The New Therapeutic Frontiers in the Treatment of Eosinophilic Esophagitis: Biological Drugs.

Eosinophilic esophagitis (EoE) is a multifaceted disease characterized by a wide heterogeneity of clinical manifestations, endoscopic and histopathologic patterns, and responsiveness to therapy. From the perspective of an effective approach to the patient, the different inflammatory mechanisms involved in the pathogenesis of EoE and biologics, in particular monoclonal antibodies (mAbs), targeting these pathways are needed. Currently, the most relevant is dupilumab, which interferes with both interleukin (IL)-4 and IL-13 pathways by binding IL-4 receptor α, and is the only mAb approved by the European Medicine Agency and US Food and Drug Administration for the treatment of EoE. Other mAbs investigated include mepolizumab, reslizumab, and benralizumab (interfering with IL-5 axis), cendakimab and dectrekumab (anti-IL-13s), tezepelumab (anti-TSLP), lirentelimab (anti-SIGLEG-8), and many others. Despite the undeniable economic impact of biologic therapies, in the near future, there will be room for further reflection about the opportunity to prescribe biologic agents, not only as a last-line therapy in selected cases such as patients with comorbidities involving common pathways. Although recent findings are very encouraging, the road to permanent success in the treatment of EoE is still long, and further studies are needed to determine the long-term effects of mAbs and to discover new potential targets.

Factors and co-factors influencing clinical manifestations in nsLTPs allergy: between the good and the bad.

Non-specific lipid transfer proteins (nsLTPs) are a family of plant pan-allergens that represent the primary cause of food allergies in the Mediterranean area, characterized by a wide range of clinical manifestations, ranging from the total absence of symptoms up to anaphylaxis. This wide variety of symptoms is related to the intrinsic capacity of nsLTPs to cause an allergic reaction in a specific subject, but also to the presence of co-factors exacerbating (i.e., exercise, NSAIDs, PPIs, alcohol, cannabis, prolonged fasting, menstruation, acute infections, sleep deprivation, chronic urticaria) or protecting from (i.e., co-sensitization to PR10, profilin or polcalcin) severe reactions. In this picture, recognizing some nsLTPs-related peculiarities (i.e., route, type and number of sensitizations, concentration of the allergen, cross-reactions) and eventual co-factors may help the allergist to define the risk profile of the single patient, in order to promote the appropriate management of the allergy from dietary advices up to the prescription of life-saving epinephrine autoinjector.

Causes of Non-Adherence to Allergen-Specific Immunotherapy: A Foundation towards a Patient-Personalized Approach.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only disease-modifying therapy for allergic conditions, resulting in a long-lasting tolerance beyond the duration of the treatment. Due to the strong relationship between the effectiveness, its optimal duration (at least three years) and the observation of the correct administration protocol, appropriate adherence to the plan of treatment represents a critical factor for the therapeutical success of AIT. METHODS: Analysis of studies about the rate of adherence in subcutaneous and sublingual immunotherapy, which are the main routes of administration of AIT. RESULTS: There are different causes leading to a premature interruption of the therapy or to it being incorrectly carried out; the most reported include erroneous expectations of the effectiveness and the adverse effects, economic issues, inconvenience and unrelated clinical conditions. CONCLUSIONS: An attentive analysis of the main causes of dropouts may be useful to improve the management of these patients and to develop new strategies for a personalized approach. These strategies should be dynamic, involving attentive communication between the physician and the patient about all the possible criticalities, especially in the initial phase of the therapy, and facilitating, as much as possible, access to healthcare providers over the course of the maintenance phase, including by exploiting technological tools.