Next DMTs to come

[frodo]

Ozanimod, laquinimod, BTK inhibitors (fenebrutinib, ibrutinib, and evobrutinib), Ibudilast, Lipoic acid and (maybe) Biotin.

Source:

https://www.mdpi.com/1422-0067/21/12/4312/htm

Emerging Treatments

In addition to the available medication options for treating MS, new drugs that act on different biologic pathways are always being developed and improved upon. Below are medications that were recently approved or are under development.

Ozanimod: A recently FDA- approved selective S1P immunomodulator, not launched yet, showed very promising results in cognition and brain atrophy. In 2 phase III trials (SUNBEAM and RADIANCE) ozanimod slowed the rate of BLV, cortical grey matter, and thalamic volume compared to intramuscular interferon beta-1a [87].

Laquinimod: A novel oral immunomodulatory drug with a complex mechanism of action significantly decreased BVL versus placebo (ALLEGRO trial) and versus interferon beta-1a (BRAVO trial) in RRMS cases [88].

Bruton’s tyrosine kinase (BTK) inhibitors: A class of newer agents, the BTK inhibitors block the activation of B-lymphocytes both in vivo and in vitro [89]. This class includes fenebrutinib, ibrutinib, and evobrutinib; some of them are about to start entering multicenter trials and their effect on axonal integrity is currently unknown. A phase II trial of evobrutinib versus placebo showed a significant reduction in gadolinium-enhancing lesions with a non-significant effect on annualized relapse rate. Data on BVL were not reported [90].

Ibudilast: A phosphodiesterase inhibitor, originally used in asthma. In a phase II trial (SPRINT-MS) with progressive MS (both PPMS and SPMS) patients, it has shown a 48% difference in atrophy progression compared to placebo over 96 weeks [91].

Lipoic acid: A powerful anti-oxidant showed a very high impact on the annualized rate of whole-brain atrophy versus placebo in SPMS patients in a single-center study having BVL as the primary outcome [92].

High dose biotin: A member of the B-complex showed conflicting results in different clinical trials. An open-label pilot study showed reversal of disability at 9 months with a sustainable effect; however, the MRI data were disappointing and consistent with more new or enlarging lesions than the placebo group [93]. In a single-center study with SPMS, the biotin group showed worsening of disability versus placebo, despite stable MRI scans. More results are pending and atrophy data have not been reported as yet [94].

Cell-based therapies: Experimental therapies, with autologous hematopoietic stem cell transplantation (AHSCT) being the most known. AHSCT is in clinical trials and it might be a good option for patients with aggressive RRMS and pronounced inflammation [95]. Early administration and reduction of toxicity are important factors to be addressed before pursuing this therapeutic option [96]. It was observed that brain atrophy increased sharply in the first 2 years after treatment and decreased dramatically after the 2-year time point [97,98,99].

Aerobic exercise: Cardiorespiratory fitness was found to be associated with the preservation of gray matter volumes in the right post-central gyrus and midline cortical structures that are more commonly involved in MS, suggesting a protective role of high-intensity exercise on neurodegeneration [100].