Table 2

Determinants of progression to the confirmed outcome disability level

	Study epoch
	EDSS 3–6		EDSS 4–6		EDSS 6–6.5*
	HR (95% CI)	p Value	HR (95% CI)	p Value	WAF (95% CI)	p Value
Sex (male)	1.11 (0.86 to 1.43)	0.42	1.33 (1.08 to 1.63)	0.008	1.20 (1.04 to 1.37)	0.01
Age at baseline (per year)	1.01 (1.00 to 1.02)	0.19	1.01 (1.00 to 1.02)	0.07	0.99 (0.98 to 1.00)	0.02
Disease duration at baseline (per year)	0.99 (0.89 to 1.11)	0.93	0.91 (0.83 to 1.00)	0.05	0.96 (0.91 to 1.02)	0.21
Annualised relapse rate
Prebaseline (per relapse/year)	0.92 (0.75 to 1.13)	0.41	0.93 (0.76 to 1.13)	0.44	0.79 (0.68 to 0.91)	0.001
During epoch (per relapse/year)	3.07 (2.56 to 3.70)	<0.001	2.41 (2.05 to 2.84)	<0.001	1.58 (1.45 to 1.73)	<0.001
Rate of prebaseline therapy initiation (per initiation/year)	1.07 (0.60 to 1.91)	0.81	1.10 (0.70 to 1.72)	0.69	0.93 (0.69 to 1.24)	0.60
Proportion of time on lower efficacy therapies
Prebaseline (per 25% increase)	1.01 (0.92 to 1.11)	0.88	0.97 (0.90 to 1.05)	0.51	1.04 (0.99 to 1.09)	0.15
During epoch (per 25% increase)	0.98 (0.90 to 1.07)	0.61	1.00 (0.93 to 1.07)	0.92	1.02 (0.97 to 1.06)	0.49
Proportion of time on higher efficacy therapies
Prebaseline (per 25% increase)	0.74 (0.32 to 1.68)	0.47	1.59 (1.22 to 2.07)	<0.001	1.10 (0.94 to 1.28)	0.22
During epoch (per 25% increase)	0.72 (0.59 to 0.89)	0.002	0.79 (0.69 to 0.91)	<0.001	0.91 (0.84 to 0.99)	0.02

Results of multivariable survival models for each epoch. Unless stated otherwise, Cox proportional hazard models were used.
*Weibull accelerated failure time model was used for this epoch.
EDSS, Expanded Disability Status Scale; WAF, Weibull acceleration factor.