Immunomodulation profile of the biosimilar trastuzumab MYL-1401O in a bioequivalence phase I study.

The initial Phase-I single centre, single dose, randomized, double-blind, cross-over study was planned to assess the pharmacokinetic and pharmacodynamic bioequivalence of the trastuzumab biosimilar (MYL-1401O) compared to the reference Herceptin®. Their respective immunomodulation profile presented in this paper involved healthy males receiving a single infusion of both monoclonals, separated by a washout period. Sixty parameters were assessed in total, including serum cytokines, peripheral mononuclear cell (PBMC) subsets, cell activation and response to recall antigens and mitogen, pre- and post- infusion, as well as a cytokine release assay (CRA) at baseline. Trastuzumab infusion induced a transient and weak peak of serum IL-6 at 6 h, and a modulation of mononuclear cell subset profile and activation level, notably CD16 + cells. Except for CD8 + T cells, there were no significant differences between Herceptin® and MYL-1401O. In CRA, PBMC stimulated with MYL-1401O or Herceptin® similarly secreted IL-6, TNF-α, IL-1ß, GM-CSF, IFN-γ, and IL-10, but no or low level of IL-2. Interestingly, some observed adverse events correlated with IL-2 and IFN-γ in CRA. MYL-1401O exhibited a very similar immunomodulation profile to Herceptin®, strongly supporting its bioequivalence. This approach may thus be included in a proof-of-concept study. CRA may be used as a predictive assay for the evaluation of clinical monoclonals.

Non-immediate drug hypersensitivity reactions secondary to intravitreal anti-vascular endothelial growth factors.

PURPOSE: To describe a series of non-immediate drug hypersensitivity reactions after intravitreal anti-vascular endothelial growth factors (anti-VEGFs). PATIENTS AND METHODS: Retrospective report of 6 patients with cutaneous non-immediate drug hypersensitivity reactions following intravitreal anti-VEGF injections, 4 after ranibizumab, 1 after bevacizumab and 1 after aflibercept. RESULTS: Clinical manifestations ranged from mild maculopapular rash, purpura to severe generalized erythroderma, with or without systemic involvement such as microscopic hematuria and proteinuria or fever. In two out of the six patients, reintroduction of either the same or an alternative anti-VEGF drug did induce a recurrence of the drug hypersensitivity reaction, while 4 patients showed no recurrence. CONCLUSION: Cutaneous non-immediate drug hypersensitivity reactions secondary to intravitreal anti-VEGF may occur. Continuation of the same drug or switch to another anti-VEGF may either induce recurrence or be well supported by the patient. The decision of drug discontinuation should be guided by the severity of the disease.

Treatment of allergic rhinitis during and outside the pollen season using mobile technology. A MASK study.

BACKGROUND: The analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross-sectional real-world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users. METHODS: The Allergy Diary-MASK-air-mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1-antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis. RESULTS: 9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1-antihistamines. CONCLUSIONS: This study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year.

[Subcutaneous immunoglobulin and support program: what level of interest of patients?]. / Immunogtobulines sous-cutanées et programme d'accompagnement: quel est l'intérêt des patients?

Two different routes of administration exist for the immunoglobulin therapy: intravenous (Ig IV - monthly administration in medical setting) and subcutaneous (Ig SC - weekly self-administration at home). According to the literature, efficacy and safety are similar,. but Ig SC could improve quality of life and treatment satisfaction. The Policlinique Médicale Universitaire of Lausanne has developed an interdisciplinary program for the long-term support of Ig SC patients. Moreover, it conducted an exploratory survey interviewing Ig IV patients about their interest for Ig SC: patients interested judged less favourably efficacy and/or tolerance of Ig IV and considered that Ig SC would improve their motivation for treatment and its impact on their private and professional life.

EAACI IG Biologicals task force paper on the use of biologic agents in allergic disorders.

Biologic agents (also termed biologicals or biologics) are therapeutics that are synthesized by living organisms and directed against a specific determinant, for example, a cytokine or receptor. In inflammatory and autoimmune diseases, biologicals have revolutionized the treatment of several immune-mediated disorders. Biologicals have also been tested in allergic disorders. These include agents targeting IgE; T helper 2 (Th2)-type and Th2-promoting cytokines, including interleukin-4 (IL-4), IL-5, IL-9, IL-13, IL-31, and thymic stromal lymphopoietin (TSLP); pro-inflammatory cytokines, such as IL-1ß, IL-12, IL-17A, IL-17F, IL-23, and tumor necrosis factor (TNF); chemokine receptor CCR4; and lymphocyte surface and adhesion molecules, including CD2, CD11a, CD20, CD25, CD52, and OX40 ligand. In this task force paper of the Interest Group on Biologicals of the European Academy of Allergy and Clinical Immunology, we review biologicals that are currently available or tested for the use in various allergic and urticarial pathologies, by providing an overview on their state of development, area of use, adverse events, and future research directions.

[Allergic rhinitis: still insufficiently responsive to therapies]. / Allergologie--immunologie clinique. (1.) Rhinite allergique: une efficacité thérapeutique encore insuffisante.

Allergic rhinitis is still in need of efficient therapies, in particular for its most severe manifestations, including polyposis, and despite rather satisfying treatments for the benign to moderate presentations. A better understanding of its mechanisms, although still incomplete, of its phenotypes and endotypes, a better evaluation of its severity with adequate scoring systems, and of its risk factors pave the way to innovative but eagerly awaited therapies.

[Food allergy or food intolerance?]. / Allergie ou intolérance alimentaire?

