BERLIN – Rheumatoid arthritis patients who respond favorably to a first course of rituximab and later need retreatment do as well with a follow-up single 1-g intravenous infusion as with the approved dosing regimen consisting of two 1-g infusions given 2 weeks apart, according to a randomized trial presented at the annual European Congress of Rheumatology.
The study findings point the way to a simpler, less costly, and more patient friendly dosing regimen than the one now contained in the product labeling, noted Dr. Maxime Dougados, professor of rheumatology at René Descartes University, Paris.
He presented data from a 2-year, prospective, multicenter, randomized, controlled trial involving 224 patients with moderate to severe RA that was inadequately responsive to antitumor necrosis factor–alpha therapy. All the study subjects had received a first induction cycle of rituximab (Rituxan) at the approved dosage of two 1-g intravenous infusions delivered 2 weeks apart.
The good or moderate response rate at 6 months by EULAR (European League Against Rheumatism) criteria was 71%. At that point, 100 responders were randomized to either open-label retreatment with the licensed regimen of two 1-g infusions 2 weeks apart or the investigational dose consisting of a single 1-g infusion.
Participants were reassessed for disease activity every 8 weeks. Additional retreatment with the assigned regimen was carried out as warranted by return of active RA, defined as a DAS28 (disease activity score based on a 28-joint count) greater than 3.2), as long as at least 6 months had elapsed since the last course of treatment.
The primary study end point was the area under the curve for the DAS28-CRP (C-reactive protein) score at week 104. It averaged 2,761 in the single-infusion retreatment group and was similar at 2,666 in the standard retreatment group, demonstrating the noninferiority of the investigational retreatment regimen.
The median time to a second retreatment was 263 days in the single-infusion group and similar at 255 days in the two-infusion group.
The safety profiles were comparable. Serious adverse events occurred in 29% of single-infusion retreatment patients over the course of the 2-year study, compared with 37% of those who received the approved two-infusion regimen. In all, 2% of patients in the single-infusion group had an IgG level less than 6.82 g/L (the lower limit of normal) at the 2-year mark, compared with 11% in the twin-infusion arm.
The serious infection rate was 7.2 per 100 person-years in the single-infusion group and 1.5 per 100 person-years in those retreated with two 1-g infusions 2 weeks apart.
A caveat regarding this study is that the radiographic or structural effect of the two retreatment strategies wasn’t assessed, the rheumatologist observed.
This clinical trial was supported by Roche. The presenter reported having received research grant support from the sponsor to conduct the study.