key: cord-0850988-53r4muxf
authors: Dalal, Deepan S.; Zhang, Tingting; Shireman, Theresa I.
title: Medicare Expenditures for Conventional and Biologic Disease Modifying Agents Commonly Used for Treatment of Rheumatoid Arthritis
date: 2020-08-28
journal: Semin Arthritis Rheum
DOI: 10.1016/j.semarthrit.2020.08.002
sha: e282736c653eca22779af62497fbdf7d08dd477d
doc_id: 850988
cord_uid: 53r4muxf

BACKGROUND: Biologic disease modifying agents (bDMARDs) are an integral part of rheumatoid arthritis treatment guidelines but are associated with significant cost in the US. We present the trends in total spending and unit cost of conventional DMARDs (cDMARDs) as compared to bDMARDs in Medicare program. METHODS: We used the Medicare drug spending data for the year 2012-2017 covering all part B (fee-for-service) and part D drugs. Total spending was calculated by summing spending across various drug formulations and unit drug cost by dividing total spending by number of doses dispensed. We present the 6-year trends in total spending, total beneficiary count and unit costs of each of the commonly used cDMARDs and bDMARDs. RESULTS: Between 2012 and 2017, the total spending on the cDMARDs increased 5-folds from $98 million to $579 million; this was fraction of total spending on bDMARDs which increased from $4.3 to $10.0 billion. This increase was driven largely by unit costs of drug rather than number of beneficiaries. There was a 6-fold increase in the unit cost of generic hydroxychloroquine followed by methotrexate and leflunomide. Amongst bDMARDs, adalimumab and etanercept unit cost increased by 2-folds. The increase was less pronounced for office-administered products. CONCLUSIONS: Despite the availability of several generic cDMARDs over decades, there were steep increases in the unit cost of these agents to “keep pace” with the increases in bDMARDs. As the number of elderly rheumatoid arthritis patients increases, policy interventions might be required to reduce the spending on both biologics and conventional DMARDs.

Biologic disease modifying agents (DMARD) are now an integral component of treatment guidelines for rheumatoid arthritis (RA) and other inflammatory arthritis, and currently more than one-third of RA patients use biologics.(1-3) Several clinical trials have demonstrated the efficacy of biologics in reducing disease activity as well as retarding disease progression and with an increased emphasis on early and tight control of the disease, the use of biologic DMARDs is becoming more common. (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) Adoption of biologic agents for RA treatment, however, comes at a price. Biologic agents are substantially more expensive per dose than conventional DMARDs, adding an additional $20,000 per year to direct medical care costs ($12,509 if not on a biologic versus $36,053 if on a biologic) in the United States. While the cost of drugs in RA patients using conventional agents is $1,500-2,000 annually, the cost of drugs in RA patients using biologics is as much as $30,000 a year. (15) Biologic agents administered as an intravenous infusion have a facility/administration fee associated with it which further adds to the cost of care of RA.

RA is twice as prevalent in older population as compared to young (2% versus 1%). And given the chronic nature of the disease and our aging population, the number of elderly RA patients is expected to rise. (16) (17) (18) (19) Medicare is largest payer for healthcare of older individuals. A study conducted by

McCormick et al noted more than 2-fold increase in Medicare and Medicaid spending on biologic disease modifying agents commonly used for treatment of rheumatic diseases which was largely driven by post-marketing increases in drug price. (20) In the context of increasing spending on biologic DMARDs, we compared the trends in Medicare spending on conventional and biologic DMARDs commonly used to treat RA, to broadly document the impact of new therapeutic agents alongside more traditional products. While the conventional and biologic agents included have approved indications 4 besides RA, their pricing is independent of the indication for use and trends will be applicable to RA care costs.

Study design: The current study was an observational study assessing national trends in spending on disease modifying agents used for rheumatoid arthritis using aggregated Medicare data. 

We included all the commonly used disease modifying agents used for rheumatoid arthritis captured through Part B (office-administered) and Part D (self-administered drugs) claims. Conventional agents were methotrexate, sulfasalazine, hydroxychloroquine and leflunomide.

