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      Real-World Data of Adherence and Drug Survival of Biologics in Treatment-Naïve and Treatment-experienced Adult Patients with Rheumatoid Arthritis

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          Abstract

          Introduction

          Biologic disease-modifying anti-rheumatics drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are important treatments for rheumatoid arthritis (RA). As more of these drugs become available, there is a greater need to assess their real-world adherence and drug survival.

          Methods

          Treatment-naïve and treatment-experienced patients with RA who initiated treatment with bDMARDs and tofactinib during 2015–2018 in a large Israeli health maintenance organization were included. Adherence and time to treatment suspension were recorded. Odds for adherence were estimated using a multivariable logistic regression model. Risk for treatment suspension was estimated using a mixed-effect Cox proportional hazard model.

          Results

          The analysis included 753 eligible patients (61.8% treatment-naïve) treated with 1287 treatment episodes (tofacitinib 24.2%, tocilizumab 17.5%, etanercept 16.0%, adalimumab 10.4%, abatacept 9.9%, rituximab 9.0%, golimumab 6.9%, certolizumab pegol 3.6%, infliximab 1.9%, and sarilumab 0.5%). Good adherence was measured for almost all drugs, yet over 50% of all treatment episodes were suspended. Older age was associated with reduced risk for treatment suspension while higher number of primary care visits and higher Charlson’s comorbidity score were associated with increased risk. Compared to etanercept, treatment with adalimumab, certolizumab, or rituximab was associated with increased risk for treatment suspension (HR 1.68 95% CI 1.27–2.22, HR 1.62 95% CI 1.00–2.60, and HR 2.72 95% CI 2.02–3.67, respectively).

          Conclusion

          Treatment choice primarily depends on disease activity and prognosis. Real-world data, showing differences in drug survival of bDMARDs and tsDMARD, can also be used in the variety of considerations when choosing treatment. Future studies could separate patients with RA into subgroups, which would also account for potential drug survival differences and enable personalized therapy.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s12325-023-02607-w.

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          A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation

          Mary Charlson, Peter Pompei, Kathy Ales … (1987)
          The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
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            Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies

            Qiang Guo, Yuxiang Wang, Dan Xu … (2018)
            Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages: (i) triggering, (ii) maturation, (iii) targeting, and (iv) fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies (including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs) remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our  understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA.
            Article 0 comments Cited 472 times – based on 0 reviews     Review now
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              Medication compliance and persistence: terminology and definitions.

              Joyce Cramer, Anuja Roy, Anita Burrell … (2008)
              The aim of the study is to provide guidance regarding the meaning and use of the terms "compliance" and "persistence" as they relate to the study of medication use. A literature review and debate on appropriate terminology and definitions were carried out. Medication compliance and medication persistence are two different constructs. Medication compliance (synonym: adherence) refers to the degree or extent of conformity to the recommendations about day-to-day treatment by the provider with respect to the timing, dosage, and frequency. It may be defined as "the extent to which a patient acts in accordance with the prescribed interval, and dose of a dosing regimen." Medication persistence refers to the act of continuing the treatment for the prescribed duration. It may be defined as "the duration of time from initiation to discontinuation of therapy." No overarching term combines these two distinct constructs. Providing specific definitions for compliance and persistence is important for sound quantitative expressions of patients' drug dosing histories and their explanatory power for clinical and economic events. Adoption of these definitions by health outcomes researchers will provide a consistent framework and lexicon for research.
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                Author and article information

                Contributors
                Howard Amital:
                ORCID: http://orcid.org/0000-0002-5406-7716
                Howard.Amital@sheba.health.gov.il
                Journal
                Journal ID (nlm-ta): Adv Ther
                Journal ID (iso-abbrev): Adv Ther
                Title: Advances in Therapy
                Publisher: Springer Healthcare (Cheshire )
                ISSN (Print): 0741-238X
                ISSN (Electronic): 1865-8652
                Publication date (Electronic): 11 August 2023
                Publication date PMC-release: 11 August 2023
                Publication date (Print): 2023
                Volume: 40
                Issue: 10
                Pages: 4504-4522
                Affiliations
                [1 ]GRID grid.425380.8, Maccabi Institute for Research and Innovation, , Maccabi Healthcare Services, ; Tel Aviv, Israel
                [2 ]GRID grid.12136.37, ISNI 0000 0004 1937 0546, Faculty of Medicine, , Tel Aviv University, ; Tel Aviv, Israel
                [3 ]GRID grid.431072.3, ISNI 0000 0004 0572 4227, AbbVie Inc., ; North Chicago, IL USA
                [4 ]GRID grid.413795.d, ISNI 0000 0001 2107 2845, Department of Medicine ‘B’ and Zabludowicz Center of Autoimmune Diseases, , Sheba Medical Center, ; Tel-Hashomer, 52621 Ramat Gan, Israel
                Author information
                http://orcid.org/0000-0002-1535-7091
                http://orcid.org/0000-0002-5189-8995
                http://orcid.org/0000-0002-3535-7152
                http://orcid.org/0000-0002-5406-7716
                Article
                Publisher ID: 2607
                DOI: 10.1007/s12325-023-02607-w
                PMC ID: 10499743
                PubMed ID: 37566157
                SO-VID: a7cae712-2c4a-4973-9d99-c8328acb4c20
                Copyright © © The Author(s) 2023
                License:

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                Date received : 21 March 2023
                Date accepted : 3 July 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100006483, AbbVie;
                Categories
                Subject: Original Research
                Custom metadata
                issue-copyright-statement © Springer Healthcare Ltd., part of Springer Nature 2023

                Keywords: biologics,tofacitinib,adherence,drug survival,rheumatoid arthritis,real-world
                Data availability:
                Keywords: biologics, tofacitinib, adherence, drug survival, rheumatoid arthritis, real-world

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