Long-Term Effectiveness and Safety of Biologic and Small Molecule Drugs for Moderate to Severe Atopic Dermatitis: A Systematic Review

Abstract

Introduction: Atopic dermatitis (AD) is a genetically based chronic inflammatory dermatosis associated with multiple triggers and complex pathophysiological mechanisms. Nowadays, an authentic therapeutic revolution is taking place with the incorporation of biological drugs for the treatment of moderate and severe atopic dermatitis. A new systematic revision (RS) is necessary to support decision-making for specialists treating AD. Methods: A literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials was performed between 1 January 2000 and 30 April 2022. Phase III randomized clinical trials (RCTs) of EMA-approved molecules were included. The main variables analyzed were a 75% improvement in the Eczema Area and Severity Index (EASI 75) and the number of patients who reached 0 in the Investigator Global Assessment (IGA) (fully cleared patients) or IGA 1 (almost cleared patients) at the end of the study period (week 48–60). The risk of bias was analyzed with the Cochrane Risk of Bias Assessment (ROB-2) tool, focused on the primary objectives. Before carrying out the study, the protocol was registered in PROSPERO with the number CRD42022331109. Results: A total of 3299 studies were systematically identified via databases and registers (442 from PubMed/MEDLINE, 2857 from Embase and 719 from CENTRAL). Finally, five publications containing seven RCTs were included in the final sample of detailed data extraction and data analyses. Regarding efficacy, the best results are obtained with Upadacitinib 30 mg (84.7% (77.3–92.1)) at 52 weeks, slightly improving its results when TCS is added (84.9% (80.3–89.5)). These results are replicated in the measurement of vIGA 0/1 for Updacitinib 30 mg + TCS, where 65.5% (55.7–75.2) of patients maintain it at 52 weeks. Of the four drugs, no long-term safety results have been reported for baricitinib. In relation to the safety findings, there were no significant differences in the dropout rates for this reason in the remaining three drugs. Discussion: Today, different therapeutic options for AD patients can be prescribed. Individualizing the treatment allows for better therapeutic consistency, in addition to being cost-efficient to avoid primary therapeutic failures. The results of the present SR may provide us with a useful basis for the preparation of management guidelines for the use of new generation therapies in moderate to severe atopic dermatitis.

Keywords

• atopic dermatitis
• EASI
• IGA
• pruritus NRS
• systematic literature review
• treatment