A Practical Guide to Management of Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Abstract

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common immune-mediated demyelinating peripheral neuropathy. CIDP is characterized by progressive muscle weakness, areflexia, and often sensory loss. The etiology is not well understood, but autoimmune pathophysiology is evident, and immunomodulatory treatments such as intravenous immunoglobulin, corticosteroids, and plasma exchange are commonly used. The 2021 revision of the international CIDP guideline by the European Academy of Neurology and Peripheral Nerve Society offers recommendations on CIDP diagnosis and treatment; however, local guidelines and protocols can provide additional insights into CIDP management in clinical practice. In this article, a group of EU and US physicians with experience in CIDP management aims to provide insights into CIDP treatment considerations using regional resources and professional experience. Owing to the heterogeneity of the disease and its variable clinical course, CIDP treatment response varies among patients. It is therefore important to consider not only regional pressures, such as immunoglobulin availability, which may limit its use, but also how to monitor treatment response and make informed decisions about when to adjust, withdraw, or switch treatment for the patient's benefit. As misdiagnosis of CIDP is common, diagnosis should be reconsidered in cases where there is a lack of treatment response. Using example cases, this article draws on regional treatment frameworks and the expert experience of EU and US professionals to provide a resource for trainee physicians and professionals involved in the management of CIDP.

Key Summary Points

Why carry out this study?

The purpose was to describe how variability in healthcare systems and facilities, treatment availability, and local clinical practice contribute to differing regional approaches to CIDP management

Existing international and local guidelines emphasize diagnosis and induction therapy but offer limited practical direction for maintenance, adjustment, and withdrawal

What was learned from the study?

Regional treatment frameworks from Europe and the US described in this review can complement the EAN/PNS guidelines by providing additional insight and practical guidance for treatment, especially for long-term maintenance therapy

Early treatment, tailored IVIG strategies, and structured weaning approaches outlined in regional frameworks provide valuable insight for physicians treating CIDP

Effective long-term care requires regular reassessment, individualized dose optimization, and multidisciplinary support to address the chronic and often unpredictable nature of CIDP

Introduction

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common form of immune-mediated demyelinating peripheral neuropathy [1, 2], with a prevalence estimated at 1–9 cases per 100,000 people and an incidence ranging from 0.2 to 1.6 per 100,000 people per year [3, 4]. CIDP is characterized by progressive, symmetric, proximal, and distal muscle weakness, areflexia, and often sensory loss [3, 5, 6]. The etiology of CIDP is not well understood, but there is evidence of autoimmune involvement in the disease's pathogenesis in which cellular and humoral responses contribute to inflammatory processes and peripheral nerve demyelination [2, 7, 8]. Patients with CIDP often show improvement with immunomodulatory therapies, such as immunoglobulins, corticosteroids, and plasma exchange (PE) [9–13].

Although patients with CIDP can achieve remission, for most others, treatment can be long term, with a chronic progressive or relapsing-remitting disease course [5, 7, 14–16]. Evidence of the efficacy and safety of immunoglobulin therapies in CIDP in randomized controlled trials is typically limited to observations for up to 48 weeks with maintenance doses ranging from 1.0 g/kg of bodyweight every 3 weeks to 2.0 g/kg every 4 weeks (or lower weekly doses for subcutaneous immunoglobulin [SCIG]) [12, 17–19]. Observational studies of immunoglobulin therapies have demonstrated their effectiveness over extended follow-up periods from 2 to 7 years [15, 20]; however, immunoglobulin therapies carry significant cost and supply limitations [9]: long-term treatment with corticosteroids is limited by the risk of serious side effects [5, 11], and evidence for PE is limited to a few short-term trials [10].

Intravenous immunoglobulin (IVIG), corticosteroids, and PE are commonly used in CIDP and can achieve short-term improvement, but there is no clear difference in effectiveness between treatment options, and why some patients respond to a particular treatment is not understood [9, 21]. In a meta-analysis of 21 studies, the pooled fraction of patients with CIDP in 1-year remission (stable disease without treatment) was approximately 40%; hence, there is an unmet need for effective long-term management [1, 22]. Recently, a neonatal Fc receptor (FcRn) inhibitor, efgartigimod alfa with recombinant human hyaluronidase (efgartigimod PH20), has been shown to reduce the risk of relapse versus placebo in a phase 2 clinical trial [23]. This therapy has been approved in the USA and offers short infusion times that may be convenient for patients [24]; however, treatment effectiveness may be limited by the underlying pathophysiology in individual CIDP cases [25, 26]. Rozanolixizumab, a different anti-FcRn binding antibody, has not shown efficacy in a clinical trial in patients with CIDP [27].

