Dataset Information

Sarilumab: patient-reported outcomes in rheumatoid arthritis.

ABSTRACT: In the last few decades, strategies for the management of rheumatoid arthritis (RA) have been increasingly oriented toward more comprehensive control of the disease, taking into account even RA extra-articular manifestations, comorbidities, and the patient's perception about the disease. The need for improving the shared decision-making process suggested by European League Against Rheumatism recommendations is leading to an increasing interest in the role of patient-reported outcomes (PROs) beside the usual more objective criteria for defining clinical response based on disease-activity composite indices. Measurement of such PROs as pain or fatigue may be significantly influenced by mood disorders often complicating RA, the pathogenesis of which is deeply interconnected with phlogistic processes mediated by proinflammatory cytokines. IL6 is a pleiotropic mediator involved in neuroendocrine and neuropsychological processes, besides its well known effects on immune, cardiovascular, and metabolic systems. Therefore, there is a growing body of evidence about the efficacy of IL6 blockade in PRO improvement in RA patients. Sarilumab is a monoclonal antibody binding both soluble and membrane-bound IL6R?, inhibiting the IL6-mediated signaling pathway with favorable efficacy and safety profile. This review analyzes the importance of PROs in strategies for the management of RA and the pathogenic mechanisms linking IL6 with the patient's perception of the disease. Moreover, the main findings from sarilumab randomized controlled trials are summarized in detail, emphasizing the potential role of this IL6 blocker in the holistic treatment of RA.

SUBMITTER: Crotti C

PROVIDER: S-EPMC6108331 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Sarilumab: patient-reported outcomes in rheumatoid arthritis.

Crotti Chiara C Biggioggero Martina M Becciolini Andrea A Favalli Ennio Giulio EG

Patient related outcome measures 20180820

In the last few decades, strategies for the management of rheumatoid arthritis (RA) have been increasingly oriented toward more comprehensive control of the disease, taking into account even RA extra-articular manifestations, comorbidities, and the patient's perception about the disease. The need for improving the shared decision-making process suggested by European League Against Rheumatism recommendations is leading to an increasing interest in the role of patient-reported outcomes (PROs) besi ...[more]

PMID: 30154675

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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:BackgroundSarilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-6 receptor complex. In the MOBILITY phase III randomized controlled trial (RCT), sarilumab + methotrexate (MTX) treatment resulted in clinical improvements at 24 weeks that were maintained at 52 weeks in adults with rheumatoid arthritis (RA), who have inadequate response to MTX (MTX-IR). These analyses indicate the effects of sarilumab + MTX versus placebo on patient-reported outcomes (PROs) in this RCT.MethodsPatients (n = 1197) were randomized to receive placebo, sarilumab 150 or 200 mg subcutaneously + MTX every 2 weeks for 52 weeks; after 16 weeks, patients without ≥20 % improvement from baseline in swollen or tender joint counts on two consecutive assessments were offered open-label treatment. PROs included patient global assessment of disease activity (PtGA), pain, health assessment questionnaire disability index (HAQ-DI), Short Form-36 Health Survey (SF-36), and functional assessment of chronic illness therapy-fatigue (FACIT-F). Changes from baseline at weeks 24 and 52 were analyzed using a mixed model for repeated measures. Post hoc analyses included percentages of patients reporting improvements equal to or greater than minimal clinically important differences (MCID) and normative values in the FACIT-F and SF-36. Pearson correlation between observed PRO scores and clinical measures of disease activity was tested at week 24.ResultsBoth doses of sarilumab + MTX vs placebo + MTX resulted in improvement from baseline by week 24 in PtGA, pain, HAQ-DI, SF-36 and FACIT-F scores (p < 0.0001) that was clinically meaningful, and persisted until week 52. In post hoc analyses, the percentages of patients with improvement equal to or greater than the MCID across all PROs were greater with sarilumab than placebo (p < 0.05), with differences ranging from 11.6 to 26.2 %, as were those reporting equal to or greater than normative scores.ConclusionsIn this RCT in patients with MTX-IR RA, sarilumab + MTX resulted in sustained improvement in PROs that were clinically meaningful, greater than placebo + MTX, and complement the previously reported clinical efficacy and safety of sarilumab.Trial registrationClinicalTrials.gov. NCT01061736 . February 2, 2010.

