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A randomized phase 2b trial of baricitinib, an oral Janus kinase ( JAK ) 1/JAK2 inhibitor, in patients with moderate‐to‐severe psoriasis
Author(s) -
Papp K.A.,
Menter M.A.,
Raman M.,
Disch D.,
Schlichting D.E.,
Gaich C.,
Macias W.,
Zhang X.,
Janes J.M.
Publication year - 2016
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.14403
Subject(s) - medicine , psoriasis area and severity index , placebo , psoriasis , adverse effect , clinical endpoint , gastroenterology , randomized controlled trial , population , plaque psoriasis , placebo controlled study , surgery , dermatology , double blind , pathology , alternative medicine , environmental health
Summary Background Plaque psoriasis is a chronic and often debilitating skin disorder and proinflammatory cytokines are known to play a key role in the disease process. Objectives To evaluate the safety and efficacy of baricitinib, an oral Janus kinase ( JAK ) 1/ JAK 2 inhibitor, in patients with moderate‐to‐severe psoriasis in a randomized, double‐blind, placebo‐controlled, dose‐ranging phase 2b study. Methods Patients were randomized ( n = 271) to receive placebo or oral baricitinib at 2, 4, 8 or 10 mg once daily for 12 weeks (Part A). Dose adjustment for 12 additional weeks was based on percentage improvement in the Psoriasis Area and Severity Index ( PASI ) score. The primary end point was Psoriasis Area and Severity Index ( PASI ) 75% ( PASI ‐75) at 12 weeks for North American patients ( n = 238); secondary end points were safety and efficacy measures in the entire population. Results At week 12, more North American patients in the 8‐mg (43%) and 10‐mg (54%) baricitinib groups than in placebo group (17%; P < 0·05) achieved PASI ‐75. All baricitinib‐treated groups had greater mean changes from baseline in their PASI scores ( P < 0·05) at 12 weeks and (except 2 mg) had higher rates of PASI ‐50 than the placebo group; statistically significant PASI ‐90 responses were achieved in the 8‐mg and 10‐mg groups at 8 and 12 weeks. More than 81% of PASI ‐75 responders maintained their scores through 24 weeks. During Part A, study discontinuations due to adverse events ( AE s) were 0%, 0%, 2·8%, 6·3% and 5·8% and treatment‐emergent AE rates were 44%, 50%, 47%, 58% and 64% for placebo and 2‐, 4‐, 8‐ and 10‐mg baricitinib groups, respectively. No opportunistic infections were observed in any treatment group. Dose‐dependent changes in laboratory values were observed. Conclusions Patients with moderate‐to‐severe psoriasis treated with baricitinib for 12 weeks achieved significant improvements in PASI ‐75.