3 Things You Should Know About Chronic Inflammatory Demyelinating Polyneuropathy

Disclosures: Consultant: Annexon, Argenx, CSL Behring, Dianthus, Grifols, Immunovant, Sanofi, Takeda

This activity was written by PER® editorial staff based on an online activity developed with Dr. Gable.

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The staff of Physicians’ Education Resource®, LLC, have no relevant financial relationships with ineligible companies.

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Release Date: March 13, 2025

Expiration Date: March 13, 2026

Learning Objectives

• Upon successful completion of this activity, you should be better prepared to:
• Identify the unmet treatment needs of patients with CIDP
• Summarize guideline recommendations for the diagnosis of CIDP
• Describe how novel therapies target the underlying disease mechanisms associated with CIDP
• Select appropriate therapies for the treatment of CIDP based on patient-specific factors and considerations
  

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Physicians’ Education Resource®, LLC, designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from argenx.

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This activity may or may not discuss investigational, unapproved, or off-label use of drugs. Learners are advised to consult prescribing information for any products discussed. The information provided in this activity is for accredited continuing education purposes only and is not meant to substitute for the independent clinical judgment of a health care professional relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER® or any company that provided commercial support for this activity.

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1. Chronic inflammatory demyelinating polynueropathy (CIDP) is associated with substantial disease burden.

CIDP is a rare, immune-mediated disorder in which an aberrant immune response causes demyelination and axonal damage to peripheral nerves. It is most commonly characterized by proximal and distal upper and lower extremity weakness, impaired sensory function, and reduced or absent reflexes. It is a long-term condition with a variable course that can be relapsing–remitting, stepwise progressive, or gradually progressive and because of this it is often associated with a high burden of disease.^1,2

In a global study of individuals (N = 595) with self-reported CIDP, 222 respondents were classified as likely to have the disease.⁴ Among this cohort, 90% reported experiencing between 8 to 10 CIDP symptoms, with the most common being hip/leg weakness, loss of balance/coordination, fatigue, and paresthesia. The symptom that was most bothersome to patients and that they most wanted relief from was loss of balance/coordination. Due to these symptoms, a significant number reported making changes to their work or home life (Table 1). Additionally, 53% were concerned that they would be dependent on others; 49% were worried their symptoms would progress, 40% had concerns that their treatment may stop working; and only 27% were optimistic that their symptoms would improve.⁴

Findings from the first systematic assessment of the burden of illness of CIDP conducted were published in 2021.⁵ Based on the 66 articles included in the analysis, the significant burden of CIDP was confirmed and further characterized. Of these, 7 were humanistic burden studies (ie, those pertaining to impact on health-related quality of life (HRQoL), functioning, psychosocial, welfare, productivity, pain, and fatigue). Results confirmed that CIDP has a substantial physical impact, with patients reporting pain, fatigue, and impaired physical functioning. Impact also may extend beyond the physical burden of the disease to depression. HRQoL is also impaired. In 2 studies from the UK and Germany included in the analysis, EuroQol-5D (EQ-5D) scores among patients with CIDP were 0.626 and 0.687, respectively. These scores denote moderate impairment when compared with healthy adult benchmarks of 0.85 to 0.95 and correlate with ongoing, meaningful HRQoL burden.⁸ Eight publications reported on the economic burden of CIDP. Most were from European countries; three reported data from the US. As expected, costs varied by country and region, however in all cases drug-related costs were the main drivers of direct CIDP expenditure (57% of total costs in the US) followed by inpatient and hospital services (35% in the US). Indirect costs were also substantial and largely attributed to impaired productivity from premature retirement, unemployment, sick leave, and reduction of work time.⁵

While recommended therapies can improve patient well-being, they are also associated with tolerability issues and challenges. Parenteral therapies such as intravenous immunoglobulin, subcutaneous immunoglobulin, and plasma exchange carry varying risks of adverse events and administration requirements that can limit patient independence. In summary, the burden of CIDP is multidimensional, encompassing physical disability, reduced quality of life, psychosocial strain, and substantial socioeconomic impact. As such, further research and increased clinician education is warranted to support developing measures for mitigating the disease burden for patients and healthcare systems.

“Helping to restore a sense of well-being matters in CIDP. Patients with CIDP who achieve higher levels of well-being are more likely to remain engaged with long-term therapy, rehabilitation, and follow-up— all critical for achieving optimal outcomes in a chronic, relapsing condition like CIDP.”⁹
– Karissa Gable, MD, Duke University Medical Center

2. CIDP diagnosis is challenging and requires methodical, stepwise evaluation.

Diagnosis of CIDP can be challenging due to a variety of factors (Figure 1)¹⁰ and this contributes to misdiagnosis, underdiagnosis and/or delayed diagnosis, which data indicate are prevalent.^11-14 In one study 54% of patients presenting with CIDP were misdiagnosed, with the most common misdiagnosis being amyotrophic lateral sclerosis and average time to diagnosis was 30 months.¹³ Other reported data have shown that 20% were underdiagnosed.¹⁴ Misdiagnosis of CIDP subjects individuals to treatment risks with little to no benefit. Delayed diagnosis exposes patients to longer periods of axonal damage and resulting disability.

Use of a systematic approach can improve diagnostic accuracy and efficiency.¹⁰ Such an approach is asserted in the 2021 joint guidelines from the European Academy of Neurology (EAN) and Peripheral Nerve Society (PNS). These guidelines emphasize that the diagnosis of CIDP be based on clinical, electrodiagnostic (mandatory), and supportive criteria (Table 2).

