CAM 20484

Immunopharmacologic Monitoring of Therapeutic Serum Antibodies

Category:Laboratory   Last Reviewed:October 2019
Department(s):Medical Affairs   Next Review:October 2020
Original Date:November 2012    

Description
Targeted inhibitors of tumor necrosis factor-alpha (TNF), including, but not limited to, infliximab, adalimumab, etanercept, and golimumab, are widely used in the treatment of a number of inflammatory conditions, including rheumatoid arthritis (RA), spondyloarthritis, inflammatory bowel disease, and psoriasis (Bendtzen, 2017a).

Immunopharmacologic monitoring of circulating drug and anti-drug antibody levels has been proposed to manage loss of response due to the development of anti-drug antibodies, which may promote adverse effects and diminish drug efficacy (Bendtzen, 2017a; Tighe & McNamara, 2017). 

Regulatory Status 
A search for “tumor necrosis factor” on the FDA website on August 27, 2019, yielded zero results. Additionally, many labs have developed specific tests that they must validate and perform in house. These laboratory-developed tests (LDTs) are regulated by the Centers for Medicare and Medicaid (CMS) as high-complexity tests under the Clinical Laboratory Improvement Amendments of 1988 (CLIA ’88). As an LDT, the U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use.

Policy 

  1. Measurement of the serum drug levels and/or measurement of the antibodies to the following drugs, either alone or as a combination test, in an outpatient setting, is investigational and/or unproven and therefore considered NOT MEDICALLY  NECESSARY:
    1. adalimumab
    2. certolizumab
    3. etanercept
    4. golimumab
    5. infliximab
    6. infliximab-dyyb
    7. infliximab-abda
    8. rituximab
    9. ustekinumab
    10. vedolizumab.

Rationale
Tumor necrosis factor (TNF) inhibitors competitively inhibit the binding of TNF to its receptors to reduce inflammation and stop disease progression (Lis, Kuzawińska, & Bałkowiec-Iskra, 2014). They are used for treatment of inflammatory conditions, such as rheumatoid arthritis (RA), psoriatic arthritis, juvenile arthritis, inflammatory bowel disease (Crohn’s and ulcerative colitis), and ankylosing spondylitis (Bendtzen, 2017b; Lis et al., 2014). Five primary biologic TNF inhibitors are used for inflammatory diseases; infliximab, adalimumab, certolizumab pegol, golimumab, and etanercept. However, these inhibitors may lead to formation of auto-drug antibodies, which may hinder treatment and cause other adverse effects, such as allergic reactions (Bendtzen, 2017a).

Therapeutic drug monitoring (TDM) of both these drugs and anti-drug antibodies has been proposed to optimize dosing of TNF inhibitors. This monitoring is thought to help clinicians manage drug regimens for these patients, such as changing the dose or changing the drug entirely. Identifying the presence and concentration of both these drugs and auto-drug antibodies may help avoid nonresponse to treatment. Most assays for assessment of serum antibodies will also report the drug concentration (MacDermott, 2018). For example, InformTx offers assays for 8 biologic agents (infliximab, adalimumab, certolizumab pegol, vedolizumab, ustekinumab, golimumab, infliximab-dyyb, and infliximab-abda), which is intended to allow providers to monitor, manage response, and optimize dose (InformTx, 2019). Prometheus Anser also offers a series of assays for assessment of these antibodies. Prometheus has assessments for four biologics (adalimumab, infliximab, ustekinumab, and vedolizumab), which also measure the levels of antibodies against the drug in question (Anser, 2019). LabCorp offers assays for 10 biologics encompassed in one portfolio called “DoseASSURE”. These biologics include adalimumab, infliximab, infliximab-dyyb, infliximab-abda, etanercept, rituximab, golimumab, vedolizumab, ustekinumab, and certolizumab (LabCorp, 2019).

