Prolonged Increases in Public-Payer Spending and Prices After Unapproved Drug Initiative Approval of Colchicine | Rheumatology | JAMA Internal Medicine | JAMA Network
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Figure.  Mean Annual Drug Unit Prices for Each Colchicine Formulation Available Before, During, and After Colcrys’s July 2009 Approval and Period of Market Exclusivity for Acute Gout by Program
Mean Annual Drug Unit Prices for Each Colchicine Formulation Available Before, During, and After Colcrys’s July 2009 Approval and Period of Market Exclusivity for Acute Gout by Program

A, Medicare data (dashed lines) only available from 2012 onward. B, Total annual Medicaid spending for all colchicine products marketed during the study period.

Table.  Spending, Prices, and Use of Colchicine Formulations Marketed Over the Study Period by Programa
Spending, Prices, and Use of Colchicine Formulations Marketed Over the Study Period by Programa
1.
Tardif  J-C, Kouz  S, Waters  DD,  et al.  Efficacy and safety of low-dose colchicine after myocardial infarction.   N Engl J Med. 2019;381(26):2497-2505. doi:10.1056/NEJMoa1912388PubMedGoogle ScholarCrossref
2.
Guglielmo  BJ.  The colchicine debacle.   JAMA Intern Med. 2013;173(3):184-185. doi:10.1001/jamainternmed.2013.1405PubMedGoogle ScholarCrossref
3.
Congressional Budget Office. Background paper: factors underlying the growth in Medicare’s spending for physicians’ services. June 2007. Accessed October 27, 2020. https://www.cbo.gov/publication/18726
4.
Hwang  TJ, Jain  N, Lauffenburger  JC, Vokinger  KN, Kesselheim  AS.  Analysis of proposed Medicare Part B to Part D shift with associated changes in total spending and patient cost-sharing for prescription drugs.   JAMA Intern Med. 2019;179(3):374-380. doi:10.1001/jamainternmed.2018.6417PubMedGoogle ScholarCrossref
5.
Kesselheim  AS, Franklin  JM, Kim  SC, Seeger  JD, Solomon  DH.  Reductions in use of colchicine after FDA enforcement of market exclusivity in a commercially insured population.   J Gen Intern Med. 2015;30(11):1633-1638. doi:10.1007/s11606-015-3285-7PubMedGoogle ScholarCrossref
6.
Luo  J, Seeger  JD, Donneyong  M, Gagne  JJ, Avorn  J, Kesselheim  AS.  Effect of generic competition on atorvastatin prescribing and patients’ out-of-pocket spending.   JAMA Intern Med. 2016;176(9):1317-1323. doi:10.1001/jamainternmed.2016.3384PubMedGoogle ScholarCrossref
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    Research Letter
    November 30, 2020

    Prolonged Increases in Public-Payer Spending and Prices After Unapproved Drug Initiative Approval of Colchicine

    Author Affiliations
    • 1Clinical Epidemiology Program,Division of Rheumatology, Allergy, and Immunology,Massachusetts General Hospital, Harvard Medical School, Boston
    • 2Division of General Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston
    • 3Department of Health Care Policy, Massachusetts General Hospital, Harvard Medical School, Boston
    JAMA Intern Med. 2021;181(2):284-287. doi:10.1001/jamainternmed.2020.5017

    The recent Colchicine Cardiovascular Outcomes Trial (COLCOT)1 suggested that colchicine could be repurposed for cost-effective, secondary prevention after myocardial infarction, with low-priced generics (approximately $0.30/pill) available worldwide, though not in the US. Colchicine, which predated the US Food and Drug Administration (FDA), had been available in unregulated/unapproved forms, for less than $0.50/pill, until the first FDA-regulated product, Colcrys, entered in 2009 at a drastically higher price ($5.00/pill),2 upending the marketplace. Under the guidance of the FDA’s Unapproved Drug Initiative, Colcrys’s manufacturer, which conducted a 1-week trial (n = 185), received 3 years’ market exclusivity for treatment of acute gout, and the unapproved formulations were soon ordered off the market, resulting in a virtual monopoly.

    Furthermore, Colcrys was granted patents for this centuries-old drug until 2029. Thus, although more than 6 independent generics have FDA approval to date, only authorized generics with price points set by brand-name companies are currently available to treat acute gout, pericarditis, and now potentially millions with myocardial infarction. We investigated national Medicaid and Medicare drug-spending data to examine colchicine prices over the period from 2008 to 2017.

    Methods

    We extracted data for all available forms of colchicine from 2008 through 2017, including unregulated/unapproved colchicine (2008-2010), generic combination probenecid-colchicine (FDA approved, but used infrequently; 2008-2017), Colcrys (2009-2017), and authorized generics (2015-2017); details are provided in the Supplement. We used Medicaid data to estimate average colchicine prices from 2008 (pre-Colcrys) through 2017 and compared total spending with that expected if prices remained at pre-Colcrys levels, adjusting for inflation. Decomposition analysis3 was used to isolate the change in total spending over 2008 through 2017 attributable to price changes alone. We applied basic Medicaid rebates and included inflationary rebates in a sensitivity analysis.

    Because pre-Colcrys Medicare data were not available, Medicare trends (2012-2017) were analyzed separately, with and without time-varying rebates increasing from 20% to 30%, following previous analyses.4 This study was deemed exempt by the Partners Healthcare Institutional Review Board because it was classified as nonhuman research; informed consent was not required considering this analysis used publicly available data and involved no individual patient health records.