In 2021, the international CIDP guideline was revised under the leadership of the European Academy of Neurology (EAN) and Peripheral Nerve Society (PNS) [5]. This guideline mainly focuses on diagnosis and induction treatment for CIDP, distinguishes between CIDP and its variants, and highlights the use of IVIG and corticosteroids as induction treatments, with PE recommended if these options are ineffective. Some aspects of management are relatively underrepresented in the EAN/PNS guideline owing to a lack of evidence, including treatment choices, maintenance treatment, and treatment withdrawal. To build on guideline recommendations, practical guidance based on clinical experience from experts in the field can help clinicians manage this complex disorder by providing advice on monitoring and assessing treatment effectiveness over the long term, adjusting therapies to avoid complications or relapses, and helping patients manage daily life.

We aim to provide an overview of treatment considerations for CIDP, treatment challenges, and management strategies, leveraging regional treatment frameworks and expert perspectives across Europe and the US to guide clinical decision-making. The author panel for this article includes two academic clinicians from the USA and two from Europe, all with long-standing experience in the treatment of CIDP. Selection of articles for this review was based on the consensus of the authors to represent a range of perspectives. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Regional Treatment Frameworks

The European Federation of Neurological Societies/PNS criteria were first published in 2006 by an international task force to provide a consensus guideline on the definition, investigation, and treatment of CIDP [28]. It was updated in 2010 and 2021 (by EAN/PNS) and is widely consulted because it provides comprehensive diagnostic criteria with high sensitivity and specificity among CIDP diagnostic guidelines [5, 29–31]. Adherence to this guideline may differ across regions owing to differences in treatment availability and healthcare policies and to limited evidence on the comparative effectiveness of treatments and long-term treatment strategies [5]. In addition, independent, locally developed treatment frameworks, including formal national guidelines, expert-led narrative reviews, and regional protocols, draw on evidence from real-world clinical practice and local needs. Treatment frameworks included in this review were selected via consensus among the authors to represent a range of European and US perspectives.

A 2023 national protocol from The Netherlands was developed to provide guidance on monitoring IVIG maintenance therapy and titrating IVIG doses to the lowest effective dose [32]. The protocol covers how and when to initiate IVIG maintenance, how to adjust IVIG maintenance treatment, conversion to SCIG, testing for IVIG dependence, and treatment tapering and cessation [32]. A US expert review published in 2022 provided practical guidance on responding to challenges encountered during CIDP management and monitoring patient response to maintenance treatment to classify complete and partial responders to first-line therapy [1]. The Danish Medicines Council (Medicinrådet) guidelines describe in detail how to initiate treatment, monitor patient response and adjust treatment, and switch between immunoglobulin preparations [33]. Aiming to harmonize treatment practices, a task force of French neurologists and neuromuscular disease experts published advice on the management of CIDP with immunoglobulin therapies [34]. Additionally, a group of UK experts created an algorithm to optimize IVIG dosing based on patient response [35].

Treatment Considerations

In this article, the key treatment considerations in the management of CIDP are discussed, summarizing the recommendations of regional frameworks from The Netherlands, the USA, Denmark, France, and the UK, which are primarily focused on the use of immunoglobulin therapies. These recommendations are supported by evidence from clinical studies where available. An overview of framework recommendations at each treatment stage is shown in Fig. 1, with Table 1 providing a more detailed overview of the regional similarities and differences between frameworks.

Fig. 1.

Visual overview of recommendations from regional frameworks for the treatment of CIDP with immunoglobulins. CIDP chronic inflammatory demyelinating polyradiculoneuropathy, IVIG intravenous immunoglobulin, SCIG subcutaneous immunoglobulin

Table 1.

