The impact of immunogenicity of TNFα inhibitors in autoimmune inflammatory disease. A systematic review and meta-analysis

BackgroundMonoclonal antibodies drugs directed against TNFα, TNFα inhibitors, are immunogenic, and consequent anti-drug antibodies (ADA) formation may decrease the functional drug concentration, resulting in a loss of response. We evaluated the impact of ADA on TNFα therapeutic response.MethodsWe considered studies enrolling adult patients affected by autoimmune inflammatory disease in therapy with TNFα inhibitors. We collected data about study and population characteristics, treatment dosage, determination of ADA and adverse events (AE). We combined data in meta-analysis, calculating risk ratios (RR) for each study. p-Values < 0.05 were considered as statistically significant. Methodological quality was evaluated. Analyses were performed with the STATA 11 and RevMan 5.3 softwares.ResultsWe included 34 studies enrolling 4273 patients. Of these, 794 (18.6%) developed ADA. Our analysis showed a significant reduction of response (RR 0.43, 95%CI 0.3-0.63) in patients with ADA respect to patients without, especially in patients treated with Infliximab (RR 0.37) or Adalimumab (RR 0.40). Furthermore, the administration of TNFα inhibitors produced a reaction at the infusion site in 17%, infection in 30% and serious AE in 5% of patients.ConclusionDetectable ADA significantly reduced TNFα inhibitors response. Drug administration can also cause injection site reaction and infections. Early detection of serum ADA levels may improve patients' management. Currently, there are many indications about the use of immunogenicity tests to guide the therapy, but information regarding how to implement it in clinical practice is needed.