Effects of systemic therapies on pruritus in adults with atopic dermatitis: a systematic review and meta-analysis.

Pruritus is a hallmark of atopic dermatitis (AD), affecting disease severity and patients' quality of life. In AD uncontrolled with first-line topical therapies or in moderate-to-severe AD, systemic therapies are used, however, there are paucity of head-to-head trials comparing their effectiveness. The aim was to compare the effectiveness between the systemic therapies on relieving pruritus in moderate-to-severe AD in adults through meta-analysis. PubMed, EMBASE, Medline and CINAHL databases were searched from inception up to 31 May 2020 for placebo-controlled randomised controlled trials investigating the effectiveness of systemic therapies on pruritus with moderate-to-severe AD in adults aged ≥ 16. 26 studies were identified (n = 5,190 participants). There was a large reduction in pruritus compared to placebo (standard mean difference [95% confidence interval]) with dupilumab every 2 weeks (q2w) (-0.88 [-1.13, -0.63]), q2w + topical corticosteroids (-0.77 [-0.91, -0.62]); dupilumab once weekly (qw) (-0.99 [-1.29, -0.68]), qw + topical corticosteroids (-0.70 [-0.81, -0.59]); a large reduction with ciclosporin (-1.30 [-2.34, -0.26]); a small reduction with mepolizumab (-0.27 [-0.89, 0.35]), interferon gamma (-0.31 [-0.75, 0.12]); a large reduction with azathioprine (-0.85 [-2.07, 0.35]). Amongst investigational drugs, nemolizumab 2.0mg/kg was the most effective (-8.13 [-9.31, -6.94]). The majority of systemic therapies were superior to placebo in reducing pruritus. In particular, dupilumab studies consistently showed large improvements in pruritus and nemolizumab showed the strongest anti-pruritic effects, however future head-to-head trials are required for conclusive evidence.