Clinical Validity and Utility
Wang et al (2012) developed and validated a non-radiolabeled homogeneous mobility shift assay (HMSA) to measure the antibodies-to-infliximab (ATI) and infliximab levels in serum samples. The assay was validated for both items, and the sample was compared to the traditional ELISA.  Intra- and interassay precision rates for the ATI- and infliximab-HMSA were less than 4% and less than 15%, respectively, and less than 6% and less than 15%, respectively. The lower limit of quantitation of the ATI-HMSA was found to be 0.012 μg/mL in serum, and the HMSA correlated well with the ELISA for ATI levels.

Wang et al (2013) developed and validated a non-radiolabeled HMSA to measure antibodies-to-adalimumab (ATA) and adalimumab levels in serum samples. Analytic validation of performance characteristics (calibration standards, assay limits, et al) was performed for both the ATA- and adalimumab-HMSA. Because the elimination half-life of adalimumab (10-20 days) overlaps the dosing interval (every 2 weeks), ATA-positive sera to provide calibration standards were difficult to collect from human patients. The drug-free interval for antibody formation is small. Therefore, antisera from rabbits immunized with adalimumab were pooled to form calibration standards. Serial dilutions of these ATA calibration standards then generated a standard curve against which test samples were compared. Over 29 experimental runs, intra-assay precision and accuracy for the adalimumab-HMSA was <20% and <3%, respectively; interassay (run-to-run, analyst-to-analyst and instrument-to-instrument) precision and accuracy were less than 12% and less than 22%, respectively. For the ATA-HMSA, variance for intra-assay precision and accuracy were less than 3% and less than 13%, respectively; variance for interassay precision and accuracy were less than 9% and less than 18%, respectively. ELISA could not be used as a standard comparator due to competition from circulating drug.

Van Stappen et al (2016) validated a rapid, lateral flow-based assay (LFA) for quantitative determination of infliximab and to assess thresholds associated with mucosal healing in patients with ulcerative colitis. They found that the LFA agreed well with the traditional enzyme-linked immunosorbent assay (ELISA) for quantification of infliximab with correlation coefficients of 0.95 during induction. A trough concentration (TC) of ≥2.1 μg/ml was associated with mucosal healing. They concluded, “With a time-to-result of 20 min, individual sample analysis and user-friendliness, the LFA outplays ELISA as a rapid, accurate tool to monitor infliximab concentrations (Van Stappen et al., 2016).”

Steenholdt et al (2014) investigated “the cost-effectiveness of interventions defined by an algorithm designed to identify specific reasons for therapeutic failure.” 69 patients with secondary infliximab (IFX) failure were randomized to IFX dose intensification (n = 36) or interventions based on serum IFX and IFX antibody levels (n = 33). They found that “Costs for intention-to-treat patients were substantially lower (34%) for those treated in accordance with the algorithm than by infliximab (IFX) dose intensification: €6038 vs €9178.  However, disease control, as judged by response rates, was similar: 58% and 53%, respectively.” They concluded that “treatment of secondary IFX failure using an algorithm based on combined IFX and IFX antibody measurements significantly reduces average treatment costs per patient compared with routine IFX dose escalation and without any apparent negative effect on clinical efficacy (Steenholdt et al., 2014).”

Roblin et al (2014) conducted a prospective study with 82 patients with inflammatory bowel disease (IBD) having a disease flare while being on ADA 40 mg every 2 weeks.  All patients were primary responders to ADA therapy and were anti-tumor necrosis factor (TNF) naive. ADA trough levels and antibodies against ADA (AAA) were measured. All patients were optimized with ADA 40 mg weekly. Four months later, in the absence of clinical remission, patients were treated with infliximab. The researchers concluded, “The presence of low ADA trough levels without AAA is strongly predictive of clinical response in 67% of cases after ADA optimization. Conversely, low ADA levels with detectable AAA are associated with ADA failure, and switching to IFX should be considered. ADA trough levels >4.9 μg/ml are associated with failure of two anti-TNF agents (ADA and IFX) in 90% of cases and switching to another drug class should be considered (Roblin et al., 2014).”

