Achieving remission with anti–IL-5 therapy in a patient with adult-onset asthma and refractory EGPA

Presentation and history
A 57-year-old lady presented in January 2015 with bilateral lower limb numbness, vasculitic rash over her lower limb, shortness of breath, and sudden loss of vision in her left eye. She had a history of adult-onset asthma for more than 10 years (managed with inhaled corticosteroids and bronchodilator), and had two episodes of exacerbation 6 months before presentation. Other comorbidities included allergic rhinitis and paroxysmal atrial fibrillation.

Blood tests showed elevated eosinophil count (BEC; 10,700 cells/μL), C-reactive protein (CRP) level (8.9 mg/ dL), erythrocyte sedimentation rate (ESR; 51 mm/h) and immunoglobulin E (IgE) level (5,100 IU/mL). Assessments found mononeuritis multiplex in the lower limb and left central retinal artery occlusion (CROA). Skin biopsy confirmed presence of leukocytoclastic vasculitis with eosinophilic infiltration. These findings, together with her history of adult-onset asthma, led to the diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA), in spite of her testing negative for antineutrophil cytoplasmic antibodies (ANCA), antinuclear antibodies (ANA) and other autoimmune markers.

Intravenous (IV) pulse prednisolone 1 g was given for 3 days, followed by oral prednisolone 0.8 mg/kg/day and IV cyclophosphamide to induce remission. After six cycles of IV cyclophosphamide, azathiopine 100 mg QD as maintenance therapy was started. Cardiac MRI in 2016 showed no evidence of infarcts, pericardial effusion, or myocarditis.

The patient had persistent numbness, but repeat nerve conduction velocity (NCV) test showed no active mononeuritis multiplex. Her condition remained stable until October 2020, when she had a flare with eosinophilia but no rash recurrence. She was treated with prednisolone 30 mg QD for 6 weeks, after which the dose was tapered. Maintenance oral immunosuppressive therapy was switched to mycophenolate mofetil (MMF) but had to be switched back to prednisolone due to gastrointestinal upset with MMF. The patient was maintained on prednisolone 6–7.5 mg QD from May 2021 to early 2024.

Treatment with anti–IL-5 and response
From late 2023 to early 2024, the patient had recurrent episodes of chest infection and pneumonia. CT scan showed right upper and middle lobe consolidation. Azathioprine was stepped down to 50 mg QD. However, she developed frequent asthmatic symptoms with mild eosinophilia requiring twice-daily use of rescue bronchodilators.

In view of the patient’s persistent EGPA symptoms (which were not organ-threatening) and recurrent infective episodes with prednisolone and azathioprine, a joint decision with the patient was made in April 2024 to start treatment with mepolizumab (an anti–interleukin-5 [IL-5] monoclonal antibody [mAb]; 300 mg subcutaneously Q4W). (Figure 1)

The patient’s asthma was brought under control and azathioprine was discontinued in June 2024. Her BEC, CRP and ESR also normalized.

Last followed up in March 2025, the patient was in remission and enjoying good quality of life despite residual numbness in her lower limb (possibly as a result of neuropathic damage). She was asymptomatic and infection-free, with well-controlled asthma requiring infrequent rescue medication (<1 time per week), and maintained on mepolizumab 300 mg Q4W plus prednisolone 4 mg QD. (Figure 1)

Discussion
EGPA, formerly known as Churg- Strauss Syndrome, is a rare ANCA associated vasculitis (AAV) typically characterized by three different phases, namely the prodromic asthmatic phase; eosinophilic phase during which peripheral eosinophilia and organ involvement appear; and a vasculitic phase affecting predominantly small vessels (eg, mononeuritis multiplex, skin purpura or glomerulonephritis). These phases often overlap and may not necessarily develop in the aforementioned sequence. ANCAs, more commonly against myeloperoxidase, are positive in 40–60 percent of EGPA patients. A patient diagnosed with small- or medium- vessel vasculitis who has all potential “vasculitis mimics” excluded would be classified as having EGPA if he/she obtains a sum of scores of ≥6 for seven items when assessed according to the 2022 American College of Rheumatology/ European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for EGPA.^1,2

In EULAR’s 2022 guideline on ANCA-associated vasculitis (AAV) management, a combination of high-dose glucocorticoids and cyclophosphamide, or alternatively glucocorticoids and rituximab, are recommended for induction of remission in new-onset EGPA with organ- (such as CROA in our patient) or life-threatening manifestations, or in patients with poor prognostic factors.^1,2

For maintenance of remission after induction therapy for life-/organ-threatening EGPA, systemic glucocorticoids with/without conventional disease-modifying antirheumatic drugs (DMARDs; eg, azathioprine and methotrexate) have been routinely used in clinical practice.^1,2

