Editing Multiple sclerosis (section)

== Management ==
{{Main|Management of multiple sclerosis}}

Although no cure for multiple sclerosis has been found, several therapies have proven helpful. Several effective treatments can decrease the number of attacks and the rate of progression.<ref name=McGinley2021/> The primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. Starting medications is generally recommended in people after the first attack when more than two lesions are seen on MRI.<ref name=Neurology2018>{{cite journal | vauthors = Rae-Grant A, Day GS, Marrie RA, Rabinstein A, Cree BA, Gronseth GS, Haboubi M, Halper J, Hosey JP, Jones DE, Lisak R, Pelletier D, Potrebic S, Sitcov C, Sommers R, Stachowiak J, Getchius TS, Merillat SA, Pringsheim T | title = Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology | journal = Neurology | volume = 90 | issue = 17 | pages = 777–788 | date = April 2018 | pmid = 29686116 | doi = 10.1212/WNL.0000000000005347 | doi-access = free }}</ref>

The first approved medications used to treat MS were modestly effective, though were poorly tolerated and had many adverse effects.<ref name=NIH2015 /> Several treatment options with better safety and tolerability profiles have been introduced,<ref name=McGinley2021/> improving the prognosis of MS.

As with any medical treatment, medications used in the management of MS have several [[adverse effect (medicine)|adverse effects]]. [[Alternative medicine|Alternative treatments]] are pursued by some people, despite the shortage of supporting evidence of efficacy.

=== Initial management of acute flare ===
During symptomatic attacks, administration of high doses of [[intravenous therapy|intravenous]] [[corticosteroid]]s, such as [[methylprednisolone]], is the usual therapy,<ref name="pmid1897097722"/> with oral corticosteroids seeming to have a similar efficacy and safety profile.<ref>{{cite journal | vauthors = Burton JM, O'Connor PW, Hohol M, Beyene J | title = Oral versus intravenous steroids for treatment of relapses in multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 12 | pages = CD006921 | date = December 2012 | pmid = 23235634 | doi = 10.1002/14651858.CD006921.pub3 }}</ref> Although effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery.<ref>{{cite journal |vauthors=Filippini G, Brusaferri F, Sibley WA, et al. |title=Corticosteroids or ACTH for acute exacerbations in multiple sclerosis |journal=Cochrane Database Syst Rev |issue=4 |pages=CD001331 |year=2000 |volume=2013 |pmid=11034713 |doi=10.1002/14651858.CD001331 |pmc=11391333 }}</ref><ref name="RCOP_acute">{{cite book|author=The National Collaborating Centre for Chronic Conditions|title=Multiple sclerosis: national clinical guideline for diagnosis and management in primary and secondary care|year=2004|publisher=Royal College of Physicians|location=London|isbn=1-86016-182-0|chapter=Treatment of acute episodes|pages=54–58|url=https://www.ncbi.nlm.nih.gov/books/NBK48921/|pmid=21290636|access-date=5 October 2021|archive-date=10 February 2023|archive-url=https://web.archive.org/web/20230210212932/https://www.ncbi.nlm.nih.gov/books/NBK48921/|url-status=live}}</ref> The long-term benefit is unclear in optic neuritis as of 2020.<ref>{{cite journal |vauthors=Petzold A, Braithwaite T, van Oosten BW  |title=Case for a new corticosteroid treatment trial in optic neuritis: review of updated evidence |journal=J. Neurol. Neurosurg. Psychiatry |volume=91 |issue=1 |pages=9–14 |date=January 2020 |pmid=31740484 |pmc=6952848 |doi=10.1136/jnnp-2019-321653 |type= Review}}</ref><ref name="Petzold_2022" /> The consequences of severe attacks that do not respond to corticosteroids might be treatable by [[plasmapheresis]].<ref name="pmid1897097722"/>

=== Chronic management ===
==== Relapsing-remitting multiple sclerosis ====
Multiple [[Management of multiple sclerosis#Disease-modifying treatments|disease-modifying]] medications were approved by regulatory agencies for RRMS; they are modestly effective at decreasing the number of attacks.<ref name=He2016>{{cite journal | vauthors = He D, Zhang C, Zhao X, Zhang Y, Dai Q, Li Y, Chu L | title = Teriflunomide for multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | pages = CD009882 | date = March 2016 | issue = 3 | pmid = 27003123 | doi = 10.1002/14651858.CD009882.pub3 | pmc = 10493042 }}</ref> [[Interferons]]<ref name=Rice2001>{{cite journal |vauthors=Rice GP, Incorvaia B, Munari L, et al. |title=Interferon in relapsing-remitting multiple sclerosis |journal=Cochrane Database Syst Rev |issue=4 |pages=CD002002 |year=2001 |volume=2001 |pmid=11687131 |pmc=7017973 |doi=10.1002/14651858.CD002002 }}</ref> and [[glatiramer acetate]] are first-line treatments<ref name="Tsang20112"/> and are roughly equivalent, reducing relapses by approximately 30%.<ref name=Hassan2011>{{cite journal | vauthors = Hassan-Smith G, Douglas MR | title = Management and prognosis of multiple sclerosis | journal = British Journal of Hospital Medicine | volume = 72 | issue = 11 | pages = M174-6 | date = November 2011 | pmid = 22082979 | doi = 10.12968/hmed.2011.72.Sup11.M174 }}</ref> Early-initiated long-term therapy is safe and improves outcomes.<ref name="pmid21205679">{{cite journal | vauthors = Freedman MS | title = Long-term follow-up of clinical trials of multiple sclerosis therapies | journal = Neurology | volume = 76 | issue = 1 Suppl 1 | pages = S26-34 | date = January 2011 | pmid = 21205679 | doi = 10.1212/WNL.0b013e318205051d | s2cid = 16929304 }}</ref><ref name="pmid22284996">{{cite journal | vauthors = Qizilbash N, Mendez I, Sanchez-de la Rosa R | title = Benefit-risk analysis of glatiramer acetate for relapsing-remitting and clinically isolated syndrome multiple sclerosis | journal = Clinical Therapeutics | volume = 34 | issue = 1 | pages = 159–176.e5 | date = January 2012 | pmid = 22284996 | doi = 10.1016/j.clinthera.2011.12.006 }}</ref>

