Background/Purpose: Patients with rheumatoid arthritis (RA) are at an increased risk for serious hospitalized infectious events (HIEs). Research suggests that tumor necrosis factor alpha inhibitors (TNFi), as well as oral glucocorticoids (GCs) both increase the risk of HIEs.  Limited information is available regarding the contribution toward HIEs when taking into account the dose-level of oral glucocorticoids when used concomitantly among new users of TNFi.

Methods: We conducted a retrospective cohort study using an administrative claims database. Among incident and prevalent adult RA patients newly exposed to TNFi, patients were assigned to 3 fluid study cohorts: no GC exposure; low-dose GC (≤ 7.5 mg); high-dose GC (>7.5 mg). Patients were required to have at least 1 inpatient or outpatient diagnostic claim for RA (ICD-9-CM 714.0) with an accompanying claim for an incident TNFi and at least 6 months of continuous enrollment prior to TNFi initiation and 6 months after.  Patients could be considered exposed to GCs multiple times during follow-up-time and may contribute time to different categories of exposure.  Follow-up continued until disenrollment, HIE, discontinuation of TNFi, end of study (June 30, 2014), or 2 years after the index-date. The primary outcome was incident HIE and was attributed to the GC exposure category at the time of the outcome.  Incidence rates and 95% confidence intervals per 100 person years were estimated for HIEs.

Results: The mean age and sex distribution (% of female) of RA-TNFi patients for the no GC, low-dose GC, and high-dose GC were 53.7 and 77%, 55.1 and 76%, and 55.1 and 74%. The risk of HIEs increased with increasing GC dose, with a higher incremental risk from high dose to low dose than from low dose to no dose (Table). The risk of HIEs is highest among patients ages >65 years of age but the elevated dose-related effects are comparable for those <65 and those > 65.  

Conclusion: We found that both high dose and low dose steroids significantly increase the risk of HIEs.  Although steroid doses under 7.5 mg are often considered to be relatively low risk for infection, physicians should bear in mind that even low dose steroids significantly increase the risk of HIEs among patients newly initiating TNFi therapy.

¥: etanercept, adalimumab, infliximab, golimumab, certolizumab pegol

^: ≤7.5 mg of a prednisone equivalent oral glucocorticoid

*: >7.5 mg of a prednisone equivalent oral glucocorticoid

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dose-relationship-between-oral-glucocorticoids-and-tnf-inhibitors-and-the-risk-of-hospitalized-infectious-events-among-patients-with-rheumatoid-arthritis/