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Risk of gastrointestinal perforation in patients with rheumatic diseases exposed to janus kinase inhibitors versus adalimumab: nationwide cohort study

Lea Hoisnard MD, PhD

Corresponding Author

Lea Hoisnard MD, PhD

Fédération Hospitalo-Universitaire TRUE InnovaTive theRapy for immUne disordErs, Assistance Publique-Hôpitaux de Paris (AP-HP), Henri Mondor Hospital, F-94010, Créteil, France

INSERM, Centre d'Investigation Clinique 1430, F-94010, Créteil, France

EpiDermE Epidemiology in Dermatology and Evaluation of Therapeutics, EA7379, Paris Est Créteil University UPEC, F-94010, Créteil, France

Corresponding author: Dr Léa Hoisnard, TRUE FHU, Henri Mondor Hospital, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil Cedex , Tel: +33-149-812-501; Fax: +33-149-812-508 e-mail: [email protected]

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Antoine Meyer MD, PhD

Antoine Meyer MD, PhD

EPI-PHARE Scientific Interest Group in Epidemiology of Health Products, French National Agency for Medicines and Health Products Safety, French National Health Insurance, 93200, Saint-Denis, France

Department of Gastroenterology, Assistance Publique-Hôpitaux de Paris (AP-HP), Bicêtre University Hospital, Paris-Saclay University, Le Kremlin Bicêtre, France

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Rosemary Dray-Spira MD, PhD

Rosemary Dray-Spira MD, PhD

EPI-PHARE Scientific Interest Group in Epidemiology of Health Products, French National Agency for Medicines and Health Products Safety, French National Health Insurance, 93200, Saint-Denis, France

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Alain Weill MD

Alain Weill MD

EPI-PHARE Scientific Interest Group in Epidemiology of Health Products, French National Agency for Medicines and Health Products Safety, French National Health Insurance, 93200, Saint-Denis, France

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Mahmoud Zureik MD, PhD

Mahmoud Zureik MD, PhD

EPI-PHARE Scientific Interest Group in Epidemiology of Health Products, French National Agency for Medicines and Health Products Safety, French National Health Insurance, 93200, Saint-Denis, France

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Emilie Sbidian MD, PhD

Emilie Sbidian MD, PhD

Fédération Hospitalo-Universitaire TRUE InnovaTive theRapy for immUne disordErs, Assistance Publique-Hôpitaux de Paris (AP-HP), Henri Mondor Hospital, F-94010, Créteil, France

INSERM, Centre d'Investigation Clinique 1430, F-94010, Créteil, France

EpiDermE Epidemiology in Dermatology and Evaluation of Therapeutics, EA7379, Paris Est Créteil University UPEC, F-94010, Créteil, France

EPI-PHARE Scientific Interest Group in Epidemiology of Health Products, French National Agency for Medicines and Health Products Safety, French National Health Insurance, 93200, Saint-Denis, France

Department of Dermatology, Assistance Publique-Hôpitaux de Paris (AP-HP), Henri Mondor Hospital, F-94010, Créteil, France

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First published: 03 May 2024

A graphical abstract can be found in the online article at http://onlinelibrary.wiley.com/doi/10.1002/art.42862/abs.

Author disclosures and graphical abstract are available at https://onlinelibrary.wiley.com/doi/10.1002/art.42862.

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/art.42862.

Abstract

Objective

To compare the risk of gastrointestinal perforation (GIP), a rare but serious adverse event, in patients initiating a Janus kinase inhibitor (JAKi; tofacitinib, baricitinib, upadacitinib or filgotinib) versus adalimumab (tumor necrosis factor inhibitor) among a comprehensive real-world population of patients with rheumatic diseases.

Methods

We conducted a nationwide population-based cohort study of the French national health data system, the exposed group initiating a JAKi and the comparison group adalimumab. We included all individuals with a rheumatic disease who had their first dispensation of these treatments from July 2017 to December 2021. The primary endpoint was the occurrence of GIP (end of follow-up May 2022). Weighted hazard ratios (wHRs) were estimated with the inverse probability of treatment weighting method to account for confounding factors. Concomitant administration of systemic corticosteroids, non-steroidal anti-inflammatory drugs and proton pump inhibitors were time-varying variables.

Results

The cohort included 39,758 patients: 12,335 and 27,423 in the JAKi and adalimumab groups (mean age 58.2 and 47.3 years; female 76% and 58%; rheumatoid arthritis 85.3% and 27.3%, and psoriatic arthritis/axial spondyloarthritis 14.7% and 72.7%). During follow-up, 38 and 42 GIPs occurred in the JAKi and adalimumab groups, incidence rates were 2.1 (95% CI 1.5-2.8) and 1.1 (0.8-1.5) per 1000 person-years respectively. Rates of GIP did not differ between JAKi and adalimumab groups : wHR 1.1 (95% CI 0.7-1.9) (p=0.65). Despite lack of power in some subgroup analyses, results were consistent whatever the JAKi or rheumatic disease subgroup.

Conclusion

In this nationwide cohort study, the rates of GIP did not differ between groups of patients initiating JAKi and adalimumab treatment. These results need to be confirmed in other observational studies.