Subcutaneously administered methotrexate for rheumatoid arthritis, by prefilled syringes versus prefilled pens: patient preference and comparison of the self-injection experience

Figures & data

Table 1 Preference, usability, and tolerability outcomes

Primary end point – patient preference

“Overall, if you could choose, which of both self-injection systems would you prefer for future MTX treatment?”

Two categories were suggested: “I prefer the prefilled pen” and “I prefer the prefilled syringe”

Secondary end points

Six-item questionnaire related to the overall ease of use, acceptability, and satisfaction with either the MTX prefilled pen or the MTX prefilled syringe to be indicated

“The self-injection is easy to perform using few steps”

“I feel comfortable to perform the self-injection correctly without help”

“The injection system lies comfortably and secure in the hand during the injection”

“I am not scared of being hurt before the injection is done”

“I am not scared of being hurt after the injection is done”

“It does not take much effort to overcome self-injection”

Self-Injection Assessment Questionnaire (SIAQ)

At baseline, before self-injection:

“In general, how afraid are you of needles?”

“In general, how afraid are you of having an injection?”

“How anxious do you feel about giving yourself an injection?”

“How confident are you about giving yourself an injection in the right way?”

“How confident are you about giving yourself an injection in a clean and sterile way?”

“How confident are you about giving yourself an injection safely?”

Possible answers for all the above items: “not at all”; “a little”; “moderately”; “very”; “extremely”

“Overall, how satisfied are you with your current way of taking your medication?”

Possible answers: “very dissatisfied”; “dissatisfied”; “neither dissatisfied nor satisfied”; “satisfied”; “very satisfied”

After self-injection, at the end of the two periods (the questionnaire covered the following topics, each containing several questions):

Feelings about injections

Self-image

Self-confidence

Pain and skin reactions during or after the injection

Ease of use of self-injection device

Satisfaction with self-injection

(Answers were transformed to a score, where a score of one corresponded to the patient’s worst experience, and a score of ten corresponded to the patient’s best experience)

Study nurse and investigator preference of the MTX prefilled pen at the end of study

“Overall, how would you rate the experience made by the patients with the prefilled pen during the study?” The answer was given on a five-point semantic Likert-type scale, where a score of one corresponded to the worst experience, and a score of five corresponded to the best experience

“Which of both self-injection systems would you recommend to your patients for future MTX treatment?” The following answers could be chosen: “prefilled pen” or “prefilled syringe”

Pen dysfunction

“Did you notice any defects in the pen, like cracks or breaks?” (Yes/No; if yes, please specify)

“Was it possible to activate the injection by pushing the knob?” (Yes/No, if no, please give details)

“Has the whole solution been injected (the black plunger is located at the bottom of the syringe body)? (Yes/No, if no, please give details)

“Did you have any other difficulties using the prefilled pen? (Yes/No; If yes, can you tell me about it?”

Abbreviation: MTX, methotrexate.

Table 2 Demographics and baseline characteristics

Characteristic	Treatment sequence pen-syringe (n=56)	Treatment sequence syringe-pen (n=55)	Total (n=111)
Sex
Woman, n (%)	36 (64.3%)	45 (81.8%)	81 (73.0%)
Men, n (%)	20 (35.7%)	10 (18.2%)	30 (27.0%)
Age, mean ± SD (years)	56.3±11.0	52.5±10.2	54.4±10.8
Weight, mean ± SD (kg)	82.6±18.2	77.3±14.6	80.0±16.7
Height, mean ± SD (cm)	169.0±9.6	168.7±8.1	168.8±8.8
Body mass index, mean ± SD (kg/m^2)	28.8±5.2	27.2±4.9	28.0±5.1
Concomitant diseases (≥10% of patients)
Arterial hypertension, n (%)	22 (39.3%)	19 (34.5%)	41 (36.9%)
Osteoarthritis, n (%)	8 (14.3%)	3 (5.5%)	11 (9.9%)
Osteoporosis, n (%)	6 (10.7%)	5 (9.1%)	11 (9.9%)
Osteopenia, n (%)	6 (10.7%)	4 (7.3%)	10 (9.0%)
Duration of rheumatoid arthritis, mean ± SD (years)	3.0±3.0	3.5±4.6	3.3±3.9
Previous MTX treatment, n (%)	45 (80.4%)	44 (80.0%)	89 (80.2%)
Duration of previous oral MTX treatment, mean ± SD (months)	31.2±33.2	31.7±41.0	31.5±37.1
DAS28, mean ± SD	4.5±1.0	4.5±1.1	4.5±1.0
>2.6 to ≤3.2	6 (10.7%)	7 (12.7%)	13 (11.7%)
>3.2 to ≤5.1	36 (64.3%)	33 (60.0%)	69 (62.2%)
>5.1	14 (25.0%)	15 (27.3%)	29 (26.1%)

