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Extended report
High disease activity is associated with an increased risk of infection in patients with rheumatoid arthritis
  1. Karen Au1,
  2. George Reed2,
  3. Jeffrey R Curtis3,
  4. Joel M Kremer4,
  5. Jeffrey D Greenberg5,
  6. Vibeke Strand6,
  7. Daniel E Furst1 on behalf of the CORRONA Investigators
  1. 1Division of Rheumatology, University of California Los Angeles, Los Angeles, California, USA
  2. 2Division of Preventive and Behavioral Medicine, University of Massachusetts School of Medicine, Worcester, Massachusetts, USA
  3. 3Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA
  4. 4Division of Rheumatology, Albany Medical College, Albany, New York, USA
  5. 5Department of Rheumatology, New York University Hospital for Joint Diseases, New York, New York, USA
  6. 6Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, California, USA
  1. Correspondence to Daniel E Furst, UCLA Division of Rheumatology, 1000 Veteran Ave 32-59, Los Angeles, CA 90095, USA; defurst{at}


Objective To determine the relationship of disease activity to infections in patients with rheumatoid arthritis (RA).

Methods From the CORRONA database, the incidence of physician-reported infections in RA patients on stable disease-modifying antirheumatic drug, biological, and corticosteroid therapy for at least 6 months was ascertained. Two composite measures of disease activity were defined: clinical disease activity index (CDAI) and disease activity score 28 (DAS28). Incident rate ratios (IRR) were calculated using generalised estimating equation Poisson regression models adjusted for demographics, medications and clinical factors.

Results Of 1 6242 RA patients, 6242 were on stable therapy for at least 6 months and were eligible for analysis. 2282 infections were reported in the cohort, followed over 7290 patient-years. After controlling for possible confounders, disease activity was associated with an increased rate of infections. Each 0.6 unit increase in DAS28 score corresponded to a 4% increased rate of outpatient infections (IRR 1.04, p=0.01) and a 25% increased rate of infections requiring hospitalisation (IRR 1.25, p=0.03). There was a dichotomy in the relationship between infections and CDAI scores. For CDAI <10 (mild disease activity) patients had a 12% increased rate of outpatient infections with each 5 unit increase in CDAI score (IRR 1.12, p=0.003). At CDAI scores ≥10, there was no further increase in the rate of outpatient infections associated with higher disease activity. The relationship of CDAI to hospitalised infections showed similar trends to outpatient data but did not reach statistical significance after multivariate analysis (CDAI <10: IRR 1.56, p=0.08).

Conclusions In this large cohort of RA patients, higher disease activity was associated with a higher probability of developing infections.

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  • Funding The study was supported in part by funding from Amgen. Amgen had no role in the study design, data collection, data analysis, or writing of the manuscript.

  • Competing interests GR has a research contract with CORRONA. JRC receives salary support from NIH (AR053351). He is a consultant for Amgen, Centocor, CORRONA, Pfizer, Roche/Genentech, UCB and received research support from Amgen, Centocor, CORRONA, Roche/Genentech. He also serves as the director of ACIP, a clinical trials unit at UAB that studies rheumatological diseases. JMK receives research support from Amgen, Abbott, Centocor, BMS, Genentech, HGS, Pfizer, Roche and UCB as well as honoraria from Abbott, Centocor, BMS, Roche and Genentech. JDG receives salary support from research grants from the NIH (K23AR054412), the Arthritis Foundation and the Arthritis National Research Foundation. He serves as Chief Scientific Officer for CORRONA and has served on advisory boards for Centocor, Genentech and UCB. VS is a consultant for Abbott, Alder, Allergan, Almirall, Amgen, AstraZeneca, BiogenIdec, CBio, CanFite, Centocor, Chelsea, Crescendo, Cypress Biosciences, Eurodiagnostica, Fibrogen, Forest Laboratories, Genentech, GlaxoSmithKline, HGS, Idera, Incyte, Jazz Pharmaceuticals, Lexicon Genetics, Lilly, Logical Therapeutics, Lux Biosciences, Medimmune, MerckSerono, Novartis, NovoNordisk, Nicox, Nuon, Ono Pharmaceuticals, Pfizer, Rigel, Roche, Sanofi-Aventis, Savient, Schering Plough, SKK, UCB and Xdx. She serves on advisory boards for Abbott, Amgen, BiogenIdec, BMS, CanFite, Centocor, Chelsea, Crescendo, Cypress, Eurodiagnostica, Fibrogen, Forest, Genentech, GSK, HGS, Idera, Incyte, Jazz, Lilly, Nicox, Novartis, NovoNordisk, Pfizer, Rigel, Roche, Savient, Schering Plough and UCB. DEF receives funding from Abbott, Actelion, Amgen, BMS, BiogenIdec, Centocor, Corrona, Genentech, Gilead, GSK, Human Genome sciences, Merck, NIH, Nitec, Novartis, Roche, UCB, Wyeth and Xoma. He also serves as Director of Publications for CORRONA. KA delares no competing interests.

  • Ethics approval Approval from the institutional review boards of each site was obtained before the start of the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.