Chemotherapy-induced peripheral neuropathy (CIPN) and its treatment: an NIH Collaboratory study of claims data

Abstract

Purpose

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling complication of many chemotherapies. We investigated the feasibility of using health plan claims and administrative data to identify CIPN occurrence by comparing patients who received neurotoxic and non-neurotoxic chemotherapies.

Methods

The sample included over 53,000,000 patients from two regional and one national insurer in the USA (> 400,000 exposed to chemotherapy). Peripheral neuropathy was identified using a broad definition (definition 1) and a specific definition (i.e., drug-induced polyneuropathy code) (definition 2).

Results

CIPN incidence as measured by definition 1 within 6 months of chemotherapy initiation was 18.1% and 6.2% for patients who received neurotoxic and non-neurotoxic chemotherapy, respectively (relative risk neurotoxic vs. non-neurotoxic (RR), 2.93 (95% CI, 2.87–2.98)). For definition 2, these incidences were 3.6% and 0.1% (RR, 25.2 (95% CI, 22.8–27.8)). The incidences of new analgesic prescriptions for neurotoxic and non-neurotoxic groups were as follows: gabapentin, 7.1%/1.7%; pregabalin, 0.69%/0.31%; and duloxetine, 0.78%/0.76%. The incidence of CIPN as defined by definitions 1 and 2 was low compared with that of published research studies, but the relative risk of CIPN among patients who received neurotoxic chemotherapies compared with those who received non-neurotoxic chemotherapies was high using definition 2.

Conclusions

These data suggest that as used currently by clinicians, administrative codes likely underestimate CIPN incidence. Thus, studies using administrative data to estimate CIPN incidence are not currently feasible. However, the drug-induced polyneuropathy code is a specific indicator of CIPN in administrative data and may be useful for investigating predictors or potentially preventive therapies of CIPN.

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References

  1. 1.

    Staff NP, Grisold A, Grisold W, Windebank AJ (2017) Chemotherapy-induced peripheral neuropathy: a current review. Ann Neurol 81:772–781

    CAS  Article  Google Scholar 

  2. 2.

    Seretny M, Currie GL, Sena ES, Ramnarine S, Grant R, MacLeod MR, Colvin LA, Fallon M (2014) Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis. Pain 155:2461–2470

    Article  Google Scholar 

  3. 3.

    Bhatnagar B, Gilmore S, Goloubeva O, Pelser C, Medeiros M, Chumsri S, Tkaczuk K, Edelman M, Bao T (2014) Chemotherapy dose reduction due to chemotherapy induced peripheral neuropathy in breast cancer patients receiving chemotherapy in the neoadjuvant or adjuvant settings: a single-center experience. SpringerPlus 3:366

    Article  Google Scholar 

  4. 4.

    Lyman GH (2009) Impact of chemotherapy dose intensity on cancer patient outcomes. J Natl Compr Cancer Netw 7:99–108

    Article  Google Scholar 

  5. 5.

    Smith EML, Pang H, Cirrincione C, Fleishman S, Paskett ED, Ahles T, Bressler LR, Fadul CE, Knox C, Le-Lindqwister N et al (2013) Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial. JAMA 309:1359–1367

    CAS  Article  Google Scholar 

  6. 6.

    Gewandter JS, Brell J, Cavaletti G, Dougherty PM, Evans S, Howie L, McDermott MP, O’Mara A, Smith AG, Dastros-Pitei D et al (2018) Trial designs for chemotherapy-induced peripheral neuropathy prevention: ACTTION recommendations. Neurology 91:403–413

    Article  Google Scholar 

  7. 7.

    Schneeweiss S, Avorn J (2005) A review of uses of health care utilization databases for epidemiologic research on therapeutics. J Clin Epidemiol 58:323–337

    Article  Google Scholar 

  8. 8.

    Fowles JB, Fowler EJ, Craft C (1998) Validation of claims diagnoses and self-reported conditions compared with medical records for selected chronic diseases. J Ambul Care Manage 21:24–34

    CAS  Article  Google Scholar 

  9. 9.

    Hershman DL, Lacchetti C, Dworkin RH, Lavoie Smith EM, Bleeker J, Cavaletti G, Chauhan C, Gavin P, Lavino A, Lustberg MB, Paice J, Schneider B, Smith ML, Smith T, Terstriep S, Wagner-Johnston N, Bak K, Loprinzi CL (2014) Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 32:1941–1967

    CAS  Article  Google Scholar 

  10. 10.

    Platt R, Brown JS, Robb M, McClellan M, Ball R, Nguyen MD, Sherman RE (2018) The FDA sentinel initiative—an evolving national resource. N Engl J Med 379:2091–2093

    Article  Google Scholar 

  11. 11.

    Sentinel Modular Programs (2018) Querying tools: overview of functionality and technical documentation. US Food and Drug Administration, White Oak, MD

  12. 12.

    Cavaletti G, Marmiroli P (2010) Chemotherapy-induced peripheral neurotoxicity. Nat Rev Neurol 6:657–666

    Article  Google Scholar 

  13. 13.

    Dorsey SG, Kleckner IR, Barton D, Mustian K, O’Mara A, St. Germain D, Cavaletti G, Danhauer SC, Hershman DL, Hohmann AG et al (2019) The National Cancer Institute clinical trials planning meeting for prevention and treatment of chemotherapy-induced peripheral neuropathy. J Natl Cancer Inst 111:531–537

    Article  Google Scholar 

  14. 14.

