The first targeted therapy for sickle cell anemia that prevents vaso-occlusive crises, serious events characterized by rapid evolution and high mortality, arrives in Italy. It is crizanlizumab to which Aifa has recognized the requirement of conditioned innovation. Sickle cell anemia in Europe affects about 50,000 people and in Italy it is considered a rare haematological disease due to the difficulty of tracing and diagnosis: those registered with a serious clinical picture are about 2,500-2,800, although according to experts there is an important submerged about twice as many patients.
What are vaso-occlusive crises
Vaso-occlusive crises (vaso occlusive crises – VOC) are unpredictable events and can represent real health emergencies due to their rapid evolution and high mortality. As evidenced by the international Sway (Sickle Cell World Assessment Survey) research, 91% of patients report at least one vaso-occlusive crisis in the 12 months prior to the survey. Overall, patients reported an average of 5.3 VOCs in the previous 12 months, most of which managed with medical intervention.
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The new drug
The Italian Medicines Agency (Aifa) has approved the reimbursement of crizanlizumab for the prevention of recurrent vaso-occlusive crises in patients with sickle cell disease aged sixteen and over who presented at least two VOCs over the course of twelve months previous. The new drug can be administered as add-on therapy to hydroxyurea / hydroxycarbamide (HU / HC) or as monotherapy in patients for whom HU / HC is inappropriate or inadequate, i.e. has insufficient efficacy or tolerability and insufficient compliance problems. Studies for the approval of the drug in pediatric age are also underway and three Italian centers are also involved.
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Clinical studies
The approval of reimbursement by Aifa follows the positive opinion of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) and the same approval by the EMA, issued in October 2020 based on the results of the SUSTAIN clinical trial, which showed that crizanlizumab significantly reduced the median annual rate of VOC by 45%. Reductions in VOC frequency have been observed among patients regardless of sickle cell anemia genotype and / or use of hydroxyurea / hydroxycarbamide (HU / HC). There was a more than double increase in the percentage of patients without VOC who completed the study, compared to placebo. In the same study, crizanlizumab was shown to reduce the median annual rate of hospitalization days by 42%. On the basis of clinical studies, crizalizumab also has a favorable safety profile: in fact, similar adverse events were found between patients treated with the therapy and the placebo group.
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How it works
Crizanlizumab, designated orphan drug, binds to P-selectin, a cell adhesion protein that plays a central role in multicellular interactions that cause vaso-occlusion in sickle cell disease. By binding to P-selectin on the surface of the endothelium and activated platelets, crizanlizumab blocks interactions between endothelial cells, platelets, red blood cells and leukocytes by preventing vasocclusion. “The approval of the reimbursement in Italy of the first targeted therapy for recurrent vaso-occlusive crises represents very important news both for the patient community and for clinicians – he commented Lucia De Franceschi, associate professor of Internal Medicine, Aoui Verona and University of Verona. “Crizanlizumab, thanks to its peculiar mechanism, acts directly on chronic inflammatory vasculopathy, which underlies the numerous clinical complications of patients with sickle cell syndrome. Furthermore, crizanlizumab has a profile of uniqueness that makes it very interesting for us doctors because it could help us manage even those patients who have failed or do not accept therapies considered standard “.
The narrative medicine project
This pathology can have a very strong impact on the life of those who suffer from it (from the emotional sphere to the professional or scholastic one) as emerges from the SCAN (Sickle Cell Anemia Narrations) narrative medicine project of the ISTUD Foundation, promoted by Novartis. “These patients – he explains Raffaella Colombatti, Coordinator of the Red Blood Cell Pathologies Working Group, AIEOP and Researcher at the University of Padua – have a life completely devastated by the disease both for school attendance, for professional life but also in social life. In fact, in periods when symptoms occur, people with sickle cell anemia find it difficult to concentrate and carry out their study or work activities. “On average, they are absent 39 days from their work or school. of daily life, such as shopping for example, are often compromised by the disease. In addition, more than 50% of people with sickle cell anemia carry out transfusions at least once a month. However, despite these difficulties, the narratives also show the great desire to make it through these people with the right care and assistance.
The difficulty of diagnosis
Compared to the diagnosis, in 43% of cases it is carried out and communicated by a center other than the one in which one is currently being treated, often represented by a pediatric center. However, there are those who arrived at the diagnosis after a pilgrimage between several treatment centers (28%). In a few cases, the diagnosis was made following a traumatic event during childbirth, or in the same center where one is still being treated. Furthermore, in one third of the reported cases (33%) it is specified how initially a diagnosis other than sickle cell anemia was made, confused with other forms of anemia – in particular Beta Thalassemia – or other conditions such as growth pains and rheumatism .
Sickle cell anemia
Sickle cell anemia is one of the most common genetic blood disorders in the world. It is characterized by the alteration of the shape and physical properties of red blood cells and by a greater adhesiveness of the different blood cells than usual. In certain situations, these cells become activated and adhere to each other and to the inner wall of blood vessels, forming clusters that can slow, block and reduce the flow of blood and oxygen, causing damage to blood vessels and organs. This consequently leads to recurrent and unpredictable acute crises of painful vascular occlusion, also called vaso-occlusive crises responsible for organ damage. The painful crises typical of sickle cell anemia lead to acute and long-term complications, disrupting the lives of patients physically, socially and emotionally. The epidemiological data of this disease are not clear and experts believe that there are many submerged cases: “Currently in Sicily we have a register since 1984 which identifies a presence of this disease in 2019 of 658 cases of sickle cell anemia”, he declares Aurelio Maggio, Franco and Piera Cutino Hematology Campus, V. Cervello Hospital, Palermo. “We live in a dynamic social context whereby the populations follow the economic flows and move in a South-North direction taking with them diseases. Due to its rarity and ability to manifest itself acutely or in some cases not to occur, sickle cell anemia is often not diagnosed, especially in Italian regions that have not yet had contact with patients of this type. Awareness and awareness must be increased and the knowledge of this disease “.
How it is transmitted
People with sickle cell anemia have inherited two abnormal copies of the hemoglobin gene from their parents. Those with “sickle cell trait” (also called “carriers”) have inherited an abnormal gene and a normal gene. Sickle cell trait can be asymptomatic, but individuals with the disease can pass it on to their children. If both parents have the trait, their children are 25% likely to have sickle cell disease, 50% to have sickle cell trait, and 25% to have two normal genes or have no sickle cell trait or disease. sickle cell anemia. A simple blood test can determine if a person is a carrier of the sickle cell trait.
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