Comparative Safety and Effectiveness of Vedolizumab to Tumor Necrosis Factor Antagonist Therapy for Ulcerative Colitis

Abstract

Background & aims: We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice.

Methods: A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist-naïve and -exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately.

Results: A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist-naïve and -exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist-treated patients. However, in TNF-antagonist-naïve patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754).

Conclusions: Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist-naïve patients.

Keywords: Biologics; Comparative Research; Health Outcomes.

Figure 1.

Standardized mean difference and distribution of propensity scores. Standardized mean difference before (red) and after (blue) weighting for (A) serious infections, serious adverse events, clinical remission, and deep remission; (B) deep remission limited to subset with moderate-severe endoscopic inflammation at baseline; and (C) steroid-free clinical remission and steroid-free deep remission. Distribution of propensity scores between cohorts for (D) serious infections, serious adverse events, clinical remission, and deep remission; (E) steroid-free clinical remission and steroid-free deep remission. Anti-TNF, tumor necrosis factor antagonist; ATE, average treatment effect; IM, immunomodulatory; SAE, serious adverse event.

Figure 2.

Comparative safety of vedolizumab to TNF antagonist therapy in UC. (A) Comparative safety of vedolizumab to TNF antagonist therapy for serious adverse events. (B) Comparative safety of vedolizumab to TNF antagonist therapy for serious infections. CI, confidence interval; IPW, inverse probability weighting; TNF antagonist, tumor necrosis factor antagonist (infliximab, adalimumab, golimumab). Serious infections or adverse events defined as infections or non-infection adverse events requiring antibiotics, antivirals, antifungals, discontinuation of therapy, hospitalization, or resulting in death.

Figure 3.

Comparative effectiveness of vedolizumab vs TNF antagonist therapy in UC for achieving clinical remission and deep remission. (A) Comparative effectiveness of vedolizumab vs TNF antagonist therapy for clinical remission. (B) Comparative effectiveness of vedolizumab vs TNF antagonist therapy for deep remission (clinical + endoscopic remission). CI, confidence interval; IPW, inverse probability weighting; TNF antagonist, tumor necrosis factor antagonist (infliximab, adalimumab, golimumab); UC, ulcerative colitis. Deep remission was defined as achieving clinical remission (resolution of diarrhea, rectal bleeding, and/or urgency) and endoscopic remission (Mayo endoscopic subscore 0 or 1).

Figure 4.

Comparative effectiveness of vedolizumab vs TNF antagonist therapy in UC for achieving steroid-free clinical remission and steroid-free deep remission. (A) Comparative effectiveness of vedolizumab vs TNF antagonist therapy for steroid-free clinical remission. (B) Comparative effectiveness of vedolizumab vs TNF antagonist therapy for steroid-free deep remission (steroid-free clinical + endoscopic remission). CI, confidence interval; IPW, inverse probability weighting; TNF antagonist, tumor necrosis factor antagonist (infliximab, adalimumab, golimumab); UC, ulcerative colitis. Analyses restricted to patients on steroids at baseline. Steroid-free deep remission was defined as achieving clinical remission, endoscopic remission, tapering off steroids, and no repeat steroid prescription for at least 4 weeks.