Rituximab in stiff-person syndrome with glutamic acid decarboxylase 65 autoantibody: a systematic review

Abstract

Background: Stiff-person syndrome (SPS) is a rare autoimmune neurological disorder characterized by muscle rigidity and painful spasms, predominantly affecting young women. It is often associated with high titers of anti-glutamic acid decarboxylase (GAD) 65 antibodies. Current treatments for SPS include symptomatic therapies and immunomodulatory approaches, but there is a need for more effective therapies because many patients show incomplete responses and disease progression.

Methods: The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with a literature search of PubMed, Web of Knowledge, Google Scholar, and Science Direct. Studies evaluating efficacy, safety, dosage, and impact on concomitant treatments of Rituximab (RTX) in SPS were selected. Data on anti-GAD titers were also analyzed.

Results: Fourteen studies published between July 2005 and October 2022 were selected. The studies included 30 SPS patients treated with RTX. Data were heterogeneous regarding dosage, administration schedule, and patient assessment. RTX was generally well-tolerated, with rare side effects, including infusion reactions or infections. Significant clinical improvement occurred in most patients, with a small proportion achieving complete remission. Anti-GAD antibody titers decreased in some studies, with no consistent correlation with clinical outcomes.

Conclusions: Evidence supporting the efficacy of RTX in SPS is limited by the small sample sizes of the included studies and the variability in treatment protocols. However, RTX has shown efficacy for clinical improvement. Correlation with anti-GAD titers remains still unclear. Further randomized controlled trials are needed to confirm RTX as an established treatment for SPS.

Keywords: Anti-GAD antibody; Glutamic acid decarboxylase; Rituximab; Stiff-person syndrome.

Fig. 1

PRISMA flow diagram. The database search yielded 104 articles, of which 52 were excluded after reading the abstracts and 52 were eligible for inclusion in the systematic review. Of these, 38 were excluded after reading the full article, 23 because they were not original articles, 8 not focused on SPS, and 7 not focused on RTX. Finally, 14 studies met the established inclusion criteria, being 11 case reports, 1 retrospective observational study, and 2 double-blind, placebo-controlled studies

Fig. 2

Representation of the number of patients included (N, left y-axis) in each study (x-axis) and the clinical responders’ rate (%, right y-axis) to the treatment with RTX