Mitchell et al (2016) studied if infliximab (IFX) therapeutic drug monitoring (TDM) allows for objective decision making in patients with inflammatory bowel disease (IBD) and loss of response. 71 patients with IBD that had IFX TDM were examined and their serum concentration of anti-drug antibodies were measured. Patients were grouped by TDM results: group 1, low IFX/high ADA; group 2, low IFX/low ADA; group 3, therapeutic IFX, and changes in management were examined due to groupings. Of the 71 patients, 37% underwent an “appropriate” change in therapy based on group. The authors concluded, “A trend towards increased remission rates was associated with appropriate changes in management following TDM results. Many patients with therapeutic IFX concentrations did not undergo an appropriate change in management, potentially reflecting a lack of available out-of-class options at the time of TDM or due to uncertainty of the meaning of the reported therapeutic range (Mitchell et al., 2016).”

Barlow et al evaluated the clinical utility of antibodies in relation to C-reactive protein concentrations. 108 patients contributed 201 samples, and total anti-infliximab antibodies were measured in 164 samples. The authors found that median trough infliximab was 3.7 µg / mL, and 23% of the samples were ≤1 µg / mL. They also noted that “Serum C-reactive protein was found to be significantly higher where infliximab was ≤1 compared to >1 µg/mL”, but no “strict” correlation was seen. 85% of samples with positive anti-infliximab antibodies had infliximab ≤1 µg / mL, and the authors concluded, “Our findings support measurement of anti-infliximab antibodies only in the context of low infliximab concentrations <1 µg/mL. A higher therapeutic cut-off may be relevant in patients with negative antibodies. Further work is indicated to investigate the clinical significance of positive antibodies with therapeutic infliximab concentrations (Barlow, Mohammed, & Berg, 2016).”

Moore et al (2016) performed a systematic review and meta-analysis of studies that reported serum infliximab levels according to outcomes in IBD. 22 studies were examined, encompassing 3483 patients. 12 studies reported IFX levels in a manner “suitable” for estimating the effect.   They found that “During maintenance therapy, patients in clinical remission had significantly higher mean trough IFX levels than patients not in remission: 3.1 µg/ml versus 0.9 µg/ml. The standardised mean difference in serum IFX levels between groups was 0.6 µg/ml. Patients with an IFX level > 2 µg/ml were more likely to be in clinical remission (risk ratio [RR]: 2.9), or achieve endoscopic remission [RR 3] than patients with levels < 2 µg/ml.” The study concluded, “There is a significant difference between serum infliximab levels in patients with IBD in remission, compared with those who relapse. A trough threshold during maintenance > 2 µg/ml is associated with a greater probability of clinical remission and mucosal healing (Moore et al., 2016).”

Wang et al submitted an abstract to the 2018 Therapeutic Drug Management and Toxicology Division Abstract Competition conducted by the American Association for Clinical Chemistry (AACC) on July 30, 2018. This abstract focused on InformTx’s assays for TDM, and the authors reviewed TDM results for 6 biologics, adalimumab (ADA), certolizumab (CER), golimumab (GOL), infliximab (INF), ustekinumab (UST), and vedolizumab (VED). 18837 sera samples were analyzed with InformTx’s assays, and patient responses were predicted based on drug and anti-drug antibody status (ADAbs). The need for drug optimization were assessed by comparing patient drug levels to recommended therapeutic drug levels and laboratory-defined higher ADAbs. The authors found that “64.1%, 30.2%, 83.9%, 60.4%, 25.2%, and 69.1% of the patients treated with ADA, CER, GOL, INF, UST, and VED, respectively, had drug level equal to or greater than the recommended therapeutic level and undetectable ADAbs. 4.5%-33% patients had a drug concentration above the recommended therapeutic level. In contrast, patients (31.0% in ADA, 57.0% in CER, 12.1% in GOL, 32.5% in INF, 74.4% in UST, and 30.6% in VED) had undetectable or suboptimal levels of drugs and undetectable or lower levels of ADAbs (Y. Wang, Turner, Bedeir, Patel, & Gulizia, 2018).

