BACKGROUND: Immunogenicity of aTNFs is one of the mechanisms behind treatment failure. OBJECTIVE: To assess the effect of anti-drug antibodies (ADA) on drug response to infliximab, adalimumab and etanercept, and the effect of immunosuppression on ADA detection, in patients with Rheumatoid Arthritis, Spondyloarthritis, Psoriasis and Inflammatory Bowel Diseases. DATA SOURCES: PubMed, EMBASE, Cochrane databases, article reference lists (through August 19 2012). STUDY SELECTION: Out of 2082 studies, 17 were used in the meta-analysis (1RCT; 16 observational studies). DATA EXTRACTION: Two reviewers extracted data. Risk ratios (RR), 95% CI, using random-effect models, sensitivity analysis, meta-regressions and Egger's test were calculated. DATA SYNTHESIS: Of 865 patients, ADA against infliximab or adalimumab reduced drug response rate by 68% (RR=0.68, 95% CI=0.12 to 0.36), an effect attenuated by concomitant methotrexate (MTX): <74% MTX+: RR=0.23, 95% CI=0.15 to 0.36; ≥74% MTX+: RR=0.32, 95% CI=0.22 to 0.48. Anti-etanercept antibodies were not detected. Of 936 patients, concomitant MTX or azathioprine/mercaptopurine reduced ADA frequency by 47% (RR=0.53, 95% CI=0.42 to 0.67), particularly when ADA were assessed by RIA (RR=0.36, 95% CI=0.23 to 0.55) compared with ELISA (RR=0.63, 95% CI=0.53 to 0.74). CONCLUSIONS: ADA reduces drug response, an effect that can be attenuated by concomitant immunosuppression, which reduces ADA frequency. Drug immunogenicity should be considered for the management of patients receiving biological therapies.
BACKGROUND: Immunogenicity of aTNFs is one of the mechanisms behind treatment failure. OBJECTIVE: To assess the effect of anti-drug antibodies (ADA) on drug response to infliximab, adalimumab and etanercept, and the effect of immunosuppression on ADA detection, in patients with Rheumatoid Arthritis, Spondyloarthritis, Psoriasis and Inflammatory Bowel Diseases. DATA SOURCES: PubMed, EMBASE, Cochrane databases, article reference lists (through August 19 2012). STUDY SELECTION: Out of 2082 studies, 17 were used in the meta-analysis (1RCT; 16 observational studies). DATA EXTRACTION: Two reviewers extracted data. Risk ratios (RR), 95% CI, using random-effect models, sensitivity analysis, meta-regressions and Egger's test were calculated. DATA SYNTHESIS: Of 865 patients, ADA against infliximab or adalimumab reduced drug response rate by 68% (RR=0.68, 95% CI=0.12 to 0.36), an effect attenuated by concomitant methotrexate (MTX): <74% MTX+: RR=0.23, 95% CI=0.15 to 0.36; ≥74% MTX+: RR=0.32, 95% CI=0.22 to 0.48. Anti-etanercept antibodies were not detected. Of 936 patients, concomitant MTX or azathioprine/mercaptopurine reduced ADA frequency by 47% (RR=0.53, 95% CI=0.42 to 0.67), particularly when ADA were assessed by RIA (RR=0.36, 95% CI=0.23 to 0.55) compared with ELISA (RR=0.63, 95% CI=0.53 to 0.74). CONCLUSIONS:ADA reduces drug response, an effect that can be attenuated by concomitant immunosuppression, which reduces ADA frequency. Drug immunogenicity should be considered for the management of patients receiving biological therapies.
Authors: Laura I Salazar-Fontana; Dharmesh D Desai; Tarik A Khan; Renuka C Pillutla; Sandra Prior; Radha Ramakrishnan; Jennifer Schneider; Alexandra Joseph Journal: AAPS J Date: 2017-01-12 Impact factor: 4.009
Authors: Diana Hernández-Flórez; Lara Valor; Inmaculada de la Torre; Juan Carlos Nieto; Lina Martínez-Estupiñán; Carlos González; Francisco Javier López-Longo; Indalecio Monteagudo; Jesús Garrido; Esperanza Naredo; Luis Carreño Journal: Rheumatol Int Date: 2014-11-20 Impact factor: 2.631
Authors: Francisca Llinares-Tello; José Rosas-Gómez de Salazar; José Miguel Senabre-Gallego; Gregorio Santos-Soler; Carlos Santos-Ramírez; Esteban Salas-Heredia; Xavier Barber-Vallés; Juan Molina-García Journal: Rheumatol Int Date: 2014-05-10 Impact factor: 2.631