Assessment of the Sustained Response to Systemic Treatment for Atopic Dermatitis in Patients Who Achieved Disease Remission: A Systematic Review and Network Meta-Analysis Comparing Withdrawal, Dose Reduction and Dosing Interval Extension Versus Continuation Therapy.

Abstract

Background: Recent therapeutic advances transformed the management of atopic dermatitis (AD). Medication withdrawal, dose reduction and dosing interval extension are sometimes necessary when managing AD.

Objectives: This review aims to compare the effectiveness of withdrawal, dose reduction and dosing interval extension with that of continuation of systemic therapy in sustaining remission among patients with AD.

Methods: A comprehensive search was conducted using the PubMed, Embase, Web of Science, and Scopus databases. Study selection was performed independently by two reviewers, and discrepancies were resolved by a third reviewer. The risk of bias was evaluated using the Cochrane risk of bias tool for randomized trials (RoB-2) and the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. The certainty of the evidence was determined in accordance with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The primary outcome was defined as sustained clinical improvement, measured by a 75% reduction in the Eczema Area and Severity Index (EASI), which was assessed 16 to 52 weeks after treatment withdrawal, dose reduction or dosing interval extension. Risk ratios (RRs) were compared using a network meta-analysis (NMA).

Results: After the initial search yielded 21,169 references, 89 reports representing 55 studies were included. Raw data analysis indicated that most active treatments showed comparable RRs for EASI75 maintenance, whereas the discontinuation of oral therapies led to early relapses in AD activity. On the basis of 9 studies encompassing 26 pairwise comparisons and 2,585 observations across 13 regimens, our NMA revealed that lebrikizumab withdrawal and dosing interval extension conferred a lower risk of EASI75 response loss than withdrawal, dose reduction, or dosing interval extension with other active therapies did. A subgroup analysis also revealed that the maintenance of EASI75 responses after placebo withdrawal or dosing interval extension was greatest for induction dosing with lebrikizumab.

Conclusions: While the withdrawal of systemic therapy is recommended in certain circumstances, such as during vaccination and pregnancy, the evidence reveals an early risk of relapse following the withdrawal of oral treatments. In contrast, biologic therapies resulted in sustained remission rates, even after prolonged withdrawal or dosing interval extension periods.