title: A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis.
abstract: 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.
  
  
  OBJECTIVE
  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 < 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.
  
  
  CONCLUSIONS
  Patients with moderate-to-severe psoriasis treated with baricitinib for 12 weeks achieved significant improvements in PASI-75.
authors.affiliation: K.A. Papp Clinical Research and Probity Medical Research, 135 Union Street East, Waterloo, ON, N2J 1C4, Canada.
authors.forename: K A
authors.initials: KA
authors.lastname: Papp
authors.affiliation: Baylor University Medical Center, Dallas, TX, U.S.A.
authors.forename: M A
authors.initials: MA
authors.lastname: Menter
authors.affiliation: Centre for Dermatology and Probity Medical Research, Richmond Hill, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Raman
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, U.S.A.
authors.forename: D
authors.initials: D
authors.lastname: Disch
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, U.S.A.
authors.forename: D E
authors.initials: DE
authors.lastname: Schlichting
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, U.S.A.
authors.forename: C
authors.initials: C
authors.lastname: Gaich
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, U.S.A.
authors.forename: W
authors.initials: W
authors.lastname: Macias
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, U.S.A.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, U.S.A.
authors.forename: J M
authors.initials: JM
authors.lastname: Janes
mesh_terms: D001384:Azetidines / Q000008:administration & dosage* / Q000009:adverse effects; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D011687:Purines; D011720:Pyrazoles; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D001384:Azetidines; D003879:Dermatologic Agents; D011687:Purines; D011720:Pyrazoles; D013449:Sulfonamides; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; C000596027:baricitinib