BlueCross BlueShield of Tennessee Medical Policy Manual

Measurement of Serum Antibodies to Infliximab, Adalimumab, and Vedolizumab

DESCRIPTION

Infliximab (Remicade®) is an intravenous monoclonal antibody that inhibits tumor necrosis factor a (TNF-a). A TNF inhibitor suppresses the inflammatory response to TNF and is used for the treatment of rheumatoid arthritis (RA), Crohn’s disease (CD), ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Takayasu’s arteritis, ulcerative colitis, and uveitis associated with Behçet’s Syndrome.  Adalimumab (Humira®) is a similar drug given subcutaneously used for treatment of CD and ulcerative colitis (UC) in adults and juvenile idiopathic arthritis. Vedolizumab (Entyvio®) is an intravenous humanized monoclonal antibody which acts as an a4B7 integrin receptor antagonist (IRA), thought to be a major factor in the chronic inflammation associated with ulcerative colitis and Crohn’s disease.

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, adalimumab, and vedolizumab some individuals become secondary nonresponders. The development of antidrug antibodies (ADA) is considered a cause of this secondary nonresponse.

Laboratory developed tests that detect and measure antidrug antibodies have been proposed as a means to manage individuals with the various disorders who receive evaluation for antibodies to infliximab (e.g. Anser® IFX), adalimumab (e.g., Anser® ADA), or vedolizumab (e.g., Anser® VDZ). However, the clinical usefulness of measuring antidrug antibodies compared with management directed by symptoms, clinical assessment, and standard laboratory evaluation has not been established.

POLICY

IMPORTANT REMINDERS

ADDITIONAL INFORMATION

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. 

SOURCES

American Gastroenterologic Association (2017) Guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology, 153 (3), 827-834.

BlueCross BlueShield Association. Evidence Positioning System. (11:2018). Measurement of Serum Antibodies to Infliximab and Adalimumab (2.04.84). Retrieved February 5, 2019 from https://www.evidencepositioningsystem.com/. (30 articles and/or guidelines reviewed)

ECRI Institute. Product Brief. (2018, November). Anser ADA assay (Prometheus Laboratories, Inc). for guiding treatment with adalimumab for inflammatory bowel disease. Retrieved February 6, 2019 from ECRI institute. (7articles and/or guidelines reviewed)

ECRI Institute. Product Brief. (2018, November). Anser ADA assay (Prometheus Laboratories, Inc). for guiding treatment with vedolizumab for inflammatory bowel disease. Retrieved February 6, 2019 from ECRI institute. (3 articles and/or guidelines reviewed)

ECRI Institute. Product Brief. (2018, October). Anser IFX assay (Prometheus Laboratories, Inc.) for guiding treatment with infliximab for inflammatory bowel disease. Retrieved February 6, 2019 from ECRI Institute. (5 articles and/or guidelines reviewed)

Ferreira, F.S., Afonso, Joana., Lopes, P., & Magro, F. (2016). A systematic review on Infliximab and adalimumab drug monitoring: levels, clinical outcomes and assays. Oxford Academic, 22 (9), 2289-2301. (Level 4 evidence)

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)

Ley, K., Rivera-Nieves, J., Sandborn, W., and Shattil, S. (2016, March) Integrin-based therapeutics: biological basis, clinical use and new drugs. Nature Reviews. Drug Discovery, 15 (3), 173-183. (Level 5 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). (2015, August). Vedolizumab for treating moderately to severely active Crohn's disease after prior therapy. Retrieved February 28, 2018 from www.nice.org.uk.

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.

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.

Sands, B., Feagan, B., Rutgeerts, P.,  Colombel, J. Sandborn, W., Sy,R., et al. (2014). Effects of vedolizumab induction therapy for patients with crohn’s disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology, 147 (3), 618-627. (Level 3 evidence)

Sands, B., Sandborn, W., Van Assche, G., Lukas, M., Xu, J., James, A., et al. (2017). Vedolizumab as induction and maintenance therapy for Crohn's Disease in patients naïve to or who have failed tumor necrosis factor antagonist therapy. Inflammatory Bowel Disease, 23 (1), 97-16. Abstract retrieved February 27, 2018 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.

ORIGINAL EFFECTIVE DATE:  8/8/2015

MOST RECENT REVIEW DATE:  3/28/2019

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