A real-world study on inflammatory bowel disease employing originator and biosimilar biologics suggests anti–tumor necrosis factor (TNF) therapy may be more effective for Crohn disease than for ulcerative colitis.
Authors of a 1-year real-world study on anti—tumor necrosis factor (TNF) originator biologics and biosimilars for Crohn disease (CD) and ulcerative colitis (UC) found anti-TNF therapy overall was more effective for achieving remission in patients with CD compared with those with UC.
Moderate to severe inflammatory bowel disease (IBD) may be treated with the anti-TNF biologics infliximab or adalimumab or their biosimilars, and the introduction of anti-TNF agents has improved rates of remission and quality of life in IBD. However, the investigators identified a knowledge gap, noting that comparisons of effectiveness, safety, and tolerability of the anti-TNF agents between the 2 diseases have only been performed indirectly through meta-analysis.
The retrospective study included 179 patients, 89 with UC and 90 with CD. Approximately one-third of each group took the infliximab originator (Remicade), infliximab biosimilar (Remsima; CT-P13), or adalimumab (Humira).
Clinical activity and inflammatory markers were measured at baseline, after induction (14 weeks for infliximab, 8 weeks for adalimumab), at 30 weeks, and at 52 weeks. Endoscopic measures were assessed at baseline and 52 weeks.
Clinical response and remission
After the induction period, there was a significant difference (P = .05) in the percent of patients on any therapy who achieved clinical response between UC (84.3%) and CD (93.3%); the difference between diseases diminished by 30 weeks, and at 52 weeks, 82% of patients with UC and 80% with CD had achieved clinical response, although this finding was not significant (P = .6).
The rate of steroid-free clinical remission after induction was higher in CD (58.8%) compared with UC (42.7%; P = .03). At 30 and 52 weeks, remission rates were higher in CD compared with UC, with 72.2% of patients with CD in steroid-free clinical remission at 52 weeks compared with 60.7% of patients with UC (P = .03).
Among individual drugs, remission rate differences in the infliximab originator group became significant at 30 weeks between UC (56.7%) and CD (80%). At 52 weeks, remission rates were higher in CD for both the infliximab reference product and biosimilar groups, but the differences did not reach statistical significance (P = .08). At 52 weeks, steroid-free clinical remission rates for the infliximab originator were 66.7% and 80% in UC and CD, respectively, and 57.1% and 76.7% for the biosimilar.
Differences in remission rates between diseases for patients taking adalimumab did not reach significance at any point in the study. In patients taking adalimumab, the steroid-free clinical remission rates at 52 weeks were 58.1% and 60% for UC and CD, respectively.
Regarding their finding of greater remission rates overall for CD compared with UC, the authors said the differences between the disease activity scoring methods are worth noting. In particular, the Harvey Bradshaw Index for CD takes into account “the intestinal manifestations of illness, present in 48.9% of our patients, and the subjective component of perception of the patients' health status,” which do not factor into the partial Mayo score for UC.
Overall, 13 patients discontinued therapy due to adverse events (AEs). The most frequent AEs were allergic reactions, dermatologic manifestations, and infections. The infliximab biosimilar group had both the greatest number of total discontinuations (3 in UC and 5 in CD) and the most AE-related discontinuations (1 in UC and 3 in CD). The adalimumab group had the greatest number of discontinuations for lack of efficacy.
The authors observed 3 cases of malignant disease during the study, which they say necessitates “careful and comprehensive follow-up of the patient in biological therapy.”
Endoscopic response was achieved by 51% of patients on adalimumab compared with 43.4% on the infliximab originator and 41.7% on the infliximab biosimilar. In the adalimumab group, endoscopic response was more common in UC compared with CD. The authors did note, however, endoscopic data were available for all patients with UC but only about half of patients with CD.
The drugs started out at standard doses, but physicians were later allowed to optimize dosage for the individual patients. At week 30, 20% of patients with UC on the infliximab originator required optimization of therapy compared with none with CD. No other significant differences in optimization between diseases were reported. At week 52, 31.1% of patients taking adalimumab, 16.7% taking the infliximab originator, and 36.2% taking the infliximab biosimilar required treatment optimization.
Given the real-world setting of the study, the authors found several baseline characteristics were significantly different between groups. They performed multivariate analysis adjusted for those factors, which included endoscopic disease activity, disease duration, percent of biologic-naive patients, extraintestinal manifestations, use of a concomitant steroid, and C-reactive protein level. Multivariate analyses suggested a 3-to-4—fold greater likelihood of clinical remission or steroid-free clinical remission at 30 and 52 weeks for patients with CD compared with those with UC.
The investigators consider their study a step toward greater understanding of anti-TNF agents in IBD and therapy tailored to the individual patient, as well as a starting point for future, larger prospective studies and randomized controlled trials comparing biologics use between UC and CD.
Barberio B, Zingone F, DʼIncà R, et al. Infliximab originator, infliximab biosimilar, and adalimumab are more effective in Crohn's disease than ulcerative colitis: a real-life cohort study. Clin Transl Gastroenterol. 2020;11(5):e00177. doi:10.14309/ctg.0000000000000177