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Novel therapy shows promise for treating skin-predominant dermatomyositis
NEW ORLEANS – in a double-blind, placebo-controlled phase 2 trial, according to results presented as a late-breaker at the annual meeting of the American Academy of Dermatology.
“These findings support the inhibition of IFN-beta as a promising therapeutic strategy in skin-predominant disease,” said principal investigator Aaron Mangold, MD, associate professor of dermatology, Mayo Clinic, Scottsdale, Ariz.
Dermatomyositis, a rare autoimmune inflammatory condition that typically involves both skeletal muscles and skin, is a challenging disease with a diverse set of potential complications.
Immunosuppressive and immunomodulatory agents are used with mixed success for myositis, but skin manifestations, which include papular eruptions, heliotrope rash, photoerythema, burning, and pruritus, are often the most troublesome and the most difficult to control. Treatment options other than immunomodulators that target cutaneous involvement – which include steroids, emollients, and photoprotection – are generally modestly effective, according to Dr. Mangold.
Targeting an elevated cytokine
Interest in IFN-beta, which is elevated in the blood of individuals with dermatomyositis, was triggered by evidence that this cytokine plays an important role in driving the skin inflammation, Dr. Mangold explained.
“The blood concentrations of IFN-beta are positively correlated with cutaneous disease activity and severity,” he said.
The study drug, currently known as PF-06823859 (Dazukibart), “is a potent, selective humanized IgG1-neutralizing antibody directed at IFN-beta,” Dr. Mangold said. A dose-ranging phase 1 study published 2 years ago provided evidence of acceptable pharmacokinetics and safety in healthy individuals to support treatment studies for disorders associated with elevated IFN-beta levels. In addition to dermatomyositis, this includes systemic lupus erythematosus.
In this phase 2 trial, patients whose condition was not improved by at least one standard-care therapy for skin manifestations of dermatomyositis were eligible if they had moderate to severe disease as measured with the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), according to Dr. Mangold. During the study, patients were allowed to remain on a disease modifying antirheumatic drug and/or prednisone if they had been on stable doses and did not change the dose.
After a screening run-in, the trial had two blinded stages. In stage 1, 30 patients were randomly assigned either to 600 mg of PF-06823859 or to placebo, both administered intravenously every 4 weeks. A second cohort of 25 patients was randomly assigned in stage 2 to placebo, 150 mg of PF-06823859, or 600 mg of PF-06823859. The primary endpoint assessed at 12 weeks was a greater than 5-point reduction in CDASI score or greater than 40% CDASI improvement from baseline.
Both endpoints are associated with a clinically meaningful response in regard to an improved quality of life, Dr. Mangold noted.
Both doses better than placebo
In results from the stage 1 portion, the mean reduction in CDASI at 12 weeks after three doses of the assigned therapy was 18.8 points in the active-treatment group versus 3.9 points in the placebo group. In pooled data from stage 1 and 2, the reductions were 16.6 points, 19.2 points, and 2.9 points for the 150-mg, 600-mg, and placebo arms, respectively. Both doses achieved a highly significant advantage over placebo.
For both stages and doses, the response curves of the active-treatment groups and the placebo group diverged almost immediately. By 4 weeks, both measures of CDASI reductions on active therapy were significantly improved relative to placebo, and the response curves had a consistent downward slope through the end of the 12-week study, Dr. Mangold reported.
The majority of patients responded by either of the primary endpoint criteria. For a CDASI reduction of greater than 5 points, the response rates were 100% and 96% for the 150-mg and 600-mg doses of PF-06823859, respectively. The placebo response was 35.7%. For the CDASI reduction of greater than 40%, the rates were 80%, 82.1%, and 7.1% for the 150-mg, 600-mg, and placebo arms, respectively.
“There were no major safety concerns. Most of the treatment-emergent adverse events were mild, and adverse events did not have a relationship to dose,” Dr. Mangold said. Notably, there were no cases of herpes zoster, and infections of any kind were low in all study groups.
A phase 3 study is being planned with the 600-mg dose, according to Dr. Mangold, but he acknowledged that regulatory authorities have generally required endpoints for both cutaneous and muscle manifestations in previous trials of therapies for dermatomyositis.
It is not yet certain that “there will be a carve-out for skin,” he said in answer to a question about investigations moving forward. So far, studies have been focused on skin response. However, a meaningful degree of benefit against muscle involvement, which has not yet been well studied, has not been ruled out.
Even though this is a phase 2 trial with small numbers, it was controlled and blinded, and the potential of an inhibitor of IFN-beta to control the skin manifestations of dermatomyositis “is kind of a big deal,” said Paul Nghiem, MD, PhD, professor of dermatology, University of Washington, Seattle.
“There is definitely an unmet need for better therapies to control the skin involvement,” Dr. Nghiem said.
Hensin Tsao, MD, PhD, clinical director of the Melanoma and Pigmented Lesion Center at Massachusetts General Hospital, Boston, agreed. Like Dr. Nghiem, Dr. Tsao was a panelist during the late-breaker session where the study was presented, and he was impressed by the data.
“This is something that is definitely newsworthy,” Dr. Tsao said.
Dr. Mangold reports financial relationships with Actelion, Amgen, Corbus, Eli Lilly, Incyte, miRagen, Novartis, Regeneron, Solagenix, Sun Pharmaceuticals, Teva, and Pfizer, which provided funding for this trial. Both Dr. Nghiem and Dr. Tsao reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – in a double-blind, placebo-controlled phase 2 trial, according to results presented as a late-breaker at the annual meeting of the American Academy of Dermatology.
“These findings support the inhibition of IFN-beta as a promising therapeutic strategy in skin-predominant disease,” said principal investigator Aaron Mangold, MD, associate professor of dermatology, Mayo Clinic, Scottsdale, Ariz.
Dermatomyositis, a rare autoimmune inflammatory condition that typically involves both skeletal muscles and skin, is a challenging disease with a diverse set of potential complications.
Immunosuppressive and immunomodulatory agents are used with mixed success for myositis, but skin manifestations, which include papular eruptions, heliotrope rash, photoerythema, burning, and pruritus, are often the most troublesome and the most difficult to control. Treatment options other than immunomodulators that target cutaneous involvement – which include steroids, emollients, and photoprotection – are generally modestly effective, according to Dr. Mangold.
Targeting an elevated cytokine
Interest in IFN-beta, which is elevated in the blood of individuals with dermatomyositis, was triggered by evidence that this cytokine plays an important role in driving the skin inflammation, Dr. Mangold explained.
“The blood concentrations of IFN-beta are positively correlated with cutaneous disease activity and severity,” he said.
The study drug, currently known as PF-06823859 (Dazukibart), “is a potent, selective humanized IgG1-neutralizing antibody directed at IFN-beta,” Dr. Mangold said. A dose-ranging phase 1 study published 2 years ago provided evidence of acceptable pharmacokinetics and safety in healthy individuals to support treatment studies for disorders associated with elevated IFN-beta levels. In addition to dermatomyositis, this includes systemic lupus erythematosus.
In this phase 2 trial, patients whose condition was not improved by at least one standard-care therapy for skin manifestations of dermatomyositis were eligible if they had moderate to severe disease as measured with the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), according to Dr. Mangold. During the study, patients were allowed to remain on a disease modifying antirheumatic drug and/or prednisone if they had been on stable doses and did not change the dose.
After a screening run-in, the trial had two blinded stages. In stage 1, 30 patients were randomly assigned either to 600 mg of PF-06823859 or to placebo, both administered intravenously every 4 weeks. A second cohort of 25 patients was randomly assigned in stage 2 to placebo, 150 mg of PF-06823859, or 600 mg of PF-06823859. The primary endpoint assessed at 12 weeks was a greater than 5-point reduction in CDASI score or greater than 40% CDASI improvement from baseline.
Both endpoints are associated with a clinically meaningful response in regard to an improved quality of life, Dr. Mangold noted.
Both doses better than placebo
In results from the stage 1 portion, the mean reduction in CDASI at 12 weeks after three doses of the assigned therapy was 18.8 points in the active-treatment group versus 3.9 points in the placebo group. In pooled data from stage 1 and 2, the reductions were 16.6 points, 19.2 points, and 2.9 points for the 150-mg, 600-mg, and placebo arms, respectively. Both doses achieved a highly significant advantage over placebo.
For both stages and doses, the response curves of the active-treatment groups and the placebo group diverged almost immediately. By 4 weeks, both measures of CDASI reductions on active therapy were significantly improved relative to placebo, and the response curves had a consistent downward slope through the end of the 12-week study, Dr. Mangold reported.
The majority of patients responded by either of the primary endpoint criteria. For a CDASI reduction of greater than 5 points, the response rates were 100% and 96% for the 150-mg and 600-mg doses of PF-06823859, respectively. The placebo response was 35.7%. For the CDASI reduction of greater than 40%, the rates were 80%, 82.1%, and 7.1% for the 150-mg, 600-mg, and placebo arms, respectively.
“There were no major safety concerns. Most of the treatment-emergent adverse events were mild, and adverse events did not have a relationship to dose,” Dr. Mangold said. Notably, there were no cases of herpes zoster, and infections of any kind were low in all study groups.
A phase 3 study is being planned with the 600-mg dose, according to Dr. Mangold, but he acknowledged that regulatory authorities have generally required endpoints for both cutaneous and muscle manifestations in previous trials of therapies for dermatomyositis.
It is not yet certain that “there will be a carve-out for skin,” he said in answer to a question about investigations moving forward. So far, studies have been focused on skin response. However, a meaningful degree of benefit against muscle involvement, which has not yet been well studied, has not been ruled out.
Even though this is a phase 2 trial with small numbers, it was controlled and blinded, and the potential of an inhibitor of IFN-beta to control the skin manifestations of dermatomyositis “is kind of a big deal,” said Paul Nghiem, MD, PhD, professor of dermatology, University of Washington, Seattle.
“There is definitely an unmet need for better therapies to control the skin involvement,” Dr. Nghiem said.
Hensin Tsao, MD, PhD, clinical director of the Melanoma and Pigmented Lesion Center at Massachusetts General Hospital, Boston, agreed. Like Dr. Nghiem, Dr. Tsao was a panelist during the late-breaker session where the study was presented, and he was impressed by the data.
“This is something that is definitely newsworthy,” Dr. Tsao said.
Dr. Mangold reports financial relationships with Actelion, Amgen, Corbus, Eli Lilly, Incyte, miRagen, Novartis, Regeneron, Solagenix, Sun Pharmaceuticals, Teva, and Pfizer, which provided funding for this trial. Both Dr. Nghiem and Dr. Tsao reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – in a double-blind, placebo-controlled phase 2 trial, according to results presented as a late-breaker at the annual meeting of the American Academy of Dermatology.
“These findings support the inhibition of IFN-beta as a promising therapeutic strategy in skin-predominant disease,” said principal investigator Aaron Mangold, MD, associate professor of dermatology, Mayo Clinic, Scottsdale, Ariz.
Dermatomyositis, a rare autoimmune inflammatory condition that typically involves both skeletal muscles and skin, is a challenging disease with a diverse set of potential complications.
Immunosuppressive and immunomodulatory agents are used with mixed success for myositis, but skin manifestations, which include papular eruptions, heliotrope rash, photoerythema, burning, and pruritus, are often the most troublesome and the most difficult to control. Treatment options other than immunomodulators that target cutaneous involvement – which include steroids, emollients, and photoprotection – are generally modestly effective, according to Dr. Mangold.
Targeting an elevated cytokine
Interest in IFN-beta, which is elevated in the blood of individuals with dermatomyositis, was triggered by evidence that this cytokine plays an important role in driving the skin inflammation, Dr. Mangold explained.
“The blood concentrations of IFN-beta are positively correlated with cutaneous disease activity and severity,” he said.
The study drug, currently known as PF-06823859 (Dazukibart), “is a potent, selective humanized IgG1-neutralizing antibody directed at IFN-beta,” Dr. Mangold said. A dose-ranging phase 1 study published 2 years ago provided evidence of acceptable pharmacokinetics and safety in healthy individuals to support treatment studies for disorders associated with elevated IFN-beta levels. In addition to dermatomyositis, this includes systemic lupus erythematosus.
In this phase 2 trial, patients whose condition was not improved by at least one standard-care therapy for skin manifestations of dermatomyositis were eligible if they had moderate to severe disease as measured with the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), according to Dr. Mangold. During the study, patients were allowed to remain on a disease modifying antirheumatic drug and/or prednisone if they had been on stable doses and did not change the dose.
After a screening run-in, the trial had two blinded stages. In stage 1, 30 patients were randomly assigned either to 600 mg of PF-06823859 or to placebo, both administered intravenously every 4 weeks. A second cohort of 25 patients was randomly assigned in stage 2 to placebo, 150 mg of PF-06823859, or 600 mg of PF-06823859. The primary endpoint assessed at 12 weeks was a greater than 5-point reduction in CDASI score or greater than 40% CDASI improvement from baseline.
Both endpoints are associated with a clinically meaningful response in regard to an improved quality of life, Dr. Mangold noted.
Both doses better than placebo
In results from the stage 1 portion, the mean reduction in CDASI at 12 weeks after three doses of the assigned therapy was 18.8 points in the active-treatment group versus 3.9 points in the placebo group. In pooled data from stage 1 and 2, the reductions were 16.6 points, 19.2 points, and 2.9 points for the 150-mg, 600-mg, and placebo arms, respectively. Both doses achieved a highly significant advantage over placebo.
For both stages and doses, the response curves of the active-treatment groups and the placebo group diverged almost immediately. By 4 weeks, both measures of CDASI reductions on active therapy were significantly improved relative to placebo, and the response curves had a consistent downward slope through the end of the 12-week study, Dr. Mangold reported.
The majority of patients responded by either of the primary endpoint criteria. For a CDASI reduction of greater than 5 points, the response rates were 100% and 96% for the 150-mg and 600-mg doses of PF-06823859, respectively. The placebo response was 35.7%. For the CDASI reduction of greater than 40%, the rates were 80%, 82.1%, and 7.1% for the 150-mg, 600-mg, and placebo arms, respectively.
“There were no major safety concerns. Most of the treatment-emergent adverse events were mild, and adverse events did not have a relationship to dose,” Dr. Mangold said. Notably, there were no cases of herpes zoster, and infections of any kind were low in all study groups.
A phase 3 study is being planned with the 600-mg dose, according to Dr. Mangold, but he acknowledged that regulatory authorities have generally required endpoints for both cutaneous and muscle manifestations in previous trials of therapies for dermatomyositis.
It is not yet certain that “there will be a carve-out for skin,” he said in answer to a question about investigations moving forward. So far, studies have been focused on skin response. However, a meaningful degree of benefit against muscle involvement, which has not yet been well studied, has not been ruled out.
