Background The RA Disease-Modifying Anti-Rheumatic Drug (DMARD) Intervention and Utilization Study–1 (RADIUS 1) was a real-world, prospective, 5-year, observational study of 4968 patients (aged ≥18 y) with RA (per 1987 American Rheumatism Association criteria) who had required a new biologic or nonbiologic DMARD (addition or switch). Although DMARDS and comorbidities may increase risk of SIE, RA disease activity itself may also increase infectious risk.

Objectives To evaluate the impact of RA disease activity, measured by the Clinical Disease Activity Index (CDAI), on the risk of developing ≥1 SIE in RADIUS 1 patients (pts).

Methods Data from RADIUS 1 pts who received ≥1 dose of DMARDs and had been followed up for >1 day were analyzed. SIEs occurring while on DMARD treatment were analyzed, excluding SIEs without a recorded date (n=11) or recorded DMARD; multiple SIEs occurring on the same day were analyzed as 1 event. Comorbidities at baseline were classified into 2 mutually exclusive groups—(1) RA-associated extra-articular manifestations (eg, Felty syndrome, pulmonary nodules) and (2) comorbidities that were not extra-articular manifestations of RA (eg, renal disease)—as well as into nonexclusive groups: asthma and COPD, ischemic heart disease, prior hospitalization for infection and cancers. Disease activity was defined as remission (CDAI ≤2.8), low (CDAI 2.8–10.0), moderate (CDAI 10–22) or high (CDAI >22). The Anderson-Gill model was used to calculate hazard ratios (HRs) and associated 95% CIs.

Results Analysis included 4084 pts: 81% white, 76% female, 22% with extra-articular manifestations thought to be RA associated, and 5% with comorbidities not attributable to RA. Prednisone was used by 56% of pts, with 24% of these pts receiving >10 mg/d. At baseline, mean disease duration was 7.3 years and mean CDAI was 35.7 (3% in CDAI remission; 15% low, 30% moderate, 49% high disease activity). 347 SIEs were observed, and 271 pts experienced ≥1 SIE; 33 pts had 2 SIEs, 7 had 3 SIEs, 7 had 4 SIEs, and 1 had 9 SIEs. HRs, unadjusted and adjusted (for age, sex, rheumatoid factor positive, disease duration, late onset [age >65 y], health assessment questionnaire, extra-articular RA manifestations, concomitant RA medications, and medical and medicinal factors contributing to increased risk of SIE), showed that a 5-unit increase in CDAI was associated with an 11.9% (unadjusted) and 7.9% (adjusted) increased risk of SIE (95% CIs, 1.09–1.15 and 1.04–1.12, respectively). Unadjusted/adjusted HRs (95% CI) for low (3.09/2.58 [1.34–7.12/1.12–5.96]) moderate (5.81/4.04 [2.56–13.2/1.77–9.23]), and high (7.50/4.55 [3.31–16.99/1.99–10.39]) disease activity indicated that more severe RA disease activity, measured by CDAI, was associated with increased risk of SIE.

Conclusions With and without controlling for covariates, increased RA disease activity significantly raised the risk of SIEs.

This study was sponsored by Immunex, a wholly owned subsidiary of Amgen Inc. and by Wyeth, which was acquired by Pfizer Inc. in October 2009.

Disclosure of Interest A. Weaver Consultant for: Amgen Inc, Speakers Bureau: Amgen Inc, O. Troum Grant/Research support from: Amgen Inc, Consultant for: Amgen Inc, M. Hooper Employee of: Amgen Inc, A. Koenig Employee of: Pfizer Inc, S. Chaudhari Consultant for: Amgen Inc, J.-Y. Feng Employee of: Amgen Inc, D. Wenkert Employee of: Amgen Inc