Background

Ocrelizumab is a monoclonal antibody approved for relapsing-remitting primary progressive multiple sclerosis (MS) acting against B lymphocytes that expresses CD20. The CD 20 antigen is a cell surface antigen found on pre-B lymphocytes, mature B lymphocytes, memory B lymphocytes, and a T cell subtype (CD3+ CD20+) that also expresses CD20. Clinical trials have shown that the use of this drug can produce a reduction in immunoglobulin levels which might be related to infections; however, there is little data about the influence of this immunomodulatory treatment on CD3+ T lymphocytes.

Objectives

To analyze differences in CD3+ T lymphocyte counts in patients under treatment with Ocrelizumab and their relationship with the development of infections.

Methods

We performed an observational retrospective case-control study nested in a cohort of MS patients under treatment with Ocrelizumab. Cases were patients who developed infections and controls were patients who did not develop any type of infection during treatment.

Results

We included 33 patients, mean age 39 years old (SD:9.6), mean MS duration 9 years (SD:5.8), 66.7% women, 38.7% developed infections during treatment. Mean CD3+ T lymphocytes count was 1157.6 (SD:498) at baseline, 1373 (SD:621.9) CD3+ T lymphocytes at 3 months, 1221 (SD:439) CD3+ T lymphocytes at 6 months and 1405 (SD:836) at 12 months. We did not find statistical differences between groups, although there was a tendency towards a higher mean CD3+ T lymphocyte count at three months (1781.2;SD:399.9) in patients who did not develop infections as compared to the mean CD3+ T lymphocytes count at three months (1047.1; SD: 595.1) in patients who developed infections (p=0.064).

Conclusions

Our preliminary data did reveal statistical differences in the total CD3+ T lymphocyte count between patients under Ocrelizumab treatment, although there was a tendency towards a higher count at 3 months in patients who did not develop infections. Weather the putative effect of Ocrelizumab on T cell subtype (CD3+ CD20+) might be related to the development of infections needs further research.

Background

Pediatric Multiple Sclerosis (MS) is defined as MS with an onset before age 18. It is an infrequent disease that entails between 3% and 5% of all MS diagnoses. It can accrue significant disability at a younger age than adult MS, therefore it is a more aggressive disease. Disease-modifying therapies (DMTs) in children and adolescents are used based on clinical experience. Fingolimod is the first DMT approved in data sheet as a treatment for pediatric MS after the clinical trial PARADIGMS.

Objectives

We present our experience with 7 patients with pediatric MS. We describe tolerability, security and effectiveness in our patirents.

Methods

Observational, retrospective and usual clinical practice study in pediatric MS patients treated with Fingolimod.

We analyzed security and effectiveness: relapses, Expanded Disability Status Scale (EDSS) score and gadolinium enhancing lesions before and after starting Fingolimod

Results

We present 7 patients with pediatric MS (5 girls and 2 boys). The mean age of onset of the disease was 15,1 years old (DS1,5). The mean annualized relapse rate in the year before Fingolimod was 1,6 (DS0). The mean number of enhancing lesions in basal Magnetic Resonance Imaging (MRI) was 3,7 (DS6,4) and the mean number of lesions in T2 sequences was 20 (DS2,8). Six patients had spinal cord lesions. The median age at onset of Fingolimod was 16 years old. Three patients were naive and the rest of them had been previously treated with injectable agents. Patients were exposed to Fingolimod for 22,3 months as an average (DS25). They did not present new relapses nor radiological activity on MRI after starting Fingolimod. No adverse effects were reported during the treatment.

Conclusions

The mean age of our patients is similar to the pivotal clinical trial, mostly postpubertal and with a highly active disease. Fingolimod seems to be a very effective and secure treatment in our patients with pediatric MS, with a very good tolerability and adhesion.