Individualized immunoglobulin therapy in chronic immune‐mediated peripheral neuropathies*

Abstract

Despite the well‐recognized importance of immunoglobulin therapy individualization during the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP), the pathway to best achieve optimization is unknown. There are many pharmacokinetic and immunobiologic variables that can potentially influence the appropriateness of any individual therapy. Although identification of specific autoantibodies and their targets has only been accomplished in a minority of patients with CIDP, already the diagnostic and treatment implications of specific autoantibody detection are being realized. Individual variability in IgG pharmacokinetic properties including IgG catabolic rates and distribution, as well as the IgG level necessary for disease control also require consideration during the optimization process. For optimization to be successful there must be a measure of treatment response that has a clinically meaningful interpretation. There are currently available well‐defined and validated clinical assessment tools and outcome measures that are well suited for this purpose. While there remains much to learn on how best to manipulate immunopathology and immunoglobulin pharmacokinetics in the most favorable way, there currently exists an understanding of these principles to a degree sufficient to begin to develop rational and evidence‐based treatment optimization strategies.

Diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy in clinical practice: A survey among Dutch neurologists

“…This guideline states that an IVIg maintenance dose of 1.0 g/kg over 1 to 2 days every 3 weeks has been shown to be efficacious, but the appropriate dose needs to be individualized (usually 0. in the next version of the EFNS/PNS guideline on treatment. 16,17,[29][30][31][32] About one-third of respondents indicated that they would start initial therapy in all CIDP patients irrespective of the severity of symptoms and the interference with daily life activities, while the EFNS/ PNS 2010 guideline recommends only to treat patients with moderate or severe disability. Although 5% to 30% of CIDP patients only needs one IVIg course (2 g/kg) to induce remission, almost one-third of the respondents indicated starting maintenance therapy after improvement on the first IVIg induction course without subsequent deterioration.…”

“…15 Furthermore, the best approach to manage wear-off signs and withdrawal of IVIg is unclear. 16,17 Because of these challenges, we expect that both the diagnostic workup and treatment strategies for CIDP patients are highly variable.…”

An international multicenter efficacy and safety study of IqYmune in initial and maintenance treatment of patients with chronic inflammatory demyelinating polyradiculoneuropathy: PRISM study

“…A better understanding of the reasons for this heterogeneity between patients might help however to better individualize therapy with IVIg. 18 The safety is in line with the use of IVIg in CIDP. Regarding headaches, they were also the most frequent drug-related AEs reported in previous clinical studies.…”

Measuring disease activity and predicting response to intravenous immunoglobulin in chronic inflammatory demyelinating polyneuropathy

“…Anti-neurofascin 155 (anti-NF155) and anti-contactin 1 (anti-CNTN1) antibodies have been identified in approximately 3–10% of patients with chronic infammatory polyneuropathies [16–18]. Patients who tested positive to these paranodal antibodies responded favourably to B-cell depleting therapies like rituximab over more traditional therapeutic options like IVIg or plasmapheresis.…”

“…Many individuals with CIDP require long term maintenance treatment with IVIg to effect disease stability and studies of serum IgG levels in treatment responders have revealed that patients actually achieve a steady state wherein both pre- and post-treatment IgG levels are almost identical [23]. The implications of this are profound, as it suggests there is an individual threshold above which patients remain stable [16]. Although at the present time identifying this threshold in any given patient is a matter of trial and error, further validation of reference ranges in which disease control is achieved provides promise for a future wherein IVIg is administered with the aim to achieve pre-specified IgG levels [23].…”