Claire Rempenault1, Cédric Lukas1, Bernard Combe1, Astrid Herrero2, Isabelle Pane3, Thierry Schaeverbeke4, Daniel Wendling5, Thao Pham6, Jacques-Eric Gottenberg7, Xavier Mariette8, Jacques Morel1. 1. Rheumatology Department. 2. Digestive Surgery Department, CHU and University of Montpellier, Montpellier. 3. Clinical Epidemiology, Hôtel-Dieu Hospital, Paris. 4. Rheumatology Department, CHU and University of Bordeaux, Bordeaux. 5. Rheumatology Department, CHU of Besançon, and EA 4266 University of Franche-Comté, Besançon. 6. Department of Rheumatology, Aix Marseille Univ, APHM, CHU Sainte-Marguerite, Marseille. 7. Department of Rheumatology, Strasbourg University Hospital, National Center For Rare Systemic Autoimmune Diseases, CNRS, UPR3572, IBMC, University of Strasbourg, Strasbourg. 8. Rheumatology Department, Université Paris-Saclay, INSERM, CEA, Centre de Recherche en Immunologie des Infections Virales et des Maladies Auto-Immunes, AP-HP.Université Paris-Saclay, Hôpital Bicêtre, Le Kremlin Bicêtre, France.
Abstract
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.
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.