Indirect Comparison Trial Favors Adalimumab for Psoriasis

PRAGUE – Recognizing the slim chances of a direct comparison study of two biologics for treatment of psoriasis, Dr. Kristian Reich and his coworkers have done the next best thing: they’ve conducted an indirect comparison study.

They used existing data from four randomized trials to compare two biologics adalimumab (Humira) and etanercept (Enbrel) and adjusted for between-trial differences in baseline patient demographics, treatment history, and numerous measures of psoriasis severity.

The analysis was supported by Abbott, the maker of adalimumab. The drug had a significantly better benefit-risk profile as measured by the number of days patients spent with at least a 75% improvement from baseline in Psoriasis Area and Severity Index (PASI) scores while also remaining free of study drug–related adverse events, Dr. Reich reported at the annual congress of the European Academy of Dermatology and Venereology.

The four phase III, double-blind, randomized, placebo-controlled, 12-week clinical trials included REVEAL (J. Am. Acad. Dermatol. 2008;56:106-15) and CHAMPION (Br. J. Dermatol. 2008;158:558-66), studies that pitted adalimumab against placebo in 1,302 subjects. The analysis also included the M10-114 and M10-315 trials, which included 390 patients randomized to briakinumab (Abbott), etanercept, or placebo.

Prior to propensity score weighting, participants in the adalimumab studies differed from those in the etanercept trials in terms of disease duration, percent body surface area involvement, extent of prior medication use, PASI scores, and other important variables. After matching, however, the two groups were closely similar across the board, explained Dr. Reich of the Hamburg (Germany) Dermatology Clinic.

Through 12 weeks of study participation, adalimumab-treated patients spent an average of 22.4 more days at PASI 75 with no study drug–related side effects than did those on placebo in the same two studies. In contrast, etanercept-treated patients spent 11.5 more days than did controls in this optimal state.

At week 4, the proportion of biologic-treated subjects who were PASI 75 responders free of moderate-to-severe study drug–related adverse events was 15.7% in the adalimumab group compared with 5.5% with etanercept. At week 8, these rates climbed to 46.3% in the adalimumab-treated patients and 16.2% in the etanercept group. By week 12, the figures were 58% for adalimumab compared with 39.4% with etanercept.

An obvious limitation of this indirect comparison is the potential for confounding due to unobserved baseline differences. But Dr. Reich said he and his coinvestigators adjusted and balanced for everything they could think of.

"To further adjust for potential differences between trials, outcomes were compared relative to the corresponding placebo arms after applying propensity weights and before comparing across trials. Thus, unobserved factors that equally impact outcomes on the drug and placebo arms would not bias this comparison of adalimumab and etanercept," the dermatologist said.

Dr. Reich has received research grants from and serves as a consultant to Abbott, which supported this analysis, as well as to numerous other pharmaceutical companies.

PRAGUE – Recognizing the slim chances of a direct comparison study of two biologics for treatment of psoriasis, Dr. Kristian Reich and his coworkers have done the next best thing: they’ve conducted an indirect comparison study.

They used existing data from four randomized trials to compare two biologics adalimumab (Humira) and etanercept (Enbrel) and adjusted for between-trial differences in baseline patient demographics, treatment history, and numerous measures of psoriasis severity.

The analysis was supported by Abbott, the maker of adalimumab. The drug had a significantly better benefit-risk profile as measured by the number of days patients spent with at least a 75% improvement from baseline in Psoriasis Area and Severity Index (PASI) scores while also remaining free of study drug–related adverse events, Dr. Reich reported at the annual congress of the European Academy of Dermatology and Venereology.

The four phase III, double-blind, randomized, placebo-controlled, 12-week clinical trials included REVEAL (J. Am. Acad. Dermatol. 2008;56:106-15) and CHAMPION (Br. J. Dermatol. 2008;158:558-66), studies that pitted adalimumab against placebo in 1,302 subjects. The analysis also included the M10-114 and M10-315 trials, which included 390 patients randomized to briakinumab (Abbott), etanercept, or placebo.

