Martin A. Menter M.D.

Papp, K., M. A. Menter, M. Raman, D. Disch, D. E. Schlichting, C. Gaich, W. Macias, X. Zhang and J. M. Janes (2016). “A Randomized Phase 2b Trial of Baricitinib, an Oral JAK1/JAK2 Inhibitor, in Patients with Moderate-to-Severe Psoriasis.” Br J Dermatol. Jan 22. doi: 10.1111/bjd.14403. [Epub ahead of print]

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BACKGROUND: The safety and efficacy of baricitinib, an oral JAK1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis was evaluated 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 Psoriasis Area and Severity Index (PASI) score. OBJECTIVES: Primary endpoint was PASI-75 at 12 weeks for North American patients (n=238); secondary were safety and efficacy measures in the entire population. RESULTS: At week 12, more North American patients in 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 PASI score (p<0.05) at 12 weeks and (except 2 mg) had higher rates of PASI-50 than 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. CONCLUSION: Patients with moderate-to-severe psoriasis treated with baricitinib for 12 weeks achieved significant improvements in PASI-75.

Bissonnette, R., M. Luchi, R. Fidelus-Gort, S. Jackson, H. Zhang, R. Flores, R. Newton, P. Scherle, S. Yeleswaram, X. Chen and A. Menter (2016). “A randomized, double-blind, placebo-controlled, dose-escalation study of the safety and efficacy of INCB039110, an oral janus kinase 1 inhibitor, in patients with stable, chronic plaque psoriasis.” J Dermatolog Treat: 1-7.

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BACKGROUND: Chronic plaque psoriasis is partially mediated by elevation of proinflammatory cytokines, including several within the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. OBJECTIVE: To evaluate the safety and efficacy of the oral selective JAK1 inhibitor INCB039110 in stable, chronic plaque psoriasis. METHODS: This was a phase 2, randomized, double-blind, placebo-controlled, dose-escalation study of INCB039110 (100 mg once daily, 200 mg once daily, 200 mg twice daily and 600 mg once daily) for 28 days. The primary endpoint was mean percent change from baseline in the static Physician Global Assessment (sPGA) at day 28. The protocol was institutional review board approved. RESULTS: Of 50 patients, 48 completed the study. At day 28, mean percent reduction from baseline in sPGA was 22.2% for INCB039110 100 mg once daily (p = 0.270 vs. placebo), 29.4% for 200 mg once daily (p = 0.118), 35.2% for 200 mg twice daily (p = 0.053), 42.4% for 600 mg once daily (p = 0.003) and 12.5% for placebo. Across groups, 11.1% to 45.5% achieved an sPGA score of 1 versus 0% for placebo. INCB039110 was generally well tolerated; the most common treatment-emergent adverse event was nasopharyngitis (18.4%). CONCLUSION: INCB039110 produced significant improvements in sPGA, demonstrating proof of concept in chronic plaque psoriasis.