Randomized, open-label study to evaluate patient-reported outcomes with fingolimod after changing from prior disease-modifying therapy for relapsing multiple sclerosis: EPOC study rationale and design

Figures & data

Figure 1. Study design. * IFNβ-1b 0.25 mg SC every other day, IFNβ-1a 30 µg IM once weekly, IFNβ-1a 22 or 44 µg SC 3 times weekly, or glatiramer acetate 20 mg SC once daily. † Patients in the MS DMT arm who completed the study were eligible for a 3-month open-label fingolimod extension study. DMT, disease-modifying therapy; IFN, interferon; IM, intramuscular; MS, multiple sclerosis; SC, subcutaneous.

Table 1. Schedule of PRO and CGI-I assessments.

Assessment	Screening	3 Months	6 Months*
TSQM	X	X	X
PRIMUS-Activities	X		X
FSS	X	X	X
BDI-II	X	X	X
SF-36 v2 standard	X		X
CGI-I		X	X

*End of study or early termination visit.

BDI-II, Beck Depression Inventory; CGI-I, Clinical Global Impression of Improvement; FSS, Fatigue Severity Scale; PRIMUS, Patient-Reported Indices for Multiple Sclerosis; PRO, patient-reported outcome; SF-36 v2 standard, Short Form Health Survey v2 standard; TSQM, Treatment Satisfaction Questionnaire for Medication.

Table 2. PRO instrument characteristics.

Assessment	Type	No. of items	Domains/sub-scales
TSQM15	General	14	Global satisfaction, effectiveness, side-effects, and convenience
PRIMUS5	MS	15	Activity limitations
FSS25	General; validated for MS	10	N/A
BDI-II26	General; validated for MS	21	N/A
SF-36 v2 standard27	General	36	Physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, general mental health

BDI-II, Beck Depression Inventory; FSS, Fatigue Severity Scale; MS, multiple sclerosis; N/A, not applicable; PRIMUS, Patient-Reported Indices for Multiple Sclerosis; PRO, patient-reported outcome; SF-36 v2 standard, Short Form Health Survey v2 standard; TSQM, Treatment Satisfaction Questionnaire for Medication.

Table 3. Baseline demographics, disease characteristics, and MS treatment history of patients enrolled in the EPOC study.

	Total study population (n = 1053)
Demographic
Mean (SD) age, years	45.8 (9.8)
Women, n (%)	809 (76.8)
Ethnicity, n (%)
White	853 (81.0)
Black	156 (14.8)
Asian	3 (0.3)
Native American	5 (0.5)
Pacific Islander	0
Other	36 (3.4)
Disease characteristic, mean (SD)
Duration,^a years	12.0 (8.5)
Relapses, n
Within previous 1 year^b	0.8 (1.2)
Within previous 2 years^c	1.4 (2.0)
EDSS score^d	2.4 (1.3)
MS treatment history, n (%)
Glatiramer acetate	355 (33.7)
IFNβ-1a SC	260 (24.7)
IFNβ-1a IM	267 (25.4)
IFNβ-1b	170 (16.1)
Other	1 (0.1)

EDSS, Expanded Disability Status Scale; EPOC, Evaluate Patient Outcomes; IFN, interferon; IM, intramuscular; MS, multiple sclerosis; SC, subcutaneous.

^aDuration of MS symptoms; n = 1052.

^bn = 1053.

^cn = 1051.

^dn = 1041.

Table 4. Comparison of EPOC study population characteristics with phase 3 studies of fingolimod.

Study	Comparator	Mean age, years	Mean disease duration, years	Mean relapses in past year, n	Mean relapses in past 2 years, n	Mean baseline EDSS score	Treatment-naive, %
EPOC	DMT	45.8 (9.8)	12.0 (8.5)	0.8 (1.2)	1.4 (2.0)	2.4 (1.3)	0
FREEDOMS II28	Placebo	40.5 (8.6)	10.0 (7.4)	1.5 (0.9)	2.3 (1.7)	2.5 (1.3)	26.6
FREEDOMS11	Placebo	37.1 (8.8)	8.2 (6.6)	1.5 (0.8)	2.1 (1.2)	2.4 (1.3)	59.1
TRANSFORMS9	IFN-β1a IM	36.2 (8.5)	7.4 (6.2)	1.5 (1.0)	2.2 (1.6)	2.2 (1.3)	43.3
TRANSFORMS patients with prior DMT treatment	IFN-β1a IM	36.9 (8.5)	9.0 (6.2)	1.5 (1.1)	2.4 (1.9)	2.5 (1.3)	0

DMT, disease-modifying therapy; EDSS, Expanded Disability Status Scale; EPOC, Evaluate Patient Outcomes; FREEDOMS, FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis; IFN, interferon; IM, intramuscular; TRANSFORMS, Trial Assessing Injectable Interferon vs FTY720 Oral in Relapsing–Remitting Multiple Sclerosis.

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