In patients with persistently active disease or intolerance to glucocorticoids plus conventional DMARDs, the use of biologics (mepolizumab or rituximab) can be considered. The histological hallmark of EGPA is necrotizing small-vessel vasculitis with eosinophil infiltrates and granulomas. IL-5 plays an important role in eosinophil activation, maturation and survival. Mepolizumab, a humanized anti–IL-5 mAb, is recommended by EULAR’s 2022 AAV guideline for induction of remission in patients with relapsing or refractory EGPA without active organor life-threatening disease (strength of recommendation [SoR], B).²

The randomized, placebo-controlled MIRRA trial showed that mepolizumab (300 mg Q4W for 52 weeks) treatment led to longer accrued remission than placebo in 136 patients with refractory or relapsing EGPA (28 vs 3 percent with ≥24 weeks of accrued remission; odds ratio [OR], 5.91; 95 percent confidence interval [CI], 2.68– 13.03; p<0.001). Patients in the mepolizumab group also had higher rates of remission at both weeks 36 and 48 (32 vs 3 percent; OR, 16.74; 95 percent CI, 3.61–77.56; p<0.001). Annualized relapse rate was also lower with mepolizumab (1.14 vs 2.27; rate ratio, 0.50; 95 percent CI, 0.36–0.70; p<0.001). In this trial, patients with organ- or life-threatening EGPA within 3 months of screening were excluded. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS), version 3, of 0 (on a scale of 0–63) and receipt of prednisolone at a dose of ≤4.0 mg/day over the 52-week period.⁴

In a real-world clinical practice study involving a large European EGPA cohort (2015–2020), where 191 patients were receiving stable doses of mepolizumab (100 mg Q4W, n=158; 300 mg Q4W, n=33), 54.6 percent of patients on mepolizumab 300 mg achieved complete or partial response at 3 months. Response to treatment was defined as no disease activity (BVAS, 0) and a prednisolone dose (or equivalent) of ≤4 mg/ day.⁵

The MARS study, a real-world, Japanese observational study of patients (n=118) who had previously completed ≥96 weeks of mepolizumab (baseline) and continued receiving mepolizumab 300 mg Q4W for a further 96 weeks (observation period), showed that clinical remission rate increased from 6 percent in the pre-mepolizumab period to 27 percent at baseline and 32 percent at the end of the observation period, respectively. ⁷ (Figure 2)

The chronic relapsing course of EGPA necessitates long-term glucocorticosteroid use, and high cumulative doses of glucocorticoids put patients at risk of various complications. Use of biologics could enable glucocorticoid dose reduction to mitigate the risk of glucocorticoid-related toxicity. A longer duration spent in remission with mepolizumab was associated with reduced glucocorticoid use in the MIRRA, LAP (Long-term Access Programme involving patients who completed MIRRA and required prednisolone [or equivalent] ≥5 mg/day within 6 months of MIRRA completion), European EGPA cohort and MARS studies.^4-8

In MIRRA, 44 vs 7 percent of mepolizumab- vs placebo-treated patients had an average daily dose of prednisolone ≤4.0 mg/day during weeks 48–52 (OR, 0.20; 95 percent CI, 0.09–0.41; p<0.001). LAP reported that 66 percent of participants achieved a ≥50 percent reduction in glucocorticoid dose at 16–18 months compared with MIRRA baseline, while reduced glucocorticoid use was maintained for up to 7.4 years of treatment.^4,8

In the MARS study, the mean glucocorticoid dose decreased from 6.9 mg (pre-mepolizumab treatment) to 2.0 mg (after 144 weeks of mepolizumab use), and >30 percent of patients tapered off glucocorticoid after ≥96 weeks of mepolizumab.

Mepolizumab was generally well tolerated when used long-term by EGPA patients in the above-cited studies.^5,7,8 Common adverse events (AEs) include headache, injection site reactions and infection such as herpes zoster. Consistent with findings from randomized controlled studies, the MARS study showed that infections and infestations were one of the most commonly reported AEs with mepolizumab use in the real-world setting. However, the risk was not increased compared with background infection risk in the general AAV population in Japan.⁶

Early recognition of EGPA is key to improved survival. It is important to be aware of the systemic features and consider EGPA as a differential diagnosis, especially in patients with adult-onset asthma with eosinophilia. This will enable prompt diagnosis and earliest initiation of treatment to reduce disease-related damage. Enhancing patient access to anti–IL5 therapy (eg, Samaritan funding for eligible patients) can improve EGPA management in Hong Kong. 

Related MIMS Drugs

NUCALA