Patient SAtisfaction with the TYSabri SC Formulation – A Swiss multi-centriC, prospective non-intervenTIONal study: the SATYSFACTION study

Abstract

Background:

Natalizumab (NTZ) is a highly effective disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS), originally administered intravenously (IV). A subcutaneous formulation (SC_NTZ) became available in Switzerland in 2021, offering potential advantages.

Objective:

To investigate satisfaction and convenience of use of SC_NTZ in MS patients.

Design:

Swiss, prospective, multicenter study.

Methods:

Consecutive RRMS patients treated with either ⩽6 (starters) or > 6 (long-term users) SC_NTZ injections completed the Treatment Satisfaction Questionnaire with Medication-II (TSQM-II, higher scores indicating greater satisfaction) and the Patient Satisfaction Questionnaire (PSQ) at baseline (Visit 1, V1). Starters were reassessed at the 9th SC_NTZ dose (Visit 2, V2). Non-parametric tests were applied to compare long-term users with starters at V1, and changes from V1 to V2 in starters.

Results:

One hundred six patients (73.6% female, median age 39.6 years, prior IV_NTZ 81.1%) were enrolled, including 79 long-term users and 27 starters. At V1, in the overall group the median (IQR) TSQM-II effectiveness, side effects, convenience and global satisfaction scores were 83 (67–100), 100 (92–100), 83 (72–89) and 83 (75–100), respectively. On the PSQ, the most commonly cited benefit was short administration time (80.2%). SC_NTZ treatment “never” affected work attendance in 54/87 (62.1%) employed patients. Seventy-nine percent participants reported spending ⩽1 h for SC_NTZ administration. Nonetheless, 76/86 (88.4%) of switchers from IV_NTZ found opportunities for discussions with healthcare professionals to be “similar”/”improved,” and 78 (90.7%) preferred SC_NTZ. Findings were consistent across subgroups and time points.

Conclusion:

This real-world, multicenter Swiss study supports SC_NTZ as a well-tolerated, highly accepted, and patient-preferred alternative to IV_NTZ.

Introduction

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system representing the most common cause of nontraumatic neurological disability in young adults. ¹ While no curative treatments are available for MS, several disease-modifying treatments (DMTs) have been approved in recent years that reduce relapse rate and slow disability progression, particularly in the relapsing-remitting (RR) form of the disease. ²

The humanized monoclonal antibody Natalizumab (NTZ) is a highly effective DMT for individuals with RRMS.^3,4 It acts by targeting α4β1 integrin, an adhesion molecule expressed on the surface of lymphocytes, thereby preventing their transmigration across endothelium into the central nervous system.^3,4

Intravenous NTZ (IV_NTZ) was originally developed and approved for RRMS at the dose of 300 mg every 4 weeks.^{3 –5} Comparable pharmacokinetic and pharmacodynamic profiles of SC_NTZ and IV_NTZ have been demonstrated in two studies (Phase II DELIVER and Phase III REFINE).^6,7 Since 2021, a subcutaneous formulation of NTZ (SC_NTZ) has also become available in Europe and Switzerland. ⁵

In Switzerland, SC_NTZ and IV_NTZ must be initiated and monitored by specialists in neurology, due to the potential risk including infusion-related reactions (IRRs) and progressive multifocal leukoencephalopathy. ⁸ IV_NTZ is conventionally administered over 1 h, followed by an additional 1 h-observation period for monitoring possible IRRs, including hypersensitivity reactions. In contrast, SC_NTZ is administered by two consecutive injections of 150 mg each within 30 min, followed by 1 h-observational period for the first six doses. ⁵

The availability of two possible routes of administration for NTZ provides flexibility and potential advantages. SC_NTZ does not require infusion facilities and may reduce treatment-associated costs. Additionally, it allows for shorter administration times, which may improve patient convenience and satisfaction. However, real-world data on patient acceptance, satisfaction, and convenience with SC_NTZ remain limited.

Therefore, we decided to investigate the patients’ satisfaction and convenience concerning the use of SC_NTZ in the Swiss routine clinical setting.

