ABSTRACT
Introduction: Registries of spondyloarthritis (SpA) patients' follow-up provided evidence that tumor necrosis factor inhibitors (TNFi) increase the incidence of active tuberculosis infection (TB). However, most of these registries are from low burden TB areas. Few studies evaluated the safety of biologic agents in TB endemic areas. This study compares the TB incidence rate (TB IR) in anti-TNF-naïve and anti-TNF-experienced subjects with SpA in a high TB incidence setting.Methods: In this retrospective cohort study, medical records from patients attending a SpA clinic during 13 years (2004 to 2016) in a university hospital were reviewed. The TB IR was calculated and expressed as number of events per 105 patients/year; the incidence rate ratio (IRR) associated with the use of TNFi was calculated.Results: A total of 277 patients, 173 anti-TNF-naïve and 104 anti-TNF-experienced subjects, were evaluated; 35.7% (N = 35) of patients who were prescribed an anti-TNF drug were diagnosed with latent tuberculosis infection (LTBI). Total follow-up time (person-years) was 1667.8 for anti-TNF-naïve and 394.9 for anti-TNF-experienced patients. TB IR (95% CI) was 299.8 (37.4-562.2) for anti-TNF naïve and 1012.9 (25.3-2000.5) for anti-TNF experienced subjects. The IRR associated with the use of TNFi was 10.4 (2.3- 47.9).Conclusions: In this high TB incidence setting, SpA patients exposed to anti-TNF therapy had a higher incidence of TB compared to anti-TNF-naïve subjects, although the TB incidence in the control group was significant.(AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Tuberculosis/chemically induced , Tuberculosis/epidemiology , Biological Products/adverse effects , Antirheumatic Agents/adverse effects , Spondylarthritis/drug therapy , Tumor Necrosis Factor Inhibitors/adverse effects , Spondylitis, Ankylosing/drug therapy , Biological Products/therapeutic use , Arthritis, Psoriatic/drug therapy , Incidence , Retrospective Studies , Follow-Up Studies , Antirheumatic Agents/therapeutic use , Endemic Diseases , Latent Tuberculosis/drug therapy , Tumor Necrosis Factor Inhibitors/therapeutic useABSTRACT
ABSTRACT Most people infected by Mycobacterium tuberculosis (Mtb) do not have any signs or disease symptoms, a condition known as latent tuberculosis infection (LTBI). The introduction of biological agents, mainly tumor necrosis factor (TNF) inhibitors, for the treatment of immune-mediated diseases such as Rheumatoid Arthritis (RA) and other rheumatic diseases, increased the risk of reactivation of LTBI, leading to development of active TB. Thus, this review will approach the aspects related to LTBI in patients with rheumatologic diseases, especially those using iTNF drugs. For this purpose it will be considered the definition and prevalence of LTBI, mechanisms associated with diseases and medications in use, criteria for screening, diagnosis and treatment. Considering that reactivation of LTBI accounts for a large proportion of the incidence of active TB, adequate diagnosis and treatment are crucial, especially in high-risk groups such as patients with rheumatologic diseases.
RESUMO A maioria das pessoas infectadas por Mycobacterium tuberculosis (Mtb) não possui sinais ou sintomas da doença, quadro conhecido como infecção latente por tuberculose (ILTB). A introdução de agentes biológicos, sobretudo inibidores do fator de necrose tumoral (iTNF), para o tratamento de doenças imunomediadas, como artrite reumatoide (AR) e outras doenças reumatológicas, aumentou o risco de reativação de ILTB, levando ao desenvolvimento de tuberculose (TB) ativa. Assim, esta revisão abordará os aspectos relacionados à ILTB em pacientes com doenças reumatológicas, especialmente naqueles em uso de medicamentos iTNF. Para tanto, serão considerados a definição e a prevalência de ILTB, os mecanismos associados às doenças e às medicações em uso, bem como os critérios para rastreamento, diagnóstico e tratamento da ILTB. Como a reativação da ILTB é responsável pela grande proporção de casos de TB ativa, o diagnóstico e o tratamento adequados são cruciais, principalmente em grupos de alto risco, como os pacientes com doenças reumatológicas.
Subject(s)
Humans , Rheumatic Diseases/complications , Rheumatic Diseases/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Latent Tuberculosis/etiology , Tuberculin Test , Risk Factors , Antirheumatic Agents/adverse effects , Latent Tuberculosis/diagnosis , Latent Tuberculosis/drug therapy , Interferon-gamma Release TestsABSTRACT
Patients with inflammatory bowel disease (IBD) have shown to be at increased risk of developing extraintestinal malignancies. Immunomodulators (immunosuppressant and anti-tumor necrosis factor) diminish the mucosal inflammatory response changing the evolution of the disease, especially when these strategies are introduced earlier. However, therapies that alter the immune system may also promote carcinogenesis. Treatment of IBD in patients with prior malignancy is challenging and the final decision regarding therapeutic strategy should be made on a case-by-case basis. The purpose of this review is to show the characteristics of extra-colonic cancer in patients with IBD, including risks, pathogenesis and management of IBD after cancer diagnosis, the effect of neoplasm treatment on IBD, and the effect of IBD and its treatments on cancer outcomes.
