Other Treatments

As suggested by some authors, based on case series [75, 76], IV immunoglobulins are another option for second-line therapy for EGPA fares of some patients, after other therapeutic agents have failed, especially those with myocardial or neural involvement.

As for other AAVs, selected ANCA-positive patients with rapidly progressive glomerulonephritis or severe pulmonary renal syndrome [77] might bene t from therapeutic plasma exchanges, even though their ef cacy continues to be debated [78].

Although interferon-alpha has successfully induced remission of refractory EGPA, its ef cacy to maintain remission seems limited, and, its numerous AEs lead us to think that it is probably not a good choice, if other options are still available [79, 80].

Rituximab is a chimeric monoclonal antibody directed against CD20-expressing B lymphocytes. Its ef cacy and safety to induce and sustain GPA and MPA remissions have been clearly demonstrated [13, 14]. However, so far, prescribing rituximab to treat EGPA has been limited to case reports and case series [81–84]. Notably, rituximab indeed seems to induce remissions effectively and safely, mainly for ANCA-positive patients [85]. The ongoing French Vasculitis Study Group’s prospective, randomized, REOVAS trial (NCT02807103) is evaluating rituximab ef cacy to induce remissions, and its prospective randomized MAINRITSEG trial (NCT03164473) is examining its use as maintenance therapy. Until those results become available, rituximab should be reserved for second-line therapy of severe EGPA refractory to conventional therapy or when that strategy is not possible.

Omalizumab, a monoclonal antibody targeting IgE, is prescribed to treat allergic asthma and allergic rhinitis, but controversy surrounds its ef cacy against EGPA. It could be effective against active disease, but a possible association between omalizumab administration and EGPA onset has been suggested [31, 32, 36, 37]. In a French retrospective study on 17 EGPA patients, omalizumab indeed had a glucocorticoid-­sparing effect, as the median prednisone dose could be lowered from 16 mg/day at baseline to 9 mg/day at month 12 [86]. However, possible safety questions have emerged, with 8 patients stopping omalizumab because of relapses (50%) and refractory disease (25%) and 2 stopping omalizumab because of severe asthma fares.

The ef cacy of mepolizumab, an anti-IL-5 monoclonal antibody, was proven in a double-blind, multicenter, phase 3 trial on 136 patients with relapsing or refractory EGPA who received a stable prednisone dose for at least 4 weeks [87]. Mepolizumab, compared to placebo, obtained signi cantly higher percentages of participants with ≥24 weeks of accrued remission (28% vs. 3%, respectively; P < 0.001). Moreover, glucocorticoid tapering was possible. Although its ef cacy

as induction therapy remains to be investigated in randomized controlled trials, mepolizumab was used to induce remissions in a single-center, phase 2, uncontrolled trial on ten consecutive patients with active refractory or relapsing EGPA; eight of them entered remission [88].

Prevention of AEs

EGPA prognosis has improved to such an extent that it is now considered a chronic relapsing disease. Because most patients remain on long-term glucocorticoids, prevention of glucocorticoid-related complications is a major issue (i.e., calcium, vitamin D, and bisphosphonates).

Moreover, cyclophosphamide is also associated with serious AEs (e.g., hemorrhagic cystitis and gonadal toxicity) that can be prevented, and concomitant cotrimoxazole or pentamidine aerosol prophylaxis should be prescribed to avoid

Pneumocystis jiroveci infections.

Although vaccinations have been a suspected of being a factor triggering EGPA [27], immunization with inactivated vaccines against infuenza and Streptococcus pneumoniae is supported to counter the high risk of potentially mortal infections under immunosuppressants. According to a prospective vaccine phase III study on 199 patients with autoimmune diseases, including 20 with EGPA, seasonal fu vaccines were safe and effective; notably, 80.3% patients obtained seroprotection [89]. However, seroprotection rates were impacted by EGPA therapeutic agents as follows: 86.7% for patients with autoimmune diseases and no immunosuppressant, 79.8% for those with immunosuppressants alone, or 60% for those administered targeted biotherapy (including rituximab). Concerning AAVs, the ongoing French Vasculitis Study Group’s prospective, the PNEUMOVAS trial (NCT03069703), is testing different vaccination regimens against pneumococcal pneumonia in GPA and MPA patients treated with rituximab.

Finally, patients must still be encouraged to quit smoking and participate in speci c patient education programs [90].

Conclusions

Our understanding of the pathophysiology and disease management of EGPA has progressed notably over the past few decades, as attested by patients’ improved prognoses. Two distinct ANCA-status phenotypes have been de ned, and investigations to elucidate their different clinical ndings, prognoses, and genetic backgrounds are being conducted.

However, EGPA relapse rates remain persistently high, and it is not unusual for patients to experience several treatment-­related AEs. Thus, additional studies are needed to further improve the overall care of EGPA patients.

Clinical Vignette

Mr. J., 65 years old, was hospitalized for atrial brillation and cardiac insuf ciency, in the context of severe chronic asthma, necessitating long-term treatment with bronchodilators and inhaled and oral glucocorticoids (7 mg/day). Over 3 months, his asthma worsened and oral prednisone (30 mg/day) was prescribed for the asthma fare. Eosinophilia, which had been ~500/ mm3 during the last few years, rose to 2000/mm3 at the time of hospitalization. The patient was febrile and complained of arthralgias, myalgias, and extreme fatigue. A chest X-ray showed multiple lung in ltrates (Fig. 7.1). Some purpuric lesions were present on the lower limbs. A histology of a skin biopsy found brinoid necrosis of small-sized arteries.

Eosinophilic granulomatous with polyangiitis (EGPA) was diagnosed. Treatment was immediately started with prednisone (1 mg/kg/day) and intravenous cyclophosphamide (0.6 g/m2 on days 0, 14, and 28, and then every 4 weeks, until 6 pulses, followed by maintenance therapy with azathioprine (2 mg/kg/day)). Oral prednisone was progressively tapered to 10 mg/day, under which asthma fared again.

Treatment also comprised of a combination of diuretics, enzyme-converting inhibitors, and an antiarrhythmic.

The patient improved quickly, with lung in ltrates resolving within a week. Eosinophilia was normalized. His general condition improved, and the general symptoms disappeared.

Fig. 7.1  Chest X-ray showing multiple lung in ltrates

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