Author(s)

Julia F. Simard, Murray A. Mittleman, Nancy A. Shadick, Elizabeth W. Karlson

Department of Epidemiology, Harvard School of Public Health, Boston, MA.
Department of Epidemiology, Harvard School of Public Health, Boston, USA.
Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, Boston, MA.

Background: Anti-TNF treatment may increase infection risk, although this has been difficult to study because the timing of anti-TNF treatment is driven by disease activity, which may influence infection susceptibility leading to confounding that varies over time. We evaluated the association between anti-TNF initiation in rheumatoid arthritis (RA) patients on disease modifying anti-rheumatic drugs (DMARD) and infection using multiple approaches adjusting for time-varying confounding. Methods: 383 anti-TNF-na?ve RA patients on ≥ 1 non-biologic-DMARD at enrollment from the Brigham and Women’s Rheumatoid Arthritis Sequential Study (BRASS) were followed up to two years. Pooled logistic regressions estimated the association between anti-TNF and infection by including time-varying covariates in the adjusted models and inverse probability treatment weighting (IPTW). Results: Adjustment for time-varying disease activity and other suspected confounders yielded non-statistically significant positive associations between anti-TNF start and infection regardless of analytic approach (RR_{mvar_adj} = 2.1, 95% CI: 0.8 - 5.8). Conclusions: Incorporating changing clinical status, and treatment indications and consequences, yielded consistently (though not significantly) elevated relative risks of infection associated with anti-TNF initiation. Due to limited statistical power, we cannot draw firm conclusions. However, we have illustrated multiple approaches adjusting for potential time-varying confounding in longitudinal studies and hope to replicate the approaches in larger studies.

Inverse Probability Weighting; Anti-TNF; Infection; Rheumatoid Arthritis

J. Simard, M. Mittleman, N. Shadick and E. Karlson, "TNF-α Antagonist and Infection in Rheumatoid Arthritis," Open Journal of Rheumatology and Autoimmune Diseases, Vol. 2 No. 2, 2012, pp. 14-20. doi: 10.4236/ojra.2012.22004.