Follow Up of Total B Cells (CD 19) Count after B Cell Depleting Therapy in Relapse Remitting Multiple Sclerosis Disorder in Egyptian Patients
Authors: Amin Aref Hany Mohamed , Abdelaziz Azza Abd El-Nasser , Ali Shehab Abeer Al-Sayed , ZamZam Dina Abdel-Gawad , Abou Steit Alaa Mohamed , Mahmoud Salem Amira El-Hussien 
Published: November 2024

Background

Multiple Sclerosis (MS) is a chronic neurological disorder affecting central nervous system. It is classified as the most common neurological cause of disability in young adults. However the aetiology is not well understood, but most propably multifactorial involvement is the most convenient theory till now. It is characterized by inflammation, demyelinaion, axonal loss and degeneration. Ocrelizumab (ocrevus®) (OCR) was approved as treatment for relapsing and progressive patients in 2017. It is a humanized IgG1 monoclonal antibody anti CD20, a cell surface antigen found on pre-B cells, mature B cells and memory B cells.

Aim of the Work

To follow up total B cell count along the course of B cell depletion therapy in MS patients, correlating it with disease activity, in an attempt to investigate whether routine measurement of B cell counts may serve for dosage and time-to-infusion decision making in those patients.

Subjects and Methods

It was a prospective cohort study carried on 30 Egyptian patients diagnosed with Relapse remitting multiple sclerosis according to McDonald criteria 2017. They were recruited from Multiple sclerosis unit at Ain Shams University Hospitals, both genders were included and age older than 18 years old.

Results

This study showed that most of patients were females by 73.3%, but males were 26.7%. The mean age at onset of illness was 29.93 ± 5.55 years and the mean duration of illness was 6.9 ± 4.96. 70% of patients had ≤3 relapses in previous 2 years, while 86.7% had improvement in the annual relapse rate. Regarding history of DMT most patients (66.7%) had two, but only 13.3% were naïve. The mean count of CD19 B cells was cells/µl 65.98 ± 79.04 and significantly depleted to, 3.59 ± 2.94, 25.6 ± 43.98 and 11.11 ± 19.53 cells/µl after 1, 6 and 12 months respectively. this was associated with significant decline in the median (IQR) ARR from 20 (66.67%) to 0 (0%) after 12 months of ocrelizumab therapy and the median (IQR) EDSS from 4.5 (3.5 – 5.5) pretreatment to 3.5 (2.5 - 4.5) and 2.5(2.5-4.5) after 6 and 12 months respectively. Most patients showed either stationary cerebral and cord lesions (as regards number and size of the lesions) and also as regard gadolinium enhanced cerebral lesions, there was a statistically significant decrease in number of patients after 1 year as p-value was &lt;0.05. In our study, the changes in the Multiple Sclerosis Functional Composite score (a composite measure of walking speed, upper-limb movements, and cognition) show statistically significant improvement in all parameters of assessment across three time points. As long as, the depletion of CD19 B cell counts was associated with marked clinical and radiological improvement. We found statistically significant correlation between CD19 B cell counts and EDSS. Furthermore, there was no statistically significant correlation with changes in the multiple sclerosis functional composite score (a composite measure of walking speed, upper-limb movements, and cognition) and MRI Disease activity.

Conclusion

Ocrelizumab was highly efficacious in reducing relapses, preventing disability progression and reducing activity either clinically as EDSS and functional composite score or radiologically in Egyptian MS patients. A fixed-dose schedule of 6-monthly infusion achieved a good relapse free rate. Repeated treatment with ocrelizumab in patients with MS leads to sustained CD19 B cells depletion.