Rituximab versus placebo for chronic inflammatory demyelinating polyradiculoneuropathy: a randomized trial

Abstract

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) often requires prolonged ongoing treatment to prevent worsening. The efficacy of rituximab in preventing worsening after the discontinuation of immunoglobulin therapy in patients with CIDP was assessed. In this randomized, double-blind, placebo-controlled study, conducted at seven Italian hospitals, CIDP patients under immunoglobulin therapy were assigned to receive either rituximab (1 g on Days 1, 15 and 180 ± 7) or placebo. Both groups continued their regular immunoglobulin doses for 6 months post-intervention. The primary end point was the proportion of patients who worsened in any of the following three measures at Month 12, within 6 months after immunoglobulin discontinuation: a decrease of at least one point on the adjusted INCAT score, two points on the MRC sum score, or four points on the RODS centile score. Secondary end points included the proportion of patients deteriorating at Month 18 (within 12 months after immunoglobulin discontinuation), treatment cessation due to adverse events or voluntary reasons, and the time until deterioration after immunoglobulin discontinuation. This study was registered with ClinicalTrials.gov (NCT06325943) and EUDRACT (number 2017-005034-36), and is now complete. From April 2019 to March 2022, 39 patients were recruited; two withdrew consent. The remaining 37 patients were assigned to rituximab (n = 19) or placebo (n = 18). Median age was 53 (interquartile range 45-64), with 11 (30%) females. A similar proportion of patients in both the rituximab (12/19, 63.2%) and placebo (12/18, 66.6%) groups worsened at Month 12 [odds ratio (OR) 0.86; 95% confidence interval (CI) 0.22-3.32]. No significant differences were noted at Month 18 (OR 0.62; 95% CI 0.14-2.70), or in the mean scores of each scale at Months 6, 12 and 18. The median time to worsening was 5 months for rituximab and 2 months for placebo (Log-rank P = 0.4372). Treatment was suspended due to adverse events in one rituximab patient. In this study, rituximab was not more effective than placebo in preventing clinical deterioration following the discontinuation of immunoglobulin therapy in CIDP. Further studies might evaluate the efficacy of more frequent or earlier administration of rituximab.

Keywords: CIDP; randomized clinical trial; randomized controlled trial; therapy: immunosuppressive therapy; treatment.

Figure 1

Study diagram. CIDP = chronic inflammatory demyelinating polyradiculoneuropathy.

Figure 2

Cumulative probability of worsening after immunoglobulin discontinuation in the rituximab and placebo groups. The figure displays the cumulative probability of relapse in the rituximab and placebo groups following discontinuation of immunoglobulin therapy. Time is measured in months. Shaded bands represent 95% confidence intervals. The number of patients at risk in each treatment group at each time point is shown below the x-axis. IVIg = intravenous immunoglobulins; SCIg = subcutaneous immunoglobulins.