Methods

Setting

This was a prospective, observational, multicenter study conducted between September 2023 and December 2024 and involving five hospital- and office-based Swiss MS centers. Consecutive MS patients treated with SC_NTZ were proposed to participate and were included after signing written inform consent. The study was approved by the local cantonal Ethics committee, Bellinzona (Ref. CE4426).

Main inclusion criteria were (1) age ⩾ 18 years; (2) diagnosis of RRMS according to 2017 McDonald criteria ⁹ ; (3) having received either ⩽6 (starters) or > 6 (long-term users) SC_NTZ administrations in accordance to the Swiss label; (4) having started SC_NTZ independently of study participation. Patients with contraindications to NTZ or unwilling to participate were excluded.

Outcome measures

At baseline (Visit 1, V1) demographic and clinical characteristics were collected. In addition, all participants were asked to complete the Treatment Satisfaction Questionnaire with Medication II (TSQM II), ¹⁰ and the Patient Satisfaction Questionnaire (PSQ).

Starters also completed TSQM II and PSQ at the 9th SC_NTZ administration (Visit 2, V2), a timepoint when the postinfusion observation period is not required any longer potentially influencing treatment satisfaction and convenience.

TSQM II ¹⁰ is a validated patient-reported outcome measure designed to assess treatment satisfaction with medications across four key domains: effectiveness (perceived benefits and control of the condition); side effects (frequency and impact); convenience (ease of use, dosing, and integration into daily life); global satisfaction (overall contentment with the medication). It consists of 11 items, each rated on a Likert-type scale, and generates standardized scores (0–100), where higher scores indicate greater satisfaction. The PSQ is an on-purpose constructed set of 15 questions concerning patients’ satisfaction with the SC_NTZ, main reasons for satisfaction, confirmation of SC_NTZ choice, absenteeism related to SC_NTZ, opportunity to discuss illness or treatments with healthcare professionals during SC_NTZ administration, time needed for the SC_NTZ administration, and preference between SC_NTZ and IV_NTZ.

The primary objective was measuring patient satisfaction related to the SC_NTZ use at V1 (long term-users and starters) and V2 (starters only) by using the TSQM-II total score and effectiveness, side effects, and convenience subscores.

Additional study objective was to evaluate the PSQ at V1 (long-term users and starters) and V2 (starters only). Switching from SC_NTZ to IV_NTZ and SC-NTZ discontinuation were also assessed.

Statistics

Variables were described using counts with percentage and median with interquartile range (IQR). Comparisons of demographic and clinical variables between starters and long-term users were conducted using independent T Test, Pearson’s chi-square test, and the Mann–Whitney U test, as appropriate.

Results of the two questionnaires were analyzed using within- and between-group comparisons. Within-group differences were assessed using Pearson’s chi-square test, McNemar test for binary variables, and McNemar-Bowker test and Wilcoxon signed-rank test for paired data, as appropriate. Comparisons of questionnaire scores between starters and long-term users were performed using the nonparametric Mann–Whitney U test. For PSQ scores, Fisher’s exact test or Pearson’s chi-square test was applied depending on the expected cell frequencies.

Results

A total of 106 patients were included in the study. Of these, 78 (73.6%) were female. The median (IQR) age was 39.6 (34.3–48.9) years, and the median EDSS score was 2.0 (1.5–3.0). The median time since initiation of SC_NTZ was 14 (6.5–18.9) months.

Based on treatment duration, 79 (72%) patients of the overall population were classified as long-term users and 27 (28%) as starters. Eighty-six (81.1%) patients had previously been treated with IV_NTZ, of whom 67 were classified as long-term users, and 19 as starters (Table 1).

Table 1.

Demographic and clinical characteristics of study participants.

