Rituximab Shows No Effect Over Placebo in Preventing CIDP Disease Deterioration

Eduardo Nobile-Orazio, MD, PhD

A recent randomized, double-blind study (NCT06325943) found that rituximab was no more effective than placebo in preventing clinical deterioration after discontinuing immunoglobulin therapy in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The investigators concluded that future studies are warranted to explore the efficacy of treatment with rituximab in CIDP either earlier in the disease course or more frequently.¹

In total, 37 patients with the disease were randomly assigned to either rituximab (1 g on days 1,15 and 180 [±7]; n = 19) or placebo (n = 18) for a 12-month period, with patients discontinuing immunoglobulin treatment 6 months in. All told, results showed a similar proportion of patients who relapsed at month 12 in both the rituximab (12 of 19; 63.2%) and placebo (12 of 18; 66.7%) groups (OR, 0.86; 95% CI, 0.22-3.32), with no significant differences upon adjusting for disease duration MRC sum score (adjusted OR, 1.15; 95% CI, 0.23-5.82) and steroid use (adjusted OR, 0.88; 95% CI, 0.16-4.88).

Led by Eduardo Nobile-Orazio, MD, PhD, the neurology unit director at Humanitas Research Hospital, 24 of the patients included were receiving IVIg and 13 SCIg as effective maintenance treatment. By month 18, within 12 months after therapy discontinuation, the proportions of patients who relapsed were 68.4% for rituximab and 77.8% for placebo (OR, 0.62; 95% CI, 0.14-2.70), with the adjusted outcome also showing no statistical significance (adjusted OR, 0.59; 95% CI, 0.09-3.71). these results remained the same when considering a 4-point decrease as the threshold for change on the MRC sum score (OR, 0.86; 95% CI, 0.22-3.32).

While there was a difference in cumulative probability of relapse at month 8 (rituximab: 22%; placebo: 47%), the gap narrowed and Kaplan-Meier curves showed no significant difference by month 12, 6 months after discontinuation (Log-rank; P = .4372). Most patients had typical CIDP (31/37), with treatment responses aligning with the overall cohort: 66.7% in the rituximab group worsened by Months 12 and 18, compared to 75% and 81.3% in the placebo group, showing no significant differences. Among six patients with CIDP variants, 50% of those on rituximab deteriorated by Month 12 and 75% by Month 18, while none worsened at Month 12 and only one by Month 18 in the placebo group.

READ MORE: Clinical and Ultrasound Scores Helps Differentiate CIDP from Diabetic Polyneuropathy

Rituximab appeared to show no impact on disease progression, as it failed to distinguish itself from placebo on outcomes of the INCAT, I-RODS, and MRC total scores. The adjusted INCAT score showed no significant change from baseline during the study (P = 0.3420), with similar 6-month increases in both placebo (0.166 points) and rituximab (0.141 points) groups. Likewise, the I-RODS centile score showed no significant variation (P = 0.8789), with placebo increasing by 0.649 and rituximab decreasing by −1.151 every 6 months, with no meaningful differences between groups.

The MRC sum score showed no significant change from baseline during the follow-up (P = 0.8559), with a 6-month increase of 0.308 in the placebo group and a decrease of −0.154 in the rituximab group, with no significant difference between slopes (−0.462; P = 0.5825). Similarly, SF36 quality-of-life analysis showed no significant changes over time or differences between groups in any domain or standardized physical and mental component scores.

In terms of safety, more rituximab-treated patients experienced at least 1 adverse event (AE; 47.4%) vs the placebo group (27.8%), though these differences were not statistically significant (P = .2194). Between the 2 groups, changes in CD19 counts, which were significantly decreased (P <.001) in the rituximab group, were the only difference in hematological parameters.

"In this study, non-zero CD19 levels at Months 12 and 18 suggest that additional doses of rituximab might have given greater benefit,” Nobile-Orazio et al wrote. "Our decision to assess the response to rituximab at Months 12 and 18 (6 and 12 months, respectively, after discontinuation of immunoglobulin therapy) was informed by previous studies of rituximab in anti-MAG antibody neuropathy. It is also possible that immune reactivity in our patients, treated on average of 6.1 years after disease onset, had stabilized, resulting in a plasma cell pool less responsive to rituximab."

REFERENCES
1. Nobile-Orazio E, Cocito D, Manganelli F, et al. Rituximab versus placebo for chronic inflammatory demyelinating polyradiculoneuropathy: a randomized trial. Brain. 2024;awae400. doi:10.1093/brain/awae400