Exploring the Unmet Needs in CIDP

Author: Dr Karissa Gable

Sponsored by Sanofi

Key Takeaways

• Research is expanding to encompass both clinical stability and long-term functional outcomes in chronic inflammatory demyelinating polyneuropathy (CIDP) populations.
• Emerging research is advancing our understanding of the immunological mechanisms underlying demyelination and axonal damage in CIDP.
• One of the goals of emerging research in biomarkers and targeted immune therapies may be to refine patient stratification and monitoring to detect subclinical nerve damage and guide treatment decisions.

A Timely Conversation

During the 2026 medical conference season, we collectively had an opportunity to reflect on and discuss how chronic inflammatory demyelinating polyneuropathy, or CIDP, care is evolving. CIDP remains a rare but treatable chronic immune-mediated neuropathy in which earlier recognition, accurate diagnosis, and sustained disease control can materially affect long-term outcomes.¹ For neuromuscular specialists, these realities are familiar. CIDP is not uniform in presentation or trajectory, and caring for these patients extends beyond initiating therapy to include disciplined diagnostic evaluation, longitudinal reassessment, consistent measurement of response, and ongoing efforts to help function and quality of life.^1-4

Progress in CIDP—but an Incomplete Picture

Current standard therapies, including immunoglobulin, biologics, corticosteroids, and plasma exchange, have helped patients achieve clinical stability, yet emerging data suggest a need for an evolving understanding of what true disease control means for long-term function and disability prevention.^1,4,5 In addition, what drives increased activity of disease and remission is still unclear. Evolving research on CIDP's pathobiology shows that some people do not fully respond to current standard-of-care therapies, revealing a persistent unmet need to quell the immune overactivation present in CIDP. ⁵ Understanding the underlying pathobiology of CIDP and how it relates to clinical response to treatment is essential to evolving care.

For patients, those gaps are not abstract. Even with treatment, some patients may experience inadequate or partial response resulting in residual disability.^5,6 For these patients, ongoing nerve damage may continue despite therapy. The real-world burden of persistent disability extends beyond clinical measures, affecting patients’ daily function and quality of life.³ For some people living with CIDP, starting treatment only marks the beginning of an ongoing journey to find optimal disease control, rather than the end of their struggle.

Understanding the Evolution in CIDP Care

The diagnosis and management of CIDP sometimes can be quite challenging and so it is recommended to rely on consensus guidelines like the EAN/PNS 2021 guidelines.⁷ Referrals to a center of excellence can also be helpful in complex cases. Current clinical practice relies heavily on nerve conduction studies and needle electromyography; however, the marked heterogeneity of CIDP can make it difficult to define distinct clinical phenotypes and establish a definitive diagnosis. ^2,8 Variants of CIDP are often where rates of misdiagnosis are higher as opposed to typical CIDP, so extra care in diagnosis of these variants is required. Patients often see multiple specialists before they reach an accurate diagnosis. The median diagnosis time for patients with CIDP is 7 months, and each delay can compound irreversible nerve damage.²

Further complicating the journey, one study found that 1 in 3 people living with CIDP do not adequately respond to standard of care first-line therapies.⁶ Although they work for some, many patients remain inadequately controlled, with some responders having partial responses with residual disability.⁵ Although “clinical stability” has been our traditional benchmark, the heterogeneity of CIDP means that a patient who appears stable may still face a gap in long-term functional outcomes. Also, while appearing clinically stable, there can still be markers of inflammatory disease present serologically. Historically, this gap was often accepted due to a lack of therapeutic alternatives. Earlier recognition and understanding of disease mechanisms may offer the opportunity to move beyond solely focusing on stabilization towards other critical factors that matter to people living with CIDP.

Measuring What Matters

Once treatment begins, the challenge is determining whether patients are truly improving. Clinical experience suggest that traditional measurement may not fully track disease trajectory over time, particularly in treated patients.^5,9 There is a growing dialogue among specialists that “clinical stability” may not fully capture the heterogeneity of CIDP. As we integrate emerging data on functional outcomes, the focus is shifting toward refining our tools to better recognize the nuances of the lived experience that traditional clinical assessments can sometimes overlook.

Disability scales and impairment measures remain valuable while other tools are explored to capture the full burden of disease, particularly in areas such as fatigue, dexterity, endurance, pain, or day-to-day participation in activities that define quality of life.⁵ Information presented at the 2026 International Congress on Neuromuscular Diseases (ICNMD) includes data from the ORBIT study sponsored by Sanofi that aims to address this gap by integrating artificial intelligence, digital biomarkers, and patient-centric data collection methods that could potentially lay the groundwork for more regular virtual and in-person assessments of disease progression and treatment response.

A more comprehensive view of treatment benefit is needed—one that includes objective examination, validated outcome measures, and additional functional outcomes alongside patient-reported experience. This means applying established tools consistently while integrating emerging measurement strategies and interpreting them alongside the functional domains that matter most to patients—recognizing that the goal for each patient may differ.