Fernandes et al examined whether TDM can improve clinical outcomes in Crohn's disease (CD) and ulcerative colitis (UC) patients. 205 patients were included, and 56 patients were placed in a “proactive” regimen. This proactive regimen involved measuring infliximab (IFX) trough levels and antidrug antibodies before the fourth infusion and every 2 infusions. The regimen aimed to establish an IFX trough level of 3-7 ug/mL for CD patients and 5-10 ug/mL for UC patients. The control group was made of patients treated with IFX but without TDM. The authors found that treatment escalation was more common in the proactive TDM (pTDM) group (76.8% vs 25.5%), mucosal healing was more common, (73.2% vs 38.9%) and surgery was less common (8.9% vs 20.8%). Proactive TDM also decreased the odds of any unfavorable outcome by an odds ratio of 0.358. The authors concluded that “Proactive TDM is associated with fewer surgeries and higher rates of mucosal healing than conventional non-TDM-based management (Fernandes et al., 2019).”

Negoescu et al performed a cost-effectiveness analysis of proactive vs reactive TDM in a simulated population of Crohn's disease on IFX. The proactive strategy measured IFX concentration and antibody status every 6 months, at the time of a flare, then dosed IFX appropriately. The reactive strategy measured IFX concentration and antibodies at the time of a flare. The authors found that the proactive strategy led to fewer flares, finding an “incremental cost-effectiveness ratio of $146,494 per quality-adjusted life year”. More patients stayed on IFX in the proactive strategy (63.4% vs 58.8% at year 5). The authors concluded that “assuming 40% of the average wholesale acquisition cost of biologic therapies, proactive TDM for IFX is marginally cost-effective compared with a reactive TDM strategy. As the cost of infliximab decreases, a proactive monitoring strategy is more cost-effective (Negoescu et al., 2019).”

National Institute for Health and Clinical Excellence (NICE)
The 2016 Guidelines for therapeutic monitoring of TNF-alpha inhibitors in Crohn’s disease stated that “enzyme‑linked immunosorbent assay (ELISA) kits show promise for therapeutic monitoring of tumor necrosis factor (TNF)‑alpha inhibitors in people with Crohn's disease but there is insufficient evidence to recommend their routine adoption” (NICE, 2016).

NICE also states that use of ELISA tests should be used as part of research and/or data collection and that more research is needed to determine the clinical effectiveness of ELISA tests for therapeutic monitoring of TNF-alpha inhibitors for rheumatoid arthritis (NICE, 2019).

American Gastroenterological Association (AGA)
The AGA published guidelines on Therapeutic Drug Monitoring in Inflammatory Bowel Disease recommending:

“In adults with active IBD treated with anti-TNF agents, the AGA suggests reactive therapeutic drug monitoring to guide treatment changes. Conditional recommendation, very low quality of evidence.”

In adult patients with quiescent IBD treated with anti-TNF agents, the AGA makes no recommendation regarding the use of routine proactive therapeutic drug monitoring (Feuerstein, Nguyen, Kupfer, Falck-Ytter, & Singh, 2017).

A technical report released by the AGA in the same year noted that for patients with quiescent IBD being treated with anti-TNF agents, the benefit of routine proactive TDM was “uncertain” compared to no monitoring. However, they observe a potential benefit for reactive TDM (Vande Casteele, Herfarth, Katz, Falck-Ytter, & Singh, 2017).

American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis (2019)
These guidelines do not mention monitoring of TNF inhibitors for antidrug antibodies or TNF inhibitor levels (Singh et al., 2019).

