b'theeectsofcurrentlyavailableDMTsonPhysiological factors and non-MS factorsbrain atrophy. (e.g.,dehydration,alcoholconsumption,Brain atrophy is now an endpoint smoking, genetic variation, comorbidities,in many clinical trialsand age) can also decrease brain volume. Brain atrophy is now a recognized endpoint In addition to the available medicationin all Phase III clinical trials for MS. It can be options for treating MS, new modalities thatevaluated using traditional MRI scans; however, act on dierent biologic pathways are alwayslimitations do exist. being developed and improved upon. Thegure below describes the proposed eects of Atrophy accumulates very slowly; therefore, these modalities on brain atrophy in patientslonger follow-up studies (more than two years) with MS.are needed to detect signicant changes.More knowledge on neurodegeneration In the short-term, DMTs that have immuno- is still neededsuppressivepropertiesactuallydecrease In recent years, knowledge about thebrain volume because of the resolution of proposed mechanisms that may be responsibleinammation. This volume loss is not a sign for axonal injury and loss has rapidly increased.of neurodegeneration, because there is no loss A better understanding of the mechanismsof brain volume. This phenomenon (known responsible for neurodegeneration will contributeas pseudo atrophy) can last for up to a year to the development of novel therapies thatafter treatment with immunosuppressant may further delay, eliminate, or even reverseDMTs. neurodegeneration. Injectable Preservation of +ray matter volume inOral DMTs DMTs Infusions Aerobic exercise ri+ht post-central and midline corticalstructuresAuba!io: Protective Copaxone:Possibly Lemtrada: Protective Brutons tyrosine kinasee\x1dect on brain loss e\x1dect on brain volume and white protective e\x1dect on volume inhibitors (i.e., fenebrutinib, No atrophy data have been reportedmatter loss \x1eray matter loss loss in RRMS ibrutinib, evobrutinib)Gilenya: Protective Interferons:Possibly Ocrevus: Protective Brain atrophy increased sharply ine\x1dect on brain loss late protective e\x1dect e\x1dect on brainvolume and \x1eray volume loss in RRMS Cell-based therapies rst two years but decreasedmatter loss in RRMS on brain volume loss and PPMS dramatically after the two-year periodMavenclad: Possibly Tysabri: Protectiveprotective e\x1dect on e\x1dect on brainbrain volume loss in volume loss in RRMS Hi+h-dose biotin No atrophy data have been reportedRRMSMayzent: Protectivee\x1dect on brain Decreased atrophy pro+ression involume loss Ibudilast PPMS and SPMSin RRMSTecdera: Protectivee\x1dect on brainloss volumeLaquinimod Decreased brain volume loss in RRMSin RRMSZeposia: Slowedrateof volume loss,cortical \x1eray matter loss, Lipoic acid Decreased whole brain atrophy in SPMSand thalamic volume Source: Bross et al. Int J Mol Sci. 2020FIGURE: : Eect of currently approved DMTson brain atrophy. FIGURE: Eect of other modalities on brain atrophy.57 msfocusmagazine.org'