medical oncologist, New York University Perlmutter Cancer Center, who was approached for an independent comment.

“For decades, there were limited to zero treatment options in the postsurgical setting for urothelial cancer patients with a high recurrence risk,” he said.

The standard of care for muscle-invasive urothelial carcinoma is surgery, which may include neoadjuvant cisplatin-based chemotherapy, but most patients will experience disease recurrence, he explained.

“When urothelial cancer recurs outside the urinary tract, the prognosis quickly changes from curable to incurable,” he said, “making this area of research paramount.”

Dr. Niglio emphasized that these updated results show continued benefit from nivolumab on disease-free survival, as well as nonurothelial tract recurrence-free survival and distant metastasis-free survival, supporting its use as standard of care therapy.

“Even though the overall survival data is still maturing, the current data remains promising,” he said. “Patients with urothelial cancer meeting the criteria for high risk now have a treatment option to mitigate the potential of distant recurrence.”

In his own practice, Dr. Niglio added that he will “continue to discuss adjuvant nivolumab as a potential treatment option with all patients who are eligible based on this study.”
 

Met all endpoints

The Checkmate 274 trial involved 353 patients (of whom 140 patients had PD-L1 ≥ 1%) randomly assigned to take nivolumab 240 mg every 2 weeks and 356 patients (with 142 patients with PD-L1 ≥ 1%) randomized to placebo. All patients had pathologic evidence of urothelial cancer at high risk of recurrence and Eastern Cooperative Oncology Group performance status (ECOG PS) of1 or less.

Previous results, at a median follow-up of about 20 months, show that the study met its primary endpoint, showing significant prolongation of disease-free survival in the intention-to-treat population, with nivolumab at 21 months versus placebo at 10.9 months (hazard ratio, 0.70; P < .001).

When the analysis considered only patients with tumors expressing PD-L1 of at least 1%, the median disease-free survival was even higher (not reached vs. 10.8 months; HR, 0.53; P < .001).

Nivolumab was also superior to placebo for NUTRFS, in both in the entire ITT population and in the subset with PD-L1–positive tumors.

The latest results come from a median follow-up of 36.1 months. The median disease-free survival was 22 months with nivolumab, compared with 10.9 months with placebo in ITT patients and 52.6 months on nivolumab versus 8.4 months in patients with PD-L1 of at least 1%.

Nivolumab was superior to placebo for secondary and exploratory endpoints, NUTRFS (ITT: HR, 0.72 and PD-L1 ≥ 1%: HR, 0.53) and DMFS (ITT: HR, 0.74; PD-L1 ≥ 1%: HR, 0.58). However, overall survival data remained immature and will be assessed as a future data cutoff, Dr. Galsky explained.

The updated analysis also included another exploratory endpoint, progression-free survival 2 (PFS2), defined as time from randomization to disease progression after subsequent next-line systemic therapy, start of second subsequent next-line systemic therapy, or death.

Median PFS2 was 61.2 months for all-patients who received nivolumab versus 47.1 months with placebo (HR, 0.79). In the PD-L1 of 1% or greater subgroup, median PFS2 was not reached with nivolumab versus 39.4 months with placebo (HR, 0.54).

Grade 3-4 treatment-related adverse events occurred in 18.2% and 7.2% of patients (nivolumab vs. placebo), and this was consistent with the primary analysis. “No new safety signals were identified,” said Dr. Galsky.

The CheckMate 274 trial was funded by Bristol-Myers Squibb, manufacturer of nivolumab. Dr. Galsky reported relationships with numerous pharmaceutical companies.

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

SAN FRANCISCO – New findings lend further support to adjuvant nivolumab (Opdivo) as a standard of care for patients with metastatic urothelial cancer.

Extended follow-up data from the phase 3 CheckMate 274 trial continue to show that, compared with placebo, nivolumab improves disease-free survival, nonurothelial tract recurrence-free survival (NUTRFS), and distant metastasis-free survival (DMFS) in patients with high-risk, muscle-invasive urothelial cancer after undergoing radical surgery.

The benefit was observed in both in the intent-to-treat population (ITT) and in the subset of patients with programmed death–ligand 1 (PD-L1) expression of at least 1%.

“In the ITT population, median disease-free survival with nivolumab was doubled compared to placebo,” said lead author Matthew Galsky, MD, director of genitourinary medical oncology and codirector of the Center of Excellence for Bladder Cancer at Tisch Cancer Institute, New York. “For the patients with high PD-L1 expression, the median disease-free survival with nivolumab reached 52.6 months, more than six times that of the placebo arm.

