Cargando…

Long-term safety and efficacy of sarilumab with or without background csDMARDs in rheumatoid arthritis

OBJECTIVE: To evaluate the long-term safety and efficacy of sarilumab with/without conventional synthetic (cs)DMARDs in RA. METHODS: The analyses evaluated two open-label extensions (OLEs): EXTEND and MONARCH OLE, which included patients from six randomized trials. Patients received sarilumab 200 mg...

Descripción completa

Detalles Bibliográficos
Autores principales: Burmester, Gerd R, Strand, Vibeke, Kivitz, Alan J, Hu, Chih-Chi, Wang, Sheldon, van Hoogstraten, Hubert, Klier, Gabriella L, Fleischmann, Roy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10547516/
https://www.ncbi.nlm.nih.gov/pubmed/36727470
http://dx.doi.org/10.1093/rheumatology/kead062
_version_ 1785115073084129280
author Burmester, Gerd R
Strand, Vibeke
Kivitz, Alan J
Hu, Chih-Chi
Wang, Sheldon
van Hoogstraten, Hubert
Klier, Gabriella L
Fleischmann, Roy
author_facet Burmester, Gerd R
Strand, Vibeke
Kivitz, Alan J
Hu, Chih-Chi
Wang, Sheldon
van Hoogstraten, Hubert
Klier, Gabriella L
Fleischmann, Roy
author_sort Burmester, Gerd R
collection PubMed
description OBJECTIVE: To evaluate the long-term safety and efficacy of sarilumab with/without conventional synthetic (cs)DMARDs in RA. METHODS: The analyses evaluated two open-label extensions (OLEs): EXTEND and MONARCH OLE, which included patients from six randomized trials. Patients received sarilumab 200 mg once every 2 weeks (q2w) for at least 264 weeks up to 516 weeks (EXTEND: Sarilumab Monotherapy and Sarilumab + csDMARD groups) or for 276 weeks (MONARCH OLE: Continuation and Switch groups). Primary endpoints included safety, immunogenicity and changes in laboratory parameters. Secondary endpoints included clinical signs and symptoms along with health-related quality-of-life (HRQOL) questionnaires. RESULTS: The Sarilumab Monotherapy (n = 111), Continuation (n = 165) and Switch (n = 155) groups received sarilumab monotherapy, while the Sarilumab + csDMARD group (n = 1910) received sarilumab in combination with csDMARDs. Incidence of one or more treatment-emergent adverse events was 126 (Sarilumab Monotherapy group), 169 (Sarilumab + csDMARD group), 159 (Continuation group) and 159 (Switch group) events/100 patient-years. Neutropenia was the most common adverse event. Neutropenia was not associated with an increased incidence of infections. Most neutropenia cases normalized on-treatment. Adverse events of special interests, such as malignancies, major adverse cardiovascular events, venous thromboembolism and gastrointestinal perforations, were rare. Immunogenicity was low and not associated with hypersensitivity reactions or discontinuations due to lack or loss of efficacy. Improvements in clinical signs and symptoms and HRQOL, observed during the initial blinded trials, were maintained throughout the OLE assessment period. CONCLUSIONS: Long-term sarilumab treatment with/without csDMARDs in patients with RA revealed no new safety findings. Efficacy and HRQOL were maintained or further increased over the open-label assessment period. TRIAL REGISTRATION: EXTEND, ClinicalTrials.gov, https://www.clinicaltrials.gov/ct2/show/NCT01146652, NCT01146652; MONARCH OLE, ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02332590, NCT02332590
format Online
Article
Text
id pubmed-10547516
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-105475162023-10-04 Long-term safety and efficacy of sarilumab with or without background csDMARDs in rheumatoid arthritis Burmester, Gerd R Strand, Vibeke Kivitz, Alan J Hu, Chih-Chi Wang, Sheldon van Hoogstraten, Hubert Klier, Gabriella L Fleischmann, Roy Rheumatology (Oxford) Clinical Science OBJECTIVE: To evaluate the long-term safety and efficacy of sarilumab with/without conventional synthetic (cs)DMARDs in RA. METHODS: The analyses evaluated two open-label extensions (OLEs): EXTEND and MONARCH OLE, which included patients from six randomized trials. Patients received sarilumab 200 mg