Volume 172, Issue 2 pp. 504-512
Therapeutics

Comparative efficacy of biological treatments for moderate-to-severe psoriasis: a network meta-analysis adjusting for cross-trial differences in reference arm response

J.E. Signorovitch

Corresponding Author

J.E. Signorovitch

Analysis Group, Inc., 111 Huntington Avenue, 10th floor, Boston, MA, 02199 U.S.A

Correspondence

James E. Signorovitch.

E-mail: [email protected]

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K.A. Betts

K.A. Betts

Analysis Group, Inc., 111 Huntington Avenue, 10th floor, Boston, MA, 02199 U.S.A

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Y.S. Yan

Y.S. Yan

University of California, Santa Cruz, CA, U.S.A

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C. LeReun

C. LeReun

Independent Biostatistician, Carrigaline, Ireland

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M. Sundaram

M. Sundaram

AbbVie Inc., North Chicago, IL, U.S.A

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E.Q. Wu

E.Q. Wu

Analysis Group, Inc., 111 Huntington Avenue, 10th floor, Boston, MA, 02199 U.S.A

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P. Mulani

P. Mulani

AbbVie Inc., North Chicago, IL, U.S.A

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First published: 07 October 2014
Citations: 59
Funding sources Funding for this study was provided by AbbVie. AbbVie participated in the interpretation of data, review and approval of the manuscript.
Conflicts of interest J.E.S, K.A.B. and E.Q.W. are employed by Analysis Group, Inc., which received payment from AbbVie Inc. for participation in this research. Y.S.Y. is a former employee of Analysis Group, Inc., which received payment from AbbVie Inc. for participation in this research. C.L. is an independent statistician who received payment from AbbVie for this research. M.S. and P.M. are employees of AbbVie and may own AbbVie stock or stock options.

Summary

Background

Multiple biological therapies are approved for the treatment of moderate-to-severe psoriasis.

Objectives

To assess the short-term efficacy of biological treatments for moderate-to-severe psoriasis via a network meta-analysis that adjusts for reference arm response rates.

Methods

Fifteen randomized trials of biological treatments for moderate-to-severe psoriasis were identified. Rates of response, assessed as 50%, 75% and 90% reductions in the Psoriasis Area and Severity Index (PASI), were compared using a network meta-analysis. To account for variation across trials, the model was adjusted for placebo responses, the relevance of which was assessed by testing its statistical significance, impact on model fit, and extent to which lack of adjustment confounded the efficacy estimates for biologics.

Results

Psoriasis Area and Severity Index 75 response rates for placebo arms ranged from 1·8% to 18·9%. The probability of achieving a PASI 75 response was 80·5% [95% credible interval (CrI) 74·8–85·7] with infliximab 5 mg kg−1; 72·5% (95% CI 66·1–78·3) with ustekinumab 90 mg; 67·5% (95% CI 60·7–73·9) with ustekinumab 45 mg; 66·2% (95% CI 57·3–73·3) with adalimumab 40 mg; 51·9% (95% CI 45·7–58·4) with etaner-cept 50 mg; and 38·0% (95% CI 31·6–45·1) with etanercept 25 mg. Infliximab had the highest PASI 75 response. Adalimumab and both ustekinumab doses had significantly higher PASI 75 responses than both etanercept doses. There were no significant differences among adalimumab and ustekinumab doses.

Conclusions

A model adjusted for reference arm response rates was found to fit clinical trial data significantly better than unadjusted models.

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