Summary of treatment considerations from regional frameworks in patients diagnosed with CIDP

Treatment consideration	Allen and Lewis 2022 [1] USA Expert narrative review	Cintas et al. 2023 [34] France National guideline on immunoglobulin treatment	Lucke et al. 2023 [32] The Netherlands Immunoglobulin maintenance treatment protocol	Medicinrådet 2024 [33] Denmark National guideline on immunoglobulin treatment	Lunn et al. 2016 [35] UK Immunoglobulin dosing algorithm
Induction therapy	Intravenous immunoglobulin (IVIG) 2.0 g/kg or corticosteroids (e.g., oral prednisolone 60 mg/day. If no response, plasma exchange (PE) and other immunotherapies are alternative options	Initiate IVIG (2.0 g/kg every 4–6 weeks) upon diagnosis and agreement from multidisciplinary consultation	IVIG 2.0 g/kg over 3–5 days followed by several infusions of 0.4–1.0 g/kg every 2–3 weeks if recovery is incomplete or another 2.0 g/kg if no response (reconsider the diagnosis before switching to corticosteroids or PE)	Loading infusions with IVIG 2.0 g/kg over 5 days can be repeated 1–2 times. If no response, reconsider diagnosis or switch to corticosteroids or PE	IVIG 2.0 g/kg with an optional second dose after 6 weeks if not fully normalized after the first dose. Wait until deterioration to determine dosing interval
Patient monitoring
Induction phase	Response to treatment is expected within 3–6 months	Monitor clinical disability every 2 months, minimum	Test for IVIG dependence during induction therapy and monitor for objective deterioration/improvement throughout treatment	Monitoring of treatment response 2–3 weeks after initial treatment	Assess treatment response 3 weeks after the initial dose
Dependent phase	Continue to monitor	Assess functional ability every 6 months during maintenance and test for IVIG dependence “periodically”	Test IVIG dependence every 6–12 months for the first 2–3 years and then every 1–2 years	Patients on stable maintenance treatment are monitored every 6 months for the first 2–3 years of treatment and then once per year	Assessed using at least two validated outcomes. Clinically important differences used as thresholds for response decisions
Maintenance
IVIG dose	1.0 g/kg (or 2.0 g/kg in select patients) every 3 weeks. Corticosteroids not favored for long-term management	0.4–1.0 g/kg every 2–6 weeks	0.4–1.0 g/kg every 3–4 weeks	1.0–2.0 g/kg every 2–10 weeks	Determined by time to relapse upon withdrawal during induction phase
Dose adjustment	Treatment weaning for complete responders to determine the lowest effective dose	If stable or responsive to maintenance therapy, determine the minimum effective dose	In case of improvement, reduce the dose by 25% or increase the interval (no longer than 4 weeks)	If needed, adjust maintenance therapy individually according to clinical scores and clinical symptoms	Reduce dose by 20% per course until relapse to determine dose
Treatment withdrawal	Discontinue therapy if no deterioration upon weaning	Treatment can be stopped upon regression of symptoms	Tapering is preferred (e.g., maximum 25% reduction in dose per infusion)	Withdrawal attempts follow stepwise dose reduction to 90%, 75%, 50%, 25%, and 0 over 6–12 weeks. Continue therapy at lowest dose without relapse. Subsequent withdrawal attempts every 1–2 years	Withdrawal attempts are made annually in nonfluctuating patients over at least the first 3 years
Treatment switching	If long-term maintenance is needed, or if the patient has issues with intravenous access, subcutaneous immunoglobulin (SCIG) is an option	Possible once the minimum effective dose as well as dependence have been determined, or upon deterioration/no response to induction therapy	If no improvement with IVIG and other diagnoses are ruled out, switch to corticosteroids or PE if there is severe failure. SCIG is an option for patients with end-of-dose symptoms, intravenous complaints, or frequent travel	Patients with treatment response who can manage subcutaneous infusions can switch to SCIG	Not reported

IVIG intravenous immunoglobulin, PE plasma exchange, SCIG subcutaneous immunoglobulin