“These results further support adjuvant nivolumab as a standard of care in high-risk muscle-invasive urothelial cancer after resection,” he concluded.

Dr. Galsky presented the findings at the 2023 ASCO Genitourinary Cancers Symposium.

Practice changing

The earlier results of this study have already led to an approval from the Food and Drug Administration. In August 2021, nivolumab became the first adjuvant immunotherapy for use in patients with urothelial carcinoma at high risk for recurrence after radical resection

“This is a practice-changing study,” said Scot Niglio, MD, medical oncologist, New York University Perlmutter Cancer Center, who was approached for an independent comment.

“For decades, there were limited to zero treatment options in the postsurgical setting for urothelial cancer patients with a high recurrence risk,” he said.

The standard of care for muscle-invasive urothelial carcinoma is surgery, which may include neoadjuvant cisplatin-based chemotherapy, but most patients will experience disease recurrence, he explained.

“When urothelial cancer recurs outside the urinary tract, the prognosis quickly changes from curable to incurable,” he said, “making this area of research paramount.”

Dr. Niglio emphasized that these updated results show continued benefit from nivolumab on disease-free survival, as well as nonurothelial tract recurrence-free survival and distant metastasis-free survival, supporting its use as standard of care therapy.

“Even though the overall survival data is still maturing, the current data remains promising,” he said. “Patients with urothelial cancer meeting the criteria for high risk now have a treatment option to mitigate the potential of distant recurrence.”

In his own practice, Dr. Niglio added that he will “continue to discuss adjuvant nivolumab as a potential treatment option with all patients who are eligible based on this study.”
 

Met all endpoints

The Checkmate 274 trial involved 353 patients (of whom 140 patients had PD-L1 ≥ 1%) randomly assigned to take nivolumab 240 mg every 2 weeks and 356 patients (with 142 patients with PD-L1 ≥ 1%) randomized to placebo. All patients had pathologic evidence of urothelial cancer at high risk of recurrence and Eastern Cooperative Oncology Group performance status (ECOG PS) of1 or less.

Previous results, at a median follow-up of about 20 months, show that the study met its primary endpoint, showing significant prolongation of disease-free survival in the intention-to-treat population, with nivolumab at 21 months versus placebo at 10.9 months (hazard ratio, 0.70; P < .001).

When the analysis considered only patients with tumors expressing PD-L1 of at least 1%, the median disease-free survival was even higher (not reached vs. 10.8 months; HR, 0.53; P < .001).

Nivolumab was also superior to placebo for NUTRFS, in both in the entire ITT population and in the subset with PD-L1–positive tumors.

The latest results come from a median follow-up of 36.1 months. The median disease-free survival was 22 months with nivolumab, compared with 10.9 months with placebo in ITT patients and 52.6 months on nivolumab versus 8.4 months in patients with PD-L1 of at least 1%.

Nivolumab was superior to placebo for secondary and exploratory endpoints, NUTRFS (ITT: HR, 0.72 and PD-L1 ≥ 1%: HR, 0.53) and DMFS (ITT: HR, 0.74; PD-L1 ≥ 1%: HR, 0.58). However, overall survival data remained immature and will be assessed as a future data cutoff, Dr. Galsky explained.

The updated analysis also included another exploratory endpoint, progression-free survival 2 (PFS2), defined as time from randomization to disease progression after subsequent next-line systemic therapy, start of second subsequent next-line systemic therapy, or death.

Median PFS2 was 61.2 months for all-patients who received nivolumab versus 47.1 months with placebo (HR, 0.79). In the PD-L1 of 1% or greater subgroup, median PFS2 was not reached with nivolumab versus 39.4 months with placebo (HR, 0.54).

Grade 3-4 treatment-related adverse events occurred in 18.2% and 7.2% of patients (nivolumab vs. placebo), and this was consistent with the primary analysis. “No new safety signals were identified,” said Dr. Galsky.

The CheckMate 274 trial was funded by Bristol-Myers Squibb, manufacturer of nivolumab. Dr. Galsky reported relationships with numerous pharmaceutical companies.

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

Testing for nonictal cephalic allodynia can help predict response to the anti–calcitonin gene-related peptide (CGRP) galcanezumab (Emgality, Eli Lilly) for patients with migraine, new research suggests.

