When do we dare to stop biological or immunomodulatory therapy for Crohn's disease? Results of a multidisciplinary European expert panel

Abstract

Background: Safety and economic issues have increasingly raised concerns about the long term use of immunomodulators or biologics as maintenance therapies for Crohn's disease (CD). Despite emerging evidence suggesting that stopping therapy might be an option for low risk patients, criteria identifying target groups for this strategy are missing, and there is a lack of recommendations regarding this question. Methods: Multidisciplinary European expert panel (EPACT-II Update) rated the appropriateness of stopping therapy in CD patients in remission. We used the RAND/UCLA Appropriateness Method, and included the following variables: presence of clinical and/or endoscopic remission, CRP level, fecal calprotectin level, prior surgery for CD, and duration of remission (1, 2 or 4 years). Results: Before considering withdrawing therapy, the prerequisites of a C-reactive protein (CRP) and fecal calprotectin measurement were rated as "appropriate" by the panellists, whereas a radiological evaluation was considered as being of "uncertain" appropriateness. Ileo-colonoscopy was considered appropriate 1 year after surgery or after 4 years in the absence of prior surgery. Stopping azathioprine, 6-mercaptopurine or methotrexate mono-therapy was judged appropriate after 4 years of clinical remission. Withdrawing anti-TNF mono-therapy was judged appropriate after 2 years in case of clinical and endoscopic remission, and after 4 years of clinical remission. In case of combined therapy, anti-TNF withdrawal, while continuing the immunomodulator, was considered appropriate after two years of clinical remission. Conclusion: A multidisciplinary European expert panel proposed for the first time treatment stopping rules for patients in clinical and/or endoscopic remission, with normal CRP and fecal calprotectin levels.

Relapse rates of inflammatory bowel disease patients in deep and clinical remission after discontinuing anti-tumor necrosis factor alpha therapy

“…Given the potential risks and burdens of long-term biological therapy, it has been asked how long it should be continued and when it can be safely stopped (10). However, the data on these issues are scarce and confl icting, and consequently generally accepted stopping rules have not yet been developed.…”

Low Discontinuation Rate of Infliximab Treatment in Steroid-Dependent/Refractory Crohn’s Disease Patients

“…In order to be discontinued from IFX therapy, patients had to be in deep remission, defined as clinical and biochemical remission during an observation period of ≥2 years and endoscopic and histological remission before discontinuation of IFX [3]. Endoscopic and histological remission was defined as complete mucosal healing.…”

“…Existing guidelines have concluded that because of limited evidence, no recommendations can be made on when and in whom to discontinue TNFα-blocking therapy after having obtained clinical remission [1]. Currently, withdrawal of biological therapy is suggested in CD patients who have both complete mucosal healing and no biological evidence of inflammation [2,3]. However, several studies have shown that a substantial number of patients with IBD in stable remission relapsed within 2 years after stopping TNFα-blocking therapy.…”

Faecal calprotectin: Management in inflammatory bowel disease

“…For de-escalation of any drug or cessation of corticosteroids or mesalamine, a confirmation of biological remission with biomarkers such as CRP or FC can be sufficient. However, if we are willing to stop immunosuppressants or anti-TNF drugs, a confirmation of mucosal healing by endoscopy seems desirable [44] .…”