Los pacientes con enfermedad inflamatoria intestinal (EII) presentan un mayor riesgo de desarrollar neoplasias extraintestinales. Los inmunomoduladores (inmunosupresores y terapia biológica anti-TNF) disminuyen la respuesta inflamatoria a nivel de la mucosa, modificando la evolución de la enfermedad, especialmente cuando son introducidos precozmente. Sin embargo, estas terapias pueden alterar el sistema inmune y promover la carcinogénesis. El tratamiento de la EII en pacientes con antecedentes de cáncer es un desafío y la decisión final sobre la estrategia terapéutica debe ser determinada caso a caso. Esta revisión tiene como objetivo mostrar las características de las neoplasias extra-intestinales en pacientes con EII, incluyendo los riesgos, patogénesis y manejo de la EII posterior al diagnóstico del cáncer, el efecto de la neoplasia sobre el tratamiento de la EII y el efecto de la EII y su tratamiento sobre el cáncer.
Subject(s)
Humans , Male , Female , Inflammatory Bowel Diseases/complications , Immunosuppressive Agents/adverse effects , Neoplasms/diagnosis , Inflammatory Bowel Diseases/pathology , Inflammatory Bowel Diseases/drug therapy , Risk Factors , Immunosuppression Therapy/adverse effects , Immunosuppressive Agents/therapeutic use , Neoplasms/etiologyABSTRACT
OBJETIVOS: Avaliar a resposta clínica após a estratégia de troca entre agentes antifator de necrose tumoral alfa (anti-TNF-alfa) em pacientes com artrite reumatoide (AR). PACIENTES E MÉTODOS: Foram incluídos 99 pacientes com diagnóstico de AR (American College of Rheumatology, 1987), em uso de terapia anti-TNF-alfa, para avaliação da resposta terapêutica após 24 semanas. A estratégia de troca foi feita se, após 12 a 24 semanas, houvesse relato de evento adverso sério (T: toxicidade) ou se não ocorresse redução maior que 0,6 do índice de atividade da doença (DAS28) inicial (RI: resposta inadequada). Nesse último caso, o paciente foi considerado como falência primária (FP). Falência secundária (FS) foi definida se houvesse perda de resposta após melhora inicial. Remissão (DAS28 < 2,6), baixa atividade de doença (2,61 < 3,2) e melhora funcional [aumento > 0,2 do questionário de avaliação da saúde (HAQ) inicial] foram avaliadas por análise de regressão linear. P < 0,05 foi considerado significante. RESULTADOS: A estratégia de troca foi realizada em 39 (39,4 por cento) pacientes, especialmente por FP (24,3 por cento), FS (35,1 por cento) e T (40,5 por cento). A taxa de retenção ao primeiro agente foi de 60,1 por cento, e o tempo médio para a troca foi de 14,2 ± 10,9 meses. Após a troca, houve tendência à queda do DAS28 (4,7 ± 1,4; P = 0,08), mas não do HAQ (1,2 ± 0,77; P = 0,11). Cerca de 43 por cento deles alcançaram boa/moderada resposta EULAR. O principal determinante da troca foi o DAS28 inicial mais elevado, independente de idade, tempo de doença e capacidade funcional. CONCLUSÃO: A estratégia de troca entre agentes anti-TNF-alfa é válida para o controle da atividade de doença, embora com baixa probabilidade de remissão e sem melhora significativa da capacidade funcional.
OBJECTIVES: To assess clinical response after switching between anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: This study included 99 patients diagnosed with RA American College of Rheumatology, 1987), on anti-TNF-alpha therapy, to assess the therapeutic response after 24 weeks. Switching was performed if, after 12 to 24 weeks, a severe adverse event was reported (toxicity: T) or if no reduction greater than 0.6 in the initial Disease Activity Score 28 (DAS28) occurred (inadequate response: IR). In case of IR, the patient was considered as primary failure (PF). Secondary failure (SF) was defined as loss of response after initial improvement. Remission (DAS28 < 2.6), low disease activity (between 2.61 and 3.2), and functional improvement [increase in the initial Health Assessment Questionnaire (HAQ) > 0.2] were assessed by use of linear regression analysis. The significance level adopted was P < 0.05. RESULTS: Switching was performed in 39 (39.4 percent) patients, especially due to PF (24.3 percent), SF (35.1 percent) and T (40.5 percent). The retention rate of the first agent was 60.1 percent, and the mean time for switching was 14.2 ± 10.9 months. After switching, a tendency towards a decrease in DAS28 was observed (4.7 ± 1.4; P = 0.08), but not in the HAQ (1.2 ± 0.77; P = 0.11). Around 43 percent of the patients achieved good/moderate EULAR response. The major determinant of switching was a higher initial DAS28, independent of age, duration of disease, and functional capacity. CONCLUSION: Switching between anti-TNF-alpha agents is a valid strategy to control disease activity, despite the low likelihood of remission and no significant improvement in functional capacity.
Subject(s)
Female , Humans , Male , Middle Aged , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/physiopathology , Drug Substitution , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Retrospective Studies , Treatment OutcomeABSTRACT
One of the severe adverse reactions to anti-tumor necrosis factor (TNF)-alpha therapy is the reactivation of tuberculosis. We present a case of tuberculous peritonitis in a 57-year-old woman with rheumatoid arthritis (RA) that appeared during treatment with infliximab. Confirming a diagnosis of tuberculous peritonitis is difficult and can be delayed because of the nonspecific symptoms, the rarity of the disease and the low detection rate of mycobacteria in ascites fluid. This case illustrates that prompt anti-tuberculous therapy is needed for suspected cases of tuberculous peritonitis in RA patients treated with infliximab.