Clinical Trials May Overestimate Benefits of Psoriasis Drugs

RALEIGH, N.C. – Absolute differences in response rates for treatments of moderate to severe plaque psoriasis as commonly used in everyday clinical practice "are small and may not be clinically significant," Dr. Joy Wan said at the annual meeting of the Society for Investigative Dermatology.

The results of a multicenter, comparative effectiveness study provide a picture of how psoriasis treatments are performing in real-world practice as opposed to the setting of clinical trials, which typically feature a nonrepresentative patient population and physician investigators having expertise in the treatment under study, according to Dr. Wan.

The results suggest that the go-to treatments for moderate to severe plaque psoriasis aren’t as effective in routine practice as they were in randomized trials (Arch. Dermatol. 2012;148:487-94). For example, only 48% of patients on adalimumab (Humira) were clear or almost clear based on Physician Global Assessment (PGA) ratings, compared with a 73% rate in an earlier clinical trial, noted Dr. Wan of the University of Pennsylvania, Philadelphia.

The comparative effectiveness study was cross sectional, and involved 713 consecutive patients with moderate to severe plaque psoriasis seen for routine follow-up care in 10 practices participating in the Dermatology Clinical Effectiveness Research Network (DCERN), a nationwide network of private and academic dermatology practices established in 2010.

The study participants (mean age, 49 years; 50% men) had a median 19-year duration of psoriasis; 23% also had psoriatic arthritis. All patients in the study were on monotherapy with methotrexate, etanercept, adalimumab, ustekinumab, or narrow-band UVB phototherapy (NBUVB). In all, 27% of the patients were on etanercept, 24% on methotrexate, 21% on adalimumab, 17% on NBUVB, and the rest on ustekinumab. Patients had been on methotrexate, adalimumab, or etanercept for a median of 12 months; ustekinumab for 4 months; and NBUVB for 2 months. On average, participants had been on only one systemic therapy or phototherapy prior to their current treatment. Patients were evaluated using PGA ratings and the Dermatology Life Quality Index.

One striking finding, noted Dr. Wan, was that recommended dosing often was not optimal. Notably, 36% of patients on etanercept were on 50 mg twice weekly and 12% on adalimumab were on 40 mg once weekly; those are double the recommended maintenance doses based on clinical trial data. And only 11% of patients on NBUVB received the optimal dosing frequency of at least 12 sessions within the previous 4 weeks.

The primary study end point was the proportion of patients rated clear or almost clear on PGA. The rates were 24% with methotrexate, 48% with adalimumab, 34% with etanercept, 36% for ustekinumab, and 28% with NBUVB.

Using methotrexate as the reference standard in analyses adjusted for more than 20 factors, including patient age, gender, and treatment duration, patients on adalimumab were 2.15-fold more likely to have clear or almost clear skin. Patients on ustekinumab were 1.57-fold more likely and those on etanercept 1.45-fold more likely to have clear or almost clear skin than those on methotrexate. The response rate to NBUVB wasn’t significantly different from that for methotrexate.

The results suggest that the biologic agents are outperforming methotrexate. That being said, the median PGA scores for all of the therapies hovered in the range of 1.3-1.7 on a scale of 0 to 5. This indicates that the absolute differences in treatment effectiveness are "quite small," Dr. Wan said. Moreover, there were no significant differences between treatments in terms of quality of life.

"The proportion of patients who said psoriasis had no or only a small effect on their quality of life was generally high across the board, ranging from 68% with narrow-band UVB to 78% with adalimumab," she said.

The number of patients who would need to be treated with a given agent in order to achieve one additional "clear" or "almost clear" response beyond what would be expected if patients were treated with methotrexate – was 4 for adalimumab, 8 for ustekinumab, 10 for etanercept, and 12 for NBUVB.

This cross-sectional study provides a useful snapshot of how psoriasis therapies are performing in current practice. The next step will be to perform a longitudinal comparative effectiveness study, according to Dr. Wan.

The DCERN network was formed in response to the fact that comparative effectiveness research was becoming a hot research trend, she said. The Institute of Medicine has identified comparative effectiveness research as a top priority, with psoriasis and acne as the main diseases of interest within dermatology.

"Congress has spent billions of dollars to jump-start comparative effectiveness research efforts," Dr. Wan noted.

Dr. Alexa B. Kimball rose from the audience to comment on the interpretation of the study data.

"There’s a relatively consistent pattern in clinical practice: Many patients are started on methotrexate; then if need be they are moved to etanercept or adalimumab, then to ustekinumab. So in a sense, since you’re finding that the clinical improvement is not so different across these therapies, doesn’t that suggest that patients get to a certain level of improvement and then are no longer switched? In fact, it may be that what you’re really showing is the level of improvement patients tend to be satisfied at," said Dr. Kimball of Harvard Medical School, Boston.

The study was sponsored by the National Institutes of Health. Dr. Wan reported having no financial conflicts. Dr. Kimball is a clinical trial investigator of biologic agents.

