Measurement of Serum Antibodies to Selected Biologic Agents
DESCRIPTION
Tumor necrosis factor (TNF) inhibitors (e.g., infliximab, adalimumab, vedolizumab, or ustekinumab) are used to treat multiple inflammatory conditions, including rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, inflammatory bowel disease (e.g., Crohn disease, ulcerative colitis), ankylosing spondylitis, and plaque psoriasis. These agents are highly effective for induction and maintenance of clinical remission in some individuals who fail conventional medical therapy. It is estimated that 1 in 3 individuals do not respond to induction therapy (primary nonresponse) and among initial responders, response wanes over time in approximately 20% to 60% of individuals (secondary nonresponse). The reasons for therapeutic failures include accelerated drug clearance (pharmacokinetics) and neutralizing agent activity (pharmacodynamics) due to antidrug antibodies (ADA).
The detection and quantitative measurement of antidrug antibodies is difficult, owing to drug interference and identifying when antibodies likely have a neutralizing effect. First-generation assays (i.e., enzyme-linked immunosorbent assays [ELISA]) can measure only ADA in the absence of detectable drug levels due to the interference of the drug with the assay. Other techniques available for measuring antibodies include the radioimmunoassay method and, more recently, the homogenous mobility shift assay using high-performance liquid chromatography. Disadvantages of the radioimmunoassay method are associated with the complexity of the test and prolonged incubation time, along with safety concerns related to the handling of radioactive material. Studies evaluating the validation of results among different assays are lacking.
Prometheus Laboratories offers four non-radio-labeled, fluid-phase homogenous mobility shift assay tests: Anser IFX (for infliximab), Anser ADA (for adalimumab), Anser VDZ (for vedolizumab), and Anser UST (for ustekinumab).
POLICY
Measurement of antibodies to tumor necrosis factor (TNF) blocking agents in an individual receiving treatment with a TNF blocking agent, either alone or as a combination test which includes the measurement of serum TNF blocking agent levels, is considered investigational.
IMPORTANT REMINDERS
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan or government program (e.g., TennCare), the express terms of the health plan or government program will govern.
ADDITIONAL INFORMATION
The clinical utility of measuring antibodies to tumor necrosis factor (TNF) has not been determined. ADA threshold values that are informative for discriminating treatment responses have not been established.
SOURCES
American Gastroenterologic Association. (2017). Guideline on therapeutic drug monitoring in inflammatory bowel disease. Retrieved July 14, 2021 from www.gastro.org.
American Gastroenterologic Association. (2018). ACG clinical guideline: management of crohn’s disease in adults. Retrieved September 20, 2022 from www.gastro.org.
American Gastroenterologic Association. (2019). ACG clinical guideline: ulcerative colitis in adults. Retrieved September 20, 2022 from www.gastro.org.
BlueCross BlueShield Association. Evidence Positioning System. (12:2021). Measurement of serum antibodies to Infliximab and Adalimumab (2.04.84). Retrieved September 20, 2022 from https://www.evidencepositioningsystem.com/. (30 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 3 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.
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.
National Institute for Health and Care Excellence (NICE). (2019). Therapeutic monitoring of TNF-alpha inhibitors in rheumatoid arthritis. Retrieved September 20, 2022 from www.nice.org.uk.
Pecoraro, V., De Santis, E., Melegari, A., & Trenti, T. (2017). The impact of immunogenicity of TNFα inhibitors in autoimmune inflammatory disease. A systematic review and meta-analysis. Autoimmunity Reviews, 16 (6), 564-575. Abstract retrieved October 21, 2020 from PubMed database.
Silva-Ferreira, F., Afonso, J., 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 2 evidence)
ORIGINAL EFFECTIVE DATE: 8/8/2015
MOST RECENT REVIEW DATE: 11/10/2022
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