A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate‐to‐severe psoriasis
Top Cited Papers
Open Access
- 5 April 2016
- journal article
- research article
- Published by Oxford University Press (OUP) in British Journal of Dermatology
- Vol. 174 (6), 1266-1276
- https://doi.org/10.1111/bjd.14403
Abstract
Plaque psoriasis is a chronic and often debilitating skin disorder and proinflammatory cytokines are known to play a key role in the disease process. To evaluate the safety and efficacy of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis in a randomized, double-blind, placebo-controlled, dose-ranging phase 2b study. 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. 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 (AEs) 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. Patients with moderate-to-severe psoriasis treated with baricitinib for 12 weeks achieved significant improvements in PASI-75.This publication has 27 references indexed in Scilit:
- Efficacy and safety of apremilast in subjects with moderate to severe plaque psoriasis: results from a phase II, multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group, dose‐comparison studyJournal of the European Academy of Dermatology and Venereology, 2012
- Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging studyBritish Journal of Dermatology, 2012
- PsoriasisThe New England Journal of Medicine, 2009
- Therapeutic targeting of Janus kinasesImmunological Reviews, 2008
- Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2)The Lancet, 2008
- Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1)The Lancet, 2008
- Adalimumab therapy for moderate to severe psoriasis: A randomized, controlled phase III trialJournal of the American Academy of Dermatology, 2008
- Prevalence and Treatment of Psoriasis in the United KingdomArchives of Dermatology, 2005
- Regulation of JAK–STAT signalling in the immune systemNature Reviews Immunology, 2003
- Cyclosporin a for PsoriasisThe New England Journal of Medicine, 1979