American College of Gastroenterology (ACG)
The ACG released an update regarding management of Crohn’s Disease (CD), stating that “if active CD is documented, then assessment of biologic drug levels and antidrug antibodies (therapeutic drug monitoring) should be considered” (Lichtenstein et al., 2018).

The ACG published guidelines on management of ulcerative colitis. In it, they observe that “the patient with nonresponse or loss of response to therapy should be assessed with therapeutic drug monitoring to identify the reason for lack of response and whether to optimize the existing therapy or to select an alternate therapy”.  However, they remark that there is “insufficient evidence” to support a benefit for proactive TDM in “all unselected patients with UC in remission” (Rubin, Ananthakrishnan, Siegel, Sauer, & Long, 2019).  

References:

  1. Anser. (2019). Integrated IBD Monitoring. Retrieved from https://www.anserifx.com/
  2. Barlow, N. L., Mohammed, P., & Berg, J. D. (2016). Serum trough infliximab and anti-infliximab antibodies in a cohort of gastroenterology and rheumatology patients' infliximab therapeutic drug monitoring. Ann Clin Biochem, 53(Pt 4), 477-484. doi:10.1177/0004563215604866
  3. Bendtzen, K. (2017a). Tumor necrosis factor-alpha inhibitors: Induction of antibodies, autoantibodies, and autoimmune diseases - UpToDate. In P. Romain (Ed.), UpToDate. Retrieved from https://www.uptodate.com/contents/tumor-necrosis-factor-alpha-inhibitors-induction-of-antibodies-autoantibodies-and-autoimmune-diseases?source=search_result&search=infliximab%20antibodies&selectedTitle=1~150
  4. Bendtzen, K. (2017b). Tumor necrosis factor-alpha inhibitors: Induction of antibodies, autoantibodies, and autoimmune diseases - UpToDate. In P. Romain (Ed.), UpToDate. Retrieved from https://www.uptodate.com/contents/tumor-necrosis-factor-alpha-inhibitors-induction-of-antibodies-autoantibodies-and-autoimmune-diseases?source=search_result&search=infliximab%20antibodies&selectedTitle=1~150
  5. Fernandes, S. R., Bernardo, S., Simoes, C., Goncalves, A. R., Valente, A., Baldaia, C., . . . Tato Marinho, R. (2019). Proactive Infliximab Drug Monitoring Is Superior to Conventional Management in Inflammatory Bowel Disease. Inflamm Bowel Dis. doi:10.1093/ibd/izz131
  6. Feuerstein, J. D., Nguyen, G. C., Kupfer, S. S., Falck-Ytter, Y., & Singh, S. (2017). American Gastroenterological Association Institute Guideline on Therapeutic Drug Monitoring in Inflammatory Bowel Disease. Gastroenterology, 153(3), 827-834. doi:10.1053/j.gastro.2017.07.032
  7. InformTx. (2019). InformTx™ Therapeutic Drug Monitoring. Retrieved from https://www.informdx.com/Our-Services/Gastrointestinal-Pathology/InformTx-Therapeutic-Drug-Monitoring.aspx
  8. LabCorp. (2019). 10 results for "DoseASSURE"
  9. Retrieved from https://www.labcorp.com/test-menu/46121/certolizumab-and-anti-certolizumab-antibody-idose-iassure%E2%84%A2-ctz
  10. Lichtenstein, G. R., Loftus, E. V., Isaacs, K. L., Regueiro, M. D., Gerson, L. B., & Sands, B. E. (2018). ACG Clinical Guideline: Management of Crohn's Disease in Adults. 113(4), 481-517. doi:10.1038/ajg.2018.27
  11. Lis, K., Kuzawińska, O., & Bałkowiec-Iskra, E. (2014). Tumor necrosis factor inhibitors – state of knowledge. In Arch Med Sci (Vol. 10, pp. 1175-1185).
  12. MacDermott, R., Lichtenstein, Gary. (2018). Treatment of Crohn disease in adults: Dosing and monitoring of tumor necrosis factor-alpha inhibitors. Retrieved from https://www.uptodate.com/contents/treatment-of-crohn-disease-in-adults-dosing-and-monitoring-of-tumor-necrosis-factor-alpha-inhibitors?search=Tumor%20necrosis%20factor-alpha%20inhibitors%20antibodies&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2#H3350433340
  13. Mitchell, R. A., Shuster, C., Shahidi, N., Galorport, C., DeMarco, M. L., Rosenfeld, G., . . . Bressler, B. (2016). The Utility of Infliximab Therapeutic Drug Monitoring among Patients with Inflammatory Bowel Disease and Concerns for Loss of Response: A Retrospective Analysis of a Real-World Experience. Can J Gastroenterol Hepatol, 2016, 5203898. doi:10.1155/2016/5203898
