An individually tailored treatment with Rituxan (rituximab) is as effective as the standard fixed-schedule regimen in preventing relapses over 28 months in ANCA-associated vasculitis (AAV) patients in remission.
The data also indicated that the less frequent infusions in the tailored approach may improve safety, according to a Duke University Medical Center (DUMC) expert.
The commentary, “In ANCA-associated vasculitis in remission, tailored vs fixed-schedule rituximab did not differ for relapse at 28 months,” was written by Eugene William St. Clair, MD, chief of the division of rheumatology and immunology at DUMC. It was published in the journal Annals of Internal Medicine.
It addressed a recent study, “Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2),” which appeared in the journal Annals of the Rheumatic Diseases.
Rituxan – marketed by Genentech and Biogen — or the immunosuppressant cyclophosphamide are used with high doses of glucocorticoids to induce remission of severe AAV. This is followed by maintenance therapy with less toxic combinations, which may also include Rituxan.
Aiming to assess whether individually tailored and fixed-schedule Rituxan regimens differ in AAV remission maintenance, the team conducted the open-label, randomized MAINRITSAN 2 Phase 3 trial (NCT01731561) in 59 centers in France with a 28-month follow-up period.
There were 162 adult patients (mean age 60, 58% men) included. They had newly diagnosed or relapsing granulomatosis with polyangiitis (GPA, 117 patients — 72.2%) or microscopic polyangiitis (MPA, 45 patients — 27.8%) — two types of ANCA vasculitis.
Enrolled patients were in complete remission after induction therapy with glucocorticoids plus cyclophosphamide (in 100 patients, 61.7%), Rituxan (61 patients, 37.6%), or the immunosuppressant methotrexate (one patient, 0.6%).
Active disease, severe immunosuppression, chronic obstructive pulmonary disease, severe infection in the prior three months, and cancer within the five years before AAV diagnosis were among the exclusion criteria.
Specifically, the individually tailored approach consisted of 500 mg Rituxan intravenous infusion on day 0 and when laboratory parameters assessed every three months (up to 18 months) met pre-specified criteria — a change in ANCA antibodies status and a greater than 0 count of immune B-cells containing the cell surface molecule CD19.
In turn, fixed-schedule infusions of 500 mg of Rituxan were performed at days 0 and 14, and at 6, 12 and 18 months. Each regimen was used in 81 patients.
The trial primarily focused on relapse at 28 months — assessed with the Birmingham Vasculitis Activity Score — with major relapse and adverse events also analyzed. Follow-up was completed by 94% of patients.
At the study’s end, patients on the tailored regimen had received a median of three Rituxan infusions, versus the five established infusions in the fixed approach. Overall, 21 patients experienced 22 relapses: 14 (17.3%) in tailored-infusion patients and eight (9.9%) in fixed-schedule patients, which was not a statistically significant difference.
The rate of severe adverse events also did not differ — 32% with individually tailored versus 38% with fixed-schedule treatment. Infectious complications were found in nine patients (11%) in the individually tailored group versus 16 patients (20%) in the fixed-schedule group.
“In [ANCA] vasculitis in remission, individually tailored and fixed-schedule [Rituxan] regimens did not differ for relapse at 28 months,” the researchers wrote. This result is in agreement with MAINRITSAN 2 results presented in 2017.
In his commentary, St. Clair cautioned that the high relapse prevention found in the trial may have been partially due to the fact that over 80% of participants were on prednisolone therapy during the study. He also mentioned that assessing ANCA and B-cells levels at each study site rather than in a unique location may have caused variability, and is not a reliable strategy for individualized maintenance therapy with Rituxan.
“The results of MAINRITSAN2 confirm the effectiveness of rituximab maintenance therapy for preventing relapses in AAV, regardless of dosing regimen,” he wrote. “They also underscore that less frequent doses of rituximab may improve safety”.
St. Clair also said that as 17 of 117 patients (14.5%) with GPA and only four of 45 patients (8.9%) with MPA had relapses, the findings suggest these two AAV types may not need the same intensity of maintenance treatment.
“Although fixed-schedule rituximab infusions are the current standard for maintenance management of AAV, MAINRITSAN2 shows that an individualized treatment approach (with the advantage of fewer infusions) is a worthy goal for the future,” he said.
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