RESUMO
INTRODUCTION: Anti-tumour necrosis factor (TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). In 2001, BSRBR was established to evaluate the safety of these agents. This paper addresses the safety of anti-TNF therapy in RA with specific reference to serious skin and soft tissue infections (SSSI) and shingles. METHODS: A cohort of anti-TNF-treated patients was recruited alongside a comparator group with active RA treated with non-biological disease-modifying antirheumatic drugs (nbDMARD). 11 881 anti-TNF and 3673 nbDMARD patients were analysed. Follow-up was by 6-monthly questionnaires to patients and clinicians. Analyses considered SSSI and shingles separately. Incidence rates (IR) were calculated and then compared using survival analyses. RESULTS: The crude IR for SSSI were: anti-TNF 1.6/100 patient-years (95% CI 1.4 to 1.8); nbDMARD 0.7/100 patient-years (95% CI 0.5 to 1.0) and shingles: anti-TNF 1.6/100 patient-years (95% CI 1.3 to 2.0); nbDMARD 0.8/100 patient-years (95% CI 0.6 to 1.1). Adjusted HR were SSSI 1.4 (95% CI 0.9 to 2.4), shingles 1.8 (95% CI 1.2 to 2.8). For SSSI, no significant differences were seen between anti-TNF agents. For shingles, the lowest risk was observed for adalimumab (adjusted HR vs nbDMARD) 1.5 (95% CI 1.1 to 2.0) and highest for infliximab (HR 2.2; 95% CI 1.4 to 3.4)). CONCLUSION: A significantly increased risk of shingles was observed in the anti-TNF-treated cohort. The risk of SSSI tended towards being greater with anti-TNF treatment but was not statistically significant. As with any observational dataset cause and effect cannot be established with certainty as residual confounding may remain. This finding would support the evaluation of zoster vaccination in this population.
Assuntos
Antirreumáticos/efeitos adversos , Herpes Zoster/epidemiologia , Dermatopatias Infecciosas/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Adalimumab , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Etanercepte , Humanos , Imunoglobulina G/efeitos adversos , Incidência , Infliximab , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral , Fatores de Risco , Fator de Necrose Tumoral alfa/antagonistas & inibidoresAssuntos
Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Meningite Criptocócica/induzido quimicamente , Idoso , Cryptococcus neoformans/isolamento & purificação , Humanos , Infliximab , Masculino , Rituximab , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
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.
Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Infecções/etiologia , Inibidores do Fator de Necrose Tumoral , Idoso , Anticorpos Monoclonais/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Análise de Regressão , Fatores de Risco , Fatores de Necrose Tumoral/efeitos adversos , Reino UnidoRESUMO
Early in the HIV epidemic it was feared that the disease would undermine leprosy control, as has occurred with tuberculosis. It was predicted that patients with leprosy and HIV coinfection would have an increased risk of lepromatous disease and a faster clinical evolution, and that the leprosy would be more difficult to treat. None of these concerns have materialised and the interaction between HIV and Mycobacterium leprae seems to be far more subtle than that between HIV and tuberculosis. We review the epidemiological, clinical, and pathological data relating to leprosy/HIV coinfection. The published epidemiological data are limited in quality but show neither an increased HIV prevalence among leprosy cases nor an alteration in clinical spectrum of leprosy among coinfected patients. Some data suggest that immune-mediated reactions that complicate leprosy occur at a higher frequency in coinfected patients. Leprosy has now been reported presenting as immune reconstitution disease among patients commencing highly active antiretroviral treatment. Histopathological observations reveal a normal spectrum of appearances in biopsies of leprosy lesions from coinfected patients, even among those with advanced immunodeficiency. These observations suggest that cell-mediated immune responses to M leprae are preserved at the site of disease despite evidence that these responses are abrogated systemically, by contrast with tuberculosis, in which the host granulomatous response is impaired by HIV coinfection. We speculate that this paradox may relate to differences between the activation state and rates of cell turnover within leprosy and tuberculosis granulomas that differentially affect the susceptibility of the granulomas to HIV. The interactions between leprosy and HIV have been little studied and further research on the clinical, pathological, and management aspects of this coinfection is warranted.