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. 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 diagnosed in more recent
diagnostic criteria periods had a lower risk of reaching age at EDSS ≥3.0
compared to 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.