Combination targeted therapy with two biologic/targeted synthetic DMARDs in 1200 patients with immune mediated inflammatory diseases. A systematic literature review for current landscape in safety and efficacy.
Angeliki Zoi Lignou, Konstantinos D Vassilakis, Xenofon Baraliakos, Petros P Sfikakis, Jacques-Eric Gottenberg, George E Fragoulis
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Abstract
Background: Immune-mediated inflammatory diseases (IMID) include rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), Crohn's disease (CD), ulcerative colitis (UC), and psoriasis (PsO). While biologic (b) and targeted synthetic (ts) DMARDs are effective, nearly 60 % of patients fail to achieve low disease activity status. Combination targeted therapy (CTT) using concomitantly two different b- or ts-DMARDs has been explored, but results on safety and efficacy are unclear.
Objective: To systematically review the literature on CTT in IMID.
Methods: Following the PICO framework, we included literature of adult patients (≥18 years) with IMID receiving CTT. Three databases (PubMed, Scopus, Epistemonikos) were searched up to June 2024. Studies in non-English, pediatric populations, and non-approved treatments were excluded. Risk of bias was assessed using approved tools.
Results: Of 2038 records, 70 studies (6 RCTs, 11 cohorts, 22 case series, 31 case reports) involving 1200 patients were analyzed. About 75 % of them demonstrated low risk of bias. The most studied combinations were TNFi+IL/23i, JAKi+bDMARDs, and vedolizumab+TNFi. Approximately 40-60 % of patients with PsA, axSpA, and IBD with refractory disease improved with TNFi+IL/23i CTT. About half of patients with inflammatory arthritis and up to 80 % of IBD cases benefited with JAKi+bDMARD CTT, whereas favorable outcomes were observed in 30-50 % of IBD patients following Vedolizumab+TNFi CTT. Safety profiles were generally acceptable, without emerging signals so far.
Conclusion: CTT benefits about half of refractory IMID patients, particularly TNFi/IL-23i, JAKi/bDMARD, and vedolizumab/TNFi combinations, without raising significant safety issues. Further research is needed to clarify safety and efficacy across diseases.
期刊介绍：
Autoimmunity Reviews is a publication that features up-to-date, structured reviews on various topics in the field of autoimmunity. These reviews are written by renowned experts and include demonstrative illustrations and tables. Each article will have a clear "take-home" message for readers.
The selection of articles is primarily done by the Editors-in-Chief, based on recommendations from the international Editorial Board. The topics covered in the articles span all areas of autoimmunology, aiming to bridge the gap between basic and clinical sciences.
In terms of content, the contributions in basic sciences delve into the pathophysiology and mechanisms of autoimmune disorders, as well as genomics and proteomics. On the other hand, clinical contributions focus on diseases related to autoimmunity, novel therapies, and clinical associations.
Autoimmunity Reviews is internationally recognized, and its articles are indexed and abstracted in prestigious databases such as PubMed/Medline, Science Citation Index Expanded, Biosciences Information Services, and Chemical Abstracts.
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