Rapid worsening of IgM anti‐MAG demyelinating polyneuropathy during rituximab treatment

Dear Editor, There are no proven treatments for polyneuropathy associated with IgM monoclonal gammopathy and anti-myelin associated glycoprotein (anti-MAG) antibodies (Lunn and Nobile-Orazio, 2012). Two recent randomized trials (RCTs) comparing rituximab to placebo failed to demonstrate improvement on the primary endpoints (Dalakas et al., 2009; Leger et al., 2011). In these trials, treatment with rituximab was safe and well tolerated. The total published experience with rituximab in anti-MAG polyneuropathy encompasses fewer than 100 patients (Renaud et al., 2003; RojasGarcia et al., 2003; Niermeijer et al., 2009). Because rituximab is at best effective only in a small subgroup of patients, even fairly rare side effects would be relevant to the decision to prescribe it for antiMAG neuropathy. Some side effects could have been missed because of the low numbers of patients in published series. We report three patients with IgM monoclonal gammopathy-associated polyneuropathy and anti-MAG antibodies who rapidly worsened within weeks after the start of rituximab treatment. One patient presented with mild weakness of the dorsiflexors of foot and toes (Medical Research Council [MRC] grade 4), glove and sock-patterned hypoesthesia, and sensory ataxia, which had developed slowly over the previous 2 years. His anti-MAG titer before treatment was 7,180 BTU (Buehlmann Titer Units, normal values below 2,000 BTU), total serum IgM was 13 g/l, and the M protein was 9 g/l. Nerve conduction studies showed demyelination in nerves of both arms and legs, distally more than proximally, as well as axonal loss, more pronounced in the nerves of the legs than in those of the arms (Table 1). After the second of a planned four weekly rituximab infusions (375 mg/m2), he developed proximal weakness and severe progression of the distal weakness in the legs