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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.

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.

SUBMITTER: Fournier M

PROVIDER: S-EPMC6368117 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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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.

Fournier Marie M Chen Chieh-I CI Kuznik Andreas A Proudfoot Clare C Mallya Usha G UG Michaud Kaleb K

ClinicoEconomics and outcomes research : CEOR 20190205

<h4>Purpose</h4>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.<h4>Patients and methods</h4>Short-term analysis was based on 24-week wholesale acqui ...[more]

PMID: 30787625

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Project description:BACKGROUND:The phase III MONARCH randomized controlled trial (NCT02332590) demonstrated that in patients with rheumatoid arthritis (RA), sarilumab (anti-interleukin-6 receptor monoclonal antibody) monotherapy is superior to adalimumab monotherapy in reducing disease activity and signs and symptoms of RA, as well as in improving physical function, with similar rates of adverse and serious adverse events. We report the effects of sarilumab versus adalimumab on patient-reported outcomes (PROs). METHODS:Patients with active RA intolerant of, or inadequate responders to, methotrexate were randomized to sarilumab 200 mg plus placebo every 2 weeks (q2w; n?=?184) or adalimumab 40 mg plus placebo q2w (n?=?185). Dose escalation to weekly administration of adalimumab or matching placebo was permitted at week 16. PROs assessed at baseline and weeks 12 and 24 included patient global assessment of disease activity (PtGA), pain and morning stiffness visual analogue scales (VASs), Health Assessment Questionnaire Disability Index (HAQ-DI), 36-item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Rheumatoid Arthritis Impact of Disease (RAID), and rheumatoid arthritis-specific Work Productivity Survey (WPS-RA). Between-group differences in least-squares mean (LSM) changes from baseline were analyzed. p?<?0.05 was considered significant for PROs in a predefined hierarchy. For PROs not in the hierarchy, nominal p values are provided. Proportions of patients reporting improvements greater than or equal to the minimal clinically important difference (MCID) and achieving normative values were assessed. RESULTS:At week 24, sarilumab treatment resulted in significantly greater LSM changes from baseline than adalimumab monotherapy in HAQ-DI (p?<?0.005), PtGA (p?<?0.001), pain VAS (p?<?0.001), and SF-36 Physical Component Summary (PCS) (p?<?0.001). Greater LSM changes were reported for sarilumab than for adalimumab in RAID (nominal p?<?0.001), morning stiffness VAS (nominal p?<?0.05), and WPS-RA (nominal p?<?0.005). Between-group differences in FACIT-F and SF-36 Mental Component Summary (MCS) were not significant. More patients reported improvements greater than or equal to the MCID in HAQ-DI (nominal p?<?0.01), RAID (nominal p?<?0.01), SF-36 PCS (nominal p?<?0.005), and morning stiffness (nominal p?<?0.05), as well as greater than or equal to the normative values in HAQ-DI (p?<?0.05), with sarilumab versus adalimumab. CONCLUSIONS:In parallel with the clinical efficacy profile previously reported, sarilumab monotherapy resulted in greater improvements across multiple PROs than adalimumab monotherapy. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02332590 . Registered on 5 January 2015.

Project description:BACKGROUND:The interleukin-6 receptor inhibitor sarilumab demonstrated efficacy in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or as monotherapy in patients with moderately to severely active rheumatoid arthritis (RA) with an inadequate response (IR) or intolerant (INT) to methotrexate (MTX) or tumour necrosis factor (TNF)-? inhibitors. This analysis investigated the efficacy and safety of sarilumab in patient subgroups. METHODS:Data were included from phase III studies: two placebo-controlled studies of subcutaneous sarilumab 150/200?mg every 2?weeks (q2w) either + MTX in MTX-IR patients (52?weeks) or + csDMARDs in TNF-IR/INT patients (24?weeks), and a monotherapy study of sarilumab 200?mg q2w vs. adalimumab 40?mg q2w in MTX-IR/INT patients (24?weeks). Prespecified and post hoc subgroups included patient demographics, disease characteristics, and prior treatments. Prespecified and post hoc endpoints included clinical, radiographic, and physical function measures, and p values are considered nominal. Safety was assessed during double-blind treatment. RESULTS:The superiority of sarilumab (either as monotherapy vs. adalimumab or in combination with csDMARDs vs. placebo?+?csDMARDs) across clinical endpoints was generally consistent across subgroups defined by patient demographics, disease characteristics, and prior treatments, demonstrating the benefit of sarilumab treatment for a wide range of patient types. Interaction p values of <?0.05 were consistently observed across studies only for baseline anti-cyclic citrullinated peptide antibody (ACPA) status for American College of Rheumatology 20% response, but not American College of Rheumatology 50% or 70% response. Adverse events and worsening laboratory parameters occurred more frequently in sarilumab-treated vs. placebo-treated patients and were more frequent in the small number of patients ??65?years (n?=?289) vs. patients <?65?years (n?=?1819). Serious infections occurred in six patients aged ??65?years receiving sarilumab, although the incidence of serious infections was generally higher in patients aged ??65?years regardless of treatment. CONCLUSIONS:Apart from ACPA status, there were no consistent signals indicating differential effects of sarilumab in any of the subpopulations assessed. Sarilumab demonstrated consistent efficacy and safety across a wide range of patients with RA. TRIAL REGISTRATION:ClinicalTrials.gov NCT01061736, registered on February 03, 2010; ClinicalTrials.gov NCT01709578, registered on October 18, 2012; ClinicalTrials.gov NCT02332590, registered on January 07, 2015.

