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Risk of diverticulitis and gastrointestinal perforation in rheumatoid arthritis treated with tocilizumab compared to rituximab or abatacept

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  • Additional Information
    • Contributors:
      Département de Rhumatologie Hôpital Lapeyronie - CHU Montpellier; Hôpital Lapeyronie CHU Montpellier; Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier)-Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier); Département de Chirurgie Digestive B et Transplantation Hôpital Saint-Eloi - CHU Montpellier; Hôpital Saint Eloi CHU Montpellier; Centre d'épidémiologie Clinique Hôtel-Dieu; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu; Département de Rhumatologie; Université de Bordeaux (UB)-Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux); Epigénétique des infections virales et des maladies inflammatoires (UR 4266) (EPILAB); Université de Franche-Comté (UFC); Université Bourgogne Franche-Comté COMUE (UBFC)-Université Bourgogne Franche-Comté COMUE (UBFC); Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon); Rhumatologie Sainte- Marguerite - APHM (Hôpitaux Sud); Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite CHU - APHM (Hôpitaux Sud); Institut de biologie moléculaire et cellulaire (IBMC); Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS); Service de rhumatologie Strasbourg; Centre Hospitalier Universitaire Strasbourg (CHU Strasbourg); Les Hôpitaux Universitaires de Strasbourg (HUS)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Hôpital de Hautepierre Strasbourg; Infectious Diseases Models for Innovative Therapies (IDMIT); Université Paris-Saclay-Institut de Biologie François JACOB (JACOB); Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA); Institut National de la Santé et de la Recherche Médicale (INSERM); The French Society of Rheumatology received unrestricted grants from Bristol-Myers Squibb for Orencia and Rheumatoid Arthritis (ORA), Roche for Autoimmunity and Rituximab (AIR) and REGistry-RoAcTEmra (REGATE), and Roche-Chugai for REGATE. These funders had no role in the collection, analysis or interpretation of data, of preparation, review, or approval of the manuscript for publication.
    • Publication Information:
      CCSD
      Oxford University Press (OUP)
    • Publication Date:
      2022
    • Collection:
      HAL-CEA (Commissariat à l'énergie atomique et aux énergies alternatives)
    • Abstract:
      International audience ; Objective To compare the risk of diverticulitis and gastrointestinal perforation (GIP) in RA treated with tocilizumab (TCZ) compared with rituximab (RTX) and abatacept (ABA).Methods We conducted a population-based study using three observational French registries on TCZ, RTX and ABA in RA. Using a propensity score approach, we compared the risk of diverticulitis or GIP in these patients.Results With inverse probability weighting, there was an increased risk of diverticulitis in TCZ-treated patients compared with RTX- or ABA-treated patients [hazard ratio (HR)=3.1 (95% CI: 1.5, 6.3), P =0.002]. Moreover, patients treated with TCZ had also an increased risk of GIP due to diverticulitis compared with those treated with RTX or ABA [HR=3.8 (1.1–13.6), P =0.04], resulting in an overall increased risk of GIP [HR=2.9 (1.1–7.8), P =0.03], while no significant increased risk of GIP due to any other aetiology was found in TCZ treated patients. Diverticulitis and GIP occurred earlier with TCZ than other drugs after the last perfusion (P =0.01), with atypical clinical presentation (slow transit in 30%, P =0.04) and lower acute-phase reactants at the time of the event (P =0.005).Conclusion TCZ for RA was associated with increased odds of diverticulitis as well as GIP due to diverticulitis as compared with RTX and ABA. Our study confirms the increased odds of GIP in patients receiving TCZ, which might be explained by an increased risk of diverticulitis with misleading clinical presentation.
    • Accession Number:
      10.1093/rheumatology/keab438
    • Online Access:
      https://hal.science/hal-03619916
      https://hal.science/hal-03619916v1/document
      https://hal.science/hal-03619916v1/file/2022%20Rempenault%20%20et%20al.,%20Risk%20of%20diverticulitis.pdf
      https://doi.org/10.1093/rheumatology/keab438
    • Rights:
      http://hal.archives-ouvertes.fr/licences/copyright/ ; info:eu-repo/semantics/OpenAccess
    • Accession Number:
      edsbas.4CC41352