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

"The clinical course of [patients with CIDP] is the most important marker for treatment decisions. As the disease course is slowly progressive in many patients, [nerve conduction studies] and ultrasound findings are important additional aspects that can lead to increased vigilance or support a treatment decision," senior author Thomas Grüter, MD, professor of neurology at St. Josef Hospital Ruhr University Bochum in Germany, told NeurologyLive^® in a recent interview.

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.

"If the diagnosis is uncertain, the available diagnostic tools should be exhausted, including nerve biopsy in cases of doubt," Grüter explained. "As intravenous immunoglobulins and cortisone are well tolerated first-line treatments, they should be started as soon as possible. The treatment response can also be used as a diagnostic tool."

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.

"The outcome of the [patients with CIDP] in our cohort was analyzed using various clinical and instrumental methods. Clinically, we analyzed the patients using established scores such as the mRS, INCAT-ODSS and vigorometry. Additionally, we used [nerve conduction studies] and nerve ultrasound," Grüter noted in the interview. "Reduced amplitudes in [nerve conduction studies], pathological spontaneous activity in myography, and a fibrotically remodeled muscle in muscle ultrasound are indications of axonal damage. This was done by the same operator in a prospective approach as part of the INHIBIT rigestry."

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.

"Many people with CIDP are sufficiently stable with available first-line therapy. However, there is a significant proportion of patients who experience rapid progression despite this therapy. In these patients, escalation of therapy, such as B-cell depletion, should be considered, even if it is not yet approved. In this case, the potential risks and side effects must be discussed very thoroughly with the patient," Grüter added.

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.

"Multimodal monitoring is essential in [patients with CIDP] because the slowly progressive nature of the disease makes monitoring difficult. Axonal damage is the most important predictor of clinical disability. It should therefore be assessed multimodally," Grüter said. "Monitoring with [nerve conduction studies] is often not possible, especially in cases of severe axonal damage. Nerve and muscle ultrasound offers new possibilities."

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