Project description:BackgroundAnemia is common in patients with rheumatoid arthritis (RA). Higher hemoglobin (Hb) levels may be associated with better clinical outcomes and patient-reported outcomes (PROs). To assess this hypothesis, we conducted two post hoc analyses in three sarilumab phase III studies: TARGET, MOBILITY, and MONARCH.MethodsPooled data from combination therapy from placebo-controlled MOBILITY (sarilumab + methotrexate) and TARGET (sarilumab + conventional synthetic disease-modifying antirheumatic drugs [csDMARDs]) and monotherapy data from active-controlled MONARCH (sarilumab vs. adalimumab) studies were included. Associations between Hb levels and clinical measures and PROs were assessed over 24 weeks. The mean changes from baseline in clinical outcomes and PROs (to week 24) and radiographic outcomes (to week 52) were evaluated between low and normal Hb levels (based on the World Health Organization [WHO] criteria).ResultsFrom TARGET, MOBILITY, and MONARCH, 546, 1197, and 369 patients, respectively, were stratified according to Hb levels (low vs. normal). Over 24 weeks, higher Hb levels were found to be consistently associated with better clinical outcomes and PROs in combination therapy and monotherapy groups and were more pronounced among the patients treated with sarilumab than those treated with placebo and adalimumab. The mean change from baseline to week 24 in clinical efficacy measures and PROs was similar in patients with low vs. normal Hb at baseline. Differences between sarilumab and/or adalimumab, for all outcomes, were larger for low Hb subgroups. In MOBILITY, by week 52, the inhibition of progression of structural damage (assessed via Modified Total Sharp Score [mTSS]) was 84% (sarilumab 200 mg) and 68% (sarilumab 150 mg) vs. placebo in patients with low Hb and 97% (sarilumab 200 mg) and 68% (sarilumab 150 mg) vs. placebo in patients with normal Hb. Similar results were observed for other radiographic outcomes.ConclusionsIn these post hoc analyses, a consistent relationship was observed between higher Hb levels and better clinical outcomes and PROs in patients with RA. Irrespective of the baseline Hb levels, sarilumab treatment was associated with improvements in clinical measures and PROs over 24 weeks (improvements were more pronounced than those with adalimumab treatment) and mitigation of joint damage progression over 52 weeks.Trial registrationClinTrials.gov NCT01061736, NCT01709578, and NCT02332590.

Project description:IntroductionRheumatoid arthritis (RA) is a chronic inflammatory disease that causes a considerable burden for the patient and society. It is not clear yet whether aiming for remission (REM) is worthwhile, especially when compared with low disease activity (LDA).MethodsIn 356 consecutive RA patients, we obtained data on physical function (health assessment questionnaire (HAQ)), health-related quality of life (HRQoL: Short Form 36 (SF36), Short Form 6 dimensions (SF-6D), Euro QoL 5D (EQ-5D)), work productivity (work productivity and activity impairment questionnaire (WPAI)), as well as estimation of direct and indirect costs. Cross-sectionally, data were compared in patients within different levels of disease activity according to the simplified disease activity index (SDAI; remission (REM ≤3.3); n = 87; low disease activity (LDA: 3.3 < SDAI ≤11); n = 103; moderate to high disease activity (MDA/HDA) >11 n = 119) by using analyses of variance (ANOVA). Longitudinal investigations assessed patients who changed from LDA to REM and vice versa.ResultsWe found differences in patients achieving REM compared with LDA for HAQ (0.39 ± 0.58 versus 0.72 ± 68), WPAI (percentage impairment while working 11.8% ± 18.7% versus 26.8% ± 23.9%; percentage of overall activity impairment, 10.8% ± 14.1% versus 29.0% ± 23.6%)), EQ-5D (0.89 ± 0.12 versus 0.78 ± 0.6) and SF-36 (physical component score (PCS): 46.0 ± 8.6 versus 38.3 ± 10.5; mental component score (MCS): 49.9 ± 11.1 versus 47.9 ± 12.3) (P < 0.01 for all, except for SF36 MCS). Regarding costs, we found significant differences of direct and indirect costs (P < 0.05) within different levels of disease activity, with higher costs in patients with higher states of disease activity. Longitudinal evaluations confirmed the main analyses.ConclusionPatients with REM show better function, HRQoL, and productivity, even when compared with another good state, such as LDA. Also from a cost perspective, REM appears superior to all other states.

Dataset Information

Sarilumab: patient-reported outcomes in rheumatoid arthritis.

Publications

Sarilumab: patient-reported outcomes in rheumatoid arthritis.

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