Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Current Therapeutic Approaches and Future Outlooks

Abstract

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable autoimmune disorder, for which different treatment options are available. Current first-line evidence-based therapies for CIDP include intravenous and subcutaneous immunoglobulins, corticosteroids and plasma exchanges. Despite lack of evidence, cyclophosphamide, rituximab and mycophenolate mofetil are commonly used in circumstances of refractoriness and, more debatably, of perceived overdependence on first-line therapies. Rituximab is currently the object of a randomized controlled trial for CIDP. Based on case series, and although rarely considered, haematopoietic autologous stem cell transplants may be effective in refractory disease, with low mortality and high remission rates. A new therapeutic option has appeared with efgartigimod, a neonatal Fc receptor blocker, recently shown to significantly lower relapse rate versus placebo, after withdrawal from previous immunotherapy. Other neonatal Fc receptor blockers, nipocalimab and batoclimab, are under study. The C1 complement-inhibitor SAR445088, acting in the proximal portion of the classical complement system, is currently the subject of a new study in treatment-responsive, refractory and treatment-naïve subjects. Finally, Bruton Tyrosine Kinase inhibitors, which exert anti-B cell effects, may represent another future research avenue. The widening of the therapeutic armamentarium enhances the need for improved evaluation of treatment effects and reliable biomarkers in CIDP.

Keywords: CIDP; corticosteroids; efgartigimod; immunoglobulins; plasma exchange.

Figure 1

Postulated mechanisms of action of treatments in CIDP: current vs novel. Created with Biorender.com. (A) Immunoglobulins are postulated to exert their action in multiple ways in CIDP: they modulate B-cell repertoire with impact upon antibody production, neutralise pathogenic antibodies, inhibit complement, suppress macrophage-mediated demyelination, downregulate production of inflammatory cytokines and inhibit antigen-presenting cells as well as cellular cytotoxicity. (B) FcRn-blockers exert their action in reducing binding of pathogenic antibodies to the FcRn. This reduces the protective effect of the FcRn on these antibodies from lysosomal degradation, and hence reducing auto-antibody serum life-span and pathogenic effects in CIDP. (C) Complement inhibitors selectively block downstream complement activation involved in the inflammatory processes causing demyelinating damage. (D) Corticosteroid act through genomic effects leading to increased production of anti-inflammatory proteins and reduced production of pro-inflammatory proteins, as well as rapid direct non-genomic anti-inflammatory effects, through heterogeneous receptors. (E) BTK-inhibitors inhibit B-cell activation and proliferation, and consequently pathogenic auto-antibody production, and reduce macrophage activity. (F) Plasma Exchange primarily removes pathogenic auto-antibodies from blood circulation.