Initiation Patterns of Disease-Modifying Antirheumatic Drugs That Have Potential to Exacerbate Heart Failure.

HomeJournal of the American Heart AssociationAhead of PrintInitiation Patterns of Disease‐Modifying Antirheumatic Drugs That Have Potential to Exacerbate Heart Failure Open AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessLetterPDF/EPUBInitiation Patterns of Disease‐Modifying Antirheumatic Drugs That Have Potential to Exacerbate Heart Failure Su Been Lee, Elvira D'Andrea and Rishi J. Desai Su Been LeeSu Been Lee , Division of Pharmacoepidemiology and Pharmacoeconomics, , Brigham and Women’s Hospital & Harvard Medical School, , Boston, , MA, , USA, Search for more papers by this author , Elvira D'AndreaElvira D'Andrea https://orcid.org/0000-0002-5263-3964 , Division of Pharmacoepidemiology and Pharmacoeconomics, , Brigham and Women’s Hospital & Harvard Medical School, , Boston, , MA, , USA, Search for more papers by this author and Rishi J. DesaiRishi J. Desai *Correspondence to: Rishi J. Desai, MS, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030‐R, Boston, MA 02120. Email: E-mail Address: [email protected] https://orcid.org/0000-0003-0299-7273 , Division of Pharmacoepidemiology and Pharmacoeconomics, , Brigham and Women’s Hospital & Harvard Medical School, , Boston, , MA, , USA, Search for more papers by this author Originally published14 Jul 2023https://doi.org/10.1161/JAHA.123.029589Journal of the American Heart Association. 2023;0:e029589Compared with the general population, patients with rheumatoid arthritis (RA) have ≈2‐fold increased risk of heart failure (HF).1 As a result, RA and HF are frequently presented as comorbid diagnoses. To improve the quality of care for these patients, the American Heart Association has identified several commonly used disease modifying antirheumatic drugs (DMARDs), including hydroxychloroquine and tumor necrosis factor inhibitor (TNFi) agents, as drugs that may exacerbate HF.2 However, little is known about prescribing practices for DMARDs among patients with comorbid RA and HF in routine clinical care.Using Medicare Fee‐for‐Service Parts A (inpatient coverage), B (outpatient coverage), and D (prescription benefits) data, we analyzed initiation patterns of DMARDs in patients with comorbid RA and HF in a national sample of older adults between 2012 and 2019. Our study was approved by the Mass General Brigham Institutional Review Board, and individual patient‐level informed consent was not required due to use of anonymized data. Based on the Data Use Agreement with the Centers for Medicare and Medicaid Services, individual‐level data are not shareable to protect patient privacy. Aggregated data will be made available upon reasonable request to the corresponding author.We identified 2 study populations: (1) The first cohort included patients initiating a nonbiologic DMARD (hydroxychloroquine, leflunomide, methotrexate, and sulfasalazine) and represented likely patients with early RA as evidenced by no DMARD use in the year before treatment; and (2) the second cohort included patients initiating biologics or targeted synthetic DMARDs including a TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) or non‐TNFi (abatacept, rituximab, tocilizumab, and tofacitinib) and represented patients with established RA who may be initiating biologics due to inadequate response with nonbiologics in the year before treatment. Both populations were restricted to patients with ≥12 months of continuous enrollment in Medicare Parts A, B, and D and had at least 2 separate inpatient or outpatient diagnoses for both RA and HF within 12 months before drug initiation. In the 2 populations, we described proportions of initiation for each individual DMARD over the study period. We tested for linear trends in the annual initiation percentage to report statistical significance of the time trends.A total of 5781 patients with early RA and 3659 patients with established RA with comorbid HF were included, with an average age (SD) of 76 (7) and 75 (6) years, respectively. In patients with early RA, hydroxychloroquine and methotrexate were the most frequently used agents, accounting for nearly 83% of total initiations, with no appreciable change in patterns between 2012 and 2019 (P=0.53 for methotrexate, 0.96 for hydroxychloroquine; Figure [A]). Among patients with established RA, rituximab and abatacept were the most frequently