Infections in patients with rheumatoid arthritis receiving tofacitinib versus tumour necrosis factor inhibitors: results from the open-label, randomised controlled ORAL Surveillance trial

• Published in: Annals of the rheumatic diseases Vol. 81; no. 11; pp. 1491 - 1503
• Main Authors: Balanescu, Andra-Rodica, Citera, Gustavo, Pascual-Ramos, Virginia, Bhatt, Deepak L, Connell, Carol A, Gold, David, Chen, All-Shine, Sawyerr, Gosford, Shapiro, Andrea B, Pope, Janet E, Schulze-Koops, Hendrik
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and European League Against Rheumatism 01.11.2022; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Analgesics, Opioid - therapeutic use; antirheumatic agents; Antirheumatic Agents - adverse effects; arthritis, rheumatoid; Arthritis, Rheumatoid - chemically induced; Arthritis, Rheumatoid - drug therapy; C-Reactive Protein; Cardiovascular diseases; Drug dosages; Female; Humans; Infections; Joint diseases; Lung diseases; Lung Diseases - drug therapy; Necrosis; Patients; Piperidines; Pyrimidines; Pyrroles - adverse effects; Rheumatoid Arthritis; Risk factors; Steroids; Surveillance; therapeutics; Tuberculosis; Tumor necrosis factor; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Tumor necrosis factor-TNF; Tumors; Canada; United States > US; arthritis, rheumatoid; therapeutics; tumor necrosis factor inhibitors; antirheumatic agents
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/ard-2022-222405

ObjectivesTo characterise infections in patients with rheumatoid arthritis (RA) in ORAL Surveillance.MethodsIn this open-label, randomised controlled trial, patients with RA aged≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg two times per day or a tumour necrosis factor inhibitor (TNFi). Incidence rates (IRs; patients with first events/100 patient-years) and hazard ratios (HRs) were calculated for infections, overall and by age (50–<65 years; ≥65 years). Probabilities of infections were obtained (Kaplan-Meier estimates). Cox modelling identified infection risk factors.ResultsIRs/HRs for all infections, serious infection events (SIEs) and non-serious infections (NSIs) were higher with tofacitinib (10>5 mg two times per day) versus TNFi. For SIEs, HR (95% CI) for tofacitinib 5 and 10 mg two times per day versus TNFi, respectively, were 1.17 (0.92 to 1.50) and 1.48 (1.17 to 1.87). Increased IRs/HRs for all infections and SIEs with tofacitinib 10 mg two times per day versus TNFi were more pronounced in patients aged≥65 vs 50–<65 years. SIE probability increased from month 18 and before month 6 with tofacitinib 5 and 10 mg two times per day versus TNFi, respectively. NSI probability increased before month 6 with both tofacitinib doses versus TNFi. Across treatments, the most predictive risk factors for SIEs were increasing age, baseline opioid use, history of chronic lung disease and time-dependent oral corticosteroid use, and, for NSIs, female sex, history of chronic lung disease/infections, past smoking and time-dependent Disease Activity Score in 28 joints, C-reactive protein.ConclusionsInfections were higher with tofacitinib versus TNFi. Findings may inform future treatment decisions.Trial registration number NCT02092467.