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      Maintenance of Sustained Low Disease Activity or Remission in Patients With Rheumatoid Arthritis Treated With Etanercept Monotherapy: Results from the Corrona Registry

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          Abstract

          Objective

          The purpose of this study was to evaluate maintenance of remission/low disease activity (LDA) in patients with rheumatoid arthritis (RA) who achieved remission/LDA with etanercept (ETN) plus a conventional synthetic disease‐modifying antirheumatic drug (csDMARD) and to compare patients who discontinued csDMARD to receive ETN monotherapy (Mono) with those remaining on combination therapy (Combo).

          Methods

          Patients from the Corrona RA registry between October 1, 2001, and August 31, 2017, were eligible. The index date for the Mono cohort was the csDMARD discontinuation date; the index visit for the Combo cohort was estimated from time between ETN initiation and csDMARD discontinuation in the Mono cohort. The main outcome calculated was maintenance of remission/LDA. Patients were censored if they switched to or added a biologic DMARD, discontinued ETN, when a csDMARD was reintroduced (Mono), or if methotrexate increased more than 5 mg/d (Combo). Trimming was used to balance demographic and clinical characteristics between groups. Cox regression models were adjusted for the remaining differences across groups.

          Results

          We identified 182 Mono and 403 Combo patients; 120 Mono and 207 Combo patients remained after trimming. Most patients (approximately 80%) were biologic medication–naive before initiating ETN. At 24 months postindex, modeled percentages of patients remaining in remission/LDA were 75% for Mono and 86% for Combo (overall adjusted P = 0.057). More patients were censored for therapy change in Mono than in Combo groups (37% versus 5%), largely due to reintroduction of csDMARDs in the Mono group.

          Conclusion

          Many patients with RA who achieved remission/LDA on combination therapy maintained remission/LDA with ETN monotherapy for 2 years after csDMARD discontinuation. ETN monotherapy may be a viable option for patients who discontinue csDMARDs after achieving LDA/remission.

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          Most cited references21

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          EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update.

          Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to-or adding-another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.
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            Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial.

            Etanercept and methotrexate are effective in the treatment of rheumatoid arthritis but no data exist on concurrent initiation or use of the combination compared with either drug alone. We aimed to assess combination treatment with etanercept and methotrexate versus the monotherapies in patients with rheumatoid arthritis. In a double-blind, randomised, clinical efficacy, safety, and radiographic study, 686 patients with active rheumatoid arthritis were randomly allocated to treatment with etanercept 25 mg (subcutaneously twice a week), oral methotrexate (up to 20 mg every week), or the combination. Clinical response was assessed by criteria of the American College of Rheumatology (ACR). The primary efficacy endpoint was the numeric index of the ACR response (ACR-N) area under the curve (AUC) over the first 24 weeks. The primary radiographic endpoint was change from baseline to week 52 in total joint damage and was assessed with the modified Sharp score. Analysis was by intention to treat. Four patients did not receive any drug; thus 682 were studied. ACR-N AUC at 24 weeks was greater for the combination group compared with etanercept alone and methotrexate alone (18.3%-years [95% CI 17.1-19.6] vs 14.7%-years [13.5-16.0], p<0.0001, and 12.2%-years [11.0-13.4], p<0.0001; respectively). The mean difference in ACR-N AUC between combination and methotrexate alone was 6.1 (95% CI 4.5-7.8, p<0.0001) and between etanercept and methotrexate was 2.5 (0.8-4.2, p=0.0034). The combination was more efficacious than methotrexate or etanercept alone in retardation of joint damage (mean total Sharp score -0.54 [95% CI -1.00 to -0.07] vs 2.80 [1.08 to 4.51], p<0.0001, and 0.52 [-0.10 to 1.15], p=0.0006; respectively). The mean difference in total Sharp score between combination and methotrexate alone was -3.34 (95% CI -4.86 to -1.81, p<0.0001) and between etanercept and methotrexate was -27 (-3.81 to -0.74, p=0.0469). The number of patients reporting infections or adverse events was similar in all groups. The combination of etanercept and methotrexate was significantly better in reduction of disease activity, improvement of functional disability, and retardation of radiographic progression compared with methotrexate or etanercept alone. These findings bring us closer to achievement of remission and repair of structural damage in rheumatoid arthritis.
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              2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis

              To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA).
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                Author and article information

                Contributors
                dpappas@corrona.org
                Journal
                ACR Open Rheumatol
                ACR Open Rheumatol
                10.1002/(ISSN)2578-5745
                ACR2
                ACR Open Rheumatology
                John Wiley and Sons Inc. (Hoboken )
                2578-5745
                29 September 2020
                October 2020
                : 2
                : 10 ( doiID: 10.1002/acr2.v2.10 )
                : 588-594
                Affiliations
                [ 1 ] Corrona, LLC, Waltham, Massachusetts, and Columbia University College of Physicians and Surgeons New York New York
                [ 2 ] Corrona, LLC Waltham Massachusetts
                [ 3 ] DOCS Global, Inc. North Wales Pennsylvania
                [ 4 ] Amgen Inc. Thousand Oaks California
                Author notes
                [*] [* ] Address correspondence to Dimitrios A. Pappas, MD, MPH, Columbia University, College of Physicians and Surgeons, 630 W 168th St., P&S Building, Suite 10‐445, New York, NY 10032. E‐mail: dpappas@ 123456corrona.org .

                Author information
                https://orcid.org/0000-0001-8338-027X
                Article
                ACR211168
                10.1002/acr2.11168
                7571397
                32990361
                8c54f560-54d7-421e-8b2c-175839691849
                © 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 04 September 2019
                : 27 April 2020
                Page count
                Figures: 1, Tables: 3, Pages: 7, Words: 5409
                Funding
                Funded by: Amgen Inc.
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                October 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.7 mode:remove_FC converted:22.02.2021

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