The ictal phase refers to “sensitization occurring during a time when central trigeminovascular neurons receive massive nociceptive input from active meningeal nociceptors,” whereas the nonictal phase refers to “sensitization occurring during a time when central trigeminovascular neurons receive no or subliminal nociceptive input from meningeal nociceptors,” investigators noted.

In an observational, open-label cohort study, pretreatment nonictal cephalic allodynia identified galcanezumab responders with nearly 80% accuracy, and it identified nonresponders with nearly 85% accuracy.

“Detection of nonictal allodynia with a simplified paradigm of Quantitative Sensory Testing (QST) may provide a quick, affordable, noninvasive, and patient-friendly way to prospectively distinguish between responders and nonresponders to the prophylactic treatment of chronic and high-frequency episodic migraine with drugs that reduce CGRP signaling,” Sait Ashina, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, and colleagues wrote.

The findings were published online in Cephalalgia.
 

Immediate clinical relevance

Investigator Rami Burstein, PhD, also with Beth Israel Deaconess Medical Center and Harvard Medical School, developed the concept of predicting response to anti-CGRP treatment by testing for the presence or absence of nonictal cephalic allodynia in collaboration with the company CGRP Diagnostics.

In 43 anti–CGRP-naive patients with migraine, the researchers used a simplified QST algorithm to determine the presence/absence of cephalic or extracephalic allodynia during the nonictal phase of migraine – defined as the period from less than 12 hours after a migraine attack to less than 12 hours before the next attack.

Patients were considered to have allodynia if heat pain thresholds were between 32° C and 40° C, if cold pain thresholds were between 32° C and 20° C, or if the mechanical pain was threshold was less than 60 g.

Using these strict criteria, pretreatment nonictal cephalic allodynia was a statistically significant predictor of response to anti-CGRP therapy. It was present in 84% of the 19 nonresponders and was absent in 79% of the 24 responders, for an overall accuracy rate of 86% (P < .0001).

Nonictal cephalic allodynia was “consistently” predictive of response for patients with chronic migraine as well as for those with high-frequency episodic migraine, the researchers reported.

In contrast, they noted that assessing nonictal extracephalic allodynia with QST missed nearly 50% of the patients with allodynia among the nonresponders (accuracy rate of 42%) and added little to the assessment of allodynia among the responders.

Mark Hasleton, PhD, CEO of CGRP Diagnostics, said in an interview that the study shows it’s possible to determine response to anti-CGRP therapy and to prescribe these medications to patients who are most likely to respond.

Dr. Hasleton, who was not personally involved with the current study, noted that pretreatment testing for nonictal cephalic allodynia may also allow for earlier prescription of anti-CGRP therapy and potentially dispense without the need for the current trial-and-error approach to prescribing. He noted that if one anti-CGRP fails the patient, it is highly likely that others will also fail.

Given the “very high correlation of the presence of nonictal cephalic allodynia in responders to galcanezumab, our recommendation would be to routinely pretest all potential anti-CGRP candidates prior to prescription,” he said.
 

End of trial-and-error prescribing

In a comment, Shaheen Lakhan, MD, a neurologist and researcher in Boston, said this research is “very noteworthy, moving us one step closer to predictive, precision medicine and away from the practice of trial-and-error prescribing.

“The trial-and-error approach to migraine management is daunting. These are very costly therapies, and when they don’t work, there is continued tremendous suffering and loss of quality of life for patients,” said Dr. Lakhan, who was not involved in the study.

He added that the failure of drugs to benefit individual patients “may lead to distrust of the health care provider” and to the system as a whole, which in turn could lead to less access to care for other conditions or for preventive measures.

“I envision a time when these predictive measures collectively (interictal allodynia, as in this study, plus biobehavioral data) will assist us neurologists in appropriately selecting migraine therapies,” Dr. Lakhan said.

“Beyond that, we will eventually test new therapies not in cells, animals, and even humans but in silico. In the very near future, we will have solutions tailored to not people suffering a disease but to you – an individual with a unique genetic, protein, physical, developmental, psychological, and behavioral makeup,” he added.

The study was funded in part by Eli Lilly, the National Institutes of Health, and the anesthesia department at Beth Israel Deaconess Medical Center. Galcanezumab was provided by Eli Lilly. Dr. Lakhan reported no relevant financial relationships.

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

Testing for nonictal cephalic allodynia can help predict response to the anti–calcitonin gene-related peptide (CGRP) galcanezumab (Emgality, Eli Lilly) for patients with migraine, new research suggests.

