Mepolizumab: A New Therapy for Rare Disease Hypereosinophilic Syndrome Using Monoclonal Antibodies, According to Multicenter Study – Symptoms, Manifestation, and Treatment Options Explored.

2023-05-04 15:58:39

There is another new therapy for a rare disease – thanks to monoclonal antibodies. You can read here how hypereosinophilic syndrome can now be treated.

Eosinophilic granulocytes play an important role in the immune system. In the rare hypereosinophilic syndrome (HES), however, these immune cells are produced in excessive quantities. The result can be damage to the lungs, blood formation system, heart, skin and other organs. A new active substance is now available for ad-on therapy: mepolizumab.

The incidence of hypereosinophilic syndrome is 1-2 in 200,000. Men are affected much more frequently than women (ratio m : f = 9 : 1) and the main age of onset is between 20 and 50 years of age.

How is the disease manifested?

Eosinophile are white blood cells granulocyte linewhich play an important role in innate immune functions and develop in the bone marrow from stem cells called CD34 ⁺ CD125 ⁺ express antigens. During inflammatory processes such as allergic diseases, asthma, parasites, bacteria and viruses, a release.

The term eosinophilia is used for a small increase in the AEC (absolute eosinophil count) in the blood (up to 1500/mm³) used while Hypereosinophilie (HE) an AEC greater than 1500/mm ³ for two consecutive blood draws a month apart designated. Die symptoms of HE and HES are variable. They include:

• Weakness,
• Fatigue,
• Cough,
• dyspnea and rhinitis,
• Myalgien,
• angioedema,
• Skin rash,
• Fever,
• severe tissue damage or end-organ failure.

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Leukocytosis, anemia, abnormal platelet counts, elevated levels of vitamin B12 (>1000 pg/mL) and tryptase (>12 ng/mL) represent additional changes associated with the disease are associated.

Mediators are a problem

Secondary granules contain many mediators, such as major basic protein (MBP), eosinophilic cationic protein (ECP), eosinophilic peroxidase (EPO), and eosinophil-derived neurotoxin (EDN), all of which are capable of inducing both inflammation and tissue damage. In addition, eosinophils are equipped with lipid bodies, which play a crucial role in asthma as they regulate the production of eicosanoids cause. Finally, they are potent producers of both reactive oxygen species and nitric oxide that promote antibacterial activity, while the ability to internalize respiratory syncytial (RSV) and influenza viruses has documented the role of eosinophils in the viral response. Detection of tissue-resident eosinophils showedthat they are distributed in the heart, skin, lungs and kidneys.

The stomach is also affected

Despite this observation, eosinophils are also particularly abundant in the gastrointestinal (GI) tract under the condition of homeostasis, where they are involved in various biological processes. Both beneficial and non-beneficial roles of eosinophils in the gastrointestinal tract have been postulated.

For example, gastrointestinal eosinophils can cause Eosinophil Gastrointestinal Disorders (EGIDs) and Inflammation Bowel Disease (IBD) trigger. The pathogenesis of both diseases is dependent on tissue infiltration of eosinophils, followed by accumulation of activated immune cells, such as B and T cells, and production of pro-inflammatory cytokines.

Subtype determines therapy regimen

The absolute number and biology of eosinophils are both normally controlled by type 2 cytokines such as Interleukin-5 (IL-5) affected. Therefore, IL-5 is an important therapeutic target for the treatment of eosinophil-mediated diseases.

However, the best clinical management of HES depends on the etiology and subtypes of the disease. Even when there is no known cause, HES must be treated promptly to reduce the potential morbidity that can result from organ damage. The main therapeutic options for HES patients can be divided into five groups:

• Corticosteroids,
• cytostatics,
• tyrosine kinase inhibitors,
• monoclonal antibodies (mAb) and
• Chemotherapy.

A new treatment option has recently become available: Mepolizumab. It is a fully humanized IgG monoclonal antibody that inhibits IL-5 binding to the IL-5 receptor chain and is expressed on eosinophils, thereby reducing their survival and TGF-B production be reduced. The FDA currently has this compound for severe asthma and eosinophilic granulomatosis with polyangiitis and HES authorized.

Multicenter study gives hope

A large-scale, randomized, multicenter, double-blind, placebo-controlled Phase-III-Study was conducted at 39 centers in 13 countries. The proportion of patients who had one or more relapses or who dropped out of the study was 50% lower with mepolizumab than with placebo. Similar proportions of patients in the mepolizumab and placebo groups experienced treatment-emergent adverse events (48 of 54 [89 %] versus 47 out of 54 [87 %]).

Mepolizumab treatment was also associated with a 92% reduction in blood eosinophil counts from baseline compared to placebo. The symptom of tiredness also improved significantly. “Compared to placebo, mepolizumab significantly reduced the incidence of relapses in patients with HES without identifying new safety signals,” the authors said. Another Study von Reiter et al, confirmed the success of the therapy.

Many patients with HES continue to experience flare-ups despite receiving standard therapies. The post-hoc analysis shows the added benefit of mepolizumab in addition to existing treatments, as mepolizumab was associated with a lower incidence of relapses compared to placebo in all background therapy groups. Once again, a monoclonal antibody wins the race in the treatment of rare diseases. In recent years, the group of biologics attained outstanding importance.

Image source: Bilge Şeyma Kütükoğlu, pexels