Even though this is a phase 2 trial with small numbers, it was controlled and blinded, and the potential of an inhibitor of IFN-beta to control the skin manifestations of dermatomyositis “is kind of a big deal,” said Paul Nghiem, MD, PhD, professor of dermatology, University of Washington, Seattle.
“There is definitely an unmet need for better therapies to control the skin involvement,” Dr. Nghiem said.
Hensin Tsao, MD, PhD, clinical director of the Melanoma and Pigmented Lesion Center at Massachusetts General Hospital, Boston, agreed. Like Dr. Nghiem, Dr. Tsao was a panelist during the late-breaker session where the study was presented, and he was impressed by the data.
“This is something that is definitely newsworthy,” Dr. Tsao said.
Dr. Mangold reports financial relationships with Actelion, Amgen, Corbus, Eli Lilly, Incyte, miRagen, Novartis, Regeneron, Solagenix, Sun Pharmaceuticals, Teva, and Pfizer, which provided funding for this trial. Both Dr. Nghiem and Dr. Tsao reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT AAD 2023
Studies validate IL-17 as hidradenitis suppurativa drug target
NEW ORLEANS – In two phase 3 trials, bimekizumab, a monoclonal antibody targeting two types of interleukin-17 — IL-17A and IL-17F — reduced the abscess and inflammatory nodule count better than placebo in the chronic inflammatory skin condition hidradenitis suppurativa (HS), according to results presented together during a late-breaker session at the annual meeting of the American Academy of Dermatology.
“We are very excited to add this data to what we already have around IL-17 inhibition. This clearly validates this target for the control of HS,” reported lead investigator Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston.
The trials, called BE HEARD I and BE HEARD II, enrolled 505 and 509 patients with HS, respectively. About 50% of patients in BE HEARD I and 60% of patients in BE HEARD II had Hurley stage 3 disease, which is the most severe of the three stratifications. The remainder were in Hurley stage 2. The mean duration of HS was 8.3 and 7.1 years, respectively.
Patients in both studies were randomized to one of four groups – either to a dosing regimen of 320 mg of bimekizumab administered by subcutaneous injection or to a placebo group. Both trials comprised double-blind 16-week initial and 32-week maintenance treatment periods.
In one experimental group, bimekizumab was given once every 2 weeks for the full course of the 48-week study (Q2W/Q2W). In another, patients started on the every-2-week schedule for 16 weeks and then were switched to every-4-week dosing (Q2W/Q4W). In the third group, patients started and remained on the every-4-week schedule (Q4W/Q4W). Patients in a fourth group started on placebo and switched at 16 weeks to the every-2-week bimekizumab schedule (placebo/Q2W).
Results at primary endpoint
The primary endpoint was HiSCR50, signifying a 50% reduction from baseline in abscess and inflammatory nodule count on the Hidradenitis Suppurativa Clinical Response (HiSCR) assessment tool. At 16 weeks, the initial Q2W dose in two of the groups outperformed the placebo in both BE HEARD I (47.8% vs. 28.7%) and BE HEARD II (52.0% vs. 32.2%). The response rates in the Q4W arm in BE HEARD I (45.3%) and BE HEARD II (53.8%) were also higher than the placebo, but the difference was only significant in BE HEARD II.
At 48 weeks, the proportion of patients with an HiSCR50 response climbed in all groups in both trials. The patterns were generally the same with slightly higher numerical responses among the groups that received the every-2-week dosing schedule relative to the every-4-week schedule.
In BE HEARD I at 48 weeks, the HiSCR50 response rate was about 60% for those who started and remained on every-2-week bimekizumab (Q2W/Q2W) or were switched at 16 weeks to every-4-week bimekizumab (Q2W/Q4W). For those who started and remained on every-4-week bimekizumab and the group started on placebo and switched to every-2-week bimekizumab, the response rates were 52.7% and 45.3%, respectively.
In BE HEARD II, the HiSCR50 response rates were higher in all groups, including the placebo, and the patterns of response were similar at 48 weeks. Most patients reached the HiSCR50 response – 79.8% (Q2W/Q2W), 78.4% (Q2W/Q4W), 76.7% (Q4W/Q4W), and 65.9 % (placebo/Q2W) of patients.
It is notable that, although there was rapid increase in the proportion of placebo patients reaching HiSCR50 after the switch at 16 weeks, there appeared to be an advantage at 48 weeks for starting on full-dose bimekizumab over starting on placebo.
In this trial, patients were listed as nonresponders if they received antibiotics at any time and for any reason after randomization. This might have concealed an even greater benefit of bimekizumab, Dr. Kimball said, but the study design element was considered necessary to isolate the activity of the study drug.
“In future HS trials, it will be helpful to address the difficulty of handling the impact of antibiotics and pain medications [in assessing results],” Dr. Kimball said.
Clinically meaningful secondary endpoint
For HS patients, the secondary endpoint of HiSCR75 might be considered the most meaningful, according to Dr. Kimball. She said that this higher bar not only documents a higher level of efficacy but correlates with meaningful improvement in quality of life. In the two trials combined, more than 55% of patients on continuous bimekizumab achieved HiSCR75 at week 48 in the observed case analysis, according to a news release from biopharmaceutical company UCB, developer of bimekizumab.
In BE HEARD I, the HiSCR75 rates were 33.4% and 24.7% for the every-2-week and every-4-week bimekizumab doses, respectively. The 33.4% response was statistically superior to placebo (18.4%). In BE HEARD II, both the every-2-week dose (35.7%) and the every-4-week dose (33.7%) were superior to the 15.6% response in placebo patients.
The improvements in quality of life as measured with the Dermatology Life Quality Index (DLQI), reflected the changes in disease activity. Relative to about a 3-point reduction from baseline in the placebo groups of the two trials, the 5-point reduction for either the 2-week or 4-week bimekizumab groups in each clinical trial were highly significant, Dr. Kimball said.
Bimekizumab was relatively well tolerated, although it shares the increased risk for candidiasis observed with this agent when used in psoriasis and with other IL-17 inhibitors, such as secukinumab (Cosentyx), in general. The risk of candidiasis appeared to be dose related, but cases were generally mild and easily managed, according to Dr. Kimball. She noted that only three patients discontinued treatment for this reason. Discontinuations for a treatment-related adverse event overall was less than 4% at 16 weeks.
This is only the third phase 3 trial ever completed in patients with HS. In fact, Dr. Kimball has led all of the phase 3 trials so far, including clinical studies of adalimumab (Humira), published in 2016, and of secukinumab, published earlier this year. All were positive studies.
“This is amazing news for our patients,” Dr. Kimball said. HS remains a challenging disease, even with a growing number of options showing benefit in large studies, she said, and the high rate of response, particularly at the level of HiSCR75, “is a huge milestone for what we can achieve.”
Multiple treatment options important
Her assessment was echoed by other experts, including Christopher J. Sayed, MD, an associate professor of dermatology at the University of North Carolina at Chapel Hill, who publishes frequently about this disease.
“It is incredibly exciting to see the strong phase 3 data on bimekizumab, particularly the deep responses at the HiSCR75 in a majority of patients after the first year,” he said.
Importantly, he does not see the growing array of treatment options as necessarily competitive for a disease with heterogeneous manifestations and variable responses to any one agent.
“While this may be a major step forward, it will still be critical to see more drugs come along for those who do not respond fully enough or have comorbidities that prevent the use of IL-17 and TNF [tumor necrosis factor] antagonists,” he said.
Bimekizumab is not approved for any indication in the United States; it is approved for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy in the EU/EEA, where it is marketed as Bimzelx, according to UCB. Dr. Kimball reports financial relationships with AbbVie, Janssen, Kymera, Lilly, Novartis, Pfizer, and UCB. Dr. Sayed reports financial relationships with AbbVie, InflaRx, and UCB.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – In two phase 3 trials, bimekizumab, a monoclonal antibody targeting two types of interleukin-17 — IL-17A and IL-17F — reduced the abscess and inflammatory nodule count better than placebo in the chronic inflammatory skin condition hidradenitis suppurativa (HS), according to results presented together during a late-breaker session at the annual meeting of the American Academy of Dermatology.
“We are very excited to add this data to what we already have around IL-17 inhibition. This clearly validates this target for the control of HS,” reported lead investigator Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston.
The trials, called BE HEARD I and BE HEARD II, enrolled 505 and 509 patients with HS, respectively. About 50% of patients in BE HEARD I and 60% of patients in BE HEARD II had Hurley stage 3 disease, which is the most severe of the three stratifications. The remainder were in Hurley stage 2. The mean duration of HS was 8.3 and 7.1 years, respectively.
Patients in both studies were randomized to one of four groups – either to a dosing regimen of 320 mg of bimekizumab administered by subcutaneous injection or to a placebo group. Both trials comprised double-blind 16-week initial and 32-week maintenance treatment periods.
In one experimental group, bimekizumab was given once every 2 weeks for the full course of the 48-week study (Q2W/Q2W). In another, patients started on the every-2-week schedule for 16 weeks and then were switched to every-4-week dosing (Q2W/Q4W). In the third group, patients started and remained on the every-4-week schedule (Q4W/Q4W). Patients in a fourth group started on placebo and switched at 16 weeks to the every-2-week bimekizumab schedule (placebo/Q2W).
Results at primary endpoint
The primary endpoint was HiSCR50, signifying a 50% reduction from baseline in abscess and inflammatory nodule count on the Hidradenitis Suppurativa Clinical Response (HiSCR) assessment tool. At 16 weeks, the initial Q2W dose in two of the groups outperformed the placebo in both BE HEARD I (47.8% vs. 28.7%) and BE HEARD II (52.0% vs. 32.2%). The response rates in the Q4W arm in BE HEARD I (45.3%) and BE HEARD II (53.8%) were also higher than the placebo, but the difference was only significant in BE HEARD II.
At 48 weeks, the proportion of patients with an HiSCR50 response climbed in all groups in both trials. The patterns were generally the same with slightly higher numerical responses among the groups that received the every-2-week dosing schedule relative to the every-4-week schedule.
In BE HEARD I at 48 weeks, the HiSCR50 response rate was about 60% for those who started and remained on every-2-week bimekizumab (Q2W/Q2W) or were switched at 16 weeks to every-4-week bimekizumab (Q2W/Q4W). For those who started and remained on every-4-week bimekizumab and the group started on placebo and switched to every-2-week bimekizumab, the response rates were 52.7% and 45.3%, respectively.
In BE HEARD II, the HiSCR50 response rates were higher in all groups, including the placebo, and the patterns of response were similar at 48 weeks. Most patients reached the HiSCR50 response – 79.8% (Q2W/Q2W), 78.4% (Q2W/Q4W), 76.7% (Q4W/Q4W), and 65.9 % (placebo/Q2W) of patients.
It is notable that, although there was rapid increase in the proportion of placebo patients reaching HiSCR50 after the switch at 16 weeks, there appeared to be an advantage at 48 weeks for starting on full-dose bimekizumab over starting on placebo.
In this trial, patients were listed as nonresponders if they received antibiotics at any time and for any reason after randomization. This might have concealed an even greater benefit of bimekizumab, Dr. Kimball said, but the study design element was considered necessary to isolate the activity of the study drug.
“In future HS trials, it will be helpful to address the difficulty of handling the impact of antibiotics and pain medications [in assessing results],” Dr. Kimball said.
Clinically meaningful secondary endpoint
For HS patients, the secondary endpoint of HiSCR75 might be considered the most meaningful, according to Dr. Kimball. She said that this higher bar not only documents a higher level of efficacy but correlates with meaningful improvement in quality of life. In the two trials combined, more than 55% of patients on continuous bimekizumab achieved HiSCR75 at week 48 in the observed case analysis, according to a news release from biopharmaceutical company UCB, developer of bimekizumab.
In BE HEARD I, the HiSCR75 rates were 33.4% and 24.7% for the every-2-week and every-4-week bimekizumab doses, respectively. The 33.4% response was statistically superior to placebo (18.4%). In BE HEARD II, both the every-2-week dose (35.7%) and the every-4-week dose (33.7%) were superior to the 15.6% response in placebo patients.
The improvements in quality of life as measured with the Dermatology Life Quality Index (DLQI), reflected the changes in disease activity. Relative to about a 3-point reduction from baseline in the placebo groups of the two trials, the 5-point reduction for either the 2-week or 4-week bimekizumab groups in each clinical trial were highly significant, Dr. Kimball said.
Bimekizumab was relatively well tolerated, although it shares the increased risk for candidiasis observed with this agent when used in psoriasis and with other IL-17 inhibitors, such as secukinumab (Cosentyx), in general. The risk of candidiasis appeared to be dose related, but cases were generally mild and easily managed, according to Dr. Kimball. She noted that only three patients discontinued treatment for this reason. Discontinuations for a treatment-related adverse event overall was less than 4% at 16 weeks.
This is only the third phase 3 trial ever completed in patients with HS. In fact, Dr. Kimball has led all of the phase 3 trials so far, including clinical studies of adalimumab (Humira), published in 2016, and of secukinumab, published earlier this year. All were positive studies.
“This is amazing news for our patients,” Dr. Kimball said. HS remains a challenging disease, even with a growing number of options showing benefit in large studies, she said, and the high rate of response, particularly at the level of HiSCR75, “is a huge milestone for what we can achieve.”
Multiple treatment options important
Her assessment was echoed by other experts, including Christopher J. Sayed, MD, an associate professor of dermatology at the University of North Carolina at Chapel Hill, who publishes frequently about this disease.
“It is incredibly exciting to see the strong phase 3 data on bimekizumab, particularly the deep responses at the HiSCR75 in a majority of patients after the first year,” he said.
Importantly, he does not see the growing array of treatment options as necessarily competitive for a disease with heterogeneous manifestations and variable responses to any one agent.
“While this may be a major step forward, it will still be critical to see more drugs come along for those who do not respond fully enough or have comorbidities that prevent the use of IL-17 and TNF [tumor necrosis factor] antagonists,” he said.
Bimekizumab is not approved for any indication in the United States; it is approved for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy in the EU/EEA, where it is marketed as Bimzelx, according to UCB. Dr. Kimball reports financial relationships with AbbVie, Janssen, Kymera, Lilly, Novartis, Pfizer, and UCB. Dr. Sayed reports financial relationships with AbbVie, InflaRx, and UCB.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – In two phase 3 trials, bimekizumab, a monoclonal antibody targeting two types of interleukin-17 — IL-17A and IL-17F — reduced the abscess and inflammatory nodule count better than placebo in the chronic inflammatory skin condition hidradenitis suppurativa (HS), according to results presented together during a late-breaker session at the annual meeting of the American Academy of Dermatology.
“We are very excited to add this data to what we already have around IL-17 inhibition. This clearly validates this target for the control of HS,” reported lead investigator Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston.
