Rituximab as treatment for anti-MuSK myasthenia gravis: Multicenter blinded prospective review

Neurology. 2017 Sep 5;89(10):1069-1077. doi: 10.1212/WNL.0000000000004341. Epub 2017 Aug 11.

Abstract

Objective: To evaluate the efficacy of rituximab in treatment of anti-muscle-specific kinase (MuSK) myasthenia gravis (MG).

Methods: This was a multicenter, blinded, prospective review, comparing anti-MuSK-positive patients with MG treated with rituximab to those not treated with rituximab. The primary clinical endpoint was the Myasthenia Gravis Status and Treatment Intensity (MGSTI), a novel outcome that combines the Myasthenia Gravis Foundation of America (MGFA) postintervention status (PIS) and the number and dosages of other immunosuppressant therapies used. A priori, an MGSTI of level ≤2 was used to define a favorable outcome. Secondary outcomes included modified MGFA PIS of minimal manifestations or better, mean/median prednisone dose, and mean/median doses of other immunosuppressant drugs.

Results: Seventy-seven of 119 patients with anti-MuSK MG evaluated between January 1, 2005, and January 1, 2015, at 10 neuromuscular centers were selected for analysis after review of limited clinical data by a blinded expert panel. An additional 22 patients were excluded due to insufficient follow-up. Baseline characteristics were similar between the rituximab-treated patients (n = 24) and the controls (n = 31). Median follow-up duration was >3.5 years. At last visit, 58% (14/24) of rituximab-treated patients reached the primary outcome compared to 16% (5/31) of controls (p = 0.002). Number needed to treat for the primary outcome is 2.4. At last visit, 29% of rituximab-treated patients were taking prednisone (mean dose 4.5 mg/day) compared to 74% of controls (mean dose 13 mg/day) (p = 0.001 and p = 0.005).

Classification of evidence: This study provides Class IV evidence that for patients with anti-MuSK MG, rituximab increased the probability of a favorable outcome.

Trial registration: ClinicalTrials.gov NCT02110706.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / therapeutic use
  • Autoantibodies / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunologic Factors / therapeutic use*
  • Male
  • Middle Aged
  • Myasthenia Gravis / drug therapy*
  • Myasthenia Gravis / immunology*
  • Prednisone / therapeutic use
  • Prospective Studies
  • Receptor Protein-Tyrosine Kinases / immunology*
  • Receptors, Cholinergic / immunology*
  • Rituximab / therapeutic use*
  • Severity of Illness Index
  • Single-Blind Method
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Autoantibodies
  • Immunologic Factors
  • Receptors, Cholinergic
  • Rituximab
  • MUSK protein, human
  • Receptor Protein-Tyrosine Kinases
  • Prednisone

Associated data

  • ClinicalTrials.gov/NCT02110706