1275 Weaver, et al: RADIUS serious infection events Personal non-commercial use only. The Journal of Rheumatology Copyright © 2013. All rights reserved. Rheumatoid Arthritis Disease Activity and Disability Affect the Risk of Serious Infection Events in RADIUS 1 Arthur Weaver, Orrin Troum, Michele Hooper, Andrew S. Koenig, Sandeep Chaudhari, JingYuan Feng, and Deborah Wenkert ABSTRACT. Objective. To determine whether disease activity and disability independently correlate with serious infection event (SIE) risk in a large rheumatoid arthritis (RA) cohort. Methods. The associations between SIE and Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in the Rheumatoid Arthritis Disease-Modifying Antirheumatic Drug Intervention and Utilization Study (RADIUS 1) cohort were evaluated using the Andersen-Gill model (a proportional HR model allowing > 1 event per patient). Results. Of 4084 patients with 347 SIE, 271 patients experienced ≥ 1 SIE. A 5-unit CDAI increase and 0.4-unit HAQ-DI increase corresponded to an increase in SIE risk with and without covariate adjustments. A 5-unit CDAI increase corresponded with a 7.7% increased SIE risk (adjusted HR 1.077, 95% CI 1.044–1.112, p < 0.0001) and a 0.4-unit HAQ-DI increase with a 30.1% increased risk (adjusted HR 1.301, 95% CI 1.225–1.381, p < 0.0001). Categorical analysis showed that more severe RA activity (even after controlling for disability) and disability were associated with an increased SIE risk. Conclusion. Increased RA disease activity and disability were each associated with a significantly increased SIE risk in the RADIUS 1 cohort, which could not be completely accounted for by disability. (First Release June 15 2013; J Rheumatol 2013;40:1275–81; doi:10.3899/jrheum.121288) Key Indexing Terms: RHEUMATOID ARTHRITIS INFECTION ANTIRHEUMATIC DRUGS DISEASE-MODIFYING ANTIRHEUMATIC DRUGS From the University of Nebraska Medical Center, Omaha, Nebraska; Keck School of Medicine/University of Southern California, Los Angeles, California; Amgen Inc., Thousand Oaks, California; Pfizer Inc., Collegeville, Pennsylvania; and Kforce Clinical Research, Tampa, Florida, USA. Sponsored by Immunex, a wholly owned subsidiary of Amgen Inc., and by Wyeth, which was acquired by Pfizer Inc. in October 2009. A. Weaver, MD, University of Nebraska Medical Center; O. Troum, MD, University of Southern California; M. Hooper, MD, MS, Amgen Inc.; A.S. Koenig, DO, Pfizer Inc., S. Chaudhari, MS, Kforce Clinical Research; J. Feng, MS; D. Wenkert, MD, Amgen Inc. Address correspondence to Dr. A. Weaver, 9914 Weavers Point Road, Pequot Lakes, MN 56472, USA. E-mail: arthur.weaver@earthlink.net Accepted for publication April 30, 2013. Epidemiologic evidence suggests increased rates of serious infections in patients with rheumatoid arthritis (RA) 1,2,3 . Serious infections contribute to increased morbidity and mortality in patients with RA 4,5,6,7 . Comorbidities associated with RA such as pulmonary and cardiovascular disease 1,2,8,9,10,11,12 as well as immunosuppression due to treatment with disease-modifying antirheumatic drugs (DMARD) 9,13,14 may increase the risk of infection. Several studies have shown that increased RA disease activity itself may also increase the risk of infection 1,2,3,8,9,11,15,16,17 , often concluding that this increase in infection risk is due to the associated disability 2,9,11 . However, it is unclear whether this increased infectious risk is indeed due to a concomitant increase in disability or whether at least some of the risk is independently due to the disease activity itself. This posthoc analysis evaluated the association between DMARD, comorbidities, RA disease activity, and disability on the risk of infection in RADIUS 1 (Rheumatoid Arthritis Dis- ease-Modifying Antirheumatic Drug Intervention and Utilization Study), a 5-year, multicenter observational study 18,19 to determine whether RA activity itself increases the risk of serious infection events (SIE). MATERIALS AND METHODS Study design. The methodology for RADIUS 1 has been reported 18,19 . RADIUS 1 was a prospective, multicenter observational study designed to systematically collect and document data regarding use patterns, effec- tiveness, and safety of DMARD treatments used in the management of RA. The RADIUS 1 cohort (n = 4968) consisted of patients with RA who required a change or addition of DMARD. They were enrolled from October 2001 through January 2003 from community-based private practices (88%), academic institutions (7%), and hospitals (5%). The frequency and scope of clinical evaluations were performed according to the investigator’s routine clinical practice rather than protocol-driven. Visits were frequent: 68.7% of patient visits were within 3 months of one another and 93.1% were within 6 months of one another. Data were entered by the site at baseline and at followup visits (for up to 5 years), and included laboratory values, information on comorbid condi- tions, Health Assessment Questionnaire-Disability Index (HAQ-DI) 20,21 , joint counts, Physician Global Assessment (PhGA), Patient Global Assessment (PtGA), antirheumatic drug therapy, and serious adverse events. Study monitoring was performed on 96% of the sites that partici- www.jrheum.org Downloaded on January 21, 2022 from