RIMAG Study: Trial of Rituximab Versus Placebo in Polyneuropathy Associated With Anti-MAG IgM Monoclonal Gammopathy

RIMAG Study: Trial of Rituximab Versus Placebo in Polyneuropathy Associated With Anti-MAG IgM Monoclonal Gammopathy

Double-blind Randomized Trial of Rituximab Versus Placebo in Polyneuropathy Associated With Anti-MAG IgM Monoclonal Gammopathy

Groupe Hospitalier Pitie-Salpetriere, University Hospital, Bordeaux, University Hospital, Limoges, Henri Mondor University Hospital, University Hospital, Marseille, Hospices Civils de Lyon, University Hospital, Basel, Switzerland

Polyneuropathy associated with anti-MAG monoclonal IgM gammopathy is responsive of mainly a sensory deficit in predominantly males ,aged 40-70 years. Significantly high serum anti-MAG antibodies are linked with demyelinating features of the peripheral nerves.Rituximab, an anti-CD 20 monoclonal antibody is a new drug which reduces B-lymphocytes. This study will test the safety and efficacy of rituximab in the treatment of patients with anti-MAG polyneuropathy.

Acting of a polyneuropathy for which there is not any treatment of reference today (see supra), a test of double-knowledge versus placebo is justified. Acting of a chronic polyneuropathy, the clinical evaluation must be led over one one year period. Acting of a sensitive polyneuropathy and the awaited benefit being the IMPROVEMENT OF the CLINICAL SIGNS, the principal criterion is a sensitive score in addition validated in chronic sensitive polyneuropathies immunodeficiency syndrome. The patients answering the criteria of inclusion and none inclusion (see V-2) will be randomized in 2 groups: the first group will receive a perfusion IV of rituximab to the amount of 375 mg/m2 of body surface, once per week, during 4 weeks (see VII-3); the second group will receive 4 perfusions IV of placebo according to same methods'. The evaluation (see VI-1) will be carried out at the time of the randomization, then repeated in 3 months, 6 months, 9 months and 1 year.

Inclusion Criteria: IgM monoclonal gammopathy Anti-MAG antibody titers > 1.1000 BTU (ELISA) Worsening polyneuropathy with INCAT score > 4 Informed consent Exclusion Criteria: Severe comorbidity Other concurrent causes of polyneuropathy Concurrent immunosuppressive therapies (wash-out > 3 months) Previous treatment with rituximab Lymphoproliferative disease indicating other immunosuppressive treatment Unability to follow-up Previous documented side-effects with components involved in the tested drug White cell count < 1500/mm3 or platelet count < 75.000/mm3 Patient under law

Leger JM. A review of the medical management of chronic inflammatory demyelinating polyradiculoneuropathy. Expert Opin Pharmacother. 2005 Apr;6(4):569-82. doi: 10.1517/14656566.6.4.569.