PET-measurable innate immune cell activation reduction in chronic active lesions in PPMS brain after rituximab treatment: a case report

Objectives: To evaluate the effects of rituximab treatment on innate immune cell activation in primary progressive multiple sclerosis (PPMS). Methods: A 48-year-old woman with PPMS was started on rituximab shortly after diagnosis. [¹¹C]PK11195 PET imaging was employed to assess innate immune cell activation with special interest in the white matter around chronic lesions. PET, MRI, and disability measurements were performed at baseline and after 18 months of rituximab treatment. Specific binding of [¹¹C]PK11195 was quantified using mean distribution volume ratios (DVRs), and at voxel-level based on proportions of active voxels. Results: The PPMS patient had higher PK11195 DVRs and higher proportions of active voxels in the thalamus and the normal appearing white matter compared to the healthy control group. The thalamic and perilesional white matter DVRs and the proportions of active voxels decreased after rituximab treatment. The patient remained clinically stable during the 5-years follow-up. Conclusions: This case suggests that while a degree of smoldering activity persists, high efficacy B-cell-targeting therapy may contribute to reduced innate immune cell activation in PPMS brain areas relevant for disease progression. This case supports the therapeutic concept that controlling smoldering brain inflammation is beneficial for slowing down progression independent of relapses.