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Padoan et al. Vessel Plus 2021;5:41 https://dx.doi.org/10.20517/2574-1209.2021.41 Page 11 of 18

RTX was reported to be effective in the management of tracheobronchial stenosis (SGS and bronchial
[42]
stenosis). Girard et al. reported a remission rate in 80% in GPA patients with tracheobronchial stenosis
when treated with RTX. However, the remission rate was lower with SGS (67%) and in patients requiring
[42]
local treatment (67%) .

Other SGS case reports treated with RTX have been published, in addition to the French case series. Most
reported a good outcome even in pediatric cases, but there are reports of no response. Moreover, most
patients received glucocorticoids and were also locally or surgically treated, so the real effect of RTX alone is
difficult to assess [91-93] .

Despite aggressive immunosuppressant treatment, SGS seems to respond less than other GPA
manifestations and to be burdened with a high risk of relapse. In these cases, the patients could require a
surgical treatment, so an expert laryngologist is crucial in the patient’s monitoring and management .
[49]
For EGPA management, treatment is usually borrowed from the GPA/MPA experience, because EGPA is
frequently excluded from AAV randomized clinical trials, and, when included, EGPA patients are only a
minority. Moreover, very few clinical trials are specifically designed for EGPA and only one considered a
monoclonal antibody (mAb) [94-96]

Upper and lower airway involvement management in EGPA is challenging because ENT and asthma
exacerbations are an expression of non-severe disease but very common and dependent on glucocorticoids
(up to 84% of patients) .
[97]

In the last years, new treatments have been proposed for these manifestations; however, more evidence is
focused on refractory and glucocorticoid-dependent asthma than ENT manifestations such as chronic
rhinitis and nasal polyposis.

The pathogenesis of EGPA is still not fully clarified, but a direct pathogenic effect of eosinophil infiltration
into different tissues has been demonstrated. Eosinophils are strongly activated and regulated by IL-5,
[98]
which is primary produced by Th2 cells .
Recently, a phase 3 randomized controlled trial including relapsing, refractory, or glucocorticoid-dependent
EGPA, the MIRRA trial, was published. This trial demonstrates that mepolizumab, an anti-IL-5 mAb,
significantly reduced the frequency of disease relapses, including asthma and sinonasal relapses, and allowed
the tapering or reduction of glucocorticoids .
[94]
Regarding mepolizumab, a large observational respective study confirmed the efficacy of this drug for
EGPA patients with severe glucocorticoid-dependent asthma. The study included patients treated with
mepolizumab (100 mg monthly, compared to the 300 mg monthly dosage administered in the MIRRA
trial). Canzian et al. reported some benefit even with the low dosage that could be acceptable as first-line
[99]
therapy, but they highlighted that it has not been compared to the validated dosage of 300 mg monthly.

Since the results of the MIRRA trial were published, other anti-IL-5 medications have been considered
promising in EGPA. Reslizumab, for example, has been investigated in an open label pilot study in EGPA
[100]
with apparent favorable outcome on disease exacerbations . Similarly, a prospective open label pilot study
on benralizumab, an anti-IL-5 receptor mAb, was recently published considering a few EGPA patients,
which reported a good glucocorticoid sparing effect and improvement of EGPA exacerbations, including