Alemtuzumab in the treatment of IVIG-dependent chronic inflammatory demyelinating polyneuropathy

Abstract

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an idiopathic immune mediated neuropathy causing demyelination and conduction block thought to occur as the result of an aberrant autoimmune response resulting in peripheral nerve inflammation mediated by T cells and humoral factors. Diagnosis commonly prompts initial treatment with steroids or intravenous immunoglobulin (IVIG) on which 5-35% subsequently become dependent to maintain function. Despite a number of small scale trials, the role for alternative long-term immunosuppression remains unclear. Alemtuzumab is a humanised monoclonal antibody targeting the CD52 antigen present on the surface of lymphocytes and monocytes. A single intravenous infusion results in rapid and profound lymphopoenia lasting >12 months. We report its use and clinical outcome in a small series of patients with severe IVIG-dependent CIDP. Seven patients (4 Males; 3 Females) who had failed to respond to conventional immunosuppression were treated in 5 centres receiving 9 courses of alemtuzumab (dose range 60-150 mg). Following treatment, mean monthly IVIG use fell 26% from 202 to 149 g and IVIG administration frequency from 22 to 136 days. Two patients had prolonged remission, two patients had a partial response and no clear benefit was observed in the remaining three patients (2 Males, 1 Females). Responding patients had a younger age at onset (19.5 years) and shorter disease duration than non-responders. Three patients developed autoimmune disease following treatment. Alemtuzumab may offer an alternative treatment for a subset of early onset IVIG dependent CIDP patients failing conventional immunosuppressive agents, but concerns about toxicity may limit its use.

Alemtuzumab: the future of chronic inflammatory demyelinating polyradiculoneuropathy treatment?

“…Her remission lasted for 9 months, at which time she relapsed again and was again given alemtuzumab. She experienced no adverse effects [10,23].…”

“…Of the seven patients, two developed high levels of anti-thyroperoxidase antibodies and one of these two patients developed thyroidstimulating hormone receptor antibodies and Grave's disease [23].…”

“…Since the initial report of their patient who experienced longterm remission after treatment with alemtuzumab, the authors have provided further follow-up information, as well as a description of six other patients whose data were collected retrospectively from those treated in the UK and Ireland [23]. Among this group, patients had previously been treated with prednisolone, IVIg, azathioprine, cyclophosphamide, rituximab, plasma exchange, tacrolimus, methotrexate and mycophenolate, and one had received an autologous stem-cell transplantation.…”

Immunotherapy in Peripheral Neuropathies

“…Scarce information is reported in patients with CIDP. A study in 7 patients pointed to a prolonged remission or partial response in 4 patients [64]. However, 3/7 patients developed an autoimmune condition (high levels of antithyroperoxidase antibodies in 2 patients, 1 of whom was Table 1 Good practice points for treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) [29] For induction of treatment 1.…”

Disease-modifying therapy in multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy: common and divergent current and future strategies

“…In a small study, four of seven CIDP patients showed improvement following alemtuzumab; two of these achieved complete remission [67]. An open-label Phase IV clinical trial is currently being initiated to evaluate the impact of alemtuzumab in patients with CIDP (an openlabel trial of alemtuzumab in CIDP).…”