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.

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.