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Skopis et al. Vessel Plus 2020;4:30 I http://dx.doi.org/10.20517/2574-1209.2020.42 Page 11 of 14

Continued use of RTX increases the risk of serious infections depending upon the indication for its use
and, the dose at which it is being administered. With regard to AAV patients, a retrospective case review
demonstrated that severe infections occurred most commonly within the first year of receiving RTX
[37]
treatment. Old age and lack of ENT involvement was a risk factor for developing severe infection .
Another study found that bronchiectasis and endobronchial involvement were notable risk factors
for development of severe respiratory infections, and that antibiotic prophylaxis with Trimethoprim-
sulfamethoxazole was effective in preventing infections in patients with AAV who were receiving RTX
[38]
infusions .

Rituximab as induction and maintenance therapy in EGPA
Due to the fact that the pathogenesis of EGPA is dictated by eosinophil mediated inflammation and
eosinophilic pneumonia as opposed to the other ANCA associated vasculitides (which are driven by
the pathogenesis of B cell autoimmunity, neutrophil abnormalities and complement activation), the
treatment of this specific subset of AAV can differ, which is why EGPA was excluded from most of the
studies mentioned above. Induction therapy of life-threatening organ involvement in EGPA is commonly
accomplished with CYC and glucocorticoids. A study in 2017 sought to investigate RTX vs. CYC as induction
therapy in patients with EGPA who were refractory to prior induction therapy with CYC. This retrospective
analysis studied 28 patients with EGPA and measured their treatment response when treated with RTX
induction therapy vs. cyclophosphamide. Five of the patients in the RTX arm (36%) achieved disease
remission as opposed to four patients in the CYC arm (29%). The remainder of the patients achieved partial
remission. There was no difference in response to treatment between the two groups. Rituximab was well
[39]
tolerated but did result in a decrease in serum immunoglobulin levels . Further research is yet to be done
on effective maintenance therapies for EGPA and would be an interesting subject of continued studies.

EFFICACY OF RITUXIMAB IN TREATING PROTEINASE 3-ANCA VS. MYELOPEROXIDASE-

ANCA
During the RAVE trial, patient responses to RTX vs. CYC were analyzed based on ANCA-type (PR-3
vs. MPO). The data concluded that RTX was also superior to CYC in maintaining remission specifically
[9]
in ANCA PR-3 positive patients vs. patients who were positive for ANCA-MPO . The MAINRITSAN
trial enrolled more patients who were positive for anti-PR-3 ANCA in the study than patients who were
positive for anti-MPO ANCA, so the results were more indicative of the response of the anti-PR3 ANCA
patient population to RTX [Table 1]. Earlier trials also enrolled greater numbers of PR-3 ANCA positive
patients [17,21] . This poses an interesting question as to whether RTX is more effective in treating and
preventing disease relapse in patients who are specifically PR-3-ANCA positive and, would be a good
subject of future research.

RISK FACTORS FOR DISEASE RELAPSE IN ANCA ASSOCIATED VASCULITIS
The utility of monitoring the presence of autoreactive ANCA antibodies, ANCA titers and, presence of
circulating CD19+B cells as a risk factor for disease relapse in AAV has been a matter of debate due to
conflicting data on this subject throughout the years. It is particularly useful to know this information as
prevention of relapses is paramount in reducing organ damage and increasing survival in AAV patients.
There is conflicting evidence regarding this subject because while ANCA titers do often drastically decrease
in patients who have received induction therapy, some patients who have achieved disease remission can
remain ANCA positive and certain patients who are negative for ANCA autoantibodies can still relapse.
The same question is posed regarding the presence of circulating CD19+ B cells as relapses have occurred
regardless of the presence of B cells in AAV patients. The MAINRITSAN 2 trial addresses this fact as the
study notes that four patients experienced disease relapses despite being ANCA negative and having no B
cells in the circulation.