Journal Article

Tofacitinib Safety and Effectiveness in Canadian Patients with Rheumatoid Arthritis by Cardiovascular Risk Enrichment: Subanalysis of the CANTORAL Study

Gruben, David, Keystone, Edward C., Choquette, Denis, Haraoui, Boulos, Kinch, Cassandra D., Galos, Corina, Fortin, Isabelle, Khraishi, Majed, Roy, Patrice, Vaillancourt, Julie, Sampalis, John S.

2024

Overview

Introduction ORAL Surveillance, a post-authorisation safety study of patients with rheumatoid arthritis (RA) enriched for cardiovascular (CV) risk, demonstrated increased risk of major adverse CV events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) for tofacitinib versus tumour necrosis factor inhibitors (TNFi). This analysis of a real-world Canadian observational study evaluated tofacitinib safety/effectiveness in patients meeting or not meeting CV risk criteria. Methods CANTORAL included patients with moderate-to-severe RA initiating tofacitinib (10/2017–07/2020; N  = 504) . Interim data (data-cut: 07/2021) were stratified as CV risk-enriched (CV+ ; patients ≥ 50 years with ≥ 1 additional CV risk factor) or not CV risk-enriched (CV−; ≥ 50 years without additional CV risk factors and 18–49 years with/without CV risk factors). Safety and persistence were evaluated to month (M) 36. Effectiveness outcomes to M18 included Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA)/remission (CANTORAL co-primary endpoints) and Disease Activity Score in 28 joints, C-reactive protein (DAS28-4[CRP]) < 3.2/ < 2.6. Results Overall, 272/232 patients were included in CV+ /CV− cohorts (full analysis set) (435/356 patient-years [safety analysis set]). Incidence rates (events/100 patient-years) in CV+ /CV− cohorts were 138.5/112.5 for treatment-emergent adverse events (AEs); 17.0/5.6 for serious AEs; 1.2/0.3 for deaths; 5.5/1.7 for serious infections; 1.4/1.1 for herpes zoster; 1.6/0.0 for MACE; 2.1/0.3 for malignancies (excluding NMSC); 0.7/0.6 for NMSC; 0.5/0.0 for venous thromboembolic events. Persistence was generally comparable between cohorts. In CV+ /CV− cohorts, at M6, CDAI LDA and remission rates were 51.5%/54.6% and 12.0%/19.6%; DAS28-4(CRP) < 3.2/ < 2.6 rates were 44.0%/39.3% and 31.5%/28.8%, respectively; effectiveness was generally maintained to M18. Conclusions In concordance with studies of background risk, AEs were more common in patients with CV risk enrichment, particularly those aged ≥ 65 years. Tofacitinib effectiveness/persistence were generally similar regardless of CV risk enrichment. These findings support individualised treatment benefit–risk assessment, including CV assessment/management, to optimise RA outcomes.

• Publisher: Springer Healthcare,Springer Nature B.V,Adis, Springer Healthcare
• Subject: Antirheumatic agents / Cardiovascular diseases / Family Medicine / General Practice / Internal Medicine / JAK inhibitors / Medicine / Medicine & Public Health / Original Research / Orthopedics / Patients / Quality of Life Research / Remission (Medicine) / Rheumatoid arthritis / Rheumatology / Skin cancer / Therapeutics / Tofacitinib