Аннтотация

Over the last decade, biologic agents have become an important component of therapy for systemic vasculitides, e.g., rituximab for granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis, or tocilizumab for giant cell arteritis. However, a risk/benefit ratio of biologic therapy for eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA) has not been well studied. Jachiet et al have reported results of a retrospective study of treatment with omalizumab (an anti‐IgE monoclonal antibody) in 17 patients with refractory and/or relapsing EGPA and severe steroid‐dependent asthma and/or sinonasal involvement 1. Treatment response was defined as improvement of asthma and/or ear/nose/throat (ENT) exacerbations. Therefore, this was an “asthma” study rather than a “vasculitis” study, and efficacy of omalizumab in vasculitis remains unclear. Notably, 7 patients described in Jachiet and colleagues' report had other signs and symptoms (skin disease, myalgia, arthralgia, pulmonary infiltrates) in addition to asthma and/or ENT involvement. Following treatment, these relatively mild manifestations of active vasculitis had improved significantly in only 3 patients. Thus, omalizumab does not appear to be a promising agent for management of vasculitis. Moreover, treatment with omalizumab may result in manifestation of other disease features due to steroid tapering: 2 of the patients in Jachiet et al's study developed retrobulbar optic neuritis related to disease relapse. Unlike GPA, severe eye disease is a rare finding in EGPA; therefore, this high incidence (∼12%) of retrobulbar optic neuritis in patients treated with omalizumab would not have been expected.

It has previously been suggested that clinical vasculitis manifestations, such as peripheral neuropathy or renal involvement, occur more frequently in patients with antineutrophil cytoplasmic antibody (ANCA)–positive EGPA than those with ANCA‐negative disease 2. It can be speculated that the risk/benefit ratio of omalizumab may be more favorable in patients with ANCA‐negative EGPA. Jachiet et al did not report the ANCA status of patients with vasculitis relapse, though they stated in the Discussion that response to omalizumab seemed to be independent of ANCA positivity.

Omalizumab induced a complete or partial response (i.e., absence of asthma and/or ENT exacerbations) in 65% of patients. However, the moderate reduction in prednisone dosage following biologic therapy raises a question as to whether the same effect could have been achieved by intensification of treatment with inhaled corticosteroids and/or long‐acting bronchodilators. Jachiet et al did not present data on concomitant use of antiasthmatic medications (this information was likely not available given the retrospective design of the study). Recently, Detoraki et al reported on 5 patients with EGPA and moderate‐to‐severe asthma who were treated with omalizumab as add‐on therapy to prednisone, inhaled corticosteroids, and bronchodilators 3. Over a treatment period of 36 months, omalizumab was found to be safe and enabled corticosteroid tapering while reducing eosinophilia and improving asthma symptoms. Although the steroid‐sparing effect of omalizumab is apparently beneficial, it should not be overestimated. In a Cochrane systematic review, a significant benefit of subcutaneous omalizumab versus placebo was noted with regard to reduction in the frequency of hospitalization or discontinuation of inhaled corticosteroids in patients with bronchial asthma 4. However, there was no significant difference between omalizumab and placebo groups in the proportion of participants who were able to discontinue oral corticosteroid therapy.

Unlike omalizumab, rituximab (an anti‐CD20 monoclonal antibodу) has no antiasthmatic activity and is being used to treat relapsing and/or refractory vasculitis. Mohammad et al have reported on 41 patients with EGPA treated with rituximab in 4 centers 5. At 6 months and 12 months, respectively, remission or partial response was achieved in 83% and 87% of patients. In our own series, complete or partial remission was achieved following rituximab administration in all 6 patients with moderately severe or severe relapsing EGPA that was refractory to conventional immunosuppression 6. Notably, in 2 patients, attempts to reduce the dosage of or discontinue corticosteroids led to a minor relapse that required intensification of treatment (increase in corticosteroid dosage or addition of mycophenolate mofetil), while 1 patient developed severe bronchospasm following rituximab infusion. Therefore, along with infections, the risk of aggravating asthma during rituximab infusion should be taken into account.

Mepolizumab (an anti–interleukin‐5 monoclonal antibody) is another promising biologic treatment for EGPA. Its efficacy in patients with refractory, relapsing, or steroid‐dependent EGPA manifestations was preliminarily shown in small open‐label studies 7, 8 and is currently under investigation in a randomized clinical trial (MIRRA; ClinicalTrials.gov: NCT00527566). Mepolizumab may have advantages over omalizumab and rituximab, as it seems to be effective in both vasculitis and eosinophilic asthma.

In conclusion, Jachiet et al have provided important data for rheumatologists caring for patients with EGPA. Regretfully, the future of omalizumab in EGPA does not look bright. Therefore, we should focus on other biologic agents that would ideally have activity against both vasculitis and asthmatic/sinonasal manifestations of EGPA.