Baricitinib, an oral selective inhibitor of Janus kinase 1 and Janus kinase 2, modulates proinflammatory cytokine signaling.
The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD).
In this phase 2, randomized, double-blind, placebo-controlled study, 124 patients with moderate-to-severe AD applied topical corticosteroids (TCSs) for 4 weeks before randomization to once-daily placebo, 2 mg of baricitinib, or 4 mg of baricitinib for 16 weeks. Use of TCSs was permitted during the study. The primary outcome was the proportion of patients achieving at least a 50% reduction in the Eczema Area and Severity Index (EASI-50) compared with placebo.
Significantly more patients who received baricitinib, 4 mg, achieved EASI-50 than did patients receiving placebo (61% vs 37% [P = .027]) at 16 weeks. The difference between the proportion of patients receiving baricitinib, 2 or 4 mg, who achieved EASI-50 and the proportion of patients receiving placebo and achieving EASI-50 was significant as early as week 4. Baricitinib also improved pruritus and sleep loss. Treatment-emergent adverse events were reported in 24 of the patients receiving placebo (49%), 17 of those receiving 2 mg of baricitinib (46%), and 27 of those receiving 4 mg of baricitinib (71%).
A TCS standardization period before randomization reduced disease severity, limiting the ability to compare results with those of baricitinib monotherapy. Longer studies are required to confirm baricitinib's efficacy and safety in patients with AD.
Baricitinib used with TCSs reduced inflammation and pruritus in patients with moderate-to-severe AD.Le texte complet de cet article est disponible en PDF.
Key words : atopic dermatitis, baricitinib, EASI, JAK-STAT signaling, phase 2, pruritus, SCORAD, topical corticosteroids
Abbreviations used : AD, CPK, DLQI, EASI, EASI-50, HRQoL, IL, IRT, JAK, LOCF, MMRM, NRS, SCORAD, TCS
| Supported by Eli Lilly and Company.
| Disclosure: Dr Guttman-Yassky reports grants from Eli Lilly and Company during the conduct of the study and grants from Dermira, Leo Pharma, Novartis, Galderma, Regeneron Pharmaceuticals, Pfizer, Vitae Pharmaceuticals, Glenmark, Abbvie, Celgene, Medimmune, Innovaderm Research, Immune Pharmaceuticals, and Asana BioSciences and personal fees from Regeneron Pharmaceuticals, Sanofi, Stiefel/GSK, Pfizer, Galderma, Celgene, Dermira, Anacor Pharmaceuticals, AnaptysBio, Glenmark, Novartis, Abbvie, Sun Pharmaceutical Industries, Mitsubishi Tanabe, Vitae Pharmaceuticals, Allergan, Almirall, PuriCore, Asana BioSciences, Gilead Sciences, Concert Pharmaceuticals, Immune Pharmaceuticals, Kyowa Kirin Co, Ziarco Group, DS Biopharma, DBV Technologies, Eli Lilly and Company, and Escalier Biosciences outside the submitted work. Dr Silverberg reports grants from GSK and Regeneron-Sanofi and personal fees from Abbvie, Eli Lilly and Company, Galderma, Kiniksa Pharmaceuticals, Leo Pharma, Menlo Therapeutics, Pfizer, Realm Therapeutics, Regeneron-Sanofi, and Roivant Sciences during the conduct of the study and personal fees from Eli Lilly and Company outside the submitted work. Dr. Forman reports personal fees and nonfinancial support from Eli Lilly and Company during the conduct of the study and personal fees and nonfinancial support from Eli Lilly and Company, Pfizer, Abbvie, Regeneron/Sanofi and personal fees from Asana BioSciences, Valeant Pharmaceuticals, Genentech/Roche, Innovaderm Research, and Novartis outside the submitted work. Dr Donley is an employee of EMB Statistical Solutions, which was hired by Eli Lilly and Company for statistical support. Drs Wilke, Prescilla, de la Peña, Nunes, Janes, Gamalo, Paik, and Nickoloff and Ms DeLozier are employees of and stockholders in Eli Lilly and Company. Dr Simpson reports grants, personal fees, and nonfinancial support from Eli Lilly and Company during the conduct of the study and grants and personal fees from Anacor Pharma, Glaxo Smith Kline, and Regeneron Pharmaceuticals; personal fees from AbbVie, Celgene Corporation, Dermira, Galderma, Genentech, Leo Pharma, and Menlo Therapeutics; grants and personal fees from Sanofi Genzyme and Valeant Pharmaceuticals; and grants from MedImmune, Novartis, Roivant Sciences, Tioga Pharmaceuticals, and Vanda Pharmaceuticals outside the submitted work. Dr. Nemoto has no conflicts of interest to disclose.
| This study was designed jointly by consultant experts and representatives of the funder, Eli Lilly and Company. Data were collected by investigators and analyzed by the funder. Safety data were reviewed at regular intervals by an independent data monitoring committee. All authors participated in data analysis and interpretation and review of the draft and final manuscript, and they provided critical comment, including regarding the decision to submit the manuscript for publication with medical writing support paid by the funder. The authors had full access to the data and verified the veracity, accuracy, and completeness of the data and analyses, as well as the fidelity of this report to the protocol. All authors made the decision to submit the manuscript for publication.
| Presented at the 26th European Academy of Dermatology and Venereology Congress, Geneva, Switzerland; September 14, 2017; the 2018 American Academy of Dermatology, San Diego, CA; and the 27th European Academy of Dermatology and Venereology Congress, Paris, France; 2018.
| Reprints not available from the authors.