Variables	All		Long-term users		Starters		p
	n/median	%/IQR	n/median	%/IQR	n/median	%/IQR	Long-term users versus starters
N	106	100	79	100	27	100
Age	39.6	34.3–48.9	39.8	34.4–49.2	38.8	34.1–48.4	0.573
Age category
18–25	7	6.6	4	5.1	3	11.1
26–35	26	24.5	19	24.1	7	25.9
36–45	39	36.8	30	38.0	9	33.3
46–55	19	17.9	14	17.7	5	18.5
56–65	11	10.4	9	11.4	2	7.4
⩾66	4	3.8	3	3.8	1	3.7
Sex
Male	28	26.4	23	29.1	5	18.5	0.324
Female	78	73.6	56	70.9	22	81.5
EDSS	2	1.5–3	2	1.5–3	2	1–3	0.643
Disease duration	9	3–16	10	4–16	6	3–14	0.362
Prior DMTs
Yes (injectables/orals/monoclonals)	56	52.8	44	55.7	12	44.4	0.374
No	(35/18/3) 50	47.2	(29/13/2) 35	44.3	(6/5/1) 15	55.6
Prior NTZ iv
No	20	18.9	12	15.2	8	29.6	0.151
Yes	86	81.1	67	84.8	19	70.4
Prior NTZ iv infusions	10	4–14	12	10–15	2	1–4	0.411
NTZ sc injections
⩽6	27	25.5	0	0.0	27	100.0	<0.001
7–9	10	9.4	10	12.7	0	0.0
⩾10	69	65.1	69	87.3	0	0.0
Months since NTZ sc start	14	6.5–18.9	17	12.1–20.8	2.3	0.9–4.8	<0.001
JCV status							1.00
NEGATIVE	95	89.6	71	90.0	24	89.0	0.072
POSITIVE	11	10.4	8	10.0	3	11.0
⩽0.9	8	72.7	7	87.5	1	33.3
1.0–1.5	0	0	0	0	0	0
>1.5	3	27.3	1	12.5	2	66.9

TSQM-II scores during SC_NTZ treatment

At V1, the median (IQR) TSQM-II scores for effectiveness were 83 (67–100) for the overall study population, 83 (67–100) for long-term users, and 79 (67–100) for starters. For the side effects domain, scores were 100 (92–100) in the whole cohort, 100 (87.5–100) among long-term users, and 100 (100–100) among starters. Similarly, the convenience sub-score showed values of 83 (72–89) for all participants, 83 (72–89) for long-term users, and 83 (67–89) for starters. Finally, the global satisfaction score among all study participants was 83 (75–100). When stratified according to SC_NTZ treatment duration, long-term users reported a score of 92 (75–100) and treatment starters 83 (67–98). No statistically significant differences were observed between long-term users and starters in all TSQM-II sub-scores (p > 0.1 for all comparisons; see Supplemental Table 1 and Figure 1).

Figure 1.

(a) TSQM-II effectiveness score in long-term users and starters patients. (b) TSQM-II side effects score in long-term users and starters patients. (c) TSQM-II convenience score in long-term users and starters patients. (d) TSQM-II global satisfaction score in long-term users and starters patients.

TSQM-II, Treatment Satisfaction Questionnaire with Medication-II.

At V2, in the starter group the median (IQR) TSQM-II scores for effectiveness, side effects, convenience and global satisfaction were 79 (63–100), 100 (100–100), 83 (61–90), and 83 (67–100), respectively, with no statistical differences compared to V1 (p > 0.1 for all comparisons).

In the overall group at V1, the proportion of patients with a TSQM-II scores for effectiveness, convenience, and global satisfaction equal to or greater than 67 (indicating “satisfied” or above) was 66%, and 75.5% and 76%, respectively. Additionally, 82.1% of patients had a TSQM-II side effects score equal to or greater than 75 (indicating “a little bothersome” or better). These proportions remained similarly high across all time-points in both long-term users and starters, with the exception of long-term users showing significantly higher proportion TSQM convenience scores ⩾ 67 compared to starters (81% vs 59.3%, p = 0.023) at V1 (Table 2).

Table 2.

TSQM scores in Long-term users and Starters.