Project description:BACKGROUND:Increased levels of cytokines, including interleukin-6 (IL-6), reflect inflammation and have been shown to be predictive of therapeutic responses, fatigue, pain, and depression in patients with rheumatoid arthritis (RA), but limited data exist on associations between IL-6 levels and health-related quality of life (HRQoL). This post hoc analysis of MONARCH phase III randomized controlled trial data evaluated the potential of baseline IL-6 levels to differentially predict HRQoL improvements with sarilumab, a fully human monoclonal antibody directed against both soluble and membrane-bound IL-6 receptor ? (anti-IL-6R?) versus adalimumab, a tumor necrosis factor ? inhibitor, both approved for treatment of active RA. METHODS:Baseline serum IL-6 levels in 300/369 randomized patients were categorized into low (1.6-7.1?pg/mL), medium (7.2-39.5?pg/mL), and high (39.6-692.3?pg/mL) tertiles. HRQoL was measured at baseline and week (W)24 and W52 by Short Form 36 (SF-36) physical/mental component summary (PCS/MCS) and domain scores, Functional Assessment of Chronic Illness Therapy -fatigue, and duration of morning stiffness visual analog scale (AM-stiffness VAS). Linear regression of changes from baseline in HRQoL (IL-6 tertile, treatment, region as a stratification factor, and IL-6 tertile-by-treatment interaction as fixed effects) assessed predictivity of baseline IL-6 levels, with low tertile as reference. Pairwise comparisons of improvements between treatment groups were performed by tertile; least squares mean differences and 95% CIs were calculated. Similar analyses evaluated W24 patient-level response on minimum clinically important differences (MCID). RESULTS:At baseline, patients with high versus medium or low IL-6 levels (n?=?100, respectively) reported worse (nominal p?<?0.05) SF-36 MCS and role-physical, bodily pain, social functioning, role-emotional domain, and AM-stiffness VAS scores. There was a greater treatment effect with sarilumab versus adalimumab in high tertile versus low tertile groups in SF-36 PCS, physical functioning domain, and AM-stiffness VAS (nominal interaction p?<?0.05). PCS improvements ?MCID were higher in high (odds ratio [OR] 6.31 [2.37, 16.81]) versus low (OR 0.97 [0.43, 2.16]) tertiles with sarilumab versus adalimumab (nominal interaction p?<?0.05). Adverse events between IL-6 tertiles were similar. CONCLUSIONS:Patients with high baseline IL-6 levels reported better improvements in PCS, physical functioning domain, and AM-stiffness scores with sarilumab versus adalimumab and safety consistent with IL-6R blockade. TRIAL REGISTRATION:NCT02332590 . Registered on 5 January 2015.

Project description:IntroductionAssess the cost-effectiveness (US healthcare payer perspective) of sarilumab subcutaneous (SC) 200 mg?+?methotrexate versus conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or targeted DMARD?+?methotrexate for moderate-to-severe rheumatoid arthritis (RA) in adults with inadequate response to methotrexate.MethodsMicrosimulation based on patient profiles from MOBILITY (NCT01061736) was conducted via a 6-month decision tree and lifetime Markov model with 6-monthly cycles. Treatment response at 6 months was informed by a network meta-analysis and based on American College of Rheumatology (ACR) response. Responders: patients with ACR20 response who continued with therapy; non-responders: ACR20 non-responders who transitioned to the subsequent treatment. Utilities and quality-adjusted life-years (QALYs) were estimated via mapping 6-month ACR20/50/70 response to relative change in Health Assessment Questionnaire Disability Index score (short term) and based on published algorithms (long term). Direct costs considered drugs (wholesale acquisition costs), administration and routine care.ResultsLifetime QALYs and costs for treatment sequences on the efficiency frontier were 3.43 and $115,019 for active csDMARD, 5.79 and $430,918 for sarilumab, and 5.94 and $524,832 for etanercept (all others dominated). Sarilumab was cost-effective versus tocilizumab and csDMARD (incremental cost-effectiveness ratios of $84,079/QALY and $134,286/QALY). Probabilistic sensitivity analysis suggested comparable costs and slightly improved health benefits for sarilumab versus tocilizumab, irrespective of threshold.ConclusionIn patients with moderate-to-severe RA, sarilumab 200 mg SC every 2 weeks?+?methotrexate can be considered a cost-effective treatment option, with lower costs and greater health benefits than alternative treatment sequences (+?methotrexate) beginning with adalimumab, certolizumab, golimumab and tofacitinib and below commonly accepted cost-effectiveness thresholds against tocilizumab?+?methotrexate or csDMARD active treatment.FundingSanofi and Regeneron Pharmaceuticals, Inc.

Dataset Information

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.

Publications

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.

Similar Datasets

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