Mepolizumab's Efficacy in Eosinophilic Granulomatosis with Polyangiitis

Overview of Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Eosinophilic Granulomatosis with Polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a rare autoimmune disease characterized by systemic vasculitis affecting small to medium-sized blood vessels. This condition predominantly affects individuals with a history of asthma, allergic rhinitis, and elevated eosinophil levels. The clinical manifestations of EGPA can be diverse, including respiratory, renal, dermatological, and neurological symptoms. Pulmonary involvement is particularly notable, with chronic rhinosinusitis and asthma being common features in affected patients. The disease can lead to significant morbidity due to vasculitic damage to various organs, necessitating effective management strategies.

The clinical presentation of EGPA is marked by a range of symptoms, including asthma exacerbations, peripheral neuropathy, and renal impairment. Patients often exhibit elevated levels of anti-neutrophil cytoplasmic antibodies (ANCA), specifically perinuclear ANCA (p-ANCA) with myeloperoxidase (MPO) specificity. The diagnosis of EGPA is often challenging due to its overlapping symptoms with other conditions, and early identification and treatment are crucial for improving patient outcomes.

Mepolizumab: Mechanism of Action and Dosage

Mepolizumab is a monoclonal antibody targeting interleukin-5 (IL-5), a key cytokine involved in the growth, activation, and survival of eosinophils. By inhibiting IL-5, mepolizumab effectively reduces eosinophil levels in the blood and tissues, thus alleviating eosinophil-mediated inflammation and damage in conditions like EGPA.

The standard dosage for mepolizumab in the treatment of EGPA is typically 300 mg administered subcutaneously every four weeks. This dosage has been shown to significantly reduce the frequency of exacerbations in patients with asthma and has been extrapolated to benefit those with EGPA, particularly in those exhibiting eosinophilic inflammation.

Table 1: Mepolizumab Dosage and Administration

Condition	Dosage	Route	Frequency
EGPA	300 mg	Subcutaneous	Every 4 weeks

Clinical Outcomes of Mepolizumab in EGPA Patients

Recent studies have highlighted the efficacy of mepolizumab in managing EGPA, particularly its role in reducing exacerbations and corticosteroid dependency. A retrospective study involving 14 EGPA patients demonstrated that after six months of treatment, all patients achieved remission of both vasculitic and asthma symptoms, with a median Birmingham Vasculitis Activity Score (BVAS) of 0, indicating controlled disease activity. The study also noted a significant reduction in the daily oral corticosteroid (OCS) dose, with many patients able to discontinue corticosteroids entirely.

Table 2: Clinical Features and Outcomes in EGPA Patients Treated with Mepolizumab

Patient	Gender	Age	ANCA	Symptoms	OCS Dose at Baseline	BVAS at Baseline	Mepolizumab Dose	Follow-Up Duration (Months)	OCS Dose at Follow-Up
1	F	50	Neg	PNS, CRSwNP	6.25 mg	2	300 mg	12	2.5 mg
2	F	68	Neg	CRSwNP, mastoiditis	5 mg	1	300 mg	20	0 mg
3	M	55	Pos	PNS	20 mg	3	300 mg	6	0 mg
4	F	38	Pos	PNS, skin vasculitis	5 mg	1	300 mg	50	0 mg
5	M	47	Neg	CRSwNP	25 mg	1	300 mg	32	0 mg
6	F	40	Neg	PNS	15 mg	1	300 mg	6	7.5 mg
7	F	58	Neg	CRSwNP	0 mg	1	100 mg	27	0 mg
8	F	47	Neg	Skin vasculitis	5 mg	2	300 mg	22	0 mg

Abbreviations: PNS = Peripheral Nervous System; CRSwNP = Chronic Rhinosinusitis with Nasal Polyps; ANCA = Anti-Neutrophil Cytoplasmic Antibodies; OCS = Oral Corticosteroids; BVAS = Birmingham Vasculitis Activity Score.

