Clinical Outcome After Anti-tumour Necrosis Factor Therapy Discontinuation in 1000 Patients With Inflammatory Bowel Disease

The EVODIS Long-term Study

María José Casanova; María Chaparro; Óscar Nantes; José Manuel Benítez; María Rojas-Feria; Jesús Castro-Poceiro; José María Huguet; Albert Martín-Cardona; Marta Aicart-Ramos; Joan Tosca; María del Mar Martín-Rodríguez; Carlos González-Muñoza; Miriam Mañosa; Eduardo Leo-Carnerero; Luis Javier Lamuela-Calvo; Isabel Pérez-Martínez; Luis Bujanda; Joaquín Hinojosa; Ramón Pajares; Federico Argüelles-Arias; José Lázaro Pérez-Calle; Gloria Esther Rodríguez-González; Jordi Guardiola; Manuel Barreiro-de Acosta; Javier P. Gisbert


Aliment Pharmacol Ther. 2021;53(12):1277-1288. 

In This Article

Abstract and Introduction


Background: The long-term outcome of patients after antitumour necrosis factor alpha (anti-TNF) discontinuation is not well known.

Aims: To assess the risk of relapse in the long-term after anti-TNF discontinuation.

Methods: This was an extension of the evolution after anti-TNF discontinuation in patients with inflammatory bowel disease (EVODIS) study (Crohn's disease or ulcerative colitis patients treated with anti-TNFs in whom these drugs were withdrawn after achieving clinical remission) based in the same cohort of patients whose outcome was updated. Clinical remission was defined as a Harvey–Bradshaw index ≤4 points in Crohn's disease, a partial Mayo score ≤2 in ulcerative colitis and the absence of fistula drainage despite gentle finger compression in perianal disease.

Results: This was an observational, retrospective, multicenter study. A total of 1055 patients were included. The median follow-up time was 34 months. The incidence rate of relapse was 12% per patient-year (95% confidence interval [CI] = 11–14). The cumulative incidence of relapse was 50% (95% CI = 47–53): 19% at one year, 31% at 2 years, 38% at 3 years, 44% at 4 years and 48% at 5 years of follow-up. Of the 60% patients retreated with the same anti-TNF after relapse, 73% regained remission. Of the 75 patients who did not respond, 48% achieved remission with other therapies. Of the 190 patients who started other therapies after relapse, 62% achieved remission with the new treatment.

Conclusions: A significant proportion of patients who discontinued the anti-TNF remained in remission. In case of relapse, retreatment with the same anti-TNF was usually effective. Approximately half of the patients who did not respond after retreatment achieved remission with other therapies.


In the last two decades, the efficacy of antitumour necrosis factor-alpha (anti-TNF) drugs in inducing and maintaining clinical remission and mucosal healing in inflammatory bowel disease (IBD) has been well established.[1] However, exacerbation can take place upon cessation of therapy. For this reason, continuous treatment has been the rule in most patients in order to avoid relapse and disease progression.[2] Nevertheless, several concerns, such as the risk of side effects or costs, have raised the possibility of discontinuing the therapy after achieving remission, at least in some groups of patients.[3] In this sense, to identify the right time and specific patients in which these drugs could be withdrawn is extremely relevant. A recent systematic review and meta-analysis showed that the risk of relapse after anti-TNF withdrawal in patients in clinical remission was 44% in Crohn's disease (CD) and 38% in ulcerative colitis (UC).[4] However, most of the studies analysed in this meta-analysis included a small number of patients and had a short follow-up time. Long-term data after anti-TNF discontinuation are scant, and the few studies that reported long-term relapse rates after withdrawal included limited number of patients.[5–7] Thus, the real long-term clinical outcome of patients after anti-TNF discontinuation is not well known.

The evolution after anti-TNF discontinuation in patients with inflammatory bowel disease (EVODIS) study was a previous retrospective and multicenter study that included 1055 IBD patients in whom anti-TNF therapy was stopped after achieving clinical remission.[8] Approximately half of the patients who discontinued anti-TNF because of clinical remission relapsed after a median follow-up time of 19 months, but retreatment with the same anti-TNF was effective and safe in the majority of patients.[8] Although it seems that retreatment with the same anti-TNF after relapse has remarkable rates of success, the long-term follow-up data on the outcome of these patients are limited.[6,8–10] Furthermore, the outcome of patients who do not respond to retreatment with the same anti-TNF or who start other therapies after relapse is also unknown.

Despite the novel data from EVODIS study, the median follow-up time was relatively short.[8] In the present study, the follow-up of the patients included in the EVODIS study was extended, obtaining data about their long-term outcome. The data obtained will allow to have a broader perspective to make the crucial decision about maintaining or discontinuing the anti-TNF therapy in those patients in remission.

The aims of the present study were to assess the risk of relapse in the long-term after anti-TNF discontinuation in patients included in the EVODIS study, to identify the factors associated with relapse in these patients, to investigate the clinical outcome of the patients after relapse.