Baricitinib Versus Azathioprine in Patients With Moderate-to-Severe Atopic Dermatitis

Summary

Atopic dermatitis, which is also known as atopic eczema, is a common inflammatory and chronic skin disease that is characterized by severe recurrent erythematous and pruritic lesions. Patients suffer from decreased quality of life and poor work productivity due to the disease complications like persistent scratching, skin pain, skin damage, sleep disturbances, and social/emotional distress. In the United States (US), the prevalence of adults with atopic dermatitis ranges from 5% to 10%. The mainstay treatment for atopic dermatitis is emollient and tropical corticosteroids which could be efficient for less severe atopic dermatitis patients but moderate to severe patients usually need additional therapies like phototherapy or systemic medications. It is revealed that Janus kinase signal transducers and activators of transcription (JAK-STAT) pathway has a prominent role in the development and progression of atopic dermatitis. JAK1/JAK2 inhibitor, baricitinib is a new-class orally available drug that is approved for systemic treatment of adult patients with moderate to severe atopic dermatitis. In the phase III clinical trial baricitinib 2-mg and 4-mg were shown efficient results as monotherapy of adult patients with moderate to severe atopic dermatitis who have an inadequate response to topical corticosteroids (TCS). Azathioprine is an immunosuppressant and antimetabolite agent interferes with the formation of lymphocytes, and suppresses prostaglandin synthesis, both of which are implicated in the inflammation associated with eczema. Azathioprine can be used (off-label) for moderate to severe atopic dermatitis patients. Multiple studies have demonstrated that azathioprine might be effective for patients with moderate-to-severe atopic dermatitis. Azathioprine is usually prescribed when cyclosporine is either contraindicated or not effective. This trial will be conducted to test the hypothesis that baricitinib 4-mg daily in combination with TCS is superior to azathioprine 1.5-2.5 mg/kg a day in combination with TCS for moderate-to-severe AD at week 12 in terms of efficacy and safety.

