Multiple sclerosis - Emerging treatments

Ublituximab

Ublituximab, an anti-CD20 monoclonal antibody, is approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of adults with relapsing forms of MS. In two identical, phase 3, double-blind, double-dummy trials, ublituximab was associated with lower relapse rates and fewer brain lesions on MRI than teriflunomide over 96 weeks, but did not result in a significantly lower risk of worsening of disability, in patients with relapsing MS.[163]

Ofatumumab

Ofatumumab, an anti-CD20 monoclonal antibody, is approved by the FDA and EMA for the treatment of adults with relapsing forms of MS. In a phase 2b double-blind study of patients with relapsing-remitting MS, ofatumumab decreased the number of new magnetic resonance imaging (MRI) gadolinium-enhancing lesions 12 weeks after treatment initiation.[164] In two double-blind, double-dummy, phase 3 trials, ofatumumab was associated with lower annualized relapse rates than teriflunomide in patients with relapsing MS.[165]

Other sphingosine 1-phosphate (S1P) receptor modulators

Ozanimod is approved by the FDA and EMA for the treatment of adults with relapsing forms of MS. One randomized, double-blind phase 3 trial reported that ozanimod was well tolerated, and associated with a significantly lower relapse rate compared with interferon beta-1a, in patients with relapsing MS treated for at least 12 months.[166] Ponesimod is also approved by the FDA and the EMA to treat adults with relapsing forms of MS. One randomized, double-blind phase 3 study reported that ponesimod significantly reduced annual relapses compared with teriflunomide in patients with relapsing MS.[167] Other agents at different stages of development include ceralifimod, GSK2018682, and MT-1303.[88][168]

Stem cell therapy

The premise of hematopoietic stem cell transplantation (HSCT) is that the dysregulated, autoreactive immune system of patients with MS could be eradicated and replaced by a new, tolerant one.[169] One meta-analysis concluded that autologous HSCT can induce long-term remission for patients with MS with a high degree of safety; greatest benefit was observed with low- and intermediate-intensity regimens, and for patients with relapsing-remitting MS with the presence of gadolinium-enhancing lesions at baseline MRI.[170] In a preliminary study in patients with relapsing-remitting MS, nonmyeloablative HSCT resulted in prolonged time to disease progression compared with continued disease-modifying therapy.[171] The American Society for Blood and Marrow Transplantation recommends that treatment-refractory relapsing MS with high risk of future disability is considered as a "standard of care, clinical evidence available" indication for autologous HSCT.[172] Other stem cell approaches under investigation include the use of mesenchymal stem cells, placental stem cells, and intrathecal administration.[173][174][175]

Evobrutinib

Evobrutinib is a selective oral inhibitor of Bruton's tyrosine kinase that blocks B-cell activation. One double-blind, randomized, phase 2 trial reported that patients with relapsing MS who received evobrutinib once daily had significantly fewer enhancing lesions during weeks 12 to 24 than those who received placebo. There were no significant differences in annualized relapse rate or disability progression.[176]

Ibudilast

Ibudilast inhibits some cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and Toll-like receptor 4, and can cross the blood–brain barrier. In a phase 2 trial involving patients with primary or secondary progressive MS, ibudilast was associated with slower progression of brain atrophy than placebo.[177] Adverse events reported in patients receiving ibudilast included gastrointestinal symptoms, headache, and depression.

Alpha-lipoic acid

In a single-center, 2-year, double-blind, randomized trial, oral alpha-lipoic acid was associated with a 68% reduction in annualized percent change brain volume, with some suggestion of clinical benefit, in patients with secondary progressive MS. Safety, tolerability, and compliance were favorable.[178]

Deep brain stimulation (DBS)

DBS has been evaluated in MS patients with tremor. Results have been variable, and patients should be selected carefully for consideration of DBS.[179][180]

Dietary approaches

The influence of modifiable lifestyle factors such as diet and exercise on the development and course of MS, and on the quality of life of people with MS, is increasingly recognized.[181][182] Many patients with MS and those who care for them are interested in the effects of diet on MS activity and/or symptoms. Various dietary approaches such as paleolithic, gluten-free, Swank, Wahls, or the Mediterranean diet have been promoted for people with MS. There are currently no high-quality studies to provide sufficient evidence to recommend one approach over another. This is a key area of ongoing research.[183][184] [ ]

Cannabinoids

Cannabinoids may be effective for treating symptoms of spasticity in MS.[185][186][187][188] The College of Family Physicians of Canada recommends that clinicians may consider medical cannabinoids for refractory spasticity in MS, and specifies delta-9-tetrahydrocannabinol/cannabidiol oromucosal spray (also known as nabiximols) as the medical cannabinoid of choice.[189] The National Institute of Health and Care Excellence in England recommends a trial of delta-9-tetrahydrocannabinol/cannabidiol oromucosal spray to treat moderate to severe spasticity in adults with MS in whom other pharmacologic treatments for spasticity are not effective.[190]