Background

The landscape of multiple sclerosis (MS) management is rapidly evolving in last few years . With the introduction of new MS therapies the neurologists and the patients are able to make treatment decisions based on many factors including , disease severity, modes of administration as well as efficacy and safety profiles. Oral Cladribine (MAVENCLAD), is a synthetic small molecule which selectively targets B and T lymphocytes resulting in their transient reduction. It has been suggested that Oral Cladribine is classified as immune reconstitution therapy (IRT), because of its impact on key cellular components of the immune system. Oral Cladribine was launched in United Arab Emirates (UAE) in Feb 2018.

Objectives

To study and present the real life experience of oral Cladribine in UAE. To present the clinical profile of patients selected , medications switched from , side effects and clinical outcome of patients started on oral cladribine .

Methods

Clinical data from all patients who have received oral Cladribine for treatment of Multiple sclerosis in UAE was collected and analyzed.

Results

Total of 88 patients, have been initiated on oral Cladribine for relapsing remitting Multiple sclerosis since in the period from June 2018 till January 2020 in UAE. 30 patients have completed the 2 year dose and rest have taken only one course till Jan 2020. Mean age at treatment initiation was 34 years (range 23- 54years). Average duration of Multiple sclerosis was 7.5 years (range2-20years). Average number of disease modifying agents prior to Cladribine were 1.4 (range 0-4 agents). Average EDSS was 2.4 (range 0-7). 37% were naïve, 29% were switched from Fingolimod, 12% from Natalizumab, 10.4 % from Teriflunomide, 10% from dimethyl fumarate and 3% from interferons. Mild transient headache was observed in 6 patients during first few days which did not require medications. There was no grade 4 lymphopenia, grade 3 lymphopenia was observed in 1 patient , 3 patients had grade 2 lymphopenia and 72 had grade 1 lymphopenia at month3 , all except 4 ,become grade 0 by month 7 . By month 12 only 1 had persistent grade 2 lymphopenia. 1 patient had a relapse after 2 months of first year treatment and 1 patient had persistent MRI activity end of first year. I patient had to stop therapy as she became pregnant after 6 months of first year course. No patient had progression in EDSS score

Conclusions

Oral Cladribine (MAVENCLAD) is a safe effective and well tolerated medication for the treatment of Multiple sclerosis especially for those who have had an inadequate response to, or are unable to tolerate, one or more therapies for relapsing remitting Multiple Sclerosis .

Background

Teriflunomide is a once-daily oral immunomodulator approved for treating relapsing multiple sclerosis (RMS) and relapsing-remitting MS, depending on the local label. Efficacy and safety of teriflunomide were established in the phase 2 (NCT01487096) and phase 3 trials of patients with RMS (TEMSO [NCT00134563], TOWER [NCT00751881], TENERE [NCT00883337]) and clinically isolated syndrome (TOPIC [NCT00622700]). In post hoc analysis of TEMSO patients stratified by age, structural image evaluation using normalization of atrophy (SIENA) revealed teriflunomide 14 mg significantly reduced the percentage of brain volume change in patients aged >25 to ≤35 years (48%; P=0.0217) and >45 to ≤55 years (35%; P=0.0092) versus placebo over 2 years.

Objectives

To analyze the effect of teriflunomide treatment on MRI lesion activity in TEMSO study patients with RMS stratified by age.

Methods

In TEMSO, patients were randomized 1:1:1 to receive either placebo or teriflunomide 7 mg or 14 mg for ≤108 weeks (Year 2). Through Year 2, MRI lesion activity (unique combined active lesions [UCAL], contrast-enhancing T1 weighted lesions [CEL], and T2 weighted [T2w] lesions) and safety were assessed in the SIENA analysis subgroup; patients were stratified by age at baseline: ≥18 to ≤25 years (n=97 [10%]); >25 to ≤35 years (n=283 [29%]); >35 to ≤45 years (n=388 [40%]); and >45 to ≤55 years (n=201 [21%]). P values between treatment groups were determined for MRI lesions using a Poisson model.

Results

Of 1086 patients in the TEMSO core study, 969 (89%) had scans appropriate for SIENA analysis. Compared with placebo, teriflunomide 14 mg significantly reduced the number of UCAL (0.31–1.44 vs 0.92–6.11 lesions; P≤0.0013) and CEL (0.10–0.46 vs 0.54–3.42 lesions; P≤0.0001) per scan across all age groups. In all age groups except the >45 to ≤55 years group, teriflunomide 14 mg significantly reduced the number of T2w lesions (0.50–0.93 vs 1.07–2.80 lesions; P≤0.001) per scan versus placebo. Similar effects on MRI lesion activity were seen with teriflunomide 7 mg versus placebo. Incidence of adverse events (AEs) generally increased with age, with no deaths reported through Year 2.

Conclusions

Over 2 years in TEMSO RMS patients, teriflunomide reduced the number of new MRI lesions versus placebo across age groups. Significant treatment effects were seen with teriflunomide 14 mg across all age groups for UCAL and CEL. Age-related increases in AEs were observed through Year 2.

STUDY SUPPORT: Sanofi.