Comparative efficacy and safety of systemic therapies used in moderate-to-severe atopic dermatitis: a systematic literature review and network meta-analysis

Abstract

Given the lack of head-to-head studies of systemic therapies in moderate-to-severe atopic dermatitis (AD), network meta-analyses (NMAs) can provide comparative efficacy and safety data to inform clinical decision-making. In this NMA, eligible randomized controlled trials (RCTs) published before 24 October 2019 were identified by a systematic literature review. Short-term (12-16 weeks) efficacy (Investigator's Global Assessment [IGA] and Eczema Area and Severity Index [EASI] responses), patient-reported outcomes (PROs) and safety data from each trial were abstracted and analysed separately for monotherapy and combination therapy (systemic plus topical anti-inflammatory therapy). RCTs were analysed in fixed-effects and random-effects Bayesian NMA models. Overall, 19 phase 2 and phase 3 RCTs of abrocitinib, baricitinib, dupilumab, lebrikizumab, nemolizumab, tralokinumab and upadacitinib were included. In monotherapy RCTs, upadacitinib 30 mg once daily (QD) had the numerically highest efficacy (83.6% achieved ≥50% improvement in EASI [EASI-50 response]), followed by abrocitinib 200 mg QD (74.6%), upadacitinib 15 mg QD (70.5%), dupilumab 300 mg every 2 weeks (Q2W) (63.4%) and abrocitinib 100 mg QD (56.7%). Similar trends in EASI-75 and EASI-90 response were observed. In combination therapy RCTs, abrocitinib 200 mg QD had the highest EASI-50 (86.6%), followed by dupilumab 300 mg Q2W (82.4%) and abrocitinib 100 mg QD (79.7%). Similar findings were observed for IGA response and PROs. In monotherapy and combination therapy RCTs, the probability of treatment-emergent adverse events (TEAEs) was higher among all active treatments than with placebo (except for dupilumab 300 mg Q2W [odds ratio (OR), 0.96; 95% credible interval (CrI), 0.45-2.18] and abrocitinib 100 mg QD [OR, 0.95; 95% CrI, 0.35-2.66] in combination therapy RCTs), although active treatments did not significantly differ from one another. Abrocitinib, dupilumab and upadacitinib were consistently the most effective systemic therapies in adult and adolescent patients with AD, with no significant TEAE differences in short-term RCTs.

Figure 1

PRISMA study attrition diagram. ^aBibliographies were searched for relevant citations. DARE, database of abstracts of reviews of effects; HTA, health technology assessment; NMA, network meta‐analysis; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta‐Analyses; SLR, systematic literature review.

Figure 2

Network diagram for (a) monotherapy and (b) combination therapy trials. Not all outcomes were available for all trials. TCS, topical corticosteroids.

Figure 3

Odds ratios of achieving an IGA response compared with placebo in (a) monotherapy and (b) combination therapy. IGA response defined as clear (0) or almost clear (1) with ≥2‐point reduction from baseline. CrI, credible interval; IGA, Investigator’s Global Assessment; QD, once a day; Q2W, every 2 weeks; Q4W, every 4 weeks; TCS, topical corticosteroids.

Figure 4

Odds ratios of achieving a PP‐NRS4 response with (a) monotherapy and (b) combination therapy compared with placebo. PP‐NRS4 response was defined as ≥4‐point improvement from baseline. CrI, credible interval; PP‐NRS, Peak Pruritus Numerical Rating Scale; QD, once a day; Q2W, every 2 weeks; Q4W, every 4 weeks; TCS, topical corticosteroids.

Figure 5

Odds ratios of experiencing a treatment‐emergent AE with (a) monotherapy and (b) combination therapy compared with placebo. AE, adverse event; CrI, credible interval; QD, once a day; Q2W, every 2 weeks; TCS, topical corticosteroids.

Figure 6

Odds ratios of experiencing an AE leading to discontinuation with (a) monotherapy and (b) combination therapy compared with placebo. AE, adverse event; CrI, credible interval; QD, once a day; Q2W, every 2 weeks; Q4W, every 4 weeks; TCS, topical corticosteroids.