The level of remission in patients with remitting inflammatory bowel disease (IBD) appears to play a major role in whether they will relapse after treatment when biologic therapies are discontinued, according to a new prospective study.
Patients with complete endoscopic healing have half the rate of relapse after withdrawal of anti-tumor necrosis factor alpha (anti-TNF) treatment than those with only partial healing, according to a study published online in Clinical Gastroenterology and Hepatology.
“Applying strict criteria for endoscopic healing and mesalamine treatment ... may lower the risk of relapse after withdrawal of anti-TNF treatment,” write Bas Oldenburg, MD, PhD, a professor at University Medical Center Utrecht, the Netherlands, and colleagues in their analysis of 81 patients.
De-escalation of anti-TNF treatment in IBD patients in remission has the potential to “reduce side effects, including risks of serious infections and malignancies, decrease health care expenditures, and meet patients’ preferences,” they note.
However, withdrawal of the drugs increases the risk of relapse by 30%-45% at 12 months. When patients relapse, reintroduction of anti-TNF therapy returns over 80% to remission.
Although no consensus exists on how to select patients for therapy de-escalation, evidence suggests that persistent inflammation affects outcomes and that the “depth” of endoscopic healing is a key indicator, the authors note.
To further the knowledge base, they conducted a prospective study of patients in remission to determine the relapse rate following de-escalation of anti-TNF therapy; evaluate relapse factors, including degree of endoscopic healing; and assess outcomes after reintroduction of anti-TNF therapy.
The study was limited to adult patients with IBD with at least 6 months of corticosteroid-free clinical remission, confirmed baseline clinical remission and endoscopic healing, no current hospitalization, and no pregnancy.
The patients underwent elective discontinuation of anti-TNF therapy between 2018 and 2020. The recommended protocol was to measure C-reactive protein (CRP) and fecal calprotectin at 3, 6, 12, and 24 months and to perform endoscopy at 12 months.
Patients also completed questionnaires at baseline and at 3, 6, 12, and 24 months. The authors selected the patient–Harvey-Bradshaw Index for patients with Crohn’s disease and the patient–Simple Clinical Colitis Activity Index for patients with ulcerative colitis and unclassified IBD, as well as the short IBD Quality of Life measure.
Of the 81 patients from 13 centers who took part, 51% had Crohn’s disease. The median duration of remission at baseline was 3.5 years, and the median disease duration was 9.1 years.
All patients had evidence of endoscopic healing, and 88% met the strict criteria for complete endoscopic healing. In 34%, trough levels of anti-TNF treatments were judged to be subtherapeutic.
After withdrawal of the drugs, 25.9% of patients continued on immunomodulators.
Over a median follow-up of 2 years, 49% of patients relapsed, which was confirmed via endoscopy, fecal calprotectin, or CRP in 83% of cases and inferred from treatment escalation for clinical flare in 17%. Rates of relapse were comparable between patients with Crohn’s disease and ulcerative colitis or unclassified IBD and between those discontinuing adalimumab and those stopping infliximab.
Better healing, better outcomes
However, analysis showed that partial endoscopic healing was independently associated with a higher risk of relapse, at an adjusted hazard ratio versus complete endoscopic healing of 3.28.