once every 2 weeks (q2w) for at least 264 weeks up to 516 weeks (EXTEND: Sarilumab Monotherapy and Sarilumab + csDMARD groups) or for 276 weeks (MONARCH OLE: Continuation and Switch groups). Primary endpoints included safety, immunogenicity and changes in laboratory parameters. Secondary endpoints included clinical signs and symptoms along with health-related quality-of-life (HRQOL) questionnaires. RESULTS: The Sarilumab Monotherapy (n = 111), Continuation (n = 165) and Switch (n = 155) groups received sarilumab monotherapy, while the Sarilumab + csDMARD group (n = 1910) received sarilumab in combination with csDMARDs. Incidence of one or more treatment-emergent adverse events was 126 (Sarilumab Monotherapy group), 169 (Sarilumab + csDMARD group), 159 (Continuation group) and 159 (Switch group) events/100 patient-years. Neutropenia was the most common adverse event. Neutropenia was not associated with an increased incidence of infections. Most neutropenia cases normalized on-treatment. Adverse events of special interests, such as malignancies, major adverse cardiovascular events, venous thromboembolism and gastrointestinal perforations, were rare. Immunogenicity was low and not associated with hypersensitivity reactions or discontinuations due to lack or loss of efficacy. Improvements in clinical signs and symptoms and HRQOL, observed during the initial blinded trials, were maintained throughout the OLE assessment period. CONCLUSIONS: Long-term sarilumab treatment with/without csDMARDs in patients with RA revealed no new safety findings. Efficacy and HRQOL were maintained or further increased over the open-label assessment period. TRIAL REGISTRATION: EXTEND, ClinicalTrials.gov, https://www.clinicaltrials.gov/ct2/show/NCT01146652, NCT01146652; MONARCH OLE, ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02332590, NCT02332590 Oxford University Press 2023-02-02 /pmc/articles/PMC10547516/ /pubmed/36727470 http://dx.doi.org/10.1093/rheumatology/kead062 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Clinical Science
Burmester, Gerd R
Strand, Vibeke
Kivitz, Alan J
Hu, Chih-Chi
Wang, Sheldon
van Hoogstraten, Hubert
Klier, Gabriella L
Fleischmann, Roy
Long-term safety and efficacy of sarilumab with or without background csDMARDs in rheumatoid arthritis
title Long-term safety and efficacy of sarilumab with or without background csDMARDs in rheumatoid arthritis
title_full Long-term safety and efficacy of sarilumab with or without background csDMARDs in rheumatoid arthritis
title_fullStr Long-term safety and efficacy of sarilumab with or without background csDMARDs in rheumatoid arthritis
title_full_unstemmed Long-term safety and efficacy of sarilumab with or without background csDMARDs in rheumatoid arthritis
title_short Long-term safety and efficacy of sarilumab with or without background csDMARDs in rheumatoid arthritis
title_sort long-term safety and efficacy of sarilumab with or without background csdmards in rheumatoid arthritis
topic Clinical Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10547516/
https://www.ncbi.nlm.nih.gov/pubmed/36727470
http://dx.doi.org/10.1093/rheumatology/kead062
work_keys_str_mv AT burmestergerdr longtermsafetyandefficacyofsarilumabwithorwithoutbackgroundcsdmardsinrheumatoidarthritis
AT strandvibeke longtermsafetyandefficacyofsarilumabwithorwithoutbackgroundcsdmardsinrheumatoidarthritis
AT kivitzalanj longtermsafetyandefficacyofsarilumabwithorwithoutbackgroundcsdmardsinrheumatoidarthritis
AT huchihchi longtermsafetyandefficacyofsarilumabwithorwithoutbackgroundcsdmardsinrheumatoidarthritis
AT wangsheldon longtermsafetyandefficacyofsarilumabwithorwithoutbackgroundcsdmardsinrheumatoidarthritis
AT vanhoogstratenhubert longtermsafetyandefficacyofsarilumabwithorwithoutbackgroundcsdmardsinrheumatoidarthritis
AT kliergabriellal longtermsafetyandefficacyofsarilumabwithorwithoutbackgroundcsdmardsinrheumatoidarthritis
AT fleischmannroy longtermsafetyandefficacyofsarilumabwithorwithoutbackgroundcsdmardsinrheumatoidarthritis