Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.

BACKGROUND: Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS: In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS: A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS: In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

Effects of add-on montelukast on airway hyperresponsiveness in patients with well-controlled asthma - a pilot study.

OBJECTIVE: Control of airway inflammation is the cornerstone of asthma management. The aim of the present pilot study was to assess the effects of a leukotriene receptor antagonist (LTRA) added to a basic treatment of inhaled corticosteroids (ICS) and long-acting beta-agonist (LABA) on airway hyperresponsiveness, inflammation, and quality of life in well-controlled patients with asthma. RESEARCH DESIGN AND METHODS: Seventeen patients (age 18-65, 11 women) with well-controlled asthma presenting airway hyperresponsiveness to mannitol and methacholine challenge were given add-on montelukast on a stable ICS + LABA for 4 weeks. Quality of life and selected parameters of airway inflammation were measured at baseline and at study end. (ClinicalTrials.gov (NCT01725360)). RESULTS: Adding montelukast to ICS + LABA resulted in an increase in mean FEV1 (+4.5%, p = 0.057), cumulated higher dose of mannitol (+32.5%, p = 0.023) and methacholine (+17.2%, 0.237) in the provocation test, lower airway reactivity with mannitol and methacholine (response dose ratio (RDR) -50.0%, p = 0.024 and -44.3%, p = 0.006, respectively), and improved airway sensitivity to mannitol and methacholine (+12.1%, p = 0.590 and +48.0%, p = 0.129 for PD15 and PD20 FEV1, respectively). Changes in inflammation parameters (blood eosinophil count, serum eosinophil cationic protein, and exhaled nitric oxide) were consistent with these findings. Asthma-related quality of life improved significantly in all domains and overall (from 5.3 at baseline to 6.1 at the final visit, p < 0.001). The main limitation was the absence of a control group. CONCLUSION: The consistency of the changes in airway hyperresponsiveness and inflammation as well as in quality of life observed with an add-on therapy with montelukast in well-controlled asthma patients during 4 weeks suggests that residual inflammation may represent an area for further improvement of asthma control to be explored in adequately powered randomized controlled trials.

Hypersensitivity reaction against patent blue during sentinel lymph node removal in three melanoma patients.

BACKGROUND: In order to identify the sentinel lymph node (SLN) in melanoma patients intradermal injection of a radiocolloid tracer and a blue dye are commonly used. Life-threatening side effects such as allergic reactions to the injected dye have been described. We report 3 cases with systemic allergic reactions. METHODS: Three patients suffering from systemic reactions such as hypotension and rash during SLN biopsy were tested for sensitisation against patent blue and methylene blue with skin prick, scratch, and intradermal test. RESULTS: All 3 patients showed positive skin tests to patent blue confirming allergic reaction to the injected dye. In addition, all patients showed positive skin tests with methylene blue indicating immunologic cross-reactivity between patent blue and methylene blue. CONCLUSIONS: Although allergic reactions to blue dye during SLN biopsy are rare, they may be life threatening. It is important that the attending anesthetist is aware of this.