The trials, called BE HEARD I and BE HEARD II, enrolled 505 and 509 patients with HS, respectively. About 50% of patients in BE HEARD I and 60% of patients in BE HEARD II had Hurley stage 3 disease, which is the most severe of the three stratifications. The remainder were in Hurley stage 2. The mean duration of HS was 8.3 and 7.1 years, respectively.
Patients in both studies were randomized to one of four groups – either to a dosing regimen of 320 mg of bimekizumab administered by subcutaneous injection or to a placebo group. Both trials comprised double-blind 16-week initial and 32-week maintenance treatment periods.
In one experimental group, bimekizumab was given once every 2 weeks for the full course of the 48-week study (Q2W/Q2W). In another, patients started on the every-2-week schedule for 16 weeks and then were switched to every-4-week dosing (Q2W/Q4W). In the third group, patients started and remained on the every-4-week schedule (Q4W/Q4W). Patients in a fourth group started on placebo and switched at 16 weeks to the every-2-week bimekizumab schedule (placebo/Q2W).
Results at primary endpoint
The primary endpoint was HiSCR50, signifying a 50% reduction from baseline in abscess and inflammatory nodule count on the Hidradenitis Suppurativa Clinical Response (HiSCR) assessment tool. At 16 weeks, the initial Q2W dose in two of the groups outperformed the placebo in both BE HEARD I (47.8% vs. 28.7%) and BE HEARD II (52.0% vs. 32.2%). The response rates in the Q4W arm in BE HEARD I (45.3%) and BE HEARD II (53.8%) were also higher than the placebo, but the difference was only significant in BE HEARD II.
At 48 weeks, the proportion of patients with an HiSCR50 response climbed in all groups in both trials. The patterns were generally the same with slightly higher numerical responses among the groups that received the every-2-week dosing schedule relative to the every-4-week schedule.
In BE HEARD I at 48 weeks, the HiSCR50 response rate was about 60% for those who started and remained on every-2-week bimekizumab (Q2W/Q2W) or were switched at 16 weeks to every-4-week bimekizumab (Q2W/Q4W). For those who started and remained on every-4-week bimekizumab and the group started on placebo and switched to every-2-week bimekizumab, the response rates were 52.7% and 45.3%, respectively.
In BE HEARD II, the HiSCR50 response rates were higher in all groups, including the placebo, and the patterns of response were similar at 48 weeks. Most patients reached the HiSCR50 response – 79.8% (Q2W/Q2W), 78.4% (Q2W/Q4W), 76.7% (Q4W/Q4W), and 65.9 % (placebo/Q2W) of patients.
It is notable that, although there was rapid increase in the proportion of placebo patients reaching HiSCR50 after the switch at 16 weeks, there appeared to be an advantage at 48 weeks for starting on full-dose bimekizumab over starting on placebo.
In this trial, patients were listed as nonresponders if they received antibiotics at any time and for any reason after randomization. This might have concealed an even greater benefit of bimekizumab, Dr. Kimball said, but the study design element was considered necessary to isolate the activity of the study drug.
“In future HS trials, it will be helpful to address the difficulty of handling the impact of antibiotics and pain medications [in assessing results],” Dr. Kimball said.
Clinically meaningful secondary endpoint
For HS patients, the secondary endpoint of HiSCR75 might be considered the most meaningful, according to Dr. Kimball. She said that this higher bar not only documents a higher level of efficacy but correlates with meaningful improvement in quality of life. In the two trials combined, more than 55% of patients on continuous bimekizumab achieved HiSCR75 at week 48 in the observed case analysis, according to a news release from biopharmaceutical company UCB, developer of bimekizumab.
In BE HEARD I, the HiSCR75 rates were 33.4% and 24.7% for the every-2-week and every-4-week bimekizumab doses, respectively. The 33.4% response was statistically superior to placebo (18.4%). In BE HEARD II, both the every-2-week dose (35.7%) and the every-4-week dose (33.7%) were superior to the 15.6% response in placebo patients.
The improvements in quality of life as measured with the Dermatology Life Quality Index (DLQI), reflected the changes in disease activity. Relative to about a 3-point reduction from baseline in the placebo groups of the two trials, the 5-point reduction for either the 2-week or 4-week bimekizumab groups in each clinical trial were highly significant, Dr. Kimball said.
Bimekizumab was relatively well tolerated, although it shares the increased risk for candidiasis observed with this agent when used in psoriasis and with other IL-17 inhibitors, such as secukinumab (Cosentyx), in general. The risk of candidiasis appeared to be dose related, but cases were generally mild and easily managed, according to Dr. Kimball. She noted that only three patients discontinued treatment for this reason. Discontinuations for a treatment-related adverse event overall was less than 4% at 16 weeks.
This is only the third phase 3 trial ever completed in patients with HS. In fact, Dr. Kimball has led all of the phase 3 trials so far, including clinical studies of adalimumab (Humira), published in 2016, and of secukinumab, published earlier this year. All were positive studies.
“This is amazing news for our patients,” Dr. Kimball said. HS remains a challenging disease, even with a growing number of options showing benefit in large studies, she said, and the high rate of response, particularly at the level of HiSCR75, “is a huge milestone for what we can achieve.”
Multiple treatment options important
Her assessment was echoed by other experts, including Christopher J. Sayed, MD, an associate professor of dermatology at the University of North Carolina at Chapel Hill, who publishes frequently about this disease.
“It is incredibly exciting to see the strong phase 3 data on bimekizumab, particularly the deep responses at the HiSCR75 in a majority of patients after the first year,” he said.
Importantly, he does not see the growing array of treatment options as necessarily competitive for a disease with heterogeneous manifestations and variable responses to any one agent.
“While this may be a major step forward, it will still be critical to see more drugs come along for those who do not respond fully enough or have comorbidities that prevent the use of IL-17 and TNF [tumor necrosis factor] antagonists,” he said.
Bimekizumab is not approved for any indication in the United States; it is approved for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy in the EU/EEA, where it is marketed as Bimzelx, according to UCB. Dr. Kimball reports financial relationships with AbbVie, Janssen, Kymera, Lilly, Novartis, Pfizer, and UCB. Dr. Sayed reports financial relationships with AbbVie, InflaRx, and UCB.
A version of this article first appeared on Medscape.com.
AT AAD 2023
Early exercise intervention improves knee osteoarthritis
DENVER – Initiating exercise therapy early on in people who develop symptoms of knee osteoarthritis – even within their first year of pain or reduced function – is associated with modestly lower pain scores and modestly better function than in those whose symptoms have lasted longer, according to a study presented at the OARSI 2023 World Congress.
Although the benefits of exercise therapy for advanced knee osteoarthritis had already been well established, this study looked specifically at benefits from exercise therapy earlier on, in patients with a shorter duration of symptoms.
“Exercise indeed seems especially beneficial in patients with shorter symptom duration and should therefore be encouraged at first symptom presentation,” Marienke van Middelkoop, PhD, of Erasmus MC Medical University in Rotterdam, the Netherlands, told attendees at the meeting, sponsored by Osteoarthritis Research Society International. “It is, however, still a challenge how we can identify patients but also how we can motivate these patients with early symptoms of osteoarthritis.” She noted that a separate pilot study had experienced difficulty recruiting people with short-term symptom duration.
The researchers compared the effect of exercise therapy and no exercise among adults at least 45 years old with knee osteoarthritis, relying on individual participant data from the STEER OA study, a meta-analysis of 31 studies that involved 4,241 participants. After excluding studies that didn’t report symptom duration, lacked a control group or consent, or focused on hip osteoarthritis, the researchers ended up with 10 studies involving 1,895 participants. These participants were stratified based on the duration of their symptoms: up to 1 year (14.4%), 1-2 years (11%), and 2 years or longer (74%).
About two-thirds of the participants were women (65.9%), with an average age of 65 years and an average body mass index (BMI) of 30.7 kg/m2. Any land-based or water-based therapeutic exercise counted for the 62% of participants in the intervention group, while the control group had no exercise. Outcomes were assessed based on self-reported pain or physical function at short-term and long-term follow-up, which were as close as possible to 3 months for short-term and the closest date to 12 months for longer term. At baseline, the participants reported an average pain score of 41.7 on a 0-to-100 scale and an average physical function score of 37.4 on a 0-to-100 scale where lower scores indicate better function.
Among those doing exercise therapy, average pain scores dropped 4.56 points in the short term and 7.43 points in the long term. Short-term and long-term pain scores were lower among those whose symptom durations were shorter. For example, those with symptoms for less than a year reported a short-term pain score of 29, compared with 30 for those with 1-2 years of pain and 32 for those with at least 2 years of pain. Results were similar for long-term pain (a score of 26, compared with 28 and 33, respectively).
Participants engaging in exercise therapy also improved average function scores, with a pattern of improvement that was similar to pain scores based on patients’ symptom duration. The average short-term function score was 26 among those with less than a year of symptoms, compared with 28 for those with symptoms for 1-2 years, and 30 for those with symptoms for at least 2 years. Longer-term function scores were 21, 24, and 29, respectively, based on increasing symptom durations.
Chris Yun Lane, PT, DPT, a physical therapist and a fourth-year PhD student at the University of North Carolina at Chapel Hill, was not surprised at the exercise benefit given the extensive evidence already showing that exercise is beneficial for patients with osteoarthritis whose symptoms have lasted longer.
“Just spending a little bit of time on education, designing kind of simple exercise programs, such as walking programs, can be very helpful,” Dr. Lane said in an interview. “Of course, some of it is dependent on the patient itself, but strengthening range of motion is often very helpful.” Dr. Lane said it’s particularly important for physicians and physical therapists to emphasize the importance of exercise to their patients because that guidance doesn’t always occur as often as it should.
Ron Ellis Jr., DO, MBA, chief strategy officer of Pacira BioSciences in Tampa, Fla., noted that a lot of patients with knee osteoarthritis have weakness in their quads, so quad strengthening is “a typical part of our improvement program for patients with osteoarthritis,” he said in an interview. Dr. Ellis also referenced a session he attended the previous day that showed exercise results in reduced inflammation.
“So you may not have weight loss, but you can lower the inflammatory state of the overall body and of the specific joints,” Dr. Ellis said, “so that would support [this study’s] conclusion.”
The STEER OA study was funded by the Chartered Society of Physiotherapy Charitable Trust and the National Institute for Health Research School of Primary Care Research. Dr. van Middelkoop and Dr. Lane both reported having no relevant financial relationships.
DENVER – Initiating exercise therapy early on in people who develop symptoms of knee osteoarthritis – even within their first year of pain or reduced function – is associated with modestly lower pain scores and modestly better function than in those whose symptoms have lasted longer, according to a study presented at the OARSI 2023 World Congress.
Although the benefits of exercise therapy for advanced knee osteoarthritis had already been well established, this study looked specifically at benefits from exercise therapy earlier on, in patients with a shorter duration of symptoms.
“Exercise indeed seems especially beneficial in patients with shorter symptom duration and should therefore be encouraged at first symptom presentation,” Marienke van Middelkoop, PhD, of Erasmus MC Medical University in Rotterdam, the Netherlands, told attendees at the meeting, sponsored by Osteoarthritis Research Society International. “It is, however, still a challenge how we can identify patients but also how we can motivate these patients with early symptoms of osteoarthritis.” She noted that a separate pilot study had experienced difficulty recruiting people with short-term symptom duration.
The researchers compared the effect of exercise therapy and no exercise among adults at least 45 years old with knee osteoarthritis, relying on individual participant data from the STEER OA study, a meta-analysis of 31 studies that involved 4,241 participants. After excluding studies that didn’t report symptom duration, lacked a control group or consent, or focused on hip osteoarthritis, the researchers ended up with 10 studies involving 1,895 participants. These participants were stratified based on the duration of their symptoms: up to 1 year (14.4%), 1-2 years (11%), and 2 years or longer (74%).
About two-thirds of the participants were women (65.9%), with an average age of 65 years and an average body mass index (BMI) of 30.7 kg/m2. Any land-based or water-based therapeutic exercise counted for the 62% of participants in the intervention group, while the control group had no exercise. Outcomes were assessed based on self-reported pain or physical function at short-term and long-term follow-up, which were as close as possible to 3 months for short-term and the closest date to 12 months for longer term. At baseline, the participants reported an average pain score of 41.7 on a 0-to-100 scale and an average physical function score of 37.4 on a 0-to-100 scale where lower scores indicate better function.
Among those doing exercise therapy, average pain scores dropped 4.56 points in the short term and 7.43 points in the long term. Short-term and long-term pain scores were lower among those whose symptom durations were shorter. For example, those with symptoms for less than a year reported a short-term pain score of 29, compared with 30 for those with 1-2 years of pain and 32 for those with at least 2 years of pain. Results were similar for long-term pain (a score of 26, compared with 28 and 33, respectively).
Participants engaging in exercise therapy also improved average function scores, with a pattern of improvement that was similar to pain scores based on patients’ symptom duration. The average short-term function score was 26 among those with less than a year of symptoms, compared with 28 for those with symptoms for 1-2 years, and 30 for those with symptoms for at least 2 years. Longer-term function scores were 21, 24, and 29, respectively, based on increasing symptom durations.
Chris Yun Lane, PT, DPT, a physical therapist and a fourth-year PhD student at the University of North Carolina at Chapel Hill, was not surprised at the exercise benefit given the extensive evidence already showing that exercise is beneficial for patients with osteoarthritis whose symptoms have lasted longer.
“Just spending a little bit of time on education, designing kind of simple exercise programs, such as walking programs, can be very helpful,” Dr. Lane said in an interview. “Of course, some of it is dependent on the patient itself, but strengthening range of motion is often very helpful.” Dr. Lane said it’s particularly important for physicians and physical therapists to emphasize the importance of exercise to their patients because that guidance doesn’t always occur as often as it should.
Ron Ellis Jr., DO, MBA, chief strategy officer of Pacira BioSciences in Tampa, Fla., noted that a lot of patients with knee osteoarthritis have weakness in their quads, so quad strengthening is “a typical part of our improvement program for patients with osteoarthritis,” he said in an interview. Dr. Ellis also referenced a session he attended the previous day that showed exercise results in reduced inflammation.
“So you may not have weight loss, but you can lower the inflammatory state of the overall body and of the specific joints,” Dr. Ellis said, “so that would support [this study’s] conclusion.”
The STEER OA study was funded by the Chartered Society of Physiotherapy Charitable Trust and the National Institute for Health Research School of Primary Care Research. Dr. van Middelkoop and Dr. Lane both reported having no relevant financial relationships.
DENVER – Initiating exercise therapy early on in people who develop symptoms of knee osteoarthritis – even within their first year of pain or reduced function – is associated with modestly lower pain scores and modestly better function than in those whose symptoms have lasted longer, according to a study presented at the OARSI 2023 World Congress.
