Multiple sclerosis RRMS When to change disease modifying therapy

Changing Disease Modifying Therapy (DMT) in RRMS is considered for poor response, adherence issues, side effects, pregnancy, or COVID-19 risks. Alternatives are chosen based on the individual's response, with factors like JC Virus status and pregnancy affecting decisions. Some DMTs, particularly those causing lymphopenia, may heighten COVID-19 infection risks.

Physicians should consider changing disease modifying therapy (DMT) in case of poor response, drug adherence concern, side effects, pregnancy, Covid-19 pandemic and other situations.

1.Poor response to DMT agents:

Some patients with RRMS have disease activity which is refractory to initial DMT. Guideline from the American Academy of Neurology suggests switching to another DMT for people with MS who are adherent to DMT therapy when they experience one or more relapses, two or more unequivocally new MRI lesions or increased disability on examination over a year period. There is no standard protocol for changing DMT. The overall goal is to balance the risks posed by the medication to the risks posed by the disease, though long term outcomes in MS is difficult. Consideration of the adherence and other factors to inadequate treatment response is also important. (1, 2, 3) For patients initially treated with an oral agent who have an inadequate response, it is advisable to switch to a different oral therapy, infusion therapy, such as, natalizumab, ocrelizumab or interferon injection therapy. For patients initially treated with natalizumab who have an inadequate response, stopping natalizumab is advisable and switching to a different and preferably high- efficacy, DMT, such as, ocrelizumab, dimethyl fumarate, teriflunomide or fingolimod. For patients who have an inadequate response to interferon beta (IFNB) or glatiramer, they could switch to the opposite class of injectable treatment or to an oral agent, such as, dimethyl fumarate, teriflunomide or fingolimod. (4, 5)

2.Drug adherence concerns:

A persistent poor compliance can increase the risk for disease activity, especially in those who are on oral DMT particularly fingolimod.

3.DMT side effects:

DMT adverse events play an important role in the decision to switch DMT. Cautious monitoring of side effects is required in all patients especially those with other comorbidities. Patients on natalizumab who become John Cunningham (JC) Virus seropositive are at risk for progressive multifocal leukoencephalopathy (PML). Stopping the agent is advisable. Lower dose of dimethyl fumarate may be considered for patients experiencing significant gastrointestinal side effects. (6,7, 8)

4.Pregnancy planning:

RRMS most commonly affects women of childbearing age. Fingolimod, siponimod, teriflunomide and dimethyl fumarate are not recommended during conception or pregnancy. While, glatiramer acetate and interferons are considered relatively safer in pregnancy. (9)

5.Covid 19 pandemic:

There are concerns about ocrelizumab, alemtuzumab, rituximab and cladribine as they cause lymphopenia which could increase the risk of developing severe COVID- 19 infection. (10)

References

1-Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler 2018; 24:96.

2-Rae-Grant A, Day GS, Marrie RA, et al. 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.Neurology 2018; 90:777.

3-Capra R, Cordioli C, Rasia S, et al. Assessing long-term prognosis improvement as a consequence of treatment pattern changes in MS. Mult Scler 2017; :1352458516687402.

4-Beiki O, Frumento P, Bottai M, et al. Changes in the Risk of Reaching Multiple Sclerosis Disability Milestones In Recent Decades: A Nationwide Population-Based Cohort Study in Sweden. JAMA Neurol 2019; 76:665.

5-He A, Merkel B, Brown JWL, et al. Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study. Lancet Neurol 2020; 19:307.

6- Cohan SL, Moses H, Calkwood J, et al. Clinical outcomes in patients with relapsing-remitting multiple sclerosis who switch from natalizumab to delayed-release dimthyl fumarate: A multicenter retrospective observational study (STRATEGY). Mult Scler Relat Disord. 2018;22:27-34.

7-Kappos L, Radue EW, Comi G, et al. Switching from natalizumab to fingolimod: A randomized, placebo-controlled study in RRMS. In: Neurology. Vol 85.2015:29-39.

8-Alping P, Frisell T, Novakova L, et al. Rituximab versus fingolimod after natalizumab in multiple sclerosis patients. Annals of neurology. 2016;79(6):950-958.

9- Friend S, Richman S, Bloomgren G, Cristiano LM, Wenten M. Evaluation of pregnancy outcomes from the Tysabri(R) (natalizumab) pregnancy exposure registry: a global, observational, follow-up study. BMC Neurol. 2016;16(1):150.

10-Giovannoni G, Hawkes C, Lechner-Scott J, et al. The COVID-19 pandemic and the use of MS disease-modifying therapies. Mult Scler Relat Disord 2020; 39:102073.