Treatment of CIS with interferons decreases the chance of progressing to clinical MS.<ref name="pmid1897097722"/><ref name="pmid21205678">{{cite journal | vauthors = Bates D | title = Treatment effects of immunomodulatory therapies at different stages of multiple sclerosis in short-term trials | journal = Neurology | volume = 76 | issue = 1 Suppl 1 | pages = S14-25 | date = January 2011 | pmid = 21205678 | doi = 10.1212/WNL.0b013e3182050388 | s2cid = 362182 }}</ref><ref>{{cite journal |vauthors=Clerico M, Faggiano F, Palace J, et al. |title=Recombinant interferon beta or glatiramer acetate for delaying conversion of the first demyelinating event to multiple sclerosis |journal=Cochrane Database Syst Rev |issue=2 |pages=CD005278 |date=April 2008 |pmid=18425915 |doi=10.1002/14651858.CD005278.pub3}}</ref> Efficacy of interferons and glatiramer acetate in children has been estimated to be roughly equivalent to that of adults.<ref name="pmid22642799">{{cite journal | vauthors = Johnston J, So TY | title = First-line disease-modifying therapies in paediatric multiple sclerosis: a comprehensive overview | journal = Drugs | volume = 72 | issue = 9 | pages = 1195–211 | date = June 2012 | pmid = 22642799 | doi = 10.2165/11634010-000000000-00000 | s2cid = 20323687 }}</ref> The role of some newer agents such as [[fingolimod]],<ref name=LaMantia2016>{{cite journal |vauthors=La Mantia L, Tramacere I, Firwana B, et al. |title=Fingolimod for relapsing-remitting multiple sclerosis |journal=Cochrane Database Syst Rev |volume=2016 |pages=CD009371 |date=April 2016 |issue=4 |pmid=27091121 |doi=10.1002/14651858.CD009371.pub2 |pmc=10401910 }}</ref> [[teriflunomide]], and [[dimethyl fumarate]],<ref name=Xu2015>{{cite journal |vauthors=Xu Z, Zhang F, Sun F, et al. |title=Dimethyl fumarate for multiple sclerosis |journal=Cochrane Database Syst Rev |issue=4 |pages=CD011076 |date=April 2015 |volume=2015 |pmid=25900414 |doi=10.1002/14651858.CD011076.pub2 |pmc=10663978 }}</ref> is not yet entirely clear.<ref name="pmid22014437" /> Making firm conclusions about the best treatment is difficult, especially regarding the long‐term benefit and safety of early treatment, given the lack of studies directly comparing disease-modifying therapies or long-term monitoring of patient outcomes.<ref>{{cite journal |vauthors=Filippini G, Del Giovane C, Clerico M, et al. |title=Treatment with disease-modifying drugs for people with a first clinical attack suggestive of multiple sclerosis |journal=Cochrane Database Syst Rev |volume=2017 |pages=CD012200 |date=April 2017 |issue=4 |pmid=28440858 |pmc=6478290 |doi=10.1002/14651858.CD012200.pub2 }}</ref>

The relative effectiveness of different treatments is unclear, as most have only been compared to placebo or a small number of other therapies.<ref name=Filippini2013>{{cite journal |vauthors=Filippini G, Del Giovane C, Vacchi L, et al. |title=Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis |journal=Cochrane Database Syst Rev |issue=6 |pages=CD008933 |date=June 2013 |pmid=23744561 |doi=10.1002/14651858.CD008933.pub2 |pmc=11627144 }}</ref> Direct comparisons of interferons and glatiramer acetate indicate similar effects or only small differences in effects on relapse rate, disease progression, and MRI measures.<ref>{{cite journal |vauthors=La Mantia L, Di Pietrantonj C, Rovaris M, et al |title=Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis |journal=Cochrane Database Syst Rev |volume=2016 |pages=CD009333 |date=November 2016 |issue=11 |pmid=27880972 |pmc=6464642 |doi=10.1002/14651858.CD009333.pub3}}</ref> There is high confidence that [[natalizumab]], [[cladribine]], or [[alemtuzumab]] are decreasing relapses over two years for people with RRMS.<ref name="Tramacere2015">{{cite journal |vauthors=Gonzalez-Lorenzo M, Ridley B, Minozzi S, Del Giovane C, Peryer G, Piggott T, Foschi M, Filippini G, Tramacere I, Baldin E, Nonino F |date=January 2024 |title=Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis |journal=Cochrane Database Syst Rev |volume= 2024|issue= 1|pages= CD011381|doi=10.1002/14651858.CD011381.pub3 |pmc= 10765473|pmid=38174776 |hdl-access=}}</ref> Natalizumab and [[interferon beta-1a]] ([[Interferon beta-1a#Brand names|Rebif]]) may reduce relapses compared to both placebo and interferon beta-1a (Avonex) while [[Interferon beta-1b]] ([[Interferon beta-1b#Commercial formulations|Betaseron]]), glatiramer acetate, and [[mitoxantrone]] may also prevent relapses.<ref name=Filippini2013 /> Evidence on relative effectiveness in reducing disability progression is unclear.<ref name=Filippini2013 /> There is moderate confidence that a two-year treatment with natalizumab slows disability progression for people with RRMS.<ref name=Tramacere2015 /> All medications are associated with adverse effects that may influence their risk-to-benefit profiles.<ref name=Filippini2013 /><ref name=Tramacere2015 />