TSQM	Overall V1 N = 106	Long-term users V1 N = 79	Starters V1 N = 27	p Value a (V1 long vs start)	Starters V2 N = 27	p Value b (start, V1 vs V2)
Effectiveness	70 (66.0%)	55 (69.0%)	15 (55.6%)	0.183	18 (75.0%)	0.248
Side effects	87 (82.1%)	63 (79.7%)	24 (88.9%)	0.285	24 (100%)	0.157
Convenience	80 (75.5%)	64 (81.0%)	16 (59.3%)	0.023	19 (79.2%)	0.317
Global satisfaction	81 (76%)	64 (81%)	17 (63%)	0.056	19 (79.2%)	0.366

^aMann–Whitney Test.

^bWilcoxon Test.

TSQM, Treatment Satisfaction Questionnaire with Medication.

PSQ during SC_NTZ treatment

Patients’ satisfaction with the SC_NTZ and main reasons

Consistent with TSQM-II scores, treatment satisfaction measured on a 1–10 Visual Analog Scale (VAS10) was high across the overall population, with a median (IQR) score of 10 (9–10). Similar levels of satisfaction were reported by long-term users (10 (8–10)) and starters (10 (9–10), p = 0.8), and remained stable among starters at V2 (10 (9–10), p = 0.342 vs V1).

At V1, the most commonly cited reason for satisfaction with SC_NTZ treatment was the “short time required for administration,” reported by 85 (80.2%) participants. This reason was more frequently mentioned by long-term users (67/79, 84.8%) than by starters (18/27, 66.7%), with a borderline statistical significance (p = 0.053). Among starters, this proportion remained stable at V2 (17/27, 63%, p = 0.739).

Additional reasons are reported in Table 3.

Table 3.

PSQ scores in Long-term users and Starters.

PSQ	Overall, V1 N = 106	Long-term users, V1 N = 79	Starters, V1 N = 27	p Value a (long vs start)	Starters, V2 N = 27	p Value a (start, V1 vs V2)
Flexibility	28 (26.4%)	19 (24.1%)	9 (33.3%)	0.448	4 (14.8%)	0.096
Administration time	85 (80.2%)	67 (84.8%)	18 (66.7%)	0.053	17 (63%)	0.739
Convenience	21 (19.8%)	14 (17.7%)	7 (25.9%)	0.405	3 (11.1%)	0.157
Tolerance of injections	26 (24.5%)	20 (25.3%)	6 (22.2%)	1.000	8 (29.6%)	0.480
Side effects	7 (6.6%)	5 (6.3%)	2 (7.4%)	1.000	2 (7.4%)	1.000
Other	4 (3.8%)	2 (2.5%)	2 (7.4%)	0.268	0 (0.0%)	0.157
Does not apply	0 (0.0%)	0 (0.0%)	0 (0.0%)	NA	1 (3.7%)	1.000

^aFischer’s exact test.

PSQ, Patient Satisfaction Questionnaire.

Choice of SC_NTZ

At V1, 103 (97%) participants confirmed their choice of SC_NTZ, and all 24 starters with available data reaffirmed their choice at V2.

Absenteeism due to SC_NTZ treatment

At V1, SC_NTZ treatment “never” affected work attendance in 54 out of 87 (62.1%) employed patients, “sometimes” in 22 (25.3%), and “always” in 11 (12.6%) (p < 0.001). These proportions were consistent between long-term users and new starters, as well as between V1 and V2 within the starter group (Supplemental Figure 1).

The duration of work absence due to SC_NTZ administration varied among patients: 20 (40%) reported absences of ⩽2 h, 17 (34%) reported 2–4 h, and 13 (26%) reported ⩾4 h (p = 0.477).

Time for discussion with healthcare professionals during SC_NTZ access

At V1, 66 (62.3%) participants rated the opportunity to discuss with healthcare professionals as “often” or “always,” compared to 37.7% who reported “never,” “rarely,” or “sometimes” (p = 0.012). The distribution of responses was comparable between long-term users and starters and remained consistent at V2 in the starter group (Supplemental Table 2).

Among the 86 participants who switched from IV_NTZ to SC_NTZ, 76 (88.4%) reported that the time available for discussions with healthcare professionals was “similar” or “improved,” while 10 (11.6%) felt it was reduced (p < 0.001). These proportions were comparable between long-term users and starters and remained stable at V2 among starters (data not shown).

