Background/Purpose:  Glucocorticoids (GCs) and biologic disease-modifying antirheumatic drugs (DMARDs) have previously been associated with serious infection events (SIEs) among rheumatoid arthritis (RA) patients. For patients on non-biologic DMARDs (nbDMARD) and GCs, , it is unclear whether any increased risk for SIEs associated with adding a biologic might be offset if patients are able to reduce their GC exposure.

Methods: Using 2002-2013 Corrona RA registry data contributed by U.S rheumatologists and their RA patients, we identified eligible index visits where patients were on a nbDMARD and GCs, but not on biologics. Biologic DMARDs include etanercept, adalimumab, certolizumab, golimumab, infliximab, abatacept, rituximab and tocilizumab. Patients with psoriasis arthritis and malignancy were excluded. Follow up started at this time (i.e. index date), and ended at the earliest date of: a hospitalized infection, a visit when patient was on nbDMARDs only without GC, GCs without nbDMARD or no RA treatment, death, an 18-month gap between CORRONA visits, or 6/30/13. As a time-varying exposure, we categorized each person day into the following five exposure categories:  nbDMARDs + GC (prednisone <5mg/day), nbDMARDs + GC (≥5mg/day), biologic DMARD + GC (<5mg/day), biologic DMARDs + GC (≥5mg/day), and biologic DMARD without GCs. Biologic exposure could have included concomitant nbDMARD use. At each visit, physicians reported the occurrence of SIEs. Events were confirmed in two stages, both by reporting physicians and with medical records. We calculated the incidence rate of SIEs for each exposure and compared risks using Cox regression adjusting for age, gender and clinical disease activity index (CDAI) at the index date.

Results: Of 12,851 eligible index visits where patients initiated nbDMARDs and GCs, 23% were with GC <5mg/day and 77% with GC ≥5mg. For patients were treated with nbDMARDs and GCs <5mg/day at the start of follow-up, 14.4% subsequently initiated biologics. For these individuals, 45.9% were able to discontinue GCs, 32.6% were on GC <5mg/day and 12.5 were on GC ≥5mg at the end of follow-up. Of 1,779 (20%) patients starting on nbDMARDs and GCs ≥5mg and then initiated biologics, 41.7% were able to discontinue glucocorticoids, and 9.8% were able to reduce GC dose to < 5mg by end of follow-up. After excluding 7% of SIEs that could not be confirmed, we identified 293SIEs yielding an incidence rate for SIEs of 1.8 per 100 person years across all exposures. After adjustment and compared to exposure of nbDMARDs + GCs (≥5mg/day), patients on biologic DMARDs without steroid use were less likely to have a SIE (Table). Both age and CDAI at the index date were positively associated with SIEs (not shown).

Conclusion: Many RA patients treated with nbDMARDs and glucocorticoids who initiate biologics are subsequently able to discontinue glucocorticoids. These individuals are at reduced risk for serious infections.