[[Ublituximab]] was approved for medical use in the United States in December 2022.<ref>{{cite press release | title=TG Therapeutics Announces FDA Approval of Briumvi (ublituximab-xiiy) | publisher=TG Therapeutics | via=GlobeNewswire | date=28 December 2022 | url=https://www.globenewswire.com/news-release/2022/12/28/2580377/8790/en/TG-Therapeutics-Announces-FDA-Approval-of-BRIUMVI-ublituximab-xiiy.html | access-date=29 December 2022 | archive-date=28 December 2022 | archive-url=https://web.archive.org/web/20221228194153/https://www.globenewswire.com/news-release/2022/12/28/2580377/8790/en/TG-Therapeutics-Announces-FDA-Approval-of-BRIUMVI-ublituximab-xiiy.html | url-status=live }}</ref>

=== Medications ===

Overview of medications available for MS.<ref name="MSTrust">{{Cite web|date=2023-12-03|title=MS Decisions aid|url=https://mstrust.org.uk/information-support/ms-drugs-treatments/ms-decisions-aid|access-date=2023-12-03|location=Letchworth Garden City, United Kingdom|publisher=Multiple Sclerosis Trust|language=en|archive-date=3 December 2023|archive-url=https://web.archive.org/web/20231203213822/https://mstrust.org.uk/information-support/ms-drugs-treatments/ms-decisions-aid|url-status=live}}</ref>

{| class="wikitable"
! Medication
! Compound
! Producer
! Use
! Efficacy (annualized relapse reduction rate)
! Annualized relapse rate (ARR)
|-
| Avonex
| [[Interferon beta-1a]]
| [[Biogen]]
| [[Intramuscular injection|Intramuscular]]
| 30%
| 0.25
|-
| Rebif
| [[Interferon beta-1a]]
| [[Merck Serono]]
| [[Subcutaneous administration|Subcutaneous]]
| 30%
| 0.256
|-
| Extavia
| [[Interferon beta-1b]]
| [[Bayer Schering]]
| [[Subcutaneous administration|Subcutaneous]]
| 30%
| 0.256
|-
| Copaxone
| [[Glatiramer acetate]]
| [[Teva Pharmaceuticals]]
| [[Subcutaneous administration|Subcutaneous]]
| 30%
| 0.3
|-
| Aubagio
| [[Teriflunomide]]
| [[Genzyme]]
| [[Oral administration|Oral]]
| 30%
| 0.35
|-
| Plegridy
| [[Interferon beta-1a]]
| Biogen
| [[Subcutaneous administration|Subcutaneous]]
| 30%
| 0.12
|-
| Tecfidera
| [[Dimethyl fumarate]]
| Biogen
| [[Oral administration|Oral]]
| 50%
| 0.15
|-
| Vumerity
| [[Diroximel fumarate]]
| Biogen
| [[Oral administration|Oral]]
| 50%
| 0.11-0.15
|-
| Gilenya
| [[Fingolimod]]
|
| [[Oral administration|Oral]]
| 50%
| 0.22-0.25
|-
| Zeposia
| [[Ozanimod]]
| {{Better source needed|date=November 2023}}
| [[Oral administration|Oral]]
|
| 0.18-0.24
|-
| Kesimpta
| [[Ofatumumab]]
|
| [[Subcutaneous administration|Subcutaneous]]
| 70%
| 0.09-0.14
|-
| Mavenclad
| [[Cladribine]]
|
| [[Oral administration|Oral]]
| 70%
| 0.1-0.14
|-
| Lemtrada
| [[Alemtuzumab]]
|
| [[Intravenous therapy|Intravenous]]
| 70%
| 0.08
|-
| Ocrevus
| [[Ocrelizumab]]
|
| [[Intravenous therapy|Intravenous]]
| 70%
| 0.09
|-
| Ocrevus Zunovo
| [[Ocrelizumab/hyaluronidase]]
|
| [[Subcutaneous administration|Subcutaneous]]
|
|
|-

|}

==== Progressive multiple sclerosis ====
In 2011, mitoxantrone was the first medication approved for secondary progressive MS.<ref name="BopeKellerman2011">{{cite book | vauthors = Keegan BM | chapter = Multiple Sclerosis | veditors = Bope ET, Kellerman RD |title=Conn's Current Therapy 2012: Expert Consult – Online and Print|chapter-url=https://books.google.com/books?id=pyKjGU5JdqQC&pg=PT662|date=22 December 2011|publisher=Elsevier Health Sciences|isbn=978-1-4557-0738-6|pages=626 }}</ref> In this population, tentative evidence supports mitoxantrone moderately slowing the progression of the disease and decreasing rates of relapses over two years.<ref name="CochMit2013">{{cite journal | vauthors = Martinelli Boneschi F, Vacchi L, Rovaris M, Capra R, Comi G | title = Mitoxantrone for multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 5 | issue = 5 | pages = CD002127 | date = May 2013 | pmid = 23728638 | doi = 10.1002/14651858.CD002127.pub3 | pmc = 11745300 | hdl = 2434/533488 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Marriott JJ, Miyasaki JM, Gronseth G, O'Connor PW | title = Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology | journal = Neurology | volume = 74 | issue = 18 | pages = 1463–70 | date = May 2010 | pmid = 20439849 | pmc = 2871006 | doi = 10.1212/WNL.0b013e3181dc1ae0 }}</ref>