Prior to propensity score weighting, participants in the adalimumab studies differed from those in the etanercept trials in terms of disease duration, percent body surface area involvement, extent of prior medication use, PASI scores, and other important variables. After matching, however, the two groups were closely similar across the board, explained Dr. Reich of the Hamburg (Germany) Dermatology Clinic.

Through 12 weeks of study participation, adalimumab-treated patients spent an average of 22.4 more days at PASI 75 with no study drug–related side effects than did those on placebo in the same two studies. In contrast, etanercept-treated patients spent 11.5 more days than did controls in this optimal state.

At week 4, the proportion of biologic-treated subjects who were PASI 75 responders free of moderate-to-severe study drug–related adverse events was 15.7% in the adalimumab group compared with 5.5% with etanercept. At week 8, these rates climbed to 46.3% in the adalimumab-treated patients and 16.2% in the etanercept group. By week 12, the figures were 58% for adalimumab compared with 39.4% with etanercept.

An obvious limitation of this indirect comparison is the potential for confounding due to unobserved baseline differences. But Dr. Reich said he and his coinvestigators adjusted and balanced for everything they could think of.

"To further adjust for potential differences between trials, outcomes were compared relative to the corresponding placebo arms after applying propensity weights and before comparing across trials. Thus, unobserved factors that equally impact outcomes on the drug and placebo arms would not bias this comparison of adalimumab and etanercept," the dermatologist said.

Dr. Reich has received research grants from and serves as a consultant to Abbott, which supported this analysis, as well as to numerous other pharmaceutical companies.

PRAGUE – Recognizing the slim chances of a direct comparison study of two biologics for treatment of psoriasis, Dr. Kristian Reich and his coworkers have done the next best thing: they’ve conducted an indirect comparison study.

They used existing data from four randomized trials to compare two biologics adalimumab (Humira) and etanercept (Enbrel) and adjusted for between-trial differences in baseline patient demographics, treatment history, and numerous measures of psoriasis severity.

The analysis was supported by Abbott, the maker of adalimumab. The drug had a significantly better benefit-risk profile as measured by the number of days patients spent with at least a 75% improvement from baseline in Psoriasis Area and Severity Index (PASI) scores while also remaining free of study drug–related adverse events, Dr. Reich reported at the annual congress of the European Academy of Dermatology and Venereology.

The four phase III, double-blind, randomized, placebo-controlled, 12-week clinical trials included REVEAL (J. Am. Acad. Dermatol. 2008;56:106-15) and CHAMPION (Br. J. Dermatol. 2008;158:558-66), studies that pitted adalimumab against placebo in 1,302 subjects. The analysis also included the M10-114 and M10-315 trials, which included 390 patients randomized to briakinumab (Abbott), etanercept, or placebo.

Prior to propensity score weighting, participants in the adalimumab studies differed from those in the etanercept trials in terms of disease duration, percent body surface area involvement, extent of prior medication use, PASI scores, and other important variables. After matching, however, the two groups were closely similar across the board, explained Dr. Reich of the Hamburg (Germany) Dermatology Clinic.

Through 12 weeks of study participation, adalimumab-treated patients spent an average of 22.4 more days at PASI 75 with no study drug–related side effects than did those on placebo in the same two studies. In contrast, etanercept-treated patients spent 11.5 more days than did controls in this optimal state.

At week 4, the proportion of biologic-treated subjects who were PASI 75 responders free of moderate-to-severe study drug–related adverse events was 15.7% in the adalimumab group compared with 5.5% with etanercept. At week 8, these rates climbed to 46.3% in the adalimumab-treated patients and 16.2% in the etanercept group. By week 12, the figures were 58% for adalimumab compared with 39.4% with etanercept.

An obvious limitation of this indirect comparison is the potential for confounding due to unobserved baseline differences. But Dr. Reich said he and his coinvestigators adjusted and balanced for everything they could think of.

"To further adjust for potential differences between trials, outcomes were compared relative to the corresponding placebo arms after applying propensity weights and before comparing across trials. Thus, unobserved factors that equally impact outcomes on the drug and placebo arms would not bias this comparison of adalimumab and etanercept," the dermatologist said.

Dr. Reich has received research grants from and serves as a consultant to Abbott, which supported this analysis, as well as to numerous other pharmaceutical companies.