Patient-reported outcomes from a randomized phase III trial of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis

Abstract 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 s...

Full description

Bibliographic Details
Main Authors: Vibeke Strand, Laure Gossec, Clare W. J. Proudfoot, Chieh-I Chen, Matthew Reaney, Sophie Guillonneau, Toshio Kimura, Janet van Adelsberg, Yong Lin, Erin K. Mangan, Hubert van Hoogstraten, Gerd R. Burmester
Format: Article
Language:English
Published: BMC 2018-06-01
Series:Arthritis Research & Therapy
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13075-018-1614-z
id doaj-0f4f3986999d4d779a961f01dcdc58ab
record_format Article
spelling doaj-0f4f3986999d4d779a961f01dcdc58ab2020-11-25T01:33:31ZengBMCArthritis Research & Therapy1478-63622018-06-0120111210.1186/s13075-018-1614-zPatient-reported outcomes from a randomized phase III trial of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritisVibeke Strand0Laure Gossec1Clare W. J. Proudfoot2Chieh-I Chen3Matthew Reaney4Sophie Guillonneau5Toshio Kimura6Janet van Adelsberg7Yong Lin8Erin K. Mangan9Hubert van Hoogstraten10Gerd R. Burmester11Stanford UniversitySorbonne Universités, UPMC Université Paris 6, GRC-UPMC 08 (EEMOIS)SanofiRegeneron Pharmaceuticals, Inc.SanofiSanofiRegeneron Pharmaceuticals, Inc.Regeneron Pharmaceuticals, Inc.SanofiRegeneron Pharmaceuticals, Inc.SanofiCharité - University MedicineAbstract 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.http://link.springer.com/article/10.1186/s13075-018-1614-zSarilumabAdalimumabBiologic disease-modifying antirheumatic drugsRheumatoid arthritisPatient-reported outcomes
collection DOAJ
language English
format Article
sources DOAJ
author Vibeke Strand
Laure Gossec
Clare W. J. Proudfoot
Chieh-I Chen
Matthew Reaney
Sophie Guillonneau
Toshio Kimura
Janet van Adelsberg
Yong Lin
Erin K. Mangan
Hubert van Hoogstraten
Gerd R. Burmester
spellingShingle Vibeke Strand
Laure Gossec
Clare W. J. Proudfoot
Chieh-I Chen
Matthew Reaney
Sophie Guillonneau
Toshio Kimura
Janet van Adelsberg
Yong Lin
Erin K. Mangan
Hubert van Hoogstraten
Gerd R. Burmester
Patient-reported outcomes from a randomized phase III trial of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis
Arthritis Research & Therapy
Sarilumab
Adalimumab
Biologic disease-modifying antirheumatic drugs
Rheumatoid arthritis
Patient-reported outcomes
author_facet Vibeke Strand
Laure Gossec
Clare W. J. Proudfoot
Chieh-I Chen
Matthew Reaney
Sophie Guillonneau
Toshio Kimura
Janet van Adelsberg
Yong Lin
Erin K. Mangan
Hubert van Hoogstraten
Gerd R. Burmester
author_sort Vibeke Strand
title Patient-reported outcomes from a randomized phase III trial of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis
title_short Patient-reported outcomes from a randomized phase III trial of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis
title_full Patient-reported outcomes from a randomized phase III trial of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis
title_fullStr Patient-reported outcomes from a randomized phase III trial of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis
title_full_unstemmed Patient-reported outcomes from a randomized phase III trial of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis
title_sort patient-reported outcomes from a randomized phase iii trial of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis
publisher BMC
series Arthritis Research & Therapy
issn 1478-6362
publishDate 2018-06-01
description Abstract 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.
topic Sarilumab
Adalimumab
Biologic disease-modifying antirheumatic drugs
Rheumatoid arthritis
Patient-reported outcomes
url http://link.springer.com/article/10.1186/s13075-018-1614-z
work_keys_str_mv AT vibekestrand patientreportedoutcomesfromarandomizedphaseiiitrialofsarilumabmonotherapyversusadalimumabmonotherapyinpatientswithrheumatoidarthritis
AT lauregossec patientreportedoutcomesfromarandomizedphaseiiitrialofsarilumabmonotherapyversusadalimumabmonotherapyinpatientswithrheumatoidarthritis
AT clarewjproudfoot patientreportedoutcomesfromarandomizedphaseiiitrialofsarilumabmonotherapyversusadalimumabmonotherapyinpatientswithrheumatoidarthritis
AT chiehichen patientreportedoutcomesfromarandomizedphaseiiitrialofsarilumabmonotherapyversusadalimumabmonotherapyinpatientswithrheumatoidarthritis
AT matthewreaney patientreportedoutcomesfromarandomizedphaseiiitrialofsarilumabmonotherapyversusadalimumabmonotherapyinpatientswithrheumatoidarthritis
AT sophieguillonneau patientreportedoutcomesfromarandomizedphaseiiitrialofsarilumabmonotherapyversusadalimumabmonotherapyinpatientswithrheumatoidarthritis
AT toshiokimura patientreportedoutcomesfromarandomizedphaseiiitrialofsarilumabmonotherapyversusadalimumabmonotherapyinpatientswithrheumatoidarthritis
AT janetvanadelsberg patientreportedoutcomesfromarandomizedphaseiiitrialofsarilumabmonotherapyversusadalimumabmonotherapyinpatientswithrheumatoidarthritis
AT yonglin patientreportedoutcomesfromarandomizedphaseiiitrialofsarilumabmonotherapyversusadalimumabmonotherapyinpatientswithrheumatoidarthritis
AT erinkmangan patientreportedoutcomesfromarandomizedphaseiiitrialofsarilumabmonotherapyversusadalimumabmonotherapyinpatientswithrheumatoidarthritis
AT hubertvanhoogstraten patientreportedoutcomesfromarandomizedphaseiiitrialofsarilumabmonotherapyversusadalimumabmonotherapyinpatientswithrheumatoidarthritis
AT gerdrburmester patientreportedoutcomesfromarandomizedphaseiiitrialofsarilumabmonotherapyversusadalimumabmonotherapyinpatientswithrheumatoidarthritis
_version_ 1725076613404557312