A, Medicare data (dashed lines) only available from 2012 onward. B, Total annual Medicaid spending for all colchicine products marketed during the study period.
eTable. Availability and approval status of single-ingredient colchicine formulations marketed over 2008 to 2017.
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McCormick N, Wallace ZS, Yokose C, et al. Prolonged Increases in Public-Payer Spending and Prices After Unapproved Drug Initiative Approval of Colchicine. 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.
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.
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.
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.
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 (email@example.com).
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.