New-Onset Inflammatory Bowel Diseases Among IL-17 Inhibitors-Treated Patients: Results from the Case-Control MISSIL Study

Jean-Guillaume Letarouilly¹, Benjamin Pariente², Thao Pham³, Emilie Acquacalda⁴, Béatrice Banneville⁵, Sébastien Barbarot⁶, Elodie Bauer⁷, Pauline Baudart⁸, Pascal Claudepierre⁹, Arnaud Constantin¹⁰, Emmanuelle Dernis¹¹, Renaud Felten¹², Philippe Gaudin¹³, Céline Girard¹⁴, Bruno Gombert¹⁵, Philippe Goupille¹⁶, Xavier Guennoc¹⁷, Isabelle Henry-Desailly¹⁸, Denis Jullien¹⁹, Elena Karimova²⁰, Sylvain Lanot²¹, Loïc Le Dantec²², Tristan Pascart²³, Laurianne Plastaras²⁴, Nathalie Sultan-Bichat²⁵, Xavier Truchet²⁶, Stéphane Varin²⁷, Daniel Wendling²⁸, Lousie Gaboriau²⁹, Delphine Staumont-Sallé³⁰, Laurent Peyrin-Biroulet³¹ and René-Marc Flipo¹, ¹Univ-Lille, CHU Lille, department of rheumatology, Lille, France, ²Univ-Lille, CHU Lille, department of gastroenterology, Lille, France, ³Aix Marseille Univ, APHM, department of rheumatology, Marseille, France, ⁴CHPG, department of rheumatology, Monaco, Monaco, ⁵AP-HP, Hôpital Pitié-Salpêtrière, Service de Rhumatologie, Paris, 75013, Paris, France, ⁶CHU de Nantes, department of dermatology, Nantes, France, ⁷CHRU Nancy, department of rheumatology, VANDOEUVRE LES NANCY, Lorraine, France, ⁸CHU Caen, department of rheumatology, Caen, France, ⁹Hôpital Henri Mondor, Université Paris Est Créteil, EA 7379 EpiDermE, department of rheumatology, Créteil, France, ¹⁰Hospital Pierre Paul Riquet, Toulouse, France, ¹¹CH Le Mans, department of rheumatology, Le Mans, France, ¹²Department of rheumatology, University Hospitals of Strasbourg and French National Reference Center for Rare Auto-immune diseases, Strasbourg, France, ¹³CHU Grenoble, department of rheumatology, Grenoble, France, ¹⁴CHU Montpellier, department of rheumatology, Montpellier, France, ¹⁵CH La Rochelle, department of rheumatology, La Rochelle, France, ¹⁶CHU Tours, department of rheumatology, Tours, France, ¹⁷CH Saint-Brieuc, department of rheumatology, Saint-Brieuc, France, ¹⁸CHU Amiens, department of rheumatology, Amiens, France, ¹⁹CHU Lyon, department of dermatology, Lyon, France, ²⁰CH Lens, department of dermatology, Lens, France, ²¹CH Alençon, department of rheumatology, Alençon, France, ²²Ahnac, department of rheumatology, Hénin-Beaumont, France, ²³Ghicl, Hôpital Saint-Philibert, department of rheumatology, Lomme, France, ²⁴CH Colmar, department of gastroenterology, Colmar, France, ²⁵CH Ouest-Réunion, department of dermatology, Saint Paul, La Réunion, France, ²⁶HIA Sainte-Anne, department of gastroenterology, Toulon, France, ²⁷CHD Vendée, department of rheumatology, La Roche-sur-Yon, France, ²⁸CHU Besançon, department of rheumatology, Besancon, France, ²⁹Univ-Lille, CHU Lille, department of pharmacovigilance, Lille, France, ³⁰Univ-Lille, CHU Lille, department of dermatology, Lille, France, ³¹CHU Nancy, department of gastroenterology, VANDOEUVRE LES NANCY, Lorraine, France

Meeting: ACR Convergence 2020

Keywords: Disease-Modifying Antirheumatic Drugs (Dmards), Drug toxicity, risk factors, spondyloarthritis

Session Information

Date: Sunday, November 8, 2020

Title: Spondyloarthritis Including Psoriatic Arthritis – Treatment Poster III

Session Type: Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: A warning regarding safety of Interleukin 17 inhibitors (IL-17i) has been issued from data of randomized controlled trials (RCT) showing cases of new-onset inflammatory bowel diseases (NO-IBD). Real-world data are lacking. The objectives of the MISSIL (Maladies inflammatoires chroniques de l’Intestin SouS anti-IL 17) study are to describe NO-IBD associated with IL-17i, to identify risk factors, and to assess the incidence of NO-IBD in patients receiving treatment with IL-17i in France.

