Measurement of Serum Antibodies to Infliximab and Adalimumab
Infliximab (Remicade®) is an intravenous tumor necrosis factor a (TNF-a) blocking agent used for the treatment of rheumatoid arthritis (RA), Crohn’s disease (CD), ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and ulcerative colitis. Adalimumab (Humira®) is a subcutaneous TNF-a inhibitor that is used for treatment of CD and ulcerative colitis UC in adults and juvenile idiopathic arthritis. These agents are generally given to individuals who fail conventional medical therapy, and they are typically highly effective for induction and maintenance of clinical remission. However, not all individuals respond, and a high proportion of patients lose response over time. Following primary response to infliximab and adalimumab, some individuals become secondary nonresponders. The development of antidrug antibodies (ADA) is considered a cause of this secondary nonresponse.The detection and quantitative measurement of ADA is difficult. First-generation assays (i.e., enzyme-linked immunosorbent assays [ELISA]) can measure only ADA in the absence of detectable drug levels. Other techniques available for measuring antibodies include the radioimmunoassay method, and more recently, the homogenous mobility shift assay using high-performance liquid chromatography (e.g., Anser IFX™, Anser ADA™, iLite®).
Measurement of antibodies to infliximab in an individual receiving treatment with infliximab, either alone or as a combination test which includes the measurement of serum infliximab levels, is considered investigational.
Measurement of antibodies to adalimumab in an individual receiving treatment with adalimumab, either alone or as a combination test which includes the measurement of serum adalimumab levels, is considered investigational.
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Convincing evidence for the clinical utility of ADA testing currently is lacking. ADA threshold values that are informative for discriminating treatment responses have not been established. The clinical utility of measuring antidrug antibody concentrations has not been established, and it is unknown how patient management would change based on test results.
Afif, W., Loftus, E.V. Jr., Faubion, W.A., Kane, S.V., Bruining, D.H., et al. (2010). Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease. The American Journal of Gastroenterology,105 (5),1133-1139. Abstract retrieved March 19, 2015 from PubMed database.
BlueCross BlueShield Association. Medical Policy Reference Manual. (11:2017). Measurement of Serum Antibodies to Infliximab and Adalimumab (2.04.84). Retrieved December 29, 2017 from BlueWeb. (37 articles and/or guidelines reviewed)
Jani, M., Chinoy, H., Warren, R., Griffiths, C., Plant, D., Fu, B., et al. (2015). Clinical utility of random anti-tumor necrosis factor drug-level testing and measurement of antidrug antibodies on the long-term treatment response in rheumatoid arthritis. Arthritis & Rheumatology, 67 (8), 2011-2019. (Level 4 evidence)
Meroni, P., Valentini,G., Ayala, F., Cattaneo, A., & Valesini, G. (2015). New strategies to address the pharmacodynamics and pharmacokinetics of tumor necrosis factor (TNF) inhibitors: a systematic analysis. Autoimmunity Reviews, 14 (9), 812-829. Abstract retrieved May 2, 2016 from PubMed database.
Moots, R., Xavier, R., Mok, C., Rahman, M., Tsai, W., Al-Maini, M., et al. (2017, April). The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: results from a multinational, real-world clinical practice, non-interventional study. PLOS One, 12 (4), e0175207. (Level 2 evidence)
National Institute for Health and Care Excellence (NICE). (2016). Therapeutic monitoring of TNF-alpha inhibitors in Crohn’s disease (LISA-TRACKER ELISA kits, IDK monitor ELISA kits, and Promonitor ELISA kits). Retrieved February 22, 2017 from www.nice.org.uk/guidance/dg22
Roblin, X., Rinaudo, M., Del Tedesco, E., Phelip, J.M., Genin, C., et al. (2014). Development of an algorithm incorporating pharmacokinetics of adalimumab in inflammatory bowel diseases. The American Journal of Gastroenterology, 109 (8), 1250-1256. Abstract retrieved March 20, 2015 from PubMed database.
Steenholdt, C., Bendtzen, K., Brynskov, J., Thomsen, O., & Ainsworth, M.A. (2011). Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn’s disease. Scandinavian Journal of Gastroenterology, 46 (3), 310-318. Abstract retrieved March 19, 2015 from PubMed database.
Steenholdt, C., Brynskov, J., Thomsen, O., Munck, L.K., Fallingborg, J., et al. (2014). Individualised therapy is more cost-effective than dose intensification in patients with Crohn’s disease who lose response to anti-TNF treatment: a randomized, controlled trial. Gut, 63 (6), 919-927. Abstract retrieved March 19, 2015 from PubMed database.
Thomas, S., Borazan, N., Barroso, N., Duan, L., Taroumian, S., Kretzmann, B., et al. (2015). Comparative immunogenicity of TNF inhibitors: impact on clinical efficacy and tolerability in the management of autoimmune diseases. A systematic review and meta-analysis. BioDrugs, 29 (4), 241-258. Abstract retrieved May 2, 2016 from PubMed database.
Winifred S. Hayes, Search & Summary. (2017, December). Anser ADA (Prometheus Laboratories Inc.) for monitoring adalimumab treatment of inflammatory bowel disease. Retrieved December 29, 2017 from www.hayesinc.com.
Winifred S. Hayes, Search & Summary. (2017, March). Use of anti-infliximab antibody levels using electrochemiluminescence immunoassay (ECLIA) in adults with inflammatory bowel disease (IBD). Retrieved December 29, 2017 from www.hayesinc.com.
ORIGINAL EFFECTIVE DATE: 8/8/2015
MOST RECENT REVIEW DATE: 1/25/2018
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