From the Guidelines
Ozanimod is the most reasonable sphingosine-1-phosphate receptor modulator for TT, as it does not require a first-dose observation, making it suitable for patients with transportation issues. According to the study published in the Journal of Crohn's and Colitis 1, ozanimod has been shown to be effective in treating multiple sclerosis (MS) with a relatively low incidence of adverse effects. The study reported that most ozanimod-treated patients with MS who contracted COVID-19 had non-serious infections and recovered without sequelae.
Key Considerations
- Ozanimod treatment can be continued during COVID-19 infection if warranted, as most patients with serious COVID-19 fully recovered without sequelae 1.
- The incidence of progressive multifocal leukoencephalopathy (PML) with ozanimod is low, with only one reported case in a patient with a 15-year history of MS after approximately 4 years of ozanimod treatment 1.
- Ozanimod has a pharmacodynamic effect of reducing absolute lymphocyte count (ALC), but changes in ALC were not associated with its efficacy or safety, and ALC monitoring is recommended every 3 months 1.
- The medication has a low incidence of macular oedema, and regular ophthalmic evaluations are recommended for patients with diabetes or a history of uveitis or macular oedema 1.
Treatment Initiation
Before starting ozanimod, TT should undergo baseline assessments, including complete blood count, liver function tests, cardiac evaluation, ophthalmologic examination, and varicella zoster virus antibody testing, with vaccination if needed. Ozanimod is taken orally once daily, and liver enzymes and function should be assessed periodically during treatment. Treatment should be interrupted if transaminases are confirmed to be >5 times the upper limit of normal (ULN) and discontinued in the event of liver injury 1.
From the FDA Drug Label
PONVORY is a sphingosine 1-phosphate receptor modulator indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. (1) MAYZENT is a sphingosine 1-phosphate (S1P) receptor modulator indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. (1)
The most reasonable option for TT would be Ponesimod (PO) or Siponimod (PO), as both are sphingosine-1-phosphate receptor modulators indicated for the treatment of relapsing forms of multiple sclerosis (MS) in adults 2, 3. However, the provided drug labels do not explicitly address the first-dose observation requirement for these medications.
- Key Consideration: First-dose observation requirement is not mentioned in the provided labels.
- Decision: Without explicit information on first-dose observation requirements, a conservative decision cannot be made based on the provided drug labels alone.
From the Research
Sphingosine-1-Phosphate Receptor Modulator Options for TT
Given TT's history with relapsing-remitting multiple sclerosis (RRMS) and her need to avoid a first-dose observation due to transportation issues, the most reasonable option must be selected from the available sphingosine-1-phosphate receptor modulators. The key factor here is the requirement for a medication that does not necessitate first-dose cardiac monitoring.
Analysis of Options
- Ozanimod (A): Ozanimod is noted for not requiring first-dose cardiac monitoring in the USA 4, making it a potential candidate for TT. It has been shown to be effective in reducing annualized relapse rates and the number of new or enlarging T2 lesions and gadolinium-enhancing lesions in patients with RRMS 4, 5. Ozanimod also has a favorable safety profile compared to other S1P receptor modulators like fingolimod and ponesimod 6, 7.
- Fingolimod (B): Fingolimod requires first-dose observation due to potential cardiac effects, which does not meet TT's needs.
- Ponesimod (C): Similar to fingolimod, ponesimod may require first-dose monitoring, although specific requirements can depend on the region and patient factors. However, ozanimod has been shown to have a more favorable safety profile and potentially greater efficacy in preserving brain volume compared to ponesimod 7.
- Siponimod (D): Siponimod, like fingolimod, requires first-dose observation, making it less suitable for TT given her transportation constraints.
Conclusion Based on Evidence
Considering the need to avoid first-dose observation and the efficacy and safety profiles of the available options, Ozanimod (A) appears to be the most reasonable choice for TT. It offers a favorable balance of efficacy and safety without the requirement for first-dose cardiac monitoring, addressing TT's specific needs and constraints 4, 5, 6, 7, 8.