Update upon the infection risk in patients receiving TNF alpha inhibitors.

INTRODUCTION: TNF-α inhibitors can be administered either as monotherapy or in combination with other anti-inflammatory drugs or DMARDs in the treatment of chronic immune-mediated diseases. AREAS COVERED: Patients receiving TNF-α inhibitors are at high risk of infections. An update is made on the risk of infection in patients receiving TNF-α inhibitors and the strategies for mitigating against the development of these serious adverse events. EXPERT OPINION: Infliximab than etanercept appears to be responsible for the increased risk of infections. Re-activation of latent tuberculosis infection and the overall risk of opportunistic infections should be considered before beginning a course of TNF-α inhibitors. A careful medical history, Mantoux test/quantiferon-TB Gold In-tube Test and chest-X-ray should always be performed before starting TNF-α inhibitors. Particular attention should be paid to risk factors for Pneumocystis jirovecii infection. Hepatitis B and C virological follow-up should be considered during TNF-α inhibitors treatment. Finally, appropriate vaccinations for influenza, S. pneumoniae, and HBV should be administered to decrease the risk of infection, and patients who are at high risk of herpes zoster reactivation would benefit from a second vaccination in adulthood.

Update upon efficacy and safety of etanercept for the treatment of spondyloarthritis and juvenile idiopathic arthritis.

TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis (AS), psoriasis (Ps) and/or psoriatic arthritis (PsA) and may be administered off-label to treat disseminated granuloma annulare, systemic lupus erythematosus and systemic sclerosis. There are several TNF-α inhibitors available for clinical use including infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. In this article, we discuss the efficacy and safety of etanercept in the treatment of spondyloarthritis and juvenile idiopathic arthritis (JIA). Etanercept is effective in the treatment of PsA, AS, JIA and uveitis. Independent predictors of achieving a sustained clinical improvement or MDA in children with JIA include shorter disease duration, no concurrent oral corticosteroid use, history of chronic anterior uveitis and age <9 years. IBD incidence was lower in patients receiving etanercept plus MTX. Intra-articular administration of etanercept seems to favor a prompt target joint improvement without serious adverse events. Etanercept improve endothelial function reducing the risk of acute cardiovascular and/or cerebrovascular events. The most commonly reported adverse events were nasopharyngitis, epidermal and dermal conditions, upper respiratory tract infection, cough, headache and fatigue.

Impact of pharmacogenomics upon the therapeutic response to etanercept in psoriasis and psoriatic arthritis.

INTRODUCTION: TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases. Etanercept is a decoy receptor" for TNF-α and it is composed of two p75 TNF-α receptors fused to human IgG1. Areas covered: We discuss the potential role of pharmacogenetics in predicting the response to etanercept in patients with Ps and PsA. Expert opinion: Pharmacogenetics represents the new frontier for the discovery of potential genetic markers of biological response to TNF-α inhibitors. Clinical studies showed that TNF-α -308 G/G, +489 GG and the +489 GA, TNF-α -857C (rs1799724), TNFRSF1B 676T (rs1061622), TNFAIP3 G SNP (rs610604), FcγRIIIA-V158F, HLA-C*06, IL-17 A (rs2275913 and rs10484879), IL-17F (rs763780) and IL17RA (rs4819554) SNPs favor the response to etanercept. However, most of these studies are often small and not sufficiently powered to detect an effect and markers tend to be more prognostic than predictive of therapeutic response. Furthermore, studies often examines only the effects of a single SNP, while it would be more useful to analyze more haplotypes in contemporary in the same patients. Appropriately designed clinical trials are needed before a pharmacogenetic approach may be applicable in daily clinical therapeutic practice.