Although the benefits of exercise therapy for advanced knee osteoarthritis had already been well established, this study looked specifically at benefits from exercise therapy earlier on, in patients with a shorter duration of symptoms.
“Exercise indeed seems especially beneficial in patients with shorter symptom duration and should therefore be encouraged at first symptom presentation,” Marienke van Middelkoop, PhD, of Erasmus MC Medical University in Rotterdam, the Netherlands, told attendees at the meeting, sponsored by Osteoarthritis Research Society International. “It is, however, still a challenge how we can identify patients but also how we can motivate these patients with early symptoms of osteoarthritis.” She noted that a separate pilot study had experienced difficulty recruiting people with short-term symptom duration.
The researchers compared the effect of exercise therapy and no exercise among adults at least 45 years old with knee osteoarthritis, relying on individual participant data from the STEER OA study, a meta-analysis of 31 studies that involved 4,241 participants. After excluding studies that didn’t report symptom duration, lacked a control group or consent, or focused on hip osteoarthritis, the researchers ended up with 10 studies involving 1,895 participants. These participants were stratified based on the duration of their symptoms: up to 1 year (14.4%), 1-2 years (11%), and 2 years or longer (74%).
About two-thirds of the participants were women (65.9%), with an average age of 65 years and an average body mass index (BMI) of 30.7 kg/m2. Any land-based or water-based therapeutic exercise counted for the 62% of participants in the intervention group, while the control group had no exercise. Outcomes were assessed based on self-reported pain or physical function at short-term and long-term follow-up, which were as close as possible to 3 months for short-term and the closest date to 12 months for longer term. At baseline, the participants reported an average pain score of 41.7 on a 0-to-100 scale and an average physical function score of 37.4 on a 0-to-100 scale where lower scores indicate better function.
Among those doing exercise therapy, average pain scores dropped 4.56 points in the short term and 7.43 points in the long term. Short-term and long-term pain scores were lower among those whose symptom durations were shorter. For example, those with symptoms for less than a year reported a short-term pain score of 29, compared with 30 for those with 1-2 years of pain and 32 for those with at least 2 years of pain. Results were similar for long-term pain (a score of 26, compared with 28 and 33, respectively).
Participants engaging in exercise therapy also improved average function scores, with a pattern of improvement that was similar to pain scores based on patients’ symptom duration. The average short-term function score was 26 among those with less than a year of symptoms, compared with 28 for those with symptoms for 1-2 years, and 30 for those with symptoms for at least 2 years. Longer-term function scores were 21, 24, and 29, respectively, based on increasing symptom durations.
Chris Yun Lane, PT, DPT, a physical therapist and a fourth-year PhD student at the University of North Carolina at Chapel Hill, was not surprised at the exercise benefit given the extensive evidence already showing that exercise is beneficial for patients with osteoarthritis whose symptoms have lasted longer.
“Just spending a little bit of time on education, designing kind of simple exercise programs, such as walking programs, can be very helpful,” Dr. Lane said in an interview. “Of course, some of it is dependent on the patient itself, but strengthening range of motion is often very helpful.” Dr. Lane said it’s particularly important for physicians and physical therapists to emphasize the importance of exercise to their patients because that guidance doesn’t always occur as often as it should.
Ron Ellis Jr., DO, MBA, chief strategy officer of Pacira BioSciences in Tampa, Fla., noted that a lot of patients with knee osteoarthritis have weakness in their quads, so quad strengthening is “a typical part of our improvement program for patients with osteoarthritis,” he said in an interview. Dr. Ellis also referenced a session he attended the previous day that showed exercise results in reduced inflammation.
“So you may not have weight loss, but you can lower the inflammatory state of the overall body and of the specific joints,” Dr. Ellis said, “so that would support [this study’s] conclusion.”
The STEER OA study was funded by the Chartered Society of Physiotherapy Charitable Trust and the National Institute for Health Research School of Primary Care Research. Dr. van Middelkoop and Dr. Lane both reported having no relevant financial relationships.
AT OARSI 2023
Rheumatology fellows learn about career opportunities
SAN FRANCISCO – Various career paths open to newly board-certified rheumatologists – and some of the pros and cons for each – were explored at the 2023 Fellows Conference of the Coalition for State Rheumatology Organizations.
CSRO’s annual Fellows Conference aims to helps rheumatology fellows-in-training transition into future roles as practicing physicians, said Christopher Sonntag, MD, a 2nd-year rheumatology fellow at Roger Williams Medical Center, Providence, R.I., and the Fellow-At-Large representative on CSRO’s Board of Directors. He will launch his own career at Washington Regional Medical Center in Fayetteville, Ark., close to where he grew up, when his fellowship winds up in June.
“I started going to CSRO meetings in 2019, when I was still a resident,” said Dr. Sonntag, who fell in love with rheumatology in medical school. “This conference is a great opportunity for fellows. They can learn a lot of critical issues and skills that we just don’t get enough information about in our training, basic things we ought to know about: how insurance works, medical benefits, and the like.”
Job seekers in a specialty in short supply like rheumatology have some competitive advantages, but that varies by locality in a volatile health care market. “The job I ended up taking was not one where they were initially looking to hire another rheumatologist,” Dr. Sonntag told this news organization. The Fayetteville hospital already had two busy rheumatologists, but after Dr. Sonntag had unsatisfying interviews at six other groups, he called them back and they decided to go ahead and hire him. He said the position provides an acceptable work-life balance, as well as opportunities to teach. He hopes eventually to create a rheumatology fellowship program.
Models and Career Paths
Decisions about one’s career path are very important, said CSRO’s president, Gary Feldman, MD, a rheumatologist at Pacific Arthritis in Los Angeles. “We want your choice to work for you,” he told attendees. “We need you to be happy [in your jobs] for the next 30 years. You are the future.”
Dr. Feldman cited a recent Medscape salary survey of 13,000 full-time physicians from 29 specialties, which ranked rheumatologists 22nd in average annual income at $289,000. Total income may not be the first consideration in pursuing rheumatology as a career, Dr. Feldman noted. The same Medscape survey revealed that 60% of rheumatologists believe they are fairly compensated. “Something else is going on, something to do with work/life balance, which is complicated,” he said.
Other contributors to their career fulfillment may include the in-depth, long-term therapeutic relationships rheumatologists develop with their patients who have chronic, incurable illnesses; the ability with new treatments to make such a difference in managing their pain and discomfort; and engagement with giving good medical care that is centered on the patient’s experience.
“We have drugs that work to make our patients feel better. Patients come to us with no idea what’s going on, and we can turn their lives around,” Dr. Sonntag noted.
Other important career-oriented questions to ask, Dr. Feldman said, include:
What is important to you?
Who are you going to be working alongside?
How much autonomy, agency, security, or risk are you comfortable with?
What is your best balance between being a physician and an entrepreneur?
Finding your niche
Presenter Aaron Broadwell, MD, a rheumatologist in a private specialty practice of five physicians and five advanced practice providers in Shreveport, La., discussed the prospects for a career in private practice at the Fellows Conference. Private practice is not dead as a career choice, he observed, “despite what I continue to hear.” Data show that 70% of rheumatologists currently are in employed positions, but he sees signs of a movement back toward private practice.
Other basic career paths outlined by Dr. Broadwell include:
- Academic medicine, which offers opportunities to teach future physicians (although it’s also possible for rheumatologists practicing outside of academia to teach as well).
- Hospital employment, which has a higher starting salary but also a greater emphasis on RVUs (relative value units) and productivity, with less job security than it used to enjoy.
- Military/Veterans Administration positions, which may have antiquated office systems and salary caps.
- Other paths, including corporate medical director positions with pharmaceutical companies and insurance companies.
Newer options include concierge and direct specialty care models where physician-operated practices partner with their patients to provide specialty care services under a flat or periodic membership fee, and joining one of the large, multistate, rheumatology care management groups like United Rheumatology, LLC, and American Arthritis and Rheumatology Associates.
Private practice medical groups are both single specialty and multispecialty, both large and small – as well as solo rheumatology practices, Dr. Broadwell said. “People launch solo private practices all the time. It is good for some doctors. It has the highest risk and the highest potential reward.”
Becoming profitable in solo practice may take a year or two, while the doctor remains responsible 24/7, including the need to arrange for vacation and sick leave coverage. Solo practitioners need to be up to date on billing, coding, revenue cycles, bundled payments and the like, and eventually need to hire and supervise a team the doctor can trust.
What can young rheumatologists do to learn more of the nuances of these approaches? Dr. Broadwell recommended joining their state rheumatology society as well as the American College of Rheumatology. “The National Organization of Rheumatology Management is a phenomenal source of information, not just for your office manager but also for you,” he said. He also recommended linking up with colleagues through social media outlets such as the Rheumatology Private Practice Group on Facebook.
No relevant financial relationships were reported by the conference speakers.
A version of this article originally appeared on Medscape.com.
SAN FRANCISCO – Various career paths open to newly board-certified rheumatologists – and some of the pros and cons for each – were explored at the 2023 Fellows Conference of the Coalition for State Rheumatology Organizations.
CSRO’s annual Fellows Conference aims to helps rheumatology fellows-in-training transition into future roles as practicing physicians, said Christopher Sonntag, MD, a 2nd-year rheumatology fellow at Roger Williams Medical Center, Providence, R.I., and the Fellow-At-Large representative on CSRO’s Board of Directors. He will launch his own career at Washington Regional Medical Center in Fayetteville, Ark., close to where he grew up, when his fellowship winds up in June.
“I started going to CSRO meetings in 2019, when I was still a resident,” said Dr. Sonntag, who fell in love with rheumatology in medical school. “This conference is a great opportunity for fellows. They can learn a lot of critical issues and skills that we just don’t get enough information about in our training, basic things we ought to know about: how insurance works, medical benefits, and the like.”
Job seekers in a specialty in short supply like rheumatology have some competitive advantages, but that varies by locality in a volatile health care market. “The job I ended up taking was not one where they were initially looking to hire another rheumatologist,” Dr. Sonntag told this news organization. The Fayetteville hospital already had two busy rheumatologists, but after Dr. Sonntag had unsatisfying interviews at six other groups, he called them back and they decided to go ahead and hire him. He said the position provides an acceptable work-life balance, as well as opportunities to teach. He hopes eventually to create a rheumatology fellowship program.
Models and Career Paths
Decisions about one’s career path are very important, said CSRO’s president, Gary Feldman, MD, a rheumatologist at Pacific Arthritis in Los Angeles. “We want your choice to work for you,” he told attendees. “We need you to be happy [in your jobs] for the next 30 years. You are the future.”
Dr. Feldman cited a recent Medscape salary survey of 13,000 full-time physicians from 29 specialties, which ranked rheumatologists 22nd in average annual income at $289,000. Total income may not be the first consideration in pursuing rheumatology as a career, Dr. Feldman noted. The same Medscape survey revealed that 60% of rheumatologists believe they are fairly compensated. “Something else is going on, something to do with work/life balance, which is complicated,” he said.
Other contributors to their career fulfillment may include the in-depth, long-term therapeutic relationships rheumatologists develop with their patients who have chronic, incurable illnesses; the ability with new treatments to make such a difference in managing their pain and discomfort; and engagement with giving good medical care that is centered on the patient’s experience.
“We have drugs that work to make our patients feel better. Patients come to us with no idea what’s going on, and we can turn their lives around,” Dr. Sonntag noted.
Other important career-oriented questions to ask, Dr. Feldman said, include:
What is important to you?
Who are you going to be working alongside?
How much autonomy, agency, security, or risk are you comfortable with?
What is your best balance between being a physician and an entrepreneur?
Finding your niche
Presenter Aaron Broadwell, MD, a rheumatologist in a private specialty practice of five physicians and five advanced practice providers in Shreveport, La., discussed the prospects for a career in private practice at the Fellows Conference. Private practice is not dead as a career choice, he observed, “despite what I continue to hear.” Data show that 70% of rheumatologists currently are in employed positions, but he sees signs of a movement back toward private practice.
Other basic career paths outlined by Dr. Broadwell include:
- Academic medicine, which offers opportunities to teach future physicians (although it’s also possible for rheumatologists practicing outside of academia to teach as well).
- Hospital employment, which has a higher starting salary but also a greater emphasis on RVUs (relative value units) and productivity, with less job security than it used to enjoy.
- Military/Veterans Administration positions, which may have antiquated office systems and salary caps.
- Other paths, including corporate medical director positions with pharmaceutical companies and insurance companies.
Newer options include concierge and direct specialty care models where physician-operated practices partner with their patients to provide specialty care services under a flat or periodic membership fee, and joining one of the large, multistate, rheumatology care management groups like United Rheumatology, LLC, and American Arthritis and Rheumatology Associates.
Private practice medical groups are both single specialty and multispecialty, both large and small – as well as solo rheumatology practices, Dr. Broadwell said. “People launch solo private practices all the time. It is good for some doctors. It has the highest risk and the highest potential reward.”
Becoming profitable in solo practice may take a year or two, while the doctor remains responsible 24/7, including the need to arrange for vacation and sick leave coverage. Solo practitioners need to be up to date on billing, coding, revenue cycles, bundled payments and the like, and eventually need to hire and supervise a team the doctor can trust.
What can young rheumatologists do to learn more of the nuances of these approaches? Dr. Broadwell recommended joining their state rheumatology society as well as the American College of Rheumatology. “The National Organization of Rheumatology Management is a phenomenal source of information, not just for your office manager but also for you,” he said. He also recommended linking up with colleagues through social media outlets such as the Rheumatology Private Practice Group on Facebook.
No relevant financial relationships were reported by the conference speakers.
A version of this article originally appeared on Medscape.com.
SAN FRANCISCO – Various career paths open to newly board-certified rheumatologists – and some of the pros and cons for each – were explored at the 2023 Fellows Conference of the Coalition for State Rheumatology Organizations.
CSRO’s annual Fellows Conference aims to helps rheumatology fellows-in-training transition into future roles as practicing physicians, said Christopher Sonntag, MD, a 2nd-year rheumatology fellow at Roger Williams Medical Center, Providence, R.I., and the Fellow-At-Large representative on CSRO’s Board of Directors. He will launch his own career at Washington Regional Medical Center in Fayetteville, Ark., close to where he grew up, when his fellowship winds up in June.
“I started going to CSRO meetings in 2019, when I was still a resident,” said Dr. Sonntag, who fell in love with rheumatology in medical school. “This conference is a great opportunity for fellows. They can learn a lot of critical issues and skills that we just don’t get enough information about in our training, basic things we ought to know about: how insurance works, medical benefits, and the like.”
