History and presentation
A 75-year-old male nonsmoker was diagnosed with adult-onset asthma at 54 years old in 2004, with blood eosinophil counts (BEC) rising from 1,500 cells/ μL in 2004 to 1,800 cells/μL in 2006, while serum immunoglobulin E (IgE) remained normal. He tested negative for antineutrophil cytoplasmic antibody (ANCA) and stool ova/cysts.
The patient’s asthma was initially poorly controlled despite bronchodilator treatment, leading to multiple hospital admissions between 2006 and 2008. From 2009 to 2023, his condition stabilized on bronchodilators and inhaled corticosteroids, with only occasional exacerbations. Ear, nose, and throat (ENT) evaluation in 2013 revealed bilateral sensorineural hearing loss and mild nasal symptoms without polyposis, but no ongoing follow-up was required. As of 2024, his asthma was managed with budesonide/formoterol (160/4.5 μg, 2 puffs BID plus 1 puff QD PRN) and tiotropium (2.5 μg, 2 puffs QD).
In June 2024, the patient presented with bilateral thigh myalgia for >2 weeks, new symmetrical painful paraesthesia in all limbs, and progressive weakness. Examination showed lower motor neuron weakness, mainly in proximal muscles, and glove-and-stock sensory impairment at distal extremities. On admission, laboratory tests revealed marked eosinophilia of 19,000 cells/μL, later peaking at >30,000 cells/μL (75.6 percent of total white blood cells), negative FIP1L1–PDGFRA, and elevated creatine kinase of 3,990 U/L with mild proteinuria. Serum IgE was elevated. Repeat ANCA testing remained negative. Serial chest X-rays demonstrated migratory lung opacities. Electromyography showed myopathic changes. Nerve conduction studies revealed preserved sural sensory nerve action potentials, but sensory peripheral neuropathy with possible small fibre involvement could not be excluded. ENT reassessment confirmed hearing loss without sinusitis or polyposis. (Figure 1)
In view of the elevated creatine kinase and proximal muscle weakness, a left-thigh muscle biopsy was performed. Biopsy found dense perifascicular eosinophilic inflammation and vasculitic endothelial changes. Based on these findings and high BEC, a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) was made. The patient’s Birmingham Vasculitis Activity Score (BVAS) was 11, accounting for the myalgia, pulmonary infiltrates, and sensory neuropathy.
Initial EGPA treatment and response
Upon diagnosis, the patient was started on prednisolone (30 mg QD) and intravenous (IV) cyclophosphamide (1,000 mg monthly for 6 pulses), followed by azathioprine (AZA; 75 mg QD) for maintenance. (Figure 2) After completing IV cyclophosphamide treatment in December 2024, the patient showed improvement with normalization of eosinophils (260 cells/μL), creatine kinase, and urine protein. He regained muscle strength, although sensory symptoms persisted. Chest X-rays confirmed resolution of pulmonary opacities following steroid therapy. His BVAS score had decreased to 0. (Figure 1)
However, in January 2025, as steroids were tapered to 5 mg/day alongside AZA maintenance, the patient experienced a relapse characterized by a rebound in BEC to 1,020 cells/μL, asthmatic exacerbation, and worsening exercise tolerance. He also reported recurrent limb weakness and persistent lower-limb numbness. His BVAS score had increased to 2, and prednisolone was stepped up to 10 mg daily. (Figure 1) Follow-up lung function test in February 2025 showed an obstructive ventilatory defect, with declines in both FEV₁ and FVC compared with prior baseline measurements. An episode of self-limiting bloody diarrhoea in April 2025 raised concern for gastrointestinal vasculitis, but it resolved spontaneously and was not considered persistent disease activity.
Anti–IL-5 treatment and outcomes
In view of disease relapse without organ- or life-threatening manifestations, the patient was initiated on mepolizumab (an anti–interleukin-5 [IL-5] monoclonal antibody; 300 mg subcutaneously Q4W) as add-on therapy in May 2025.1 (Figure 1) Concomitantly, entecavir (0.5 mg QD) was prescribed as the patient was anti‑HBc positive in the context of previous use of high-dose oral corticosteroids (OCS) and cyclophosphamide, while pregabalin (75 mg TID) was prescribed for neuropathic pain. Complete blood count with differential, liver function tests, erythrocyte sedimentation rate, C‑reactive protein, creatine kinase, and hepatitis B virus DNA were monitored every 3–4 months, and serial chest X‑rays were performed to assess progression.
By August 2025, the patient achieved remission with normalized BEC. No further major asthma attacks, muscle weakness, or gastrointestinal involvement were observed. Residual numbness persisted, but improvement was reported by the patient. OCS was successfully tapered to 2.5 mg daily by August 2025 and discontinued by November 2025. (Figures 1 and 2)
Overall, the patient tolerated mepolizumab treatment well, with no adverse events observed. At the last follow-up in November 2025, he remained stable on mepolizumab without the need for OCS, with normalized BEC and creatine kinase levels, a clear chest X-ray with no new lesions, and was asymptomatic apart from residual numbness. His Vasculitis Damage Index score was 4, accounting for hearing loss, asthma, impaired lung function, and peripheral neuropathy.
