[Show abstract][Hide abstract] ABSTRACT: Purpose:
Phase 3 icatibant trials showed that most hereditary angioedema (HAE) (C1 inhibitor deficiency) acute attacks were treated successfully with one injection of icatibant, a selective bradykinin B2 receptor antagonist. We conducted a post hoc analysis of icatibant reinjection for HAE type I and II attacks in a real-world setting by using data from the Icatibant Outcome Survey, an ongoing observational study that monitors the safety and effectiveness of icatibant treatment.
Descriptive retrospective analyses of icatibant reinjection were performed on Icatibant Outcome Survey data (February 2008 to December 2012). New attacks were defined as the onset of new symptoms after full resolution of the previous attack. Potential associations between the patient and attack characteristics and reinjection were explored by using logistic regression analysis.
Icatibant was administered for 652 attacks in 170 patients with HAE type I or II. Most attacks (89.1%) were treated with a single icatibant injection. For attacks that required two or three injections, the second injection was given a median of 11.0 hours after the first injection, with 90.4% of second injections administered ≥6 hours after the first injection. Time to resolution and attack duration were significantly longer for two or three injections versus one icatibant injection (p < 0.0001 and p < 0.05, respectively). Multivariate logistic regression analysis identified sex, attack severity, and laryngeal attacks as significantly correlated with reinjection (all p ≤ 0.05). These factors did not remain predictors for reinjection when two outlier patients with distinct patterns of icatibant use were excluded.
In this real-world setting, most HAE attacks resolved with one icatibant injection. There was no distinct profile for patients or attacks that required reinjection when outliers with substantially different patterns of use were excluded. Because new attacks were not distinguished from the recurrence of symptoms, reinjection rates may be slightly higher than shown here. Clinical trial identifier: NCT01034969.
[Show abstract][Hide abstract] ABSTRACT: This retrospective multicentre analysis from the Psoriasis Registry Austria (PsoRA) was conducted to determine drug effectiveness and survival of anti-tumour necrosis factor alpha (anti-TNF-α) agents in patients with moderate-to-severe chronic plaque psoriasis over a 9-year period. Data on 1019 treatment cycles with adalimumab (n = 460), etanercept (n = 501), and/or infliximab (n = 58) administered to 827 patients (272 women, 555 men) were available for analysis. Compared with etanercept, adalimumab and infliximab showed superior short-term effectiveness. Intention-to-treat-calculated median drug survivals for adalimumab (1,264 days) and etanercept (1,438 days) were similar to each other (p = 0.74), but significantly superior to that of infliximab (477 days) (p = 7.0e-07 vs. adalimumab and p=2.2e-07 vs. etanercept, respectively). Their drug survival rates at 36 months were 51.6%, 56.0%, and 22.6%, respectively. Survival rates correlated significantly with effectiveness for adalimumab and etanercept, but not for infliximab.
[Show abstract][Hide abstract] ABSTRACT: Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and above all patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma co-morbidity (ARIA 2015 revision). It is one of the implementation systems of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and the e-Allergy screening (Premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:
Icatibant, a selective bradykinin B2 receptor antagonist for the treatment of acute hereditary angio-oedema (HAE) attacks in adults, can be administered by health care professionals (HCPs) or self-administered. This analysis compared characteristics and outcomes of acute HAE attacks treated with self-administered and HCP-administered icatibant in a real-world setting.
The Icatibant Outcome Survey (Shire, Zug, Switzerland; NCT01034969) is an international observational study monitoring the safety and effectiveness of icatibant treatment. Descriptive retrospective analyses were performed (February 2008 to December 2012).
Icatibant was used in 652 attacks in 170 patients with HAE type I/II. Most icatibant injections were self-administered (431/652, 68.5%). The proportion of self-treated attacks increased over time (40.3% in 2009 vs. 89.7% in 2012). The median time to administration was significantly shorter in self- versus HCP-treated attacks (1.5 vs. 2.4 h; p = 0.016). Earlier treatment (<2 h after onset) was significantly associated with a shorter median time to resolution (2.5 vs. 5.0 h; p = 0.032) and attack duration (3.0 vs. 14.0 h; p < 0.0001), regardless of administration method. Patients self-administered icatibant for attacks of all severities; overall, 34.7% of severe and 30.2% of very severe attacks were HCP treated. Logistic regression analysis did not find use of long-term prophylaxis, attack location or gender to be predictive for self-administration.
The proportion of HAE attacks treated with self-administered icatibant increased over time. Patients successfully self-administered icatibant for a wide variety of HAE attacks, demonstrating that icatibant is generally well tolerated and effective for self-administration. Self-administration of icatibant provides a complementary option to HCP administration, enabling optimization of patient care.
International Archives of Allergy and Immunology 06/2015; 167(1):21-8. · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Drug hypersensitivity reactions are unpredictable adverse drug reactions. They manifest either within 1–6 h following drug intake (immediate reactions) with mild to life-threatening symptoms of anaphylaxis, or several hours to days later (delayed reactions), primarily as exanthematous eruptions. It is not always possible to detect involvement of the immune system (allergy). Waiving diagnostic tests can result in severe reactions on renewed exposure on the one hand, and to unjustified treatment restrictions on the other. With this guideline, experts from various specialist societies and institutions have formulated recommendations and an algorithm for the diagnosis of drug allergies.
