Ease of use of two autoinjectors in patients with multiple sclerosis treated with interferon beta-1a subcutaneously three times weekly: results of the randomized, crossover REDEFINE study

Figures & data

Table 1. Comparison of single-use and reusable autoinjectors.

	Single-use autoinjector: Rebif® Rebidose®	Reusable autoinjector: Rebiject II®
Pre-assembled?	✓	✗
Assembly/injection procedure	3 steps	12 steps
Single use?	✓^a	✗
Suitable for titration to 44-µg dose?	✓	✓
Training needs	Minimal	Moderate
Adjustable injection depth?	✗	✓
Inspection of contents?	Transparent window enables 360° inspection	✗
Needle shield	Shielded	Shield before and during injection; exposed during disposal
Safety lock?	✓	✓

✓symbol indicates characteristic present; ✗ symbol indicates characteristic not present.

^aSingle-use autoinjectors are recycled in the US via the Rebif® Rebidose® sharps disposal program.

Figure 1. Response to Question 14 of the User Trial Questionnaire, ‘Overall experience with using injection device’ (primary endpoint).

CI, confidence interval. ^aDifference (95% CI) between devices (in percentage points; single-use autoinjector minus reusable autoinjector) in the proportions of patients rating each autoinjector as ‘very easy’ or ‘easy’ to use. p value is based on the exact sign test of equality of paired proportions. Includes patients with complete data for both autoinjectors (N = 95).

Table 2. Patient characteristics and responses to questionnaire at baseline.

	Single-use autoinjector followed by reusable autoinjector (n = 46)	Reusable autoinjector followed by single-use autoinjector (n = 51)	Total (N = 97)
Age at randomization (years), mean (SD)	49.4 (9.78)	47.5 (11.20)	48.4 (10.54)
Sex, n (%)
Male	6 (13.0)	19 (37.3)	25 (25.8)
Female	40 (87.0)	32 (62.7)	72 (74.2)
Race, n (%)
White	37 (80.4)	46 (90.2)	83 (85.6)
Black/African-American	9 (19.6)	3 (5.9)	12 (12.4)
Other (Hispanic or Latino)	0	2 (3.9)	2 (2.1)
Type of previous device use, n (%)
Manual with PFS	16 (34.8)	13 (25.5)	29 (29.9)
Single-use autoinjector	10 (21.7)	13 (25.5)	23 (23.7)
Reusable autoinjector	20 (43.5)	25 (49.0)	45 (46.4)
SDMT (oral score)^a
N	41	49	90
Mean (SD)	49.9 (15.38)	49.8 (17.12)	49.9 (16.26)
Median	51.0	52.0	51.5
Min, max	(10, 75)	(3, 95)	(3, 95)
SDMT (written score)^a
N	42	47	89
Mean (SD)	46.2 (13.06)	45.7 (15.07)	45.9 (14.08)
Median	45.5	48.0	46.0
Min, max	(23, 72)	(1, 70)	(1, 72)
Average no. of nights per month spent traveling away from home
N	46	50	96
Mean (SD)	2.41 (3.263)	2.38 (5.558)	2.40 (4.580)
Median	1.00	0.00	0.00
Min, max	(0.0, 14.0)	(0.0, 30.0)	(0.0, 30.0)
Highest education completed, n (%)
High school/GED	13 (28.3)	20 (39.2)	33 (34.0)
Associate’s degree	8 (17.4)	5 (9.8)	13 (13.4)
Bachelor’s degree	13 (28.3)	18 (35.3)	31 (32.0)
Postgraduate (master’s, doctorate)	10 (21.7)	4 (7.8)	14 (14.4)
Other	2 (4.3)	3 (5.9)	5 (5.2)
Difficulty dressing, n (%)
No difficulty	36 (78.3)	34 (66.7)	70 (72.2)
A little difficulty	9 (19.6)	12 (23.5)	21 (21.6)
Moderate difficulty	1 (2.2)	3 (5.9)	4 (4.1)
A great deal of difficulty	0 (0.0)	1 (2.0)	1 (1.0)
Difficulty lifting full cup/glass to mouth, n (%)
No difficulty	38 (82.6)	39 (76.5)	77 (79.4)
A little difficulty	5 (10.9)	10 (19.6)	15 (15.5)
Moderate difficulty	3 (6.5)	1 (2.0)	4 (4.1)
A great deal of difficulty	0 (0.0)	0 (0.0)	0 (0.0)
Level of disability, n (%)
None	14 (30.4)	12 (23.5)	26 (26.8)
Mild	25 (54.3)	23 (45.1)	48 (49.5)
Moderate	6 (13.0)	14 (27.5)	20 (20.6)
Severe	1 (2.2)	1 (2.0)	1 (2.1)
Difficulty distinguishing colors, n (%)
No difficulty	41 (89.1)	42 (82.4)	83 (85.6)
A little difficulty	5 (10.9)	6 (11.8)	11 (11.3)
Moderate difficulty	0 (0.0)	1 (2.0)	1 (1.0)
A great deal of difficulty	0 (0.0)	1 (2.0)	1 (1.0)
Difficulty reading newspaper (with glasses if needed), n (%)
No difficulty	27 (58.7)	29 (56.9)	56 (57.7)
A little difficulty	13 (28.3)	14 (27.5)	27 (27.8)
Moderate difficulty	6 (13.0)	4 (7.8)	10 (10.3)
A great deal of difficulty	0 (0.0)	3 (5.9)	3 (3.1)
Anxiety about giving self-injection, n (%)
Not at all anxious	15 (32.6)	32 (62.7)	47 (48.5)
A little anxious	22 (47.8)	12 (23.5)	34 (35.1)
Moderately anxious	5 (10.9)	4 (7.8)	9 (9.3)
Very anxious	3 (6.5)	2 (3.9)	5 (5.2)
Extremely anxious	1 (2.2)	0 (0.0)	1 (1.0)
Generally afraid of needles, n (%)
Not at all	19 (41.3)	29 (56.9)	48 (49.5)
A little	19 (41.3)	15 (29.4)	34 (35.1)
Moderately	4 (8.7)	2 (3.9)	6 (6.2)
Very	3 (6.5)	3 (5.9)	6 (6.2)
Extremely	1 (2.2)	1 (2.0)	2 (2.1)

