Systematic Review With Meta-Analysis: Safety and Effectiveness of Combining Biologics and Small Molecules in Inflammatory Bowel Diseases.

Background: The systematic review and meta-analysis (SRMA) evaluates the safety and effectiveness of combining biologics and/or small molecules in treating refractory inflammatory bowel diseases (IBD).

Methods: Our 2022 SRMA identified 13 studies published until November 3, 2020. An updated systematic search was completed from May 2020 through January 31, 2024. Random-effects inverse variance model was used to calculate pooled estimates for adverse events (AEs) and clinical and endoscopic-radiologic response/remission rates in IBD patients.

Results: Twenty-seven eligible studies had 619 patients and 631 therapeutic trials (TTs). Upadacitinib (UPA) + vedolizumab (VDZ) and tofacitinib (Tofa) + anti-TNF (aTNF) had the lowest AEs rate (0%, 2 TTs) and (9.2%, 33 TTs), respectively. Higher AE rates were seen in natalizumab (NAT) + aTNF (92.3%, 52 TTs) and aTNF + guselkumab (63.4%, 71 TTs). No serious AEs (SAEs) were observed in NAT + aTNF (52 TTs), Tofa + ustekinumab (UST) (23 TTs), and UPA + VDZ (2 TTs). The highest rate of SAEs was observed in UPA + UST (23%, 17 TTs). UPA + UST and UPA + VDZ had 100% clinical response rates and the highest clinical remission rates (83.3%, 12 TTs) and (100%, 2 TTs), respectively. High clinical response rates were also seen in Tofa + aTNF (82.7%, 34 TTs), UST + aTNF (82.1%, 63 TTs), and VDZ + UST (82.0%, 71 TTs).

Conclusions: Combining biologics and/or small molecules may be effective for IBD patients who fail to achieve remission with monotherapy; however, safety profiles need to be carefully considered prior to implementing these strategies in clinical practice.