Timeline

Start

2023-08-15

Primary completion

2025-04-30

Completion

2025-11-14

Publications

• Background Lio PA, Simpson EL, Han G, Soung J, Ball S, Sun L, Casillas M, DeLozier AM, Ding Y, Eichenfield LF. Improvement in sleep and itch and enhanced quality of life in adult patients with moderate-to-severe atopic dermatitis: results from a phase 3 trial of baricitinib therapy. J Dermatolog Treat. 2022 Jun;33(4):2057-2062. doi: 10.1080/09546634.2021.1914308. Epub 2021 Jun 28.
• Background Simpson EL, Lacour JP, Spelman L, Galimberti R, Eichenfield LF, Bissonnette R, King BA, Thyssen JP, Silverberg JI, Bieber T, Kabashima K, Tsunemi Y, Costanzo A, Guttman-Yassky E, Beck LA, Janes JM, DeLozier AM, Gamalo M, Brinker DR, Cardillo T, Nunes FP, Paller AS, Wollenberg A, Reich K. Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials. Br J Dermatol. 2020 Aug;183(2):242-255. doi: 10.1111/bjd.18898. Epub 2020 Mar 5.
• Background Barbarot S, Auziere S, Gadkari A, Girolomoni G, Puig L, Simpson EL, Margolis DJ, de Bruin-Weller M, Eckert L. Epidemiology of atopic dermatitis in adults: Results from an international survey. Allergy. 2018 Jun;73(6):1284-1293. doi: 10.1111/all.13401. Epub 2018 Feb 13.
• Background Wan H, Jia H, Xia T, Zhang D. Comparative efficacy and safety of abrocitinib, baricitinib, and upadacitinib for moderate-to-severe atopic dermatitis: A network meta-analysis. Dermatol Ther. 2022 Sep;35(9):e15636. doi: 10.1111/dth.15636. Epub 2022 Jul 27.
• Background Wollenberg A, Nakahara T, Maari C, Peris K, Lio P, Augustin M, Silverberg JI, Rueda MJ, DeLozier AM, Pierce E, Yang FE, Sun L, Ball S, Tauber M, Paul C. Impact of baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-severe atopic dermatitis from the BREEZE-AD7 Phase 3 randomized trial. J Eur Acad Dermatol Venereol. 2021 Jul;35(7):1543-1552. doi: 10.1111/jdv.17278. Epub 2021 Jun 5.
• Background Bieber T, Reich K, Paul C, Tsunemi Y, Augustin M, Lacour JP, Ghislain PD, Dutronc Y, Liao R, Yang FE, Brinker D, DeLozier AM, Meskimen E, Janes JM, Eyerich K; BREEZE-AD4 study group. Efficacy and safety of baricitinib in combination with topical corticosteroids in patients with moderate-to-severe atopic dermatitis with inadequate response, intolerance or contraindication to ciclosporin: results from a randomized, placebo-controlled, phase III clinical trial (BREEZE-AD4). Br J Dermatol. 2022 Sep;187(3):338-352. doi: 10.1111/bjd.21630. Epub 2022 Jul 20.
• Background Bracho-Borro M, Franco-Ruiz PA, Magana M. The use of azathioprine in atopic dermatitis: A review. Dermatol Ther. 2022 Sep;35(9):e15665. doi: 10.1111/dth.15665. Epub 2022 Jul 10.
• Background Murphy LA, Atherton D. A retrospective evaluation of azathioprine in severe childhood atopic eczema, using thiopurine methyltransferase levels to exclude patients at high risk of myelosuppression. Br J Dermatol. 2002 Aug;147(2):308-15. doi: 10.1046/j.1365-2133.2002.04922.x.
• Background Meggitt SJ, Gray JC, Reynolds NJ. Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trial. Lancet. 2006 Mar 11;367(9513):839-46. doi: 10.1016/S0140-6736(06)68340-2.
• Background Wollenberg A, Szepietowski J, Taieb A, Ring J. Corrigendum: Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I. J Eur Acad Dermatol Venereol. 2019 Jul;33(7):1436. doi: 10.1111/jdv.15719. No abstract available.
• Background Gerbens LAA, Hamann SAS, Brouwer MWD, Roekevisch E, Leeflang MMG, Spuls PI. Methotrexate and azathioprine for severe atopic dermatitis: a 5-year follow-up study of a randomized controlled trial. Br J Dermatol. 2018 Jun;178(6):1288-1296. doi: 10.1111/bjd.16240. Epub 2018 Apr 10.
• Background Silverberg JI, Lei D, Yousaf M, Janmohamed SR, Vakharia PP, Chopra R, Chavda R, Gabriel S, Patel KR, Singam V, Kantor R, Hsu DY. What are the best endpoints for Eczema Area and Severity Index and Scoring Atopic Dermatitis in clinical practice? A prospective observational study. Br J Dermatol. 2021 May;184(5):888-895. doi: 10.1111/bjd.19457. Epub 2020 Sep 21.
• Background Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, Berger TG, Bergman JN, Cohen DE, Cooper KD, Cordoro KM, Davis DM, Krol A, Margolis DJ, Paller AS, Schwarzenberger K, Silverman RA, Williams HC, Elmets CA, Block J, Harrod CG, Smith Begolka W, Sidbury R. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014 Feb;70(2):338-51. doi: 10.1016/j.jaad.2013.10.010. Epub 2013 Nov 27.
• Background Reich K, Kabashima K, Peris K, Silverberg JI, Eichenfield LF, Bieber T, Kaszuba A, Kolodsick J, Yang FE, Gamalo M, Brinker DR, DeLozier AM, Janes JM, Nunes FP, Thyssen JP, Simpson EL. Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2020 Dec 1;156(12):1333-1343. doi: 10.1001/jamadermatol.2020.3260.

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