TABLE 2.

Randomised, placebo‐controlled studies conducted in patients with primary progressive multiple sclerosis prior to 2020 [49, 50, 51, 52]

Study	Comparators	N	Follow‐up duration	Primary endpoint	Primary efficacy occurrence	HR (95% CI) p‐value
Leary et al. 2003 [50]	Placebo	20	2 years	3‐month CDP a	NR	NR No difference between groups
	IFN‐β‐1a 30 or 60 μg	30
Montalban et al. 2009 [51]	Placebo	37	2 years	3‐month CDP b	56.8%	NR p = 0.3135
	IFN‐β‐1b 8 MU	36			65.8%
Wolinsky et al. 2007 [52]	Placebo	316	3 years (planned) 2 years (completed c )	3‐month CDP d	45.2%	0.87 (0.71–1.07) p = 0.1753
	Glatiramer acetate 20 mg	627			39.6%
OLYMPUS study [49]	Placebo	147	96 weeks	12‐week CDP e	38.5%	0.77 p = 0.1442
	Rituximab 1000 mg	292			30.2%

Abbreviations: CDP, confirmed disability progression; CI, confidence interval; EDSS, Expanded Disability Status Scale; HR, hazard ratio; IFN, interferon; MU, million units; NR, not reported.

^a A sustained increase in EDSS of ≥1.0 points from baseline if the baseline EDSS was ≤5.5 or an increase of ≥0.5 points if the baseline EDSS was >5.5.

^b A sustained increase in EDSS of ≥1.0 points from baseline if the baseline EDSS was <5.5 or an increase of 0.5 points if the baseline EDSS was >5.5.

^c Study stopped at the 2‐year interim analysis for futility.

^d A sustained increase in EDSS of ≥1.0 points from baseline if the baseline EDSS was 3.0–5.0 (inclusive) or an increase of ≥0.5 points if the baseline EDSS was 5.5–6.5.

^e A sustained increase in EDSS of ≥1.0 points from baseline if the baseline EDSS was 2.0–5.5 (inclusive) or an increase of ≥0.5 points if the baseline EDSS was >5.5, and when the change could not be attributed to another aetiology.