Early versus delayed treatment with glatiramer acetate: Analysis of up to 27 years of continuous follow-up in a US open-label extension study

Corey C Ford; Jeffrey A Cohen; Andrew D Goodman; John W Lindsey; Robert P Lisak; Christopher Luzzio; Amy Pruitt; John Rose; Horea Rus; Jerry S Wolinsky; Shaul E Kadosh; Emily Bernstein-Hanlon; Yafit Stark; Jessica K Alexander

doi:10.1177/13524585221094239

Early versus delayed treatment with glatiramer acetate: Analysis of up to 27 years of continuous follow-up in a US open-label extension study

Mult Scler. 2022 Oct;28(11):1729-1743. doi: 10.1177/13524585221094239. Epub 2022 Jun 29.

Authors

Affiliations

¹ Department of Neurology, University of New Mexico Health Sciences Center, The University of New Mexico, Albuquerque, NM, USA.
² Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
³ Department of Neurology, University of Rochester, Rochester, NY, USA.
⁴ Department of Neurology, University of Texas Health Science Center at Houston (UTHouston), Houston, TX, USA.
⁵ Department of Neurology and Department of Biochemistry, Microbiology and Immunology, School of Medicine, Wayne State University, Detroit, MI, USA.
⁶ Departments of Neurology and Engineering, University of Wisconsin-Madison, Madison, WI, USA.
⁷ Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, PA, USA.
⁸ Imaging and Neuroscience Center, School of Medicine, The University of Utah, Salt Lake City, UT, USA.
⁹ Department of Neurology, School of Medicine, University of Maryland, Baltimore, MD, USA.
¹⁰ Innovative Research and Development, Teva Pharmaceuticals, Netanya, Israel.
¹¹ Global Clinical Programming, Teva Pharmaceuticals, Netanya, Israel.
¹² Global Clinical Development, Teva Pharmaceuticals, Netanya, Israel.
¹³ Global Medical Affairs, Teva Pharmaceuticals, West Chester, PA, USA/Jazz Pharmaceuticals, Palo Alto, CA, USA.

Abstract

Background: Glatiramer acetate (GA) is US-approved for relapsing multiple sclerosis.

Objectives: To describe GA long-term clinical profile. To compare effectiveness of early start (ES) versus delayed start (DS; up to 3 years) with GA.

Methods: Phase 3 trial participants entered a randomized placebo-controlled period then an open-label extension (OLE) with GA.

Results: Overall, 208 out of 251 (82.9%) randomized participants entered the OLE; 24 out of 101 (23.8%, ES) and 28 out of 107 (26.2%, DS) participants completed the OLE. Median GA treatment was 9.8 (0.1-26.3) years. Annualized change in Expanded Disability Status Scale (EDSS) score was lower with ES versus DS (p = 0.0858: full study; p = 0.002; Year 5). Participants with improved/stable EDSS was consistently higher with ES versus DS: 40.3% versus 31.6% (p = 0.1590; full study); 70.8% versus 55.6% (p = 0.015; Year 5). ES prolonged time-to-6-month confirmed disease worsening (CDW) versus DS (9.8 vs 6.7 years), time-to-12-month CDW (18.9 vs 11.6 years), and significantly reduced time-to-second-6-month CDW (p = 0.0441). No new safety concerns arose.

Conclusion: GA long-term treatment maintained clinical benefit with a similar safety profile to phase 3 results; a key limitation was that only 25% of participants completed the OLE. Early initiation of GA had sustained benefits versus delayed treatment.

Keywords: Clinical trial; disease-modifying therapies; glatiramer acetate; multiple sclerosis; quality of life; relapsing/remitting.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Follow-Up Studies
Glatiramer Acetate / therapeutic use
Humans
Immunosuppressive Agents / therapeutic use
Multiple Sclerosis* / drug therapy
Multiple Sclerosis, Relapsing-Remitting* / drug therapy
Recurrence
Time-to-Treatment

Substances

Immunosuppressive Agents
Glatiramer Acetate