    Results

    In 2017, spending on Medicare and Medicaid claims for single-ingredient colchicine exceeded $340 million. Inflation-adjusted and rebate-adjusted Medicaid unit prices rose from $0.24/pill in 2008 (unapproved formulations) to $4.20/pill in 2011 (Colcrys only) and peaked at $4.66/pill in 2015 (Colcrys plus authorized generics) (Figure, A). Medicare prices rose similarly over 2012 through 2017 (Table). Authorized generics entered the market in 2015, priced only marginally lower than the brand-name medications, but considerably higher than the previous, unapproved formulations. Prescribing of lower-priced probenecid-colchicine ($0.66/pill in 2017) remained stable throughout.

    Accordingly, Medicaid spending on single-ingredient colchicine rose 2833% (Figure, B); 58% of this increase was attributable to price increases alone. Spending in 2017 totaled $32.2 million vs just $2.1 million if prices had remained at pre-Colcrys levels. Trends remained similar after incorporating the inflation rebate.

    Discussion

    Years after Colcrys’ FDA-mandated exclusivity ended, colchicine’s high prices remain unabated. These findings expand on a report from commercially insured patients immediately after Colcrys’s introduction5 and illustrate the prolonged public-spending burden. Authorized generics can reduce costs6 when competing with independent generics, but such competition is currently missing for colchicine. As a result of the unusual circumstances of Colcrys’s current patents, which they have defended in court, entry of the FDA-approved independent generics onto the market may be delayed until 2029. Moreover, the manufacturer of Colcrys (although not used in COLCOT) could even seek FDA approval for additional cardiovascular indications, as well as further exclusivities.

    While we could not assess indications or per-person spending, the present findings covered the entirety of these public programs. Confidential drug-specific rebates were not available, but estimated rebates did not materially influence these findings.

    Public spending on colchicine has grown exponentially, mainly from ongoing price increases after Colcrys’s approval and market exclusivity, potentially limiting millions of US patients from affording its benefits as a long-term therapy for gout or after myocardial infarction.

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    Article Information

    Accepted for Publication: July 31, 2020.

    Published Online: November 30, 2020. doi:10.1001/jamainternmed.2020.5017

    Corresponding Author: Natalie McCormick, PhD, Clinical Epidemiology Program, Massachusetts General Hospital, Division of Rheumatology, Allergy, and Immunology, Harvard Medical School, 100 Cambridge St, Suite 1600, Boston, MA (nmccormick@mgh.harvard.edu).

    Author Contributions: Drs Hsu and Choi had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: McCormick, Wallace, Hsu.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: McCormick.

    Critical revision of the manuscript for important intellectual content: Wallace, Yokose, Jorge, Sacks, Hsu, Choi.

    Statistical analysis: McCormick, Wallace.

    Obtained funding: Choi.

    Administrative, technical, or material support: Wallace.

    Supervision: Wallace, Hsu, Choi.

    Conflict of Interest Disclosures: Dr McCormick reported grants from Canadian Institutes of Health Research during the conduct of the study. Dr Hsu reported grants from the National Institutes of Health; consulting fees from USC, Community Servings, Delta Health Alliance, DaVita, and Sidley Austin LLP; and grant reviews from Columbia University and the American Association for the Advancement of Science outside the submitted work. Dr Choi reported grants from National Institute of Arthritis and Musculoskeletal and Skin Diseases during the conduct of the study, grants and personal fees from Ironwood and Horizon, and personal fees from Selecta, Takeda, Kowa, and Vaxart outside the submitted work. No other disclosures were reported.

    References
    1.
    Tardif  J-C, Kouz  S, Waters  DD,  et al.  Efficacy and safety of low-dose colchicine after myocardial infarction.   N Engl J Med. 2019;381(26):2497-2505. doi:10.1056/NEJMoa1912388PubMedGoogle ScholarCrossref
    2.
    Guglielmo  BJ.  The colchicine debacle.   JAMA Intern Med. 2013;173(3):184-185. doi:10.1001/jamainternmed.2013.1405PubMedGoogle ScholarCrossref
    3.
    Congressional Budget Office. Background paper: factors underlying the growth in Medicare’s spending for physicians’ services. June 2007. Accessed October 27, 2020. https://www.cbo.gov/publication/18726
    4.
    Hwang  TJ, Jain  N, Lauffenburger  JC, Vokinger  KN, Kesselheim  AS.  Analysis of proposed Medicare Part B to Part D shift with associated changes in total spending and patient cost-sharing for prescription drugs.   JAMA Intern Med. 2019;179(3):374-380. doi:10.1001/jamainternmed.2018.6417PubMedGoogle ScholarCrossref
    5.
    Kesselheim  AS, Franklin  JM, Kim  SC, Seeger  JD, Solomon  DH.  Reductions in use of colchicine after FDA enforcement of market exclusivity in a commercially insured population.   J Gen Intern Med. 2015;30(11):1633-1638. doi:10.1007/s11606-015-3285-7PubMedGoogle ScholarCrossref
    6.
    Luo  J, Seeger  JD, Donneyong  M, Gagne  JJ, Avorn  J, Kesselheim  AS.  Effect of generic competition on atorvastatin prescribing and patients’ out-of-pocket spending.   JAMA Intern Med. 2016;176(9):1317-1323. doi:10.1001/jamainternmed.2016.3384PubMedGoogle ScholarCrossref
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