Placebo-controlled trial of rituximab in IgM anti-myelin–associated glycoprotein neuropathy

Abstract

Objective: To determine whether rituximab 375 mg/m 2 was efficacious in patients with immunoglobulin M (IgM) anti-myelin-associated glycoprotein antibody demyelinating neuropathy (IgM anti-MAG demyelinating neuropathy).Methods: Fifty-four patients with IgM anti-MAG demyelinating neuropathy were enrolled in this randomized, double-blind, placebo-controlled trial. The inclusion criteria were inflammatory neuropathy cause and treatment (INCAT) sensory score (ISS) $4 and visual analog pain scale .4 or ataxia score $2. The primary outcome was mean change in ISS at 12 months.Results: Twenty-six patients were randomized to a group receiving 4 weekly infusions of 375 mg/m 2 rituximab, and 28 patients to placebo. Intention-to-treat analysis, with imputation of missing ISS values by the last observation carried forward method, showed a lack of mean change in ISS at 12 months, 1.0 6 2.7 in the rituximab group, and 1.0 6 2.8 in the placebo group. However, changes were observed, in per protocol analysis at 12 months, for the number of patients with an improvement of at least 2 points in the INCAT disability scale (p 5 0.027), the self-evaluation scale (p 5 0.016), and 2 subscores of the Short Form-36 questionnaire. Within the spectrum of chronic immune-mediated neuropathies, demyelinating neuropathy associated with immunoglobulin M (IgM) monoclonal gammopathy and antibodies against myelin-associated glycoprotein (MAG) is a distinct entity that typically presents with progressive sensory ataxia and painful paresthesias.1-8 Patients present with a striking immunochemical profile, suggesting the possibility of an autoimmune mechanism: monoclonal IgM recognizes a carbohydrate MAG epitope, which is shared with a number of other glycoconjugates involved in cell adhesion, including the Po glycoprotein of myelin, peripheral myelin protein-22, sulfated sphingolipid, and other related glycolipids.9,10 The disease may progress slowly over many years in some patients, whereas others develop significant disability mostly due to dysesthesias and ataxia; thus, there is a need to develop effective treatments.

Immunotherapy-based regimen in anti-MAG neuropathy: results in 45 patients

“…7,8 Moreover, even though no randomized controlled trials have provided evidence of improvement in primary outcome measures, several secondary outcomes were improved. 9,10 In WM and other indolent B-cell lymphomas, rituximab combined with nucleoside analogs or with nucleoside analogs plus alkylating agents, yields better responses than rituximab monotherapy. 4 Based on these results, we wondered whether patients with anti-MAG neuropathy might benefit more from rituximab plus chemotherapy (immunochemotherapy) than from rituximab alone (immunotherapy).…”

Lung consolidation as a rare presentation of lymphoplasmacytic lymphoma with extramedullary Waldenström’s macroglobulinemia

“…Patient with symptomatic hyperviscosity, cold agglutinemia, or cryoglobulinemia can be treated initially with plasmapheresis then induction with bortezomib followed by rituximab [18]. Patients with paraprotein-related nephropathy can be treated with plasmapheresis initially then with rituximab [19]. …”

Treatment recommendations for patients with Waldenström macroglobulinemia (WM) and related disorders: IWWM-7 consensus

“…Systemic chemotherapy with rituximab resulted in improvement in sensory function in several studies, including a placebo-controlled trial. 47 Single-agent rituximab can be considered as the first intervention in patients with mild, slowly progressive neuropathy. In patients with moderate to severe IgMrelated neuropathy, data indicate more rapid improvement with the fludarabine-rituximab combination than with rituximab alone.…”