Effect of Changes in MS Diagnostic Criteria Over 25 Years on Time to Treatment and Prognosis in Patients With Clinically Isolated Syndrome.

Objectives: To explore whether time to diagnosis, time to treatment initiation and age to reach disability milestones has changed in patients with clinically isolated syndrome (CIS) according to different multiple sclerosis (MS)-diagnostic criteria periods. Methods: Retrospective study based on data prospective collected from the Barcelona-CIS cohort between 1994 and 2020. Patients were classified into five periods according to different MS criteria, and the time to MS diagnosis and treatment initiation were evaluated. The age at which MS patients reached an EDSS ≥3.0 was assessed by Cox regression analysis according to diagnostic criteria periods. Finally, in order to remove the classical “Will Rogers” phenomenon by which the use of different MS criteria over time might result on changes of prognosis, 2017 McDonald criteria were applied and age at EDSS ≥ 3.0 was also assessed by Cox regression. Results: 1174 patients were included. The median time from CIS to MS diagnosis, and from CIS to treatment initiation showed a 77% and 82 reduction from the Poser to the McDonald 2017 diagnostic criteria periods, respectively. Patients of a given age diagnosed in more recent diagnostic criteria periods had a lower risk of reaching EDSS ≥3.0 than patients of the same age diagnosed in earlier diagnostic periods (reference category Poser period): Adjusted hazard ratio (aHR) 0.47 (95% confidence interval 0.24-0.90) for McDonald 2001, aHR 0.25 (0.12-0.54) for McDonald 2005, aHR 0.30 (0.12-0.75) for McDonald 2010 and aHR 0.07 (0.01-0.45) for McDonald 2017. Early-treatment patients displayed an aHR of 0.53 (0.33-0.85) of reaching age at EDSS ≥3.0 compared to late-treatment. Changes in prognosis together with early-treatment effect were maintained after excluding possible bias derived from the use of different diagnostic criteria over time (so called, “Will Rogers” phenomenon) Conclusion: A continuous decrease in the time to MS diagnosis and treatment initiation were observed across diagnostic criteria periods. Overall, patients diagnosed in more recent diagnostic criteria periods displayed a lower risk of reaching disability. Importantly, the prognostic improvement is maintained after discarding the “Will Rogers” phenomenon, and early treatment appears to be the most likely contributing factor.