Early improvements in signs and symptoms predict clinical response to baricitinib in patients with moderate-to-severe atopic dermatitis.

Background: Early prediction of therapeutic response can optimize treatment strategies in atopic dermatitis (AD). Baricitinib is approved for moderate-to-severe AD in Europe, Japan and other countries.
Objectives: To identify early clinical improvements that can reliably predict a later clinical response to baricitinib in adults with moderate-to-severe AD.
Methods: Using data from one topical corticosteroid combination study [BREEZE-AD7 (NCT03733301)] and data pooled from two monotherapy studies [(BREEZE-AD1 (NCT03334396) and BREEZE-AD2 (NCT03334422)], we calculated the sensitivity and specificity, along with the positive predictive value (PPV) and negative predictive value (NPV), of predefined changes in single and combined clinical scores at weeks 2, 4 and 8, to predict clinical response at week 16. Clinical response was defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI 75), ≥ 4-point improvement in Itch Numeric Rating Scale (Itch NRS ≥ 4), or a combination of both.
Results: Composite predictors had higher predictive accuracy for week 16 response outcomes than did single parameters. This was evident as early as week 4 for the combination of EASI 50 or Itch NRS ≥ 3 and of validated Investigator Global Assessment for AD (vIGA-AD) score ≤ 2 or Itch NRS ≥ 3 (sensitivity 87-100%; NPV 68-100%). The predictive accuracy of these composite clinical predictors for week 16 response outcomes was highest at week 8 (sensitivity 92-100%; NPV 80-100%). At both weeks 4 and 8, EASI 50 or Itch NRS ≥ 3 had higher sensitivity and NPV than did vIGA-AD score ≤ 2 or Itch NRS ≥ 3.
Conclusions: Improvement in signs and symptoms early during treatment with baricitinib 4 mg once daily predicts clinical response at week 16, providing a tool for dermatologists when choosing treatment strategies for patients with moderate-to-severe AD.
Competing Interests: Conflicts of interest T.B. has acted as speaker, and/or consultant and/or investigator for AbbVie, Almirall, AnaptysBio, Arena Pharmaceuticals Ltd, Asana Biosciences, Astellas Pharma, Bayer Health, BioVerSys, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Dermavant/Roivant, Dermtreat, Domain Therapeutics, DS Pharma, Eli Lilly and Company, Galapagos/MorphoSys, Galderma, Glenmark Pharmaceuticals, GSK, Incyte, Kymab, L’Oréal, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Pierre Fabre, RAPT Therapeutics/FLX Bio, Sanofi/Regeneron and UCB; and he is founder of the nonprofit biotech company Davos Biosciences. J.P.T. is an advisor for AbbVie, Almirall, Arena Pharmaceuticals, Aslan Pharmaceuticals, Eli Lilly and Company, LEO Pharma, OM Pharma, Pfizer, Regeneron, Sanofi/Genzyme and UNION Therapeutics; is a speaker for AbbVie, Almirall, Eli Lilly and Company, LEO Pharma, Pfizer, Regeneron and Sanofi/Genzyme; and has received research grants from Pfizer, Regeneron and Sanofi/Genzyme. A.D.I. is a consultant/speaker for AbbVie, Almirall, Arena, Benevolent AI, LEO Pharma, Lilly, Pfizer and Regeneron. Y.T. has received fees for lectures from Eli Lilly Japan K.K., Kyowa Kirin Co., Ltd., Maruho Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Sanofi K.K., Taiho Pharmaceutical Co., Ltd. and Torii Pharmaceutical Co., Ltd. Y.F.C., L.S., A.S. and E.R. are employees of and shareholders in Eli Lilly and Company. M.J.C. has served as a clinical trial investigator for Astellas Pharma, Atopix, Galapagos NV, Harvey Water Softeners, Hyphens Pharma, Johnson & Johnson, Kymab, LEO Pharma, L’Oréal, Novartis, Oxagen, Perrigo, Pfizer, Reckitt Benckiser, Regeneron and Sanofi Genzyme; and has served as a consultant for Astellas, Atopix Therapeutix Limited, Boots, Dermavant Sciences, Eli Lilly, Galapagos NV, Galderma, Harvey Water Softeners, Hyphens Pharma, Johnson & Johnson, Kymab, LEO Pharma, L’Oréal, Menlo Therapeutics, Novartis, Oxagen, Perrigo, Pfizer Inc., Procter & Gamble, Reckitt Benckiser, Regeneron, Sanofi/Genzyme and UCB.
(© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)