Mepolizumab add-on therapy in a real world cohort of patients with severe eosinophilic asthma: response rate, effectiveness, and safety.

Introduction: Severe eosinophilic asthma is an incapacitating disease. Mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, proved to be effective as an add-on therapy in patients with severe eosinophilic asthma. However, only data from randomized controlled trials are available and real world data are lacking.Methods: A retrospective observational longitudinal study was conducted in a real world cohort of patients with severe eosinophilic asthma treated with mepolizumab. The primary objective was to determine response rate, based on a global evaluation of treatment effectiveness by the treating pulmonologist. Secondary objectives were to assess exacerbation frequency, systemic maintenance glucocorticoid usage, Asthma Control Questionnaire (ACQ), lung function, and adverse events.Results: Seventy-eight patients were included. Treatment with mepolizumab was considered beneficial and was therefore continued in 75.6% of patients 12 months from the initiation of mepolizumab. The most common reason for drop-out was insufficient response. Secondary objectives: 12 months from the initiation of mepolizumab there was a decrease of 3.2 (CI 2.5-4.1; p < 0.001) severe asthma exacerbations per year, a decrease of ACQ of 0.80 points (CI 0.49-1.12; p < 0.001), and an increase of 3.7 (CI 0.3-7.2; p = 0.034) percent of predicted FEV1 compared to baseline. At baseline 51.3% of patients were treated with systemic glucocorticoid maintenance therapy, compared to 15.4% (p < 0.001) of patients 12 months from the initiation of mepolizumab. No serious adverse events considered to be related to mepolizumab were reported.Conclusion: This study confirms that mepolizumab add-on therapy is effective and safe in a real world cohort of patients with severe eosinophilic asthma.

Biomarkers in Sarcoidosis: Beginning of a New Era?

At present, no biomarker exists which is truly specific for sarcoidosis and the ones available have modest sensitivity and specificity. The clinical context should dictate the choice of biomarker(s) used to address different clinical questions such as diagnosis, monitoring disease activity or monitoring response to treatment. In the future, in addition to known serum biomarkers, it seems fruitful to further explore a possible role of imaging, exhaled air and even biopsy-related biomarkers in sarcoidosis to guide clinical management.

The influence of green tea extract on nintedanib's bioavailability in patients with pulmonary fibrosis.

Nintedanib is an oral small-molecule kinase inhibitor and first-line treatment for idiopathic pulmonary fibrosis. Nintedanib is a substrate of the drug efflux transporter ABCB1. Green tea flavonoids --especially epigallocatechin gallate (EGCG)-- are potent ABCB1 modulators. We investigated if concomitant administration of green tea extract (GTE) could result in a clinically relevant herb-drug interaction. Patients were randomized between A-B and B-A, with A being nintedanib alone and B nintedanib with GTE. Both periods lasted 7 days, in which nintedanib was administered twice daily directly after a meal. In period B, patients additionally received capsules with GTE (500 mg BID, >60% EGCG). Pharmacokinetic sampling for 12 h was performed at day 7 of each period. Primary endpoint was change in geometric mean for the area under the curve (AUC0-12 h). A linear mixed model was used to analyse AUCs and maximal concentration (Cmax). In 26 included patients, the nintedanib AUC0-12 h was 21% lower (95% CI -29% to -12%; P < 0.001) in period B (with GTE) compared to period A. Cmax did not differ significantly between periods; - 14% (95% CI -29% to +4%; P = 0.12). The detrimental effect was predominant in patients with the ABCB1 3435 C>T wild type variant. No differences in toxicities were observed. Exposure to nintedanib decreased with 21% when administered 60 min after GTC for only 7 days. This is a statistically significant interaction which could potentially impair treatment efficacy. Before patients and physicians should definitely be warned to avoid this combination, prospective clinical validation of an exposure-response relationship is necessary.

Developments in lung transplantation over the past decade.

With an improved median survival of 6.2 years, lung transplantation has become an increasingly acceptable treatment option for end-stage lung disease. Besides survival benefit, improvement of quality of life is achieved in the vast majority of patients. Many developments have taken place in the field of lung transplantation over the past decade. Broadened indication criteria and bridging techniques for patients awaiting lung transplantation have led to increased waiting lists and changes in allocation schemes worldwide. Moreover, the use of previously unacceptable donor lungs for lung transplantation has increased, with donations from donors after cardiac death, donors with increasing age and donors with positive smoking status extending the donor pool substantially. Use of ex vivo lung perfusion further increased the number of lungs suitable for lung transplantation. Nonetheless, the use of these previously unacceptable lungs did not have detrimental effects on survival and long-term graft outcomes, and has decreased waiting list mortality. To further improve long-term outcomes, strategies have been proposed to modify chronic lung allograft dysfunction progression and minimise toxic immunosuppressive effects. This review summarises the developments in clinical lung transplantation over the past decade.

[DRESS syndrome as a result of sulfasalazine use]. / Het DRESS-syndroom bij gebruik van sulfasalazine.

A 24-year-old female developed DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) as a result of sulfasalazine use. The DRESS syndrome is a severe and acute hypersensitivity reaction that can be caused by a variety of drugs. The clinical presentation is diverse; the most common symptoms are fever, exanthema and lymphadenopathy. Haematologic abnormalities such as leukocytosis, accompanied primarily with eosinophilia, and sometimes atypical lymphocytes are also frequently reported. In most cases the DRESS syndrome needs no further treatment after discontinuation of the associated drug. However, 20% of patients are severely affected and the DRESS syndrome is potentially life-threatening. The patient was successfully treated with a glucocorticoid and an antihistamine.