# Current clinical management of CIDP with immunoglobulins in France: An expert opinion

P. Cintas, F. Bouhour, C. Cauquil, M. Masingue, C. Tard, S. Sacconi, E.

Delmont, A. Choumert, J.-B. Chanson, M. Michaud, et al.

► To cite this version:

P. Cintas, F. Bouhour, C. Cauquil, M. Masingue, C. Tard, et al. Current clinical management of CIDP with immunoglobulins in France: An expert opinion. Revue Neurologique, 2023, 179 (8), pp.914-922. 10.1016/j.neurol.2023.03.010. hal-05232702

HAL Id: hal-05232702

https://hal.science/hal-05232702v1

Submitted on 1 Sep 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
Practice guidelines

# Current clinical management of CIDP with immunoglobulins in France: An expert opinion

<figure><img src="image_2.png" /></figure>

<figure><img src="image_3.png" /></figure>

suppl.
Informations

P. Cintas<sup>a</sup>, F. Bouhour<sup>b</sup>, C. Cauquil<sup>c</sup>, M. Masingue<sup>d</sup>, C. Tard<sup>e</sup>, S. Sacconi<sup>f</sup>, E. Delmont<sup>g</sup>, A. Choumert<sup>h</sup>, J.-B. Chanson<sup>i</sup>, M. Michaud<sup>j</sup>, G. Solé<sup>k</sup>, J. Cassereau<sup>l</sup>, J.-B. Noury<sup>m</sup>, G. Nicolas<sup>n</sup>, R. Bellance<sup>o</sup>, Y. Péréon<sup>p</sup>, J.-P. Camdessanché<sup>q</sup>, L. Magy<sup>r</sup>, S. Attarian<sup>g,*</sup> on behalf of the French Neuromuscular diseases network (Filnemus)

<footnote><sup>a</sup>Service de neurologie, CHU de Toulouse Purpan, centre de référence de pathologies neuromusculaires, Toulouse, France</footnote>

<footnote><sup>b</sup>Service d'ENMG et de pathologies neuromusculaires, hospices civils de Lyon, hôpital neurologique, Lyon, France</footnote>

<footnote><sup>c</sup>Service de neurologie, AP-HP Kremlin-Bicêtre, Paris, France</footnote>

<footnote><sup>d</sup>Service de neuromyologie, centre de référence des maladies neuromusculaires Nord/Est/Île-de-France, AP-HP Pitié-Salpêtrière, Paris, France</footnote>

<footnote><sup>e</sup>Unité d'expertise cognitivo-motrice, U1172, service de neurologie, CHU de Lille, centre de référence des maladies neuromusculaires Nord/Est/Île-de-France, Lille, France</footnote>

<footnote><sup>f</sup>Système nerveux périphérique et muscle, CHU de Nice, université Côte d'Azur, Nice, France</footnote>

<footnote><sup>g</sup>Service de neurologie, centre de référence des maladies neuromusculaires et SLA, hôpital de la Timone, Marseille, France</footnote>

<footnote><sup>h</sup>Service des maladies neurologiques rares, CHU de la Réunion, groupe hospitalier Sud Réunion, Saint-Pierre, France</footnote>

<footnote><sup>i</sup>Service de neurologie, CHRU Strasbourg, centre de référence neuromusculaire Nord/Est/Île-de-France, Strasbourg, France</footnote>

<footnote><sup>j</sup>Service de neurologie, CHU de Nancy, hôpital Central, Nancy, France</footnote>

<footnote><sup>k</sup>Service de neurologie et maladies neuromusculaires, CHU de Bordeaux, centre de référence des maladies neuromusculaires AOC, hôpital Pellegrin, Bordeaux, France</footnote>

<footnote><sup>l</sup>CHU d'Angers, centre de référence des maladies neuromusculaires AOC, Angers, France</footnote>

<footnote><sup>m</sup>Inserm, LBAI, UMR1227, centre de référence des maladies neuromusculaires AOC, CHRU de Brest, Brest, France</footnote>

<footnote><sup>n</sup>Service de neurologie, centre de référence neuromusculaire Nord-Est/Île-de-France, Université UVSQ Paris-Saclay, hôpital Raymond-Poincaré, Garches, France</footnote>

<footnote><sup>o</sup>CeRCa, site constitutif de centre de référence caribéen des maladies neuromusculaires rares, CHU de Martinique, hôpital P. Zobda-Quitman, Fort-de-France, France</footnote>

<footnote><sup>p</sup>Explorations fonctionnelles, Filnemus, Euro-NMD, Nantes université, CHU de Nantes, centre de référence AOC, Nantes, France</footnote>

<footnote><sup>q</sup>Service de neurologie, CHU de Saint-Étienne, hôpital Nord, Saint-Étienne, France</footnote>

<footnote><sup>r</sup>Service et laboratoire de neurologie, centre de référence neuropathies périphériques rares, NNERF, UR 20218 NeurIT, CHU de Limoges, hôpital Dupuytren, Limoges, France</footnote>

<footnote>* Corresponding author.</footnote>

<footnote>E-mail address: Shahram.attarian@ap-hm.fr (S. Attarian).</footnote>

<footnote>Abbreviations: 6-MWT, 6-minute walk test; 9-HPT, 9-hole peg test; CIDP, chronic inflammatory demyelinating polyradiculoneuropathy; EAN, European Academy of Neurology; IVIg, intravenous immunoglobulin; INCAT, Inflammatory Neuropathy Cause and Treatment; MCID, minimum clinically important difference; MRC, Medical Research Council; PNDS, Protocole National de Diagnostic et de Soins (French national diagnosis and care protocol); PNS, Peripheral Nerve Society; MCM, Multidisciplinary Consultation Meetings; R-ODS, Rasch-built Overall Disability Score.</footnote>

