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Review
. 2022 Apr 15:13:844873.
doi: 10.3389/fneur.2022.844873. eCollection 2022.

Treatment Challenges in Multiple Sclerosis - A Continued Role for Glatiramer Acetate?

Massimiliano Mirabella  1   2 , Pietro Annovazzi  3 , Wallace Brownlee  4 , Jeffrey A Cohen  5 , Christoph Kleinschnitz  6 , Christian Wolf  7
Affiliations
Review

Treatment Challenges in Multiple Sclerosis - A Continued Role for Glatiramer Acetate?

Massimiliano Mirabella et al. Front Neurol. .

Abstract

Earlier diagnosis, access to disease-modifying therapies (DMTs), and improved supportive care have favorably altered the disease course of multiple sclerosis (MS), leading to an improvement in long-term outcomes for people with MS (PwMS). This success has changed the medical characteristics of the population seen in MS clinics. Comorbidities and the accompanying polypharmacy, immune senescence, and the growing number of approved DMTs make selecting the optimal agent for an individual patient more challenging. Glatiramer acetate (GA), a moderately effective DMT, interacts only minimally with comorbidities, other medications, or immune senescence. We describe here several populations in which GA may represent a useful treatment option to overcome challenges due to advanced age or comorbidities (e.g., hepatic or renal disease, cancer). Further, we weigh GA's potential merits in other settings where PwMS and their neurologists must base treatment decisions on factors other than selecting the most effective DMT, e.g., family planning, conception and pregnancy, or the need for vaccination.

Keywords: comorbidities; disease modifying treatment; glatiramer acetate; multiple sclerosis; special populations.

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Conflict of interest statement

MM received consulting and/or speaking fees, research support or travel grants from Almirall, Bayer Schering, Biogen, CSL Behring, Sanofi-Genzyme, Merck, Novartis, Teva, Roche, Viatris (Mylan). JC received personal compensation for consulting for Biogen, Bristol-Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis, and PSI; speaking for H3 Communications; and serving as an Editor of Multiple Sclerosis Journal. CW is a partner at Lycalis sprl. His organization has received compensation for consulting and speaking from Viatris (Mylan), Merck KAaG, Roche, Immunic, BMS Celgene, Novartis, Teva, Synthon, 2BBB, ICON, and Desitin. WB has received speaker honoraria and/or participated in advisory boards for Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Viatris. PA received honoraria for lecturing and/or participation in advisory boards, and/or travel expenses for attending congresses and meetings from Almirall, Biogen, BMS-Celgene, Merck, Novartis, Roche, Sanofi-Genzyme, Teva Italia, and Viatris. CK received speaker honoraria and/or participated in advisory boards for Alexion, Biogen, Celgene, CSL Behring, Janssen-Cilag, MedDay, Merck, Novartis, Roche, Sanofi Genzyme, Teva and Viatris.

Figures

Figure 1
Figure 1
Anti-inflammatory mechanisms induced by glatiramer acetate (GA). GA treatment on antigen-presenting cells (APCs) leads to anti-inflammatory differentiation. Treatment modulates innate stimuli and is associated with down-regulation of type I interferon (IFN), increased T helper (Th)2, and regulatory T (Treg) cell differentiation. Reactivation of GA-reactive Th2 cells in periphery through presentation of myelin antigens is associated with bystander suppression. Th2 cells also modulate B-cell activation. Treg cells down-regulate secretion of proinflammatory cytokines by effector T (Teff) cells both in periphery and in the CNS. CD8+ T cells are generated by antigen presentation of GA in periphery and migrate to the CNS where they contribute to inhibiting myelin degradation. IL, Interleukin; TNF, tumor necrosis factor; IFNAR, interferon-receptor; MHC, major histocompatibility complex; BDNF, brain-derived neurotrophic factor; IGF, insulin-like growth factor; IDO, indoleamine-2,3-dioxygenase; solid lines, cytokines produced by the representative cells; dashed lines, reduced production of cytokines; red lines, inhibitory cytokines (72). [Figure from Prod92homme and Zamvil (72)].
See this image and copyright information in PMC

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