801 - Initiation of Biologic DMARDs and the Risk of Hospitalization for Infection in Patients with Autoimmune Diseases

Sunday, November 6, 2011: 4:30 PM
W470b (McCormick Place West)
Carlos Grijalva1, Lang Chen2, Elizabeth S. Delzell2, John Baddley2, Timothy Beukelman3, Kevin L. Winthrop4, Marie Griffin5, Lisa Herrinton6, Liyan Liu6, Parivash Nourjah7, Nivedita M. Patkar3, Daniel H. Solomon8, James Lewis9, Fenglong Xie2, Kenneth G. Saag2 and Jeffrey R. Curtis2, 1Vanderbilt University, Nashville, TN, 2University of Alabama at Birmingham, Birmingham, AL, 3Univ of Alabama-Birmingham, Birmingham, AL, 4Oregon Health Science Univ, Portland, OR, 5Vanderbilt, 6Oakland, CA, 7Rockville, MD, 8Brigham and Women's Hospital, Boston, MA, 9University of Pennsylvania
Presentation Number: 801

Background/Purpose:  Although TNF-alpha(α)  antagonists are increasingly used in place of other non-biologic disease modifying antirheumatic drugs (DMARDs), their safety profile remains debatable. The objective of this study was to determine whether initiation of TNF-α antagonists increases the risk of serious infections compared with non-biologic DMARDs in patients with autoimmune diseases.

Method: We combined data from Kaiser Permanente Northern California, Pharmaceutical Assistance Contract for the Elderly, Tennessee Medicaid and National Medicaid/Medicare, in a retrospective cohort (1998-2007). We identified patients with rheumatoid arthritis (RA); inflammatory bowel disease (IBD); and psoriasis (PsO), psoriatic arthritis (PsA) or ankylosing spondylitis (PsO-PsA-AS). The incidence of hospitalizations for serious infections was compared between initiators of TNF-α antagonists and alternate non-biologic DMARD regimens in disease specific-propensity score (PS) - matched cohorts using Cox regression models with non-biologics as reference. Baseline glucocorticoid use was categorized according to the estimated average daily dose of prednisone equivalents (none, >0-<5 (low dose), 5-10 (medium dose) and >10 mg (high dose)), and evaluated as a separate covariate.

Result:  Among RA, IBD and PsO-PsA-AS patients, we identified 10602, 3219 and 1323 PS-matched pairs of episodes of TNF-α antagonist and alternate regimen use, respectively. Among RA patients, hospitalization rates of serious infections were 8.17 and 7.66 per 100 person-years, respectively (adjusted hazard ratio [aHR]: 1.09 (95% CI: 0.94-1.25)). Among IBD patients, the respective rates were 10.91 and 9.49 per 100 person-years (aHR: 1.14, (0.86-1.52)) whereas among PsO-PsA-AS patients, the respective rates were 5.41 and 5.19 per 100 person-years (aHR: 1.10, (0.80-1.53)). Among RA patients, infliximab was associated with a significant increase in the risk of serious infections compared with etanercept and adalimumab (aHRs: 1.26 (1.08-1.49) and 1.23 (1.02-1.48), respectively). For RA and PsO-PsA-AS, baseline glucocorticoid use was associated with a dose-dependent increase in risk of infections compared with no glucocorticoid use (for RA, aHRs: 1.39, 1.76 and 2.73; and for PsO-PsA-AS, aHRs: 1.36, 2.24 and 2.28 for low, medium and high doses, respectively).

Conclusion: In this large study consisting predominantly of older and low income patients with autoimmune diseases, initiation of TNF-α antagonists (as a group) was not associated with a significant increase in the risk of hospitalization for infections compared with alternate non-biologic regimens. Glucocorticoid use was associated with a dose-dependent increase in risk.

Keywords: bacterial infections, rheumatoid arthritis (RA) and tumor necrosis factor (TNF)

Disclosure: C. Grijalva, None; L. Chen, None; E. S. Delzell, Amgen, 2 ; J. Baddley, Abbott Immunology Pharmaceuticals, 5 ; T. Beukelman, None; K. L. Winthrop, Genentech, Abbott, and Amgen, 5 ; M. Griffin, None; L. Herrinton, Research grant, 2 ; L. Liu, None; P. Nourjah, None; N. M. Patkar, None; D. H. Solomon, Abbott Immunology Pharmaceuticals, 2, Amgen, 2, Corrona, 5, Bristol-Myers Squibb, 9 ; J. Lewis, Amgen, 5, Pfizer Inc, 5, Millenium Pharmaceuticals, 5, Allos Theraeutics, 5, Centocor, Inc., 2, Shire, 2, Takeda, 2 ; F. Xie, None; K. G. Saag, None; J. R. Curtis, Merck Pharmaceuticals, 2, Novartis Pharmaceutical Corporation, 2, Proctor & Gamble Pharmaceuticals, 2, Eli Lilly and Company, 2, Merck Pharmaceuticals, 5, Eli Lilly and Company, 5, Roche Pharmaceuticals, 5, Novartis Pharmaceutical Corporation, 5 .