New approved medications continue to emerge. In March 2017, the FDA approved ocrelizumab as a treatment for primary progressive MS in adults, the first drug to gain that approval,<ref name="pmid31598138">{{cite journal | vauthors = Faissner S, Gold R | title = Progressive multiple sclerosis: latest therapeutic developments and future directions | journal = Therapeutic Advances in Neurological Disorders | volume = 12 | pages = 1756286419878323 | year = 2019 | pmid = 31598138 | pmc = 6764045 | doi = 10.1177/1756286419878323 | doi-access = free }}</ref><ref name="STATapproval">{{cite news |title=After 40-year odyssey, first drug for aggressive MS wins FDA approval |url=https://www.statnews.com/2017/03/28/multiple-sclerosis-ms-drug-ocrelizumab/ |date=28 March 2017 | vauthors = Winslow R |publisher=STAT |url-status=live |archive-url=https://web.archive.org/web/20170401151407/https://www.statnews.com/2017/03/28/multiple-sclerosis-ms-drug-ocrelizumab/ |archive-date=1 April 2017 }}</ref><ref name="Ocrevus FDA label">{{cite web | title=Ocrevus- ocrelizumab injection | website=DailyMed | date=13 December 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9da42362-3bb5-4b83-b4bb-b59fd4e55f0d | access-date=26 March 2020 | archive-date=27 June 2020 | archive-url=https://web.archive.org/web/20200627100425/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9da42362-3bb5-4b83-b4bb-b59fd4e55f0d | url-status=live }}</ref> with requirements for several [[Phases of clinical research#Phase IV|Phase IV]] clinical trials.<ref name="FDABLAapproval">{{cite web|title=BLA Approval Letter|url=https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/761053Orig1s000ltr.pdf|publisher=FDA|date=28 March 2017|url-status=dead|archive-url=https://web.archive.org/web/20170402081250/https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/761053Orig1s000ltr.pdf|archive-date=2 April 2017}}</ref> It is also used for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults.<ref name="Ocrevus FDA label" /> According to a 2021 [[Cochrane review]], ocrelizumab may reduce worsening of symptoms for primary progressive MS and probably increases unwanted effects but makes little or no difference to the number of serious unwanted effects.<ref>{{cite journal | vauthors = Lin M, Zhang J, Zhang Y, Luo J, Shi S | title = Ocrelizumab for multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 2022 | issue = 5 | pages = CD013247 | date = May 2022 | pmid = 35583174 | pmc = 9115862 | doi = 10.1002/14651858.CD013247.pub2 | collaboration = Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group }}</ref>

In 2019, [[siponimod]] and [[cladribine]] were approved in the United States for the treatment of secondary progressive multiple sclerosis (SPMS).<ref name="pmid31598138" /> Subsequently, [[ozanimod]] was approved in 2020, and [[ponesimod]] was approved in 2021, which were both approved for management of CIS, relapsing MS, and SPMS in the U.S., and RRMS in Europe.<ref>{{Cite book | vauthors = Penner IK, Schreiber H | chapter = Disease Modifying Immunotherapies and Fatigue | veditors = Penner IK |title=Fatigue in Multiple Sclerosis |publisher=Springer, Cham |year=2023 |isbn=978-3-031-13498-2 | pages = 161–177 }}</ref>

[[Ocrelizumab/hyaluronidase]] was approved for medical use in the United States in September 2024.<ref>{{cite press release | title=FDA Approves Ocrevus Zunovo as the First and Only Twice-A-Year 10-Minute Subcutaneous Injection for People With Relapsing and Progressive Multiple Sclerosis | website=Genentech | date=13 September 2024 | url=https://www.gene.com/media/press-releases/15036/2024-09-13/fda-approves-ocrevus-zunovo-as-the-first | access-date=13 September 2024 | archive-date=14 September 2024 | archive-url=https://web.archive.org/web/20240914061044/https://www.gene.com/media/press-releases/15036/2024-09-13/fda-approves-ocrevus-zunovo-as-the-first | url-status=live }}</ref><ref>{{cite press release | title=Halozyme Announces FDA Approval of Roche's Subcutaneous Ocrevus Zunovo with Enhanze for People with Relapsing and Primary Progressive Multiple Sclerosis | publisher=Halozyme Therapeutics | via=PR Newswire | date=13 September 2024 | url=https://www.prnewswire.com/news-releases/halozyme-announces-fda-approval-of-roches-subcutaneous-ocrevus-zunovo-with-enhanze-for-people-with-relapsing-and-primary-progressive-multiple-sclerosis-302247928.html | access-date=13 September 2024 | archive-date=14 September 2024 | archive-url=https://web.archive.org/web/20240914061013/https://www.prnewswire.com/news-releases/halozyme-announces-fda-approval-of-roches-subcutaneous-ocrevus-zunovo-with-enhanze-for-people-with-relapsing-and-primary-progressive-multiple-sclerosis-302247928.html | url-status=live }}</ref>

