CIDPRIT Post Hoc Analysis Finds No Biomarker Evidence Supporting Rituximab Efficacy in CIDP

A post hoc biomarker analysis from the CIDPRIT clinical trial found no clear evidence that treatment with rituximab reduces neuroaxonal injury in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), although exploratory findings suggested a potential biological signal in a subset of treated individuals.

In the study, investigators examined serum neurofilament light chain (sNfL) levels, an established biomarker associated with axonal damage, to evaluate whether biomarker changes might provide insight into rituximab’s potential therapeutic effects beyond traditional clinical outcomes.¹

Biomarker and Clinical Findings

Led by Pietro Emiliano Doneddu, MD, associate professor of neurology at the Humanitas University in Rozzano, Italy, the CIDPRIT trial included a total of 33 participants in the analysis, including 18 patients treated with rituximab and 15 who received placebo. At baseline, investigators observed significantly higher sNfL levels in the rituximab-treated group compared with the placebo group, with geometric mean concentrations of 11.51 pg/mL and 6.67 pg/mL, respectively (P = .019).¹

Despite these baseline differences, analyses over time did not reveal statistically significant differences in sNfL trajectories between the treatment groups. However, investigators noted distinct trends in biomarker patterns. Among patients treated with rituximab, sNfL levels remained relatively stable at the 6-month evaluation and showed a modest decrease by month 12. In contrast, participants in the placebo group experienced modest increases in sNfL levels during the same period.¹

Further exploratory analysis suggested that among rituximab-treated patients who remained clinically stable at 12 months, sNfL levels declined by approximately 31%, although this change did not reach statistical significance. Investigators also reported that baseline sNfL levels were not significantly associated with subsequent clinical worsening in the study population. Notably, neurofilament concentrations demonstrated correlations with neurophysiological measures of axonal damage, supporting the biomarker’s relevance in reflecting underlying nerve injury in CIDP.¹

CIDPRIT Study Design

CIDPRIT was a randomized clinical trial designed to evaluate the clinical efficacy of rituximab in individuals with CIDP, a rare immune-mediated neuropathy characterized by progressive or relapsing peripheral nerve dysfunction. Although the primary analysis of the study did not demonstrate a statistically significant clinical benefit compared with placebo, secondary analyses suggested the possibility of treatment-related effects in certain patient subgroups.¹

To further explore this possibility, investigators conducted a post hoc analysis of sNfL concentrations among trial participants. Blood samples were collected at baseline and at months 6 and 12 of follow-up. Levels of sNfL were measured using single-molecule array (Simoa) technology, a highly sensitive assay commonly used to detect low concentrations of neuroaxonal injury biomarkers in blood.¹

Statistical analyses included comparisons of geometric mean sNfL concentrations and standardized z-scores between treatment groups, as well as linear mixed-effects modeling and survival analyses to examine potential relationships between biomarker changes and clinical outcomes.¹

Interpretation

Investigators concluded that the biomarker analysis did not provide definitive evidence supporting rituximab’s clinical efficacy in CIDP. Nevertheless, the observed trends toward stabilization or reduction of sNfL levels in some rituximab-treated patients may suggest a potential biological effect on axonal injury that warrants further investigation. Future studies will be needed to clarify whether sNfL could serve as a useful biomarker for treatment monitoring or patient stratification in CIDP clinical trials.¹

Clinical Context

CIDP is an autoimmune disorder affecting the peripheral nervous system and is characterized by progressive weakness, sensory loss, and impaired reflexes due to demyelination and secondary axonal damage. Current treatment strategies typically include corticosteroids, intravenous immunoglobulin, and plasma exchange, although a subset of patients experience incomplete response or treatment resistance.²

Because B cells are thought to play a role in autoimmune mechanisms underlying CIDP, therapies targeting B-cell activity, such as rituximab, have been investigated as potential treatment options. However, robust clinical evidence supporting rituximab’s efficacy in CIDP remains limited.¹

REFERENCES
1. Doneddu P, Collet-Vidiella R, Gallo C, et al., Effect of Rituximab on Neurofilament Levels in CIDP: Results From the CIDPRIT Randomized Trial,” Journal of the Peripheral Nervous System. 2026;31(1): e70107. doi:10.1111/jns.70107.
2. Gogia B, Rocha Cabrero F, Khan Suheb M, Lui F, Rai P. Chronic Inflammatory Demyelinating Polyradiculoneuropathy. StatPearls. March 4, 2024. Accessed March 12, 2026. https://www.ncbi.nlm.nih.gov/books/NBK563249/