Abbreviations: DAS28, Disease Activity Score 28; MTX, methotrexate; SD, standard deviation.

Figure 1 Overall preference for MTX prefilled pen and stratification by baseline characteristics.

Notes: N = total number of patients, excluding three patients with missing information (n=2) and concomitant use of pen and syringe (n=1) (complete-case analysis); n= number of patients with preference for pen.
Abbreviations: BMI, body mass index; CI, confidence interval; DAS28, Disease Activity Score 28; MTX, methotrexate.

Table 3 Preference for MTX prefilled pen applying a six-item questionnaire related to the overall ease of use, acceptability, and satisfaction

Item	n (%)
“The self-injection is easy to perform using few steps”
Preference for MTX pen	81 (73.0%)
95% CI	63.7–81.0
“I feel comfortable to perform the self-injection correctly without help”
Preference for MTX pen	82 (73.9%)
95% CI	64.7–81.8
“The injection system lies comfortably and secure in the hand during the injection”
Preference for MTX pen	84 (75.7%)
95% CI	66.6–83.3
“I am not scared of being hurt before the injection is done”
Preference for MTX pen	82 (73.9%)
95% CI	64.7–81.8
“I am not scared of being hurt after the injection is done”
Preference for MTX pen	84 (75.7%)
95% CI	66.6–83.3
“It does not take much effort to overcome self-injection”
Preference for MTX pen	74 (66.7%)
95% CI	57.1–75.3

Abbreviations: CI, confidence interval; MTX, methotrexate.

Table 4 Frequency distribution of SIAQ “PRE” module items

SIAQ item	Treatment sequence pen-syringe (n=56)	Treatment sequence syringe-pen (n=55)	Total (n=111)
Feeling about injections
In general, how afraid are you of needles?
Not at all/A little	44 (78.5%)	37 (67.3%)	81 (72.9%)
Moderately	9 (16.1%)	11 (20.0%)	20 (18.0%)
Very/Extremely	3 (5.4%)	7 (12.7%)	10 (9.0%)
In general, how afraid are you of having an injection?
Not at all/A little	44 (78.6%)	43 (78.2%)	87 (78.3%)
Moderately	11 (19.6%)	7 (12.7%)	18 (16.2%)
Very/Extremely	1 (1.8%)	5 (9.1%)	6 (5.4%)
How anxious do you feel about giving yourself an injection?
Not at all/A little	39 (69.7%)	38 (69.1%)	77 (69.3%)
Moderately	8 (14.3%)	7 (12.7%)	15 (13.5%)
Very/Extremely	9 (16.1%)	10 (18.2%)	19 (17.1%)
Self-confidence
How confident are you about giving yourself an injection in the right way?
Extremely/Very	30 (53.5%)	32 (58.2%)	62 (55.8%)
Moderately	12 (21.4%)	11 (20.0%)	23 (20.7%)
A little/Not at all	13 (23.3%)	12 (21.9%)	25 (22.5%)
Missing data	1 (1.8%)	0 (0.0%)	1 (0.9%)
How confident are you about giving yourself an injection in a clean and sterile way?
Extremely/Very	35 (62.5%)	40 (72.7%)	75 (67.6%)
Moderately	10 (17.9%)	6 (10.9%)	16 (14.4%)
A little/Not at all	10 (17.9%)	9 (16.3%)	19 (17.1%)
Missing data	1 (1.8%)	0 (0.0%)	1 (0.9%)
How confident are you about giving yourself an injection safely?
Extremely/Very	33 (58.9%)	35 (63.6%)	68 (61.3%)
Moderately	12 (21.4%)	11 (20.0%)	23 (20.7%)
A little/Not at all	10 (17.9%)	9 (16.4%)	19 (17.1%)
Missing data	1 (1.8%)	0 (0.0%)	1 (0.9%)
Satisfaction with self-injection
Overall, how satisfied are you with your current way of taking your medication?
Very satisfied/Satisfied	30 (53.6%)	30 (54.5%)	60 (54.0%)
Neither dissatisfied nor satisfied	14 (25.0%)	14 (25.5%)	28 (25.2%)
Dissatisfied/Very dissatisfied	8 (14.2%)	7 (12.8%)	15 (13.5%)
Missing data	4 (7.1%)	4 (7.3%)	8 (7.2%)