Adverse food reactions can be classified into two main categories depending on wether an immune mechanism is involved or not. The first category includes immune mediated reactions like IgE mediated food allergy, eosinophilic oesophagitis, food protein-induced enterocolitis syndrome and celiac disease. The second category implies non-immune mediated adverse food reactions, also called food intolerances. Intoxications, pharmacologic reactions, metabolic reactions, physiologic, psychologic or reactions with an unknown mechanism belong to this category. We present a classification of adverse food reactions based on the pathophysiologic mechanism that can be useful for both diagnostic approach and management.

[Shingles vaccine: which recommendations in 2014?]. / Vaccin contre le zona: quelles recommandations en 2014?

Zostavax, a live attenuated vaccine against shingles (herpes zoster) has been available in Switzerland since 2008. In a population aged 60 and over, evidence suggests the vaccine effectively reduces the incidence of shingles and some of its corresponding complications. More importantly, in terms of public health, vaccination appears to reduce the burden of illness and be pharmaco-economically viable. Despite being part of the vaccination programmes in the United States and several European countries, the vaccine is not yet part of the Swiss vaccination programme. Should Switzerland follow suit by incorporating Zostavax into their vaccination policy?

[Granulomatous lymphocytic interstitial lung disease in common variable immunodeficiency]. / Pneumopathie interstitielle granulomato-lymphocytaire dans l'immunodéficience commune variable.

Common variable immunodeficiency (CVID) is the most frequent primary immune deficiency. Recurrent infections are classical consequences of CVID, but their impact has been largely reduced by immunoglobulin replacement. CVID is also associated with various inflammatory and autoimmune manifestations resulting from abnormal cellular immunity. The lungs are especially affected by a recently described entity called granulomatous lymphocytic interstitial lung disease (GLILD). GLILD currently constitutes an important cause of morbidity and mortality in these patients. It is distinct from bronchiectasis secondary to recurrent infections, and presents similarities but also striking differences with sarcoidosis.

[Systemic and neurological uses of immunosuppressive agents]. / Immunosuppresseurs: usages systémiques et neurologiques.

Involvement of the central or peripheral nervous system, frequently present in systemic inflammatory immune disorders, has to be considered a severe threat and requires aggressive immunosuppressive treatment to achieve rapid remission. This is usually obtained with high-dose systemic corticosteroids combined with cyclophosphamide. Once remission is obtained, immunosuppressive agents with a more favorable safety profile are needed to exert a corticosteroid-sparing effect and minimize adverse events. New therapeutic approaches are currently developed to treat autoimmune diseases, mostly linked to the definition of new indications for biological agents such as TNF-alpha antagonists and rituximab.

[Management of adverse events induced by TNFalpha blocking agents]. / Allergologie: 1. Anti-TNFalpha: effets indésirables et implications pratiques.

TNFalpha blocking agents are effective and essential tools in the management of many inflammatory conditions including rheumatoid arthritis, spondylarthropathies and chronic inflammatory bowel disease. With time, some known side-effects have gained in importance and others have appeared. This article focuses on the potential risks of infection and autoimmunity induced by TNFalpha blocking agents and on the strategy to prevent and treat such adverse events.

[Systemic mastocytosis--new therapeutic strategies]. / Allergologie: 2. Mastocytose systémique--nouvelles stratégies thérapeutiques.

Systemic mastocytosis is characterized by an excessive proliferation of mast cells and their accumulation in different organs. Avoidance of trigger factors leading to anaphylaxis is a general measure valid for all forms of mastocytosis. A premedication is necessary in case of surgery, anesthesia or administration of radiocontrast agents. Symptomatic treatment comprises antihistamines, anti-leukotrienes, proton pump inhibitors and topical corticosteroids. Indolent mastocytosis with refractory symptoms, the rare cases of aggressive mastocytosis with organ dysfunction and the even rarer mast cell leukemia require cytoreductive therapy. First-line agents are interferon alpha 2b and imatinib, a tyrosine kinase inhibitor. To date there is no curative treatment.

[Interests of recombinant allergens in the practice of allergy]. / Allergologie: 3. Intérêts des allergènes recombinants dans la pratique de l'allergologie.

Compared to total allergenic extracts, recombinant allergens available for specific IgE measurement represent an important advance in the diagnosis and treatment of IgE-mediated allergies. Recombinant allergens lead to define the sensitization profile of allergic patients, to identify markers of sensitization and to understand better polysensitivities related to cross-reactions and markers of severity of allergic reactions. They also contribute to the decision to establish tolerance induction (allergen specific immunotherapy) and the optimal selection of the allergenic composition of the vaccine.

[Allergy to beta-lactam antibiotics]. / Allergie aux beta-lactamines.

Beta-lactam antibiotics allergies are common. Up to 10% of the population describe a former allergy to penicillins. However only 10 to 15% of these individuals are actually allergic. In most cases, beta-lactam antibiotics will be avoided and replaced by other antibiotics such as quinolones. This fear of a serious allergic reaction has an economic impact and may lead to the emergence of antibiotic resistance. A thorough allergic work-up can accurately determine true allergic patients. Most of the patients with a proven allergy will be able to tolerate other antibiotics belonging to the beta-lactam family. This article focuses on the management of beta-lactam allergic patients.

[Sjögren's syndrome: a new approach to treatment]. / Syndrome de Sjögren: enfin une nouvelle approche de traitement.

Södgren's syndrome treatment has essentially been based on symptomatic approach and has been of limited efficacy. Novel biological therapies targeting B cells, a key player in the pathophysiology of the syndrome, have recently been tested in controlled clinical trials and raise the hope of improving glandular and extraglandular manifestations of Söigren's syndrome.