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.

Improvement of head and neck symptoms in patients with atopic dermatitis treated with baricitinib based on five Phase III clinical trials

Background: In adults with atopic dermatitis (AD), head and/or neck involvement is frequent, bothersome, and impacts quality of life, however, long-term topical corticosteroids (TCS) are contraindicated for this difficult-to-treat region. Baricitinib, an oral, selective, reversible inhibitor of Janus kinase 1/2 has demonstrated efficacy in adult patients with moderate-to-severe AD. Objectives: For this post hoc analysis, data from five Phase III trials were used to investigate the efficacy of baricitinib in patients with head and neck involvement. Materials & Methods: Data were obtained from BREEZE-AD1, -AD2, -AD4, -AD5, and -AD7; Phase III, multicenter, randomized, double-blind, placebo-controlled studies conducted in patients ≥18 years with moderate-to-severe AD. BREEZE-AD1, -AD2, and -AD5 evaluated baricitinib as monotherapy, and BREEZE-AD4 and -AD7 evaluated baricitinib in combination with TCS, topical calcineurin inhibitors, or topical PDE-4 inhibitors, where available. The proportion of patients with improvement of Eczema Area and Severity Index (EASI) total score from baseline of ≥50% (EASI50) and ≥75% (EASI75), as well as head/neck EASI50 and EASI75 and erythema head/neck EASI50 and EASI75 response rates were assessed up to Week 16. Results: Across the studies, 93-98% of patients had head/neck involvement at baseline (EASI head/neck score ≥1). Baricitinib was similarly effective based on EASI total score for the entire body in all studies. In the monotherapy studies, the proportion of patients achieving head/neck EASI50 and EASI75 scores was significantly higher for baricitinib 2-mg and 4-mg versus placebo at Weeks 1 and 16. Conclusion: Baricitinib 2-mg and 4-mg treatment showed rapid and substantial reduction in AD head and neck severity, including erythema.