ImportanceRituximab is a third-line option for refractory generalized myasthenia gravis (MG) based on empirical evidence, but its effect in new-onset disease is unknown.ObjectiveTo investigate the efficacy and safety of rituximab compared with placebo as an add-on to standard of care for MG.Design, Setting, and ParticipantsThis randomized, double-blind, placebo-controlled study took place throughout 48 weeks at 7 regional clinics in Sweden. Key inclusion criteria were age older than 18 years, onset of generalized symptoms within 12 months or less, and a Quantitative Myasthenia Gravis (QMG) score of 6 or more. Patients were screened from October 20, 2016, to March 2, 2020. Key exclusion criteria included pure ocular MG, suspected thymoma, previous thymectomy, and prior noncorticosteroid immunosuppressants or high doses of corticosteroids.InterventionsParticipants were randomized 1:1 without stratification to a single intravenous infusion of 500 mg of rituximab or matching placebo.Main Outcomes and MeasuresMinimal disease manifestations at 16 weeks defined as a QMG score of 4 or less with prednisolone, 10 mg or less daily, and no rescue treatment.ResultsOf 87 potentially eligible patients, 25 were randomized to rituximab (mean [SD] age, 67.4 [13.4] years; 7 [28%] female) and 22 to placebo (mean [SD] age, 58 [18.6] years; 7 [32%] female). Compared with placebo, a greater proportion with rituximab met the primary end point; 71% (17 of 24) in the rituximab group vs 29% (6 of 21) in the placebo group (Fisher exact test P = .007; probability ratio, 2.48 [95% CI, 1.20-5.11]). Secondary end points, comparing changes in Myasthenia Gravis Activities of Daily Living and Myasthenia Gravis Quality of Life at 16 weeks with QMG at 24 weeks did not differ between groups with censoring for rescue treatment (per-protocol analysis) but were in favor of active treatment when rescue treatment was taken into account by worst rank imputation (post hoc analysis). Rescue treatments were also more frequent in the placebo arm (rituximab: 1 [4%]; placebo, 8 [36%]). One patient in the placebo arm had a myocardial infarction with cardiac arrest and 1 patient in the active arm experienced a fatal cardiac event.Conclusions and RelevanceA single dose of 500 mg of rituximab was associated with greater probability of minimal MG manifestations and reduced need of rescue medications compared with placebo. Further studies are needed to address long-term benefit-risk balance with this treatment.Trial RegistrationClinicalTrials.gov Identifier: NCT02950155

Background and Purpose To investigate the diagnostic and prognostic value of axonal injury biomarkers in patients with inflammatory polyneuropathies. Methods Neurofilament light chain (NfL) and total tau (T‐tau) were measured in the cerebrospinal fluid (CSF) and plasma in 41 patients with Guillain–Barré syndrome (GBS), 32 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 10 with paraproteinemia‐related demyelinating polyneuropathy (PDN), and 8 with multifocal motor neuropathy (MMN), in comparison with 39 disease‐free controls and 59 other controls. Outcome was measured with the GBS‐disability score (GBS‐ds) or Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Results Neurofilament light chain levels in CSF and plasma were higher in GBS, CIDP, and PDN vs. disease‐free controls. Patients with MMN had higher NfL levels in plasma vs. disease‐free controls, but lower levels in CSF and plasma vs. patients with amyotrophic lateral sclerosis (ALS). T‐tau levels in plasma were higher in GBS, CIDP, PDN, and MMN vs. all control groups. Neurofilament light chain levels in CSF and plasma in patients with GBS correlated with GBS‐ds, as higher levels were associated with inability to run after 6 and 12 months. NfL levels in CSF and plasma in CIDP did not correlate significantly with outcome. Conclusions Acute and chronic inflammatory neuropathies are associated with an increase in levels of NfL in CSF and plasma, but NfL is validated as a prognostic biomarker only in GBS. NfL could be used in differentiating patients with MMN from ALS. T‐tau in plasma is a novel biomarker that could be used in a diagnostic assessment of patients with acute and chronic inflammatory polyneuropathies.

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