No Benefit of Concomitant Immunomodulator Therapy on Efficacy of Biologics That Are Not Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Diseases: A Meta-analysis

Abstract

BACKGROUND & AIMS:There is debate over whether patients with inflammatory bowel diseases (IBD) treated with biologics that are not tumor necrosis factor antagonists (such as vedolizumab or ustekinumab) should receive concomitant treatment with immunomodulators. We conducted a meta-analysis to compare the efficacy and safety of concomitant immunomodulator therapy vs vedolizumab or ustekinumab monotherapy. METHODS:In a systematic search of publications, through July 31, 2019, we identified 33 studies (6 randomized controlled trials and 27 cohort studies) of patients with IBD treated with vedolizumab or ustekinumab. The primary outcome was clinical benefit, including clinical remission, clinical response, or physician global assessment in patients who did vs did not receive combination therapy with an immunomodulator. Secondary outcomes were endoscopic improvement and safety. We performed random-effects meta-analysis and estimated odds ratio (OR) and 95% CIs. RESULTS:Overall, combination therapy was not associated with better clinical outcomes in patients receiving vedolizumab (16 studies: OR, 0.84; 95% CI, 0.68-1.05; I2[13.9%; Q test P [ .17) or ustekinumab (15 studies: OR, 1.1; 95% CI, 0.87-1.38; I2 [ 11%; Q test P [ .28). Results were consistent in subgroup analyses, with no difference in clinical remission or response in induction vs maintenance studies or in patients with Crohn's disease vs ulcerative colitis in studies of vedolizumab. Combination therapy was not associated with better endoscopic outcomes in patients receiving vedolizumab (3 studies: OR, 1.13; 95% CI, 0.48-2.68; I2 [ 0; Q test P[.96) or ustekinumab (2 studies: OR, 0.58; 95% CI, 0.21-1.16; I2 [ 47%; Q test P [ .17). Combination therapy was not associated with an increase in adverse events during vedolizumab therapy (4 studies: OR, 1.17; 95% CI, 0.75-1.84; I2 [ 0; Q test P [ .110). CONCLUSIONS:In a meta-analysis of data from studies of patients with IBD, we found that combining vedolizumab or ustekinumab with an immunomodulator is no more effective than monotherapy in induction or maintenance of remission.

How to Optimize Treatment With Ustekinumab in Inflammatory Bowel Disease: Lessons Learned From Clinical Trials and Real-World Data

“…However, as discussed above some cohorts have suggested that combination therapy could improve the clinical efficacy of UST ( 24 – 26 ). Nonetheless, this observation has not been confirmed in more recent cohorts and one meta-analysis ( 56 , 57 ).…”

“…Whereas, data about the efficacy of combination therapy with TNF antagonists has consistently shown an improvement in clinical and endoscopic outcomes ( 54 , 55 ), evidence with UST or vedolizumab shows controversial results. Up to now, most of the evidence suggests no benefit of combination therapy with immunomodulators ( 56 , 57 ). A recent meta-analysis including 15 studies found no improvement in clinical or endoscopic outcomes between patients receiving monotherapy or a combination of both drugs (OR, 1.1; 95% CI, 0.87–1.38; and OR, 0.58; 95% CI, 0.21–1.16, respectively) ( 57 ).…”

“…Up to now, most of the evidence suggests no benefit of combination therapy with immunomodulators ( 56 , 57 ). A recent meta-analysis including 15 studies found no improvement in clinical or endoscopic outcomes between patients receiving monotherapy or a combination of both drugs (OR, 1.1; 95% CI, 0.87–1.38; and OR, 0.58; 95% CI, 0.21–1.16, respectively) ( 57 ). Therefore, current evidence do not support a clear benefit of these strategy, but as UST is frequently used in refractory patients this decision should be carefully balanced in an individual basis.…”

Update on TDM (Therapeutic Drug Monitoring) with Ustekinumab, Vedolizumab and Tofacitinib in Inflammatory Bowel Disease

“…A meta-analysis of 31 studies (randomized controlled trial, n = 6; cohort studies, n = 25) of IBD patients treated with UST or VDZ was recently published. In this study, combination therapy was no more effective than monotherapy as induction or maintenance therapy [ 43 ].…”

Letter: effectiveness of ustekinumab or vedolizumab in Crohn's disease following anti‐TNF failure—getting closer to the truth. Authors' reply

“…In our original cohort, there was indeed a difference in concomitant medication use at baseline between vedolizumab and ustekinumab. However, concomitant immunomodulating medication does not have a significant impact on effectiveness outcomes but does come with an increased risk of severe infections 7‐10 . Therefore, we did not add concomitant medication to our multiple logistic regression model for effectiveness outcomes but did use it for the analysis of safety outcomes.…”