Abbreviations: SIAQ, Self-Injection Assessment Questionnaire; PRE module, completed prior to the first injection.

Figure 2 Distribution of domain scores of the SIAQ POST-module (histogram for each device; LS means among figures are connected).

Abbreviations: CI, confidence interval; diff, difference; LS, least square; SIAQ, Self-Injection Assessment Questionnaire.

Table 5 Frequency of patients with symptoms at the injection sites, as rated by patient or the investigator, within 48 hours after injection (safety analysis set; n=120)

Local tolerability symptoms	Pen	Syringe	P-valuea
Number of patients with available data	116 (100.0%)	117 (100.0%)
Patients with any event	52 (44.8%)	54 (46.2%)
Pain
Any event	25 (21.6%)	10 (8.5%)	0.0019
Mild	23 (19.8%)	8 (6.8%)
Moderate	2 (1.7%)	2 (1.7%)
Redness
Any event	19 (16.4%)	36 (30.8%)	0.0421
Mild	14 (12.1%)	32 (27.4%)
Moderate	5 (4.3%)	4 (3.4%)
Swelling
Any event	8 (6.9%)	9 (7.7%)	0.9648
Mild	7 (6.0%)	7 (6.0%)
Moderate	1 (0.9%)	2 (1.7%)
Hematoma
Any event	33 (28.4%)	26 (22.2%)	0.1583
Mild	24 (20.7%)	23 (19.7%)
Moderate	8 (6.9%)	3 (2.6%)
Severe	1 (0.9%)	0 (0.0%)
Itching
Any event	10 (8.6%)	10 (8.5%)	1.0000
Mild	7 (6.0%)	8 (6.8%)
Moderate	2 (1.7%)	1 (0.9%)
Severe	1 (0.9%)	1 (0.9%)

Notes:

a P-value for testing difference between devices (Wilcoxon test for matched pairs).

Table 6 Frequency of patients with adverse events (safety analysis set; n=120)

MedDRA system organ class	Pen	Syringe	Total
Preferred term	n (%)	n (%)	n (%)
Number of patients	116 (100.0%)	117 (100.0%)	120 (100.0%)
Patients with any event	24 (20.7%)	19 (16.2%)	38 (31.7%)
Infections and infestations (any event)	10 (8.6%)	8 (6.8%)	18 (15.0%)
Nasopharyngitis	7 (6.0%)	5 (4.3%)	12 (10.0%)
Cystitis	1 (0.9%)	1 (0.9%)	2 (1.7%)
Gastrointestinal disorders (any event)	10 (8.6%)	3 (2.6%)	13 (10.8%)
Nausea	6 (5.2%)	3 (2.6%)	9 (7.5%)
Vomiting	2 (1.7%)	0 (0.0%)	2 (1.7%)
Nervous system disorders (any event)	4 (3.4%)	1 (0.9%)	5 (4.2%)
Headache	3 (2.6%)	0 (0.0%)	3 (2.5%)
Dizziness	1 (0.9%)	1 (0.9%)	2 (1.7%)
Skin and subcutaneous tissue disorders (any event)	1 (0.9%)	4 (3.4%)	5 (4.2%)
General disorders and administration site conditions (any event)	1 (0.9%)	3 (2.6%)	4 (3.3%)
Investigations (any event)	2 (1.7%)	1 (0.9%)	3 (2.5%)
Hepatic enzymes increased	2 (1.7%)	0 (0.0%)	2 (1.7%)
Psychiatric disorders (any event)	1 (0.9%)	1 (0.9%)	2 (1.7%)

Abbreviation: MedDRA, Medical Dictionary for Regulatory Activities.