A double blind, placebo-controlled study of rituximab in patients with stiff person syndrome.
Dalakas MC, Rakocevic G, Dambrosia JM, Alexopoulos H, McElroy B.
Ann Neurol 2017; 82:271-277.
In Stiff-Person Syndrome (SPS), an antibody-mediated impaired GABAergic neurotransmission is believed to cause muscle stiffness and spasms. Patients improve with GABA-enhancing drugs and IVIg, but several respond poorly and remain disabled. The need for more effective therapy prompted a trial with the anti-CD20 monoclonal antibody rituximab.
This was a placebo-controlled randomized trial of rituximab (two bi-weekly infusions of 1gr each). The primary outcome was a change in stiffness scores at 6 months. Secondary outcomes were changes in heightened-sensitivity and quality of life scores. Enrolling 24 patients was calculated to detect 50% change in stiffness scores.
Randomization was balanced for age, sex, disease duration and GAD autoantibody titers. No significant changes were noted at 6 months after treatment in all outcomes. Specifically, no differences were noted in the stiffness index, the primary outcome, or sensitivity scores, the secondary outcome, at 3 or 6 months. Quality of life scores improved significantly (p<0.01) at 3 months in both groups, but not at 6 months, denoting an early placebo effect. Blinded self-assessment rating of the overall stiffness for individual patients revealed improvement in four patients in each group. At 6 months, improvement persisted in one patient in the placebo group vs. three out of 4 in the rituximab group, where these meaningful improvements were also captured by video recordings.
This is the largest controlled trial conducted in SPS patients demonstrating no statistically significant difference in the efficacy measures between rituximab and placebo. The lack of rituximab’s efficacy could be due to a considerable placebo effect; insensitivity of scales to quantify stiffness especially in the less severely affected patients; or drug effectiveness only in a small patient subset. This article is protected by copyright.