title: Tuberculosis and other opportunistic infections in tofacitinib-treated patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To evaluate the risk of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with tofacitinib.
  
  
  METHODS
  Phase 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).
  
  
  RESULTS
  We 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)).
  
  
  CONCLUSIONS
  Within 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.
authors: Oregon Health and Science University, Portland, Oregon, USA.
authors: K L
authors: KL
authors: Winthrop
authors: Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
authors: S-H
authors: SH
authors: Park
authors: Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors: A
authors: A
authors: Gul
authors: Centro de Investigación Clínica de Morelia SC, Morelia, Mexico.
authors: M H
authors: http://orcid.org/0000-0002-2731-9180
authors: MH
authors: Cardiel
authors: Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.
authors: J J
authors: JJ
authors: Gomez-Reino
authors: University of Occupational and Environmental Health, Kitakyushu, Japan.
authors: Y
authors: Y
authors: Tanaka
authors: Pfizer Inc, New York, New York, USA.
authors: K
authors: K
authors: Kwok
authors: Pfizer Inc, New York, New York, USA.
authors: T
authors: T
authors: Lukic
authors: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors: E
authors: E
authors: Mortensen
authors: Pfizer Inc, Lima, Peru.
authors: D
authors: D
authors: Ponce de Leon
authors: Pfizer Inc, Groton, Connecticut, USA.
authors: R
authors: R
authors: Riese
authors: Pfizer Inc, New York, New York, USA.
authors: H
authors: H
authors: Valdez
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D002986:Clinical Trials as Topic; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors; D009894:Opportunistic Infections / Q000139:chemically induced* / Q000453:epidemiology / Q000276:immunology; D010880:Piperidines / Q000009:adverse effects* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects* / Q000627:therapeutic use; D018570:Risk Assessment; D014376:Tuberculosis / Q000139:chemically induced* / Q000453:epidemiology / Q000276:immunology
chemical_list: D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053616:Janus Kinase 3
keywords: DMARDs (synthetic); Infections; Rheumatoid Arthritis; Treatment; Tuberculosis