Mepolizumab

Mepolizumab is a humanized monoclonal antibody that binds to the cytokine interleukin-5. IL-5 plays an important role in the development, activation, differentiation and survival of eosinophils. The IL-5 antibody reduces eosinophilic granulocytes in the blood and lowers the frequency of disease exacerbations induced by eosinophilic granulocytes.

Mepolizumab in eosinophilic asthma: Mepolizumab is administered for the treatment of "eosinophilic asthma". About 40% of all patients with COPD have eosinophilia. The exact causes are not known.

The IL-5 antibody is used in combination with other drugs in patients whose asthma is severe and is not adequately controlled by prior treatment. In several randomised studies, the IL-5 antibody has been shown to be able to reduce the number of exacerbations in patients with chronic obstructive pulmonary disease (COPD) with eosinophilic phenotype. The dosage was 100mg s.c. every 4 weeks.

Mepolizumab in eosinophilic granulomatosis with polyangiitis: In a randomized, multicenter, double-blind phase III study, mepolizumab was used in eosinophilic granulomatosis with polyangiitis over a period of 52 weeks (dose 300mg s.c. every 4 weeks). Under this therapy, there was a significant reduction in disease activity (reduction in recurrence rate, reduction in glucocorticoid consumption).

Mepolizumab in hypereosinophilic dermatitis: In addition to normalization of eosinophilic leukocytes and a decrease in the concentration of IL-5, TARC, ECP and eotaxin in the blood, the preparation leads to a significant reduction of itching and to an improvement of the skin symptoms of hypereosinophilic dermatitis. Furthermore, a glucocorticoid-saving effect can be expected. The preparation has been granted orphan drug status in Europe and the USA.

The most common possible adverse effects include headaches, injection site reactions, back pain and fatigue. In detail:

Infections and parasitic diseases

• Common: lower respiratory tract infection, urinary tract infection, pharyngitis

Diseases of the immune system Hypersensitivity reactions

• Rare: anaphylactic reactions like urticaria, angioedema, bronchospasm, hypotension. These reactions generally occur within hours of administration, but in some cases are delayed (i.e. typically within a few days). These reactions may also occur for the first time after long-term use

Diseases of the nervous system:

• Very common: headache

Diseases of the respiratory tract, chest and mediastinum

• Common: Nasal congestion

diseases of the gastrointestinal tract

• Frequently: Pain in the upper abdomen

Diseases of the skin and subcutaneous cell tissue

• Common: eczematous reactions

Skeletal muscle, connective tissue and bone diseases

• Frequent: Back pain

General illnesses and complaints at the place of administration

• Frequent: fever and uncharkateristic reactions at the injection site

Nucala®

1. Bel EH et al (2014) Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 371: 1189-1197.
2. Wechsler ME et al (2017) Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med 376:1921-1932.