Up to two extra alemtuzumab courses may help mitigate clinical and MRI disease activity in RRMS patients with breakthrough disease activity after the initial two-course regimen, research suggests.

While the drug was first approved to be given as two annual courses, a study involving 811 patients with RRMS found that giving additional third and possibly fourth courses after this abated breakthrough disease activity for up to three years by significantly improving relapse and MRI outcomes, and stabilising or improving disability in subsequent years.

The findings are from a post-hoc analysis of outcomes for patients who took part in the  CARE-MS, extension, and TOPAZ studies of alemtuzumab with follow to eight years.

In the extension studies, about 40% of patients had additional doses for breakthrough disease activity, with 27% of patients receiving three courses, 13% four courses, and around 7% receiving five or more courses.

For the third course, the annualised relapse rate was reduced from 0.73 during the 12 months before it due to disease activity  to 0.07 in the 12 months afterwards ( p < 0.0001), and the ARR remained low at 36 months (0.09).

In the four course group, the ARR was significantly reduced from 0.74 in the 12 months before to 0.08 12 months after (p < 0.0001) and relapse rates remained low (0.11) at 36 months.

At 36 months after Courses 3 and 4, 89% and 92% of patients were free of 6-month confirmed disability worsening, respectively, with 20% and 26% achieving 6-month confirmed disability improvement.

Freedom from MRI) disease activity increased after Courses 3 and 4 (12 months before: 43% and 53%, respectively; 12 months after: 73% and 74%).

The analysis also showed that the safety profile for alemtuzumab with additional courses was similar to that observed in the 2-courses group , with no increases seen in  autoimmune adverse effects, malignancies or infections with additional treatment.

The study authors said the findings confirmed clinical experience that two courses of alemtuzumab may be sufficient for controlling disease in about 60% of patients, whereas others may require additional courses to lower disease activity.

“The variable number of courses needed to control disease activity reflects the heterogeneity of the multiple sclerosis (MS) clinical course,” they wrote.

Breakthrough disease activity may reflect variations in effect of the drug in  depletion of B and T cells and reducing inflammatory cytokines, they suggested.

They noted that product labeling for alemtuzumab has recently been  amended in 2018 to include additional as-needed 3-day courses in Europe and Australia (up to two additional courses), for disease activity defined by clinical or imaging features and given at least 12 months after the most recent course.

The findings are published in Multiple Sclerosis Journal. The authors declared a financial support from the drug manufacturer Sanofi for the study.