Nonserious Infections in Patients With Rheumatoid Arthritis: Results From the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Abstract

Objective To describe the frequency and predictors of nonserious infections (NSI) and compare incidence across biologic agents within the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR‐RA). Methods The BSRBR‐RA is a prospective observational cohort study. An NSI was defined as an infection that did not require hospitalization or intravenous therapy. Infections were captured from clinician questionnaires and patient diaries. Individuals were considered “at risk” from the date of initiation of biologic treatment for up to 3 years. Drug exposure was defined by agent: tumor necrosis factor inhibitor (TNFi), interleukin‐6 (IL‐6) inhibitor, B cell depletion (rituximab), or conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) alone. A multiple‐failure Cox model was used with multivariable adjustment. Missing data were addressed using multiple imputation. Results There were 17,304 NSI in 8,145 patients, with an event rate of 27.0 per person per year (95% confidence interval [95% CI] 26.6–27.4). Increasing age, female sex, comorbidity burden, glucocorticoid therapy, higher Disease Activity Score in 28 joints, and higher Health Assessment Questionnaire disability index were associated with an increased risk of NSI. There was a significant reduction in NSI risk with csDMARDs compared to biologic treatments. Compared to TNFi, IL‐6 inhibition and rituximab were associated with a higher NSI risk (adjusted hazard ratio 1.45 [95% CI 1.29–1.63] and adjusted hazard ratio 1.28 [95% CI 1.14–1.45], respectively), while the csDMARD cohort had a lower risk (adjusted hazard ratio 0.64 [95% CI 0.59–0.70]). Within the TNFi class, adalimumab was associated with a higher NSI risk than etanercept (adjusted hazard ratio 1.11 [95% CI 1.05–1.17]). Conclusion NSI occur frequently in RA, and predictors mirror those reported with serious infections. All biologics are associated with a greater risk of NSI, with differences observed between agents. While unmeasured confounding must be considered, the magnitude of effect is large, and a relationship between NSI and targeted immunomodulatory therapy likely exists.

Infections in patients with rheumatoid arthritis receiving tofacitinib versus tumour necrosis factor inhibitors: results from the open-label, randomised controlled ORAL Surveillance trial

“…26 27 Other risk factors for NSIs, which have been previously reported in registry data analyses of patients with RA receiving bDMARDs, include female sex and comorbidities. 8 In agreement with the current findings, real-world studies of patients with RA have consistently reported a greater risk of HZ (non-serious/serious) with JAK inhibitors versus bDMARDs. 12 24 28 For example, real-world US registry and claims database studies of patients with RA reported that HZ risk was twofold higher with tofacitinib versus bDMARDs.…”

“…Baseline opioid use was also a risk factor for NSIs across all treatments combined and has previously been reported to increase the risk of infections in patients with RA 26 27. Other risk factors for NSIs, which have been previously reported in registry data analyses of patients with RA receiving bDMARDs, include female sex and comorbidities 8…”

“… 26 27 Other risk factors for NSIs, which have been previously reported in registry data analyses of patients with RA receiving bDMARDs, include female sex and comorbidities. 8 …”

“…The increased susceptibility to infections in patients with RA has been attributed to disease pathophysiology, comorbidities, lifestyle factors and use of immunomodulatory drugs 3. Analyses of real-world and clinical trial data from patients with RA have shown that the risk of serious and non-serious infections (NSIs) is increased in those receiving biologic disease-modifying antirheumatic drugs (bDMARDs) versus conventional synthetic DMARDs (csDMARDs),7 8 and the risk of infections varies across treatments. For example, the tumour necrosis factor inhibitor (TNFi), etanercept, has been associated with reduced risk of infections versus other TNFi agents9–11 and the Janus kinase (JAK) inhibitor, tofacitinib 12…”

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update

“…The Task Force also found that the SLR had not revealed new safety concerns and that the risks of GC, including CV risk, are well established. That up to 60% of patients in registries [44][45][46] and also patients entering RCTs of new drugs in patients with early or established RA are already on GCs as maintenance therapy may be explained partly by either continuing an insufficiently effective DMARD or by lack of adherence to the recommendation on GC cessation by both patients and rheumatologists. Thus, while the Task Force does not recommend adding GCs when starting a bDMARD or tsDMARD (left part of phase II in the algorithm in figure 1), it does recommend GCs when starting another csDMARD (right part of phase II in figure 1).…”