Click here to watch Dr. Simon Thebault discuss the case and your responses to the quick poll.

Catherine is a 30-year-old woman who presents following her first neurological episode. She developed numbness and paraesthesias involving her right leg and lower trunk six weeks ago. Symptoms evolved over several days but remained mild. She continued working throughout the episode and did not require corticosteroid treatment. Her symptoms resolved completely over approximately two weeks. She is otherwise healthy, takes no regular medications and has no history of recurrent or serious infections.

Neurological examination is normal. EDSS is 0. Brain MRI demonstrates six T2/FLAIR lesions typical of MS. There are three periventricular and two juxtacortical white matter lesions and one questionable L optic nerve lesion. There is a question of subtle punctate enhancement of one of the periventricular lesions with gadolinium. There are no infratentorial lesions. Spinal cord MRI is normal. CSF demonstrates CSF-restricted oligoclonal bands. sNfL is normal.
You diagnose her with mild early RRMS. She tells you: “My symptoms were pretty minor and I feel completely normal now.”

The survey is now closed. There were 36 responses. See below for a summary of the answers you provided.

Question 1: Which initial treatment approach would you recommend?
Most respondents (61%) thought that either a moderate- or high-efficacy DMT was reasonable. Another 28% said they would initiate treatment with an anti-CD20 agent, and 11% said they would opt for either a lower- or moderate-efficacy DMT.

Question 2: The patient is concerned that treatment may be disproportionate to her current disease. She says: “If I had severe MS, I could understand using a strong treatment. But everything you’ve told me sounds relatively mild. Why not see how my MS behaves first?” How would you interpret this patient’s apparently mild presentation?
Eighty percent said that current disease severity should not necessarily determine treatment intensity because the goal of therapy is prevention of future CNS injury. Another 17% said that Catherine’s prognosis is probably favourable, but not sufficiently predictable to exclude high-efficacy treatment. Three percent said her favourable features make a lower-efficacy initial treatment reasonable.

Question 3: What do you consider the strongest argument for initiating high-efficacy therapy now rather than reserving it for future disease activity?
A total of 58% said that the benefit–risk balance may be most favourable early on when inflammatory MS activity is greatest and treatment-related infectious risk is relatively low in young, healthy, minimally disabled patients. In addition, 14% said that early inflammatory CNS injury may be irreversible, making escalation after treatment failure inherently reactive; 11% noted that we cannot reliably identify which apparently mild patients will remain mild; and 11% said that high-efficacy therapies provide greater suppression of subclinical MRI disease. Six percent disagreed and said that they would reserve high-efficacy therapy for patients with greater clinical or radiological disease activity.

Question 4: Catherine then adds an important consideration. She says: “My partner and I would like to have children – probably not immediately, but perhaps in the next two or three years. I don’t want an MS treatment to interfere with that.” How does her desire for pregnancy within the next 2–3 years affect your willingness to recommend an anti-CD20 therapy such as ofatumumab?
Overall, 56% said that pregnancy considerations may actually favour an anti-CD20 strategy because disease can be strongly suppressed before conception with treatment subsequently adapted around pregnancy. Another 36% said that pregnancy does not substantially change their recommendation because therapy can be planned around conception. Eight percent said that pregnancy considerations would make them substantially less likely to recommend anti-CD20 therapy.

Question 5: Catherine raises one final concern that reframes the treatment decision: “I’m only 30. If I start suppressing my B cells now, am I going to be doing this for the next 40 years?” Which long-term treatment philosophy best reflects how you would counsel this patient?
The most common philosophies were front-loaded high efficacy (50%), in which early MS is treated intensively with planned reassessment and potential de-escalation as the benefit-risk ratio changes; and No predetermined lifetime strategy (47%), in which treatment intensity in the future would be determined by disease activity, treatment tolerance, age, the evolving individual risk and the emergence of new data. Only 3% said they prefer an Escalation approach in which treatment is started with a lower- or moderate-efficacy DMT and high-efficacy DMTs is reserved for breakthrough disease.

View the video commentary from Dr. Simon Thebault.

Further reading
1. Montalban et al. Diagnosis of MS: 2024 revisions of the McDonald criteria. Lancet Neurol 2025;24:850-865.
2. Hauser et al. Ofatumumab versus teriflunomide in MS (ASCLEPIOS I/II). N Engl J Med 2020;383:546-557.
3. Gärtner et al. Efficacy and safety of ofatumumab in recently diagnosed, treatment-naive patients with multiple sclerosis: Results from ASCLEPIOS I and II. Mult Scler 2022;28:1562-1575.
4. Harding et al. Clinical outcomes of escalation vs early intensive disease-modifying therapy in patients with multiple sclerosis. JAMA Neurol 2019;76:536-541.
5. He et al. Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study. Lancet Neurol 2020;19:307-316.
6. Spelman et al. Treatment escalation vs immediate initiation of highly effective treatment for patients with relapsing-remitting multiple sclerosis: data from 2 different national strategies. JAMA Neurol 2021;78:1197-1204.
7. Tallantyre et al. Disease-modifying treatment preferences and decision-making in a multiple sclerosis randomized and observational clinical trial (DELIVER-MS). Mult Scler 2026;32:722-736.
8. Tintore et al. Defining high, medium and low impact prognostic factors for developing multiple sclerosis. Brain 2015;138:1863-1874.
9. Ziemssen et al. Prognostic value of serum neurofilament light chain for disease activity and worsening in patients with relapsing multiple sclerosis: results from the phase 3 ASCLEPIOS I and II trials. Front Immunol 2022;13:852563.
10. Kappos et al. Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials. JAMA Neurol 2020;77:1132-1140.
11. UCSF MS-EPIC Team. Silent progression in disease activity-free relapsing MS. Ann Neurol 2019;85:653-666.
12. Weideman AM et al. Meta-analysis of the age-dependent efficacy of multiple sclerosis treatments. Front Neurol 2017;8:577.
13. Luna et al. Infection risks with fingolimod, natalizumab, rituximab and injectables. JAMA Neurol 2020;77:184-191.
14. Hauser et al. Six-year safety and efficacy outcomes with first-line ofatumumab in recently diagnosed treatment-naive patients with relapsing multiple sclerosis. Mult Scler Relat Disord 2025;105:106886.
15. Gavoille et al. Therapeutic management during pregnancy and relapse risk in women with multiple sclerosis. JAMA Neurol 2025;82:994-1003.
16. Bongol et al. B-cell repopulation and postpartum MS disease activity following ofatumumab cessation for pregnancy in women with multiple sclerosis. Mult Scler. 2026 July 22:13524585261471448.
17. Vukusic et al. Pregnancy and infant outcomes in women with multiple sclerosis treated with ocrelizumab. Neurol Neuroimmunol Neuroinflamm 2024;12:e200349.
18. Witt et al. Safety of breastfeeding under monoclonal antibodies in the offspring of mothers with multiple sclerosis or neuromyelitis optica spectrum disorder. J Neurol Neurosurg Psychiatry 2026;97:522-531.
19. Dobson et al. Anti-CD20 therapies in pregnancy and breast feeding: a review and ABN guidelines. Pract Neurol 2023;23:6-14.
20. Corboy et al. Risk of new disease activity in patients with multiple sclerosis who continue or discontinue disease-modifying therapies (DISCOMS): a multicentre, randomised, single-blind, phase 4, non-inferiority trial. Lancet Neurol 2023;22:568–577.
21. Coerver et al. Discontinuation of First-Line Disease-Modifying Therapy in Patients With Stable Multiple Sclerosis: The DOT-MS randomized clinical trial. JAMA Neurol 2025;82:123-131.