The ictal phase refers to “sensitization occurring during a time when central trigeminovascular neurons receive massive nociceptive input from active meningeal nociceptors,” whereas the nonictal phase refers to “sensitization occurring during a time when central trigeminovascular neurons receive no or subliminal nociceptive input from meningeal nociceptors,” investigators noted.

In an observational, open-label cohort study, pretreatment nonictal cephalic allodynia identified galcanezumab responders with nearly 80% accuracy, and it identified nonresponders with nearly 85% accuracy.

“Detection of nonictal allodynia with a simplified paradigm of Quantitative Sensory Testing (QST) may provide a quick, affordable, noninvasive, and patient-friendly way to prospectively distinguish between responders and nonresponders to the prophylactic treatment of chronic and high-frequency episodic migraine with drugs that reduce CGRP signaling,” Sait Ashina, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, and colleagues wrote.

The findings were published online in Cephalalgia.
 

Immediate clinical relevance

Investigator Rami Burstein, PhD, also with Beth Israel Deaconess Medical Center and Harvard Medical School, developed the concept of predicting response to anti-CGRP treatment by testing for the presence or absence of nonictal cephalic allodynia in collaboration with the company CGRP Diagnostics.

In 43 anti–CGRP-naive patients with migraine, the researchers used a simplified QST algorithm to determine the presence/absence of cephalic or extracephalic allodynia during the nonictal phase of migraine – defined as the period from less than 12 hours after a migraine attack to less than 12 hours before the next attack.

Patients were considered to have allodynia if heat pain thresholds were between 32° C and 40° C, if cold pain thresholds were between 32° C and 20° C, or if the mechanical pain was threshold was less than 60 g.

Using these strict criteria, pretreatment nonictal cephalic allodynia was a statistically significant predictor of response to anti-CGRP therapy. It was present in 84% of the 19 nonresponders and was absent in 79% of the 24 responders, for an overall accuracy rate of 86% (P < .0001).

Nonictal cephalic allodynia was “consistently” predictive of response for patients with chronic migraine as well as for those with high-frequency episodic migraine, the researchers reported.

In contrast, they noted that assessing nonictal extracephalic allodynia with QST missed nearly 50% of the patients with allodynia among the nonresponders (accuracy rate of 42%) and added little to the assessment of allodynia among the responders.

Mark Hasleton, PhD, CEO of CGRP Diagnostics, said in an interview that the study shows it’s possible to determine response to anti-CGRP therapy and to prescribe these medications to patients who are most likely to respond.

Dr. Hasleton, who was not personally involved with the current study, noted that pretreatment testing for nonictal cephalic allodynia may also allow for earlier prescription of anti-CGRP therapy and potentially dispense without the need for the current trial-and-error approach to prescribing. He noted that if one anti-CGRP fails the patient, it is highly likely that others will also fail.

Given the “very high correlation of the presence of nonictal cephalic allodynia in responders to galcanezumab, our recommendation would be to routinely pretest all potential anti-CGRP candidates prior to prescription,” he said.
 

End of trial-and-error prescribing

In a comment, Shaheen Lakhan, MD, a neurologist and researcher in Boston, said this research is “very noteworthy, moving us one step closer to predictive, precision medicine and away from the practice of trial-and-error prescribing.

“The trial-and-error approach to migraine management is daunting. These are very costly therapies, and when they don’t work, there is continued tremendous suffering and loss of quality of life for patients,” said Dr. Lakhan, who was not involved in the study.

He added that the failure of drugs to benefit individual patients “may lead to distrust of the health care provider” and to the system as a whole, which in turn could lead to less access to care for other conditions or for preventive measures.

“I envision a time when these predictive measures collectively (interictal allodynia, as in this study, plus biobehavioral data) will assist us neurologists in appropriately selecting migraine therapies,” Dr. Lakhan said.

“Beyond that, we will eventually test new therapies not in cells, animals, and even humans but in silico. In the very near future, we will have solutions tailored to not people suffering a disease but to you – an individual with a unique genetic, protein, physical, developmental, psychological, and behavioral makeup,” he added.

The study was funded in part by Eli Lilly, the National Institutes of Health, and the anesthesia department at Beth Israel Deaconess Medical Center. Galcanezumab was provided by Eli Lilly. Dr. Lakhan reported no relevant financial relationships.

