Tofacitinib Proves Safe in Postoperative Care for Acute Severe Ulcerative Colitis

A recent study has provided reassuring findings regarding the use of tofacitinib, a Janus kinase (JAK) inhibitor, in patients with acute severe ulcerative colitis (ASUC). Conducted by a team of researchers from Michigan Medicine and published in the Clinical Gastroenterology and Hepatology journal, the study offers a head-to-head comparison between tofacitinib and infliximab, a chimeric monoclonal antibody, with a focus on postoperative complications. According to Dr. Jeffrey A. Berinstein, a senior author and gastroenterologist at Michigan Medicine, the findings indicate that tofacitinib does not worsen postoperative complications and may even reduce the necessity for colectomy, a surgical procedure to remove part of the colon.

The study addressed longstanding concerns among clinicians regarding the safety of JAK inhibitors in surgical settings. "Tofacitinib has shown efficacy in managing ASUC, but concerns about postoperative complications have limited its adoption," Berinstein stated. The research involved a multicenter, retrospective, case-control study that evaluated 109 patients hospitalized for ASUC at two U.S. centers and 14 in France. Of these patients, 41 received treatment with tofacitinib, while 68 were treated with infliximab prior to colectomy.

The results revealed that patients treated with tofacitinib experienced significantly lower overall rates of postoperative complications, with 31.7% compared to 64.7% in the infliximab group (odds ratio [OR], 0.33; P = .006). Furthermore, serious postoperative complications were also lower in the tofacitinib group (12% vs 28.9%; OR, 0.20; P = .016). After controlling for variables such as age, inflammatory burden, and nutritional status, a trend favoring tofacitinib persisted, although it was not statistically significant (P = .061). Importantly, a subanalysis indicated that patients receiving the FDA-approved induction dose of 10 mg twice daily of tofacitinib had significantly lower overall rates of complications (OR, 0.23; P = .003).

Dr. Charlotte Larson, the first author of the study, emphasized the importance of understanding the potential risks associated with JAK inhibitors. "Anecdotally, gastroenterologists and surgeons have expressed concern about JAK inhibitors leading to poor wound healing, as well as increasing both intraoperative and postoperative complications," she noted. However, the current study's findings alleviate some of these concerns. The tofacitinib group also showed no increased risk for postoperative venous thromboembolic events, which is particularly important given previous associations of tofacitinib exposure with increased VTE risk independent of other prothrombotic factors.

In context, ASUC is a severe form of ulcerative colitis characterized by symptoms such as fecal urgency, rectal bleeding, and severe abdominal pain, often requiring hospitalization. Conventional treatment typically involves rapid induction with intravenous corticosteroids, yet up to 30% of patients may not respond, leading to a significant portion requiring surgery. Recent advancements in treatment options, including JAK inhibitors like tofacitinib and upadacitinib, have emerged as promising alternatives.

The implications of this study are significant for clinical practice. Dr. Joseph D. Feuerstein, a gastroenterology specialist at Harvard Medical School, commented on the findings, stating that knowing the complication rates are similar for both treatments is reassuring for clinicians. He acknowledged the study's retrospective design as a limitation but affirmed its contributions to the existing body of knowledge regarding ASUC management.

In conclusion, the research underscores the safety of tofacitinib in the context of surgical intervention for ASUC, suggesting that healthcare providers can utilize this medication without hesitation regarding postoperative complications. As treatment protocols continue to evolve, further studies will be necessary to solidify these findings and explore the long-term outcomes associated with JAK inhibitors in diverse patient populations.