Biologic DMARDs available during the period included etanercept, abatacept, adalimumab, 5 certolizumab, golimumab, inflixiumab, rituximab, tocilizumab, and tofacitinib. All conventional DMARDs have been available as generic agents and approved several years before 2012. All the biologic DMARDs were approved for use in RA prior to 2012 except for office-administered certolizumab and golimumab, both approved in 2014. Hence, there was at least 4 years of data to assess the trend of spending on each drug. The dataset contains aggregated national level spending on individual drugs administered through part D and part B (without any administration fee for part B drugs). CMS data summarizes expenditures total spending which includes amounts paid by Medicare, beneficiaries as deductibles and copayments and third parties (for e.g. supplemental insurances). It also includes beneficiary counts, total claims, total dosage units, average cost per unit (calculated as total spending/total dosage units), average spend per claim, average spending per beneficiary, and changes over time at the brand or generic drug name level.

Their data combines utilization/cost data across dosage forms to the product brand, if applicable, or generic, if multisource, name. (Figure 2) . There was nearly a doubling in the price per unit of most self-administered biologic DMARDs, and the increase in unit cost of office administered DMARDs was less pronounced, except for abatacept. Table 2 We noted that, over the study period, there was a tremendous relative increase in total spending on conventional synthetic DMARDs, almost entirely driven by cost/unit of these drugs and outpacing inflation. The cost/unit of hydroxychloroquine, methotrexate and leflunomide increased almost 3-fold, most notably for hydroxychloroquine which increased 6-fold even though these medications have been available for several decades as generics. Branded oral and injectable methotrexate were the only agents whose actual cost in 2017 was lower than what would be expected by inflation alone. A study by considerably more expensive than conventional DMARDs, hence providing an opportunity to manufacturers of conventional DMARDs to increase the unit cost of these agents.

During the same period, there was also a considerable increase in the total spending on biologic DMARDs; the proportion of spending and beneficiaries on self-administered biologics compared to office-administered biologics increased during the study period. Across all biologic agents, the unit cost of office administered agent increased less than the unit cost of self-administered agents. As such, when drug administration costs are factored in, office administered agents are considerably more expensive than self-administered agents. Across all biologic agents, the price of drug in 2017 was much higher than what would be anticipated with inflation using the 2012 base cost except for office administered golimumab. Biosimilar agents were in their early approval phases during the year 2012-9 continue to remain high considering the lengthy process of development, regulatory restrictions, patent laws, and clinical trials required to demonstrate safety and efficacy of biosimilar agents. (25, 26) Hydroxychloroquine is being extensively investigated as a potential therapeutic option for the treatment of COVID-19 caused by the novel coronavirus (SARS-CoV2). uveitis, inflammatory bowel disease and hidradenitis. However, rheumatoid arthritis is the most common inflammatory arthritis amongst senior and hence, most of the spending is likely to be on rheumatoid arthritis. Second, we are unable to assess rebates provided by the pharmaceutical industry to pharmacy benefits manager and Part D plans. Finally, given the categorization of several conventional DMARDs like methotrexate tablets and methotrexate injections under "methotrexate sodium" OR leflunomide 10 mg and 20 mg under "leflunomide", precluded our ability to calculate annual costs different drug regimens like that for biologics.

Despite the limitations, the study provides useful national trends of spending on disease modifying agents in the United States. The findings of this study call for a 2-fold action. First, as the population ages, it is expected that the number of beneficiaries covered through Medicare will increase. If the post-marketing unit costs of DMARDs continue to increase at the pace noted in this study, with the increasing number of Medicare beneficiaries, the total spending on these agents increase at an even faster pace. Hence, policy changes targeting the post-marketing drug prices are required. Second, further studies are required to answer the central question, is the increased spending on DMARDs, particularly biological agents, resulting in improved outcomes in older RA patients. There is growing long-term data to suggest increasing safety of these medications, at least in average RA patients. However, outcomes of interest to geriatric population continue to remain an understudied area in RA care. 

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Adalimumab $26,491 $58,135 $30

Abatacept $27,087 $50,314 $30

056 $47,155 $30

036 $45,830 $29,691 54% OFFICE ADMINISTERED DRUGS Abatacept $19,494 $41

Certolizumab* $30,992 $38,116 $35