Job seekers in a specialty in short supply like rheumatology have some competitive advantages, but that varies by locality in a volatile health care market. “The job I ended up taking was not one where they were initially looking to hire another rheumatologist,” Dr. Sonntag told this news organization. The Fayetteville hospital already had two busy rheumatologists, but after Dr. Sonntag had unsatisfying interviews at six other groups, he called them back and they decided to go ahead and hire him. He said the position provides an acceptable work-life balance, as well as opportunities to teach. He hopes eventually to create a rheumatology fellowship program.
Models and Career Paths
Decisions about one’s career path are very important, said CSRO’s president, Gary Feldman, MD, a rheumatologist at Pacific Arthritis in Los Angeles. “We want your choice to work for you,” he told attendees. “We need you to be happy [in your jobs] for the next 30 years. You are the future.”
Dr. Feldman cited a recent Medscape salary survey of 13,000 full-time physicians from 29 specialties, which ranked rheumatologists 22nd in average annual income at $289,000. Total income may not be the first consideration in pursuing rheumatology as a career, Dr. Feldman noted. The same Medscape survey revealed that 60% of rheumatologists believe they are fairly compensated. “Something else is going on, something to do with work/life balance, which is complicated,” he said.
Other contributors to their career fulfillment may include the in-depth, long-term therapeutic relationships rheumatologists develop with their patients who have chronic, incurable illnesses; the ability with new treatments to make such a difference in managing their pain and discomfort; and engagement with giving good medical care that is centered on the patient’s experience.
“We have drugs that work to make our patients feel better. Patients come to us with no idea what’s going on, and we can turn their lives around,” Dr. Sonntag noted.
Other important career-oriented questions to ask, Dr. Feldman said, include:
What is important to you?
Who are you going to be working alongside?
How much autonomy, agency, security, or risk are you comfortable with?
What is your best balance between being a physician and an entrepreneur?
Finding your niche
Presenter Aaron Broadwell, MD, a rheumatologist in a private specialty practice of five physicians and five advanced practice providers in Shreveport, La., discussed the prospects for a career in private practice at the Fellows Conference. Private practice is not dead as a career choice, he observed, “despite what I continue to hear.” Data show that 70% of rheumatologists currently are in employed positions, but he sees signs of a movement back toward private practice.
Other basic career paths outlined by Dr. Broadwell include:
- Academic medicine, which offers opportunities to teach future physicians (although it’s also possible for rheumatologists practicing outside of academia to teach as well).
- Hospital employment, which has a higher starting salary but also a greater emphasis on RVUs (relative value units) and productivity, with less job security than it used to enjoy.
- Military/Veterans Administration positions, which may have antiquated office systems and salary caps.
- Other paths, including corporate medical director positions with pharmaceutical companies and insurance companies.
Newer options include concierge and direct specialty care models where physician-operated practices partner with their patients to provide specialty care services under a flat or periodic membership fee, and joining one of the large, multistate, rheumatology care management groups like United Rheumatology, LLC, and American Arthritis and Rheumatology Associates.
Private practice medical groups are both single specialty and multispecialty, both large and small – as well as solo rheumatology practices, Dr. Broadwell said. “People launch solo private practices all the time. It is good for some doctors. It has the highest risk and the highest potential reward.”
Becoming profitable in solo practice may take a year or two, while the doctor remains responsible 24/7, including the need to arrange for vacation and sick leave coverage. Solo practitioners need to be up to date on billing, coding, revenue cycles, bundled payments and the like, and eventually need to hire and supervise a team the doctor can trust.
What can young rheumatologists do to learn more of the nuances of these approaches? Dr. Broadwell recommended joining their state rheumatology society as well as the American College of Rheumatology. “The National Organization of Rheumatology Management is a phenomenal source of information, not just for your office manager but also for you,” he said. He also recommended linking up with colleagues through social media outlets such as the Rheumatology Private Practice Group on Facebook.
No relevant financial relationships were reported by the conference speakers.
A version of this article originally appeared on Medscape.com.
AT CSRO 2023
Marathon running does not increase arthritis risk: Survey
Runners who had undergone knee or hip surgery or had a previous hip or knee injury that prevented running were most likely to have arthritis, researchers found. Family history of arthritis, higher body mass index (BMI), and older age were also associated with increased risk of the condition.
The study was presented at the American Academy of Orthopaedic Surgeons 2023 Annual Meeting.
It has generally been thought that running may increase risk of osteoarthritis because it puts more load on joints than walking or standing, noted Grace Hsiao-Wei Lo, MD, an assistant professor of immunology, allergy, and rheumatology at the Baylor College of Medicine, Houston, who was not involved with the work. Research in this area has yielded mixed results: A 2017 analysis of multiple studies found that competitive runners did have higher rates of arthritis than recreational runners, while another study conducted by Dr. Lo found that runners did not have an increased risk of knee osteoarthritis, compared with nonrunners. A 2018 study showed that marathon runners had lower instances of arthritis, compared with the general population.
In this new study, researchers surveyed 3,804 runners who participated in the 2019 or 2021 Chicago Marathon about their running history, average mileage per week, and average running pace. The survey also asked about known risk factors for osteoarthritis, including BMI, family history of arthritis, and past knee and hip injuries that prevented running.
Runners, on average, were about 44 years old and ran 27.9 miles per week. The largest proportion of respondents had completed 2-5 marathons (37.3%), around 21% of respondents had finished 6-10 marathons, and 17% were running their first marathon. Study participants had an average of 15 years of running experience, 1,892 reported a previous hip or knee injury, and 413 had undergone knee or hip surgery. Overall, 36.4% reported experiencing hip or knee pain in the past year, and 7.3% had been diagnosed with arthritis.
Researchers found that there was no association between the risk of osteoarthritis and weekly mileage, years spent running, number of marathons completed, or running pace. Respondents who had undergone knee or hip surgery had the highest risk of osteoarthritis (odds ratio, 5.85; P < .0001), followed by those with a history of knee or hip injuries that prevented running (OR, 5.04; P < .0001). Other identified risk factors were family history of arthritis (OR, 3.47; P < .0001), BMI (OR, 1.10; P < .0001), and older age (OR, 1.08; P < .0001).
The news should be encouraging for runners, said Matthew Hartwell, MD, an orthopedic surgeon at the University of California, San Francisco, who led the research. If someone does not have injuries or surgeries that keep them from running, “you can still continue to run,” he said. “There may not necessarily be this dose-response relationship where the more you run, the more you break down your knee or your hip.”
Still, 24.2% of runners reported that their physician had advised them to reduce their mileage or stop running altogether. Most runners (94.2%) said they planned to run another marathon.
“The results of this study are consistent with the experiences of many lifelong runners and observations of sports medicine professionals that osteoarthritis is not an inevitable consequence of distance running,” said Brett Toresdahl, MD, a sports medicine physician at the Hospital for Special Surgery in New York, who was not involved with the study.
Still, he emphasized that more research is necessary to understand whether running contributes to the risk of developing osteoarthritis. The participants in the study were current marathoners, he noted, so it is likely they have healthy joints that can tolerate running longer distances. “If there is a subset of people who have joints that are negatively affected by running, they wouldn’t likely be registering for a marathon,” he said in an email interview.
Dr. Lo added that comparing these marathoners to a group who did not run would help assess whether running can be harmful to joints. “To be fair, this is a challenging subject to study,” she said. “Osteoarthritis has a long natural history, and so it is difficult to evaluate this kind of question over many years of running and many years of evaluation of arthritis.”
While the research does not answer the question of whether running can lead to osteoarthritis, it helps show the need for long-term research on how running affects joints over time as well as one’s general health, Dr. Toresdahl noted. “I would not be surprised if future longitudinal research will come to the same conclusion that running for the majority of patients is a net benefit for overall health and at least net neutral for joint health when done in moderation,” he said.
Dr. Hartwell, Dr. Lo, and Dr. Toresdahl report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Runners who had undergone knee or hip surgery or had a previous hip or knee injury that prevented running were most likely to have arthritis, researchers found. Family history of arthritis, higher body mass index (BMI), and older age were also associated with increased risk of the condition.
The study was presented at the American Academy of Orthopaedic Surgeons 2023 Annual Meeting.
It has generally been thought that running may increase risk of osteoarthritis because it puts more load on joints than walking or standing, noted Grace Hsiao-Wei Lo, MD, an assistant professor of immunology, allergy, and rheumatology at the Baylor College of Medicine, Houston, who was not involved with the work. Research in this area has yielded mixed results: A 2017 analysis of multiple studies found that competitive runners did have higher rates of arthritis than recreational runners, while another study conducted by Dr. Lo found that runners did not have an increased risk of knee osteoarthritis, compared with nonrunners. A 2018 study showed that marathon runners had lower instances of arthritis, compared with the general population.
In this new study, researchers surveyed 3,804 runners who participated in the 2019 or 2021 Chicago Marathon about their running history, average mileage per week, and average running pace. The survey also asked about known risk factors for osteoarthritis, including BMI, family history of arthritis, and past knee and hip injuries that prevented running.
Runners, on average, were about 44 years old and ran 27.9 miles per week. The largest proportion of respondents had completed 2-5 marathons (37.3%), around 21% of respondents had finished 6-10 marathons, and 17% were running their first marathon. Study participants had an average of 15 years of running experience, 1,892 reported a previous hip or knee injury, and 413 had undergone knee or hip surgery. Overall, 36.4% reported experiencing hip or knee pain in the past year, and 7.3% had been diagnosed with arthritis.
Researchers found that there was no association between the risk of osteoarthritis and weekly mileage, years spent running, number of marathons completed, or running pace. Respondents who had undergone knee or hip surgery had the highest risk of osteoarthritis (odds ratio, 5.85; P < .0001), followed by those with a history of knee or hip injuries that prevented running (OR, 5.04; P < .0001). Other identified risk factors were family history of arthritis (OR, 3.47; P < .0001), BMI (OR, 1.10; P < .0001), and older age (OR, 1.08; P < .0001).
The news should be encouraging for runners, said Matthew Hartwell, MD, an orthopedic surgeon at the University of California, San Francisco, who led the research. If someone does not have injuries or surgeries that keep them from running, “you can still continue to run,” he said. “There may not necessarily be this dose-response relationship where the more you run, the more you break down your knee or your hip.”
Still, 24.2% of runners reported that their physician had advised them to reduce their mileage or stop running altogether. Most runners (94.2%) said they planned to run another marathon.
“The results of this study are consistent with the experiences of many lifelong runners and observations of sports medicine professionals that osteoarthritis is not an inevitable consequence of distance running,” said Brett Toresdahl, MD, a sports medicine physician at the Hospital for Special Surgery in New York, who was not involved with the study.
Still, he emphasized that more research is necessary to understand whether running contributes to the risk of developing osteoarthritis. The participants in the study were current marathoners, he noted, so it is likely they have healthy joints that can tolerate running longer distances. “If there is a subset of people who have joints that are negatively affected by running, they wouldn’t likely be registering for a marathon,” he said in an email interview.
Dr. Lo added that comparing these marathoners to a group who did not run would help assess whether running can be harmful to joints. “To be fair, this is a challenging subject to study,” she said. “Osteoarthritis has a long natural history, and so it is difficult to evaluate this kind of question over many years of running and many years of evaluation of arthritis.”
While the research does not answer the question of whether running can lead to osteoarthritis, it helps show the need for long-term research on how running affects joints over time as well as one’s general health, Dr. Toresdahl noted. “I would not be surprised if future longitudinal research will come to the same conclusion that running for the majority of patients is a net benefit for overall health and at least net neutral for joint health when done in moderation,” he said.
Dr. Hartwell, Dr. Lo, and Dr. Toresdahl report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Runners who had undergone knee or hip surgery or had a previous hip or knee injury that prevented running were most likely to have arthritis, researchers found. Family history of arthritis, higher body mass index (BMI), and older age were also associated with increased risk of the condition.
The study was presented at the American Academy of Orthopaedic Surgeons 2023 Annual Meeting.
It has generally been thought that running may increase risk of osteoarthritis because it puts more load on joints than walking or standing, noted Grace Hsiao-Wei Lo, MD, an assistant professor of immunology, allergy, and rheumatology at the Baylor College of Medicine, Houston, who was not involved with the work. Research in this area has yielded mixed results: A 2017 analysis of multiple studies found that competitive runners did have higher rates of arthritis than recreational runners, while another study conducted by Dr. Lo found that runners did not have an increased risk of knee osteoarthritis, compared with nonrunners. A 2018 study showed that marathon runners had lower instances of arthritis, compared with the general population.
In this new study, researchers surveyed 3,804 runners who participated in the 2019 or 2021 Chicago Marathon about their running history, average mileage per week, and average running pace. The survey also asked about known risk factors for osteoarthritis, including BMI, family history of arthritis, and past knee and hip injuries that prevented running.
Runners, on average, were about 44 years old and ran 27.9 miles per week. The largest proportion of respondents had completed 2-5 marathons (37.3%), around 21% of respondents had finished 6-10 marathons, and 17% were running their first marathon. Study participants had an average of 15 years of running experience, 1,892 reported a previous hip or knee injury, and 413 had undergone knee or hip surgery. Overall, 36.4% reported experiencing hip or knee pain in the past year, and 7.3% had been diagnosed with arthritis.
Researchers found that there was no association between the risk of osteoarthritis and weekly mileage, years spent running, number of marathons completed, or running pace. Respondents who had undergone knee or hip surgery had the highest risk of osteoarthritis (odds ratio, 5.85; P < .0001), followed by those with a history of knee or hip injuries that prevented running (OR, 5.04; P < .0001). Other identified risk factors were family history of arthritis (OR, 3.47; P < .0001), BMI (OR, 1.10; P < .0001), and older age (OR, 1.08; P < .0001).
The news should be encouraging for runners, said Matthew Hartwell, MD, an orthopedic surgeon at the University of California, San Francisco, who led the research. If someone does not have injuries or surgeries that keep them from running, “you can still continue to run,” he said. “There may not necessarily be this dose-response relationship where the more you run, the more you break down your knee or your hip.”
Still, 24.2% of runners reported that their physician had advised them to reduce their mileage or stop running altogether. Most runners (94.2%) said they planned to run another marathon.
“The results of this study are consistent with the experiences of many lifelong runners and observations of sports medicine professionals that osteoarthritis is not an inevitable consequence of distance running,” said Brett Toresdahl, MD, a sports medicine physician at the Hospital for Special Surgery in New York, who was not involved with the study.
Still, he emphasized that more research is necessary to understand whether running contributes to the risk of developing osteoarthritis. The participants in the study were current marathoners, he noted, so it is likely they have healthy joints that can tolerate running longer distances. “If there is a subset of people who have joints that are negatively affected by running, they wouldn’t likely be registering for a marathon,” he said in an email interview.
