We read with great interest the prospective observational study by Monterubbianesi et al. of infliximab (IFX) for the treatment of severe ulcerative colitis (UC) 1 . The authors noted 3- and 12-month colectomy rates of 18.6% and 25.6%, respectively. Three-dose induction was completed in 82%; importantly, 75% of those unable to complete induction required surgery. In multivariate analysis, high baseline CRP concentrations and severe endoscopic disease were associated with risk of colectomy. At our center, we also observed that patients who completed induction dosing fared better, irrespective of whether IFX was given in the inpatient or outpatient setting.
At our institution, we retrospectively observed 351 patients with UC who had received at least one dose of IFX between September 2005 and June 2009. The median follow-up was 8.1 months (range, 0.1–44.5). At the first infusion, 59.5% were on oral steroids, 17.4% on IV steroids, 46.5% on immunomodulators, and 1.1% had prior exposure to biologic agents. Seventy patients (19.9%) were hospitalized at the time of first IFX.
One hundred thirty-four patients (38.2%) required colectomy, with cumulative probabilities at 6 months, 12 months, and 24 months of 22.8%, 35.6%, and 51.7%, respectively. In proportional hazard regression analysis, hospitalization at first IFX was neither associated with likelihood nor time to colectomy (HR 1.19; 95% CI, 0.78– 1.82). In addition, immunosuppression at time of first IFX (HR 0.95; 95% CI, 0.68–1.34), extent of disease (HR 1.10; 95% CI, 0.78–1.57), and primary sclerosing cholangitis (HR 0.84; 95% CI, 0.37–1.92) were not associated with time to colectomy. We observed differences in patients who completed induction dosing (76.1% of the entire cohort and 70% of those hospitalized). At 6 months, 84% of patients who received partial or complete induction dosing (n = 185) were colectomy-free, compared to 49% of patients who did not receive induction dosing (n = 24) (p b 0.001) ( Fig. 1 ). One hundred four patients required dose escalation (29.6%). At last follow-up, 125 patients (35.6%) were still on IFX. Adverse events occurred in 78 patients (22.2%), and these precluded continuation of IFX in 47 patients. The retrospective nature of our study impeded correlation of colectomy with serologic or endoscopic markers.
While these colectomy rates are higher than reported in the ACT 1 and 2 studies of UC, it is important to remember that patients in these trials completed an induction regimen 2 . Two recent studies of hospitalized patients also noted relatively high colectomy rates (32.5–34.1%), but did not analyze induction dosing as a predictor of colectomy 3 , 4 . McGinnis and Murray observed that patients who did not respond despite two doses of IFX had higher colectomy rates than the responders 5 . Our study was limited by its retrospective nature, and our results may be skewed by the setting at a tertiary referral center for surgical treatment of UC. Nevertheless, our results in some respects corroborate the findings of Monterubbianesi et al. 1 , and highlight the importance of full induction dosing.
Conflict of interest statement
Drs. Tung and Enders have no conflicts of interest to report.
Dr. Loftus has consulted for and has received research support from AbbVie, Janssen Biotech, Takeda, and UCB Pharma.