Rheumatoid Arthritis: Anti-TNF Therapy and Infections
Rheumatoid Arthritis: Anti-TNF Therapy and Infections
Objectives. To evaluate the risk of serious infections (SIs) in patients with RA treated with anti-TNF therapy with emphasis on the risk across different ages.
Methods. Using data from the British Society for Rheumatology Biologics Register, a prospective observational study, we compared the risk of SI between 11 798 anti-TNF-treated patients and 3598 non-biologic DMARD (nbDMARD)-treated patients.
Results. A total of 1808 patients had at least one SI (anti-TNF: 1512; nbDMARD: 296). Incidence rates were: anti-TNF 42/1000 patient-years of follow-up (95% CI 40, 44) and nbDMARD 32/1000 patient-years of follow-up (95% CI 28, 36). The adjusted hazard ratio (adjHR) for SI in the anti-TNF cohort was 1.2 (95% CI 1.1, 1.5). The risk did not differ significantly between the three agents adalimumab, etanercept and infliximab. The risk was highest during the first 6 months of therapy [adjHR 1.8 (95% CI 1.3, 2.6)]. Although increasing age was an independent risk factor for SI in both cohorts, there was no difference in relative risk of infection in patients on anti-TNF therapy in the older population. There was no difference in hospital stay for SI between cohorts. Mortality within 30 days of SI was 50% lower in the anti-TNF cohort [odds ratio 0.5 (95% CI 0.3, 0.8)].
Conclusions. These data add to currently available evidence suggesting that anti-TNF therapy is associated with a small but significant overall risk of SI. This must be balanced against the risks associated with poor disease control or alternative treatments.
RA has detrimental effects on a wide range of health outcomes, reaching far beyond the damage to the musculoskeletal system. RA is associated with increased mortality and comorbidity from a number of causes compared with the general population, including infection. Biologic therapies now bring the opportunity to target precise pathways within the immune system and inflammatory pathway leading to improved outcome for RA patients through better disease control and thus a reduction in the associated comorbidity and mortality. The anti-TNF drugs were the first biologic agents to become established in the management of RA patients who fail to respond to traditional non-biologic DMARDs (nbDMARDs). However, TNF plays an important role in host defence. Therefore, the introduction of anti-TNF agents was accompanied by a need to study and understand the effect on infection risk of modifying this key pathway.
This article summarizes the latest results from the British Society for Rheumatology Biologics Register (BSRBR) on rates of all serious infections (SIs), comparing nbDMARD with anti-TNF, as well as comparing between the three anti-TNF agents that were licensed in the UK between 2001 and 2009 [infliximab (INF), etanercept (ETN) and adalimumab (ADA)]. As follow-up has accrued, the BSRBR has acquired sufficient statistical power to be able to examine time-varying risk, age-specific risks and differences in outcome of infection.
Abstract and Introduction
Abstract
Objectives. To evaluate the risk of serious infections (SIs) in patients with RA treated with anti-TNF therapy with emphasis on the risk across different ages.
Methods. Using data from the British Society for Rheumatology Biologics Register, a prospective observational study, we compared the risk of SI between 11 798 anti-TNF-treated patients and 3598 non-biologic DMARD (nbDMARD)-treated patients.
Results. A total of 1808 patients had at least one SI (anti-TNF: 1512; nbDMARD: 296). Incidence rates were: anti-TNF 42/1000 patient-years of follow-up (95% CI 40, 44) and nbDMARD 32/1000 patient-years of follow-up (95% CI 28, 36). The adjusted hazard ratio (adjHR) for SI in the anti-TNF cohort was 1.2 (95% CI 1.1, 1.5). The risk did not differ significantly between the three agents adalimumab, etanercept and infliximab. The risk was highest during the first 6 months of therapy [adjHR 1.8 (95% CI 1.3, 2.6)]. Although increasing age was an independent risk factor for SI in both cohorts, there was no difference in relative risk of infection in patients on anti-TNF therapy in the older population. There was no difference in hospital stay for SI between cohorts. Mortality within 30 days of SI was 50% lower in the anti-TNF cohort [odds ratio 0.5 (95% CI 0.3, 0.8)].
Conclusions. These data add to currently available evidence suggesting that anti-TNF therapy is associated with a small but significant overall risk of SI. This must be balanced against the risks associated with poor disease control or alternative treatments.
Introduction
RA has detrimental effects on a wide range of health outcomes, reaching far beyond the damage to the musculoskeletal system. RA is associated with increased mortality and comorbidity from a number of causes compared with the general population, including infection. Biologic therapies now bring the opportunity to target precise pathways within the immune system and inflammatory pathway leading to improved outcome for RA patients through better disease control and thus a reduction in the associated comorbidity and mortality. The anti-TNF drugs were the first biologic agents to become established in the management of RA patients who fail to respond to traditional non-biologic DMARDs (nbDMARDs). However, TNF plays an important role in host defence. Therefore, the introduction of anti-TNF agents was accompanied by a need to study and understand the effect on infection risk of modifying this key pathway.
This article summarizes the latest results from the British Society for Rheumatology Biologics Register (BSRBR) on rates of all serious infections (SIs), comparing nbDMARD with anti-TNF, as well as comparing between the three anti-TNF agents that were licensed in the UK between 2001 and 2009 [infliximab (INF), etanercept (ETN) and adalimumab (ADA)]. As follow-up has accrued, the BSRBR has acquired sufficient statistical power to be able to examine time-varying risk, age-specific risks and differences in outcome of infection.
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