OFSEP - Cohort description

Description of the OFSEP cohort on 8 December 2023

The patients monitored within the framework of OFSEP come from the 40 centers participating in the project corresponding to 46 databases of which 2 includes only NMOSD patients. Each center recruits patients either within a hospital or from a healthcare network.

All data are entered using EDMUS, a specialist medical file enabling the monitoring of multiple sclerosis (MS) patients in routine medical practice.

On 15 June 2013, in an effort to harmonize collection methods and improve data quality, a precise set of data (minimal data) was defined for systematic collection: personal and sociodemographic data, clinical data (neurological episodes, clinical evaluations, irreversible disability), para-clinical data (MRI, etc.) and therapeutic data (disease-modifying treatments). These data can also be used for research purposes.

Number of patients

By 8 December 2023, 40 centers were participing in the compilation of the OFSEP clinical database..

The database comprises 90,176 files, 64,120 (71.1%) of which are for patients who have consulted since 15 June 2013 and for which the minimal data has been collected. Each center has an average of 1,919 files (standard deviation ± 2,163).

Number of patients registered on EDMUS per centre

Since patients may consult doctors in different cities during the course of their lives, it is possible that some have several clinical files: these are what we call duplicates. Furthermore, the MS diagnosis can be difficult to confirm, and the elements in the computer file do not enable diagnostic certainty. Thus, in the presentation below, duplicates, uncertain diagnosis files and patients with acute neuromyelitis optica (Devic's disease) or related neurological syndromes, radiologically isolated syndromes (RIS) or with antibody anti-AQP4 or with antibody anti-MOG have been excluded. A total of 72,859 patients are thus included in the analysis.

Age and gender of patients

Distribution of patient age at disease onset

A majority of women (N=51,639; 71%) compared with men (N=21,220; 29%).

The age of disease onset varies from 1 to 83 years, but the disease starts in most patients between the ages of 20 and 39 (N=47,015; 64.5%). 3,919 patients (5.4%) were identified as having MS before the age of 18 and 5,039 (6.9%) were "late" starters, i.e. after the age of 50 years.

Disease courses

In most cases, the clinical onset of the disease is characterized by a relapse (also called “attack”) (N=64,754; 88.9%), at an average age of 31.4 years (± 10.1); only 11.1% of patients (N=8,105) have an onset disease with a primary progressive course, and much later (43.1 years old ± 11.2 years).

In 14.3% of patients in the OFSEP cohort, the first relapse is isolated (clinically isolated syndrome, CIS); 53.8% of patients have relapsing-remitting MS, 20.7% secondary progressive MS.

Distribution of disease courses

Patient medical follow-up

The duration of the disease, i.e. the time between the first neurological episode and the last consultation, varies from 0 to 77.8 years. Half of the patients have been followed for more than 13 years and 25% for more than 22 years.

Distribution of disease duration

Distribution by date of last clinical evaluation

On 8 December 2023, 50% of patients had consulted for the last time during the 2.9 years prior to export, and 31.6% during the past year. All these patients can be considered as being part of the active patient population of the participating neurology departments, and their data are therefore updated regularly. Conversely, 25% of patients had not consulted within the past 10 years or longer.

In view of the progressive nature of the disease, the distribution between the different courses is highly correlated with the duration of the disease and represents only the state of the patients followed by OFSEP on 8 December 2023.

Distribution of disease courses according to disease duration

Clinically isolated syndromes are very highly represented when the disease first starts, but their number falls over time as patients suffer relapses and the disease evolves towards a relapsing-remitting course.
Similarly, the proportion of relapsing-remitting MS falls as disease duration increases, since more patients develop a secondary progressive course of the disease.

Distribution of disease courses according to patient age at the last clinical evaluation

Using a similar process, the distribution of disease courses varies according to patient age. This is compounded by the fact that primary progressive courses generally start later than the other courses. Thus, at the age of 30, 68.6% of patients have relapsing-remitting MS whereas at 70, 70.2% of patients have a progressive course (27.5% primary progressive and 42.7% secondary progressive).