The key principles of diagnosing allergic/hypersensitivity drug reactions are presented. Where possible, the objective is to perform allergy diagnostics within 4 weeks–6 months following the reaction. A clinical classification of symptoms based on the morphology and time course of the reaction is required in order to plan a diagnostic work-up. In the case of typical symptoms of a drug hypersensitivity reaction and unequivocal findings from validated skin and/or laboratory tests, a reaction can be attributed to a trigger with sufficient confidence. However, skin and laboratory tests are often negative or insufficiently reliable. In such cases, controlled provocation testing is required to clarify drug reactions. This method is reliable and safe when attention is paid to indications and contraindications and performed under appropriate medical supervision. The results of the overall assessment are discussed with the patient and documented in an „allergy passport“ in order to ensure targeted avoidance in the future and allow the use of alternative drugs where possible.
Allergo Journal International 05/2015; 24(3):94-105. DOI:10.1007/s40629-015-0052-6
[Show abstract][Hide abstract] ABSTRACT: Patients with elevated basal tryptase (sBT) >15μg/L and anaphylaxis may have an underlying mastocytosis. A monoclonal mast cell activation syndrome (MMAS) with aberrant mast cells (MC) at extracutaneous sites has been described in patients with severe hypotension or anaphylaxis.
Since MC in patients with elevated sBT might be altered in the skin as well, we studied MCs in normal neck skin in anaphylaxis and urticaria patients with elevated sBT.
A mean of 93.1 (SD 19.1) MC/mm² was counted in normal neck skin in 14 patients with anaphylaxis, 84.0 (SD 13.6) in 7 patients with urticaria, 142.0 (SD 24.0) in 2 patients with eczema, 124.4 (SD 43.2) in 5 patients with systemic mastocytosis (SM) in comparison to autopsy skin (39.1 MC/mm², SD 12.4). In 5/14 (35.7%) of the anaphylaxis and 3/5 (60%) SM patients more than 25% of MCs were spindle shaped and expressed CD 25 antigen.
We could show for the first time that the normal skin can harbour clonal MC in anaphylaxis patients. Analogous to the criteria for mastocytosis, we suggest a skin score criteria including an elevated number of MC, spindle shape, CD 25 expression, c-Kit mutation and sBT values >20μg/L. In patients with anaphylaxis and elevated sBT skin should be biopsied and, as with the approach for mastocytosis diagnosis in the bone marrow, MC should be analysed for their number, clonality and c-Kit mutation. This approach should be confirmed in further studies. Patients with aberrant skin MC should be handled as mastocytosis patients. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Mastocytosis is a clonal disorder characterized by the proliferation and accumulation of mast cells (MC) in different tissues, with a preferential localization in skin and bone marrow (BM). The excess of MC in mastocytosis as well as the increased releasability of MC may lead to a higher frequency and severity of immediate hypersensitivity reactions. Mastocytosis in adults is associated with a history of anaphylaxis in 22-49%. Fatal anaphylaxis has been described particularly following hymenoptera stings, but also occasionally after intake of drugs such as non-steroidal antiinflammatory drugs, opioids and in the perioperative setting. However, data on the frequency of drug hypersensitivity in Mastocytosis and vice-versa are scarce and evidence for an association appears to be limited. Nevertheless, clonal MC disorders should be ruled out in cases of severe anaphylaxis: basal serum tryptase determination, physical examination for Cutaneous Mastocytosis lesions and clinical characteristics of anaphylactic reaction might be useful for differential diagnosis. In this position paper, the ENDA group performed a literature search on immediate drug hypersensitivity reactions in clonal MC disorders using MEDLINE EMBASE, and Cochrane Library, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: In Germany over 2.5 million employees have an increased risk of skin cancer due to their occupational exposure to natural UV-irradiation. The medical consultation board “Occupational diseases” of the Ministry of Labor and Social affairs has investigated the association between occupational UV-irradiation and skin cancer risk and recommends to add the following new occupational disease into the appendix1 of the German ordinance on occupational diseases: “Squamous cell carcinoma and multiple actinic keratosis due to natural UV-irradiation”.In this article we report in the view of the German Society of Occupational and Environmental Dermatology (ABD) and the German Statutory accident insurance (DGUV), whose criteria have to be fulfilled for the notification and recognition of an occupational skin cancer due to natural UV-irradiation.
Journal der Deutschen Dermatologischen Gesellschaft 12/2014; 12(12). DOI:10.1111/ddg.12537 · 2.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ZusammenfassungIn Deutschland sind über 2,5 Millionen Arbeitnehmer aufgrund ihrer beruflichen Tätigkeit als Outdoor-Worker im besonderen Maße gegenüber natürlicher UV-Strahlung exponiert. Der Ärztliche Sachverständigenbeirat „Berufskrankheiten“ beim Bundesministerium für Arbeit und Soziales hat den Zusammenhang zwischen beruflicher UV-Strahlung und Hautkrebs geprüft und empfohlen, in die Anlage1 zur Berufskrankheiten-Verordnung folgende neue Berufskrankheit aufzunehmen: „Plattenepithelkarzinome oder multiple aktinische Keratosen der Haut durch natürliche UV-Strahlung“.Es wird aus Sicht der Arbeitsgemeinschaft für Berufs- und Umweltdermatologie (ABD) in der Deutschen Dermatologischen Gesellschaft (DDG) und der Deutschen Gesetzlichen Unfallversicherung (DGUV) dargestellt, welche Voraussetzungen für eine Meldung und Anerkennung einer beruflichen Hautkrebserkrankung durch natürliche UV-Strahlung erfüllt sein müssen.
Journal der Deutschen Dermatologischen Gesellschaft 12/2014; 12(12). DOI:10.1111/ddg.12537_suppl · 2.05 Impact Factor