Tuberculosis and other opportunistic infections in tofacitinib-treated patients with rheumatoid arthritis

• Published in: Annals of the rheumatic diseases Vol. 75; no. 6; pp. 1133 - 1138
• Main Authors: Winthrop, K L, Park, S-H, Gul, A, Cardiel, M H, Gomez-Reino, J J, Tanaka, Y, Kwok, K, Lukic, T, Mortensen, E, Ponce de Leon, D, Riese, R, Valdez, H
• Format: Journal Article
• Language: English
• Published: England Elsevier Limited 01.06.2016; BMJ Publishing Group
• Series: Extended report
• Subjects: Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - epidemiology; Arthritis, Rheumatoid - immunology; Clinical and Epidemiological Research; Clinical Trials as Topic; Cytomegalovirus; Herpes viruses; Humans; Immunocompromised Host; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Incidence; Infections; Janus Kinase 3 - antagonists & inhibitors; Kinases; Opportunistic Infections - chemically induced; Opportunistic Infections - epidemiology; Opportunistic Infections - immunology; Patients; Piperidines - adverse effects; Piperidines - therapeutic use; Pneumonia; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Pyrroles - adverse effects; Pyrroles - therapeutic use; Regions; Rheumatoid arthritis; Risk Assessment; Steroids; Tuberculosis; Tuberculosis - chemically induced; Tuberculosis - epidemiology; Tuberculosis - immunology; Tumor necrosis factor-TNF; Viral infections; United States > US; Japan; DMARDs (synthetic); Infections; Treatment; Tuberculosis; Rheumatoid Arthritis
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2015-207319

ObjectivesTo evaluate the risk of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with tofacitinib.MethodsPhase II, III and long-term extension clinical trial data (April 2013 data-cut) from the tofacitinib RA programme were reviewed. OIs defined a priori included mycobacterial and fungal infections, multidermatomal herpes zoster and other viral infections associated with immunosuppression. For OIs, we calculated crude incidence rates (IRs; per 100 patient-years (95% CI)); for tuberculosis (TB) specifically, we calculated rates stratified by patient enrolment region according to background TB IR (per 100 patient-years): low (≤0.01), medium (>0.01 to ≤0.05) and high (>0.05).ResultsWe identified 60 OIs among 5671 subjects; all occurred among tofacitinib-treated patients. TB (crude IR 0.21, 95% CI of (0.14 to 0.30)) was the most common OI (n=26); median time between drug start and diagnosis was 64 weeks (range 15–161 weeks). Twenty-one cases (81%) occurred in countries with high background TB IR, and the rate varied with regional background TB IR: low 0.02 (0.003 to 0.15), medium 0.08 (0.03 to 0.21) and high 0.75 (0.49 to 1.15). In Phase III studies, 263 patients diagnosed with latent TB infection were treated with isoniazid and tofacitinib concurrently; none developed TB. For OIs other than TB, 34 events were reported (crude IR 0.25 (95% CI 0.18 to 0.36)).ConclusionsWithin the global tofacitinib RA development programme, TB was the most common OI reported but was rare in regions of low and medium TB incidence. Patients who screen positive for latent TB can be treated with isoniazid during tofacitinib therapy.