New-onset Inflammatory Bowel Diseases Among IL-17 Inhibitor-Treated Patients

Results From the Case-Control MISSIL Study

Jean-Guillaume Letarouilly; Thao Pham; Adeline Pierache; Émilie Acquacalda; Béatrice Banneville; Sébastien Barbarot; Pauline Baudart; Élodie Bauer; Pascal Claudepierre; Arnaud Constantin; Emmanuelle Dernis; Renaud Felten; Philippe Gaudin; Céline Girard; Bruno Gombert; Philippe Goupille; Xavier Guennoc; Isabelle Henry-Desailly; Denis Jullien; Elena Karimova; Sylvain Lanot; Loïc Le Dantec; Tristan Pascart; Laurianne Plastaras; Nathalie Sultan; Xavier Truchet; Stéphane Varin; Daniel Wendling; Louise Gaboriau; Delphine Staumont-Sallé; Laurent Peyrin-Biroulet; René-Marc Flipo


Rheumatology. 2022;61(7):2848-2855. 

In This Article

Abstract and Introduction


Objectives: To describe new-onset IBD (new IBD) in patients treated with IL-17 inhibitors (IL-17i), to assess their incidence and to identify their risk factors in real life.

Methods: A French national registry (MISSIL) aimed to report all cases of new IBD in patients treated with IL-17i from January 2016 to December 2019. Using the estimated number of patients treated by IL-17 in France during the study period, the annual incidence rates of new IBD was reported in IL-17i-treated patients. A case–control study was performed with two controls per new IBD case matched by gender, age and underlying inflammatory disease.

Results: Thirty-one cases of new IBD under IL-17i were collected: 27 patients treated for spondyloarthritis and four patients for psoriasis. All were observed with secukinumab (SEK). The median time to onset of new IBD symptoms was 4.0 (1.5–7.5) months. SEK was discontinued in all patients. The evolution was favourable with complete resolution (17/31), improvement (7/31) or stabilization (5/31). Two patients died: one due to a massive myocardial infarction and one due to post-colectomy complications. The incidence of new IBD decreased from 0.69/100 patient-years [PY] (7/1010) in 2016 to 0.08/100 PY (6/7951) in 2019. No previous treatment with etanercept (odds ratio [OR] = 0.33, 95% CI: 0.14–0.80, P = 0.014) and low number of previous biologic therapies (OR = 0.67, 95% CI: 0.47, 0.94, P = 0.021) were significantly associated with new IBD.

Conclusion: The incidence of new IBD was low and decreased from 2016 to 2019. The outcome was favourable in 24 out of 31 patients, but two patients died.


IL-17 inhibitors (IL-17i) are now part of the therapeutic strategy to manage patients with psoriasis (PsO), PsA and axial spondyloarthritis (SpA) according to the recommendations from the EULAR, the ACR and the European Dermatology Forum.[1–3] Three IL-17i are currently available: secukinumab (SEK), brodalumab and ixekizumab. SEK and ixekizumab target IL-17A and brodalumab targets the receptor of IL-17 (IL-17RA).[4] A warning from the European Medicines Agency regarding safety of IL-17i has been issued from data of randomized controlled trials (RCT) showing cases of new-onset IBD (new IBD).[5–7] New IBD are considered by the European Medicines Agency as important potential risks in patients treated with IL-17i.[8] Moreover, IL-17i did not show any efficacy to treat IBD in RCT.[9,10] The phase II RCT assessing brodalumab in Crohn's disease was terminated early based on an imbalance in worsening Crohn's disease in active treatment groups.[9] A proof-of-concept study assessing SEK in Crohn's disease showed a greater reduction in the Crohn's Disease Activity Index in the placebo group than in the SEK group.[10]

Several analyses of pooled data from randomized clinical trials with PsO, PsA and SpA patients concluded that cases of new IBD events were uncommon.[11–13] Yet, patients included in clinical trials are highly selected and are not broadly representative of patients encountered in daily practice.[14,15] Thus, real-world evidence is needed.[16]

In France, SEK has been granted market authorization for PsO since 2015 and for PsA and SpA since June 2016. Ixekizumab has been granted market authorization for PsO since 2016 and for PsA and SpA since June 2018. Brodalumab has only been granted market authorization for PsO since April 2018, as there was a suicide signal in the RCT assessing brodalumab in PsA.[17] Prescriptions for IL-17i have increased over the past few years. In a recent cohort study of 63 598 PsA patients from the French health insurance database, the prescription for SEK increased from 2015 to 2018 and was ranked third out of seven biologic therapies in 2018.[18]

The objectives of this retrospective multicentre real-world study were to describe new IBD associated with IL-17i, to identify risk factors, and to assess the incidence of new IBD in patients receiving treatment with IL-17i in France.