==== Adverse effects ====
[[File:Copaxone Injection Site Reaction.JPG|thumb|Irritation zone after injection of glatiramer acetate]]
The [[disease-modifying treatment]]s have several adverse effects. One of the most common is irritation at the injection site for glatiramer acetate and the interferons (up to 90% with subcutaneous injections and 33% with intramuscular injections).<ref name=Rice2001 /><ref name=Balak2012>{{cite journal | vauthors = Balak DM, Hengstman GJ, Çakmak A, Thio HB | title = Cutaneous adverse events associated with disease-modifying treatment in multiple sclerosis: a systematic review | journal = Multiple Sclerosis | volume = 18 | issue = 12 | pages = 1705–17 | date = December 2012 | pmid = 22371220 | doi = 10.1177/1352458512438239 | hdl = 1765/73097 | hdl-access = free }}</ref> Over time, a visible dent at the injection site, due to the local destruction of fat tissue, known as [[lipoatrophy]], may develop.<ref name=Balak2012 /> Interferons may produce [[flu-like symptoms]];<ref name="pmid17131933">{{cite journal | vauthors = Sládková T, Kostolanský F | title = The role of cytokines in the immune response to influenza A virus infection | journal = Acta Virologica | volume = 50 | issue = 3 | pages = 151–62 | year = 2006 | pmid = 17131933 }}</ref> some people taking glatiramer experience a post-injection reaction with flushing, chest tightness, heart palpitations, and anxiety, which usually lasts less than thirty minutes.<ref>{{cite journal | vauthors = La Mantia L, Munari LM, Lovati R | title = Glatiramer acetate for multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD004678 | date = May 2010 | pmid = 20464733 | doi = 10.1002/14651858.CD004678.pub2 }}</ref> More dangerous but much less common are [[hepatotoxicity|liver damage]] from interferons,<ref name="pmid15592724">{{cite journal | vauthors = Tremlett H, Oger J | title = Hepatic injury, liver monitoring and the beta-interferons for multiple sclerosis | journal = Journal of Neurology | volume = 251 | issue = 11 | pages = 1297–303 | date = November 2004 | pmid = 15592724 | doi = 10.1007/s00415-004-0619-5 | s2cid = 12529733 }}</ref> [[systolic dysfunction]] (12%), [[infertility]], and [[acute myeloid leukemia]] (0.8%) from mitoxantrone,<ref name=CochMit2013 /><ref name="pmid19882365">{{cite journal | vauthors = Comi G | title = Treatment of multiple sclerosis: role of natalizumab | journal = Neurological Sciences | volume = 30 | issue = S2 | pages = S155-8 | date = October 2009 | pmid = 19882365 | doi = 10.1007/s10072-009-0147-2 | series = 30 | s2cid = 25910077 }}</ref> and [[progressive multifocal leukoencephalopathy]] occurring with natalizumab (occurring in 1 in 600 people treated).<ref name="Tsang20112"/><ref>{{cite journal | vauthors = Hunt D, Giovannoni G | title = Natalizumab-associated progressive multifocal leucoencephalopathy: a practical approach to risk profiling and monitoring | journal = Practical Neurology | volume = 12 | issue = 1 | pages = 25–35 | date = February 2012 | pmid = 22258169 | doi = 10.1136/practneurol-2011-000092 | s2cid = 46326042 }}</ref>

Fingolimod may give rise to [[hypertension]] and [[bradycardia|slowed heart rate]], [[macular edema]], elevated liver enzymes, or a [[lymphopenia|reduction in lymphocyte levels]].<ref name=LaMantia2016 /><ref name="pmid22014437">{{cite journal | vauthors = Killestein J, Rudick RA, Polman CH | title = Oral treatment for multiple sclerosis | journal = The Lancet. Neurology | volume = 10 | issue = 11 | pages = 1026–34 | date = November 2011 | pmid = 22014437 | doi = 10.1016/S1474-4422(11)70228-9 | s2cid = 206160178 }}</ref> Tentative evidence supports the short-term safety of teriflunomide, with common side effects including headaches, fatigue, nausea, hair loss, and limb pain.<ref name=He2016 /> There have also been reports of liver failure and PML with its use and it is [[Teratology|dangerous for fetal development]].<ref name="pmid22014437" /> Most common side effects of dimethyl fumarate are flushing and gastrointestinal problems.<ref name=Xu2015 /><ref name=fumarate>{{cite press release|url=http://www.biogenidec.com/press_release_details.aspx?ID=5981&ReqId=1801165|title=Biogen Idec's TECFIDERA™ (Dimethyl Fumarate) Approved in US as a First-Line Oral Treatment for Multiple Sclerosis|publisher=Biogen Idec|date=27 March 2013|access-date=4 June 2013|url-status=dead|archive-url=https://web.archive.org/web/20130512021453/http://www.biogenidec.com/press_release_details.aspx?ID=5981&ReqId=1801165|archive-date=12 May 2013}}</ref><ref name="pmid22014437" /> While dimethyl fumarate may lead to a [[neutropenia|reduction in the white blood cell count]] there were no reported cases of opportunistic infections during trials.<ref name=fumarateNDA>{{cite web |title=NDA 204063 – FDA Approved Labeling Text |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204063lbl.pdf |date=27 March 2013 |access-date=5 April 2013 |publisher=US Food and Drug Agency |url-status=live |archive-url=https://web.archive.org/web/20131004220910/http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204063lbl.pdf |archive-date=4 October 2013 }}<br />{{cite web |title=NDA Approval |date=27 March 2013 |url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2013/204063Orig1s000ltr.pdf |access-date=5 April 2013 |publisher=US Food and Drug Agency |url-status=dead |archive-url=https://web.archive.org/web/20131004220451/http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2013/204063Orig1s000ltr.pdf |archive-date=4 October 2013 }}</ref>

=== Associated symptoms ===
Both medications and neurorehabilitation have been shown to improve some symptoms, though neither changes the course of the disease.<ref name="pmid16168933">{{cite journal | vauthors = Kesselring J, Beer S | title = Symptomatic therapy and neurorehabilitation in multiple sclerosis | journal = The Lancet. Neurology | volume = 4 | issue = 10 | pages = 643–52 | date = October 2005 | pmid = 16168933 | doi = 10.1016/S1474-4422(05)70193-9 | s2cid = 28253186 }}</ref> Some symptoms have a good response to medication, such as bladder [[spasticity]], while others are little changed.<ref name="pmid1897097722"/> Equipment such as [[catheter]]s for [[neurogenic bladder dysfunction]] or mobility aids can help improve functional status.