Path Forward: Exploring Care Through Precision and Innovation

As understanding of disease progression evolves, clinical experience continues to refine our approach to CIDP management, especially for treated patients who experience ongoing disease progression or activity. The 2021 EAN/PNS guidelines provide a vital framework and evidence-based expert consensus guidelines for diagnosis and management and are important to utilize routinely in everyday clinical practice. There remains a need for continued investigation into the underlying immune overactivation seen in CIDP.

There is recognition that CIDP is immunologically heterogeneous and that differences in immune mechanisms may help explain variation in presentation, severity, and treatment response.² That has prompted growing interest in more targeted therapeutic approaches, including therapies directed at specific inflammatory pathways. Specifically, researchers are mapping the distinct cellular and humoral pathways driving peripheral nerve damage.¹⁰On the cellular side, cell-mediated pathology involves T-cells and macrophages that infiltrate the nerves to actively strip away myelin.^{8, 11,12} On the humoral side, an important advancement has been the identification of specific autoimmune variants driven by IgG4 autoantibodies targeting the nodes of Ranvier. ⁷ Because IgG4 antibodies typically do not activate complement, nerve injury occurs through direct antibody interference with nerve signaling rather than complement-mediated destruction.⁷ Recognizing these distinct pathways has directed therapeutic research toward mechanisms that bypass the complement cascade entirely, such as B-cell depleting therapies like rituximab to halt autoantibody productionand neonatal Fc receptor (FcRn) inhibitors to rapidly clear pathogenic IgG antibodies from the bloodstream.⁴

Current research is exploring the complement system as one of several immune mechanisms involved in autoimmune attack on the peripheral nerves in CIDP.⁴ In some patients, complement activation contributes to inflammatory cascades that may drive both demyelination and axonal damage^4,13,14 processes associated with irreversible nerve injury and functional decline. Despite available therapies, a subset of patients continue to experience significant disease burden, highlighting the need for a deeper understanding of the underlying mechanisms driving the progression.⁴

For clinicians, the evolving understanding of CIDP immunopathology raises important questions about therapeutic strategy. Current standard-of-care first-line therapies include immunologic modulating therapies such as immunoglobulin, steroids, and plasma exchange, which can provide benefit for the majority of patients.^1,4 Despite the availability of therapies, there are patients who experience inadequate or partial response, highlighting the continued unmet need in this therapeutic area.

And for patients who are inadequate or partial responders to guideline-recommended first-line therapies addressing distinct pathways, including FcRn blockers and complement inhibitors, may represent promising areas of investigation. This research continues alongside other advancements, including digital biomarkers enabling earlier detection and treatment response monitoring, and real-world data collection that move beyond traditional clinical stability measures.^4,5 Additional targets within the immune response of CIDP, and who may best benefit from which targeted therapy, is an area of active research.

Looking Ahead

The next phase of progress in CIDP is unlikely to come from any single advancement alone. More likely, it will come from a better combination of factors: earlier recognition of ongoing symptoms and disease progression beyond diagnosis; biomarkers for diagnosis and management; more precise classification and definitions; evolved measurement and data collection that allows functional outcomes to be captured and addressed; and continued research and innovation for patients whose disease remains inadequately controlled.

As a community, we need to continue to partner not only with each other but with industry and researchers—alongside the patient community and advocacy—to drive a greater understanding of the underlying immune mechanisms to understand the future potential of mechanism-targeted therapies.

The most productive path forward may be one that balances optimism with rigor: embracing scientific progress, remaining disciplined about diagnosis and measurement of symptoms and disease across the patient journey, and focusing on outcomes that matter for patients’ and in their daily lives.

To learn more about ongoing research informing evolving approaches in CIDP patient management and care, please visit https://www.sanofi.com/en/magazine/our-science/cidp-treatment-and-disability-prevention-immune-targeted-care.

References

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2. Arvin-Berod C, Brackx F, Van De Veire L, et al. The journey to diagnosis for patients with CIDP: results from a real-world international survey. Front Neurol. 2026;16:1748903. doi:10.3389/fneur.2025.1748903
3. What is chronic inflammatory demyelinating polyneuropathy (CIDP)? GBS/CIDP Foundation International. 2026. https://www.gbs-cidp.org/cidp/
4. McCoy A. Exploring second-line therapies for CIDP. Everyday Health. January 30, 2026. https://www.everydayhealth.com/autoimmune-diseases/exploring-second-line-therapies-for-cidp/
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12. Mathey EK, Pollard JD, Armati PJ. TNF alpha, IFN gamma and IL-2 mRNA expression in CIDP sural nerve biopsies. J Neurol Sci. 1999;163:47-52.
13. Rumsey JW, Lorance C, Jackson M, et al. Classical Complement Pathway Inhibition in a “Human-On-A-Chip” Model of Autoimmune Demyelinating Neuropathies. Adv Therap. 2022;5:2200030.
14. Querol LA, Hartung HP, Lewis RA, et al. The Role of the Complement System in Chronic Inflammatory Demyelinating Polyneuropathy: Implications for Complement-Targeted Therapies. Neurotherapeutics. 2022;19(3):864-873.
    

Dr. Karissa Gable, Neurologist, is receiving honoraria for this work with Sanofi.