Time required for SC_NTZ treatment

Travel time to reach the facility for SC_NTZ administration varied widely among participants, ranging from less than 15 min to more than 3 h. For the majority (84 out of 105; 80%), travel time was less than 2 h.

At V1, 83/105 (79%) participants reported spending ⩽1 h at the hospital or medical office for SC_NTZ administration, while 22 (21%) reported spending more than 1 h (p < 0.001). The proportion of participants who spent ⩽1 h at the hospital or medical office was significantly higher among long-term users (68 of 79; 86.1%) compared to starters (15 of 26; 57.7%; p = 0.002). However, this proportion increased significantly among starters at V2 compared to V1 (20 of 22; 90.9%; p = 0.016).

Among the 86 participants who switched from IV_NTZ to SC_NTZ, 85 (98.8%) described the switch as a “certain benefit,” “advantage,” or “great benefit” in terms of time required for treatment, while only 1 participant (1.2%) reported “no benefit” (p < 0.001). This perception was consistent across long-term users (N = 67) and starters (N = 19), and sustained at V2 among starters (Supplemental Table 3).

Preference for SC_NTZ over IV_NTZ

At V1, 78 out of 86 (90.7%) participants who had switched from IV_NTZ expressed a preference for SC_NTZ, while 3 (3.5%) preferred IV_NTZ, and 5 (5.8%) had no preference (p < 0.001). The preference for SC_NTZ was significantly higher among long-term users (65 of 67 (97%)) compared to starters (13 of 19 (68.4%); p = 0.001), and remained similarly high among starters at V2 [15 of 17 (88.22%); p = 0.223 vs V1).

Among those who preferred SC_NTZ at V1, the majority (59 of 78; 75.6%) considered it to be “much better” than IV_NTZ, while 17 (21.8%) rated it as “better,” and 2 (2.6%) as “a bit better” (p < 0.001). The distribution of these responses was similar between long-term users and starters, and remained consistent at V2 among starters (Supplemental Figure 2).

SC_NTZ discontinuations

In the starter group, one patient was switched from SC_NTZ to ocrelizumab after seven administrations due to disease progression. Another patient returned to IV_NTZ after five SC_NTZ administrations based on personal preference.

Discussion

The availability of SC administration as an alternative to IV delivery of NTZ offers practical advantages for both healthcare systems and patients.

SC_NTZ can alleviate pressure on infusion facilities, reduce NTZ-administration related costs and serve as a suitable option for individuals with poor venous access. Nonetheless, patient acceptance is essential to ensure treatment adherence and maintain quality of life.

This prospective, multicenter, real-world study in a Swiss MS population demonstrated high satisfaction with SC_NTZ, as reflected by robust TSQM-II scores across treatment-naïve and patients switching from IV_NTZ. These results were supported by findings from a purpose-built PSQ, providing further insight into factors driving patient’s satisfaction.

Shared decision-making between patients and healthcare professionals is a cornerstone of MS care, particularly when selecting among different routes of administration. ¹¹ Therefore, having data on patient acceptance and satisfaction with SC versus IV formulations—when both options are available—would be relevant to support informed decision-making and optimize care. Despite its importance, there is a lack of real-world evidence exploring specifically these topics and the factors being mostly relevant to patients.

In our study, the median TSQM-II global satisfaction score of 83 at V1 indicates that most patients were satisfied or very satisfied with SC_NTZ treatment. The similarly high median scores across specific domains of effectiveness (83), side effects (100), and convenience (83) further emphasize the favorable patient experience with SC_NTZ.

These results were consistent between starters and long-term users, suggesting broad acceptability of SC_NTZ. Our findings align with those of the German-Austrian SISTER study, ¹² which explored patient preference and satisfaction with SC_NTZ versus IV_NTZ in real-world clinical practice. Additionally, they are consistent with the study by Silva et al, which extends investigation of patient satisfaction with SC_NTZ versus IV_NTZ to Latin America MS populations. ¹³ SC_NTZ use was associated with high mean global scores on the TSQM-II, with patients who switched from IV_NTZ to SC_NTZ reporting the highest scores, compared to those initiating IV_NTZ or SC_NTZ.

