Efficacy and safety of baricitinib in combination with topical corticosteroids in paediatric patients with moderate-to-severe atopic dermatitis with an inadequate response to topical corticosteroids: results from a phase III, randomized, double-blind, placebo-controlled study (BREEZE-AD PEDS).

BACKGROUND

Baricitinib, an oral selective Janus kinase (JAK)1/JAK2 inhibitor, is approved in many countries for moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

OBJECTIVES

To evaluate the efficacy and safety of three doses of baricitinib in combination with low-to-moderate potency topical corticosteroids in paediatric patients with moderate-to-severe AD.

METHODS

Patients (aged 2 to < 18 years) were randomized (1 : 1 : 1 : 1) to once-daily baricitinib low dose (1 mg equivalent), medium dose (2 mg equivalent), high dose (4 mg equivalent) or placebo for 16 weeks. The primary endpoint was the proportion of patients achieving a validated Investigator Global Assessment® (vIGA-AD) of 0/1 with a ≥ 2-point improvement at week 16. Key secondary endpoints included the proportions of patients achieving ≥ 75% and ≥ 90% improvement in the Eczema Area and Severity Index (EASI-75 and EASI-90, respectively), ≥ 75% improvement in the SCORing Atopic Dermatitis (SCORAD 75), mean change from baseline in EASI score and proportion of patients achieving a 4-point improvement in the Itch Numeric Rating scale (NRS) for patients aged ≥ 10 years. Primary and key secondary efficacy analyses were conducted on the intent-to-treat population and adjusted for multiplicity. Safety analyses included all randomized patients who received ≥ 1 dose of study treatment.

RESULTS

A total of 483 patients were randomized (mean age 12 years). The baricitinib 4 mg equivalent achieved a statistically significant (P < 0.05) improvement vs. placebo on all 16-week endpoints (vIGA 0/1 with ≥ 2-point improvement, EASI-75, EASI-90, SCORAD 75, mean change in EASI score and Itch NRS 4-point improvement for patients aged ≥ 10 years). Improvement (P < 0.05, non-multiplicity adjusted) was also observed for baricitinib 4 mg equivalent vs. placebo in the ability to fall asleep and in reduction of topical corticosteroid use. Few patients discontinued due to adverse events (1.6% for placebo and 0.6% for those treated with baricitinib). There were no deaths, venous thromboembolic events, arterial thrombotic events, major adverse cardiovascular events, malignancies, gastrointestinal perforations or opportunistic infections seen.

CONCLUSIONS

The results indicate that baricitinib offers a potential therapeutic option with a favourable benefit-risk profile for paediatric patients with moderate-to-severe AD who are candidates for systemic therapies.

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.

Déclaration de conflit d'intérêts

Conflicts of interest A.T. reports other financial or nonfinancial interests in Eli Lilly and Company during the conduct of the study; and other financial or nonfinancial interests in AbbVie, Novartis, Pfizer, Pierre Fabre and Sanofi outside the submitted work. B.R. has participated in advisory boards and/or served as a Principal Investigator in clinical trials for ALK-Abelló, Almirall, Amgen, AstraZeneca, Bausch Health, Bayer Pharmaceuticals, Biocon, Boehringer Ingelheim, Chiesi, Connect Biopharma, Dermira, Eli Lilly and Company, Galapagos, Galderma, Gedeon Richter, GlaxoSmithKline, Glenmark Pharmaceuticals/Ichnos Sciences, Idorsia, Janssen, LEO Pharma, Pfizer, Roche and Sanofi. M.G. reports being an investigator for Eli Lilly and Company, Pfizer, Novartis, Boehringer Ingelheim, MSD and Amgen. A. Paller reports being an investigator or consultant for AbbVie, Abeona, Aegerion Pharma, Azitra, BioCryst, Boehringer Ingelheim, Bristol Myers Squibb, Castle Creek, Catawba, Dermavant, Eli Lilly, Galderma, InMed, Janssen, Krystal, LEO Pharma, Novartis, Regeneron, Sanofi/Genzyme, Seanergy, TWI Biotechnology and UCB. C.-Y.Y. reports being an investigator for Eli Lilly and Company, AbbVie, Pfizer and Sanofi. A. Prakash, D.Z., M.A.G.P.F. and W.-S.W. are employees of and stockholders in Eli Lilly and Company. L.E. reports serving as a scientific adviser, consultant and/or clinical study investigator for AbbVie, Almirall, Amryt Pharma, ASLAN Pharmaceuticals, Arcutis Biotherapeutics, Arena, Castle Biosciences, Dermavant Sciences, Eli Lilly and Company, Forté, Galderma, Incyte, LEO, Novartis, Ortho Dermatologics, Pfizer, Regeneron and Sanofi Genzyme.