<footnote>https://doi.org/10.1016/j.neurol.2023.03.010</footnote>

<footnote>0035-3787/© 2023 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).</footnote>
## INFO ARTICLE

Article history:

Received 13 September 2022

Received in revised form

5 January 2023

Accepted 13 March 2023

Available online 3 April 2023

Keywords:

CIDP

IVIg

Treatment

Maintenance

Efficacy criteria

MCIDs

## ABSTRACT

Treatment strategies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) must be adapted on a case-to-case basis. Validated and reproducible tools for monitoring treatment response are required at diagnosis, when initiating treatment and throughout follow-up. A task force of French neurologists, experts in neuromuscular disease reference centers, was assembled to provide expert advice on the management of typical CIDP with intravenous immunoglobulins (Ig), and to harmonize treatment practices in public and private hospitals. The task force also referred to the practical experience of treating CIDP with Ig at the diagnostic, induction and follow-up stages, including the assessment and management of Ig dependence, and following the recommendations of the French health agency.

© 2023 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

## 1. Introduction

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory neuropathy with a relapsing or progressive course [1,2]. Its phenotype is diverse and includes typical and variant forms. The typical form of CIDP is characterized by the progressive or relapsing symmetric proximal and distal muscle weakness, sensory involvement of at least 2 limbs, and decreased or absent deep tendon reflexes, over 8 weeks [3]. Patients often report impaired balance, difficulties walking and climbing stairs, loss of grip strength (such as when opening a bottle or turning a key in a lock) and paresthesia. CIDP variants include distal, multifocal, focal, pure motor and pure sensory forms.

CIDP is an acquired immune-mediated neuropathy typically characterized by macrophage-induced demyelination, and affects approximately 2.81 per 100,000 people [4]. Diagnosis of CIDP relies on a combination of clinical, electro-physiological, imaging and laboratory features and exclusion of other disorders that share similar symptoms. In typical CIDP, the diagnosis is mainly based on the clinical presentation and electrodiagnostic signs of demyelination. European Academy of Neurology (EAN)/Peripheral Nerve Society (PNS) diagnostic criteria for CIDP are commonly used in clinical practice with some variation reported [5,6]. Moreover, the importance of using outcome measures in inflammatory neuropathies, to evaluate disease severity, to detect clinical improvement following treatment and to provide evidence of disease relapse has been discussed [7].

First-line treatments, as recommended by international recommendations [3] and French National diagnosis and care protocol (PNDS, *Protocole National de Diagnostic et de Soins* [8]) guidelines, involve the use of immunoglobulins (Ig), corticosteroids and plasma exchanges, and are effective in 85% of cases [1]. In France, Ig are often preferred for their good tolerance, their practicality and because the costs of Ig treatment are covered by the French national healthcare system.

Spurred on in part by recurrent global Ig shortages, exacerbated by the COVID-19 pandemic, the authors conducted this review. Such shortages have been shown to induce changes in patient treatments that can negatively impact the patient's clinical status in some cases [9]. A task force of French neuromuscular experts assembled to discuss the management of typical CIDP patients, with a focus on intravenous Ig (IVIg) treatment. The resulting expert opinion presented here aims to provide neurologists in public and private hospitals with practical guidance on therapeutic strategies, based on actual current practice, using a therapeutic algorithm that addresses patient management from the initiation of treatment with IVIg to the follow-up period, including the evaluation and management of treatment dependence.

## 2. Prescription of immunoglobulins

### 2.1. Guidelines

French neurologists follow the French national diagnosis and care protocol (PNDS [8]) that is based on the European Academy of Neurology and Peripheral Nerve Society (EAN/PNS) guidelines on diagnosis and treatment of CIDP [1]. This protocol provides guidance for the diagnosis, therapeutic management and clinical care of a CIDP patient, with the goal of optimizing and harmonizing the management and follow-up of this rare disease throughout France. A national network of 26 reference centers for rare neuromuscular diseases was set up to improve diagnosis by reducing diagnostic errors and coordinating care for patients with these disorders, including CIDP (Flinnemus, the list of these centers is available at www.flinnemus.fr). Filnemus is one of the 23 rare diseases health networks recognized by the French Ministry of Health. In France and in Europe, organizations exist for patients living with a rare immune-mediated peripheral neuropathy whose
<figure><img src="image_4.png" /></figure>

Fig. 1 – Organization of care as recommended by French Health authority (https://ansm.sante.fr/actualites/tensions-dapprovisionnement-en-immunoglobulines-humaines-rappel-de-la-hierarchisation-des-indications). Multidisciplinary Consultation Meetings (MCM) provide an opportunity for neurologists to engage in formal discussions over diagnostic and therapeutic strategies with peripheral nerve specialists from a reference center. In simple clinical situations (i.e., typical CIDP), a sheet can be transmitted for validation (see Online material Appendix 1). Specialists discuss medical decisions collectively before starting IVIg. In complex clinical situations (i.e., variants of CIDP), specialists discuss medical decisions collectively with the neurologist in order to confirm the diagnosis and to decide together whether the IVIg therapy must be initiated or not. During the maintenance phase, IVIg must be reassessed every 6 months. This can be done using a simple sheet (see Online material Appendix 2).

purpose is to improve quality of life and promote the exchange of information (AFNP, French organization for peripheral neuropathies [AssociationFrançaise contre lesNeuropathiesPériphériques] and EPODIN, European Patient Organisation for Dysimmune and Inflammatory Neuropathies).

