T-helper 1 (Th1) lymphocytes release interferon-gamma (IFN-γ) and TNF-alpha. These cytokines are involved in the transformation of macrophages into specialized Fedratinib cost histiocytic cells with bactericidal and bacteriostatic functions. Activated macrophages, under T-lymphocyte influence, organize and form the tuberculoid granulomas. In contrast, TNF-blockade is associated with granuloma lysis [9, 15]. Many randomized, controlled studies have evaluated the safety of etanercept, infliximab, and adalimumab [16, 17], the majority
of which have been conducted in patients with rheumatologic Quisinostat research buy conditions or Crohn’s disease. However, according to the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS), only a single case of TB occurred during initial clinical trials of infliximab [18] and none of the patients treated with etanercept and adalimumab developed TB during the initial studies [9]. Despite these results, TB has been continuously reported in association with biologic therapy [19–22].
Data from learn more the British Society for Rheumatology Biologics Register (BSRBR), analyzing 10,712 patients with rheumatoid arthritis treated with anti-TNF agents, reported 39 cases of active TB. The risk for TB was as follows: 144 events/100,000 patient-years for adalimumab; 136/100,000 patient-years for infliximab; and 39/100,000 patient-years for etanercept, confirming that infliximab and adalimumab are associated with a three- to fourfold higher rate of TB compared with etanercept. The median time to TB diagnosis was 13.4 months for patients exposed to etanercept, 5.5 months for infliximab, and 18.5 months for patients exposed to adalimumab [20]. Other publications have indicated a lower risk of TB in patients treated with etanercept else compared with infliximab or adalimumab [17, 22–27]. The safety data from patients with rheumatoid arthritis can only partially be generalized to patients with psoriasis vulgaris, as psoriasis is typically treated with monotherapy whereas rheumatoid arthritis is commonly based on treatment
regimens consisting of systemic immunosuppressants and biologics, which can increase the risk of infection [28]. The present authors searched the MEDLINE database for randomized, placebo-controlled studies of the three currently used anti-TNF agents (infliximab, etanercept, and adalimumab) published between 2003 and 2012. Study participants were adult patients with moderate-to-severe psoriasis treated with anti-TNF agents for at least 12 weeks. Based on these criteria, 13 clinical trials [29–41] were identified that collectively included 3,657 adult patients with moderate-to-severe psoriasis who were treated with adalimumab, etanercept, or infliximab (Table 2). The total number of patients receiving the placebo was 1,709. The treatment duration ranged from 12 to 52 weeks.
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