A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate‐to‐severe psoriasis

Abstract

SummaryBackground 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/JAK2 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 < 0Á05) achieved PASI-75. All baricitinib-treated groups had greater mean changes from baseline in their PASI scores (P < 0Á05) 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%, 2Á8%, 6Á3% and 5Á8% 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.

JAK inhibitors in dermatology: The promise of a new drug class

“…In this 12 week dose ranging study, patients treated with 8mg and 10mg once daily achieved PASI 75 responses of 43% and 54% respectively 11 .…”

“…Baricitinib, still in clinical trials and not yet FDA approved for any condition, was recently reported to be efficacious in moderate-to-severe plaque psoriasis in a phase 2b trial 11 . In this 12 week dose ranging study, patients treated with 8mg and 10mg once daily achieved PASI 75 responses of 43% and 54% respectively 11 .…”

“…Ruxolitinib is FDA approved to treat myelodysplastic disorders. Baricitinib is not yet FDA approved, but is in clinical trials for rheumatoid arthritis (RA) (Phase 3) 10 , psoriasis (Phase 2) 11 , and atopic dermatitis (Phase 2, NCT02576938). The first FDA-approved JAK inhibitor for treatment of an autoimmune disease was tofacitinib, although it was initially studied as an anti-rejection agent in organ transplantation 12 .…”

Janus kinase inhibitors for autoimmune disorders

“…17 A phase 2 trial suggests that baricitinib may offer similar efficacy in patients with moderate to severe plaque psoriasis. 18 Topical formulations of JAK inhibitors have also been evaluated; early trials suggest that ruxolitinib compares well with established topical treatments but trials of topical tofacitinib have been inconclusive. 13 Other early trials suggest that JAK inhibitors show promise in the treatment of vitiligo and atopic dermatitis.…”

Janus Kinase Inhibitors against Other Biological Treatments in Alopecia Areata

“…These results are implying to the high potential of JAK inhibitors to treating AA disease. Although there is no study on safety of these drugs in AA patients, no serious safety concern associated with the use of baricitinib was reported in rheumatoid arthritis and psoriasis patients [9,10]. In addition to JAK inhibitors, fontolizumab, an anti-IFN-c may be another novel biological treatment of AA, which needs for further studies, associated with its efficiency and safety in patients with AA.…”