## 2.2. Prescription of Ig in France

In France, national health authorities have required since 2010 that the use of Ig must be rationalized due to shortages of fresh plasma. This prioritization protocol for the use of IVIg was then updated in 2019 [10]. According to French health authorities (ANSM, National Agency for Medicines and Health Products Safety), the initial management strategy for a CIDP patient should be discussed in a Multidisciplinary Consultation Meeting (MCM) within the national network coordinated by Filnemus (i.e. in reference or competence centers) [10].

The MCM should validate the diagnosis, IVIg induction phase and continuation of Ig treatment. IVIg therapy should only be initiated in patients with moderate or severe disability that impacts the patient's daily life [3,8]. In the experts' experience, a minority of patients requires only one single course of IVIg. However, some patients require long-term management (maintenance treatment). The treatment should be reassessed every 6 months in order to determine whether

or not it should be continued, to evaluate whether the criteria for therapeutic dependence are met and to discuss therapeutic alternatives (Fig. 1). In everyday practice, it is not always feasible to follow these recommendations, and some local or regional strategies may be preferred by the healthcare teams involved. Moreover, the MCM procedure does not seem to be necessary for typical forms. Thus, the task force proposes here an easy-to-follow, straightforward validation form (Online material Appendix 1) including checklists that the neurologist can submit to the MCM for remote validation of the initiation of treatment with IVIg in typical CIDP. This form can be filled out by the neurologist, e-mailed to the regional reference center and submitted to the MCM for validation.

For CIDP variants, consultation in the regional reference center is recommended (Fig. 1).

In conclusion, this suggested framework could ensure that treatments given are relevant and prevent the overtreatment of CIDP. Decisions by the MCM (i.e. validation and continuation of Ig treatment) are based on objective clinical criteria adapted to each patient's clinical presentation.

## 2.3. Outcome measures

Throughout patient's care, CIDP disability should be measured and quantified using clinical tools. Several clinical scales
<table><caption>Table 1 – Clinical relevance of outcome measures in CIDP.</caption><thead><tr><th>Scale</th><th>MCID</th></tr></thead><tbody><tr><td>INCAT (adjusted)</td><td>1 point</td></tr><tr><td>R-ODS</td><td>Individual SE (difference on the scale) on centile score or 4 points on the centile score</td></tr><tr><td>Grip strength, Martin vigorimeter</td><td>8-14 kPa</td></tr><tr><td>Grip strength, Jamar vigorimeter</td><td>10% change (kg or lb)</td></tr><tr><td>MRC sum score (60 points: 6 paired muscle groups)</td><td>2-4 points</td></tr><tr><td>ONLS (adjusted) [13]</td><td>1 point</td></tr><tr><td>6-MWT [14]</td><td>30.1 meters</td></tr><tr><td>9-HPT [15]</td><td>20%</td></tr></tbody><tfoot><tr><td colspan="2">6-MWT: 6-minute walk test; 9-HPT: 9-hole peg test; CIDP: chronic inflammatory demyelinating polyradiculoneuropathy; INCAT: Inflammatory Neuropathy Cause and Treatment; MCID: minimum clinically important difference; MRC: Medical Research Council; ONLS: Overall Neuropathy Limitations Scale; R-ODS: Rasch-built Overall Disability Score; SE: standard error. Adapted from [12].</td></tr></tfoot></table>

are available for defining the disability impairment, but the minimum scores (i.e., cut-off value) at which treatment should be initiated are still debated. Likewise, changes in clinical scales over time can be used to evaluate a patient's response to treatment, but no thresholds for clinical improvement have been validated. Minimum Clinically Important Differences (MCIDs), defined as the smallest change in health status that an individual patient would identify as important [11], have been reported in clinical trials and recent guidelines and are available as a guide [12] (Table 1). The best method for defining the MCID remains under discussion. During treatment, tests must be conducted under the same conditions in order to be reproducible (for instance by taking the “wear-off” effect into account). Functional evaluations based on a clinically relevant

criterion are done to ensure that the benefit of the treatment is significant [12].

Tools used to assess patients with CIDP include the INCAT (Inflammatory Neuropathy Cause and Treatment) and modified INCAT disability scores, R-ODS (Rasch-built Overall Disability Scale), ONLS (Overall Neuropathy Limitations Scale) and MRC (Medical Research Council) score [2,16]. It is not established which clinical tool would be the most indicated for use in clinical practice; however, according to the task force experts, the R-ODS and ONLS scales are the most practical and fastest to perform in clinical practice, and could be used systematically.

The R-ODS is a widely used patient-based scale [17,18]. The ONLS is quick and easy for the neurologist to perform, but is

<figure><img src="image_5.png" /><figcaption>Fig. 2 – IVIg treatment algorithm. The therapeutic algorithm addresses patient management from the initiation of treatment with IVIg to the follow-up period, including the evaluation and management of treatment dependence. MCM: multidisciplinary consultation meeting; IVIg: intravenous immunoglobulin.</figcaption></figure>
less sensitive to changes in the gait perimeter [16]. The task force recommends measuring clinical scores (ONLS, R-ODS) every 2 months during the treatment induction phase, and every 6 months during the maintenance phase, or earlier in the event of changes in dosing, dosage intervals, or patient symptoms, in order to determine the minimum effective dose (Fig. 2).

Furthermore, depending on the patient's clinical presentation, other tests may be useful. For example, the grip strength test is sensitive for patients with upper extremity involvement and correlates with the overall neurological status [12]. The timed up-and-go (TUG) or the timed 10-meter walking distance tests can be useful for patients with gait impairment. The walking perimeter can also be assessed by the patient using a step-counting application to encourage self-awareness about any changes in distances travelled. The walking test is particularly useful in ataxic patients because it increases awareness of adapted physical activities. The 9-hole peg test (9-HPT) and the 6-minute walk test (6-MWT) can also be used to assess patients with CIDP [12,19], but are more time-consuming and thus more cumbersome to use in routine practice.