A [[multidisciplinary]] approach is important for improving quality of life; however, it is difficult to specify a 'core team' as many health services may be needed at different points in time.<ref name="pmid1897097722"/> Multidisciplinary rehabilitation programs increase activity and participation of people with MS but do not influence impairment level.<ref name="pmid17443610">{{cite journal | vauthors = Khan F, Turner-Stokes L, Ng L, Kilpatrick T | title = Multidisciplinary rehabilitation for adults with multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD006036 | date = April 2007 | volume = 2011 | pmid = 17443610 | doi = 10.1002/14651858.CD006036.pub2 | pmc = 8992048 | veditors = Khan F }}</ref> Studies investigating information provision in support of patient understanding and participation suggest that while interventions (written information, decision aids, coaching, educational programmes) may increase knowledge, the evidence of an effect on decision making and quality of life is mixed and low certainty.<ref>{{cite journal | vauthors = Köpke S, Solari A, Rahn A, Khan F, Heesen C, Giordano A | title = Information provision for people with multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | pages = CD008757 | date = October 2018 | issue = 10 | pmid = 30317542 | pmc = 6517040 | doi = 10.1002/14651858.CD008757.pub3 }}</ref> There is limited evidence for the overall efficacy of individual therapeutic disciplines,<ref name="pmid15859525">{{cite journal | vauthors = Steultjens EM, Dekker J, Bouter LM, Leemrijse CJ, van den Ende CH | title = Evidence of the efficacy of occupational therapy in different conditions: an overview of systematic reviews | journal = Clinical Rehabilitation | volume = 19 | issue = 3 | pages = 247–54 | date = May 2005 | pmid = 15859525 | doi = 10.1191/0269215505cr870oa | hdl = 1871/26505 | url = https://research.vu.nl/en/publications/6f3a1a11-d73e-42e6-a372-79aa1a265df3 }}</ref><ref name="pmid12917976">{{cite journal | vauthors = Steultjens EM, Dekker J, Bouter LM, Cardol M, Van de Nes JC, Van den Ende CH | title = Occupational therapy for multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD003608 | year = 2003 | volume = 2010 | pmid = 12917976 | doi = 10.1002/14651858.CD003608 | pmc = 9022193 | veditors = Steultjens EE }}</ref> though there is good evidence that specific approaches, such as exercise,<ref>{{cite journal | vauthors = Amatya B, Khan F, Galea M | title = Rehabilitation for people with multiple sclerosis: an overview of Cochrane Reviews | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD012732 | date = January 2019 | issue = 1 | pmid = 30637728 | pmc = 6353175 | doi = 10.1002/14651858.CD012732.pub2 }}</ref><ref>{{cite journal | vauthors = Heine M, van de Port I, Rietberg MB, van Wegen EE, Kwakkel G | title = Exercise therapy for fatigue in multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | issue = 9 | pages = CD009956 | date = September 2015 | volume = 2015 | pmid = 26358158 | doi = 10.1002/14651858.CD009956.pub2 | pmc = 9554249 }}</ref><ref name="pmid17482708">{{cite journal | vauthors = Gallien P, Nicolas B, Robineau S, Pétrilli S, Houedakor J, Durufle A | title = Physical training and multiple sclerosis | journal = Annales de Réadaptation et de Médecine Physique | volume = 50 | issue = 6 | pages = 373–6, 369–72 | date = July 2007 | pmid = 17482708 | doi = 10.1016/j.annrmp.2007.04.004 }}</ref><ref>{{cite journal | vauthors = Rietberg MB, Brooks D, Uitdehaag BM, Kwakkel G | title = Exercise therapy for multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD003980 | date = January 2005 | volume = 2005 | pmid = 15674920 | pmc = 6485797 | doi = 10.1002/14651858.CD003980.pub2 | veditors = Kwakkel G }}</ref> and psychological therapies are effective.<ref>{{cite journal | vauthors = Thomas PW, Thomas S, Hillier C, Galvin K, Baker R | title = Psychological interventions for multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD004431 | date = January 2006 | volume = 2010 | pmid = 16437487 | doi = 10.1002/14651858.CD004431.pub2 | veditors = Thomas PW | pmc = 8406851 }}</ref> Cognitive training, alone or combined with other neuropsychological interventions, may show positive effects for memory and attention though firm conclusions are not possible given small sample numbers, variable methodology, interventions and outcome measures.<ref>{{cite journal | vauthors = Rosti-Otajärvi EM, Hämäläinen PI | title = Neuropsychological rehabilitation for multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD009131 | date = February 2014 | volume = 2014 | pmid = 24515630 | doi = 10.1002/14651858.CD009131.pub3 | pmc = 10966661 }}</ref> The effectiveness of [[Palliative care|palliative approaches]] in addition to standard care is uncertain, due to lack of evidence.<ref>{{cite journal | vauthors = Latorraca CO, Martimbianco AL, Pachito DV, Torloni MR, Pacheco RL, Pereira JG, Riera R | title = Palliative care interventions for people with multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | pages = CD012936 | date = October 2019 | issue = 10 | pmid = 31637711 | pmc = 6803560 | doi = 10.1002/14651858.CD012936.pub2 }}</ref> The effectiveness of interventions, including exercise, specifically for the prevention of falls in people with MS is uncertain, while there is some evidence of an effect on balance function and mobility.<ref>{{cite journal | vauthors = Hayes S, Galvin R, Kennedy C, Finlayson M, McGuigan C, Walsh CD, Coote S | title = Interventions for preventing falls in people with multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | pages = CD012475 | date = November 2019 | issue = 11 | pmid = 31778221 | pmc = 6953359 | doi = 10.1002/14651858.CD012475.pub2 }}</ref> [[Cognitive behavioral therapy]] has shown to be moderately effective for reducing MS fatigue.<ref>{{cite journal | vauthors = van den Akker LE, Beckerman H, Collette EH, Eijssen IC, Dekker J, de Groot V | title = Effectiveness of cognitive behavioral therapy for the treatment of fatigue in patients with multiple sclerosis: A systematic review and meta-analysis | journal = Journal of Psychosomatic Research | volume = 90 | pages = 33–42 | date = November 2016 | pmid = 27772557 | doi = 10.1016/j.jpsychores.2016.09.002 }}</ref> The evidence for the effectiveness of non-pharmacological interventions for chronic pain is insufficient to recommend such interventions alone, however their use in combination with medications may be reasonable.<ref>{{cite journal | vauthors = Amatya B, Young J, Khan F | title = Non-pharmacological interventions for chronic pain in multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 12 | pages = CD012622 | date = December 2018 | issue = 12 | pmid = 30567012 | pmc = 6516893 | doi = 10.1002/14651858.CD012622.pub2 | doi-access = free }}</ref>

