Table 3.

Transition time between milestone EDSS scores for placebo- versus any-DMT-treated patients by treatment effect and by mechanism of worsening

	Effect of treatment			By mechanism of worsening in RRMS patients who had a 6-month CDW event
EDSS score	Placebo-treated (years)	DMT-treated (years)	Time gained due to treatment (years): Delta 95% CI	PIRA, with relapses (years, 95% CI)	PIRA, without relapses (years, 95% CI)	RAW (years, 95% CI)
1 to 4	8.95	12.46	3.51 (3.19, 3.96)	2.60 (2.30, 2.93)	3.56 (3.31, 3.85)	3.97 (3.61, 4.35)
1 to 6	18.48	21.57	3.09 (2.60, 3.72)	6.14 (5.51, 6.89)	7.31 (6.84, 7.89)	8.11 (7.36, 8.90)
4 to 6	9.91	11.31	1.40 (0.86, 1.92)	4.10 (3.49, 4.82)	4.34 (3.98, 4.88)	4.82 (4.41, 5.36)

Mean transition times between milestone disability levels in the full dataset as measured using a continuous time Markov model. The time between milestone EDSS values considers all-cause disability worsening and improvement. The distribution of baseline disability stages (as measured by EDSS scores), as a function of the patient’s age, is presented in Supplementary Fig. 5. Based on inclusion and exclusion criteria for the clinical trials included in this study, the majority of the data points covered the range from EDSS 0 (normal neurological assessment) to EDSS 6 (requiring a walking aid), which is why we focused the analysis on this disability range. The gain in time between DMT- and placebo-treated patients (Delta) is statistically significant if the 95% CI does not include the value of zero. Transition times to milestone EDSS scores with corresponding 95% CI were also summarized by mechanism of worsening within the subgroup of RRMS patients who had a 6-month CDW event in the full dataset using continuous time Markov models; the 95% CI is to the time to milestone EDSS scores.