  14. Moore, C., Corbett, G., & Moss, A. C. (2016). Systematic Review and Meta-Analysis: Serum Infliximab Levels During Maintenance Therapy and Outcomes in Inflammatory Bowel Disease. J Crohns Colitis, 10(5), 619-625. doi:10.1093/ecco-jcc/jjw007
  15. Negoescu, D. M., Enns, E. A., Swanhorst, B., Baumgartner, B., Campbell, J. P., Osterman, M. T., . . . Vaughn, B. P. (2019). Proactive Vs Reactive Therapeutic Drug Monitoring of Infliximab in Crohn's Disease: A Cost-Effectiveness Analysis in a Simulated Cohort. Inflamm Bowel Dis. doi:10.1093/ibd/izz113
  16. NICE. (2016). Therapeutic monitoring of TNF-alpha inhibitors in Crohn’s disease (LISA-TRACKER ELISA kits, IDKmonitor ELISA kits, and Promonitor ELISA kits) | Guidance and guidelines | NICE. Retrieved from https://www.nice.org.uk/guidance/dg22/chapter/1-Recommendations. from NICE https://www.nice.org.uk/guidance/dg22/chapter/1-Recommendations
  17. NICE. (2019). Therapeutic monitoring of TNF-alpha inhibitors in Crohn’s disease (LISA-TRACKER ELISA kits, IDKmonitor ELISA kits, and Promonitor ELISA kits) | Guidance and guidelines | NICE. Retrieved from https://www.nice.org.uk/guidance/dg36/chapter/1-Recommendations. from NICE https://www.nice.org.uk/guidance/dg36/chapter/1-Recommendations
  18. Roblin, X., Rinaudo, M., Del Tedesco, E., Phelip, J. M., Genin, C., Peyrin-Biroulet, L., & Paul, S. (2014). Development of an algorithm incorporating pharmacokinetics of adalimumab in inflammatory bowel diseases. Am J Gastroenterol, 109(8), 1250-1256. doi:10.1038/ajg.2014.146. Epub 2014 Jun 10.
  19. Rubin, D. T., Ananthakrishnan, A. N., Siegel, C. A., Sauer, B. G., & Long, M. D. (2019). ACG Clinical Guideline: Ulcerative Colitis in Adults. Am J Gastroenterol, 114(3), 384-413. doi:10.14309/ajg.0000000000000152
  20. Singh, J. A., Guyatt, G., Ogdie, A., Gladman, D. D., Deal, C., Deodhar, A., . . . Reston, J. (2019). 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis. Arthritis Care & Research, 71(1), 2-29. doi:10.1002/acr.23789
  21. Steenholdt, C., Brynskov, J., Thomsen, O. O., Munck, L. K., Fallingborg, J., Christensen, L. A., . . . Ainsworth, M. A. (2014). Individualised therapy is more cost-effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment: a randomised, controlled trial. Gut, 63(6), 919-927. doi:10.1136/gutjnl-2013-305279
  22. Tighe, D., & McNamara, D. (2017). Clinical impact of immunomonitoring in the treatment of inflammatory bowel disease. World J Gastroenterol, 23(3), 414-425. doi:10.3748/wjg.v23.i3.414
  23. Van Stappen, T., Bollen, L., Vande Casteele, N., Papamichael, K., Van Assche, G., Ferrante, M., . . . Gils, A. (2016). Rapid Test for Infliximab Drug Concentration Allows Immediate Dose Adaptation. Clin Transl Gastroenterol, 7(12), e206. doi:10.1038/ctg.2016.62
  24. Vande Casteele, N., Herfarth, H., Katz, J., Falck-Ytter, Y., & Singh, S. (2017). American Gastroenterological Association Institute Technical Review on the Role of Therapeutic Drug Monitoring in the Management of Inflammatory Bowel Diseases. Gastroenterology, 153(3), 835-857.e836. doi:10.1053/j.gastro.2017.07.031
  25. Wang, S. L., Hauenstein, S., Ohrmund, L., Shringarpure, R., Salbato, J., Reddy, R., . . . Singh, S. (2013). Monitoring of adalimumab and antibodies-to-adalimumab levels in patient serum by the homogeneous mobility shift assay. J Pharm Biomed Anal, 78-79, 39-44. doi:10.1016/j.jpba.2013.01.031
  26. Wang, S. L., Ohrmund, L., Hauenstein, S., Salbato, J., Reddy, R., Monk, P., . . . Singh, S. (2012). Development and validation of a homogeneous mobility shift assay for the measurement of infliximab and antibodies-to-infliximab levels in patient serum. J Immunol Methods, 382(1-2), 177-188. doi:10.1016/j.jim.2012.06.002
  27. Wang, Y., Turner, K., Bedeir, A., Patel, P., & Gulizia, J. (2018). Therapeutic Drug Monitoring of Monoclonal Antibody in Inflammatory Bowel Diseases: Laboratory Evidence to Predict Patient Responses. Retrieved from https://www.informdx.com/documents/Articles/Abstract-AACC-2018.pdf