    Wadia RJ, Stolar M, Grens C, Ehrlich BE, Chao HH (2018) The prevention of chemotherapy induced peripheral neuropathy by concurrent treatment with drugs used for bipolar disease: a retrospective chart analysis in human cancer patients. Oncotarget 9:7322–7331

    PubMed  Google Scholar 

  15. 15.

    Shah A, Hoffman EM, Mauermann M, Loprinzi CL, Windebank AJ, Klein CJ, Staff NP (2018) Incidence and disease burden of chemotherapy-induced peripheral neuropathy in a population-based cohort. J Neurol Neurosurg Psychiatry 0:1–6

    Google Scholar 

  16. 16.

    Raphael MJ, Fischer HD, Fung K, Austin PC, Anderson GM, Booth CM, Singh S (2017) Neurotoxicity outcomes in a population-based cohort of elderly patients treated with adjuvant oxaliplatin for colorectal cancer. Clin Colorectal Cancer 16:397–404 e391

    Article  Google Scholar 

  17. 17.

    Greenwald MK, Ruterbusch JJ, Beebe-Dimmer JL, Simon MS, Albrecht TL, Schwartz AG (2019) Risk of incident claims for chemotherapy-induced peripheral neuropathy among women with breast cancer in a Medicare population. Cancer 125(2):269–277

  18. 18.

    Tesfaye S, Stevens LK, Stephenson JM, Fuller JH, Plater M, Ionescu-Tirgoviste C, Nuber A, Pozza G, Ward JD, Group TEIS (1996) Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study. Diabetologia 39:13377–11384

    Google Scholar 

  19. 19.

    Barginear M, Dueck AC, Allred JB, Bunnell C, Cohen HJ, Freedman RA, Hurria A, Kimmick G, Le-Rademacher JG, Lichtman S, et al (2018) Age and the risk of paclitaxel-induced neuropathy in women with early-stage breast cancer (Alliance A151411): results from 1,881 patients from cancer and leukemia group B (CALGB) 40101. Oncologist 24(5):617–623

  20. 20.

    Park SB, Kwok JB, Asher R, Lee CK, Beale P, Selle F, Friedlander M (2017) Clinical and genetic predictors of paclitaxel neurotoxicity based on patient- versus clinician-reported incidence and severity of neurotoxicity in the ICON7 trial. Ann Oncol 28:2733–2740

    CAS  Article  Google Scholar 

  21. 21.

    Bulls HW, Hoogland AI, Kennedy B, James BW, Arboleda BL, Apte S, Chon HS, Small BJ, Gonzalez BD, Jim HSL (in press) A longitudinal examination of associations between age and chemotherapy-induced peripheral neuropathy in patients with gynecologic cancer. Gynecol Oncol 152(2):310–315

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Acknowledgments

The authors would like to thank Dr. Cheryl McMahill-Walraven of Aetna, a CVS Health company, and Dr. Kevin Haynes of Healthcore, Inc., for their contributions to this project.

Data sharing

Comprehensive aggregate data tables will be shared upon request.

Funding

This study was funded by the NIH U24AT009676 (The Collaboratory) and NIH/NCI UG1CA189961 (University of Rochester Cancer Center NCORP Research Base to KMM and G. Morrow).

Author information

Affiliations

Authors

Contributions

Study concept and design: JSG, JSB, LHC, RHD, SGM, and KMM

Acquisition, analysis, or interpretation of data: JSG, ASK, JHM, LHC, JSB, JB, and RHD

Drafting of the manuscript: JSG and ASK

Critical revision of the manuscript for important intellectual content: all authors

Statistical analysis: JHM and JB

Obtained funding: LHC, JSB, and KMM

Study supervision: JSG

Corresponding author

Correspondence to Jennifer S. Gewandter.

Ethics declarations

Competing interests

Jennifer S. Gewandter has received consulting income in the past 36 months from MundiPharma, Disarm Therapeutics, Asahi Kasei Pharma, and SK Life Science. Ian R. Kleckner has received funding from the National Institutes of Health (K07CA221931). Robert H. Dworkin has received in the past 36 months research grants and contracts from US Food and Drug Administration and US National Institutes of Health, and compensation for consulting on clinical trial methods from Abide, Adynxx, Analgesic Solutions, Aptinyx, Asahi Kasei, Astellas, AstraZeneca, Biogen, Biohaven, Boston Scientific, Braeburn, Celgene, Centrexion, Chromocell, Clexio, Concert, Decibel, Dong-A, Eli Lilly, Eupraxia, Glenmark, Grace, Hope, Immune, Lotus Clinical Research, Mainstay, Neumentum, NeuroBo, Novaremed, Novartis, Pfizer, Phosphagenics, Quark, Reckitt Benckiser, Regenacy (also equity), Relmada, Sandoz, Scilex, Semnur, Sollis, Teva, Theranexus, Trevena, and Vertex.

Ethics approval

The Harvard Pilgrim Health Care Institutional Review Board (IRB) determined that the project does not meet the definition of human subject research under the purview of the IRB according to federal regulations.

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Gewandter, J.S., Kleckner, A.S., Marshall, J.H. et al. Chemotherapy-induced peripheral neuropathy (CIPN) and its treatment: an NIH Collaboratory study of claims data. Support Care Cancer 28, 2553–2562 (2020). https://doi.org/10.1007/s00520-019-05063-x

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Keywords

  • Chemotherapy-induced peripheral neuropathy
  • CIPN
  • Neuropathy
  • Claims data
  • Incidence