Dr. Lo added that comparing these marathoners to a group who did not run would help assess whether running can be harmful to joints. “To be fair, this is a challenging subject to study,” she said. “Osteoarthritis has a long natural history, and so it is difficult to evaluate this kind of question over many years of running and many years of evaluation of arthritis.”
While the research does not answer the question of whether running can lead to osteoarthritis, it helps show the need for long-term research on how running affects joints over time as well as one’s general health, Dr. Toresdahl noted. “I would not be surprised if future longitudinal research will come to the same conclusion that running for the majority of patients is a net benefit for overall health and at least net neutral for joint health when done in moderation,” he said.
Dr. Hartwell, Dr. Lo, and Dr. Toresdahl report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAOS 2023
New rheumatologists need insurance awareness to give best care
SAN FRANCISCO – New rheumatologists face a wide range of significant challenges brought on by the increasing complexity of insurance billing and rapid changes to managed care practices, especially techniques of utilization management and pharmacy benefit managers (PBMs), speakers said at the 2023 Fellows Conference of the Coalition for State Rheumatology Organizations (CSRO).
“We are seeing the impact of the environment eroding the patient-doctor relationship,” CSRO President Gary Feldman, MD, told participants.
Michael Saitta, MD, MBA, a rheumatologist in Fayetteville, Ark., said fellows should learn more about health insurance to take better care of their patients and their practice. “Your training includes a variable level of discourse on the health insurance market,” he said. Health insurance today is a mess. Costs have exploded. “Is anybody really happy with the current system?”
Although the health care system is sometimes compared to a dumpster fire, he said, a plate of spaghetti, with its multiple interconnected pathways, might be a better metaphor for understanding all that’s happening in the health care system and, more importantly, how it might be fixed.
Madelaine Feldman, MD, a rheumatologist in private practice in New Orleans and CSRO’s vice president of advocacy and government affairs, is a frequent advocate in Congress, state legislatures, and elsewhere regarding the utilization management techniques used by managed care and PBMs and how these are negatively affecting the ability of rheumatology patients to get the treatments they need. Such techniques include the following:
- Prior authorizations imposed by the health plan before a medication can be dispensed.
- Step therapy, which requires the patient to fail as many as three or four payer-preferred drugs before trying the one recommended by the rheumatologist.
- Nonmedical switching, in which a patient is forced to change medications for a nonmedical reason related to the PBM’s formulary.
- Accumulator adjustment programs, which increase the patient’s out-of-pocket and deductible commitments.
“There is very little transparency in how the money flows with PBMs,” Dr. Madelaine Feldman said. “In reality, PBMs are able to make profits by the perverse incentive of putting higher-priced drugs on their formularies, thus increasing the amount of rebates paid to them, without sharing any of the benefit with patients.”
PBMs have resisted disclosing this information, saying it would inhibit competition and cause drug prices to go up. The key thing to understand, she said, is that there is huge competition today to get preferred formulary placement. “Consequently, treatment choice for patients is not based on doctor-patient shared decision-making but on the highest rebate promised to the PBM,” she said.
“A rheumatology fellow recently told me that his patients will sometimes blame him for the lack of choice and high prices of the medications,” she noted. What she has started to do with patients, after discussing all the available drugs appropriate to their condition, is to ask: “What is your insurance? The reason I’m asking is that we can come up with a game plan, but the entity that will determine what you will receive is the insurance company.”
What does Dr. Madelaine Feldman want fellows to take away from the CSRO conference? “I hope to arouse their anger, initially, which then works its way into a passion to change the system. We’re all so busy. Sometimes it takes lighting a fire under people,” she said.
CSRO has an online action center to facilitate sending letters to legislators, as well as a map tool for looking up any active legislation in their state. “Spread the word to your peers. Use your voice to help pass PBM reforms. Tell other fellows to come to the next CSRO fellows meeting,” she said.
“We got into this space because a few community rheumatologists were angry over decisions about how drug infusions would be paid for,” she said. “A group went to Washington, to Congress and Medicare, and changed the policy,” Dr. Madelaine Feldman said. A few passionate people really can make a difference. “Join the action. We’re always looking for rheumatologists and their patients to testify on these issues.”
No relevant financial relationships were reported by the conference speakers.
A version of this article originally appeared on Medscape.com.
SAN FRANCISCO – New rheumatologists face a wide range of significant challenges brought on by the increasing complexity of insurance billing and rapid changes to managed care practices, especially techniques of utilization management and pharmacy benefit managers (PBMs), speakers said at the 2023 Fellows Conference of the Coalition for State Rheumatology Organizations (CSRO).
“We are seeing the impact of the environment eroding the patient-doctor relationship,” CSRO President Gary Feldman, MD, told participants.
Michael Saitta, MD, MBA, a rheumatologist in Fayetteville, Ark., said fellows should learn more about health insurance to take better care of their patients and their practice. “Your training includes a variable level of discourse on the health insurance market,” he said. Health insurance today is a mess. Costs have exploded. “Is anybody really happy with the current system?”
Although the health care system is sometimes compared to a dumpster fire, he said, a plate of spaghetti, with its multiple interconnected pathways, might be a better metaphor for understanding all that’s happening in the health care system and, more importantly, how it might be fixed.
Madelaine Feldman, MD, a rheumatologist in private practice in New Orleans and CSRO’s vice president of advocacy and government affairs, is a frequent advocate in Congress, state legislatures, and elsewhere regarding the utilization management techniques used by managed care and PBMs and how these are negatively affecting the ability of rheumatology patients to get the treatments they need. Such techniques include the following:
- Prior authorizations imposed by the health plan before a medication can be dispensed.
- Step therapy, which requires the patient to fail as many as three or four payer-preferred drugs before trying the one recommended by the rheumatologist.
- Nonmedical switching, in which a patient is forced to change medications for a nonmedical reason related to the PBM’s formulary.
- Accumulator adjustment programs, which increase the patient’s out-of-pocket and deductible commitments.
“There is very little transparency in how the money flows with PBMs,” Dr. Madelaine Feldman said. “In reality, PBMs are able to make profits by the perverse incentive of putting higher-priced drugs on their formularies, thus increasing the amount of rebates paid to them, without sharing any of the benefit with patients.”
PBMs have resisted disclosing this information, saying it would inhibit competition and cause drug prices to go up. The key thing to understand, she said, is that there is huge competition today to get preferred formulary placement. “Consequently, treatment choice for patients is not based on doctor-patient shared decision-making but on the highest rebate promised to the PBM,” she said.
“A rheumatology fellow recently told me that his patients will sometimes blame him for the lack of choice and high prices of the medications,” she noted. What she has started to do with patients, after discussing all the available drugs appropriate to their condition, is to ask: “What is your insurance? The reason I’m asking is that we can come up with a game plan, but the entity that will determine what you will receive is the insurance company.”
What does Dr. Madelaine Feldman want fellows to take away from the CSRO conference? “I hope to arouse their anger, initially, which then works its way into a passion to change the system. We’re all so busy. Sometimes it takes lighting a fire under people,” she said.
CSRO has an online action center to facilitate sending letters to legislators, as well as a map tool for looking up any active legislation in their state. “Spread the word to your peers. Use your voice to help pass PBM reforms. Tell other fellows to come to the next CSRO fellows meeting,” she said.
“We got into this space because a few community rheumatologists were angry over decisions about how drug infusions would be paid for,” she said. “A group went to Washington, to Congress and Medicare, and changed the policy,” Dr. Madelaine Feldman said. A few passionate people really can make a difference. “Join the action. We’re always looking for rheumatologists and their patients to testify on these issues.”
No relevant financial relationships were reported by the conference speakers.
A version of this article originally appeared on Medscape.com.
SAN FRANCISCO – New rheumatologists face a wide range of significant challenges brought on by the increasing complexity of insurance billing and rapid changes to managed care practices, especially techniques of utilization management and pharmacy benefit managers (PBMs), speakers said at the 2023 Fellows Conference of the Coalition for State Rheumatology Organizations (CSRO).
“We are seeing the impact of the environment eroding the patient-doctor relationship,” CSRO President Gary Feldman, MD, told participants.
Michael Saitta, MD, MBA, a rheumatologist in Fayetteville, Ark., said fellows should learn more about health insurance to take better care of their patients and their practice. “Your training includes a variable level of discourse on the health insurance market,” he said. Health insurance today is a mess. Costs have exploded. “Is anybody really happy with the current system?”
Although the health care system is sometimes compared to a dumpster fire, he said, a plate of spaghetti, with its multiple interconnected pathways, might be a better metaphor for understanding all that’s happening in the health care system and, more importantly, how it might be fixed.
Madelaine Feldman, MD, a rheumatologist in private practice in New Orleans and CSRO’s vice president of advocacy and government affairs, is a frequent advocate in Congress, state legislatures, and elsewhere regarding the utilization management techniques used by managed care and PBMs and how these are negatively affecting the ability of rheumatology patients to get the treatments they need. Such techniques include the following:
- Prior authorizations imposed by the health plan before a medication can be dispensed.
- Step therapy, which requires the patient to fail as many as three or four payer-preferred drugs before trying the one recommended by the rheumatologist.
- Nonmedical switching, in which a patient is forced to change medications for a nonmedical reason related to the PBM’s formulary.
- Accumulator adjustment programs, which increase the patient’s out-of-pocket and deductible commitments.
“There is very little transparency in how the money flows with PBMs,” Dr. Madelaine Feldman said. “In reality, PBMs are able to make profits by the perverse incentive of putting higher-priced drugs on their formularies, thus increasing the amount of rebates paid to them, without sharing any of the benefit with patients.”
PBMs have resisted disclosing this information, saying it would inhibit competition and cause drug prices to go up. The key thing to understand, she said, is that there is huge competition today to get preferred formulary placement. “Consequently, treatment choice for patients is not based on doctor-patient shared decision-making but on the highest rebate promised to the PBM,” she said.
“A rheumatology fellow recently told me that his patients will sometimes blame him for the lack of choice and high prices of the medications,” she noted. What she has started to do with patients, after discussing all the available drugs appropriate to their condition, is to ask: “What is your insurance? The reason I’m asking is that we can come up with a game plan, but the entity that will determine what you will receive is the insurance company.”
What does Dr. Madelaine Feldman want fellows to take away from the CSRO conference? “I hope to arouse their anger, initially, which then works its way into a passion to change the system. We’re all so busy. Sometimes it takes lighting a fire under people,” she said.
CSRO has an online action center to facilitate sending letters to legislators, as well as a map tool for looking up any active legislation in their state. “Spread the word to your peers. Use your voice to help pass PBM reforms. Tell other fellows to come to the next CSRO fellows meeting,” she said.
“We got into this space because a few community rheumatologists were angry over decisions about how drug infusions would be paid for,” she said. “A group went to Washington, to Congress and Medicare, and changed the policy,” Dr. Madelaine Feldman said. A few passionate people really can make a difference. “Join the action. We’re always looking for rheumatologists and their patients to testify on these issues.”
No relevant financial relationships were reported by the conference speakers.
A version of this article originally appeared on Medscape.com.
Novel single-use patch shows promise for primary axillary hyperhidrosis
NEW ORLEANS – , results from a pivotal randomized trial showed.
“This is a new kind of device that is going to be a nice tool to have for treating patients who have hyperhidrosis of the axilla,” the study’s lead investigator, David M. Pariser, MD, who practices dermatology in Norfolk, Va., said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.
In a study known as SAHARA, investigators at 11 sites evaluated the efficacy of the targeted alkali thermolysis (TAT) patch, a single-use disposable device. The patch consists of a thin sodium layer on an adhesive overlay. It’s applied to the dry axilla, and as the patient sweats during treatment, the sweat reacts with the sodium. According to Dr. Pariser, this interaction generates precisely targeted thermal energy that targets sweat glands, leading to a reduction in excessive sweat production for up to three months.
The researchers enrolled 110 individuals with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 and randomized them to either an active TAT or a sham patch for up to 3 minutes. Their mean age was about 33 years, and slightly more than half were women. “If significant discomfort or pain was noted, [the patch] treatment was halted; otherwise, it was left on for 3 minutes,” said Dr. Pariser, professor of dermatology at Eastern Virginia Medical School, Norfolk. “The treated area was thoroughly cleaned after treatment, and the TAT patch was deactivated. This process was repeated on the other axilla.”
The HDSS, Gravimetric Sweat Production (GSP), and quality of life assessments for bother and impact were measured through 12 weeks. The quality of life assessments were an exploratory endpoint and scored from 0 to 4, with 4 being extremely bothered or impacted and 0 not being bothered or impacted at all. The primary efficacy endpoint was the proportion of treated patients achieving a 1 or 2 on the HDSS at week 4, compared with sham treatment.
Secondary endpoints included the proportion of patients with an improvement of at least 2 grades from baseline to 4 weeks in HDSS by treatment group; mean improvement in the quality of life scale bother by treatment group; mean improvement in the quality of life scale impact by treatment group; and the proportion of subjects with at least 50% improvement in GSP from baseline to 4 weeks in the active patch group only.
Adverse events (AEs) were divided into 3 categories: AEs at the treatment site (or skin reactions within the treated part of the axilla); procedure-related AEs (those that are the result of treatment, but not in the treated part of the axilla), and non-axillary AEs.
Dr. Pariser reported that at 4 weeks, 63.6% of patients in the active patch group versus 44.2% of those in the sham group improved to an HDSS score of 1 or 2 (P = .0332) and that 43.2% of those in the active patch group versus 16.3% of those in the sham group (P = .0107) achieved a 2-point or greater HDSS improvement. In addition, 9.1% of those in the active patch group achieved a 3-point improvement on the HDSS, compared with none in the sham group. “That’s an amazing improvement; you’re basically going from moderate or severe to none,” he commented.
In other findings, 60.5% of patients in the active patch group showed at least a 50% reduction in GSP, compared with 32.6% of those in the sham group (P = .0102), with mean reductions of 57.3 mg/5min and 18.2 mg/5min, respectively (P = .0036). As for quality-of-life outcome scores, bother associated with hyperhidrosis was reduced by 1.52 points in active versus 0.61 in sham subjects (P = .0005), while impact was reduced by 1.44 in active versus 0.57 in sham subjects (P = .0004).
Adverse events
A total of 13 patients in the active patch group experienced AEs at the treatment site, including six with erythema; four with erosion; two with burning, itching or stinging; and one with underarm odor. “The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” said Dr. Pariser said.
Most adverse events resolved in fewer than 2 weeks, and all were mild to moderate. No serious adverse events occurred. Only five adverse events occurred in the sham group.
The TAT patch is currently undergoing review by the Food and Drug Administration, and according to Dr. Pariser, no other body sites have been treated with the device.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, characterized hyperhidrosis as “an exceedingly common medical condition that is commonly overlooked even though it has a tremendous burden on quality of life. I should know, as both someone who manages a large cohort of these patients but also as someone who suffers from it.”