Induction Therapy

Early start of treatment, at the time of CIDP diagnosis, is recommended to limit the extent and progression of underlying axonal degradation [33, 36], which is the main cause of residual disability and functional decline [37–39]. A population-based cross-sectional study showed that long-term peripheral neuropathy-related disability is related to a delay in therapy [40]. The regional frameworks largely concur with the EAN/PNS guideline, finding that IVIG, corticosteroids, and PE are all options for induction therapy. IVIG and corticosteroids are typically favored, but their use depends on the CIDP variant, contraindications, patient preference, and, for IVIG in particular, availability [1, 36]. IVIG is used as a first-line therapy more often than corticosteroids [41] owing to faster improvement among patients and fewer short- and long-term adverse effects [5]. PE is often only considered as a second-line induction therapy after failure of IVIG and corticosteroids given the need for specialized equipment, which is not available in all hospitals, as well as central or peripheral venous access in the patient [1, 34, 36, 42]. In The Netherlands and Denmark, IVIG is the primary first-line therapy offered to patients [32, 33]. There are slight variations in IVIG induction dosing recommendations in the regional frameworks and the dosage of 2.0 g/kg divided over 2–5 days highlighted in the EAN/PNS guideline (Table 1). Among the treatment frameworks included in this review, corticosteroid induction therapy dosing is only explicitly defined in the US expert narrative review. Doses recommended are either oral prednisolone 60 mg/day for 4–8 weeks, pulsed intravenous (IV) methylprednisolone 500 mg/day, or pulsed oral dexamethasone 40 mg/day for 4 days repeated every 4 weeks [1]. The potential for IVIG and corticosteroid combination therapy was investigated in a randomized, double-blind placebo-controlled study, but it did not show superiority to IVIG alone and was prematurely stopped owing to safety concerns [43].

The purpose of induction therapy is to improve signs and symptoms of CIDP and to maintain patients’ functional ability. The decision to proceed with further doses or full maintenance dosing, or to adjust or withdraw therapy, depends on the outcomes at this stage. Approximately 15% of patients achieve clinical remission after 1–2 IVIG doses without the need for further treatment [21, 32]. Therefore, the Dutch protocol recommends a test for IVIG dependence prior to maintenance treatment; however, this recommendation is not shared by all regional frameworks [32].

Patient Monitoring

To monitor patient response to treatment, a variety of objective measures of functional impairment/disability and strength impairment are available, such as the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) and the Inflammatory Rasch‐built Overall Disability Scale (I-RODS) [5]. It is generally agreed that objective measures of response to treatment are needed, and these are well defined in the EAN/PNS guidelines [5]. Cintas et al. (2023) note that in France, the panel of tests for disease monitoring throughout treatment should be specified before initiation, with disability assessments every 2 months in the induction phase and every 6 months during maintenance [34]. The US expert narrative review suggests using one measure of disability and one of strength [1], and a French national guideline recommends supplementing objective tests with subjective patient measures [36]. Some subtypes of CIDP, such as Lewis Sumners syndrome and distal acquired demyelinating neuropathy, are associated with less generalized disability, making it necessary to consider modified monitoring instruments [5]. CIDP does not yet have a reliable biomarker for disease monitoring, but serum neurofilament light chain levels (also linked to other neurological and immune-mediated conditions) may be associated with disease activity in some patients with CIDP [44].

Maintenance Therapy

Maintenance dosing of immunoglobulin therapy should be highly individualized and guided by patient response and the time of symptom recurrence after dosing [45]. Maintenance strategies vary considerably from the standard 1.0 g/kg every 3 weeks used in the ICE study [45, 46]. No universally accepted treatment protocol exists, but the regional frameworks provide insight into feasible dosing strategies. The decision to start maintenance therapy depends in part on the response to induction therapy (and, in some strategies, on a relapse thereafter), and approaches vary among the regional frameworks. The need to avoid overuse of immunoglobulin supplies is frequently cited as justification for appropriate dose-finding and for avoiding maintenance therapy when not needed [32–34, 36].

Response to treatment with IVIG or corticosteroids typically occurs within 3 months for most patients, with all patients expected to respond within 6 months [1]. Some patients may experience an even earlier response with IVIG [21, 32]. If patients are responsive to induction therapy with IVIG, testing for IVIG dependence can determine whether deterioration occurs in the absence of therapy [32]. According to the protocol from The Netherlands, maintenance dosing of IVIG 0.4–1.0 g/kg every 3–4 weeks should be sufficient for most patients; however, in patients with pronounced deterioration during a test for IVIG dependence, a loading infusion of 2.0 g/kg (over 2–5 days) prior to maintenance is advisable [32]. The US expert review favors 1.0 g/kg every 3 weeks, or up to 2.0 g/kg if needed [1]. In practice, longer dosing intervals of 2–6 weeks (0.4–1.0 g/kg) and 2–10 weeks (1.0–2.0 g/kg) are sometimes used, depending on treatment response and the time to the emergence of end-of-dose symptoms [32–34]. Conversely, the Dutch framework does not recommend intervals longer than 4 weeks owing to the half-life of IVIG [32]. Objectively measuring post-dose deterioration can help to determine the lowest effective maintenance dose and interval. The appropriate maintenance dose can be estimated using the number of weeks elapsed between a further dose of 2.0 g/kg and reappearance of symptoms [33, 35]. Depending on the region, various IVIG brands may be available, but clinical evidence suggests they are typically considered equivalent [33, 47, 48].