Discussion
Classically, EGPA is characterized by a triphasic progression comprising the prodromal, eosinophilic, and vasculitis phases, with some patients demonstrating prolonged prodromal or eosinophilic phases prior to vasculitis development, while others may not experience all three phases.2 Our patient illustrates this classical progression, with adult‑onset asthma first noted in 2004 as initial manifestation, followed by full EGPA presentation in 2024, indicating a quiescent period of >20 years. Due to the disease’s indolent early course, diagnosis can be challenging. Suspicious features of EGPA include eosinophilia with multisystem involvement, asthma or nasal polyposis accompanied by systemic symptoms, and clinical evidence of vasculitis. The condition also needs to be distinguished from a wide range of diseases, and a comprehensive set of investigations should be tailored on a case‑by‑case basis through multidisciplinary team assessment.3-5
Currently, combination therapy with OCS and immunosuppressants is the standard of care (SoC) for EGPA.6,7 However, multiple unmet needs remain. While the SoC approach results in remission in most patients, over one-third of patients experience relapse, as illustrated in our case, where relapse occurred during AZA maintenance.4,8 Steroid dependence is another key challenge, given the risk of adverse effects associated with long-term OCS use.4,7
Several clinical studies demonstrated the limitations of conventional immunosuppressants in EGPA for both remission induction and maintenance, as well as for reducing steroid use. Compared with use of glucocorticoids (GC) alone, addition of AZA to GC was not shown to improve remission rates, lower relapse rate, spare steroids, or diminish EGPA asthma/rhinosinusitis exacerbation rate.9 In the recently published REOVAS study, rituximab added to GC did not improve remission induction at day 180 or day 360 vs conventional therapy (GC alone or in combination with cyclophosphamide), with similar relapse rates and average daily GC dose between the two groups.10 The MAINRITSEG study also showed that rituximab was not superior to AZA in maintaining vasculitis remission or sparing GC in patients with previous remission within the prior year after a new EGPA diagnosis or vasculitis relapse.11
To address the limited effectiveness of immunosuppressants, mepolizumab has become an important treatment option, particularly in non–organ‑threatening EGPA, and was selected for our patient based on its established efficacy and safety profile in relapsing disease.7 The European League Against Rheumatism (EULAR) 2022 guidelines recommend mepolizumab as first-line therapy for induction of remission in patients with relapsing or refractory EGPA without organ- or life-threatening disease. Mepolizumab is also recommended as maintenance therapy for patients with non–organ- or non–life-threatening disease, as well as those with previously organ- or life-threatening disease who achieved remission with conventional induction therapies such as cyclophosphamide or rituximab.6 (Figure 3)
The British Society of Rheumatology (BSR) 2025 update also recommends anti–IL-5 therapies for both remission induction in non–life- or non–organ-threatening EGPA (Grade 1A) and maintenance of remission to support tapering of GC (Grade 1A). In both scenarios, conventional immunosuppressants may be considered if anti–IL‑5 therapy is not available. GC should be reduced to the lowest effective dose while maintaining remission and accounting for the patient’s clinical situation. A slow taper is advised to support adrenal recovery and reduce the risk of long-term adrenal insufficiency.3
Mepolizumab’s efficacy in relapsing or refractory EGPA was well demonstrated in the multicentre, double‑blind, parallel‑group, phase III MIRRA trial (n=136), where mepolizumab added to SoC significantly increased accrued weeks in remission (28 vs 3 percent achieving ≥24 weeks of remission; p<0.001) and resulted in a greater proportion of patients achieving remission at both weeks 36 and 48 (p<0.001) vs placebo. Mepolizumab was also associated with a lower annualized relapse rate (1.14 vs 2.27; p<0.001). In addition, reduced OCS use was observed with mepolizumab vs placebo (p<0.001).7
The open‑label extension (OLE) study of MIRRA further demonstrated mepolizumab’s long‑term safety and steroid‑sparing effect. The OLE included 100 patients who required OCS of ≥5 mg/day up to 6 months after completing MIRRA, with all patients receiving mepolizumab 300 mg subcutaneously Q4W plus SoC. The median duration of mepolizumab exposure was 27.0 months, with a total of 320.5 patient‑years of follow‑up. Over the course of the study, median daily OCS use steadily decreased from 10.0 mg/day at OLE baseline to 5.0 mg/day at study exit. The proportion of patients receiving >7.5 mg/day of OCS decreased from 75 to 32 percent, and 28 percent of patients discontinued OCS entirely. No new long‑term safety concerns were identified.12
Consistent with clinical trial results, the Japanese real‑world, observational MARS study also demonstrated meaningful benefits with mepolizumab. In 118 patients who had previously completed ≥96 weeks of mepolizumab (baseline) and continued receiving mepolizumab 300 mg Q4W for a further 96 weeks (observation period), the proportion of patients with no clinical symptoms increased from 6 percent in the pre‑mepolizumab period to 32 percent at the end of the observation period. Median OCS dose decreased from 6.9 to 2.0 mg/day, and the proportion of steroid‑free patients increased from 8 to 36 percent.13
Based on personal clinical experience, EGPA patients typically respond well to treatment with OCS. However, steroid dependence remains a major therapeutic challenge, with flares during tapering (such as seen in our patient) contributing to accrued organ damage alongside glucocorticoid-induced toxicity. Timely access to anti–IL-5 biologics offers a steroid-sparing strategy to mitigate these issues.
In Hong Kong, the Samaritan Fund supports mepolizumab treatment for EGPA patients with financial need.14 Support is provided to those with relapsing or refractory disease despite treatment with OCS and conventional immunosuppressive agents.
Take-home messages
This EGPA case illustrates progression from adult-onset asthma with eosinophilia, stabilized for many years before evolving to systemic vasculitis with myositis, sensory peripheral neuropathy, proteinuria and pulmonary involvement. While initial remission induction was successful with cyclophosphamide, conventional immunosuppressant such as AZA had limited efficacy in steroid sparing and remission maintenance.
Relapses and steroid dependence are common in EGPA. Anti–IL‑5 agents such as mepolizumab can be used safely for remission maintenance in patients with severe EGPA after successful induction with cyclophosphamide.