RALEIGH, N.C. – Absolute differences in response rates for treatments of moderate to severe plaque psoriasis as commonly used in everyday clinical practice "are small and may not be clinically significant," Dr. Joy Wan said at the annual meeting of the Society for Investigative Dermatology.

The results of a multicenter, comparative effectiveness study provide a picture of how psoriasis treatments are performing in real-world practice as opposed to the setting of clinical trials, which typically feature a nonrepresentative patient population and physician investigators having expertise in the treatment under study, according to Dr. Wan.

The results suggest that the go-to treatments for moderate to severe plaque psoriasis aren’t as effective in routine practice as they were in randomized trials (Arch. Dermatol. 2012;148:487-94). For example, only 48% of patients on adalimumab (Humira) were clear or almost clear based on Physician Global Assessment (PGA) ratings, compared with a 73% rate in an earlier clinical trial, noted Dr. Wan of the University of Pennsylvania, Philadelphia.

The comparative effectiveness study was cross sectional, and involved 713 consecutive patients with moderate to severe plaque psoriasis seen for routine follow-up care in 10 practices participating in the Dermatology Clinical Effectiveness Research Network (DCERN), a nationwide network of private and academic dermatology practices established in 2010.

The study participants (mean age, 49 years; 50% men) had a median 19-year duration of psoriasis; 23% also had psoriatic arthritis. All patients in the study were on monotherapy with methotrexate, etanercept, adalimumab, ustekinumab, or narrow-band UVB phototherapy (NBUVB). In all, 27% of the patients were on etanercept, 24% on methotrexate, 21% on adalimumab, 17% on NBUVB, and the rest on ustekinumab. Patients had been on methotrexate, adalimumab, or etanercept for a median of 12 months; ustekinumab for 4 months; and NBUVB for 2 months. On average, participants had been on only one systemic therapy or phototherapy prior to their current treatment. Patients were evaluated using PGA ratings and the Dermatology Life Quality Index.

One striking finding, noted Dr. Wan, was that recommended dosing often was not optimal. Notably, 36% of patients on etanercept were on 50 mg twice weekly and 12% on adalimumab were on 40 mg once weekly; those are double the recommended maintenance doses based on clinical trial data. And only 11% of patients on NBUVB received the optimal dosing frequency of at least 12 sessions within the previous 4 weeks.

The primary study end point was the proportion of patients rated clear or almost clear on PGA. The rates were 24% with methotrexate, 48% with adalimumab, 34% with etanercept, 36% for ustekinumab, and 28% with NBUVB.

Using methotrexate as the reference standard in analyses adjusted for more than 20 factors, including patient age, gender, and treatment duration, patients on adalimumab were 2.15-fold more likely to have clear or almost clear skin. Patients on ustekinumab were 1.57-fold more likely and those on etanercept 1.45-fold more likely to have clear or almost clear skin than those on methotrexate. The response rate to NBUVB wasn’t significantly different from that for methotrexate.

The results suggest that the biologic agents are outperforming methotrexate. That being said, the median PGA scores for all of the therapies hovered in the range of 1.3-1.7 on a scale of 0 to 5. This indicates that the absolute differences in treatment effectiveness are "quite small," Dr. Wan said. Moreover, there were no significant differences between treatments in terms of quality of life.

"The proportion of patients who said psoriasis had no or only a small effect on their quality of life was generally high across the board, ranging from 68% with narrow-band UVB to 78% with adalimumab," she said.

The number of patients who would need to be treated with a given agent in order to achieve one additional "clear" or "almost clear" response beyond what would be expected if patients were treated with methotrexate – was 4 for adalimumab, 8 for ustekinumab, 10 for etanercept, and 12 for NBUVB.

This cross-sectional study provides a useful snapshot of how psoriasis therapies are performing in current practice. The next step will be to perform a longitudinal comparative effectiveness study, according to Dr. Wan.

The DCERN network was formed in response to the fact that comparative effectiveness research was becoming a hot research trend, she said. The Institute of Medicine has identified comparative effectiveness research as a top priority, with psoriasis and acne as the main diseases of interest within dermatology.

"Congress has spent billions of dollars to jump-start comparative effectiveness research efforts," Dr. Wan noted.

Dr. Alexa B. Kimball rose from the audience to comment on the interpretation of the study data.

"There’s a relatively consistent pattern in clinical practice: Many patients are started on methotrexate; then if need be they are moved to etanercept or adalimumab, then to ustekinumab. So in a sense, since you’re finding that the clinical improvement is not so different across these therapies, doesn’t that suggest that patients get to a certain level of improvement and then are no longer switched? In fact, it may be that what you’re really showing is the level of improvement patients tend to be satisfied at," said Dr. Kimball of Harvard Medical School, Boston.

The study was sponsored by the National Institutes of Health. Dr. Wan reported having no financial conflicts. Dr. Kimball is a clinical trial investigator of biologic agents.