Methods: A French national registry was designed (MISSIL) to collect all cases of NO-IBD in patients treated with IL-17i from 2016 to 2019 in departments of rheumatology, dermatology and gastro-enterology, whatever the indication. A case–control study was performed with 3 controls per case randomly matched by gender, age (within 6 years), duration of disease (within 5 years) and underlying inflammatory disease from a database of previous studies of patients treated with IL-17i for spondyloarthritis and from centers participating in the MISSIL registry for psoriasis. NO-IBD events were analyzed using incidence rates (patient incidence rates per 100 patient-years – PY). We estimated the annual incidence rate of NO-IBD in patients treated with IL-17i. The numerator of the annual incidence rates consisted in the validated cases of NO-IBD from the MISSIL registry every year (from 2016 to 2019). The pharmaceutical firm provided its estimation of the annual number of patient-years (PY) treated with IL-17i for the denominator (from 2016 to 2019) in France.

Results: 31 cases of NO-IBD under secukinumab (SEK) were collected between January 2016 and December 2019: 27 patients treated for spondyloarthritis and 4 patients for psoriasis (Table 1). No case of NO-IBD was identified under ixekizumab. Mean age was 49.2 ± 14.6 years old and 14/31 were female; 14/24 were HLA-B27 positive, 10/25 had a radiographic sacroiliitis and 15/25 a MRI sacroiliitis. Only 4 were biological Disease-modifying antirheumatic drug (bDMARD)-naïve. The median time to onset of NO-IBD symptoms was 4.0 (1.5-7.5) months. The main symptoms were diarrhoea and loss of weight. Median CRP at the onset of symptoms was 68.0 mg/L (34.0-177.5). SEK was discontinued in all patients. Treatments received after SEK were: corticosteroids in 19 cases, infliximab in 14 cases, adalimumab in 7 cases, golimumab in 3 cases, ustekinumab in 7 cases and colectomy in 2 cases. The evolution was favourable with complete resolution (17/31), improvement (7/31) or stabilization (5/31). 2 patients died: one due to a massive myocardial infarction related to the severe undernutrition due to NO-IBD and one due to post-operative complications. The incidence of NO-IBD was 0.69/100 PY (7/1010) in 2016, 0.23/100 PY (11/4704) in 2017, 0.11/100 PY(7/6550) in 2018 and 0.08/100PY (6/7951). There was no independent risk factor for NO-IBD in the case-control study (Table 2).

Conclusion: The outcome of NO-IBD was favorable after SEK discontinuation and introduction of IBD treatment in the vast majority of patients. No independent risk factor associated with NO-IBD in patients initiating SEK was identified.

Table 1 Characteristics of the 31 NO-IBD cases IL-17i= Interleukin 17 inhibitors. IQR= Interquartile. NO-IBD= new-onset inflammatory bowel diseases. SD= Standard Deviation. TNFi= Tumour Necrosis Factor inhibitor

Table 2 Risk Factor of NO-IBD receiving secukinumab bDMARD= biological Disease-modifying antirheumatic drug. csDMARD= conventional synthetic Disease-modifying antirheumatic drug. MTX= methotrexate

