Slowing progression of rare pulmonary disease
Nintedanib (Ofev), a kinase inhibitor, was recently approved to slow the rate of decline in pulmonary function in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). It had been previously approved to treat idiopathic pulmonary fibrosis.
Nintedanib is the first FDA-approved treatment for SSc-ILD, a rare, progressive pulmonary disorder that is debilitating and life-threatening. In clinical trials, the most common adverse reactions were diarrhea, nausea, abdominal pain, vomiting, liver enzyme elevation, anorexia, headache, weight loss, and hypertension. Before therapy begins, all patients should undergo liver function testing and women of reproductive potential should have a pregnancy test and receive counseling about the risk of embryo-fetal toxicity.
The drug received Priority Review and Orphan Drug designations, which the FDA grants to encourage the development of drugs for rare diseases.
Source: US Food and Drug Administration. FDA approves first treatment for patients with rare type of lung disease. News release. September 6, 2019.
Renal impairment does not affect dabigatran reversal
The anticoagulant dabigatran, a direct thrombin inhibitor, and its reversal agent idarucizumab are both renally cleared. To determine if idarucizumab effectively reverses dabigatran's anticoagulant effect in patients with impaired renal function, researchers conducted a retrospective cohort study that enrolled 503 adult patients from 34 countries who were taking dabigatran. The patients were divided into two groups: Group A included patients with overt, uncontrolled, or life-threatening bleeding; Group B included patients who required urgent surgery or an invasive procedure that could not be delayed for at least 8 hours and for which normal hemostasis was required. The extent of dabigatran reversal and clinical outcomes were compared according to baseline renal function (creatinine clearance: normal ≥80, mild 50 to <80, moderate 30 to <50, and severe <30 mL/min). The results showed that idarucizumab completely reversed dabigatran in more than 98% of patients regardless of renal function. Although patients with renal impairment were more likely to experience re-elevation of dabigatran levels 12 or 24 hours after receiving idarucizumab, the time to bleeding cessation and the extent of hemostasis during procedures were similar in both groups.
Findings were based on analysis of data from the RE-VERSE AD (Reversal of Effects of Idarucizumab in Patients on Active Dabigatran) study.
Source: Eikelboom JW, van Ryn J, Reilly P, et al. Dabigatran reversal with idarucizumab in patients with renal impairment. J Am Coll Cardiol. 2019;74(14):1760-1768.
Be aware: Biotin may affect lab results
During medication reconciliation, nurses should take care to document patients' use of all medications, including over-the-counter dietary supplements and vitamins. In a recent Safety Communication, the FDA warns healthcare professionals that biotin, which is found in various dietary supplements, can interfere with many crucial lab reports—notably, levels of troponin, a clinically important biomarker for myocardial infarction. The FDA continues to receive adverse event reports indicating that biotin interference can result in falsely low troponin levels.
The Safety Communication offers specific recommendations for healthcare professionals, lab personnel, and patients. For example, nurses should:
- educate patients about any supplements or multivitamins, including prenatal multivitamins, that may contain biotin, including supplements marketed for hair, skin, and nail growth. Tell them that biotin may interfere with lab test results.
- inform the lab if a patient being tested is taking biotin.
- consider biotin interference as a possible source of error if a lab test result does not match the patient's clinical presentation.
- report to the lab test manufacturer and the FDA if a patient experiences an adverse event following potentially incorrect lab test results due to biotin interference. The MedWatch Voluntary Reporting Form can be accessed at www.accessdata.fda.gov/scripts/medwatch/index.cfm.
Source: Food and Drug Administration. Update: the FDA warns that biotin may interfere with lab tests: FDA Safety Communication. November 5, 2019. www.fda.gov.
Gene-based therapy hailed as a breakthrough
Impressive results from a phase 3, randomized, double-blind, placebo-controlled trial confirm the efficacy and safety of a triple-drug therapy, elexacaftor–tezacaftor–ivacaftor, in patients age 12 years or older who have cystic fibrosis (CF) with Phe508del–minimal function genotypes. Nearly 90% of patients with CF have at least one copy of this gene mutation.
For this study, 403 patients with Phe508del–minimal function genotypes were randomized to receive at least one dose of active treatment or placebo. The primary endpoint was absolute change from baseline in percentage of predicted forced expiratory volume in 1 second (FEV1) at week 4. Compared with placebo, elexacaftor–tezacaftor–ivacaftor therapy resulted in a percentage of predicted FEV1 that was 13.8 points higher at 4 weeks and 14.3 points higher through 24 weeks. In addition, the rate of pulmonary exacerbations was 63% lower, the respiratory domain score on the Cystic Fibrosis Questionnaire–Revised was 20.2 points higher, and sweat chloride concentrations were 41.8 mmol/L lower. The treatment was well tolerated by patients. The authors concluded that the triple-drug therapy “can modulate a single Phe508del allele in people with cystic fibrosis, thus addressing the underlying cause of disease in the large majority of patients.”
In an accompanying editorial, Francis S. Collins, MD, PhD, writes that “this should be a cause for major celebration. Yet we must not abandon the patients with cystic fibrosis who have null mutations and will not have a response to these drugs.”
The study was reported at the annual North American Cystic Fibrosis Conference last fall.
Sources: Middleton PG, Mall MA, Dřevinek P, et al. Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele. N Engl J Med. 2019;381(19):1809-1819. Collins FS. Realizing the dream of molecularly targeted therapies for cystic fibrosis. N Engl J Med. 2019;381(19):1863-1865.