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Page 12 of 14 Skopis et al. Vessel Plus 2020;4:30 I http://dx.doi.org/10.20517/2574-1209.2020.42

A single center cohort study conducted in June 2020 sought to investigate the role of the presence of
ANCA autoantibodies, ANCA titers and, the appearance of CD19+ B cells in the circulation as predictors
of the risk of disease relapse in AAV patients. The study found that ANCA negativity regardless of B cell
presence was a strong predictor that disease remission would be maintained. Additionally, PR-3 ANCA
positivity or persistence of PR-3 ANCA levels was a strong predictor of relapse. Relapses in the MPO-
ANCA population occurred exclusively when B cells were present. This research provides the interesting
possibility that a tailored regimen of therapy based on ANCA positivity and presence of B cells could be
effective in preventing disease relapse in AAV patients. The question that remains is if this method could
lead to overtreatment, as some patients are able to achieve clinical remission despite ANCA positivity and
relapses have been known to occur in patients regardless of B cell presence. This will be an interesting topic
[40]
of further research .

CONCLUSION
Treatment of AAV has always provided a challenge for physicians both because of its severe, life threatening
manifestations and, the multitude of side effects caused by the cytotoxic medications needed to induce
and maintain disease remission. Despite these therapies, patients with AAV still experienced high rates
of relapse. Cyclophosphamide was the gold standard of induction therapy for many years however, given
its extensive risk of cytotoxic side effects, it was not an ideal long-term maintenance therapy for patients
with AAV and other agents were explored for disease maintenance remission. Among these medications
are MTX and AZA, which gained recognition for their ability to induce disease remission and shorten the
length of time of CYC exposure, however, these medications had high relapse rates and were associated
with numerous adverse effects. The RAVE and RITUXVAS trials demonstrated that RTX was non-inferior
to CYC in successfully achieving disease remission in AAV patients and, had a similar safety profile to
CYC.

After the discovery that RTX was a promising induction agent for AAV, early retrospective reviews were
conducted exploring RTX as a maintenance therapy for AAV. The MAINRITSAN trial provided evidence
of the superiority of RTX to AZA in preventing disease relapse in AAV patients, and the MAINRITSAN
2 trial demonstrated that individually tailored regimens of RTX infusions based on the reappearance of
ANCA autoantibodies, increase of ANCA titers or, reappearance of CD19+ B lymphocytes from treatment
randomization had similarly low relapse rates as fixed dose regimens of RTX and, enabled patients to
receive fewer infusions. The RITAZAREM trial demonstrated the superiority of RTX as a maintenance
therapy compared to AZA in the prevention of disease relapse in patients with a history of relapsing AAV
and, showed that RTX had fewer associated adverse events. Additionally, despite being left out of the above
trials due to its distinct pathogenesis, RTX maintenance was also investigated in EGPA as compared to
CYC in another study and was deemed an effective and well tolerated treatment option for EGPA.

These studies are monumental in the advancement of therapy for AAV because up until recently, the gold
standard induction therapy for this disease was extremely cytotoxic and even though alternate maintenance
strategies were aimed at reducing the toxic effects of CYC, they had high rates of relapse and were
associated with adverse effects of their own. The above literature reveals that RTX is a safe, effective and
well tolerated induction and maintenance therapy in AAV that can be given in a tailored dosing regimen,
thus exposing patients to fewer infusions. This has important implications in the treatment of AAV as
patients treated with RTX will have better disease control with lower relapse rates, fewer exposures to the
medication and, a decreased incidence of adverse events. As a result, patients with AAV receiving RTX
therapy will have higher survival rates and longer relapse free periods, leading to an overall enhanced
quality of life and improvement in patient outcomes.