Treatment options “have historically been limited, many of which are off-label and some which are difficult to access due to cost and/or duration/frequency of treatment,” added Dr. Friedman, who was not involved with the study. “The TAT patch offers a new, targeted, in-office, practical procedure-based approach to treat primary axillary hyperhidrosis. Innovation is certainly welcomed and needed, and I am curious to see how this technology is employed in practice once approved.”
The device is being developed by Candesant Biomedical. Dr. Pariser disclosed that he is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol Myers Squibb, Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.
Dr. Friedman reported having no relevant disclosures.
NEW ORLEANS – , results from a pivotal randomized trial showed.
“This is a new kind of device that is going to be a nice tool to have for treating patients who have hyperhidrosis of the axilla,” the study’s lead investigator, David M. Pariser, MD, who practices dermatology in Norfolk, Va., said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.
In a study known as SAHARA, investigators at 11 sites evaluated the efficacy of the targeted alkali thermolysis (TAT) patch, a single-use disposable device. The patch consists of a thin sodium layer on an adhesive overlay. It’s applied to the dry axilla, and as the patient sweats during treatment, the sweat reacts with the sodium. According to Dr. Pariser, this interaction generates precisely targeted thermal energy that targets sweat glands, leading to a reduction in excessive sweat production for up to three months.
The researchers enrolled 110 individuals with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 and randomized them to either an active TAT or a sham patch for up to 3 minutes. Their mean age was about 33 years, and slightly more than half were women. “If significant discomfort or pain was noted, [the patch] treatment was halted; otherwise, it was left on for 3 minutes,” said Dr. Pariser, professor of dermatology at Eastern Virginia Medical School, Norfolk. “The treated area was thoroughly cleaned after treatment, and the TAT patch was deactivated. This process was repeated on the other axilla.”
The HDSS, Gravimetric Sweat Production (GSP), and quality of life assessments for bother and impact were measured through 12 weeks. The quality of life assessments were an exploratory endpoint and scored from 0 to 4, with 4 being extremely bothered or impacted and 0 not being bothered or impacted at all. The primary efficacy endpoint was the proportion of treated patients achieving a 1 or 2 on the HDSS at week 4, compared with sham treatment.
Secondary endpoints included the proportion of patients with an improvement of at least 2 grades from baseline to 4 weeks in HDSS by treatment group; mean improvement in the quality of life scale bother by treatment group; mean improvement in the quality of life scale impact by treatment group; and the proportion of subjects with at least 50% improvement in GSP from baseline to 4 weeks in the active patch group only.
Adverse events (AEs) were divided into 3 categories: AEs at the treatment site (or skin reactions within the treated part of the axilla); procedure-related AEs (those that are the result of treatment, but not in the treated part of the axilla), and non-axillary AEs.
Dr. Pariser reported that at 4 weeks, 63.6% of patients in the active patch group versus 44.2% of those in the sham group improved to an HDSS score of 1 or 2 (P = .0332) and that 43.2% of those in the active patch group versus 16.3% of those in the sham group (P = .0107) achieved a 2-point or greater HDSS improvement. In addition, 9.1% of those in the active patch group achieved a 3-point improvement on the HDSS, compared with none in the sham group. “That’s an amazing improvement; you’re basically going from moderate or severe to none,” he commented.
In other findings, 60.5% of patients in the active patch group showed at least a 50% reduction in GSP, compared with 32.6% of those in the sham group (P = .0102), with mean reductions of 57.3 mg/5min and 18.2 mg/5min, respectively (P = .0036). As for quality-of-life outcome scores, bother associated with hyperhidrosis was reduced by 1.52 points in active versus 0.61 in sham subjects (P = .0005), while impact was reduced by 1.44 in active versus 0.57 in sham subjects (P = .0004).
Adverse events
A total of 13 patients in the active patch group experienced AEs at the treatment site, including six with erythema; four with erosion; two with burning, itching or stinging; and one with underarm odor. “The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” said Dr. Pariser said.
Most adverse events resolved in fewer than 2 weeks, and all were mild to moderate. No serious adverse events occurred. Only five adverse events occurred in the sham group.
The TAT patch is currently undergoing review by the Food and Drug Administration, and according to Dr. Pariser, no other body sites have been treated with the device.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, characterized hyperhidrosis as “an exceedingly common medical condition that is commonly overlooked even though it has a tremendous burden on quality of life. I should know, as both someone who manages a large cohort of these patients but also as someone who suffers from it.”
Treatment options “have historically been limited, many of which are off-label and some which are difficult to access due to cost and/or duration/frequency of treatment,” added Dr. Friedman, who was not involved with the study. “The TAT patch offers a new, targeted, in-office, practical procedure-based approach to treat primary axillary hyperhidrosis. Innovation is certainly welcomed and needed, and I am curious to see how this technology is employed in practice once approved.”
The device is being developed by Candesant Biomedical. Dr. Pariser disclosed that he is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol Myers Squibb, Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.
Dr. Friedman reported having no relevant disclosures.
NEW ORLEANS – , results from a pivotal randomized trial showed.
“This is a new kind of device that is going to be a nice tool to have for treating patients who have hyperhidrosis of the axilla,” the study’s lead investigator, David M. Pariser, MD, who practices dermatology in Norfolk, Va., said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.
In a study known as SAHARA, investigators at 11 sites evaluated the efficacy of the targeted alkali thermolysis (TAT) patch, a single-use disposable device. The patch consists of a thin sodium layer on an adhesive overlay. It’s applied to the dry axilla, and as the patient sweats during treatment, the sweat reacts with the sodium. According to Dr. Pariser, this interaction generates precisely targeted thermal energy that targets sweat glands, leading to a reduction in excessive sweat production for up to three months.
The researchers enrolled 110 individuals with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 and randomized them to either an active TAT or a sham patch for up to 3 minutes. Their mean age was about 33 years, and slightly more than half were women. “If significant discomfort or pain was noted, [the patch] treatment was halted; otherwise, it was left on for 3 minutes,” said Dr. Pariser, professor of dermatology at Eastern Virginia Medical School, Norfolk. “The treated area was thoroughly cleaned after treatment, and the TAT patch was deactivated. This process was repeated on the other axilla.”
The HDSS, Gravimetric Sweat Production (GSP), and quality of life assessments for bother and impact were measured through 12 weeks. The quality of life assessments were an exploratory endpoint and scored from 0 to 4, with 4 being extremely bothered or impacted and 0 not being bothered or impacted at all. The primary efficacy endpoint was the proportion of treated patients achieving a 1 or 2 on the HDSS at week 4, compared with sham treatment.
Secondary endpoints included the proportion of patients with an improvement of at least 2 grades from baseline to 4 weeks in HDSS by treatment group; mean improvement in the quality of life scale bother by treatment group; mean improvement in the quality of life scale impact by treatment group; and the proportion of subjects with at least 50% improvement in GSP from baseline to 4 weeks in the active patch group only.
Adverse events (AEs) were divided into 3 categories: AEs at the treatment site (or skin reactions within the treated part of the axilla); procedure-related AEs (those that are the result of treatment, but not in the treated part of the axilla), and non-axillary AEs.
Dr. Pariser reported that at 4 weeks, 63.6% of patients in the active patch group versus 44.2% of those in the sham group improved to an HDSS score of 1 or 2 (P = .0332) and that 43.2% of those in the active patch group versus 16.3% of those in the sham group (P = .0107) achieved a 2-point or greater HDSS improvement. In addition, 9.1% of those in the active patch group achieved a 3-point improvement on the HDSS, compared with none in the sham group. “That’s an amazing improvement; you’re basically going from moderate or severe to none,” he commented.
In other findings, 60.5% of patients in the active patch group showed at least a 50% reduction in GSP, compared with 32.6% of those in the sham group (P = .0102), with mean reductions of 57.3 mg/5min and 18.2 mg/5min, respectively (P = .0036). As for quality-of-life outcome scores, bother associated with hyperhidrosis was reduced by 1.52 points in active versus 0.61 in sham subjects (P = .0005), while impact was reduced by 1.44 in active versus 0.57 in sham subjects (P = .0004).
Adverse events
A total of 13 patients in the active patch group experienced AEs at the treatment site, including six with erythema; four with erosion; two with burning, itching or stinging; and one with underarm odor. “The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” said Dr. Pariser said.
Most adverse events resolved in fewer than 2 weeks, and all were mild to moderate. No serious adverse events occurred. Only five adverse events occurred in the sham group.
The TAT patch is currently undergoing review by the Food and Drug Administration, and according to Dr. Pariser, no other body sites have been treated with the device.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, characterized hyperhidrosis as “an exceedingly common medical condition that is commonly overlooked even though it has a tremendous burden on quality of life. I should know, as both someone who manages a large cohort of these patients but also as someone who suffers from it.”
Treatment options “have historically been limited, many of which are off-label and some which are difficult to access due to cost and/or duration/frequency of treatment,” added Dr. Friedman, who was not involved with the study. “The TAT patch offers a new, targeted, in-office, practical procedure-based approach to treat primary axillary hyperhidrosis. Innovation is certainly welcomed and needed, and I am curious to see how this technology is employed in practice once approved.”
The device is being developed by Candesant Biomedical. Dr. Pariser disclosed that he is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol Myers Squibb, Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.
Dr. Friedman reported having no relevant disclosures.
AT AAD 2023
CSU in children: Study identifies biomarkers associated with responses to different treatments
NEW ORLEANS – , results from a single-center prospective study showed.
“Given that the majority of CSU cases in adults are due to autoimmunity and there being very [few] studies on biomarkers for CSU in children, our study furthers our current understanding of the role of different biomarkers in treatment response,” lead study author Alex Nguyen, MsC, said in an interview at the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
To identify biomarkers with treatment and disease resolution in children with CSU, Mr. Nguyen, a 4-year medical student at McGill University, Montreal, and colleagues prospectively recruited 109 children from the Montreal Children’s Hospital Allergy and Immunology Clinic who reported hives for at least 6 weeks from 2013 to 2022. They obtained levels of thyroid stimulating hormone (TSH), anti-thyroxine peroxidase (anti-TPO), total immunoglobulin E (IgE), CD63, tryptase, eosinophils, MPV, and platelets; the weekly urticaria activity score (UAS7) was recorded at study entry.
Levels of treatment included antihistamines at standard dose, four times the standard dose, omalizumab, and resolution of treatment. The researchers used univariate and multivariate logistic regressions to determine factors associated with different treatment levels and resolution.
Slightly more than half of the study participants (55%) were female, and their mean age was 9 years. Mr. Nguyen and colleagues observed that elevated MPV was associated with the four times increased dose of antihistamines treatment level (odds ratio = 1.052, 95% confidence interval = 1.004-1.103). Lower age was associated with disease resolution (OR = 0.982, 95% CI = 0.965-0.999).
After adjustment for age, sex, TSH, anti-TPO, total IgE, CD63, eosinophils, MPV, and platelets, elevated tryptase was associated with the antihistamine use at standard dose level (OR = 1.152, 95% CI = 1.019-1.302) and lower tryptase levels with disease resolution (OR = .861, 95% CI = 0.777-0.955).
“We were fascinated when we found that tryptase levels in patients with chronic spontaneous urticaria were associated with standard dose of antihistamines and even disease resolution,” Mr. Nguyen said. “Higher tryptase levels were associated with standard dose antihistamines, which potentially could imply an increase in mast cell activation. Furthermore, we saw that lower tryptase levels were associated with disease resolution likely given if the disease may not have been as severe.”
He acknowledged certain limitations of the study, including a limited sample size and an unbalanced sample size among treatment groups. In the future, he and his colleagues plan to increase the sample size and to include other biomarkers such as interleukin (IL)-6, D-dimer, vitamin D, and matrix mettaloproteinase-9.
“Much as the name suggests, CSU often arises without a clear trigger,” said Raj Chovatiya, MD, PhD, assistant professor in the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study. “Particularly in children, little is known about potential biomarkers that may guide treatment or disease resolution. While a larger, prospective analysis would better characterize temporal trends in serum biomarkers in relation to disease activity, these data suggest that underlying mechanisms of tryptase may be worth an in-depth look in children with CSU.”
The study was recognized as the second-best poster at the meeting. The researchers reported having no financial disclosures. The other study coauthors were Michelle Le MD, Sofianne Gabrielli MSc, Elena Netchiporouk, MD, MSc, and Moshe Ben-Shoshan, MD, MSc. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for several pharmaceutical companies.
NEW ORLEANS – , results from a single-center prospective study showed.
“Given that the majority of CSU cases in adults are due to autoimmunity and there being very [few] studies on biomarkers for CSU in children, our study furthers our current understanding of the role of different biomarkers in treatment response,” lead study author Alex Nguyen, MsC, said in an interview at the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
To identify biomarkers with treatment and disease resolution in children with CSU, Mr. Nguyen, a 4-year medical student at McGill University, Montreal, and colleagues prospectively recruited 109 children from the Montreal Children’s Hospital Allergy and Immunology Clinic who reported hives for at least 6 weeks from 2013 to 2022. They obtained levels of thyroid stimulating hormone (TSH), anti-thyroxine peroxidase (anti-TPO), total immunoglobulin E (IgE), CD63, tryptase, eosinophils, MPV, and platelets; the weekly urticaria activity score (UAS7) was recorded at study entry.
Levels of treatment included antihistamines at standard dose, four times the standard dose, omalizumab, and resolution of treatment. The researchers used univariate and multivariate logistic regressions to determine factors associated with different treatment levels and resolution.
Slightly more than half of the study participants (55%) were female, and their mean age was 9 years. Mr. Nguyen and colleagues observed that elevated MPV was associated with the four times increased dose of antihistamines treatment level (odds ratio = 1.052, 95% confidence interval = 1.004-1.103). Lower age was associated with disease resolution (OR = 0.982, 95% CI = 0.965-0.999).
After adjustment for age, sex, TSH, anti-TPO, total IgE, CD63, eosinophils, MPV, and platelets, elevated tryptase was associated with the antihistamine use at standard dose level (OR = 1.152, 95% CI = 1.019-1.302) and lower tryptase levels with disease resolution (OR = .861, 95% CI = 0.777-0.955).
“We were fascinated when we found that tryptase levels in patients with chronic spontaneous urticaria were associated with standard dose of antihistamines and even disease resolution,” Mr. Nguyen said. “Higher tryptase levels were associated with standard dose antihistamines, which potentially could imply an increase in mast cell activation. Furthermore, we saw that lower tryptase levels were associated with disease resolution likely given if the disease may not have been as severe.”
