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      Sarilumab monotherapy compared with adalimumab monotherapy for the treatment of moderately to severely active rheumatoid arthritis: an analysis of incremental cost per effectively treated patient

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          Abstract

          Purpose

          Treatment outcomes and direct medical costs were examined, from a US health payer perspective, of monotherapy with sarilumab 200 mg subcutaneous (SC) every 2 weeks (Q2W) vs adalimumab 40 mg SC Q2W/QW in adult patients with moderately to severely active rheumatoid arthritis who are intolerant of, inadequate responders to, or considered inappropriate candidates for continued methotrexate treatment.

          Patients and methods

          Short-term analysis was based on 24-week wholesale acquisition costs of drugs and treatment response observed in the MONARCH Phase III trial (NCT02332590) per American College of Rheumatology (ACR) 20/50 criteria and European League Against Rheumatism (EULAR) Moderate/Good Disease Activity Score 28-joint count erythrocyte sedimentation rate. Long-term analysis, which also considered drug administration and routine care costs, was conducted via a 6-month decision tree and a 1- to 10-year Markov model with microsimulation of patient profiles from the MOBILITY Phase III trial (NCT01061736). Utilities and quality-adjusted life-years (QALYs) were estimated by mapping 6-month ACR levels to a relative change in Health Assessment Questionnaire – Disability Index score and via published algorithms.

          Results

          For sarilumab and adalimumab, respectively, 24-week drug costs were $18,954 and $29,232, and costs per responder were $26,435 vs $50,055 on ACR20; $41,475 vs $98,425 on ACR50; and $22,511 vs $41,230 on EULAR Moderate/Good. Base case results at 10 years for total costs and QALYs were $176,977 and 2.75 for sarilumab and $212,136 and 2.61 for adalimumab, respectively. Sarilumab was consistently the more effective and cost-saving treatment across all short-term and long-term incremental analyses.

          Conclusion

          Sarilumab monotherapy was the economically dominant treatment on incremental cost per responder and incremental cost per QALY compared with adalimumab monotherapy. These results were maintained within the sensitivity analyses.

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          Most cited references25

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          The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.

          The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a "classification tree" schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91-94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.
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            The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment.

            To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment. This was a 2-year, multicenter, double-blind, active comparator-controlled study of 799 RA patients with active disease of < 3 years' duration who had never been treated with MTX. Treatments included adalimumab 40 mg subcutaneously every other week plus oral MTX, adalimumab 40 mg subcutaneously every other week, or weekly oral MTX. Co-primary end points at year 1 were American College of Rheumatology 50% improvement (ACR50) and mean change from baseline in the modified total Sharp score. Combination therapy was superior to both MTX and adalimumab monotherapy in all outcomes measured. At year 1, more patients receiving combination therapy exhibited an ACR50 response (62%) than did patients who received MTX or adalimumab monotherapy (46% and 41%, respectively; both P < 0.001). Similar superiority of combination therapy was seen in ACR20, ACR70, and ACR90 response rates at 1 and 2 years. There was significantly less radiographic progression (P < or = 0.002) among patients in the combination treatment arm at both year 1 and year 2 (1.3 and 1.9 Sharp units, respectively) than in patients in the MTX arm (5.7 and 10.4 Sharp units) or the adalimumab arm (3.0 and 5.5 Sharp units). After 2 years of treatment, 49% of patients receiving combination therapy exhibited disease remission (28-joint Disease Activity Score <2.6), and 49% exhibited a major clinical response (ACR70 response for at least 6 continuous months), rates approximately twice those found among patients receiving either monotherapy. The adverse event profiles were comparable in all 3 groups. In this population of patients with early, aggressive RA, combination therapy with adalimumab plus MTX was significantly superior to either MTX alone or adalimumab alone in improving signs and symptoms of disease, inhibiting radiographic progression, and effecting clinical remission.
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              The Health Assessment Questionnaire (HAQ).

              Patient-reported outcomes (PROs) provide intrinsic knowledge about a patient's health, functional status, symptoms, treatment preferences, satisfaction, and quality of life. They have become an established approach for assessing health outcomes. The Health Assessment Questionnaire (HAQ), introduced in 1980, is among the first PRO instruments designed to represent a model of patient-oriented outcome assessment. The HAQ is based on five patient-centered dimensions: disability, pain, medication effects, costs of care, and mortality. It has been validated by mail, in the office, by telephone, and by comparison with paraprofessional and physician judgments as a reliable instrument, and has been significantly correlated with other PRO instruments. Typically, one of two HAQ versions is used: the Full HAQ, which assesses all five dimensions, and the Short or 2-page HAQ, which contains only the HAQ disability index (HAQ-DI) and the HAQ's patient global and pain visual analog scales (VAS). The HAQ-DI and the global and pain VAS (i.e., the short HAQ) have essentially retained their original content since their inception, while the Full HAQ undergoes periodic revision to address issues of contemporary scientific interest. The HAQ-DI has been translated or culturally adapted into more than 60 different languages or dialects and has become part of the National Institutes of Health "Road-map" Project, the Patient-Reported Outcomes Measurement Information System (PROMIS).
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                Author and article information

                Journal
                Clinicoecon Outcomes Res
                Clinicoecon Outcomes Res
                ClinicoEconomics and Outcomes Research
                ClinicoEconomics and Outcomes Research: CEOR
                Dove Medical Press
                1178-6981
                2019
                05 February 2019
                : 11
                : 117-128
                Affiliations
                [1 ]Health Economics & Value Assessment, Sanofi France, Chilly-Mazarin, France, Marie.Fournier@ 123456sanofi.com
                [2 ]Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA
                [3 ]Sanofi, Guildford, UK
                [4 ]Sanofi, Bridgewater, NJ, USA
                [5 ]University of Nebraska Medical Center, Omaha, NE, USA
                [6 ]The National Databank for Rheumatic Diseases, Wichita, KS, USA
                Author notes
                Correspondence: Marie Fournier, Sanofi France, 1 Avenue Pierre Brossolette, 91380 Chilly-Mazarin, France, Tel +33 1 60 49 77 77, Email Marie.Fournier@ 123456sanofi.com
                Article
                ceor-11-117
                10.2147/CEOR.S183076
                6368117
                04d86916-6de7-4b76-88f9-9f4d75ef2567
                © 2019 Fournier et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Economics of health & social care
                treatment costs,disease-modifying anti-rheumatic drug,il-6 inhibitor,rheumatoid arthritis,cost per responser

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