The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis
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, S...
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| Published in | Annals of the rheumatic diseases Vol. 72; no. 12; pp. 1947 - 1955 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
BMJ Publishing Group Ltd and European League Against Rheumatism
01.12.2013
Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
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| Abstract | 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. |
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| AbstractList | BackgroundImmunogenicity of aTNFs is one of the mechanisms behind treatment failure.ObjectiveTo 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 sourcesPubMed, EMBASE, Cochrane databases, article reference lists (through August 19 2012).Study selectionOut of 2082 studies, 17 were used in the meta-analysis (1RCT; 16 observational studies).Data extractionTwo reviewers extracted data. Risk ratios (RR), 95% CI, using random-effect models, sensitivity analysis, meta-regressions and Egger's test were calculated.Data synthesisOf 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; greater than or equal to 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).ConclusionsADA 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. Immunogenicity of aTNFs is one of the mechanisms behind treatment failure. 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. PubMed, EMBASE, Cochrane databases, article reference lists (through August 19 2012). Out of 2082 studies, 17 were used in the meta-analysis (1RCT; 16 observational studies). Two reviewers extracted data. Risk ratios (RR), 95% CI, using random-effect models, sensitivity analysis, meta-regressions and Egger's test were calculated. 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). 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; â[per thousand]¥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. Immunogenicity of aTNFs is one of the mechanisms behind treatment failure.BACKGROUNDImmunogenicity of aTNFs is one of the mechanisms behind treatment failure.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.OBJECTIVETo 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.PubMed, EMBASE, Cochrane databases, article reference lists (through August 19 2012).DATA SOURCESPubMed, EMBASE, Cochrane databases, article reference lists (through August 19 2012).Out of 2082 studies, 17 were used in the meta-analysis (1RCT; 16 observational studies).STUDY SELECTIONOut of 2082 studies, 17 were used in the meta-analysis (1RCT; 16 observational studies).Two reviewers extracted data. Risk ratios (RR), 95% CI, using random-effect models, sensitivity analysis, meta-regressions and Egger's test were calculated.DATA EXTRACTIONTwo reviewers extracted data. Risk ratios (RR), 95% CI, using random-effect models, sensitivity analysis, meta-regressions and Egger's test were calculated.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).DATA SYNTHESISOf 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).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.CONCLUSIONSADA 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. |
| Author | Demengeot, Jocelyne Garcês, Sandra Benito-Garcia, Elizabeth |
| Author_xml | – sequence: 1 givenname: Sandra surname: Garcês fullname: Garcês, Sandra email: sandragarcesmail@gmail.com, sgama@igc.gulbenkian.pt organization: Lymphocyte Physiology Group, Instituto Gulbenkian de Ciência, Oeiras, Portugal – sequence: 2 givenname: Jocelyne surname: Demengeot fullname: Demengeot, Jocelyne email: sandragarcesmail@gmail.com, sgama@igc.gulbenkian.pt organization: Lymphocyte Physiology Group, Instituto Gulbenkian de Ciência, Oeiras, Portugal – sequence: 3 givenname: Elizabeth surname: Benito-Garcia fullname: Benito-Garcia, Elizabeth email: sandragarcesmail@gmail.com, sgama@igc.gulbenkian.pt organization: Department of Epidemiology, BioEPI Clinical & Translational Research Center, Oeiras, Portugal |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23223420$$D View this record in MEDLINE/PubMed |
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| CODEN | ARDIAO |
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| Snippet | Background Immunogenicity of aTNFs is one of the mechanisms behind treatment failure. Objective To assess the effect of anti-drug antibodies (ADA) on drug... Immunogenicity of aTNFs is one of the mechanisms behind treatment failure. To assess the effect of anti-drug antibodies (ADA) on drug response to infliximab,... Immunogenicity of aTNFs is one of the mechanisms behind treatment failure.BACKGROUNDImmunogenicity of aTNFs is one of the mechanisms behind treatment... BackgroundImmunogenicity of aTNFs is one of the mechanisms behind treatment failure.ObjectiveTo assess the effect of anti-drug antibodies (ADA) on drug... |
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| StartPage | 1947 |
| SubjectTerms | Adalimumab Anti-Inflammatory Agents, Non-Steroidal - immunology Anti-Inflammatory Agents, Non-Steroidal - therapeutic use Anti-TNF Antibodies, Monoclonal - immunology Antibodies, Monoclonal - therapeutic use Antibodies, Monoclonal, Humanized - immunology Antibodies, Monoclonal, Humanized - therapeutic use Antibody Formation - drug effects Antirheumatic Agents - immunology Antirheumatic Agents - therapeutic use Arthritis - drug therapy Arthritis - immunology Autoimmune Diseases Autoimmune Diseases - drug therapy Autoimmune Diseases - immunology Biological products Clinical medicine Clinical trials Crohn's disease Drug dosages Evidence-Based Medicine - methods Humans Immunoglobulins Immunosuppressive Agents - pharmacology Immunotherapy Inflammatory bowel disease Inflammatory Bowel Diseases - drug therapy Inflammatory Bowel Diseases - immunology Infliximab Literature reviews Measurement techniques Meta-analysis Methotrexate Methotrexate - pharmacology Patients Studies Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor necrosis factor-TNF |
| Title | The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis |
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