The correlation between the clinical symptoms and patient perception and the grip, ONLS, and R-ODS tests was recently reported to be excellent [20].

Self-administered quality of life (QoL) questionnaires, such as the EQ-5DL or SF-36, are also useful for assessing patients with CIDP, but their main limitation is that QoL depends on many factors external to the disease and its treatment [12].

As CIDP is very often misdiagnosed and overtreated, these outcomes measures are also useful as supportive tools for the diagnosis. Indeed, according to guidelines, an objective improvement following immunomodulatory treatment is considered supportive of a CIDP diagnosis [3].

# 3. Use of IVIg in therapeutic strategies

IVIg and/or corticosteroids as well as plasma exchanges are strongly recommended as initial treatment in typical CIDP, though plasma exchanges require good vascular access and specialized equipment. Issues with vascular access can make plasma exchanges less attractive despite its efficacy and relative safety [3,8]. Corticosteroids may be chosen as first-line therapy in cases where IVIg are not available or are contraindicated according to the prioritization protocol put in place by the ANSM and supported by Filnemus [10].

In most cases, CIDP with isolated sensory signs that are not disabling does not justify treatment with IVIg, especially in the context of Ig shortages and given the low benefit/risk balance [8]. For isolated painful forms, symptomatic treatment should be preferred.

## 3.1. Safety: initial pre-therapeutic assessment and monitoring

The assessment must be tailored to the individual patient and take comorbidities into account. The task force agreed that the pre-treatment assessment should include the measurement of plasma creatinine. Systematic monitoring for adverse events is crucial. If severe, persistent, or recurrent functional

renal failure occurs, patients should be referred to a nephrologist. Cardiac workup is needed in patients with cardiovascular risks to avoid cardiac overload. While infection, hyperthermia or elevated C-reactive proteins are not contraindications to treatment, hyperthermia complicates the monitoring of Ig therapy (risk of infusion reactions). For patients with severe neurological signs and a concomitant infection, treatment should be continued after normalizing temperature with antipyretics. Adequate hydration must be ensured in all patients during IVIg treatment.

## 3.2. IVIg induction

### 3.2.1. IVIg treatment induction

In CIDP, the authorized IVIg dose is 2 g/kg given over 2-5 consecutive days for the first course of treatment, followed by 1 g/kg-courses every 3 weeks [3,8]. However, in France, IVIg is generally used at a dose of 2 g/kg every 4 to 6 weeks to increase the time between infusions (see the therapeutic algorithm in Fig. 2) and reduce the frequency of visits to the hospital, thus improving patient QoL. In common practice, the initial IVIg dose is adjusted based on the patient's weight (up to 90-100 kg) and, for a body mass index ≥ 30 kg/m², the dose is lowered to 1.6 g/kg.

One course of treatment may not be sufficient to observe a response to IVIg, as the response can be delayed (i.e., consecutive to up to 3-4 courses) in some CIDP patients [21].

For example, in the phase 3 PRISM study, which evaluated the efficacy and safety of IVIg, the median time to response was 15 weeks (i.e., after 4 courses), and 29% of patients had a late response (i.e., ≥ 12 weeks), which prompted the authors to suggest that patients should be maintained on IVIg therapy for 6 months [22].

Thus, depending on the IVIg loading dose, the response to treatment should be evaluated after a maximum of 4 courses, as described in the algorithm (Fig. 2). For patients whose condition worsens under IVIg treatment, therapeutic alternatives should be considered before the end of the 4 courses.

### 3.2.2. Clinical assessment of IVIg efficacy

An objective response to treatment is defined as significant improvement on at least one disability scale and one impairment scale [3].

As stated previously, clinical scores (ONLS, R-ODS, Grip strength, 6-MWT) should be measured at least every 2 months during the treatment induction phase. Furthermore, it is important to monitor treatment efficacy every 6 months during the maintenance phase, or earlier if there are changes in dosing, dosage intervals or symptoms, in order to define the minimum effective dose.

Clinical, electrophysiological (especially ENMG), biological and functional assessments should be standardized. The standardized follow-up form proposed here (Online material Appendix 2) can be submitted to the MCM for its validation of the continuation of IVIg treatment (Fig. 1). This form could be computerized to make it widely accessible and easy to use.

According to the task force and in agreement with the international guidelines [3], for patients treated with IVIg who do not respond or whose CIDP worsens, the diagnosis should be reconsidered during follow-up in a MCM.
### 3.2.3. Response to IVIg

IVIg have been shown to be effective over the long-term (48 weeks) in patients with CIDP. The response may vary according to the form of CIDP in question: sensory forms respond more slowly, whereas pure motor forms generally respond very well to Ig [23]. Indeed, there are 3 possible scenarios after the initiation of IVIg treatment, depending on how the patient's symptoms evolve:

* complete regression of symptoms after up to 4 courses of treatment - i.e., remission - in which case the treatment can be stopped;

* partial response after initiation of IVIg treatment: treatment should be continued without change until maximal improvement. Maintenance treatment should be based on clinical evaluation of disability (see section 3.3);

* no response to IVIg after 3 to 4 courses of treatment or deterioration: treatment should be discontinued and the patient should be referred to a reference center for a MCM to discuss a differential diagnosis (Table 2) or alternative treatment options.

