Background

Progressive multifocal leukoencephalopathy (PML) is a serious and potentially fatal complication of some multiple sclerosis (MS) disease-modifying therapies, including fingolimod. Precise estimates and risk stratification tools are not available for fingolimod-related PML.

Objectives

To estimate the global risk of PML in MS patients receiving fingolimod, and to investigate the effect of treatment duration and age on the risk of PML.

Methods

The number of PML cases identified from the manufacturer safety database, attributed to fingolimod by expert adjudication (based on criteria published by Berger et al. in 2014) as of 28 February 2020, was compared with the estimated global number of fingolimod-treated patients at risk (overall, by treatment duration, and by assumed age at fingolimod treatment initiation).

Results

It was estimated that approximately 299,600 patients were treated with fingolimod globally as of 28 February 2020, corresponding to >778,900 patient-years (PYs) of exposure. Of the 188 suspected PML cases reported during fingolimod treatment, 37 confirmed cases were clearly attributed to fingolimod through expert adjudication. In 17 cases, PML was attributed to previous natalizumab treatment. The remaining 134 cases either had inadequate information to confirm the diagnosis of PML or were classified as either possible or not PML. The estimated incidence rate was 4.75 (95% confidence interval [CI]: 3.34; 6.55) per 100,000 PYs. The estimated crude incidence was 0.12 (95% CI: 0.09–0.17) per 1,000 patients. The incidence of PML appears to increase with treatment duration and approach a plateau at approximately 0.13 per 1,000 patients during Year 5, after which data were scarce. Incidence of PML appears to increase between 30 and 50 years of age and then stabilize but the exact shape of the relationship with age is uncertain due to wide CIs, underlying assumptions, and other unknown confounding factors. For both treatment duration and age at treatment initiation, the precision of the incidence estimates was low due to the small number of cases.

Conclusions

PML risk associated with fingolimod is low. Although, the estimated risk of fingolimod-associated PML appears to increase with cumulative exposure, the precise pattern of this relationship remains uncertain. There may be an increase in PML risk with increased age at treatment initiation, although the exact pattern of this possible relationship is also uncertain.

Background

MSProDiscuss^TM is a validated, physician-completed tool aimed at facilitating physician–patient conversation on signs of progression in multiple sclerosis (MS). A set of weighted questions on relapses, symptoms and their impacts as experienced by the patient generate a traffic light system output to aid the discussion. The tool is available online at www.msprodiscuss.com.

Objectives

Evaluate the usability and usefulness of MSProDiscuss in discussing disease progression in daily clinical practice.

Methods

An online qualitative survey consisting of individual questionnaires completed by healthcare professionals (HCPs) after using MSProDiscuss in patient consultations and a final questionnaire to capture overall experience on the tool was conducted in 34 countries. General feedback and recommendations for improving the tool were also collected.

Results

In total, 301 HCPs participated in the survey. The HCPs first completed individual questionnaires after using MSProDiscuss on 6974 MS patients and then a final questionnaire. In 97% (initial questionnaire, i) and 98% (final questionnaire, f) of the time MSProDiscuss was used, the time taken to complete the tool was considered satisfactory (1-4min). The questions were found to be comprehensible in 94% (i) to 97% (f) of cases, and HCPs are willing to use the tool again in the same patient 91% (i) of the time. MSProDiscuss was also useful in discussing MS symptoms and its impact on daily activities (88% i / 92% f) and cognitive function (79% both i and f) and in discussing progression in general (88% i / 90% f).

Moreover, in the final questionnaire, 95% agreed that the questions were similar to those asked by a HCP in a regular consultation. MSProDiscuss was also found to be helpful for understanding the impact of MS symptoms on daily activities (91%) and cognitive function (80%). Overall, 92% of the HCPs would recommend MSProDiscuss to a colleague; 92% think that it is feasible and 86% are willing to integrate MSProDiscuss into their clinical practice. Key recommendations were to allow for longitudinal follow-up, expand on cognitive assessments, and provide a patient-completed version. These have been considered for implementation in the updated version of MSProDiscuss.

Conclusions

The survey results established MSProDiscuss as useful and easy to use tool to facilitate patient-physician discussion of MS progression by structured capturing of patient clinical profile. Most HCPs were willing to integrate MSProDiscuss into their daily clinical practice.