Tailoring infusions of Rituxan (rituximab) according to ANCA status and/or levels of CD19-positive lymphocytes has no significant impact on the number of relapses experienced by ANCA-associated vasculitis (AAV) patients compared to those given systematic infusions, according to a Phase 3 trial.
These findings were announced at the recent American College of Rheumatology Annual Meeting, in San Diego, in a presentation titled “Comparison of Individually Tailored Vs Systematic Rituximab Regimens to Maintain ANCA-Associated Vasculitis Remissions: Results of a Prospective, Randomized–Controlled, Phase 3 Trial.”
The Phase 3 trial (NCT01731561), called MAINRITSAN2, included patients with systemic AAV who were in complete remission after induction therapy with either glucocorticoids and cyclophosphamide, Rituxan, or methotrexate. It aimed to compare the efficacy of two Rituxan regimens in maintaining AAV remission.
In the experimental group, patients received Rituxan tailored according to their ANCA status and reappearance of circulating CD19 B-cells. In the control group, patients received systemic infusions of Rituxan, a treatment marketed by Genentech.
In total, the study recruited 162 patients with either granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), two AAV subtypes.
The experimental group received a fixed infusion dose of 500 mg of Rituxan at study start. Researchers then measured ANCA status and the number of CD19-positive white blood cells every three months until month 18. Patients received a new infusion whenever their CD19 lymphocytes exceeded 0/mm3, when they become ANCA positive, or if the levels of ANCA antibodies increased significantly since the last measurement.
The control group also received a fixed 500 mg dose of Rituxan at study start, and following doses were given at day 14, and then at months six, 12, and 18.
The trial’s primary outcome was the number of relapses in each group after the 18-month treatment period, followed by a 10-month follow-up (28 months total).
Researchers defined relapses as new or re-emerging symptoms or worsening disease, measured via a Birmingham Vasculitis Activity Score (BVAS) higher than 0 at month 28.
During the trial period, researchers registered a total of 22 relapses experienced by 21 patients — 13 people in the experimental group had 14 relapses, and eight patients in the control group had eight relapses. The differences showed no statistical significance.
Relapse-free survival rate at 28 months was also similar between both groups – 83.8 percent versus 86.4 percent, respectively – as were the number of patients who suffered one severe adverse event: 26 patients in the experimental arm and 31 in the control arm. Four patients died.
Overall, the results showed that a tailored Rituxan regimen had no effects on the relapse rate of AAV patients. Still, measuring the levels of ANCA antibodies and of circulating B-cells is useful to lower the number of Rituxan reinfusions needed, the researchers concluded.