Omitting Rituxan Dose Does Not Affect AAV Relapse Rates, Analysis Suggests

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by Margarida Azevedo |

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Omitting one dose of Rituxan (rituximab) in a previously tested, tailored treatment regimen did not impact the short-term relapse-free rate of people with ANCA-associated vasculitis (AAV), a post-hoc analysis of a Phase 3 trial showed.

The findings suggest this particular dose could be eliminated from the treatment protocol, according to the investigators. That would lower treatment-related toxicity and improve patients’ prognosis, while maintaining clinical remission.

However, these results do not imply causation as other factors may be at play, the researchers noted.

The analysis’ findings were reported in “Reducing the initial number of rituximab maintenance-therapy infusions for ANCA-associated vasculitides: randomized-trial post-hoc analysis,” published in the journal Rheumatology.

Rituxan has become the standard of care, both for induction — the first treatment given — and maintenance therapy, in AAV patients.

Several dosing schedules for the therapy have been investigated. A previous study, in which patients had received initial rituxan treatment followed by maintenance therapy with 500 mg infusions on day 0, then at months 6, 12, and 18, suggested that the infusion at day 14 could be omitted.

The MAINRITSAN 2 Phase 3 trial (NCT01731561) sought to assess whether individually tailored and fixed-schedule Rituxan regimens differed in AAV remission maintenance.

The tailored approach consisted of giving patients an intravenous (into-the-vein) infusion of Rituxan (500 mg) on day 0, and then again when laboratory parameters met pre-specified criteria, such as the presence of ANCA antibodies and immune B-cells containing the cell surface molecule CD19. The laboratory parameters were assessed every three months, up to 18 months.

Conversely, the fixed-schedule regimen consisted of giving participants IV infusions of Rituxan (500 mg) at days 0 and 14, and then again at 6, 12, and 18 months.

The results showed that, after 28 months, relapse rates were similar in AAV patients who were in remission and those receiving both treatment regimens. Importantly, in this clinical trial, the infusion on day 14 was systematically omitted.

“Despite the trial not being designed to evaluate the effect of that omission, we thought that studying the initial MAINRITSAN 2 trial data might be informative about the effect of lowering the initial rituximab dose,” the researchers said.

Now, the team reported the findings of a post-hoc analysis of the trial focused on evaluating AAV-relapse rates at month 3, 6, 9, and 12.

Among the 161 participants in the MAINRITSAN 2 study, 98.8% of those in the tailored-therapy group were alive and relapse-free at month 3. Data at the later time points showed 95%  were alive and relapse-free at month 6, and 92.5% at month 9. The percentage at month 12 was 91.3%.

In the fixed regimen group, 98.8% of individuals were alive and relapse-free at month 3, and 96.3% at month 6. At month 9, that percentage was 93.8% — and it stayed the same, at 93.8%, at month 12.

No significant difference was found between the two groups. Moreover, having received cyclophosphamide or rituxan as the initial treatment, being newly diagnosed, or experiencing a relapse, did not change the results, the researchers noted.

Two patients passed away in the fixed-regimen group, one from carcinomatous meningitis seven months into the trial, and one from nosocomial pneumonia six months into the trial.

Regarding the frequency of CD19-positive B-cells, the two groups were similar, except at months 9 and 12. At those two time points, patients in the tailored-regimen group were more likely to have circulating CD19-positive B cells.

This was attributed to the fact that all patients in the fixed-regimen group received a rituxan infusion at month 6, while in the personalized therapy group, patients only received an infusion if these cells or ANCA antibodies had been detected.

“These post-hoc analyses of that trial’s data suggest that the D14 rituximab infusion may be omitted, regardless of the induction regimen that had been administered,” the researchers said.

However, they noted the study had several limitations. “It is a post-hoc analysis of a randomized, controlled trial, not powered to detect difference(s) at M3, M6, M9 and M12. Pertinently, the absence of difference does not mean equivalence,” they added.

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Margarida Azevedo avatar
Margarida Azevedo Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.

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fixed-schedule regimen, MAINRITSAN 2, omitted dose, post-hoc analysis, Rituxan, rituximab, tailored treatment

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