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

Testing for nonictal cephalic allodynia can help predict response to the anti–calcitonin gene-related peptide (CGRP) galcanezumab (Emgality, Eli Lilly) for patients with migraine, new research suggests.

The ictal phase refers to “sensitization occurring during a time when central trigeminovascular neurons receive massive nociceptive input from active meningeal nociceptors,” whereas the nonictal phase refers to “sensitization occurring during a time when central trigeminovascular neurons receive no or subliminal nociceptive input from meningeal nociceptors,” investigators noted.

In an observational, open-label cohort study, pretreatment nonictal cephalic allodynia identified galcanezumab responders with nearly 80% accuracy, and it identified nonresponders with nearly 85% accuracy.

“Detection of nonictal allodynia with a simplified paradigm of Quantitative Sensory Testing (QST) may provide a quick, affordable, noninvasive, and patient-friendly way to prospectively distinguish between responders and nonresponders to the prophylactic treatment of chronic and high-frequency episodic migraine with drugs that reduce CGRP signaling,” Sait Ashina, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, and colleagues wrote.

The findings were published online in Cephalalgia.
 

Immediate clinical relevance

Investigator Rami Burstein, PhD, also with Beth Israel Deaconess Medical Center and Harvard Medical School, developed the concept of predicting response to anti-CGRP treatment by testing for the presence or absence of nonictal cephalic allodynia in collaboration with the company CGRP Diagnostics.

In 43 anti–CGRP-naive patients with migraine, the researchers used a simplified QST algorithm to determine the presence/absence of cephalic or extracephalic allodynia during the nonictal phase of migraine – defined as the period from less than 12 hours after a migraine attack to less than 12 hours before the next attack.

Patients were considered to have allodynia if heat pain thresholds were between 32° C and 40° C, if cold pain thresholds were between 32° C and 20° C, or if the mechanical pain was threshold was less than 60 g.

Using these strict criteria, pretreatment nonictal cephalic allodynia was a statistically significant predictor of response to anti-CGRP therapy. It was present in 84% of the 19 nonresponders and was absent in 79% of the 24 responders, for an overall accuracy rate of 86% (P < .0001).

Nonictal cephalic allodynia was “consistently” predictive of response for patients with chronic migraine as well as for those with high-frequency episodic migraine, the researchers reported.

In contrast, they noted that assessing nonictal extracephalic allodynia with QST missed nearly 50% of the patients with allodynia among the nonresponders (accuracy rate of 42%) and added little to the assessment of allodynia among the responders.

Mark Hasleton, PhD, CEO of CGRP Diagnostics, said in an interview that the study shows it’s possible to determine response to anti-CGRP therapy and to prescribe these medications to patients who are most likely to respond.

Dr. Hasleton, who was not personally involved with the current study, noted that pretreatment testing for nonictal cephalic allodynia may also allow for earlier prescription of anti-CGRP therapy and potentially dispense without the need for the current trial-and-error approach to prescribing. He noted that if one anti-CGRP fails the patient, it is highly likely that others will also fail.

Given the “very high correlation of the presence of nonictal cephalic allodynia in responders to galcanezumab, our recommendation would be to routinely pretest all potential anti-CGRP candidates prior to prescription,” he said.
 

End of trial-and-error prescribing

In a comment, Shaheen Lakhan, MD, a neurologist and researcher in Boston, said this research is “very noteworthy, moving us one step closer to predictive, precision medicine and away from the practice of trial-and-error prescribing.

“The trial-and-error approach to migraine management is daunting. These are very costly therapies, and when they don’t work, there is continued tremendous suffering and loss of quality of life for patients,” said Dr. Lakhan, who was not involved in the study.

He added that the failure of drugs to benefit individual patients “may lead to distrust of the health care provider” and to the system as a whole, which in turn could lead to less access to care for other conditions or for preventive measures.

“I envision a time when these predictive measures collectively (interictal allodynia, as in this study, plus biobehavioral data) will assist us neurologists in appropriately selecting migraine therapies,” Dr. Lakhan said.

“Beyond that, we will eventually test new therapies not in cells, animals, and even humans but in silico. In the very near future, we will have solutions tailored to not people suffering a disease but to you – an individual with a unique genetic, protein, physical, developmental, psychological, and behavioral makeup,” he added.

The study was funded in part by Eli Lilly, the National Institutes of Health, and the anesthesia department at Beth Israel Deaconess Medical Center. Galcanezumab was provided by Eli Lilly. Dr. Lakhan reported no relevant financial relationships.

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