Rituximab therapy in monoclonal IgM-related neuropathies

Monoclonal IgM-related neuropathies constitute a heterogeneous group of disorders, which are generally poorly responsive to treatment. Rituximab, a chimeric monoclonal antibody against the CD20 molecule, has been used with success in patients with neuropathy and monoclonal IgM with anti-MAG or anti-GM1 ganglioside activity. Based on this observation, four patients were treated with IgM-related neuropathy with rituximab. Between January 1999 - December 2000, four patients with IgM-related neuropathy (one with chronic inflammatory demyelinating polyneuropathy (CIDP) and three with sensorimotor demyelinating neuropathy) were treated with rituximab. Rituximab was administered at a standard dose of 375 mg m(-2) iv weekly for a consecutive 4 weeks; 3 months later, four additional weekly courses were administered to patients who did not experience deterioration of their neuropathy symptoms. Neurological evaluation was performed before each rituximab infusion and at 1 week and 2 months after last infusion and every 6 months the following years; including motor (MRC in six muscle groups, 9-hole peg test, 10 m walk, hand grip strength), sensory neuropathy (vibration threshold and sensory subjective score) assessment. Neurophysiological parameters were also assessed (MNCV, SNCV, CMAP, SNAP). Strength improved in three of four patients; including the patient with CIDP. This patient developed a significant worsening of her weakness 3 weeks after the initiation of rituximab. This phenomenon coincided with a serum monoclonal IgM flare and resolved spontaneously 1 week later. Her improvement is ongoing for more than 5 years. Considering neurophysiological parameters, two patients showed a slight improved regarding conduction velocities and CMAP (10%) and the patient with IgM flare had a transient worsening of conduction velocities followed by improvement. In conclusion, rituximab is a safe and well-tolerated treatment which may be effective in some patients with IgM-related neuropathy.