3. An FcRn blocking therapy is FDA approved for treatment of CIDP.

The neonatal Fc receptor (FcRn) plays a central role in CIDP pathophysiology. When FcRN binds the IgG autoantibodies in CIDP that cause myelin destruction, they are protected from lysosomal degradation, thereby prolonging their half-life.¹⁵ Efgartigimod is an FcRn blocker that binds to FcRn preventing it from recycling IgG antibodies, which leads to a reduction in overall IgG levels, including the problematic ones that drive CIDP. Efgartigimod alfa and hyaluronidase-qvfc was approved for treatment of CIDP in adults by the U.S. Food and Drug Administration in June 2024.¹⁶ The approval was based on the ADHERE trial conducted at 146 sites in Asia-Pacific, Europe, and North America.^17,18 The trial was conducted in 2 stages. Stage A was an initial treatment period of up to 12 weeks done to identify responders who had improvement in functional ability (defined as an improvement of ≥1 point on the adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT) disability scale or improvement of ≥4 points on the Inflammatory Rasch-built Overall Disability Scale (I-RODS); or strength (defined as mean ≥8 kPa improvement in mean grip strength) at 2 consecutive visits. Sixty-nine percent of patients (n=221) were responders.¹⁷ In Stage B, responders were randomized to receive once weekly subcutaneous injections (n= 111) or placebo (n=110). The primary endpoint was the time to clinical deterioration defined as a 1-point increase in aINCAT at two consecutive visits or a >1-point increase in aINCAT at one visit. The proportion of patients who experienced relapse was 53.6% with placebo versus 27.9% with efgartigimod, representing a 61% reduction in the risk of relapse vs placebo (hazard ratio 0.39 [95% CI 0·25-0·61]; P <.0001) (Figure 2).^17,18

REFERENCES

1. Svačina MKR, Lehmann HC. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): Current Therapies and Future Approaches. Curr Pharm Des. 2022;28(11):854-862.

2. Gable KL, Li Y. Chronic Inflammatory Demyelinating Polyneuropathy: How Pathophysiology Can Guide Treatment. Muscle Nerve. 2025;72(2):201-211.

3. Mendoza M, Tran C, Bril V, et al. Symptom and Treatment Satisfaction in Members of the US and Canadian GBS/CIDP Foundations with a Diagnosis of Chronic Inflammatory Demyelinating Polyneuropathy. Adv Ther. 2023;40(12):5188-5203

4. Allen JA, Butler L, Levine T, Haudrich A, et al. A Global Survey of Disease Burden in Patients Who Carry a Diagnosis of Chronic Inflammatory Demyelinating Polyneuropathy. Adv Ther. 2021;38(1):316-328.

5. Querol L, Crabtree M, Herepath M, et al. Systematic literature review of burden of illness in chronic inflammatory demyelinating polyneuropathy (CIDP). J Neurol. 2021;268(10):3706-3716.

6. Mahdi-Rogers M, McCrone P, Hughes RA. Economic costs and quality of life in chronic inflammatory neuropathies in Southeast England. Eur J Neurol. 2014;21(1):34–39.

7. Mengel D, Fraune L, Sommer N et al. Costs of illness in chronic inflammatory demyelinating polyneuropathy in Germany. Muscle Nerve. 2018;58(5):681–687.

8. Devlin N, Pickard S, Busschbach J. The Development of the EQ-5D-5L and its Value Sets. 2022 Mar 24. In: Devlin N, Roudijk B, Ludwig K, editors. Value Sets for EQ-5D-5L: A Compendium, Comparative Review & User Guide [Internet]. Cham (CH): Springer; 2022. Chapter 1. PMID: 36810043.

9. Karissa Gable, MD, email communication, January 10, 2026.

10. Van den Bergh PYK, van Doorn PA, Hadden RDM, 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(3):242-268.

11. Allen JA. The misdiagnosis of CIDP: A Review. Neurol Ther. 2020;9(1):43-54

12. Gable K. Taking the mis- out of CIDP misdiagnosis. Neuromuscular Notes. Practical Neurology.2020;61-63.

13. Kaplan A, Brannagan TH 3rd. Evaluation of patients with refractory chronic inflammatory demyelinating polyneuropathy. Muscle Nerve. 2017;55(4):476-482.

14. Broers MC, Bunschoten C, Drenthen J, et al. Misdiagnosis and diagnostic pitfalls of chronic inflammatory demyelinating polyradiculoneuropathy. Eur J Neurol. 2021;28(6):2065-2073.

15. Ulrichts P, et al. FcRn as a therapeutic target in autoimmune diseases: mechanism and clinical application. Front Immunol. 2020;11:580289.

16. FDA. FDA approves treatment for chronic inflammatory demyelinating polyneuropathy (CIDP) in adults. Published June 24, 2024. Accessed January 4, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-chronic-inflammatory-demyelinating-polyneuropathy-cidp-adults.

17. FDA. Highlights of Prescribing Information. VYVGART® HYTRULO (efgartigimod alfa and hyaluronidase-qvfc). Revised June 2024. Accessed January 4, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761304s005,s006lbl.pdf

18. Allen JA, Lin J, Basta I, ADHERE Study Group. Safety, tolerability, and efficacy of subcutaneous efgartigimod in patients with chronic inflammatory demyelinating polyradiculoneuropathy (ADHERE): a multicentre, randomised-withdrawal, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2024 Oct;23(10):1013-1024. Erratum in: Lancet Neurol. 2025 May;24(5):e8.