GED, General Educational Development; max, maximum; min, minimum; PFS, prefilled syringe; SD, standard deviation; SDMT, Symbol Digit Modalities Test.

^aSDMT oral and written scores range from 0 to 110, with lower scores indicating cognitive deficit.

Figure 2. Autoinjector ease of use by previous injection device experience.

Diff., difference between devices (in percentage points; single-use autoinjector minus reusable autoinjector) in the proportions of patients rating each autoinjector as ‘very easy’ or ‘easy’ to use; the numbers in parentheses show the 95% confidence interval; PFS: prefilled syringe. p values are based on the exact sign test of equality of paired proportions. ^aPatients with concordant responses.

Figure 3. Percentages of patients rating each device as very easy or easy to use by quartiles of SDMT (a) oral and (b) written scores.

SDMT oral and written scores range from 0 to 110, with lower scores indicating cognitive deficit. Quartile 4 includes the highest values, with the least cognitive deficit. SDMT, Symbol Digit Modalities Test. ^aDifference between devices (in percentage points; single-use autoinjector minus reusable autoinjector) in the proportions of patients rating each autoinjector as ‘very easy’ or ‘easy’ to use. ^bBased on exact sign test of equality of paired proportions.

Table 3. Responses to other questions of the User Trial Questionnaire.

Single-use autoinjector strongly agree/agree (n = 95)^a	Reusable autoinjector strongly agree/agree (n = 95)^a	P value^b	Difference in proportions (95% CI)^c	Strongly agree/agree for both autoinjectors (n = 95)^a	Single-use autoinjector strongly agree (n = 96)	Reusable autoinjector strongly agree (n= 96)
Satisfied overall with injection device, n (%)
62 (65.3)	79 (83.2)	0.009	−17.9 (−30.3, −5.5)	51 (53.7)	37 (38.5)	33 (34.4)
Satisfied with amount of time it took to complete injection, n (%)
84 (88.4)	83 (87.4)	1.000	1.1 (−7.9, 10.0)	74 (77.9)	45 (46.9)	36 (37.5)
Satisfied with number of steps it took to complete injection, n (%)
90 (94.7)	71 (74.7)	<0.001	20.0 (10.1, 29.9)	67 (70.5)	47 (49.0)	30 (31.3)
Overall experience with holding device, n (%)^d
65 (68.4)	74 (77.9)	0.175	−9.5 (−21.5, 2.6)	52 (54.7)	32 (33.3)	31 (32.3)
Convenience of using the device, n (%)^e
79 (83.2)	68 (71.6)	0.099	11.6 (−0.8, 23.9)	55 (57.9)	51 (53.1)	29 (30.2)
Convenient to store the injection device, n (%)
60 (63.2)	88 (92.6)	<0.001	−29.5 (−40.3, −18.6)	56 (58.9)	25 (26.0)	35 (36.5)
Features of the device help minimize safety hazards, n (%)
64 (67.4)	64 (67.4)	1.000	0.0 (−13.7, 13.7)	42 (44.2)	32 (33.3)	23 (24.0)
Trainer provided easily understandable, unbiased, and practical information about proper injection, n (%)
95 (100.0)	93 (97.9)	–	–	93 (97.9)	66 (68.8)	66 (68.8)
Recommend injection device to others needing IFN β-1a SC tiw, n (%)^f
63 (66.3)	74 (77.9)	0.135	−11.6 (−25.2, 2.1)	46 (48.4)	44 (45.8)	41 (42.7)
Anxious to self-inject with device, n (%)^g
11 (11.6)	7 (7.4)	0.424	4.2 (−3.5, 11.9)	2 (2.1)	3 (3.1)	4 (4.2)
Device allows easy access to various injection sites, n (%)
72 (75.8)	80 (84.2)	0.200	−8.4 (−19.6, 2.8)	61 (64.2)	28 (29.2)	25 (26.0)

CI, confidence interval; IFN β-1a, interferon beta-1a; SC, subcutaneously; tiw, three times weekly.

^aPatients with complete data for both autoinjectors.

^bBased on exact sign test of equality of paired proportions.

^cDifference between devices (in percentage points; single-use autoinjector minus reusable autoinjector) in the proportions of patients giving the response ‘strongly agree’ or ‘agree’.

^dResponses were ‘very easy’ or ‘easy.’

^eResponses were ‘extremely convenient’ or ‘somewhat convenient.’

^fResponses were ‘very likely’ or ‘likely.’

^gResponses were ‘extremely anxious’ or ‘very anxious.’