For patients with treatment-refractory ulcerative colitis, accelerated induction with infliximab did not appear to reduce the need for colectomy, while adding a calcineurin inhibitor to vedolizumab safely and effectively induced clinical remission in nearly half of patients, according to the results of two studies published in Clinical Gastroenterology and Hepatology.
Theretrospectively evaluated 213 patients with acute severe ulcerative colitis who received infliximab rescue therapy at three gastroenterology centers between 2005 and 2017. Rates of subsequent colectomy were similar whether patients received infliximab (5 mg/kg) at weeks 0, 2, and 6, or were on an accelerated schedule (8% vs. 9%, respectively; adjusted odds ratio, 1.35; 95% confidence interval, 0.38-4.82).
However, among patients who received accelerated treatment, those who received a higher initial dose of infliximab (10 mg/kg) were less likely to subsequently undergo colectomy than those who started at 5 mg/kg and received “chaser” 5-mg or 10-mg doses before week 2, reported Niharika Nalagatla, MD, of Massachusetts General Hospital in Boston, with her associates. “While there was no statistically significant difference [between these groups], there were numerically lower rates of in-hospital and long-term colectomy in the 10 mg/kg group, with a trend toward statistical significance at 2 years [OR, 0.44; 95% CI, 0.18-1.12; P = .08],” they added.
They reported similar results from their systematic review and meta-analysis of seven studies of infliximab induction schedules in patients with acute severe ulcerative colitis. Accordingly, they called for prospective studies to identify which patients are most likely to benefit from accelerated infliximab therapy.
The, which was prospective, included 11 patients with treatment-refractory ulcerative colitis who initially received vedolizumab immunotherapy and then started on a calcineurin inhibitor (either tacrolimus or cyclosporine) during their first 12 months of treatment. Rates of steroid-free clinical remission (Harvey-Bradshaw index score less than 4 or short clinical colitis activity index score less than 2) were 55% at week 14 and 45% at week 52, reported , of the University of Chicago and the Royal Melbourne Hospital, with her associates.
Two of these patients were hospitalized for intravenous cyclosporine plus corticosteroid therapy because they failed to respond to 3 months of treatment with vedolizumab plus prednisolone (40 mg), the investigators noted. One patient did not respond and ultimately underwent colectomy, while the other tapered off cyclosporine after 51 days of treatment and remained in steroid-and calcineurin-free clinical remission at 12 months.
Serious adverse events were uncommon, reflecting the relatively good safety profile of vedolizumab. Combination antitumor necrosis factor and calcineurin inhibitor therapy has been linked to severe infections and deaths, and clinical trials of vedolizumab excluded patients with calcineurin inhibitor exposure. However, vedolizumab primarily targets the localized immune system of the gut, so adding an agent “with broad immune-suppressing effects would not [lead to greater] infective and other complications,” the investigators wrote. “Indeed, no significant toxicity was observed in our series, despite the fact that many patients were on quadruple immunosuppressive therapy, at least initially.”
Dr. Nalagatla reported receiving support from the National Institutes of Health and the Crohn’s & Colitis Foundation. She reported having no relevant conflicts of interest. One of her coinvestigators reported ties to AbbVie, Takeda, Gilead, Merck, and Pfizer. Dr. Christensen and her associates reported receiving support from the University of Chicago and the government of Australia. Dr. Christensen reported ties to Janssen, AbbVie, Takeda, and Pfizer, and four of her coinvestigators also reported ties to a number of pharmaceutical companies.
SOURCES: Nalagatla N et al. Clin Gastroenterol Hepatol. 2018 Jun 23. ; Christensen B et al. Clin Gastroenterol Hepatol. 2018 May 8. .