He acknowledged certain limitations of the study, including a limited sample size and an unbalanced sample size among treatment groups. In the future, he and his colleagues plan to increase the sample size and to include other biomarkers such as interleukin (IL)-6, D-dimer, vitamin D, and matrix mettaloproteinase-9.
“Much as the name suggests, CSU often arises without a clear trigger,” said Raj Chovatiya, MD, PhD, assistant professor in the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study. “Particularly in children, little is known about potential biomarkers that may guide treatment or disease resolution. While a larger, prospective analysis would better characterize temporal trends in serum biomarkers in relation to disease activity, these data suggest that underlying mechanisms of tryptase may be worth an in-depth look in children with CSU.”
The study was recognized as the second-best poster at the meeting. The researchers reported having no financial disclosures. The other study coauthors were Michelle Le MD, Sofianne Gabrielli MSc, Elena Netchiporouk, MD, MSc, and Moshe Ben-Shoshan, MD, MSc. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for several pharmaceutical companies.
NEW ORLEANS – , results from a single-center prospective study showed.
“Given that the majority of CSU cases in adults are due to autoimmunity and there being very [few] studies on biomarkers for CSU in children, our study furthers our current understanding of the role of different biomarkers in treatment response,” lead study author Alex Nguyen, MsC, said in an interview at the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
To identify biomarkers with treatment and disease resolution in children with CSU, Mr. Nguyen, a 4-year medical student at McGill University, Montreal, and colleagues prospectively recruited 109 children from the Montreal Children’s Hospital Allergy and Immunology Clinic who reported hives for at least 6 weeks from 2013 to 2022. They obtained levels of thyroid stimulating hormone (TSH), anti-thyroxine peroxidase (anti-TPO), total immunoglobulin E (IgE), CD63, tryptase, eosinophils, MPV, and platelets; the weekly urticaria activity score (UAS7) was recorded at study entry.
Levels of treatment included antihistamines at standard dose, four times the standard dose, omalizumab, and resolution of treatment. The researchers used univariate and multivariate logistic regressions to determine factors associated with different treatment levels and resolution.
Slightly more than half of the study participants (55%) were female, and their mean age was 9 years. Mr. Nguyen and colleagues observed that elevated MPV was associated with the four times increased dose of antihistamines treatment level (odds ratio = 1.052, 95% confidence interval = 1.004-1.103). Lower age was associated with disease resolution (OR = 0.982, 95% CI = 0.965-0.999).
After adjustment for age, sex, TSH, anti-TPO, total IgE, CD63, eosinophils, MPV, and platelets, elevated tryptase was associated with the antihistamine use at standard dose level (OR = 1.152, 95% CI = 1.019-1.302) and lower tryptase levels with disease resolution (OR = .861, 95% CI = 0.777-0.955).
“We were fascinated when we found that tryptase levels in patients with chronic spontaneous urticaria were associated with standard dose of antihistamines and even disease resolution,” Mr. Nguyen said. “Higher tryptase levels were associated with standard dose antihistamines, which potentially could imply an increase in mast cell activation. Furthermore, we saw that lower tryptase levels were associated with disease resolution likely given if the disease may not have been as severe.”
He acknowledged certain limitations of the study, including a limited sample size and an unbalanced sample size among treatment groups. In the future, he and his colleagues plan to increase the sample size and to include other biomarkers such as interleukin (IL)-6, D-dimer, vitamin D, and matrix mettaloproteinase-9.
“Much as the name suggests, CSU often arises without a clear trigger,” said Raj Chovatiya, MD, PhD, assistant professor in the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study. “Particularly in children, little is known about potential biomarkers that may guide treatment or disease resolution. While a larger, prospective analysis would better characterize temporal trends in serum biomarkers in relation to disease activity, these data suggest that underlying mechanisms of tryptase may be worth an in-depth look in children with CSU.”
The study was recognized as the second-best poster at the meeting. The researchers reported having no financial disclosures. The other study coauthors were Michelle Le MD, Sofianne Gabrielli MSc, Elena Netchiporouk, MD, MSc, and Moshe Ben-Shoshan, MD, MSc. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for several pharmaceutical companies.
AT AAD 2023
JAK inhibitor safety warnings drawn from rheumatologic data may be misleading in dermatology
NEW ORLEANS – , even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.
Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.
The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream.
Basis of boxed warnings
In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m2.
After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.
In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.
Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
Evidence of difference in dermatology
There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.
For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.
When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.
Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.
“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.
Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.
Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”
“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
Risk-benefit considerations in dermatology
This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.
Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.
“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”
George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.
“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.
“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”
Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.
Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.
A version of this article originally appeared on Medscape.com.
NEW ORLEANS – , even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.
Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.
The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream.
Basis of boxed warnings
In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m2.
After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.
In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.
Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
Evidence of difference in dermatology
There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.
For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.
When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.
Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.
“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.
Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.
Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”
“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
Risk-benefit considerations in dermatology
This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.
Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.
“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”
George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.
“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.
“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”
Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.
Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.
A version of this article originally appeared on Medscape.com.
NEW ORLEANS – , even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.
Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.
The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream.
Basis of boxed warnings
In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m2.
After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.
In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.
Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
Evidence of difference in dermatology
There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.
For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.
When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.
Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.
“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.
Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.
Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”
“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
Risk-benefit considerations in dermatology
This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.
Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.
“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”
George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.
“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.
“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”
Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.
Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.
A version of this article originally appeared on Medscape.com.
AT AAD 2023
Lanolin gets nod for Allergen of the Year
Lanolin is a complex and varying mixture of high molecular weight esters, aliphatic alcohols, sterols, fatty acids, and hydrocarbons, but the allergic components are mainly the free lanolin alcohols, especially alkanediols, said Donald V. Belsito, MD, professor of dermatology, Columbia University, New York, who announced the Allergen of the Year at the society’s annual meeting.
Criteria for selection can include a known allergen with a new twist or increasing frequency or a newly reported allergen with mini-epidemics that may have been missed for years, Dr. Belsito said.
“The prevalence and severity of allergy to ‘lanolin’ have been hotly debated” since a potential case was first reported in the 1920s, wrote Dr. Belsito and Blair A. Jenkins, MD, PhD, a dermatology resident at New York–Presbyterian Hospital, Columbia Campus, in a review published in Dermatitis.
“ ‘Lanolin’ is indeed a paradox allergen,” wrote Dr. Jenkins and Dr. Belsito. “The most appropriate patch test preparation(s) for detecting allergy remain disputed. Detection of lanolin-induced contact dermatitis in diseased skin by patch testing on normal skin may lead to false negative results.”
And those who test positive for a lanolin allergy on diseased skin may be able to use lanolin products on normal skin, they wrote.
“From my perspective, this was a timely year to think about lanolin, as there is significant ongoing controversy about whether it is allergenic,” Dr. Jenkins said in an interview. “Numerous companies market lanolin-containing topicals as safe and effective emollients,” she said.
Medical grade and highly purified anhydrous lanolin, which contain less than 2.5% and less than 1.5% of free alcohols, respectively, can still elicit or induce a contact allergy, Dr. Belsito said in his presentation. Hydrogenated lanolin has shown more allergenicity than lanolin alcohol, while lanolin wax, lanolin acid, and lanolin esters possess lower allergenicity than lanolin alcohol, he said.
Notably, modern wool textiles do not contain lanolin, and lanolin-allergic patients need not avoid wool, Dr. Belsito added.
Amerchol L-101, a common trade name on products containing lanolin, contains 10% wool wax alcohols obtained from the hydrolysis of wool fat dissolved in mineral oil at a 1:1 ratio, said Dr. Belsito. He recommended testing lanolin alcohols (in 30% petrolatum) and Amerchol L-101 (in 50% petrolatum) simultaneously with or without other lanolin derivatives and/or the patient’s products in cases of possible allergy, he said.
Consider high-risk groups
Current evidence suggests that the prevalence of contact allergy in the western European population is 0.4%, wrote Dr. Jenkins and Dr. Belsito.
Although the frequency of lanolin allergy is relatively low, certain conditions convey greater risk, such as stasis dermatitis, leg ulcers, perianal/genital dermatitis, and atopic dermatitis, they wrote. Older adults and children are at increased risk because they are more likely to have these conditions. Demographic data also suggest that lanolin allergy is more common in non-Hispanic Whites than in non-Hispanic Blacks, they wrote.
Looking ahead, “I think further exploration of allergy across different skin types and ethnicities is warranted,” Dr. Jenkins said. “Further investigation of ideal [lanolin] allergens for patch testing is also needed.”
Dr. Jenkins and Dr. Belsito said they had no relevant financial conflicts to disclose.
Lanolin is a complex and varying mixture of high molecular weight esters, aliphatic alcohols, sterols, fatty acids, and hydrocarbons, but the allergic components are mainly the free lanolin alcohols, especially alkanediols, said Donald V. Belsito, MD, professor of dermatology, Columbia University, New York, who announced the Allergen of the Year at the society’s annual meeting.
Criteria for selection can include a known allergen with a new twist or increasing frequency or a newly reported allergen with mini-epidemics that may have been missed for years, Dr. Belsito said.
“The prevalence and severity of allergy to ‘lanolin’ have been hotly debated” since a potential case was first reported in the 1920s, wrote Dr. Belsito and Blair A. Jenkins, MD, PhD, a dermatology resident at New York–Presbyterian Hospital, Columbia Campus, in a review published in Dermatitis.
“ ‘Lanolin’ is indeed a paradox allergen,” wrote Dr. Jenkins and Dr. Belsito. “The most appropriate patch test preparation(s) for detecting allergy remain disputed. Detection of lanolin-induced contact dermatitis in diseased skin by patch testing on normal skin may lead to false negative results.”
And those who test positive for a lanolin allergy on diseased skin may be able to use lanolin products on normal skin, they wrote.
“From my perspective, this was a timely year to think about lanolin, as there is significant ongoing controversy about whether it is allergenic,” Dr. Jenkins said in an interview. “Numerous companies market lanolin-containing topicals as safe and effective emollients,” she said.
Medical grade and highly purified anhydrous lanolin, which contain less than 2.5% and less than 1.5% of free alcohols, respectively, can still elicit or induce a contact allergy, Dr. Belsito said in his presentation. Hydrogenated lanolin has shown more allergenicity than lanolin alcohol, while lanolin wax, lanolin acid, and lanolin esters possess lower allergenicity than lanolin alcohol, he said.
Notably, modern wool textiles do not contain lanolin, and lanolin-allergic patients need not avoid wool, Dr. Belsito added.
Amerchol L-101, a common trade name on products containing lanolin, contains 10% wool wax alcohols obtained from the hydrolysis of wool fat dissolved in mineral oil at a 1:1 ratio, said Dr. Belsito. He recommended testing lanolin alcohols (in 30% petrolatum) and Amerchol L-101 (in 50% petrolatum) simultaneously with or without other lanolin derivatives and/or the patient’s products in cases of possible allergy, he said.
Consider high-risk groups
Current evidence suggests that the prevalence of contact allergy in the western European population is 0.4%, wrote Dr. Jenkins and Dr. Belsito.
Although the frequency of lanolin allergy is relatively low, certain conditions convey greater risk, such as stasis dermatitis, leg ulcers, perianal/genital dermatitis, and atopic dermatitis, they wrote. Older adults and children are at increased risk because they are more likely to have these conditions. Demographic data also suggest that lanolin allergy is more common in non-Hispanic Whites than in non-Hispanic Blacks, they wrote.
Looking ahead, “I think further exploration of allergy across different skin types and ethnicities is warranted,” Dr. Jenkins said. “Further investigation of ideal [lanolin] allergens for patch testing is also needed.”
Dr. Jenkins and Dr. Belsito said they had no relevant financial conflicts to disclose.
Lanolin is a complex and varying mixture of high molecular weight esters, aliphatic alcohols, sterols, fatty acids, and hydrocarbons, but the allergic components are mainly the free lanolin alcohols, especially alkanediols, said Donald V. Belsito, MD, professor of dermatology, Columbia University, New York, who announced the Allergen of the Year at the society’s annual meeting.
Criteria for selection can include a known allergen with a new twist or increasing frequency or a newly reported allergen with mini-epidemics that may have been missed for years, Dr. Belsito said.
“The prevalence and severity of allergy to ‘lanolin’ have been hotly debated” since a potential case was first reported in the 1920s, wrote Dr. Belsito and Blair A. Jenkins, MD, PhD, a dermatology resident at New York–Presbyterian Hospital, Columbia Campus, in a review published in Dermatitis.
“ ‘Lanolin’ is indeed a paradox allergen,” wrote Dr. Jenkins and Dr. Belsito. “The most appropriate patch test preparation(s) for detecting allergy remain disputed. Detection of lanolin-induced contact dermatitis in diseased skin by patch testing on normal skin may lead to false negative results.”
And those who test positive for a lanolin allergy on diseased skin may be able to use lanolin products on normal skin, they wrote.
“From my perspective, this was a timely year to think about lanolin, as there is significant ongoing controversy about whether it is allergenic,” Dr. Jenkins said in an interview. “Numerous companies market lanolin-containing topicals as safe and effective emollients,” she said.
Medical grade and highly purified anhydrous lanolin, which contain less than 2.5% and less than 1.5% of free alcohols, respectively, can still elicit or induce a contact allergy, Dr. Belsito said in his presentation. Hydrogenated lanolin has shown more allergenicity than lanolin alcohol, while lanolin wax, lanolin acid, and lanolin esters possess lower allergenicity than lanolin alcohol, he said.
Notably, modern wool textiles do not contain lanolin, and lanolin-allergic patients need not avoid wool, Dr. Belsito added.
Amerchol L-101, a common trade name on products containing lanolin, contains 10% wool wax alcohols obtained from the hydrolysis of wool fat dissolved in mineral oil at a 1:1 ratio, said Dr. Belsito. He recommended testing lanolin alcohols (in 30% petrolatum) and Amerchol L-101 (in 50% petrolatum) simultaneously with or without other lanolin derivatives and/or the patient’s products in cases of possible allergy, he said.
Consider high-risk groups
Current evidence suggests that the prevalence of contact allergy in the western European population is 0.4%, wrote Dr. Jenkins and Dr. Belsito.
Although the frequency of lanolin allergy is relatively low, certain conditions convey greater risk, such as stasis dermatitis, leg ulcers, perianal/genital dermatitis, and atopic dermatitis, they wrote. Older adults and children are at increased risk because they are more likely to have these conditions. Demographic data also suggest that lanolin allergy is more common in non-Hispanic Whites than in non-Hispanic Blacks, they wrote.
Looking ahead, “I think further exploration of allergy across different skin types and ethnicities is warranted,” Dr. Jenkins said. “Further investigation of ideal [lanolin] allergens for patch testing is also needed.”
Dr. Jenkins and Dr. Belsito said they had no relevant financial conflicts to disclose.
FROM ACDS 2023