Recruitment dynamics

Capture rate of patients by OFSEP

The time between the onset of the disease and the date of patient inclusion by a neurologist participating in the OFSEP project is described as the "capture period". The first year after onset of the disease, 39.4% of patients with a remitting course initially and 15.1% of patients with a primary progressive course are taken on by an OFSEP neurologist. Half of the patients with a remitting course initially and half of the patients with a primary progressive course are captured by OFSEP after 2.5 and 4.3 years respectively. Ten years after disease onset, close to 75% of OFSEP patients have been captured, for both remitting and progressive courses.

Symptoms of the first neurological episode

For most patients (47.3%), the first neurological episode involved only an attack of the long tracts. An attack of the long tracts corresponds to walking or balance difficulties, motor disorders (upper and lower limbs), sensory disorders (upper and lower limbs, torso, Lhermitte's sign), urinary or bowel disorders and sexual disorders. Optic neuritis alone is the only symptom of disease onset in 18.1% of patients. Brain stem disorders alone affected 10.7% of patients: this involves oculomotor disorders, vestibular or cochlear disorders, motor and sensory disorders of the face and speech or swallowing problems. Finally, 18% of patients had a combination of symptoms during the first episode of their disease.

Distribution of symptoms of the first neurological episodes

First inter-attack interval

Distribution of period between the first inter-attack interval for relapsing-remitting patients

Among the patients with a relapsing-remitting course (N=39,220), 25% had a second relapse within a year of the first one, half after 1.8 years and 25% after 4.7 years.

Disease-modifying treatment in active patient populations, at the time of the last clinical follow-up

The active patient population is defined as being the set of patients who have consulted at least once during the two years prior to the export on 08 December 2023. This active population comprises 30,600 patients (i.e. 42% of the OFSEP cohort). Ongoing disease-modifying treatments during the last patient consultation are classed according to treatment type (moderately effective, highly effective, with no MA (market authorization) for MS and clinical trials) and according to MS course on the graphs below.

List of abbreviations for treatments: INF β: Beta interferon; DMF: Diméthyl fumarate; DRF: Diroximel fumarate; GA: Glatiramer acetate; FNG: Fingolimod; NTZ: Natalizumab; MMF: Mycophenolate mofetil.

Clinically isolated syndrome

The active patient population has 4,880 patients with a clinically isolated syndrome, i.e. 15.9% of patients in the active patient population. Among them, 31.9% are taking no disease-modifying treatment. Patients receiving treatment are mainly (39%) on moderately effective treatments: beta interferon (6.3%), dimethyl fumarate (11.7%), diroximel fumarate (2.2%), teriflunomide (13.3%) and glatiramer acetate (5.5%).

Repartition of ongoing disease-modifying treatments for CIS patients

Relapsing-remitting courses

Repartition of ongoing disease-modifying treatments for relapsing-remitting patients

There are 17,768 patients with relapsing-remitting MS in the active patient population (58.1%). Among them, 19.6% are taking no disease-modifying treatment. Highly effective treatments are the most common (48.6%), ahead of moderately effective treatments (28.7%). However, among the most frequently used molecules, three are highly effective treatments (ocrelizumab 17.3%; fingolimod 13%; natalizumab 12.5%) and two are moderately effective treatments (teriflunomide 10.1%; dimethyl fumarate 7.8%).

Secondary progressive MS

There are 5,132 patients with secondary progressive MS in the active patient population (16.8%). Half of these patients are not taking any disease-modifying treatment (51.9%). Most patients are on highly effective treatments (24.6%), in spite of having non MA for progressive courses of the disease, particularly ocrelizumab (17.4%). As many patients are on drugs with no MA for MS (16.6%), particularly rituximab (10.6%) and mycophelonate mofetil (3.0%).

Repartition of ongoing disease-modifying treatments for secondary progressive

Primary progressive MS

Repartition of ongoing disease-modifying treatments for primary progressive patients

There are 2,820 patients with primary progressive MS in the active patient population (9.2%). These are the least-treated patients: 56.6% are taking no treatment. 26.1% are on drugs with no MA for MS, including 20.3% taking rituximab and 2.6% mycophelonate mofetil. Some patients are on highly effective treatments (12.3%), particularly ocrelizumab (10.7%).