Disclosure: J. Letarouilly, Pfizer, 2; B. Pariente, Abbvie, 5, MSD, 5, Takeda, 5, Janssen, 5, Mylan, 5, Lilly, 5, Sandoz, 5, Biogaran, 5, Abbvie, 8, MSD, 8, Takeda, 8, Janssen, 8, Mylan, 8; T. Pham, Abbvie, 5, Amgen, 5, Biogen, 5, BMS, 5, Celgene, 5, Fresenius-Kabi, 5, Janssen, 5, Lilly, 5, Medac, 5, MSD, 5, Novartis, 5, Pfizer, 5, Roche-Chugai, 5, Sandoz, 5, Sanofi, 5, UCB, 5; E. Acquacalda, None; B. Banneville, None; S. Barbarot, Lilly, 8, Novartis, 8; E. Bauer, None; P. Baudart, None; P. Claudepierre, Abbvie, 5, 8, Pfizer, 5, 8, UCB, 5, 8, Merk, 5, 8, novartis, 5, 8, Lilly, 5, 8, Janssen, 5, 8, BMS, 5, 8; A. Constantin, AbbVie Inc., 5, 8, Amgen, 5, 8, Celltrion, 5, Gilead, 5, 8, Eli Lilly and Company, 5, 8, Novartis, 5, 8, Pfizer Inc., 5, 8, UCB, 5, 8, Janssen, 8; E. Dernis, Abbvie, 5, BMS, 5, Celgene, 5, Roche-Chugai, 5, Janssen, 5, Lilly, 5, Medac, 5, MSD, 5, Nordic Pharma, 5, Novartis, 5, Sanofi, 5, UCB, 5; R. Felten, Abbvie, 8, Biogen, 8, BMS, 8, Janssen, 8, Lilly, 8, Nordic Pharma, 8, Novartis, 8, MSD, 8, Pfizer, 8, UCB, 8, Abbvie, 6, Novartis, 6, Sanofi, 8; P. Gaudin, Lilly, 8, Novartis, 8; C. Girard, Novartis, 5, Leo Pharma, 5, Janssen, 5, Medac, 5, Abbvie, 5; B. Gombert, BMS, 8; P. Goupille, MSD France, 1, 2, Abbvie, 1, Amgen, 1, Biogaran, 1, 2, BMS, 1, Celgene, 1, Chugai, 1, Lilly, 1, Hospira, 1, Janssen, 1, Medac, 1, Nordic Pharma, 1, Novartis, 1, Sanofi-Genzyme, 1, Pfizer, 1, UCB Pharma, 1; X. Guennoc, None; I. Henry-Desailly, Abbvie, 8; D. Jullien, Abbvie, 5, Amgen, 5, Biogen, 5, Celgene, 5, Fresenius-Kabi, 5, Janssen, 5, Leo Pharma, 5, Lilly, 5, Medac, 5, Novartis, 5, Pfizer, 5, UCB, 5, Sanofi, 5, Abbvie, 8, Celgene, 8, Janssen, 8, Leo Pharma, 8, Medac, 8, Novartis, 8, Pfizer, 8; E. Karimova, None; S. Lanot, Abbvie, 8, Roche-Chugai, 8; L. Le Dantec, None; T. Pascart, novartis, 8, Horizon, 2; L. Plastaras, None; N. Sultan-Bichat, Janssen, 8, Abbvie, 8, Sanofi, 8, Novartis, 8, Leo Pharma, 8; X. Truchet, None; S. Varin, None; D. Wendling, None; L. Gaboriau, None; D. Staumont-Sallé, Lilly, 5, 8, Abbvie, 5, Leo Pharma, 5, Janssen, 5, 8, Novartis, 5, 8, Sanofi, 5, 8, Pfizer, 5, 8; L. Peyrin-Biroulet, Merck, 1, 2, Abbvie, 1, 2, Janssen, 1, 2, Genentech, 1, 2, Mitsubishi, 1, 2, Ferring, 1, 2, Norgine, 1, 2, Tillots, 1, 2, Vifor, 1, 2, Hospira/Pfizer, 1, 2, Celltrion, 1, 2, Takeda, 1, 2, Biogaran, 1, 2, Boehringer-Ingelheim, 1, 2, Lilly, 1, 2, HAC- Pharma, 1, 2, Index Pharmaceuticals, 1, 2, Amgen, 1, 2, Sandoz, 1, 2, Forward Pharma GmbH, 1, 2, Celgene, 1, 2, Biogen, 1, 2, Lycera, 1, 2, Samsung Bioepis, 1, 2, Theravance, 1, 2; R. Flipo, Abbvie, 1, 2, Biogen, 1, BMS, 1, Janssen, 1, 2, MSD, 1, Nordic, 1, Novartis, 1, 2, Pfizer, 1, 2, Roche-Chugai, 1, 2, Sanofi, 1.

To cite this abstract in AMA style:

Letarouilly J, Pariente B, Pham T, Acquacalda E, Banneville B, Barbarot S, Bauer E, Baudart P, Claudepierre P, Constantin A, Dernis E, Felten R, Gaudin P, Girard C, Gombert B, Goupille P, Guennoc X, Henry-Desailly I, Jullien D, Karimova E, Lanot S, Le Dantec L, Pascart T, Plastaras L, Sultan-Bichat N, Truchet X, Varin S, Wendling D, Gaboriau L, Staumont-Sallé D, Peyrin-Biroulet L, Flipo R. New-Onset Inflammatory Bowel Diseases Among IL-17 Inhibitors-Treated Patients: Results from the Case-Control MISSIL Study [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/new-onset-inflammatory-bowel-diseases-among-il-17-inhibitors-treated-patients-results-from-the-case-control-missil-study/. Accessed .

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