Background: We aimed to investigate the incidence of relapse after anti-TNF withdrawal in a real-life cohort of Crohn's disease (CD) and ulcerative colitis (UC) patients in sustained clinical remission, to identify predictors for relapse and to assess the response to restart of anti-TNF retreatment.
Methods: CD and UC patients in clinical remission receiving infliximab (IFX) or adalimumab (ADA) treatment for ≥1 year and discontinued treatment were included. Clinical relapse was defined as recurrence of symptoms and the need to (re)start anti-TNF therapy, immunomodulators and/or corticosteroids. Relapse risk and predictors for relapse were studied using cox proportional hazard analysis.
Results: In total, 92 patients discontinued anti-TNF treatment (69 CD, 23 UC). Median duration of anti-TNF therapy at the time of withdrawal was 53 months (IQR 24–87) and the median duration of follow-up was 13 months (IQR 8–16). IFX and ADA were discontinued in 52 (57%) and 40 patients (43), respectively. So far, a total of 47 patients (51%) experienced relapse (CD 33, UC 14), with a median time to relapse of 7 and 4 months in CD and UC, respectively. Of patients that were retreated with the same anti-TNF agents, 83% showed a clinical response. A serum concentration at trough ≥2 μg/ml (irrespective of the anti-TNF agent) within one year prior to anti-TNF discontinuation was associated with a significantly higher relapse rate (HR 3.6, 95% CI 1.2–10.6). Continuation of immunomodulatory treatment was not associated with a lower relapse rate in both CD and UC patients (HR 0.8, 95% CI 0.4–1.6; HR 0.6, 95% CI 0.2–1.7). Endoscopic remission in the previous year, bowel-related surgery, prior anti-TNF use, perianal disease, disease location, disease duration, duration of anti-TNF therapy and disease location were not associated with higher or lower relapse rates. Factors such as CRP and faecal calprotectin as predictors for relapse were not addressed, since they were within the normal range in most patients at the time of cessation of anti-TNF therapy.
Conclusions: Approximately 50% of patients in remission under anti-TNF treatment relapsed after anti-TNF withdrawal with a median time to relapse of 7 and 4 months in CD and UC, respectively. A trough level ≥2 μg/ml prior to discontinuation of IFX and ADA therapy was associated with an increased relapse risk. Continuation of immunomodulatory treatment was not associated with a reduced relapse risk, which is in contrast to previous work. Retreatment with the same anti-TNF was successful in 83% of patients.