Effects of Tumor Necrosis Factor-alpha Inhibitors on the Incidence of Tuberculosis

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) inhibitors are used as a treatment in various immune-mediated inflammatory diseases (IMIDs). Tuberculosis (TB) risk is reported in several meta-analyses in patients treated with TNF-alpha inhibitors. The purpose of this study is to collect, review, and evaluate the TB risk in TNF-alpha inhibitors according to IMIDs indications and between soluble-receptor TNF-alpha inhibitor and monoclonal-antibody TNF-alpha inhibitors. METHODS: A systematic literature search on systematic reviews and meta-analyses was performed in PubMed, MEDLINE, Cochrane library, and EMBASE. We identified meta-analyses that evaluated TB infection risk of TNF-alpha inhibitors in IMIDs patients. RESULTS: Thirteen meta-analyses including 41 study results were included in this umbrella review. IMIDs patients treated with TNF-alpha inhibitors had an increased risk of TB than control group (placebo with or without standard therapy patients) (relative risk ratio (RR) 2.057, 95% confidence interval (CI) 1.697 to 2.495). Among them, RA patients with TNF-alpha inhibitors had a higher risk of TB than control group (RR 1.847, 95% CI 1.385 to 2.464), and non-RA patients with TNF-alpha inhibitors had an increased risk of TB (RR 2.236, 95% CI 1.284 to 3.894). In subgroup analysis on TB risk between soluble-receptor TNF-alpha inhibitor and monoclonal-antibody TNF-alpha inhibitors in RA patients, the analysis indicated that monoclonal-antibody TNF-alpha inhibitors had higher risk of TB than solublereceptor TNF-alpha inhibitor (RR 2.880, 95% CI 1.730 to 4.792). CONCLUSION: This umbrella review confirms that the risk of TB is significantly increased in TNF-alpha inhibitor treated patients compared to control group.

A Case of Refractory Oral Aphthous Ulcer Successfully Treated with Adalimumab

Oral aphthous ulcer is a common lesion characterized by loss of dermal tissue of various shapes in many diseases. It is not serious, but may affect quality of life through pain and discomfort. In many cases, it heals spontaneously without treatment or with topical agents such as antiseptics, analgesics and corticosteroid in a few days. However, rarely, there are a few cases of aphthous ulcer that remain refractory despite appropriate treatment. Tumor necrosis factor-α inhibitors have recently been used in treatment of severe mucosal ulcer in Behçet's disease. Herein, we report a patient suffering from refractory oral aphthous ulcers that were resistant to topical and systemic agents, but were successfully treated with adalimumab.

Ideal Vaccination Strategy in Inflammatory Bowel Disease / 대한소화기학회지

Inflammatory bowel disease (IBD) is a long-standing disease that often requires long-term use of immunosuppressive agents including immunomodulators (such as azathioprine, 6-mercaptopurine and methotrexate) and tumor necrosis factor-alpha inhibitors (such as infliximab and adalimumab). Introduction of immunosuppressive therapies, however, involves the risk of host susceptibility to opportunistic infections in this patient population. Therefore, adequate immunization for vaccine-preventable infectious diseases is currently recommended for all patients with IBD and is emerging as an important target for quality improvements in IBD care. However, ongoing issues regarding underuse of immunization, safety and efficacy of vaccines in patients with IBD remain. For quality improvements in IBD care, all physicians should follow the recent immunization guidelines proposed by professional IBD societies. Additionally, there are ongoing needs for intensive educational programs regarding a role of immunization in long-term care of IBD and up-to-date immunization guidelines. Immunization status should be checked at the time of diagnosis of IBD and timely vaccination before initiation of immunosuppressive therapies can be a practical solution for maximizing the efficacy of vaccination at this point. Inactivated vaccines can be used safely irrespective of immunization status of patients, while attenuated vaccines are contraindicated in patients on immunosuppressive therapies. This article reviews an ideal strategy for vaccinating patients with IBD based on the currently recommended immunization guidelines.

Henoch-Schonlein Purpura in a Patient with Ankylosing Spondylitis after Infliximab Therapy / 대한내과학회지

Tumor necrosis factor alpha (TNF-alpha) inhibitors are used widely to treat patients with active rheumatoid arthritis and ankylosing spondylitis (AS). Although various cutaneous reactions can occur as side effects of TNF-alpha inhibitors, systemic vasculitis requiring withdrawal of the agent and immunosuppressive drugs is rare. A 59-year-old male with AS who had been treated with infliximab for 60 months visited us with complaints of palpable purpura on both legs and severe abdominal pain. Abdominal computed tomography showed diffuse wall thickening of the proximal jejunum and ileum and a skin biopsy revealed leukocytoclastic vasculitis. The patient was diagnosed with Henoch-Schonlein purpura (HSP). Infliximab was discontinued and systemic steroid therapy at 0.5 mg/kg resulted in prompt resolution of the HSP. Here, we report the first case of HSP in a patient with AS after infliximab treatment.

Dermatomiosite juvenil: revisão e atualização em patogênese e tratamento / Juvenile dermatomyositis: review and update of the pathogenesis and treatment

A dermatomiosite juvenil (DMJ) é uma doença autoimune caracterizada por vasculopatia sistêmica. Manifestações principais da DMJ incluem fraqueza muscular proximal simétrica, elevação de enzimas musculares séricas e lesões cutâneas, dentre as quais o heliotropo e as pápulas de Gottron são patognomônicas. Reconhecimento precoce e instituição rápida de terapia adequada permitem melhorar o prognóstico da doença e evitar o aparecimento de calcinose. Embora a base do tratamento seja o glicocorticoide, os imunossupressores mais frequentemente associados são metotrexato, ciclosporina, azatioprina e ciclofosfamida, dependendo da gravidade da DMJ. Atualmente investiga-se a utilidade dos imunobiológicos nos casos refratários, mas os resultados são controversos ou pouco expressivos. Pretende-se neste artigo fazer uma revisão sobre DMJ, com ênfase em recentes atualizações na sua patogênese e tratamento.

Juvenile dermatomyositis (JDM) is an autoimmune disease characterized by systemic vasculopathy. Its main manifestations include symmetrical proximal muscle weakness, elevated serum muscle enzymes and cutaneous lesions, among which the heliotrope and Gottron's papules are pathognomonic. Early recognition and prompt therapy allow better prognosis and prevent the development of calcinosis. Although the treatment is based on glucocorticoids, the more commonly associated immunosuppressors include methotrexate, azathioprine, cyclosporine, and cyclophosphamide, depending on the severity of disease. The use of immunobiologicals for refractory cases remains under investigation, but the results are controversial or inexpressive. In this review, we highlight recent updates on the pathogenesis and treatment of JDM.

Interstitial pneumonitis associated with infliximab therapy in a rheumatoid arthritis patient / 대한내과학회지

Tumor necrosis factor (TNF)-alpha inhibitors are well-established biological agents for the treatment of a wide variety of chronic autoimmune diseases and inflammatory conditions, including rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis. Although these drugs have been noted to have good safety profiles, some important side effects, including infection, injection site reactions, lupus-like syndrome, congestive heart failure, and malignancies have been reported. Therefore, utilization of TNF-alpha inhibitors demands caution. Interstitial pneumonitis is a very rare complication of TNF-alpha inhibitors. We report here a 71-year-old man with RA who developed interstitial pneumonitis after the third infusion of infliximab.