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Page 8 of 14 Skopis et al. Vessel Plus 2020;4:30 I http://dx.doi.org/10.20517/2574-1209.2020.42

renal, etc.). A lower score indicates lower disease activity, versus a higher score which indicates higher
disease activity. Median disease activity of the patients in the study was 1 at baseline and improved to 0 at
12 and 24-month follow up. Eighty-seven percent of patients were on cytotoxic immunosuppression at the
[20]
start of the study vs. 41% at 12-month follow up and 30% at 24-month follow-up [Table 1].
A single center historical cohort study in 2012 observed 53 patients with chronic relapsing GPA over 10-year
period from January 1, 2000 to May 31, 2010 in whom RTX was used to maintain remission or, to treat
disease relapses. The patients in the study received at least 2 courses of RTX (median number of courses of
RTX was 4), with 52 of these patients being PR-3 ANCA positive. All patients who were treated for relapses
achieved disease remission. Of the 53 patients, all achieved B cell depletion after induction therapy with
RTX. Thirty two out of the 53 patients relapsed and, in all cases, relapses were associated with a rise in PR-3
ANCA levels and the reappearance of CD19+ B lymphocytes in the circulation. Remission was maintained
successfully in all patients who were treated with preemptive courses of RTX based on re appearance of B
lymphocytes and increases in PR-3 ANCA titers. Overall, this study conveyed the effectiveness of RTX as
[21]
both an induction and maintenance strategy in patients with AAV [Table 1].

A retrospective study in 2012 examined the outcomes of 28 patients with AAV (4 with MPA and 24 with
GPA) treated with RTX for maintenance therapy from 2003-2010. All patients in the study had entered
remission with the use of conventional immunosuppressant therapy or RTX and were monitored for
relapse rates and tolerance after greater than or equal to 2 RTX infusions used as maintenance therapy. The
median range of RTX infusions was 4 with a median follow up time of 38 months from diagnosis or last
flare. Out of 28 patients, 2 had pulmonary relapses, 1 patient suffered alveolar hemorrhage 6 months after a
RTX infusion and 1 patient developed new lung nodules 11 months after a RTX infusion (this patient was
then started on a new induction regimen with RTX which achieved disease remission and was followed by
successful RTX maintenance). At final evaluation, 6 patients were in complete remission, 11 patients were
in complete remission with irreversible damage and, 9 patients were in partial remission. 7 of these patients
had persistent ENT involvement and 2 patients had persistent lung nodules. None of these patients had
infusion reactions, 15 patients had hypogammaglobulinemia and 3 patients developed infections. The data
[22]
of this study suggest that RTX could be used as a safe, effective maintenance therapy in AAV [Table 1].
Since the safety and efficacy of RTX as a maintenance therapy had been established in this study, the
next question posed was the efficacy and safety of RTX as compared to other conventional maintenance
therapies like AZA. This laid the framework for the largest randomized controlled trial to compare RTX
to AZA as maintenance therapy in AAV titled the Maintenance of Remission using Rituximab in Systemic
ANCA-associated Vasculitis (MAINRITSAN) trial.

In 2014, the MAINRITSAN trial investigated the use of RTX vs. AZA as a maintenance therapy in patients
with AAV. The study was a non-blinded, randomized controlled trial that studied patients with GPA, MPA
or renal-limited AAV who had received induction therapy with CYC and glucocorticoids and achieved
disease remission. These patients were randomized to receive RTX infusions vs. daily AZA for maintenance
therapy and were monitored for disease relapse. After 28 months, 5% of the patients in the RTX group had
suffered disease relapses vs. 29% of the patients in the AZA group. Additionally, adverse event rates were
similar between the two groups. This study demonstrated that patients in the RTX group had significantly
less relapses and an equal number of adverse events as the AZA group, thus conveying the superiority of
RTX to AZA in maintaining disease remission in AAV while maintaining a similar safety profile to AZA
[23]
[Table 1]. One interesting point is that the study was comprised mostly of patients who were anti PR-3
ANCA positive; patients who were anti MPO-ANCA positive and patients who had renal associated AAV
comprised a smaller patient population in the study. An interesting point of further investigation would be
to do additional trials exploring RTX as remission maintenance in patients who have anti MPO ANCA-
positive vasculitis to further determine their responsiveness to RTX treatment.