What is the recommended maintenance therapy for a multiple sclerosis (MS) patient with limited access to monoclonal antibodies?

Maintenance Therapy for Multiple Sclerosis Without Monoclonal Antibody Access

For MS patients without access to monoclonal antibodies, the recommended maintenance therapy options are oral disease-modifying therapies (DMTs) including fingolimod, dimethyl fumarate, teriflunomide, or cladribine, with the choice depending on disease activity level and patient-specific factors. 1

First-Line Oral DMT Options

High-Efficacy Oral Agents

• Fingolimod is a highly effective oral DMT with proven efficacy in reducing annualized relapse rates by approximately 54% compared to placebo (0.18 vs 0.40, p<0.001) and significantly delaying disability progression (hazard ratio 0.70,95% CI 0.52-0.96) 2

• Cladribine represents another high-efficacy option that can be considered after failure of standard DMTs, particularly for patients with highly active disease 1

Moderate-Efficacy Oral Agents

• Dimethyl fumarate and teriflunomide are appropriate for patients with less aggressive disease or as initial therapy in newly diagnosed patients 1

• Glatiramer acetate (injectable, not oral) remains a viable option with long-term safety data showing no unexpected side effects after several years of use 3

Treatment Selection Algorithm

For Highly Active or Aggressive MS:

• Prioritize fingolimod or cladribine as these provide efficacy approaching that of monoclonal antibodies 1, 2

• Consider these agents if the patient has:

  • ≥2 relapses in the past year with MRI activity 1
  • Incomplete recovery from relapses 1
  • High frequency of new MRI lesions 1
  • Rapidly increasing disability 1

For Moderate Disease Activity:

• Start with dimethyl fumarate, teriflunomide, or glatiramer acetate 1, 3

• These are appropriate for patients with:

  • 1 relapse per year with limited MRI activity 1
  • Stable disability scores 1
  • No aggressive disease features 1

Critical Monitoring Requirements

Pre-Treatment Screening

• Complete blood count with differential to establish baseline lymphocyte counts, as fingolimod causes dose-dependent lymphopenia 2

• Liver function tests as baseline, particularly for fingolimod and teriflunomide 2

• Varicella zoster virus (VZV) antibody testing is mandatory before initiating fingolimod; antibody-negative patients require VZV vaccination with a 1-month delay before starting treatment 2

• Cardiac evaluation including ECG and consideration of echocardiography for patients >40 years or with cardiac risk factors before fingolimod initiation 1

• Ophthalmologic examination at baseline and 3-4 months after fingolimod initiation to screen for macular edema 2

Ongoing Monitoring

• MRI surveillance every 6 months in the first year, then annually if stable to assess treatment response and detect breakthrough disease activity 4

• Lymphocyte counts every 3 months during fingolimod therapy; consider treatment interruption if absolute lymphocyte count falls below 0.2 × 10⁹/L 2

• Liver enzymes every 3 months for the first year, then periodically 2

Infection Risk Management

Prophylaxis Strategies

• Maintain low threshold for empiric antibiotics if fever >38°C develops during treatment 5

• Prophylactic acyclovir or valacyclovir should be considered in patients with severe immunosuppression, particularly during fingolimod therapy given the increased risk of herpes viral infections (9% vs 7% on placebo) 2

• HPV vaccination should be completed prior to initiating immunosuppressive DMTs, with appropriate cancer screening including Pap tests as per standard guidelines 2

Infection Surveillance

• Suspend DMT if serious infection develops and reassess benefit-risk before reinitiation; continue monitoring for up to 2 months after fingolimod discontinuation due to prolonged elimination 2

• Maintain high clinical suspicion for opportunistic infections including cryptococcal meningitis (particularly after 2 years of fingolimod), progressive multifocal leukoencephalopathy (PML), and disseminated herpes infections 2

• Obtain blood, urine, and respiratory cultures before initiating antimicrobials in patients with suspected infection and leukopenia 5

Common Pitfalls to Avoid

• Do not use colony-stimulating factors (G-CSF) for isolated lymphopenia from MS therapies; these are reserved for Grade ≥3 neutropenia with severe infection risk, not routine MS-related lymphopenia 5

• Avoid interpreting transient increases in disability or MRI activity during the first 3-6 months of therapy as treatment failure; allow adequate time for therapeutic effect 2

• Do not delay treatment while pursuing perfect risk stratification; the risk of disease progression from untreated MS often exceeds the risks of available therapies 1, 6

• Ensure appropriate washout periods when switching between DMTs to balance risks of MS relapse during withdrawal against complications from sequential treatments; washout should generally be kept as short as possible 1

• Never discontinue fingolimod abruptly without a transition plan, as severe disease rebound can occur; elimination takes up to 2 months 2

Special Considerations for Progressive MS

• Oral DMTs have limited efficacy in progressive MS without inflammatory activity 1

• For early progressive MS with documented inflammatory activity (gadolinium-enhancing lesions or new T2 lesions), consider the same oral DMT options as for relapsing-remitting disease 1

• Autologous hematopoietic stem cell transplantation (AHSCT) should be considered for young patients (<45 years) with early progressive MS, short disease duration, and well-documented inflammatory activity, though this requires specialized centers 1