Rituximab Doses for MS Might Be Best Timed By Measuring B-cells

Small study aims to set tailored dosing schedule for off-label use with active MS

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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An illustration of white blood cells, immune cells that protect from infection.

Timing doses of rituximab by measuring B-cell counts is a more tailored approach to treatment, and it effectively reduces relapses and disability progression in multiple sclerosis (MS), according to a small study in patients with active disease.

This tailored approach allowed patients to receive less frequent doses if their B-cell counts take longer to recover. The interval between rituximab doses in this study was 10 months, longer than the recommended six-month gap.

The study, “B-lymphocyte-guided retreatment contributes to establish good effectiveness and safety profile in MS patients treated with rituximab,” was published in Multiple Sclerosis and Related Disorders.

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Rituximab eased disease activity in most of study’s 41 patients, many with SPMS

Rituximab is an anti-CD20 monoclonal antibody that works by killing B-cells, a type of immune cell that plays a central role in the inflammatory attack that drives MS. Although not widely approved to treat MS, rituximab is often used off-label for the condition.

Several studies suggested that rituximab is effective at slowing MS progression, although long-term treatment can increase the risk of infection and other safety concerns. There is no uniform treatment schedule for this medication in MS.

Some scientists have suggested that rituximab’s use could be individualized by monitoring patients’ B-cell levels, providing a new round of treatment when levels start to rise. A research team in Spain conducted a study aiming to identify a cutoff point for such a B-cell increase.

“No randomized clinical trials have established a therapeutic scheme of rituximab. Thus, the most important unmet need for this drug is the assessment of the optimal administration route and frequency of retreatment to achieve high efficacy with lower risk,” the researchers wrote.

“We conducted an exploratory analysis to establish the best cutoff value in terms of avoiding a sharp increase of B cells but allowing low percentages of them,” they added.

In an initial analysis, the team tracked B-cell levels in 10 people with active secondary progressive MS (SPMS). Counts were measured every three months starting after the first round of rituximab therapy. Patients were re-treated with rituximab whenever their B-cell counts rose above 0.5% of the total population of lymphocytes (a class of immune cells).

In analyzing data from these 10 patients, the researchers noticed that in most cases (70%), B-cell counts rose past 0.2% right before a sharper increase that brought these counts higher than 0.5%. Based on this finding, they proposed 0.2% as a potential cutoff.

This 0.2% cutoff was then applied in a separate group of 41 patients with active MS — almost all had active SPMS — who were started on rituximab. Many had experienced continued disease activity despite treatment with other high- or moderate-efficacy disease modifying medications; five were new to treatment.

Over a median treatment duration of nearly three years, more than 90% of these patients were re-treated with rituximab, with most (58.5%) receiving at least two retreatment courses of the therapy. The time between retreatment was 10 months.

Potential for highly effective rituximab retreatment guided by B-cell counts

Average scores on the Expanded Disability Status Scale (EDSS) did not significantly change over the course of follow-up. But significantly fewer of these patients experienced confirmed disability progression (27.5%) while on rituximab compared with the year before (55%).

“Our study suggested that there is a reduction of the proportion of patients showing disability progression one year after treatment initiation. However, our cohort was small and these observations should be confirmed in larger samples,” the researchers wrote.

Five documented relapses occurred among all the patients on rituximab, representing a 78% decrease compared to relapse rates in the year before starting on the therapy. The number of new or enlarging lesions, and of lesions showing signs of inflammatory activity, also significantly reduced by over 80% after one year of treatment with rituximab.

Overall, more than 50% of patients reached no evidence of disease activity in the first year of treatment, meaning they experienced no relapses, no new or enlarging lesions, and no disability progression during that period.

Safety-related study findings were generally consistent with the known safety profile of rituximab: common side effects included infusion-related reactions and mild infections.

“Our findings suggest that a personalized retreatment protocol guided by [B-cell] count showed high efficacy in our patients, which was comparable with other reports on rituximab’s efficacy,” the researchers concluded.

A noted stud limitation was the lack of a control group against which to make comparisons. The researchers stressed a need for further studies to determine an optimal dosing regimen for rituximab in MS.

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