For patients with confirmed diagnosis of CIDP who worsen despite IVIg therapy, the EAN/PNS guidelines recommend switching to an alternative first-line therapy (corticosteroids, plasma exchanges) before considering combination treatments. Adding an immunosuppressant or immunomodulatory drug may be considered, but there is no sufficient evidence to recommend any particular drug [3]. In any case, if patients are not responsive to IVIg, the diagnosis of CIDP should be reconsidered.

If the patient is non-responsive to the first course of treatment, always reconsider a differential diagnosis.

### 3.3. Maintenance treatment

#### 3.3.1. Search for optimal treatment strategies

Although complete remission after short-term therapy occurs in some patients, the majority requires extended maintenance therapy. Ig therapy must be maintained at the full dose until the maximum improvement is observed and a plateau is reached (i.e., when no further improvement is observed between 2 courses), which may take up to 6 months after initiation of the treatment [3,22]. The disadvantage of published algorithms is that they move very quickly to a dose reduction without reaching this plateau [24,25].

For patients who are improving, the dose and treatment interval should be maintained until a plateau is achieved. Also, at each step of the management of CIDP, the value and impact of the chosen treatment strategy should be assessed.

The current practice is to periodically reduce the dose or increase the interval between treatment courses and monitor response based on validated outcome measures. There is no evidence-based recommendation on how IVIg maintenance treatment should be conducted. Even though the best IVIg maintenance dose and schedule are not known, according to EAN/PNS guidelines, the most commonly proposed IVIg maintenance regimen in clinical trials is 1 g/kg every 3 weeks, but in clinical practice, lower doses and longer treatment intervals maintaining maximal sustained improvement should be considered (e.g., 0.4-1 g/kg every 2-6 weeks). This minimum effective dose strategy should be defined on a case-by-case basis according to the patient's assessed impairment. When no wear-off symptoms occur, increasing the intervals seems to be appropriate. In practice, the intertreatment interval is increased by one week and then the minimum effective dose is determined by reducing the dose by 20% (which often has the added beneficial effect of eliminating 1

<table><caption>Table 2 - Differential diagnosis of CIDP.</caption><thead><tr><th>Differential diagnosis</th><th>Comments</th></tr></thead><tbody><tr><td><strong>Acquired neuropathies</strong></td><td></td></tr><tr><td><strong>Immune neuropathies</strong></td><td></td></tr><tr><td>Nodo/paranodopathy</td><td>Anti-NF155/NF186/contactin-1 antibodies > 0</td></tr><tr><td>AIDP</td><td>Onset duration < 6 weeks or sequalae</td></tr><tr><td>MMN</td><td>Anti-GM1 antibody > 0</td></tr><tr><td>Treatment induced neuropathy</td><td>Treatment with anti-TNF α, anti-CTLA4 or anti-PD1/PDL1</td></tr><tr><td><strong>Neuropathies with monoclonal gammopathy</strong></td><td></td></tr><tr><td>POEMS</td><td>VEGF increased, thrombocytosis, organomegaly and bone lesion</td></tr><tr><td>CANOMAD</td><td>IgM, anti-disialosyl antibodies > 0</td></tr><tr><td>MAG</td><td>IgM, anti-MAG antibodies > 0</td></tr><tr><td>AL amyloid neuropathy</td><td>Biopsy proof, Immunoglobulin light chain ↑</td></tr><tr><td>Diabetic neuropathy</td><td></td></tr><tr><td>Neurolymphomatosis</td><td>Infiltrate on nerve MRI, CSF, PET scan or biopsy</td></tr><tr><td>Sarcoidosis</td><td>Pulmonary or mediastinal involvement, biopsy proof, hypercalcemia ↑</td></tr><tr><td><strong>Inherited neuropathies</strong></td><td></td></tr><tr><td>Familial amyloid neuropathy</td><td>TTR mutation, amyloid deposit on tissue biopsy</td></tr><tr><td>CMT neuropathy</td><td>PMP22, MPZ, GJB1, SH3TC2, MME</td></tr></tbody></table>

NF: neurofascin, > 0: positif; AIDP: acute inflammatory demyelinating polyneuropathy; MMN: multifocal motor neuropathy; GM1: ganglioside M1; TNFα: tumor necrosis factor alpha; CTLA4: cytotoxic T-lymphocyte antigen 4; PD1: programmed cell death protein 1; PDL1: programmed death-ligand 1; MGUS: monoclonal gammopathy of undetermined significance; POEMS: polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin abnormalities; VEGF: vascular endothelial growth factor; CANOMAD: chronic ataxic neuropathy, ophtamoplegia, IgM paraprotein, cold agglutinins and disialosyl antibodies; MAG: myelin-associated glycoprotein; PET: positron emission tomography; AL: amyloid light chain; TTR: transthyretin; CMT: Charcot-Marie-Tooth; PMP22: peripheral myelin protein 22; MPZ: myelin protein zero; GJB1: gap junction protein beta 1; SH3TC2: SH3 Domain And Tetratricopeptide Repeats 2; MME: membrane metalloendopeptidase.
day of treatment). This dose reduction must then be
consolidated over a minimum of 2 courses before the next
step, in order to achieve a progressive reduction.

In the absence of a consensus and according to the clinical
experience of the task force, once more than 12 weeks
between courses or a dosage below 0.5 g/kg have been
achieved, Ig treatment can be discontinued.

Economic studies should be done to compare the costs of
reduction of the dose versus reduction of the infusion
frequency. There is a great unmet need for the best strategy
to achieve the minimum effective dose. It is therefore in the
patient's best interest to increase the intertreatment interval
rather than the Ig dose (fewer hospital visits, fewer infusions).