initiated biologic DMARDs, accounting for 21% of total initiations each. We observed a steady increase in initiation of rituximab and abatacept, accompanied by a reduction in some TNFi agents between 2012 and 2019, most prominently for infliximab, which decreased from 29% to 7% (P=0.04; Figure [B]). In 2019, the 5 TNFi agents accounted for 44% of the total biologic initiations.Download figureDownload PowerPointFigure . Treatment initiation trend in patients with rheumatoid arthritis (RA) with comorbid heart failure between 2012 and 2019.A, Treatment trend among patients with early RA initiating a nonbiologic disease‐modifying antirheumatic drug (DMARD; hydroxychloroquine [P for linear trend=0.96], leflunomide [P=0.41], methotrexate [P=0.53], and sulfasalazine [P=0.79]). B, Patients with established RA initiating biologics or targeted synthetic DMARDs including a tumor necrosis factor inhibitor (TNFi; adalimumab [P=0.07], certolizumab pegol [P=0.39], etanercept [P<0.01], golimumab [P=0.04], and infliximab [P=0.04]) or non‐TNFi (abatacept [P=0.02], rituximab [P=0.40], tocilizumab [P=0.08], and tofacitinib [P=0.20]).In this nationwide cohort, we observed that hydroxychloroquine remains a common treatment choice in older patients with RA and comorbid HF. Given the potential increase in adverse cardiovascular outcomes with hydroxychloroquine compared with methotrexate in this patient population,2, 3 the use of hydroxychloroquine may need reassessment. While the initiation is decreasing compared with their historical usage rates, we found that TNFi agents still account for a substantial proportion of biologic initiations in this patient population. Use of a large national cohort with comprehensive capture of medications through Part D claims is an important strength of our study. A limitation, however, is the lack of granular information regarding patients' RA activity and ejection fraction, which precluded us from describing treatment choice as a function of these important clinical parameters.In conclusion, we observed that use of potentially HF‐exacerbating DMARDs was common in patients with RA with comorbid HF in routine clinical care. Given that alternative and potentially safer DMARD options exist, a careful review of medications in this complex patient population is recommended to optimize benefit–risk trade‐offs. When use of alternative DMARDs is unachievable, special attention is needed to ensure close monitoring of the cardiac function in patients with RA with comorbid HF who are treated with DMARDs with potential to exacerbate HF.Sources of FundingNone.DisclosuresDr Desai has received research grants from Vertex, Bayer, and Novartis for unrelated studies. The remaining authors have no disclosures to report.AcknowledgmentsThe authors thank Dr Seoyoung Kim for early feedback on the design of this analysis.Footnotes*Correspondence to: Rishi J. Desai, MS, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030‐R, Boston, MA 02120. Email: [email protected]harvard.eduThis manuscript was sent to Sakima A. Smith, MD, MPH, Associate Editor, for review by expert referees, editorial decision, and final disposition.For Sources of Funding and Disclosures, see page 2.References1 Khalid Y, Dasu N, Shah A, Brown K, Kaell A, Levine A, Dasu K, Raminfard A. Incidence of congestive heart failure in rheumatoid arthritis: a review of literature and meta‐regression analysis. ESC Heart Fail. 2020; 7:3745–3753. doi: 10.1002/ehf2.12947CrossrefMedlineGoogle Scholar2 Page RL, O'Bryant CL, Cheng D, Dow TJ, Ky B, Stein CM, Spencer AP, Trupp RJ, Lindenfeld J. Drugs that may cause or exacerbate heart failure: a scientific statement from the American Heart Association. Circulation. 2016; 134:e32–e69. doi: 10.1161/CIR.0000000000000426LinkGoogle Scholar3 D'Andrea E, Desai RJ, He M, Glynn RJ, Lee H, Weinblatt ME, Kim SC. Cardiovascular risks of hydroxychloroquine vs methotrexate in patients with rheumatoid arthritis. J Am Coll Cardiol. 2022; 80:36–46. doi: 10.1016/j.jacc.2022.04.039CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetails Article InformationMetrics Copyright © 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.https://doi.org/10.1161/JAHA.123.029589PMID: 37449570 Manuscript receivedJanuary 23, 2023Manuscript acceptedMay 31, 2023Originally publishedJuly 14, 2023 Keywordshydroxychloroquineheart failureDMARDsrheumatoid arthritisPDF download SubjectsHeart Failure