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A double‐blind, placebo‐controlled study of rituximab in patients with stiff person syndrome
Author(s) -
Dalakas Marinos C.,
Rakocevic Goran,
Dambrosia James M.,
Alexopoulos Harry,
McElroy Beverly
Publication year - 2017
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25002
Subject(s) - rituximab , medicine , placebo , stiff person syndrome , randomization , randomized controlled trial , quality of life (healthcare) , clinical trial , physical therapy , pathology , glutamate decarboxylase , biochemistry , chemistry , alternative medicine , nursing , lymphoma , enzyme
Objective In stiff person syndrome (SPS), an antibody‐mediated impaired γ‐aminobutyric acidergic (GABAergic) neurotransmission is believed to cause muscle stiffness and spasms. Most patients improve with GABA‐enhancing drugs and intravenous immunoglobulin, but some respond poorly and remain disabled. The need for more effective therapy prompted a trial with the anti‐CD20 monoclonal antibody rituximab. Methods This was a placebo‐controlled randomized trial of rituximab (2 biweekly infusions of 1g 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. Results Randomization was balanced for age, sex, disease duration, and glutamic acid decarboxylase 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 4 patients in each group. At 6 months, improvement persisted in 1 patient in the placebo group versus 3 of 4 in the rituximab group, where these meaningful improvements were also captured by video recordings. Interpretation This is the largest controlled trial conducted in SPS patients and demonstrates no statistically significant difference in the efficacy measures between rituximab and placebo. Rituximab's lack of 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 in only a small patient subset. Ann Neurol 2017;82:271–277