Introduction
Multiple treatment choices are available for patients with either Ulcerative Colitis (UC) or Crohn’s Disease (CD) requiring a first biologic therapy, but there is very limited data on comparative efficacy of different agents. Outcomes from robust, large-scale cohort studies can help to inform therapeutic decisions.
Aims & Methods
To compare the efficacy of first line biologic therapies [infliximab (IFX), adalimumab (ADA), golimumab (GLM), vedolizumab (VDZ)] in biologic-naïve patients with UC and CD and enrolled in the UK Inflammatory Bowel Disease (IBD) BioResource. Patients receiving first-line tofacitinib and ustekinumab were excluded from the analysis due to low numbers. Demographic, disease, treatment and outcome data were retrieved. Inverse probability of treatment weighting (IPTW) was used to balance groups using a propensity score-weighting approach accounting for baseline patient or disease related clinical characteristics. Balancing success was assessed with standardized mean differences (SMDs). Effectiveness of treatment was based on persistence free of treatment discontinuation or treatment failure. Failure was defined as occurring if any of the following occurred: (a) clinician-recorded treatment failure (b)start of treatment with a different biologic drug (c)occurrence of resectional or defunctioning bowel surgery. We compared Kaplan Meier curves for treatment failure-free survival after IPTW and used a log rank test for differences between the groups.Cox proportionate hazard ratios (HR)were used for comparisons between treatments.
Results
In total, 12747 patients were included in the analysis (UC=3967, CD=8780). Over a four-year follow up period, treatment survival free of treatment failure or treatment escalation was significantly different between different treatment groups both in UC and CD (log rank p=0.007 and p=0.011 respectively). For UC, we found that VDZ was superior to all anti-TNF agents [vs GLM HR 3.4 (95% CIs 2.2-5.2), vs ADA HR 3.1 (95% CIs 2.1-4.5), vs IFX HR 1.9 (95% CIs 1.3-2.8), all p values <0.001]. When compared between anti-TNF agents IFX was superior to both ADA and GLM [vs ADA HR 1.6 (95% CIs 1.4-1.8), vs GLM HR 1.7 (95% CIs 1.3-2.2)] while no significant difference was detected when ADA and GLM were compared. For CD, IPTW did not achieve optimal balancing for baseline differences in the presence of perianal disease. Restricting analysis to the subgroup with the absence of perianal disease, we did not observe a significant difference in treatment outcomes.
Conclusion
Our study showed superiority of VDZ over anti-TNF agents in biologic naïve patients with UC. This is in accordance with, and extends the findings of, a prior head-to-head trial in UC comparing VDZ and ADA1. In patients with luminal CD, no difference was detected between VDZ and anti-TNF agents. Our data offer guidance to physicians and patients as to relative drug efficacy for first line therapies in IBD.
References
1. Sands BE, Peyrin-Biroulet L, Loftus EV Jr, et al. Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis. N Engl J Med. 2019;381(13):1215-1226. doi:10.1056/NEJMoa1905725