=== Non-pharmaceutical ===

There is some evidence that [[aquatic therapy]] is a beneficial intervention.<ref>{{cite journal |vauthors=Corvillo I, Varela E, Armijo F, Alvarez-Badillo A, Armijo O, Maraver F |title=Efficacy of aquatic therapy for multiple sclerosis: a systematic review |journal=Eur J Phys Rehabil Med |volume=53 |issue=6 |pages=944–952 |date=December 2017 |pmid=28215060 |doi=10.23736/S1973-9087.17.04570-1 |type=Review}}</ref>

The spasticity associated with MS can be difficult to manage because of the progressive and fluctuating course of the disease.<ref>{{cite journal |vauthors=Khan F, Amatya B, Bensmail D, Yelnik A |title=Non-pharmacological interventions for spasticity in adults: An overview of systematic reviews |journal=Ann Phys Rehabil Med |volume=62 |issue=4 |pages=265–273 |date=July 2019 |pmid=29042299 |doi=10.1016/j.rehab.2017.10.001 |s2cid=207497395 |doi-access=free }}</ref> Although there is no firm conclusion on the efficacy in reducing spasticity, PT interventions can be a safe and beneficial option for patients with multiple sclerosis. Physical therapy including vibration interventions, electrical stimulation, exercise therapy, standing therapy, and radial shock wave therapy (RSWT), were beneficial for limiting spasticity, helping limit excitability, or increasing range of motion.<ref>{{cite journal |vauthors=Etoom M, Khraiwesh Y, Lena F, et al |title=Effectiveness of Physiotherapy Interventions on Spasticity in People With Multiple Sclerosis: A Systematic Review and Meta-Analysis |journal=Am J Phys Med Rehabil |volume=97 |issue=11 |pages=793–807 |date=November 2018 |pmid=29794531 |doi=10.1097/PHM.0000000000000970 |s2cid=44156766 }}</ref>

