“'It is a very fortunate historical period both for patients with eosinophilic granulomatosis with polyangiitis (EGPA) and for us doctors, because a real revolution is underway. If until a few years ago patients were treated with generous doses of cortisone associated with immunosuppressants for classic autoimmune manifestations, but they were unable to effectively and safely control the eosinophilic manifestations, therefore the entire respiratory component typical of these patients, the real revolution is being able to have a drug like mepolizumab today, which blocks interleukin 5 (IL-5)”. This was said by Roberto Padoan, medical director, rheumatologist, head of the Vasculitis Center of the Padua University Hospital, at the end of an ECM dedicated to EGPA, an eosinophilic disease also known as Churg Strauss syndrome, a rare pathology which every year, in Italy, it has between 2.5 and 7 new diagnoses per million inhabitants
“EGPA is characterized by the presence of 2 components – explains Padoan – In fact, we recognize a pathway mediated by type 2 inflammation (Th2), where the central role is mediated by IL-5” with the excessive activation of a type of white blood cells, “eosinophils, and the typical eosinophilic manifestations consisting, for example, of chronic rhinosinusitis with polyposis, asthma, but also of sometimes allergic-like symptoms on the skin with wheals and urticaria-like. The other way, so-called of type 1 (Th1), is instead mediated by true autoimmunity with manifestations such as vasculitis, which is localized at the level of the walls of small and medium-sized blood vessels, with different symptoms depending on the body area involved. Sometimes these two pathways coexist and it is difficult to separate them.” In this context, “interleukin 5, in addition to being the main driver of the type 2 pathway, by stimulating the action of B lymphocytes, also contributes to the activation of the type 1 pathway”.
Diagnosis is made difficult by the extreme heterogeneity of the disease which has very different manifestations both between patients and within the same patient, depending on the phases of the disease. “Historically, the disease was considered to have 3 phases – explains the rheumatologist – The first, erroneously defined as allergic, somewhat simulates allergic diseases with asthma and rhinosinusitis, even in the absence of true allergy. The second phase is characterized by the increase in circulating eosinophils. In the third phase, vasculitis takes over with the most severe manifestations of the disease. Today we know that, in some patients, the 3 phases can also occur all together -50 years – he specifies – are the respiratory symptoms of the upper and lower tracts and a non-allergic asthma that is difficult to control and then associated with an increase in eosinophils. The real bell then goes off when, together with these, more systemic symptoms typical of the disease appear autoimmune such as inflammatory joint pain, weight loss, low-grade fever”.
The arrival of anti-interleukin 5 in therapy is “a revolution” because, “by turning off what is the main driver of type 2 inflammation, eosinophilic manifestations are rapidly reduced and it is also possible to partially control those of the autoimmune pathway (type 1). It is a revolution – explains the specialist – because mepolizumab is a safe drug, compared to immunosuppressants, because it is an immunomodulator that does not lower patients' defenses, therefore it does not expose them to a greater infectious risk. We have seen this not only in the data from the clinical trial, but also in real-life studies. Furthermore, its safety allows us to use it also in combination with conventional immunosuppressants, at least in the most severe forms of the disease. , alone, in non-severe or moderate forms”. It is an “extremely modular therapy tailored to the patient's needs. We therefore have 2 advantages: the control of respiratory symptoms, which have a great impact on the quality of life, and the effectiveness which allows us to reduce, even suspend, in some patients , cortisone which we know is often associated with further side effects that impact patients' quality of life.”
The data from real life studies on the effectiveness of mepolizumab, a drug included in the latest Eular recommendations, have not only “confirmed the results of the registered studies, but are, perhaps, even more optimistic – underlines the rheumatologist – because the drug is proving to be effective and safe in these patients even at different times of the disease. The Egpa study group”, of which Padoan is a member, “brings together some of the most expert specialists at an international level and works on large-scale studies by creating cohorts of patients to investigate, from real life, specific characteristics of the disease, such as the presence of other pathologies, and guide therapeutic choices and future recommendations”.
In this work “we are recently also including the patient association, Apacs (Churg Strauss Syndrome Patient Association or EGPA) which is also learning to collaborate with the various other European patient organisations. At the moment – observes Padoan – we do not know, for example, how effective it is in early treatment. The data from the registration trials in fact included patients with long-lasting disease. The objective for the future will be to treat patients more and more early precisely to reduce the accumulation of damage linked to the disease. on the other hand, we do not know how long we can continue with the therapy. The trial highlights that, if we suspend it after 52 weeks, the disease tends to return. Inevitably, to date, long-term treatment is therefore envisaged, but we do not actually know for how long continue,” which could be explained with real-life data.
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