Study population characteristics
Over 2010–2015, 12,830 HA-RRMS adult prevalent patients were included in the study, of which 12,820 (72.0%) were identified in the database through drug use (criterion 1), 250 (1.4%) and 4,981 (27.6%) through relapses (criteria 2 and 3, respectively) (supplement Fig. 1). Among the prevalent patients, 9,596 were incident patients (6,704 with criterion 1 [69.9%], 173 with criterion 2 [1.8%], and 2,719 with criterion 3 [28.3%]). Incident patients were followed-up for a mean duration of 4.0 years, corresponding to 38,394 patients-years. Finally, 8,045 incident patients (83.8%), 3,167 (33.0%) and 961 (10.0%) were followed for at least 2,5 and 7 years, respectively.
Almost ¾ of incident patients were women (7,067 women, 73.7%) and the mean age at index date was 39.9 years old (SD 10.5, median 39.0) (Table 1). Most patients had obtained LTD status (9,539 patients, 99.4%), and 45.6% (4,352 patients) of those with an LTD status got it within five years prior to their index date. Over the study period, 6,646 (69.3%) incident patients had a Charlson Comorbidity Index of 0 and 632 (6.6%) had an index of 3 or above. Of the 9,238 incident patients under the age of 60, 1,835 (19.1%) had a disability pension at index date. Most of them (1,153 patients, 62.8%) had a level 2 disability pension. When considering the first change in pension level over the study period, 1,863 (20.2%) had an increase and 126 (1.4%) a decrease in pension level. Among the patients with an increase to level 2 or 3 disability pension, the change occurred, on average, after 6.4 years.
During the study, on average, incident patients experienced 1 (SD 2.0) relapse every other year. Criterion 1, 2 and 3 patients had 0.04 relapse/year (SD 0.2), 1.0 relapse/year (SD 0.8) and 1.7 relapse/year (SD 1.3), respectively.
Among adults 20 years old and above, the age-standardized prevalence rate increased from 11.0 HA-RRMS cases per 100,000 in 2010 to 26.5 HA-RRMS cases per 100,000 in 2015 (Table 2). The age-standardized incidence rate was 3 new cases per 100,000 in 2010. It increased up to 4.5 new cases per 100,000 in 2012, then remained above 3.6 case per 100,000 until 2015. Between 2010 and the end of the study follow-up in 2017, 122 HA-RRMS patients over 20 died (4 patients aged 18 to 20) and the crude mortality rate varied between 113 deaths per 100,000 HA-RRMS patients in 2010 and 389 deaths per 100,000 HA-RRMS patients in 2015 (Table 3). The mortality rate of HA-RRMS patients was significantly about twice as high as the mortality rate of the French population in 2011, 2014 and 2015.
Within the two years prior to the index date, 7,202 (75.0%) patients had taken a DMD (Table 4). During the study follow-up, 3,809 patients (39.7%) took a DMD; interferon beta was again the most common DMD (22.6% of patients treated) (Table 5). At index date, 6,704 (69.9%) patients were taking an HE-DMD (fingolimod [38.8%] and natalizumab [31.1%]) (Fig. 1). Patients took HE-DMDs (initiated at index date or later) for, on average, 3.5 years prior to discontinue it. This includes 225 women who stopped HE-DMDs and gave birth; 190 (84.4%) of them restarted an HE-DMD after childbirth. During the study, 32.5% of patients treated with natalizumab at index date switched to fingolimod, after a mean treatment duration of 4.2 years. Conversely, 7.0% of those treated with fingolimod at index date switched to natalizumab, after a mean treatment duration of 3.5 years. About a third of patients (32.8%, 1,926 patients out of 5,865) ever treated with fingolimod during the study discontinued their treatment and 63.5% (2,328 out of 3,664 patients) ever treated with natalizumab discontinued their treatment, after a mean treatment duration of 3.5 and 2.7 years, respectively. Of the patients ever treated with fingolimod, 7.4% switched to a DMD and 4.4% to natalizumab (Table 6). Meanwhile, of the patients ever treated with natalizumab, 10.0% switched to a DMD and 27.9% to fingolimod. During the study, 1,308 of 2,892 patients (45.2%) not treated with an HE-DMD at index date initiated an HE-DMD (on average, 4.4 months after the index date). Of those with fingolimod as their first HE-DMD, 102 switched to rituximab and 352 switched to a DMD; of those with natalizumab as their first HE-DMD, 96 switched to rituximab and 305 switched to a DMD. Taken as a whole, 83.5% (8,012 patients) took an HE-DMD during the study.
The following results are based on the 8,045 patients with at least two years of follow-up.
DMD: disease-modifying drug ; HE DMD: High Efficacy disease-modifying treatment (natalizumab, fingolimod). Some patients are present in several boxes and several lines.
Hospitalization, primary and secondary care visits
During the study period, 7,485 patients (93.0%) had at least one MS-related hospitalization (Table 7). The mean annual number of hospitalizations was 4.7 (SD 4.6) and higher during the first year of follow-up (6.3, SD 5.8). During the first year of follow up, almost all patients (7,920 patients, 98.5%) had visited at least once a general practitioner (GP) (Table 8). A large proportion also visited at least once other community-based specialists caring for MS. Throughout the study, patients had, on average, 28.2 (SD 145.2) nurse, 26.0 (SD 37.9) physiotherapist, 8.2 (SD 5.9) GP and 0.8 (SD 1.4) neurologist visits, per year.
Laboratory tests, imaging procedures and medical devices
During the first year of follow up, 6,831 (84.9%) of patients had at least one complete blood count and 4,812 (59.8%) at least one MRI of the central nervous system. On average, 0.9 (SD 0.7) MRI was performed, per year, throughout the study. Most patients (6,997 patients, 87.0%) had at least one medical device reimbursed during the study (Supplement Tables 2–3).