=== Alternative treatments ===
Over 50% of people with MS may use [[complementary and alternative medicine]], although percentages vary depending on how alternative medicine is defined.<ref name="pmid16420779">{{cite journal |vauthors=Huntley A |date=January 2006 |title=A review of the evidence for efficacy of complementary and alternative medicines in MS |journal=International MS Journal |volume=13 |issue=1 |pages=5–12, 4 |pmid=16420779}}</ref> Regarding the characteristics of users, they are more frequently women, have had MS for a longer time, tend to be more disabled and have lower levels of satisfaction with conventional healthcare.<ref name="pmid16420779" /> The evidence for the effectiveness for such treatments in most cases is weak or absent.<ref name="pmid16420779" /><ref name="pmid19222053">{{cite journal|vauthors=Olsen SA|year=2009|title=A review of complementary and alternative medicine (CAM) by people with multiple sclerosis|journal=Occupational Therapy International|volume=16|issue=1|pages=57–70|doi=10.1002/oti.266|pmid=19222053}}</ref> Treatments of unproven benefit used by people with MS include dietary supplementation and regimens,<ref name="pmid16420779" /><ref>{{cite journal | vauthors = Parks NE, Jackson-Tarlton CS, Vacchi L, Merdad R, Johnston BC | title = Dietary interventions for multiple sclerosis-related outcomes | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | pages = CD004192 | date = May 2020 | issue = 5 | pmid = 32428983 | doi = 10.1002/14651858.CD004192.pub4 | pmc = 7388136 }}</ref><ref name="pmid21965673">{{cite journal | vauthors = Grigorian A, Araujo L, Naidu NN, Place DJ, Choudhury B, Demetriou M | title = N-acetylglucosamine inhibits T-helper 1 (Th1)/T-helper 17 (Th17) cell responses and treats experimental autoimmune encephalomyelitis | journal = The Journal of Biological Chemistry | volume = 286 | issue = 46 | pages = 40133–41 | date = November 2011 | pmid = 21965673 | pmc = 3220534 | doi = 10.1074/jbc.M111.277814 | doi-access = free }}</ref> [[vitamin D]],<ref>{{cite journal | vauthors = Pozuelo-Moyano B, Benito-León J, Mitchell AJ, Hernández-Gallego J | title = A systematic review of randomized, double-blind, placebo-controlled trials examining the clinical efficacy of vitamin D in multiple sclerosis | journal = Neuroepidemiology | volume = 40 | issue = 3 | pages = 147–53 | year = 2013 | pmid = 23257784 | pmc = 3649517 | doi = 10.1159/000345122 | type = Systematic review | quote = the available evidence substantiates neither clinically significant benefit nor harm from vitamin D in the treatment of patients with MS }}</ref> [[relaxation technique]]s such as [[yoga as exercise|yoga]],<ref name="pmid16420779" /> [[herbal medicine]] (including [[medical cannabis]]),<ref name="pmid16420779" /><ref>{{cite journal | vauthors = Chong MS, Wolff K, Wise K, Tanton C, Winstock A, Silber E | title = Cannabis use in patients with multiple sclerosis | journal = Multiple Sclerosis | volume = 12 | issue = 5 | pages = 646–51 | date = October 2006 | pmid = 17086912 | doi = 10.1177/1352458506070947 | s2cid = 34692470 }}</ref><ref>{{cite journal | vauthors = Torres-Moreno MC, Papaseit E, Torrens M, Farré M | title = Assessment of Efficacy and Tolerability of Medicinal Cannabinoids in Patients With Multiple Sclerosis: A Systematic Review and Meta-analysis | journal = JAMA Network Open | volume = 1 | issue = 6 | pages = e183485 | date = October 2018 | pmid = 30646241 | pmc = 6324456 | doi = 10.1001/jamanetworkopen.2018.3485 }}</ref> [[hyperbaric oxygen therapy]],<ref name="pmid14974004">{{cite journal | vauthors = Bennett M, Heard R | title = Hyperbaric oxygen therapy for multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD003057 | year = 2004 | volume = 2011 | pmid = 14974004 | doi = 10.1002/14651858.CD003057.pub2 | veditors = Bennett MH | pmc = 8407327 }}</ref> [[helminthic therapy|self-infection with hookworms]], [[reflexology]], [[acupuncture]],<ref name="pmid16420779" /><ref>{{cite news | vauthors = Adams T | title=Gut instinct: the miracle of the parasitic hookworm | url=https://www.theguardian.com/lifeandstyle/2010/may/23/parasitic-hookworm-jasper-lawrence-tim-adams | newspaper=The Observer | date=23 May 2010 | url-status=live | archive-url= https://web.archive.org/web/20141024051021/http://www.theguardian.com/lifeandstyle/2010/may/23/parasitic-hookworm-jasper-lawrence-tim-adams | archive-date=24 October 2014 | df=dmy-all }}</ref> and [[mindfulness]].<ref>{{cite journal | vauthors = Simpson R, Booth J, Lawrence M, Byrne S, Mair F, Mercer S | title = Mindfulness based interventions in multiple sclerosis—a systematic review | journal = BMC Neurology | volume = 14 | pages = 15 | date = January 2014 | pmid = 24438384 | pmc = 3900731 | doi = 10.1186/1471-2377-14-15 | doi-access = free }}</ref> Evidence suggests vitamin D supplementation, irrespective of the form and dose, provides no benefit for people with MS; this includes for measures such as relapse recurrence, disability, and MRI lesions while effects on health‐related quality of life and fatigue are unclear.<ref>{{cite journal | vauthors = Jagannath VA, Filippini G, Di Pietrantonj C, Asokan GV, Robak EW, Whamond L, Robinson SA | title = Vitamin D for the management of multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 9 | issue = 9 | pages = CD008422 | date = September 2018 | pmid = 30246874 | pmc = 6513642 | doi = 10.1002/14651858.CD008422.pub3 }}</ref> There is insufficient evidence supporting high-dose [[biotin]]<ref name=Motte2020>{{cite journal |vauthors=Motte J, Gold R |title=High-dose biotin in multiple sclerosis: the end of the road |journal=Lancet Neurol |volume=19 |issue=12 |pages=965–966 |date=December 2020 |pmid=33222766 |doi=10.1016/S1474-4422(20)30353-7 |s2cid=225049079 }}</ref><ref>{{cite journal |vauthors=Tryfonos C, Mantzorou M, Fotiou D, Vrizas M, Vadikolias K, Pavlidou E, Giaginis C |title=Dietary Supplements on Controlling Multiple Sclerosis Symptoms and Relapses: Current Clinical Evidence and Future Perspectives |journal=Medicines  |volume=6 |issue=3 |date=September 2019 |page=95 |pmid=31547410 |pmc=6789617 |doi=10.3390/medicines6030095 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Sedel F, Bernard D, Mock DM, Tourbah A |title=Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis |journal=Neuropharmacology |volume=110 |issue=Pt B |pages=644–653 |date=November 2016 |pmid=26327679 |doi=10.1016/j.neuropharm.2015.08.028 |doi-access=free }}</ref> and some evidence for increased disease activity and higher risk of relapse with its use.<ref name=Goldschmidt2020>{{cite journal |vauthors=Goldschmidt CH, Cohen JA |title=The Rise and Fall of High-Dose Biotin to Treat Progressive Multiple Sclerosis |journal=Neurotherapeutics |volume=17 |issue=3 |pages=968–970 |date=July 2020 |pmid=32761325 |doi=10.1007/s13311-020-00907-5 |pmc=7609671 |doi-access=free }}</ref> A 2022 review found that [[nabiximols]] ([[tetrahydrocannabinol]] and [[cannabidiol]]) can reduce the severity of spasticity in the short term, but may have unwanted neurological effects.<ref>{{cite journal | vauthors = Filippini G, Minozzi S, Borrelli F, Cinquini M, Dwan K | title = Cannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 5 | issue = 5 | pages = CD013444 | date = May 2022 | pmid = 35510826 | pmc = 9069991 | doi = 10.1002/14651858.CD013444.pub2 }}</ref>