The preferences of people with amyotrophic lateral sclerosis on riluzole treatment in Europe

Patient characteristics and treatment history

The study involved a total number of 117 participants: 58 were PALS and 59 were caregivers who responded on behalf of PALS unable to speak or use a computer autonomously. Since the caregivers reported the PALS’ preferences hereafter we use the term PALS to indicate all the respondents. 32 participants originated from Germany, 32 from Italy 49 from Spain and only 4 from France (unsuccessful recruitment).

To evaluate the reliability of the survey, 8 participants (2 per country) were asked to complete an online survey and to take part in a telephone qualitative interview. The test confirmed that the survey questions were comprehensible and appropriate in length and number.

Hereafter, this paper reports the results of the online survey which was completed by 109 participants.

The age of the respondents ranged between 30 and 70 years, and the average time from symptom onset to diagnosis was 12.5 months, 62% had a spinal onset type ALS (n = 68). Overall, 70% of PALS (n = 76) suffered from dysphagia and had problems eating (ranging from less severe form like choking during eating to complete dependence on feeding tubes). The baseline characteristics of the participants, including ALS onset and stages of ALS, are summarized in Supplementary Table 1.

Regarding their treatment history, 99% of PALS (n = 108) responded that they were on ALS-specific medications. At the time of the interview, 67% (n = 73 of patients had been treated with riluzole tablets, 29% (n = 32) with riluzole oral suspension, and 5% (n = 5) with edaravone) (Supplementary Table 2).

Mean Satisfaction with the current riluzole formulations

PALS were moderately satisfied with riluzole tablets (3.2/5, where 5 is the maximum score) and oral suspension (3.0/5) with no statistical difference between formulations (p = 0.385) (Table 1). Tablet users were less satisfied with the formulation itself (3.0/5) and with the ease of self-administration (3.1/5). Oral suspension users did not appreciate manageability (2.9/5), ease of self-administration (2.7/5) and, interestingly, the formulation itself (2.8/5) (Table 1).

Overall, the mean satisfaction was significantly lower for patients affected by dysphagia than for those not affected (2.9/5 vs. 3.7/5 respectively; p = 0.001) (Table 1).

Manipulating riluzole tablets

Due to difficulties in swallowing, 51% of tablet users (n/N = 37/72) declared that they sometimes or regularly crushed the tablets. Among dysphagic tablet users, up to 73% (n/N = 29/40) sometimes or regularly crushed the tablets compared to 25% (n/N = 8/32) in non dysphagic tablet users (p < 0.001) (Fig. 1). Notably, 19% of patients noticed some residue of crushed tablets that had not been ingested. Crushed tablets were mixed with food or liquid in 27% (n/N = 10/37) and 22% (n/N = 8/37), respectively. (Supplementary Fig. 1) These findings suggested that riluzole tablets manipulation is a widely used practice, regardless of the disease progression (i.e. the presence or absence of dysphagia). It should be noted that these practices may result in underdosing and could negatively impact patient satisfaction.

Frequency of manipulation of riluzole tablets by PALS. Current tablet manipulation. All percentages were calculated versus the answers per each group (dysphagic, non dysphagic, overall).

PALS who always crushed the tablets (35%, n/N = 25/72) showed a significantly lower mean satisfaction than those who never crushed the tablets (2.1/5 regularly/always crushing vs. 3.9/5 no crushing; p < 0.0001), while the mean satisfaction of PALS who sometimes crushed the tablets was 3.5/5 (p = 0.1363 vs no crushing) (Table 2).

Manipulating riluzole oral suspension

Among PALS treated with riluzole oral suspension, 50% (n/N = 16/32) declared that they sometimes or regularly manipulate the liquid formulation. In this subgroup, 69% of cases mixed the suspension with liquids or food (n/N = 11/16). Overall, the oral suspension was administered with a syringe (16%, n/N = 5/32), with a spoon (19%, n/N = 6/32) and through a feeding tube (22%, n/N = 7/32). It is noteworthy that in the qualitative interview, all the respondents stated that mixing with other liquids or food could facilitate administration due to the thick consistency of the riluzole oral suspension. Among oral suspension users (n = 32), PALS who always mixed the oral suspension (28%, n = 9) reported a mean satisfaction of 2.6/5 compared to 3.3/5 for PALS who never altered the oral suspension (p = 0.093). In particular, patients who regularly manipulate oral suspension showed low satisfaction with the formulation (2.0/5), with the easiness of self-administration, and with preparing the treatment before administration (2.4/5) as well as moderate satisfaction with package weight and size (3.3/5) (Table 3).

Postponing or missing a treatment

Postponing or missing the treatment is a possible consequence of low satisfaction. PPS asked all PALS if these events occurred and the rationale behind their conduct. In the overall population, 46% of the respondents (n/N = 50/109) either postponed or missed a daily treatment (n = 24 postponed and missed, n = 22 postponed, n = 4 missed) because of swallowing difficulties or a lack of independence in self-administration.

Switching, interrupting or choosing ALS-specific treatments

13% of the respondents who were on ALS-specific medication either switched or interrupted their treatment (n/N = 14/108); among these, 8 PALS reported the reason for switching: 50% (n/N = 4/8) reported difficulties in swallowing the tablets, and 63% (n = 5/8) mentioned a variety of other reasons unrelated to the formulation (i.e. side effects, disease progression). (Supplementary Table 2) In the overall population, the main criteria for a possible future treatment switch were the concern of choking and, to the same extent, a doctor’s recommendation or ease of ingesting. (Supplementary Fig. 2).

Consistently, the most important criterion for choosing a new treatment was a low risk of choking (67% of patients n/N = 73/109). (Supplementary Fig. 3).

Driving factors for choosing a different formulation

Considering the difficulties expressed by PALS taking riluzole tablets or the oral suspension formulation and the many strategies used to overcome them, PPS evaluated how the inherent characteristics of a new oral film formulation could improve satisfaction and adherence and decrease the overall burden on PALS. The most appreciated characteristics (mean scores) were ease of use and convenient packaging (4.3 and 4.0/5, respectively). The PALS also gave high scores for better self-administration (3.9/5), good oral-dissolving properties without tongue motility and no need for water or salivary stimulation (both 3.8/5). The survey results revealed mean scores above 3.0/5. also for lower risk of underdosing and lower risk of microbial contamination (both 3.7/5), followed by the reduction of metallic taste (3.6/5). Table 4 shows the results for tablets and oral suspension users, with no numerically relevant differences between the subgroups.

These findings suggested that the manageability of the treatment, the ease of self-administration and the oral-dissolving properties could be important driving factors when choosing a treatment, influencing adherence. The average level of compellingness was numerically similar between dysphagic and non-dysphagic PALS or according to the frequency of formulation manipulation (Supplementary Table 3). Taken together, these results indicated that the features of a new hypothetical product (including reducing underdosing or contamination) may be appreciated during all phases of ALS.