Furthermore, to optimize the use of IVIg, it is important to
know how to best manage and measure the “wear-off” effect.
It is still uncertain whether reducing this “wear-off” prevents
permanent damage or whether a certain degree of deteriora-
tion of response at the end of the cycle is tolerable without
affecting disability. Patients without “wear-off” could poten-
tially reduce their Ig dose [26]. Due to the important
interindividual variations in the pharmacokinetics of IVIg
(clearance), in the absence of “wear off”, it seems reasonable
to first propose spacing out the IVIg infusions. On the other
hand, in patients that show an excellent response but with
“wear off”, an initial decrease of the dose should be preferred,
while maintaining or reducing the intertreatment interval.
Connected home assessment tools could allow care teams to
more closely follow patient’s evolution between courses to
better customize the duration of the interval [27,28].

Throughout the treatment maintenance phase, it is crucial
to periodically assess Ig dependence through a withdrawal
test, and to consider the possibility of an alternative
treatment. Dependence is defined by a response to the
treatment and a significant relapse when the treatment is
stopped. In the case of dependence, a MCM should be held to
discuss the possible use of alternative or adjuvant therapy.

The rationale for maintenance therapy should ideally be
based on objective, yet personalized measurements, showing
immunoglobulin dependence [29]. EAN/PNS guidelines recom-
mend in clinical stable patients to perform an assessment of
defined outcome measures every 6 to 12 months for the first 2
to 3 years of treatment, then less frequently (e.g., every 1-2
years).

3.3.2. *Patient home treatment*

At-home maintenance therapy should be offered to patients.
Indeed, immunoglobulins, whether by IV or subcutaneous (SC)
route, can be safely administered at home [29]. However, there
are no published recommendations for home treatment of
CIDP. However, the global COVID-19 pandemic, which caused
organizational difficulties in hospitals, has highlighted the
advantages of continuing Ig treatment at home after the
second course [20]. Due to potential adverse events, home
treatment is not suitable for the treatment induction phase.
Experts generally agreed that at least the first course of Ig
should be given in hospital, and that patient's symptoms must
be evaluated within 2 to 3 months and then every 6 months, in
order to assess response and treatment dependence, as well as
tolerability. However, the experts also suggest that if the
patient continues treatment at home after the second course

of Ig, follow-up evaluations should be done promptly (e.g., on
day 15 after treatment induction).

Home treatment is economically attractive and associated
with improved quality of life [30].

Depending on the common practice followed, different
models of Ig administration can be implemented. For example,
for maintenance courses, Ig can be administered in the
hospital on the first day and at home on the subsequent days.
It was also agreed that remote consultations could be useful
for patients with chronic CIDP who are stabilized and
independent. While home administration of IVIg requires a
visit from a healthcare professional, SCIg can be self-
administered by the patient after a short training period.
Patients can schedule infusions at times that best suit their
needs, with 2 to 3 SC infusions per week. Switching from one
route to another is possible once the minimum effective dose
as well as dependence have been determined. This can be an
alternative for dependent patients who are responsive to
treatment. The modalities for switching from one route to
another are based on dose equivalences and timing, subject to
the availability of the different products [31].

For some at-risk patients (e.g., elderly or isolated patients,
renal failure, infusion reactions, etc.), treatment should be
administered solely in the hospital to allow for close
monitoring. To select those patients suitable for home
treatment, the experts recommend focusing on contraindi-
cations to home treatment: isolation, major cognitive impair-
ment and comorbidities (e.g., renal failure, unstable arterial
hypertension, moderate or severe infusion reactions, poor
tolerance to prior therapies, and cardiac pathologies). In
practice, the reasons for switching back to administrations in
hospital include tolerance problems, infusion site infections,
and patient's desire to separate the disease from his/her daily
life, poor housing conditions, and in-hospital availability.

While conventional follow-up for patients with CIDP
includes functional assessments, Ig tolerance, quality of life
and biological assessments are also important [2].

The experts agreed on a list of relevant follow-up
parameters, especially for home-treated patients, in order to
harmonize the follow-up of these patients in France. Some
experts schedule a visit 15 days after the first course of Ig to
confirm clinical improvement in CIDP (dose peak). The value of
electrophysiological monitoring in the follow-up of CIDP has
not been proven. However, electrophysiology tests (especially
ENMG) may be used to evaluate axonal loss and the occurrence
of new signs of demyelination before any therapeutic
modification.

Monitoring of Ig levels is not recommended in clinical
practice. Creatinine measurements are useful for patients at
high risk of renal failure, at the discretion of the physician, and
may be useful for follow-up after the treatment course. This is
particularly important for home-treated patients because
neurologists cannot monitor concomitant use of nephrotoxic
drugs in that setting.

4. Conclusions

In conclusion, this task force aimed to provide neurologists
with practical tools for the treatment of CIDP patients outside
reference centers. It worked to standardize practices based on the recommendations of French health authorities for the treatment of CIDP patients with Ig, in public hospitals and private centers.

Furthermore, recurrent shortages of Ig and blood products, exacerbated by the COVID-19 pandemic, have made harmo- nization of practices crucial for enabling each and every patient to be treated in the best possible conditions. In this regard, future studies regarding responder/non-responder profiles and minimum effective Ig doses would be useful.

Funding

This work was supported by LFB BIOMEDICAMENTS.

Contributions

PC, FB, CC, MM, CT, SS designed and drafted the manuscript.

All authors read, revised and approved the final version of the article.

Disclosure of interest

FB reports consulting and lecture fees or travel grants from UCB, Sanofi-Genzyme, Amicus, CSL Behring, LFB, Argenx.

MM reports consulting and lecture fees or travel grants from LFB, Roche, Sanofi.

