Description of the OFSEP cohort on 15 December 2020
The patients monitored within the framework of OFSEP come from the 37 centers participating in the project corresponding to 42 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 15 December 2020, 37 centers were actively participating in the compilation of the OFSEP clinical database.
The database comprises 79,233 files, 51,846 (65.4%) 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 1,886 files (standard deviation ± 2,023).
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 64,620 patients are thus included in the analysis.
Age and gender of patients
A majority of women (N=45,852; 71%) compared with men (N=18,768; 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=41,810; 64.7%). 3,481 patients (5.4%) were identified as having MS before the age of 18 and 4,297 (6.6%) were "late" starters, i.e. after the age of 50 years.
In most cases, the clinical onset of the disease characterized by a relapse (also called “attack”) (N=57,334; 88.7%), at an average age of 31.4 years (± 10.1); only 11.3% of patients (N=7,286) have an onset disease with a primary progressive course, and much later (42.8 years old ± 11 years).
In 12.6% of patients in the OFSEP cohort, the first relapse is isolated (clinically isolated syndrome, CIS); 54.8% of patients have relapsing-remitting MS, 21.3% secondary progressive MS.
Patient medical follow-up
On 15 December 2020, 50% of patients had consulted for the last time during the 2.7 years prior to export, and 28% 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 9 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 15 December 2020.
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.
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, 71.6% of patients have relapsing-remitting MS whereas at 70, 76.7% of patients have a progressive course (26.8% primary progressive and 49.8% secondary progressive).
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, 38.2% of patients with a remitting course initially and 15.4% 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 2.7 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 (46.9%), 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 18.2% 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, 18.1% of patients had a combination of symptoms during the first episode of their disease.
First inter-attack interval
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 15/12/2020. This active population comprises 27,281 patients (i.e. 42.2% of the OFSEP cohort). Disease-modifying treatments on going during the last patient consultation are classed according to treatment type (first-line, second-line, 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: Diméthylfumarate; GA: Glatiramer acetate; FNG: Fingolimod; NTZ: Natalizumab; MMF: Mycophenolate mofetil.
- Clinically isolated syndrome
The active patient population has 3,727 patients with a clinically isolated syndrome, i.e. 13.7% of patients in the active patient population. Among them, 40.4% are taking no disease-modifying treatment. Patients receiving treatment are mainly (48.6%) on first-line treatments: beta interferon (9.5%), dimethyl fumarate (13.4%), teriflunomide (13.4%), glatiramer acetate (8.4%) and ocrelizumab (3.9%).
- Relapsing-remitting courses
There are 15,879 patients with relapsing-remitting MS in the active patient population (58.2%). Less than one quarter (23.1%) of them are taking no disease-modifying treatment. First-line treatments are the most common (43.6%), ahead of second-line treatments (28.6%). However, among the most frequently used molecules, two are second-line treatments (fingolimod 16.1%; natalizumab 12.4%) and three are first-line treatments (beta interferons 8.7%; teriflunomide 11.4%; dimethyl fumarate 9.9%).
- Secondary progressive MS
There are 4,959 patients with secondary progressive MS in the active patient population (18.2%). A large majority of these patients are not taking any disease-modifying treatment (56.4%). Most of the treatments given to these patients have no MA for MS (22.1%), particularly rituximab (11.8%) and mycophenolate mofetil (4.6%). Some patients are on first-line treatments (in spite of having no MA for progressive courses of the disease), particularly ocrelizumab (7.2%) and beta interferons (2.5%).
- Primary progressive MS
There are 2,716 patients with primary progressive MS in the active patient population (10%). These are the least-treated patients: 62.8% are taking no treatment. 26.2% are on drugs with no MA for MS, including 16.8% taking rituximab and 3.6% mycophelonate mofetil.