Table 4.

Disability outcomes of patients with progressive forms of multiple sclerosis (MS) in phase II and III trials

Trial name		Interventions	Study outcomes
			F/U, months	3-month CDP HR (95 % CI) versus controla	6-month CDP HR (95 % CI) versus controla	Mean (SD) change in EDSS score from BL	Mean (SD) change in MSFC score from BL	Increase in EDSS for CDPb
Oral therapies
MS-STAT NCT00647348  [129]		Simvastatin 80 mg/day	24	NR	NR	−0.254 (−0.464, −0.069)*c	0.289 (−0.333, 0.961)c	NA
		Placebo
NCT01450488 [130]		Masitinib 3 or 6 mg/kg/day total	12	NR	NR	0 (0.5)	103 % (189 %)	NA
		Placebo				0.3 (1.0)	−60 % (190 %)
Intravenous therapies
Cladribine Clinical and MRI Study Groups [no trial code] [90]		Cladribine 0.7 mg/kg	12	NR	NR	NS; values NR	NR	≥0.5 if BL ≥5.5
		Cladribine 2.1 mg/kg
		Placebo
[no trial code] [89]		Cladribine 2.8 mg/kg	24	NR	NR	Figure only; values NR	NR	NA
		Placebo
OLYMPUS NCT00087529 [91]		Rituximab 1000 mg	24	30.2 %	NR	0.33 (1.0)	−0.05	≥0.5 if BL >5.5
		Placebo		38.5 %		0.45 (1.0)	−0.04
[no trial code] [93]	PPMS	IVIG 0.4 g/kg/month	24	29 %*	NR	−0.39	NR	≥0.5 if BL ≥5.0
		Placebo		71 %		−0.03
	SPMS	IVIG 0.4 g/kg/month	24	52 %	NR	NR	NR	≥0.5 if BL ≥5.0
		Placebo		61 %
MIMS [no trial code] [54]		Mitoxantrone 5 mg/m2 every 3 months	24	14 %	NR	–	NR
		Mitoxantrone 12 mg/m2 every 3 months		8 %		−0.13 (0.90)*
		Placebo		22 %		0.23 (1.01)
MAESTRO-01 NCT00869726 [92]		Dirucotide 500 mg every 6 months (haplotype DR2+ or 4+)	24	NR	30.7 %	0.22 (0.06)	−0.28	≥0.5 if BL ≥5.5
		Placebo (haplotype DR2+ or 4+)			27.8 %	0.17 (0.06)	−0.46
		Dirucotide 500 mg every 6 months (haplotype DR2−/4−)			28.3 %	0.32 (0.14)	−0.55
		Placebo (haplotype DR2−/4−)			35.8 %	0.45 (0.13)	−0.49
Injectable therapies
PROMiSe [no trial code] [102]		GA s.c. 20 mg/day	36	39.6 %	NR	0.58 (1.00)	NS; values NR	≥0.5 if BL ≥5.5
		Placebo		45.2 %		0.61 (1.13)
[no trial code] [100]		IFN beta-1a i.m. 30 µg/week IFN beta-1a i.m. 60 µg/week	24	NS; values NR	NR	NR	NR	≥0.5 if BL ≥5.5
		Placebo
[no trial code] [97]		IFN beta-1b s.c. 8 MIU e.o.d.	24	33.3 %	22.2 %	NSc; values NR	NSc; values NR	≥0.5 if BL >5.5
		Placebo		40.5 %	32.4 %
[no trial code] [99]		IFN beta-1a s.c. 22 μg once/week	36	NR	41 %	Figure only	NR	≥0.5 if BL ≥5.5
		Placebo			38 %
SPECTRIMS [no trial code] [98]		IFN beta-1a s.c. 22 μg three times/week	36	With relapses pre-study:	NR	NR	NR	≥0.5 if BL ≥5.5
		IFN beta-1a s.c. 44 μg three times/week		0.52 (0.29, 0.93)*
		Placebo		Without relapses: 1.07 (0.64, 1.78) –
European trial [no trial code] [94]		IFN beta-1b s.c. 250 μg (8 MIU) e.o.d.	33	38.9 %	NR	0.47*	NR	≥0.5 if BL ≥6.0
		Placebo		49.8 %		0.60
North American trial [no trial code] [95]		IFN beta-1b s.c. 250 μg (8 MIU) e.o.d.	36	NR	NS; values NR	0.53	NR	≥0.5 if BL ≥6.0
		IFN beta-1b s.c. 160 μg (5 MIU)/m2 e.o.d.				0.72
		Placebo				0.62

BL baseline, CDP confirmed disease progression, CI confidence interval, EDSS Expanded Disability Status Scale, e.o.d. every other day, F/U follow-up, GA glatiramer acetate, HR hazard ratio, IFN interferon, i.m. intramuscular, IVIG intravenous immunoglobulin, MIU million international units, MRI magnetic resonance imaging, MS multiple sclerosis, MSFC MS functional composite, PPMS primary progressive MS, NR not reported, pts points, s.c. subcutaneous, SD standard deviation, SPMS secondary progressive MS

* p < 0.05; ** p < 0.01; *** p < 0.001 vs. control

^aThe percentage of patients with CDP is shown when hazard ratios are not reported

^bIf no criteria are specified, the definition of CDP was a confirmed 1.0-point increase in EDSS score from baseline; criteria that are specified indicate increases in EDSS score that were used in conjunction with this definition

^cMean between-group difference (95 % CI)