RALEIGH, N.C. – Absolute differences in response rates for treatments of moderate to severe plaque psoriasis as commonly used in everyday clinical practice "are small and may not be clinically significant," Dr. Joy Wan said at the annual meeting of the Society for Investigative Dermatology.

The results of a multicenter, comparative effectiveness study provide a picture of how psoriasis treatments are performing in real-world practice as opposed to the setting of clinical trials, which typically feature a nonrepresentative patient population and physician investigators having expertise in the treatment under study, according to Dr. Wan.

The results suggest that the go-to treatments for moderate to severe plaque psoriasis aren’t as effective in routine practice as they were in randomized trials (Arch. Dermatol. 2012;148:487-94). For example, only 48% of patients on adalimumab (Humira) were clear or almost clear based on Physician Global Assessment (PGA) ratings, compared with a 73% rate in an earlier clinical trial, noted Dr. Wan of the University of Pennsylvania, Philadelphia.

The comparative effectiveness study was cross sectional, and involved 713 consecutive patients with moderate to severe plaque psoriasis seen for routine follow-up care in 10 practices participating in the Dermatology Clinical Effectiveness Research Network (DCERN), a nationwide network of private and academic dermatology practices established in 2010.

The study participants (mean age, 49 years; 50% men) had a median 19-year duration of psoriasis; 23% also had psoriatic arthritis. All patients in the study were on monotherapy with methotrexate, etanercept, adalimumab, ustekinumab, or narrow-band UVB phototherapy (NBUVB). In all, 27% of the patients were on etanercept, 24% on methotrexate, 21% on adalimumab, 17% on NBUVB, and the rest on ustekinumab. Patients had been on methotrexate, adalimumab, or etanercept for a median of 12 months; ustekinumab for 4 months; and NBUVB for 2 months. On average, participants had been on only one systemic therapy or phototherapy prior to their current treatment. Patients were evaluated using PGA ratings and the Dermatology Life Quality Index.

One striking finding, noted Dr. Wan, was that recommended dosing often was not optimal. Notably, 36% of patients on etanercept were on 50 mg twice weekly and 12% on adalimumab were on 40 mg once weekly; those are double the recommended maintenance doses based on clinical trial data. And only 11% of patients on NBUVB received the optimal dosing frequency of at least 12 sessions within the previous 4 weeks.

The primary study end point was the proportion of patients rated clear or almost clear on PGA. The rates were 24% with methotrexate, 48% with adalimumab, 34% with etanercept, 36% for ustekinumab, and 28% with NBUVB.

Using methotrexate as the reference standard in analyses adjusted for more than 20 factors, including patient age, gender, and treatment duration, patients on adalimumab were 2.15-fold more likely to have clear or almost clear skin. Patients on ustekinumab were 1.57-fold more likely and those on etanercept 1.45-fold more likely to have clear or almost clear skin than those on methotrexate. The response rate to NBUVB wasn’t significantly different from that for methotrexate.

The results suggest that the biologic agents are outperforming methotrexate. That being said, the median PGA scores for all of the therapies hovered in the range of 1.3-1.7 on a scale of 0 to 5. This indicates that the absolute differences in treatment effectiveness are "quite small," Dr. Wan said. Moreover, there were no significant differences between treatments in terms of quality of life.

"The proportion of patients who said psoriasis had no or only a small effect on their quality of life was generally high across the board, ranging from 68% with narrow-band UVB to 78% with adalimumab," she said.

The number of patients who would need to be treated with a given agent in order to achieve one additional "clear" or "almost clear" response beyond what would be expected if patients were treated with methotrexate – was 4 for adalimumab, 8 for ustekinumab, 10 for etanercept, and 12 for NBUVB.

This cross-sectional study provides a useful snapshot of how psoriasis therapies are performing in current practice. The next step will be to perform a longitudinal comparative effectiveness study, according to Dr. Wan.

The DCERN network was formed in response to the fact that comparative effectiveness research was becoming a hot research trend, she said. The Institute of Medicine has identified comparative effectiveness research as a top priority, with psoriasis and acne as the main diseases of interest within dermatology.

"Congress has spent billions of dollars to jump-start comparative effectiveness research efforts," Dr. Wan noted.

Dr. Alexa B. Kimball rose from the audience to comment on the interpretation of the study data.

"There’s a relatively consistent pattern in clinical practice: Many patients are started on methotrexate; then if need be they are moved to etanercept or adalimumab, then to ustekinumab. So in a sense, since you’re finding that the clinical improvement is not so different across these therapies, doesn’t that suggest that patients get to a certain level of improvement and then are no longer switched? In fact, it may be that what you’re really showing is the level of improvement patients tend to be satisfied at," said Dr. Kimball of Harvard Medical School, Boston.

The study was sponsored by the National Institutes of Health. Dr. Wan reported having no financial conflicts. Dr. Kimball is a clinical trial investigator of biologic agents.