For maintenance therapy with corticosteroids, both oral (e.g., prednisone, prednisolone, or dexamethasone) and IV (e.g., methylprednisolone) therapies are used [1, 36]. Doses, dosing intervals, treatment duration, and drug selection are not standardized or well defined in regional frameworks, perhaps owing to heterogeneity in local preferences, drug availability, labeling, and patient characteristics. Corticosteroids are not typically preferred for long-term maintenance (> 3 months) at high doses owing to the side effect profile [1].

Similarly, long-term IVIG dependence is not desirable because of the burden of side effects and/or frequent need for IV access; therefore, patients with difficult IV access or frequent side effects may prefer an alternative route such as subcutaneous, which can be self-administered at home and which offers a level of autonomy to these patients [1, 32, 33].

It is reasonable to start with a 1:1 conversion from IVIG to SCIG (administered at shorter intervals), although there is limited evidence that some patients with CIDP require a higher dosage of SCIG compared with IVIG [5]. The exact conversion rate from IVIG to SCIG is unknown [32]. SCIG may be better suited to patients who have end-of-dose symptoms at the end of IVIG dosing intervals [32]. A longer-acting hyaluronidase-facilitated SCIG with dosing intervals similar to those for IVIG therapies has been shown to have efficacy in CIDP [19].

Maintenance with PE is typically considered after failure of IVIG or corticosteroids and is initiated with multiple exchanges per week, followed by a treatment interval adapted to individual patients [1, 36]. Efgartigimod PH20 is an approved FcRn antagonist for CIDP maintenance therapy in the USA [24], but early deterioration has been reported in patients with CIDP switching from IVIG to efgartigimod PH20, and real-world experience in CIDP is limited [25, 26].

Dose Adjustment

IVIG maintenance dose adjustment in response to clinical deterioration (which may indicate insufficient dosing) often depends on the presence of symptoms before the next scheduled infusion. Increasing the dose or shortening the treatment interval are options to mitigate end-of-dose symptoms. In the case of deterioration with an absence of end-of-dose symptoms at the end of the treatment interval, the preferable approach should be to increase the dose (e.g., by 20–30% or more) [32]. This approach may not be suitable for all patients; those with a severe disease exacerbation may require an additional infusion or a full loading dose [32].

Recommendations for time intervals to assess the usefulness of continued maintenance treatment range from every 3–6 months [36] to every 6–12 months for the first 2–3 years, then every 1–2 years [5, 32]. Individualizing doses using periodic objective reassessments may provide cost savings versus weight-based dosing alone [49], and lower doses (e.g., 0.5 g/kg) may be as effective as higher doses (e.g., 2.0 g/kg) in some patients [50]. In the absence of deterioration, or when it is clear that maximal improvement has been achieved in a patient with stable disease, various strategies for IVIG treatment dose reduction are reported. The purpose of dose-reduction in responders is to determine the lowest effective dose [1, 34]. Options for dose adjustment include reducing in steps of 25% per infusion [32], or a stepwise reduction to 90% of the maintenance dose, then 75%, 50%, and 25%, with a step length of 6–12 weeks (ending with treatment withdrawal if suitable) [33]. The effects of dose adjustments on symptoms should be carefully monitored to avoid overtreatment [33].

As an alternative to dose reduction, the treatment interval can be extended, but there is some debate as to whether the interval for IVIG administration should be lengthened beyond 4 weeks. Extending the interval beyond 4 weeks has been suggested on a case-by-case basis if maximal improvement is sustained [34]. A UK-based dosing algorithm proposed by Lunn et al. (2016) determines the treatment interval according to the time to deterioration after one or two initial loading doses of 2.0 g/kg [35]. The interval between the last dose and patient deterioration is confirmed as the dosing interval for further treatment, and in a sample of patients with either CIDP or multifocal motor neuropathy, this resulted in dosing intervals ranging from 0.5 weeks to a long interval of 10 weeks [35]. This strategy aims to find the minimal dose that prevents relapse while minimizing the use of immunoglobulin supplies. In the case of patient deterioration after a dose adjustment, the previous suitable dose/interval can be reinstated [34].

