COAST Trial: Evaluating Ozanimod Step-Down in Multiple Sclerosis

The ongoing phase IV4 COAST trial is evaluating ozanimod as a step-down therapy for patients with Multiple Sclerosis (MS)MS who have been stable for at least two2 years on anti-CD20 disease-modifying therapies (DMTs). The inclusion criteria, which require no relapses or new MRI lesions during this period and an Igimmunoglobulin-G level of at least 400 mg/dL, appear stringent but appropriate to select a population with well-controlled disease and sufficient immune competence. In clinical practice, these criteria reflect a subset of patients who respond well to anti-CD20 agents but may benefit from a safer, oral maintenance therapy to reduce cumulative immunosuppression risks. However, some patients with fluctuating disease or lower immunoglobulin levels might be excluded, limiting generalizability.

Regarding the timing of ozanimod initiation, it seems logical to consider starting the medication shortly after the last anti-CD20 infusion once the patient’s disease is stable and immunoglobulin levels are adequate. This approach aims to maintain disease control while minimizing gaps in treatment. However, initiating ozanimod too early might risk overlapping immunosuppressive effects, whereas waiting too long could increase the risk of disease reactivation. Therefore, individualized clinical judgment and monitoring remain essential.

Ozanimod may not be suitable for patients with certain contraindications, such as those with cardiac conduction abnormalities, active infections, or significant lymphopenia. Additionally, patients with highly active or aggressive disease may require more potent therapies rather than de-escalation. The interim and final data readouts from COAST are expected over the next few years, which will provide valuable insights into the efficacy and safety of ozanimod as a step-down option. Until then, clinicians must weigh current evidence and patient factors carefully when considering therapy transitions.