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Peripheral neurotoxicity of pegylated interferon alpha: A prospective study in patients with HCV - Reply
No full textCI-PERINOMS: Chemotherapy Induced - Peripheral Neuropathy Outcome Measures Study.
No full textChemotherapy-induced peripheral neuropathy (CIPN)
is a major and potentially dose-limiting adverse event
of several chemotherapeutic agents (Windebank and
Grisold, 2008). CIPN is characterized by distal symmetrical
numbness, tingling, paresthesias, dysesthesias,
pain and/or weakness, which significantly affect functionality
and quality of life (Aaronson, 1998). The
incidence of CIPN may be as high as 100% in treated
patients, depending on dose and dose-intensity of
the chemotherapeutic regimen. The neurotoxic side
effects may be permanent, and treatment is usually
difficult. Neuroprotective agents that would either
prevent or ameliorate CIPN are currently under investigation
(Cavaletti and Marmiroli, 2006; Albers et al.,
2007). However, before studying these agents in clinical
trials, it is crucial to be able to assess CIPN in a
simple, valid, and reproducible way in accordance with
postulated international guidelines (Hobart et al., 1996;
Merkies and Lauria, 2006). Although several scales
have been used by oncologists and neurologists,
grading CIPN is still an unsolved issue (Postma and
Heimans, 2000; Cavaletti et al., 2007).Moreover,most
of the scales have not undergone rigorous clinimetric
evaluation and analysis, which are nowadays essential
requirements for any proposed clinical trial (van
Nes et al., 2008). The CI-PERINOMS: Chemotherapy
Induced-Peripheral Neuropathy Outcome Measures
Study protocol was developed by experienced neurologists
to identify the best method(s) to assess
and monitor CIPN (Cavaletti, 2008)
Therapeutic Monoclonal Antibody Therapies in Chronic Autoimmune Demyelinating Neuropathies
Full text linkAutoimmune diseases of the peripheral nervous system have so far been treated mainly with exogenous high-dose intravenous immunoglobulins (IVIg), that act through several mechanisms, including neutralization of pathogenic autoantibodies, modulation of lymphocyte activity, interference with antigen presentation, and interaction with Fc receptors, cytokines, and the complement system. Other therapeutic strategies have recently been developed, in part to address the increasing shortage of IVIg, prime among which is the use of B cell depleting monoclonal antibodies, or small molecule inhibitors targeting the B-cell specific kinases. Rituximab, a chimeric monoclonal antibody against CD20 + B lymphocytes, is currently the most used, especially in anti-MAG antibody neuropathy and autoimmune neuropathies with antibodies to nodal/paranodal antigens that are unresponsive to IVIg. After several reports of its efficacy in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), rituximab is currently under investigation in three Phase 2 trials in CIDP. In addition, the possible role of complement activation in the pathogenesis of chronic autoimmune neuropathies has brought into consideration drugs that can block the complement cascade, such as eculizumab, a monoclonal antibody already assessed in acute polyradiculoneuropathies, and approved for myasthenia gravis. Preliminary data on eculizumab in multifocal motor neuropathy have been published, but randomized controlled studies are pending. Moreover, the neonatal Fc receptor, that recycles IgGs by preventing their lysosome degradation, is an important and attractive pharmacological target. Antibodies against FcRn, which reduce circulating IgG (both pathogenic and non-pathogenic) have been developed. The FcRn blocker efgartigimod, a humanized IgG1-derived Fc fragment, which competitively inhibits the FcRn, has recently been approved for the treatment of myasthenia gravis and is currently under investigation in CIDP. In addition, the anti-human FcRn monoclonal antibody rozanolixizumab is currently being assessed in phase 2 trials in CIDP. However, none of the abovementioned monoclonal antibodies is currently approved for treatment of any immune-mediated neuropathies. While more specific and individualized therapies are being developed, the possibility of combined treatments targeting different pathogenic mechanisms deserves consideration as well. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01222-x
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