Evaluation of the Incidence of Relapses in Patients With Biotin-treated Progressive Multiple Sclerosis (IPBio-SeP)

University Hospital, Clermont-Ferrand

Status: Unknown

Conditions: Progressive Multiple Sclerosis

Treatments: Drug: biotin; Other: propensity score

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT03552211

CHU-388

Details and patient eligibility

About

Background: High dose biotin is a therapeutic option for French progressive Multiple Sclerosis (MS) patients, without relapse for at least one year, since June 1, 2016. Despite the inflammatory activity of progressive forms of MS is known to be low, several publications mentioned clinical and/or radiological activity for biotin-treated patients.

Objectives:

1. To determine if high dose biotin increase the clinical inflammatory activity of patients with a progressive form of MS.
2. To compare the clinical characteristics of the relapses that occurred with biotin or not.
3. To describe the characteristics of the patients with a clinical inflammatory activity with biotin.

Methods: This is a national, academic, observational and retrospective study comparing one group of progressive MS patients with high dose biotin to another group without this treatment using a propensity score, in intention to treat. The main judgment criterion is the annualized relapse rate (ARR) from the beginning of the biotin to the last evaluation available before the data extraction. A Student's t test will be used. A negative binomial modelling with relapses counting over a period of exposure and taking into account the inter and intra center variability will be used. The statistical tests will be adapted to the nature of the variables concerning the secondary judgment criteria.

Expected results: This French national study will provide a better knowledge of the inflammatory activity of the progressive forms of MS treated with high dose biotin. If an increased clinical inflammatory activity is highlighted with biotin a prospective study will be necessary to confirm the result before a specific information of the scientific community and the patients about this risk or even an amendment of prescription rules in order to secure the use of the product. On the contrary, the absence of increased risk of clinical inflammatory activity with biotin would help to reassure the prescriber and the patient about the innocuity of the treatment.

Full description

Investigators are going to recruit retrospectively all the patients treated with biotin since the product is available in France, in all French MS centers that agree to participate (maximum 30). They are going to collect through medical records, demographic data (as age, gender, MS center localization), but also data about the disease (as MS duration, primary progressive or secondary progressive MS), data about disability (with several Expanded Disability Status Scale -EDSS- scores at different time points) and data about treatments (as duration of biotin, existence of other concomitant disease-modifying therapy). For comparison, a control group without biotin is going also to be recruited from the European Database for Multiple Sclerosis (EDMUS). The same data as described above are going to be collected for the controls.

Enrollment: 3,000 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• For the patients treated with biotin :
• progressive form of MS (primary or secondary)
• age between 18 and 80 years
• Expanded Disability Status Scale (EDSS) between 3 and 7.5 at the beginning of biotin
• treatment with biotin 300 mg per day at least one time, ongoing or stopped
• no relapse in the year preceding biotin introduction
• follow-up in an MS expert center
• For the controls :
• progressive form of MS (primary or secondary)
• age between 18 and 80 years
• Expanded Disability Status Scale (EDSS) between 3 and 7.5 at the baseline
• EDMUS data base fulfilled at least three times during the two previous years
• no relapse in the year preceding the baseline
• follow-up in an MS expert center

Exclusion criteria

• For all participants :
• other disease modifying therapy (DMT) than interferon, methotrexate, mycophenolate mofetil, azathioprine, rituximab, ocrelizumab
• For the controls :
• treatment with biotin actually or in the past
• follow-up in an MS expert center who do not provide exhaustive information about biotin

Trial design

3,000 participants in 2 patient groups

Patients treated with biotin

Description:

This is a national, academic, observational and retrospective study comparing one group of progressive MS patients with high dose biotin to another group without this treatment using a propensity score, in intention to treat

Treatment:

Drug: biotin

Control patients

Description:

This is a national, academic, observational and retrospective study comparing one group of progressive MS patients with high dose biotin to another group without this treatment using a propensity score, in intention to treat

Treatment:

Other: propensity score