Teriflunomide levels in women whose male sexual partner is on teriflunomide for relapsing multiple sclerosis.

BACKGROUND: For small molecules such as teriflunomide, used to treat relapsing multiple sclerosis (MS), that are potentially embryotoxic, there is a theoretical risk of transmission of the medication from males on the drug to female sexual partners. However, that risk has been undefined up to now. METHODS: Teriflunomide concentrations were assayed concomitantly in ten sexually active couples, not using barrier methods of contraception, in whom the male partner with MS was on treatment with teriflunomide 14 mg daily for at least two months. These results were compared by male and female age, teriflunomide concentrations and reported average number of incidences of sexual intercourse per month. The threshold level of detection of teriflunomide was 0.020 µg/ml in females. RESULTS: The average age of the cohort was 46.70 for males and 47.10 for females. Four of ten females had detectible teriflunomide concentrations (mean 0.046 µg/ml (range 0.22-0.077, standard deviation 0.025). Male age and both female teriflunomide positive threshold and female teriflunomide concentration were inversely correlated (r = 0.67, R2=0.45, p = 0.034) for the former and (r = 0.62, R2=0.39, p = 0.05, ns) for the latter. No significant correlations were observed for female age, male teriflunomide concentrations, or reported mean monthly episodes of sexual intercourse. CONCLUSION: This limited study suggests that the small risk that low levels of teriflunomide can be transmitted from male to female partners via sexual intercourse is related to male age. This supports the recommendations found in the United States Product Insert (USPI) stating that men taking teriflunomide who do not wish to father a child, and their female partners, should use reliable contraception. Men wishing to father a child should discontinue use of teriflunomide and undergo an accelerated elimination procedure to reduce the plasma concentrations of the medication to less than 0.02 mg/L (0.02 µg/ml1.

Neurofilament light chain as an indicator of exacerbation prior to clinical symptoms in multiple sclerosis.

BACKGROUND: Biomarkers may be a sensitive measure of disease activity in patients with multiple sclerosis (pwMS). OBJECTIVE: A pwMS had a marked increase of neurofilament light chain (NfL) in CSF 9-weeks prior to a clinical exacerbation. METHODS AND RESULTS: Brain MRI, CSF, EDSS were measured at baseline, 6 weeks and 28 weeks. The patient had an exacerbation at week 15 of study but the NfL measured at week 6 were found to show a nearly 3-fold increase of CSF NfL levels prior to symptoms when the NfL levels were later measured. CONCLUSION: This is an example supporting the usefulness of NfL in monitoring disease activity in pwMS which may predict disease activity prior to a clinical exacerbation.

Reducing return of disease activity in patients with relapsing multiple sclerosis transitioned from natalizumab to teriflunomide: 12-month interim results of teriflunomide therapy.

BACKGROUND: Natalizumab is an effective treatment for relapsing multiple sclerosis. Return of disease activity upon natalizumab discontinuance creates the need for follow-up therapeutic strategies. OBJECTIVE: To assess the efficacy of teriflunomide following natalizumab discontinuance in relapsing multiple sclerosis patients. METHODS: Clinically stable relapsing multiple sclerosis patients completing 12 or more consecutive months of natalizumab, testing positive for anti-John Cunningham virus antibody, started teriflunomide 14 mg/day, 28 ± 7 days after their final natalizumab infusion. Physical examination, Expanded Disability Status Scale, laboratory assessments, and brain magnetic resonance imaging were performed at screening and multiple follow-up visits. RESULTS: Fifty-five patients were enrolled in the study. The proportion of patients relapse-free was 0.94, restricted mean time to first gadolinium-enhancing lesion was 10.9 months and time to 3-month sustained disability worsening was 11.8 months. The mean number of new or enlarging T2 lesions per patient at 12 months was 0.42. Exploratory analyses revealed an annualized relapse rate of 0.08, and a proportion of patients with no evidence of disease activity of 0.68. Forty-seven patients (85.5%) reported adverse events, 95% of which were mild to moderate. CONCLUSIONS: Teriflunomide therapy initiated without natalizumab washout resulted in a low rate of return of disease activity. Clinicians may consider this a worthwhile strategy when transitioning clinically stable patients off natalizumab to another therapy.ClinicalTrials.gov Identifier: NCT01970410.