Coding Section 

Codes Number Description
CPT  80145 (effective 01/01/2020)

Adalimumab

  80230 (effective 01/01/2020)

Infliximab

  80280 (effective 01/01/2020)

Vedolizumab

  80299  Quantitation of therapeutic drug, not elsewhere specified
  82397 Chemiluminescent assay 
  84999 Unlisted chemistry procedure 
ICD-9-CM Diagnosis   Investigational for all relevant diagnoses
ICD-10-CM (effective 10/01/15)   Investigational for all relevant diagnoses
ICD-10-PCS (effective 10/01/15)   Not applicable. ICD-10-PCS codes are only used for inpatient services. There are no ICD procedure codes for laboratory tests.
Type of Service    
Place of Service    

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2013 Forward     

12/13/2019  Added codes 80145, 80230 & 80280.   
10/15/2019  Annual review, policy rewritten for clarity to include language regarding serum antibodies and serum drug levels. Policy reformatted for clarity. 
02/15/2019  Updates made to remove medical necessity statements. Returned to investigational status. 
10/31/2018  Interim review in May 2018 was not completed. Annual review for October 2018 has no changes made to policy. 
05/02/2018  Interim review to update policy verbiage. 
11/01/2017  Annual review, no change to policy intent. Rewriting policy for clarity and specificity. Updating title, rationale and references. 
04/26/2017  Updated category to Laboratory. No other changes. 
11/01/2016  Annual review, no change to policy intent. 
11/24/2015  Annual review, no change to policy intent. Updating background, description, regulatory status, rationale and references. 
10/21/2014 Annual review, no change to policy intent. Adding coding. Updating description, rationale and references.
10/16/2013 Revisions and changes made in title, policy and rationale. References updated. 

 


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