Therapeutic monitoring of autoantibodies Tumor Necrosis Factor α inhibitor drugs: Efficacy and benefit for patients with autoimmune diseases

Abstract

Tumor necrosis factor alpha (TNFα) is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory disease, such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Chron's disease and ulcerative colitis. TNFα inhibitors (anti-TNFα) are monoclonal antibodies drugs directed against TNFα (i.e. adalimumab, infliximab, etarnecept, golimumab and certolizumab). Their effect consists in reducing the inflammatory response of autoimmune diseases. Several randomized controlled trials and observational studies evaluated the therapeutic efficacy of these drugs and reported a clear benefit for patients affected by chronic inflammatory disease treated with anti-TNFα, but also a high risk of reactions and infections in the injection site. These drugs are immunogenic, and consequent anti-drug antibodies (ADA) formation may decrease the functional drug concentration resulting in a loss of response. Therefore, we evaluated the impact of ADA on therapeutic response through meta-analyses, showing that detectable ADA significantly reduced TNFα inhibitors response. ADA could interfere with drugs and compromise their effects, so the determination of serum ADA levels could improve the patient's management. Even if the decrease of therapeutic response, due to ADA production, is well documented, the clinical benefit of serum ADA determination remains unclear. At the moment, there are many indications about the use of immunogenicity test to guide the therapy, but more information should be acquired before implementing this test in clinical practice.