Annals of the American Thoracic Society | 2021
Broad Adoption of Antifibrotics in Idiopathic Pulmonary Fibrosis: Still a Long Way to Go
Abstract
In October 2014, two antifibrotic medications (nintedanib and pirfenidone) were approved by the U.S. Food andDrug Administration (FDA) for treatment of idiopathic pulmonary fibrosis (IPF) after landmark trials showed a significant reduction in the decline in lung function as measured by forced vital capacity compared with placebo over 1 year (1, 2). Follow-up post hoc analyses of these trial data have since demonstrated that the benefits of antifibrotics are consistent across disease severity, may reduce respiratory-related hospitalizations, and could possibly improve survival (3–5). The benefits of these antifibrotics are clear; and although they are associated with unpleasant side effects in a number of patients, these are not lifethreatening and do not linger after cessation of the drugs. Considering that in a large number of patients, the benefits generally outweigh the potential risks and adverse effects, it is important to knowwhat the real-life use of antifibrotics in IPF has been over the past 5 years. Previously published data from longitudinal registries of IPF in the United States have shown that treatment rates vary, ranging from 58–70% (6, 7). However, registry participants are typically highly selected patients referred to tertiary care specialized interstitial lung disease centers. Therefore, treatment rates from registry studies may not truly reflect real-life practice outside of academic institutions. Establishing the true rate of uptake of antifibrotic medications in IPF across institutions and populations is important for identifying gaps and inequalities in medical care and in access to medications. In this issue ofAnnalsATS, Dempsey and colleagues (pp. 1121–1128) have sought to evaluate the adoption, persistence, and outof-pocket costs of antifibrotic medications (both pirfenidone and nintedanib) in the United States since their approval in 2014 (8). This is a retrospective observational study, in which the authors used deidentified United States–based administrative claims data from private and public (Medicare Advantage) health insurance plans. This database contains claims data from diverse racial and ethnic groups spanning all 50 states. There were 10,996 subjects with IPF identified in the data set using International Statistical Classification of Diseases and Related Health Problems, Ninth Revision and Tenth Revision diagnostic codes and included in this study (out of a possible 21,444,770 covered patients). The authors also looked at all prescriptions of either nintedanib or pirfenidone and added the claimants who had filled such a prescription even if they received their diagnosis of IPF at a later date. Of the patients with IPF, a total of 2,901 (26.4%) received either nintedanib or pirfenidone during the study period. Those who were younger and had fewer comorbidities were more likely to receive treatment. Importantly, there were sex-based differences in medication initiation whereby women were significantly less likely to be prescribed medications thanmen (22% vs. 30%). The number of patients who were started on antifibrotics increased over time, peaking in the last quarter studied in 2019, presumably as prescribers becamemore familiar with these novel medications. During the duration of the study, 10.5% switched from one drug to the other. Treatment discontinuation occurred in 43% of patients who had been started on treatment, with a mean duration of treatment of under 1 year (302 d). This was not due to imminent death or reaching endstage disease, as the mean time from treatment end to death was over 500 days. It is disappointing to see that in this first large-scale, real-life study of drug usage in IPF, only 26% start therapy and that nearly half of those discontinue treatment fairly early on. This study is based on administrative data in which cases are identified using diagnostic codes, which may limit the diagnostic accuracy and therefore miss some cases of IPF. However, the authors included patients who had filled prescriptions of antifibrotics before the diagnostic code was added to their chart and then added those subjects to their cohort, making it likely that there was no substantial underestimation of the uptake of antifibrotics. This raises the key question as to why the observed adoption rate is so low even 5 years after approval of antifibrotics for IPF by the FDA.Many factors are likely contributing: approximately 21% of patients experienced at least one of the common side effects associated with antifibrotic medications, which had a role to play in the discontinuation of treatment in some. Side effects and having to manage themmay also deter some patients or their physicians from initiating treatment. In some cases, patients continue to smoke despite their diagnosis, which may make some physicians reluctant to start therapy as well. Perhaps themost important reason that uptake has been low, and that discontinuation has been so high, may be the prohibitively high cost of medications in the United States. The authors of this study looked at the out-ofpocket cost of antifibrotics for patients. They report that the global cost for either antifibrotic is approximately U.S. $9,000 per month, or about U.S. $108,000 per year per patient. Outof-pocket fees by the patients (copays) vary on This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/ licenses/by-nc-nd/4.0/). For commercial usage and reprints, please contact Diane Gern ([email protected]).