Treatment with rituximab in patients with polyneuropathy with anti-MAG antibodies

Abstract

Efficacy of rituximab (RTX), a monoclonal anti-CD20 antibody, has been suggested in a recent controlled trial in polyneuropathies with antibodies against myelin-associated glycoprotein (PN-MAG) [1]. Aims of this study were to evaluate the efficacy and safety of RTX in PN-MAG and to search for predictive factors of response to treatment.Six patients fulfilling diagnosis criteria for PN-MAG [2] received four weekly infusions of RTX (375 mg/m 2 ). Clinical status of each patient was evaluated, before treatment (M0) then every 3 months during 9 months, by assessing Overall Neuropathy Limitation Scale (ONLS) [3], INCAT Sensory Score (ISS) [4], and MRC sum score on 28 muscle groups [5]. Anti-MAG titers (Buhlmann ELISA technique) and B cells expressing CD19 blood count were concomitantly quantified. Nerve conduction studies were performed before treatment and 9 months after (M9), on fibular, tibial, median and ulnar nerves [5]. Treatment was considered efficient only when ONLS score decreased by at least 1 point at M9. Demographic, clinical, biological and electrophysiological status before RTX, were statistically compared between patients with efficient and non-efficient response to treatment using the MannWhitney and Fisher's exact tests. The level of statistical significance was set at p = 0.05. Patients were asked to give informed consent for use of data in a journal publication.Mean age of patients (70 years old, range 57-86 years), duration before treatment from onset of the disease (5 years, range 2-10 years), main clinical manifestations of each patient and previous immunotherapies are detailed in Table 1. Before RTX treatment, ONLS score ranged from 2 to 6 (mean 3.7) and ISS score from 2 to 12 (mean 6.2). Nine months after the last RTX infusion, ONLS score improved by 1 point in two patients, by 2 points in one, remained stable in the three others. ISS score improved in five patients (mean 3.8 points), MRC score improved in three patients (mean 2.7 points). Decrease of anti-MAG titers was observed in all the six patients at M9 by a mean of 43% (Fig. 1). By the meantime, IgM monoclonal titers decreased in five patients but did not change in one. As expected, CD19 B-cells blood count dramatically decreased, after treatment and stayed low at M9 (138 9

Therapeutic Outcomes and Electrophysiological Biomarkers in Anti-Myelin-Associated Glycoprotein Neuropathy: A Multicenter Cohort Study in South Korea

“… 3 While these symptoms tend to gradually worsen over time, the available treatments, including corticosteroids, immunosuppressive therapies (ISTs), intravenous immunoglobulin (IVIG), and rituximab, were found to have inadequate efficacy compared with other immune-mediated neuropathies. 4 5 6 7 8 9 10 11 12 13 14 15 None of the eight randomized clinical trials (RCTs) on these treatments obtained significant or clinically meaningful results. 7 Although rituximab, an anti-CD20 monoclonal antibody, holds promise as a therapeutic option for anti-MAG neuropathy, it was effective on only 30%–50% of recipients.…”

“… 24 26 27 Although anti-MAG antibody titers have some value in monitoring the disease, they are not correlated with the disease severity, clinical phenotype, or prognosis. 10 20 21 28 Several serum biomarkers and neurophysiological tests have been explored, such as nerve conduction studies (NCSs). Amaador et al 29 found no clinical utility of neurofilament light chain, contactin-1, or complement activation products.…”