Early Immunotherapy May Be Crucial to Prevent Axonal Damage in CIDP, Study Suggests

Thomas Grüter, MD

(Credit: St. Josef Hospital)

Delays in initiating immunotherapy for chronic inflammatory demyelinating polyneuropathy (CIDP) led to worsened axonal damage and higher disability, according to a newly published study from the Immune-mediated Neuropathies Biobank (INHIBIT). Published in the Journal of Neurology, researchers also observed that comprehensive therapeutic approaches could potentially improve long-term outcomes in patients with CIDP.¹

Investigators included 30 patients diagnosed with CIDP within 1 year prior to enrollment for the study. Authors used clinical, therapeutic, and diagnostic data including nerve conduction studies and ultrasounds to analyze outcomes. Findings showed that delays in starting therapy correlated with axonal damage (r_Sp = 0.467) and increased disability (R² = 0.200). Conversely, early and combined first- or second-line therapies significantly reduced disability progression (r = 0.773) and improved axonal damage (r = 0.467).

The findings in the current study emphasized the need for prompt treatment strategies to minimize disability. Axonal damage, which was linked to higher overall disability sum scores (r_Sp = 0.581), emerged early in the disease course, highlighting the importance of early intervention. Researchers also noted the results from the study suggested that multimodal approaches, combining therapeutic and diagnostic tools, may optimize patient outcomes.

“This study highlights the significance of detecting axonal damage as the primary cause of clinical disability because signs of axonal loss, but not demyelination, were associated with clinical disability scores,” senior author Thomas Grüter, MD, professor of neurology at St. Josef Hospital Ruhr University Bochum in Germany, and colleagues noted.¹ “As axonal damage is the primary cause of clinical disability, further studies are urgently required to identify therapeutic options that can reduce neurodegeneration and support neuroregeneration.”

READ MORE: Timely Diagnosis and Monitoring Key to Preventing CIDP Disability, Study Shows

This research included patients from the INHIBIT registry, with a diagnosis-to-enrollment time averaging 22 weeks. Patients were diagnosed based on the European Federation of Neurological Societies/Peripheral Nerve Society diagnostic criteria.² Clinical and diagnostic data were assessed at baseline and after 12 months. Patients were systematically selected to ensure early disease representation, with equal monitoring of therapeutic interventions. Nerve conduction study scores, pathological spontaneous activity, and Heckmatt scale readings were key indicators, which were all significantly associated with disability progression.

Overall, therapeutic insights from the study revealed that early initiation of therapy was crucial for reducing axonal damage and preventing disability progression. First-line therapies were most strongly associated with mitigating disability (r = 0.773), demonstrating their significant role in improving patient outcomes. Second-line therapies also provided notable benefits, particularly in addressing axonal damage (r = 0.467). Importantly, the study found no significant adverse events among any of the treatment groups, suggesting that these therapeutic approaches are not only effective but also well-tolerated.

Authors noted that the study's single-center design ensured consistency but might have introduced biases related to patient demographics and disease presentation, limiting generalizability. By focusing on early CIDP, the researchers may have also excluded patients with severe cases who had already undergone multiple treatments. Additionally, the study's follow-up period may not have captured long-term effects or changes in treatment responses. Despite established criteria used to assess axonal damage and were validated, potential influences from very proximal conduction blocks and collateral sprouting could have impacted the accuracy of the results.

“The potential of axonal damage as a biomarker of disease severity and predictor of further outcomes is highlighted by its effect on functional disability, even in early disease stages. Ultrasound has shown promise as a tool for monitoring CIDP, particularly for identifying axonal damage and serving as a direct indicator of disability,” Grüter et al noted.¹ “It is also crucial to adopt a comprehensive and individualized treatment approach when considering available therapeutic options. In severe cases, combinatory first-line therapy and second-line interventions may be necessary. The second-line therapy potentially mitigates axonal damage in specific cases.”

REFERENCES
1. Schumacher A, Hieke A, Spenner M, et al. Early therapy initiation is crucial in chronic inflammatory demyelinating polyneuropathy: prospective multimodal data from the German INHIBIT registry. J Neurol. 2025;272(1):100. Published 2025 Jan 7. doi:10.1007/s00415-024-12860-w
2. 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 [published correction appears in Eur J Neurol. 2022 Apr;29(4):1288. doi: 10.1111/ene.15225]. Eur J Neurol. 2021;28(11):3556-3583. doi:10.1111/ene.14959