**3.5 Mepolizumab**

*Vascular Biology - Selection of Mechanisms and Clinical Applications*

This is one of the most rigorously studied agent, which is also a tumor necrosis

Etanercept (25 mg twice weekly) was given to 20 patients with Wegener's granu-

Wegener's granulomatosis itself is also associated with increased risk of malignancy. The specific malignancies associated with it are bladder carcinoma, squa-

Use of these two agents (Infliximab and Etanercept) have shown promising results in Takayasu arteritis as demonstrated by a case series in which 15 patients with treatment resistant disease were treated with either of the drug. After introduction of these agents, the average dose of corticosteroid dropped from 20 mg (range 12.5–40 mg) to 0 mg (range 0–20 mg). Among these 15 patients 93% showed remarkable improve-

Etanercept is one of the most widely studied agents, which is also an anti-TNF drug, and has been seen to be beneficial not only in ANCA-associated vasculitis but also in large vessel vasculitis (Takayasu arteritis). The biggest disadvantage of this

**Table 5** summarizes two trials showing clinical outcomes of Etanercept in patients

This is a human IgG1 gamma monoclonal antibody specific for soluble human B lymphocyte stimulator protein, also known as B cell-activating factor. Surprisingly, this is the only drug in late stage development for microscopic polyangiitis [12]. Currently this agent is in Phase 3 trial. Its efficacy and safety are being tested in a randomized, double blind study in combination with azathioprine. The dose given to patients is 10 mg/kg at days 0, 14, and 28 then after every 28 days till the study

WGET trial Etanercept WG No significant difference in rate of sustained remission

between Etanercept and placebo

fell significantly. Three patients developed major flare

Etanercept WG 80% patients went into disease remission and their BVAS

with Wegener's granulomatosis also known as granulomatosis with polyangiitis.

factor inhibitor. Its role has been studied in GPA and MPA for maintenance of remission. In WGET, 174 patients received methotrexate or cyclophosphamide for their remission and were then randomized to get Etanercept or placebo. Unfortunately, there was no significant difference in rate of sustained remission

lomatosis over a period of 6 months, in twice-daily dose. Out of these patients, 70% had never had remission of their disease. This drug was combined with either cyclophosphamide or methotrexate. During the treatment, 80% patients went into disease remission and their Birmingham Vasculitis Activity Score fell significantly. However, three patients experienced major flare despite the therapy [19, 20]. The major drawback is the increased incidence of cancer in patients treated with Etanercept. Six of 92 patients developed a solid tumor. These tumors included mucinous adenocarcinoma of colon, metastatic cholangiocarcinoma, renal cell

**3.3 Etanercept**

between Etanercept and placebo [18].

carcinoma and breast carcinoma [21].

mous cell carcinoma, leukemia and lymphomas [22].

ment and 67% experienced steroid free remission for up to 3 years [23].

medication is the higher incidence of different types of cancers.

**Study Agent Disease Outcome**

**162**

**Table 5.**

**3.4 Belimumab**

ends (clinical trials) [24].

Luqmani et al. and Stone et al.

*Etanercept trials [18–20].*

Mepolizumab is an Interleukin 5 humanized monoclonal antibody that binds to free Interleukin 5. It causes arrest of bone marrow eosinophil maturation. This monoclonal antibody is directed against Interleukin 5, which is a cytokine critical for activation of eosinophils. Mepolizumab when administered in a dose of 300 mg subcutaneously every 4 weeks, proved to be effective in prolonging disease remission, reducing the use of steroid [25].

Use of this agent has shown prompt normalization of peripheral eosinophil counts, as well as reduction in glucocorticoid usage. Two studies that showed use of Mepolizumab in EGPA, it led to decreased disease activity, normalization of eosinophil count and reduction of steroid use. However, cessation of this drug resulted in disease flare [26, 27].

Mepolizumab works by halting activation of eosinophils, acting directly on them. This biological agent is recommended in treating Churg-Strauss syndrome, although it is still under various trials. The major drawback is the disease flare caused after discontinuing the medication.