PC reports consulting and lecture fees or travel grants from LFB, Alnylam, Roche, Biogen.

CT reports personal fees and non-financial support from Sanofi-Genzyme, Pfizer, Alnylam and personal fees from Akcea, Ultragenyx, Biogen, Argenx; non-financial support from Santhera, LFB. CC reports consulting and lecture fees or travel grants from Alnylam, Pfizer, Akcea, CSL, LFB.

GS reports travel grants from LFB.

LM reports consultancy fees, honoraria, personal fees for lectures or travel grants from CSL Behring, LFB, Grifols.

MM reports consulting and travel grants from LFB.

YP reports consulting and lecture fees or travel grants from LFB.

J-PC declares consulting and lecturing fees from Akcea, Alexion, Alnylam, Argenx, Biogen, Bristol Myers Squibb, CSL- Behring, Genzyme, Grifols, LFB, Merck-Serono, Natus, Novar- tis, Pfizer, Pharmalliance, UCB Pharma, Teva, SNF-Floerger; travel grants from Akcea, Alexion, Alnylam, Argenx, Biogen, CSL-Behring, Genzyme, Grifols, LFB, Merck-Serono, Natus, Novartis, Pfizer, Teva, SNF-Floerger, and a patent application for the application of FGFR3 and AGO antibodies as biomarkers for autoimmune neurological diseases.

J-BN reports travel grants from LFB.

J-BC declares consultancy fees from Alnylam and travel grants from Alnylam, CSL-Behring, Sanofi-Genzyme, LFB, Pfizer.

SA reports consulting and lecture fees or travel grants from LFB, Argenx, Sanofi, Pfizer, Alnylam, Alexion, Biogen, Novartis and non-personal research grants from LFB, Pfizer, Biogen.

SS reports consultancy fees and non-personal research grants from BioMarin, Sanofi Genzyme, LFB Biomedicaments, Biogen, Roche, UCB Pharma, Dyne Therapeutics, Argenx and Fulcrum Therapeutics.

The authors JC, RB, GN, J-PC and AC declare that they have no competing interest.

Acknowledgements

The authors thank Emilie Distel for her help in manuscript preparation and Jill Rupnow for English corrections.

Appendix A. Supplementary data

Supplementary data associated with this article can be found, in the online version, at https://doi.org/10.1016/j. neurol.2023.03.010.

REFERENCES

[1] Van den Bergh PYK, Hadden RDM, Bouche P, Cornblath DR, Hahn A, Illa I, et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society – first revision. Eur J Neurol 2010;17:356–63. http://dx.doi.org/10.1111/j.1468- 1331.2009.02930.x.

[2] Fisse AL, Motte J, Grüter T, Sgodzai M, Pitarokoili K, Gold R. Comprehensive approaches for diagnosis, monitoring and treatment of chronic inflammatory demyelinating polyneuropathy. Neurol Res Pract 2020;2:42. http:// dx.doi.org/10.1186/s42466-020-00088-8.

[3] Van den Bergh PYK, van Doorn PA, Hadden RDM, Avau B, Vankrunkelsven P, Allen JA, et al. European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force-second revision. J Peripher Nerv Syst 2021;26:242–68. http:// dx.doi.org/10.1111/jns.12455.

[4] Broers MC, Bunschoten C, Nieboer D, Lingsma HF, Jacobs BC. Incidence and prevalence of chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review and meta-analysis. Neuroepidemiology 2019;52:161– 72. http://dx.doi.org/10.1159/000494291.

[5] Broers MC, van Doorn PA, Kuitwaard K, Eftimov F, Wirtz PW, Goedee S, et al. Diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy in clinical practice: a survey among Dutch neurologists. J Peripher Nerv Syst 2020;25:247–55. http://dx.doi.org/ 10.1111/jns.12399.

[6] Svačina MKR, Mehndiratta MM, Vedeler CA, Sharma Y, Bobylev I, Sprenger A, et al. Clinical management of chronic inflammatory demyelinating polyneuropathy (CIDP) in Europe and India: an exploratory study. J Neurol Sci 2021;427:117507. http://dx.doi.org/10.1016/ j.jns.2021.117507.
[7] Rajabally YA, Fatehi F. Outcome measures for chronic inflammatory demyelinating polyneuropathy in research: relevance and applicability to clinical practice. Neurodegener Dis Manag 2019;9:259-66. http://dx.doi.org/10.2217/nmt-2019-0009.

[8] Haute Autorité de santé. Polyradiculoneuropathie inflammatoire démyélinisante chronique (PIDC). Haute Autorité de santé n.d. https://www.has-sante.fr/jcms/p_3261449/fr/polyradiculoneuropathie-inflammatoire-demyelinisante-chronique-pidc.(accessed May 31, 2022).

[9] N'kaoua E, Attarian S, Delmont E, Campana-Salort E, Verschueren A, Grapperon A-M, et al. Immunoglobulin shortage: practice modifications and clinical outcomes in a reference centre. Rev Neurol (Paris) 2021. http://dx.doi.org/10.1016/j.neurol.2021.10.004 [S0035-3787(21)00768-2].

[10] ANSM. Hiérarchisation des indications des immunoglobulines humaines polyvalentes n. d.

[11] Jaeschke R, Singer J, Guyatt GH. Measurement of health status. Ascertaining the minimal clinically important difference. Control Clin Trials 1989;10:407-15. http://dx.doi.org/10.1016/0197-2456(89)90005-6.

[12] Allen JA, Eftimov F, Querol L. Outcome measures and biomarkers in chronic inflammatory demyelinating polyradiculoneuropathy: from research to clinical practice. Expert Rev Neurother 2021;21:805-16. http://dx.doi.org/10.1080/14737175.2021.1944104.

