Risk of Serious Infection in Patients With Rheumatoid Arthritis Treated With Biologic Versus Nonbiologic Disease‐Modifying Antirheumatic Drugs

Abstract

ObjectiveThe objective of this study is to examine the risk of serious infections (SIs) associated with biological disease‐modifying antirheumatic drugs (bDMARDs) compared with conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) in patients with rheumatoid arthritis (RA).MethodsWe studied patients with RA who initiated bDMARDs or csDMARDs from 2001 to 2016 in FORWARD–The National Databank for Rheumatic Diseases. Disease‐modifying antirheumatic drugs (DMARDs) were categorized into three groups: (1) csDMARDs (bDMARD‐naïve; reference), (2) tumor necrosis factor α inhibitors (TNFis), and (3) non‐TNFi biologics (abatacept, rituximab, tocilizumab, and anakinra). SIs were defined as those requiring intravenous antibiotics or hospitalization or those resulting in death. We calculated the propensity score (PS), which reflected the probability of receiving a specific DMARD group, and estimated the hazard ratio (HR) (with the 95% confidence interval [CI]) for SI from multivariable Cox models, adjusting for PS and time‐varying confounders.ResultsA total of 694 (5.9%) first SIs were identified in 11 623 patients with RA during 27 552 patient‐years of follow‐up. The SI incidence rate per 1000 patient‐years was 22.4 (95% CI 19.2‐26.1) for csDMARDs, 26.9 (95% CI 24.5‐29.6) for TNFis, and 23.3 (95% CI 19.0‐28.5) for non‐TNFi bDMARDs. Adjusted HRs for SIs were 1.33 (95% CI 1.05‐1.68) for TNFis and 1.48 (95% CI 1.02‐2.16) for non‐TNFi bDMARDs, compared with csDMARDs. The SI risk with non‐TNFi bDMARDs versus TNFis was not different. Other risk factors for SI were older age, higher comorbidity burden (particularly pulmonary disease), higher weighted cumulative prednisone dose, disability and disease activity, and number of prior csDMARD failures.Conclusion TNFis and non‐TNFi bDMARDs were associated with an increased SI risk compared with csDMARDs in RA, even after accounting for risk‐associated patient characteristics.

National registry for patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV-2 in Germany (ReCoVery): a valuable mean to gain rapid and reliable knowledge of the clinical course of SARS-CoV-2 infections in patients with IRD

“…Moreover, treatment with DMARDs can be associated with infectious complications. Most frequently, these are of bacterial origin, 12 but also certain viral infections like Herpes zoster may complicate the course of many antirheumatic therapies. 13 Treatment with tumour necrosis factor (TNF) inhibitors is associated with an increased risk of serious infections at the beginning of treatment, but when effective, the risk decreases due to better functional capacity and decreased use of GC.…”

Incidence and Complication Rates for Total Hip Arthroplasty in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis Across Four Decades

“…But, mean corticosteroid dose has remained constant (mean 4.9-5.8 mg) [3,72,77,78,106]. This appears to contradict numerous studies which suggest that patients with RA receiving bDMARDs are at a higher risk of infection than those receiving sDMARDs [107][108][109][110]. It is also worth noting that there is no difference in infection risk between the various bDMARDs [111], and hence development of new bDMARDs has not impacted infection risk.…”

Infections in Patients with Rheumatoid Arthritis in the Era of Targeted Synthetic Therapies

“… 6 , 8 – 10 History of previous infections and high disease activity are probably the most important drivers of that risk in RA patients. 4 , 9 – 14 …”

“…Regarding conventional synthetic-DMARDs (cs-DMARDs) such as methotrexate or leflunomide, there are reassuring data to suggest that they confer either a small or no increased risk for serious infections in RA patients. 3 , 9 , 10 On the contrary, for GCs, a dose-dependent increase in the risk of serious infections has been shown. 3 , 10 , 15 Although daily doses below 5–7.5 mg are frequently considered as “safe”, 16 it appears that long-term, continuous exposure even to low GC doses may also contribute to increased risk.…”

“… 3 , 10 , 15 Although daily doses below 5–7.5 mg are frequently considered as “safe”, 16 it appears that long-term, continuous exposure even to low GC doses may also contribute to increased risk. 3 , 9 …”