To treat or not to treat: Sequential individualized treatment evaluation in relapsing multiple sclerosis

Background: The frequency and long-term prognosis of relapsing multiple sclerosis (RMS) never receiving disease-modifying treatment (DMT) is unclear.

Methods: We included 1186 RMS patients with a mean of 17.4 years follow-up and divided them into patients treated with any DMT (DMT) and patients untreated by shared (USD) or patient-autonomous decision (UAD).

Results: The USD group displayed features, which significantly differed from the two other groups: higher age at onset, mainly sensory onset symptoms, complete remission of onset symptoms, less T2 and contrast-enhancing T1 lesions on initial brain MRI. In a multivariate cox regression, USD was associated with lower risk for secondary progression (SPMS) conversion (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.55-0.97, p = 0.011) compared to DMT, while UAD was associated with an increased SPMS conversion risk only in the "McDonald era" (HR 1.19, CI 1.02-1.58, p = 0.028).

Conclusion: Apart from the doubtless substantial improvement of the overall prognosis of RMS by DMT, it seems likely that not every patient necessarily needs immediate or even "hard and early" treatment. A "watchful waiting" approach with continuous clinical evaluation might be instead a viable option in RMS patients with favorable prognostic features at onset.