SAN DIEGO — In patients with ANCA-associated vasculitis, rituximab infusions customized to ANCA status do not appear to yield different relapse rates compared with systematic rituximab infusions, according to findings presented at the American College of Rheumatology Annual Meeting,
“Even though rituximab’s efficacy to induce and maintain is convincing, many questions still persist,” Pierre Charles, MD, of the Service de Médecine Interne, Hôpital Cochin, Paris and a lead author of the study, said in his presentation of the findings. “For example, what is the optimal dose, the optimal infusion schedule, fixed or adapted, the optimal duration? Is maintenance treatment mandatory when using rituximab? We address the question of the rituximab infusion schedule, and the possibility to adapt it to each patient.”
In the open-label, multicenter, randomized controlled trial, Charles and colleagues evaluated 162 patients with either granulomatosis with polyangiitis (n=117) or microscopic polyangiitis (n=45) who were in complete remission after induction therapy with glucocorticoids and cyclophosphamide, rituximab or methotrexate. Participants were randomly assigned to one of two rituximab treatment approaches: treatment individually tailored to ANCA status and/or circulating CD19 B-cell reconstitution (experimental group, n=81) or systematically infused treatment (controls, n=81).
The experimental arm regimen included fixed, 500-mg rituximab infusions on day 0 after randomization, followed by infusions every 3 months until month 18, when CD19 lymphocytes exceeded 0/mm3 or until there was a difference in ANCA status or titer from the previous assessment. The control group regimen consisted of 500 mg of rituximab on days 0 and 14 after randomization, and subsequently at 6, 12 and 18 months. The study’s primary endpoint was the number of relapses, defined as new or re-emerging symptoms or worsening disease with BVAS > 0 at month 28, as determined by a blinded, independent adjudication committee.
Cyclophosphamide was the prerandomization induction therapy for 100 (61.7%) patients, rituximab for 61 (37.7%) and methotrexate for one (0.6%) patient. The median number of rituximab infusions for the experimental arm was three and for the control arm was five. There were 22 relapses in 21 patients. Fourteen relapses were in 13 experimental group patients and eight were in eight control group patients (P = .22). The experimental arm had a relapse-free survival rate of 83.8% vs. a rate of 86.4% in the control group (P = .58).
Twenty-six patients in the experimental arm and 31 patients in the control arm experienced a severe adverse event (P = .51). There were four patient deaths, one of an infectious complication. There was no association between relapses and ANCA status and/or circulating CD19 B cells.
“Our research demonstrated that an adaptive strategy is possible to treat the patients, and that reinfusion algorithms based on ANCA and circulating CD19 cells gave good results and could be applied in clinical practice,” Charles said. “We cannot recommend this strategy at this stage, since the insignificant difference in the superiority trial does not mean equivalence. Nevertheless, the absolute difference between relapse rates was small, and patients from the adaptive treatment received fewer reinfusions.” – by Jennifer Byrne
Charles P, et al. # 2754 American College of Rheumatology Annual Meeting; Nov. 4-8, 2017; San Diego.
Dr. L. Guillevin reports a relationship with Hoffmann-LaRoche Inc.