Patients whose Crohn’s disease fully remits after resection should not wait for endoscopic recurrence to start tumor-necrosis-factor inhibitors or thiopurines, according to a new guideline from the American Gastroenterological Association.
Patients who are low risk or worried about side effects, however, “may reasonably select endoscopy-guided pharmacological treatment,” the guidelines state (doi: 10.1053/j.gastro.2016.10.038).
About half of patients need surgical resection within 10 years of a Crohn’s disease diagnosis, and about one in four of those who undergo surgery need another resection within 5 years, noted Geoffrey C. Nguyen, MD, PhD, of the University of Toronto, and his associates. Accordingly, they developed recommendations for preventing multiple surgeries in patients who have no evidence of disease after initial resection. Surgical recurrence was rare in the clinical trials these experts evaluated, so they used endoscopic recurrence as a proxy.
Early pharmacologic prophylaxis usually begins within 8 weeks of surgery, they noted. Whether this approach bests endoscopy-guided treatment is unclear: In one small trial (Gastroenterology. 2013;145:766-74.e1), early azathioprine therapy failed to best endoscopy-guided therapy for preventing clinical or endoscopic recurrence.
Early prophylaxis, however, is usually reasonable because most Crohn’s patients who undergo surgery have at least one risk factor for recurrence, Dr. Nguyen and his associates emphasize. They suggest reserving endoscopy-guided therapy for patients who have real concerns about side effects and are at low risk, such as nonsmokers who were diagnosed within 10 years and have less than 10-20 cm of fibrostenotic disease.
For prophylaxis, a moderate amount of evidence supports anti–tumor necrosis factor (TNF) agents, thiopurines, or combined therapy over other agents, the guideline also states. In placebo-controlled clinical trials, anti-TNF therapy reduced the chances of clinical recurrence by 49% and endoscopic recurrence by 76%, while thiopurines cut these rates by 65% and 60%, respectively. Evidence favors anti-TNF agents over thiopurines for preventing recurrence, but it is of low quality, the guideline says. Furthermore, only indirect evidence supports combined therapy in patients at highest risk of recurrence.
Among the antibiotics, only nitroimidazoles such as metronidazole have been adequately studied, and they posted worse results than anti-TNF agents or thiopurines. Antibiotic therapy decreased the risk of endoscopic recurrence of Crohn’s disease by about 50%, but long-term use is associated with peripheral neuropathy and disease usually recurs within 2 years of stopping treatment. Accordingly, the guidelines suggest using a nitroimidazole for only 3-12 months, and only in lower-risk patients who are concerned about the adverse effects of anti-TNF agents and thiopurines.
The AGA made a conditional recommendation against the prophylactic use of budesonide, probiotics, and 5-aminosalicylates such as mesalamine. Only low-quality evidence supports their efficacy after resection, and by using these agents, clinicians may inadvertently boost the risk of recurrence by forgoing better therapies, the guideline states.
The initial endoscopy should be timed for 6-12 months after resection, regardless of whether patients are receiving pharmacologic prophylaxis, the guideline states. If there is endoscopic recurrence, then anti-TNF or thiopurine therapy should be started or optimized.
In the Postoperative Crohn’s Endoscopic Recurrence (POCER) trial, endoscopic monitoring and treatment escalation in the face of endoscopic recurrence cut the risk of subsequent clinical and endoscopic recurrence by about 18% and 27%, respectively, compared with continuing the original treatment regimen. Most patients received azathioprine or adalimumab with 3 months of metronidazole postoperatively, so “even [those] who were already on postoperative prophylaxis benefited from endoscopic monitoring with colonoscopy at 6-12 months,” the guideline notes. However, patients who elect early prophylaxis after resection can reasonably forego colonoscopy if endoscopic recurrence is unlikely to affect their treatment plan, the AGA states. The guideline strongly recommends ongoing surveillance endoscopies if patients decide against early postresection prophylaxis, but notes a lack of evidence on how far to space out these procedures.
None of the authors had relevant financial disclosures.