Treatment Withdrawal

In the absence of adverse events, there are two primary reasons for treatment withdrawal: (1) an absence of response to therapy and (2) achievement of maximal improvement and lack of deterioration upon dose reduction. During IVIG induction therapy, an absence of response may be a sufficient reason to discontinue without tapering the dose level, to reconsider whether the diagnosis of CIDP is still correct, or to attempt a different therapy [32, 34]. However, evidence from a clinical trial suggests two induction doses may be required for initial improvement [51], and some patients may take longer than others to show improvement.

The absence of clinical decline in patients after induction therapy may suggest a complete treatment response; however, irreversible nerve damage may persist despite apparent remission [1]. The IVIG dosing interval estimation test, outlined in the Danish guidelines, provides an early opportunity to assess the suitability of IVIG withdrawal [33]. In this test, after an induction dose, the time to evidence of patient deterioration is used to infer the maintenance dosing interval, and if patient response is maintained upon treatment withdrawal, maintenance dosing is not necessary [33].

During long-term maintenance, treatment withdrawal is a possible outcome of periodic tests for IVIG dependence, which are recommended every 3 months to every 2 years in the regional frameworks [5, 32, 33, 36]. Maintenance dosing should typically be continued until no further improvement is observed [34] and, if tapering the dose, until no clear or objective deterioration is observed [1]. A trial showed that 41% of patients who were tapered off IVIG remained stable with CIDP at 24 weeks, compared with 58% of patients who continued IVIG [52]. Similarly, a trial of stepwise tapering of SCIG treatment in patients with stable CIDP showed that SCIG could be completely tapered off in 36% of patients and that only 10% experienced relapse [53]. The clinical data show that re-stabilization after IVIG tapering/withdrawal may not be possible within 12–13 weeks in a small proportion of patients [52, 54].

Treatment Switching

A specific treatment may need to be changed, depending on its effectiveness and side effect profiles, and patient convenience and preference. During induction therapy, PE can be used in the absence of response to IVIG and corticosteroids and in patients who have contraindications to these therapies [1, 33, 36].

In the absence of a response to IVIG, clinical evidence suggests that switching to another brand of IVIG is unlikely to be beneficial [47] and therefore is not recommended. SCIG is an alternative to IVIG maintenance therapy, enabling more convenient, shorter dosing intervals in the event of end-of-dose symptoms with IVIG [32, 33]. Although not suitable for all patients, SCIG and hyaluronidase-facilitated SCIG eliminate the need for venous access, enabling subcutaneous self-administration (or administration with a caregiver's help) at home [34, 36]. A phase 3 clinical trial reported that patients who preferred SCIG to IVIG cited fewer side effects [18], and treatment frameworks note that patients with systemic side effects related to IVIG may benefit from switching to the subcutaneous route of administration [1, 33, 36]. Based on these potential benefits of SCIG, the Danish guideline recommends SCIG over IVIG as a maintenance therapy for most patients [33]. Clinical data suggest that subcutaneous efgartigimod PH20 may offer convenience for patients owing to the very short infusions (30–90-s infusions) [24], although its effectiveness when switching from IVIG is unclear at this time [23, 25, 26].

Organization of Care

As with any chronic disease, patients with CIDP can be concerned about their condition and may need lifestyle adjustments to accommodate therapy and manage their symptoms [1, 55]. The involvement of mental health professionals, support networks, and social services is an important but underutilized aspect of CIDP management [1, 36]. Withdrawal of immunoglobulin therapy may lead to uncertainty among patients with CIDP; therefore, the Danish guidelines recommend offering support and advice and monitoring the clinical condition of patients going through the treatment withdrawal procedure as well as patients undergoing SCIG therapy at home [33]. This is aided by a multidisciplinary team of professionals including a specialized nurse, a physiotherapist/nurse, a rehabilitation physician, and a neuromuscular neurologist [33]. Communication between professional staff and patients regarding the results of monitoring, the status of the patient’s clinical condition, and the need for follow-up is important [33]. Furthermore, patients should be informed at the start of maintenance treatment about the need for regular reassessments to determine whether continued treatment is necessary [32].