[13] Rajabally YA, Afzal S, Ghasemi M. Minimal important differences and self-identifying treatment response in chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 2021;64:37-42. http://dx.doi.org/10.1002/mus.27250.

[14] Shoemaker MJ, Curtis AB, Vangsnes E, Dickinson MG. Clinically meaningful change estimates for the six-minute walk test and daily activity in individuals with chronic heart failure. Cardiopulm Phys Ther J 2013;24:21-9.

[15] Feys P, Lamers I, Francis G, Benedict R, Phillips G, LaRocca N, et al. The Nine-Hole Peg test as a manual dexterity performance measure for multiple sclerosis. Mult Scler 2017;23:711-20. http://dx.doi.org/10.1177/1352458517690824.

[16] Graham RC, Hughes RAC. A modified peripheral neuropathy scale: the overall neuropathy limitations scale. J Neurol Neurosurg Psychiatry 2006;77:973-6. http://dx.doi.org/10.1136/jnnp.2005.081547.

[17] van Nes SI, Vanhoutte EK, van Doorn PA, Hermans M, Bakkers M, Kuitwaard K, et al. Rasch-built Overall Disability Scale (R-ODS) for immune-mediated peripheral neuropathies. Neurology 2011;76:337-45. http://dx.doi.org/10.1212/WNL.0b013e318208824b.

[18] Allen JA, Merkies ISJ, Lewis RA. Monitoring clinical course and treatment response in chronic inflammatory demyelinating polyneuropathy during routine care: a review of clinical and laboratory assessment measures. JAMA Neurol 2020;77:1159-66. http://dx.doi.org/10.1001/jamaneurol.2020.0781.

[19] Markvardsen LK, Bruun-Sørensen S, Christiansen I, Andersen H. Retrospective correlation analysis of plasma Immunoglobulin G and clinical performance in CIDP. Peer J 2019;7:e6969. http://dx.doi.org/10.7717/peerj.6969.

[20] Rajabally YA, Goedee HS, Attarian S, Hartung H-P. Management challenges for chronic dysimmune neuropathies during the COVID-19 pandemic. Muscle Nerve 2020;62:34-40. http://dx.doi.org/10.1002/mus.26896.

[21] Merkies ISJ, van Schaik IN, Léger J-M, Bril V, van Geloven N, Hartung H-P, et al. Efficacy and safety of IVIG in CIDP: combined data of the PRIMA and PATH studies. J Peripher Nerv Syst 2019;24:48-55. http://dx.doi.org/10.1111/jns.12302.

[22] Nobile-Orazio E, Pujol S, Kasiborski F, Ouaja R, Corte GD, Bonek R, et al. An international multicenter efficacy and safety study of IqYmune in initial and maintenance treatment of patients with chronic inflammatory demyelinating polyradiculoneuropathy: PRISM study. J Peripher Nerv Syst 2020;25:356-65. http://dx.doi.org/10.1111/jns.12408.

[23] Menon D, Katzberg HD, Bril V. Treatment approaches for atypical CIDP. Front Neurol 2021;12:653734. http://dx.doi.org/10.3389/fneur.2021.653734.

[24] Lunn MP, Ellis L, Hadden RD, Rajabally YA, Winer JB, Reilly MM. A proposed dosing algorithm for the individualized dosing of human immunoglobulin in chronic inflammatory neuropathies. J Peripher Nerv Syst 2016;21:33-7. http://dx.doi.org/10.1111/jns.12158.

[25] Kuitwaard K, Fokkink W-JR, Brusse E, Vrancken AFJE, Eftimov F, Notermans NC, et al. Maintenance IV immunoglobulin treatment in chronic inflammatory demyelinating polyradiculoneuropathy. J Peripher Nerv Syst 2017;22:425-32. http://dx.doi.org/10.1111/jns.12242.

[26] Allen JA, Berger M, Querol L, Kuitwaard K, Hadden RD. Individualized immunoglobulin therapy in chronic immune-mediated peripheral neuropathies. J Peripher Nerv Syst 2018;23:78-87. http://dx.doi.org/10.1111/jns.12262.

[27] Mueller A, Hoefling HA, Muaremi A, Praestgaard J, Walsh LC, Bunte O, et al. Continuous digital monitoring of walking speed in frail elderly patients: non-interventional validation study and longitudinal clinical trial. JMIR Mhealth Uhealth 2019;7:e15191. http://dx.doi.org/10.2196/15191.

[28] Jacobs D, Farid L, Ferré S, Herraez K, Gracies J-M, Hutin E. Evaluation of the validity and reliability of connected insoles to measure gait parameters in healthy adults. Sensors 2021;21:6543. http://dx.doi.org/10.3390/s21196543.

[29] Allen JA, Gelinas DF, Freimer M, Runken MC, Wolfe GI. Immunoglobulin administration for the treatment of CIDP: IVIG or SCIG? J Neurol Sci 2020;408:116497. http://dx.doi.org/10.1016/j.jns.2019.116497.

[30] Le Masson G, Solé G, Desnuelle C, Delmont E, Gauthier-Darnis M, Puget S, et al. Home versus hospital immunoglobulin treatment for autoimmune neuropathies: a cost minimization analysis. Brain Behav 2018;8:e00923. http://dx.doi.org/10.1002/brb3.923.

[31] Menon D, Sarpong E, Bril V. Practical aspects of transitioning from intravenous to subcutaneous immunoglobulin therapy in neuromuscular disorders. Can J Neurol Sci 2021;1-7. http://dx.doi.org/10.1017/cjn.2021.56.