Recognizing the limitations of TSQM-II in capturing treatment-specific aspects of NTZ administration, we developed the PSQ to explore additional dimensions of patient experience.

Consistent with the scores provided by the TSQM-II, satisfaction ratings on a 10-point VAS were uniformly high (median 10) across subgroups and visits, and the primary driver of satisfaction was the shorter administration time. This was especially appreciated by long-term users—likely due to cumulative exposure reinforcing the benefit. Consistently, “time-saving” was also the most cited reason for preferring SC_NTZ in the SISTER study, ¹² and in the Latin America study, patients receiving SC_NTZ reported higher TSQM-II convenience subscores than those treated with IV_NTZ. ¹³

Effective communication between individuals with MS and health care providers is essential for enhancing understanding of the condition, navigating uncertainty, evaluating treatment choices, and managing the ongoing progression of MS. ¹⁴ Also, health care providers’ responses to questions from individuals with MS can influence patients’ emotions and coping strategies to manage their condition over the long term. ¹⁵ Short administration time required for SC_NTZ did not compromise the perceived quality of interaction with healthcare professionals according to our study. The majority of patients actually indicated frequent opportunities to discuss their treatment and medical condition, which remained consistent over time and were viewed as similar or improved compared to IV_NTZ, requiring longer administration.

Work absenteeism was generally low, with most employed patients reporting that SC_NTZ “never” or only “sometimes” interfered with work. When absences occurred, they were typically short, suggesting a limited impact on productivity. These results support the view that SC_NTZ minimizes disruptions to daily life, building on prior evidence that IV_NTZ already supports work participation and quality of life.^16,17 Logistically, most patients had travel times under 2 h, and nearly 80% spent <1 h at the treatment facility. This proportion was even higher in long-term users (86.1%) and increased over time in new starters (90.9%), consistent with the discontinuation of postinjection monitoring after the sixth SC_NTZ dose. These findings mirror those from Gold et al., ¹² who reported a median treatment time of 1 h for SC_NTZ. Switching from IV to SC_NTZ was perceived as beneficial in terms of time efficiency, with over 98% of patients citing it as an advantage. More than 90% expressed a preference for SC_NTZ, particularly among long-term users, suggesting growing appreciation over time. Similar to findings by Gold et al. ¹² SC_NTZ discontinuations was rare and driven primarily by clinical necessity or personal preference, reinforcing the formulation’s acceptability and tolerability.

Of note, the choice of SC versus IV natalizumab was primarily driven by patient preference and clinical judgment (e.g., in case of difficult IV access) rather than by JCV status or Index categories. Accordingly, approximately 97% of patients had a negative JCV status or an Index < 0.9, a figure similar to that observed in IV_NTZ-treated patients in our Swiss setting, reflecting that JCV status, rather than NTZ administration route, is the main determinant of PML risk. Moreover, over 50% of patients had previously received DMTs, predominantly injectable therapies, indicating that prior exposure to SC treatments did not strongly discourage the use of SC_NTZ. Center policy, infusion facility availability, and monitoring logistics also likely played a minimal role in the decision to use SC_NTZ in our Swiss setting.

Key limitations of this study include its nonrandomized design, the lack of a comparator IV_NTZ arm, the absence of longitudinal data in patients switching from IV_NTZ to SC_NTZ, and potential selection bias. Patient-reported outcomes may be subject to response and recall bias. Although the PSQ lacks formal validation, its results aligned well with the validated TSQM-II. Additionally, some subgroup analyses may be underpowered due to small sample size. However, the consistency of findings across multiple measures and time points strengthens the validity of the results.

Conclusion

This real-world, multicenter Swiss study supports SC_NTZ as a well-tolerated and highly accepted alternative to IV_NTZ. SC_NTZ offers time-saving benefits, minimal impact on work productivity, and preserves the quality of healthcare interaction—factors that may positively influence adherence and long-term outcomes in MS management.