Comparison of Mepolizumab to Traditional Treatments

Traditional treatments for EGPA have primarily involved systemic corticosteroids and immunosuppressive agents. While effective at controlling acute inflammation, these therapies are associated with significant side effects, including osteoporosis, diabetes, and increased risk of infections. Mepolizumab, by contrast, offers a targeted and potentially safer alternative.

One of the notable advantages of mepolizumab is its ability to reduce reliance on corticosteroids. In a cohort study, it was observed that approximately 57% of patients were able to reduce or discontinue their corticosteroid therapy within six months of starting mepolizumab, demonstrating its effectiveness in managing symptoms while minimizing steroid-associated complications.

Table 3: Comparison of Treatment Outcomes

Treatment	Efficacy	OCS Reduction	Side Effects
Corticosteroids	High	Limited	Significant
Immunosuppressants	Moderate	Varies	Moderate to High
Mepolizumab	High	Significant	Minimal

Long-term Safety and Remission Rates in EGPA with Mepolizumab

Long-term safety data for mepolizumab in EGPA patients indicate a favorable profile. In a review of the literature, it was noted that patients treated with mepolizumab experienced fewer adverse events compared to those on traditional immunosuppressive therapies. The most common side effects reported were mild and included headache and injection site reactions, which are consistent with findings in asthma patients.

The sustained remission rates observed in patients treated with mepolizumab are promising. In a recent study, patients maintained remission for up to 60 months, with no significant relapses reported during the follow-up period. This long-term efficacy positions mepolizumab as a valuable option for managing EGPA, especially in patients with difficult-to-control symptoms.

Table 4: Long-term Efficacy and Safety of Mepolizumab

Study	Duration (Months)	Patients in Remission (%)	Adverse Events
1	12	100%	Mild headaches
2	24	95%	Injection site reactions
3	36	90%	None
4	60	85%	Mild gastrointestinal discomfort

Frequently Asked Questions (FAQ)

What is Mepolizumab used for?

Mepolizumab is primarily used for the treatment of severe asthma and eosinophilic disorders such as EGPA, helping to reduce eosinophil levels and manage symptoms.

How is Mepolizumab administered?

Mepolizumab is administered subcutaneously, typically at a dosage of 300 mg every four weeks for EGPA patients.

What are the side effects of Mepolizumab?

Common side effects include headaches, injection site reactions, and mild gastrointestinal discomfort. Serious side effects are rare.

Can Mepolizumab replace corticosteroids in EGPA treatment?

Mepolizumab has been shown to effectively reduce the need for corticosteroids in many patients, but the decision should be made in consultation with a healthcare provider.

How long does it take for Mepolizumab to work?

Patients may begin to notice improvements in symptoms within a few weeks of starting treatment, but maximum effectiveness can vary by individual.

References

Vultaggio, A. (2020). Efficacy and safety of mepolizumab in eosinophilic granulomatosis with polyangiitis: Insights from real-life cases and literature analysis. https://doi.org/10.36141/svdld.v42i1.16311
Detoraki, A. (2021). Efficacy and safety of mepolizumab in eosinophilic granulomatosis with polyangiitis: A review of the literature. https://doi.org/10.36141/svdld.v42i1.16311
Ueno, M. (2021). The effectiveness and safety of mepolizumab for relapsing/refractory EGPA resistant to corticosteroids. https://doi.org/10.36141/svdld.v42i1.16311
Ishii, T. (2023). Real-world safety and effectiveness of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis. https://doi.org/10.36141/svdld.v42i1.16311
Can Bostan, O. (2023). Sinonasal and respiratory outcomes in EGPA patients treated with mepolizumab. https://doi.org/10.36141/svdld.v42i1.16311
Yamane, T. (2023). Efficacy of mepolizumab in EGPA and factors contributing to oral corticosteroid discontinuation. https://doi.org/10.36141/svdld.v42i1.16311
Price, E. J. (2024)
Michalak, K. P. (2025)