Example Hypothetical Cases

The following hypothetical examples are intended to provide insight into potential approaches to patient responses to treatment, considering the recommendations of the regional frameworks and the authors' clinical experience. We present five cases illustrating potential scenarios experienced by CIDP-treating physicians and identify aspects of each case that inform the approach or that lead to changes in dosing or treatment. Each case is assumed to start with a diagnosis of CIDP consistent with the EAN/PNS criteria [5], with confirmed abnormalities on appropriate electrophysiological tests indicating demyelination. Other relevant diagnostic details are included for each case, and any improvement or deterioration in CIDP is inferred from a suitable panel of objective tests and subjective patient feedback. These cases are intended for educational purposes only. Real-world cases should be assessed based on individual patient presentation, and any local regulations regarding CIDP treatment should be followed.

Hypothetical Case 1: Revisiting Diagnosis During Induction Therapy

After an initial clinical diagnosis of CIDP, IVIG induction therapy was initiated at 2.0 g/kg divided over 2–5 days. When no improvement in symptoms was observed, a second course of IVIG at 2.0 g/kg was administered, but it had no effect. A retrospective study of patients with CIDP who received induction therapy with IVIG showed that IVIG non-responders had a high chance of responding to corticosteroids, PE, or both [21]. Therefore, pulsed corticosteroids were administered (IV methylprednisolone 500 mg/day for 4 days, repeated every 4 weeks), but after two courses, there was still no improvement in symptoms. The next step would be to initiate PE, if available and feasible for the patient. However, given that a lack of response to the two prior therapies is uncommon, it would be important to reconsider whether the diagnosis of CIDP was correct: numerous other conditions can mimic CIDP, as documented in the literature, and misdiagnosis is common [5, 34, 56–58]. Clinical pearl: In this case, reevaluation of CIDP should have been considered with earlier treatment failure.

Hypothetical Case 2: Dose Adjustment After Treatment Response

The patient showed partial improvement after induction therapy with IVIG at a dose of 2.0 g/kg administered over 3 days. Subsequently, it was decided to proceed with maintenance therapy, administering IVIG at a dose of 1.0 g/kg every 3 weeks. The patient’s condition continued to improve; after several courses, the response plateaued, suggesting maximal effect. To evaluate whether a lower dose or complete withdrawal was feasible, subsequent doses were reduced incrementally by 25%. However, after reducing the dose in two steps (to 0.75 g/kg every 3 weeks, then 0.5 g/kg every 3 weeks), a deterioration in the patient’s functional ability was observed, indicating that the disease is active and that complete IVIG withdrawal is not yet appropriate. The patient should be returned to the previous effective IVIG dose to continue maintenance therapy. If the patient achieves maximal improvement on the reinstated dose, further dose adjustments can be considered, with a view to treatment withdrawal in the future if possible. An alternative approach to the initial reduction of the maintenance dose level could have been to extend the treatment interval of the initial dose (1.0 g/kg every 4 weeks rather than every 3 weeks). Clinical pearl: Treatment dependence should be evaluated frequently in patients on maintenance treatment.

Hypothetical Case 3: Complete Remission

A patient in their early 40s presented with a 3-month history of symptoms consistent with CIDP. They initially received two IVIG induction cycles (2.0 g/kg split over 3–5 days, every 3 weeks) instead of proceeding immediately to maintenance dosing of 1.0 g/kg every 3 weeks (see case 2). After the second induction course, the patient entered remission. This is close to a best-case scenario for several reasons. First, the patient’s younger age compared with the average age at CIDP diagnosis (late 50s) [59] is beneficial, as advancing age is associated with worse disability outcomes [60, 61]. Second, typical CIDP is associated with more favorable responses to treatment than atypical variants (e.g., distal and multifocal CIDP) [61]. Lastly, the patient’s condition was identified and treated early. This case also highlights the value of frequent objective clinical monitoring and multiple courses of induction therapy. Quick recognition of clinical response in the induction phase may be a more efficient use of resources because it avoids the need for maintenance treatment in some cases as approximately 15% of patients enter remission after 1–2 IVIG induction doses [21, 32]. Clinical pearl: CIDP can be monophasic without the need for maintenance treatment.

Hypothetical Case 4: Insufficient Dose

As in case 2, this patient showed improvement after receiving an IVIG induction dose of 2.0 g/kg over 3 days. Transitioning to maintenance dosing of IVIG 1.0 g/kg every 4 weeks led to deterioration in their condition. Patient feedback showed that the deterioration did not coincide with the end of treatment intervals. In response to this, a second loading dose of IVIG at 2.0 g/kg was administered, resulting in improvement, and the maintenance regimen of IVIG at 1.0 g/kg every 4 weeks was resumed. However, deterioration in functional ability after several courses again indicated that the effect of IVIG diminished. The higher dose was then attempted as a maintenance dose (e.g., 2.0 g/kg every 4 weeks), and improvement in functional ability was finally maintained. This case indicates that some patients may need high doses (e.g., 2.0 g/kg) [50] or, in some cases, very high fractionated doses (e.g., 5.0–9.0 g/kg per month) for adequate clinical response [62, 63]. Although evidence is limited, cyclophosphamide, ciclosporin, efgartigimod PH20, and rituximab have been considered for patients who do not respond adequately to or are refractory to standard treatments [5, 23]. Clinical pearl: Some patients with CIDP require very high or fractionated doses of IVIG.

Hypothetical Case 5: Severe Relapsing CIDP

This patient initially showed a favorable response to IVIG therapy; however, after 4 years of maintenance treatment, ambulation was lost. Treatment switch to either PE, steroids, or ciclosporin was attempted with no effect. Although there are no trials of combination therapy in severe relapsing CIDP, daily oral prednisolone (0.75 mg/kg) was added to the previous IVIG regimen (2.0 g/kg) for this patient, but there was no improvement. Subsequently, a triple combination therapy was attempted, starting with PE (three exchanges of 2.75 l) followed by IVIG and continued oral prednisolone every 4–5 weeks for 3–4 months. Reestablishment of ambulation occurred. The patient continued to experience severe relapses of CIDP that seemed to respond to this combined triple therapy. Clinical pearl: This case illustrates the unpredictability of CIDP and that treatment in some cases may need to be managed by expert physicians.

Conclusions

This article aims to deepen understanding of CIDP and to guide trainee physicians and other healthcare professionals by outlining clinical approaches and practices used across diverse settings. The EAN/PNS guideline is a welcome resource of evidence-based recommendations for the diagnosis and induction treatment of CIDP, but regional guidelines and protocols developed by experts provide additional insights into the nuances of treating patients with CIDP in clinical settings. This review provides an overview of regional CIDP treatment frameworks from across Europe and the USA, outlining their recommendations for treatment approaches and including aspects not comprehensively covered by the EAN/PNS guideline, such as maintenance therapy, dose adjustment, and treatment withdrawal. The differences among regional frameworks arise from regional best practices, local regulations, and the availability of therapy. A limitation of this approach is that immunoglobulin treatment is primarily delivered in Western healthcare systems; therefore, the conclusions of this article may not be fully applicable to resource-limited regions. CIDP is a heterogeneous group of conditions that require personalized treatment approaches depending on the underlying condition and response. Using information from regional frameworks and our clinical experience, the hypothetical cases presented in this review illustrate the importance of a thorough understanding of treatment options, potential responses, and the need for adjustments.

Author Contributions

Johannes Jakobsen, Chafic Karam, Krista Kuitwaard, and Todd Levine contributed to the conception of this review, original draft preparation, and manuscript review and editing. All authors have read and approved the final version of the manuscript.

Funding

The authors received no funding for their involvement in this review article. Takeda Develop Center Americas, Inc., funded the journal’s Rapid Service Fee.

Data Availability

Data sharing is not applicable because no datasets were created or analyzed in this review.

Declarations

Conflict of interest

Johannes Jakobsen has received payment or honoraria for lectures, presentations, or educational events from Takeda. Chafic Karam has received grants or contracts from Ionis and Argenx in the past 36 months and consultancy fees from Alexion, Alnylam, Alpine, Amgen, Amicus, Annexon, Argenx, AstraZeneca, Biogen, Corino, CSL Behring, Genentech, Ionis, J&J, Neuroderm, Novo Nordisk, Octapharma, Pfizer, Sanofi, Takeda, UCB, Vertex, and Zai Lab. Krista Kuitwaard has received research grants from Albert Schweitzer Hospital, Takeda, and the For Wis(h)dom Foundation in the past 36 months, consultancy fees from Takeda, speakers fees from Grifols and Octapharma, and support for attending meetings and travel from GBS-CIDP Foundation International and Octapharma. Todd Levine is a consultant for FFF Enterprises and is on the speakers bureau for Grifols.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.