Ariel Teper

Mometasone furoate nasal spray is safe and effective for 1-year treatment of children with perennial allergic rhinitis

OBJECTIVE Perennial allergic rhinitis (PAR) affects children at a young age. Current guidelines recommend intranasal corticosteroids as the first-line treatment in patients with moderate-to-severe or persistent disease or in those who have congestion. In this study, the long-term safety and efficacy of mometasone furoate nasal spray (MFNS) were assessed in children with PAR. METHODS In this multicenter, active-controlled, evaluator-blind, 12-month study, 255 children aged 6-11 years with a >or=1-year history of PAR were randomized to receive once-daily MFNS 100 microg (n=166) or the active comparator beclomethasone dipropionate (BDP) 168 microg (n=85). Changes from baseline in overall PAR symptoms and response to treatment were rated at each visit. Cosyntropin stimulation testing, as well as tonometry and slit lamp procedures, were performed. Safety variables were assessed. RESULTS A total of 137 subjects in the MFNS group and 68 in the BDP group completed treatment. The mean reductions in physician- and subject-rated overall condition of PAR at week 52 were -42.1% and -39.7%, respectively, for MFNS, compared with -44.0% and -39.0%, respectively, for BDP. A total of 94% and 100% of MFNS and BDP subjects, respectively, reported adverse events (AEs), which were mostly mild or moderate. The most frequently reported treatment-related AEs in both groups were epistaxis, headache, and pharyngitis. Response to cosyntropin was normal and no posterior subcapsular cataracts were observed in either group. Although no significant changes in intraocular pressure were observed with MFNS, one subject receiving BDP demonstrated this effect. CONCLUSIONS Treatment with MFNS 100 microg once daily for 1 year was well tolerated in children 6-11 years old, with negligible systemic exposure and no evidence of suppression of the hypothalamic-pituitary-adrenal axis or ocular changes.

Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma

BACKGROUND Dupilumab is a fully human anti–interleukin‐4 receptor α monoclonal antibody that blocks both interleukin‐4 and interleukin‐13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma. METHODS We randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add‐on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched‐volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV1) before bronchodilator use in the overall trial population. Secondary end points included the exacerbation rate and FEV1 in patients with a blood eosinophil count of 300 or more per cubic millimeter. Asthma control and dupilumab safety were also assessed. RESULTS The annualized rate of severe asthma exacerbations was 0.46 (95% confidence interval [CI], 0.39 to 0.53) among patients assigned to 200 mg of dupilumab every 2 weeks and 0.87 (95% CI, 0.72 to 1.05) among those assigned to a matched placebo, for a 47.7% lower rate with dupilumab than with placebo (P<0.001); similar results were seen with the dupilumab dose of 300 mg every 2 weeks. At week 12, the FEV1 had increased by 0.32 liters in patients assigned to the lower dose of dupilumab (difference vs. matched placebo, 0.14 liters; P<0.001); similar results were seen with the higher dose. Among patients with a blood eosinophil count of 300 or more per cubic millimeter, the annualized rate of severe asthma exacerbations was 0.37 (95% CI, 0.29 to 0.48) among those receiving lower‐dose dupilumab and 1.08 (95% CI, 0.85 to 1.38) among those receiving a matched placebo (65.8% lower rate with dupilumab than with placebo; 95% CI, 52.0 to 75.6); similar results were observed with the higher dose. Blood eosinophilia occurred after the start of the intervention in 52 patients (4.1%) who received dupilumab as compared with 4 patients (0.6%) who received placebo. CONCLUSIONS In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA QUEST ClinicalTrials.gov number, NCT02414854.)

Mometasone furoate improves nasal and ocular symptoms of seasonal allergic rhinitis in adolescents.

Seasonal allergic rhinitis (SAR) is common in adolescents. However, few studies have investigated the effectiveness of intranasal corticosteroids (INSs) for nasal and ocular symptoms of SAR solely in adolescents. The purpose of this study was to determine the safety and efficacy of the INS mometasone furoate nasal spray (MFNS) in adolescents; a post hoc analysis was conducted of adolescents who had participated in a study with adults. Data were analyzed retrospectively for subjects aged 12–17 years with moderate or severe SAR randomized to mometasone furoate, 200 meg once daily (n = 86), or placebo (n = 82) for 15 days in a multicenter, double-blind, placebo-controlled study. Symptom scores (0 = none to 3 = severe) were recorded in diaries twice daily. End points included changes from baseline in total nasal symptom score (TNSS), individual nasal symptom score (rhinorrhea, congestion, itching, and sneezing), and total ocular symptom score (TOSS). Over 15 days, a significantly greater decrease from baseline in mean TNSS was observed in subjects receiving mometasone furoate (–2.47; −28.8%) compared with those receiving placebo (–0.9; −9.6%; p < 0.001). Significant improvement versus placebo was seen for each full day of treatment. Mometasone furoate significantly improved individual nasal symptoms (p ≤ 0.03) and TOSS (p = 0.011) versus placebo. The incidence of adverse events was similar for both treatment groups. MFNS, 200 meg once daily, is an effective and well-tolerated treatment for symptoms of SAR in adolescents.

Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma

BACKGROUND Dupilumab is a fully human anti–interleukin‐4 receptor α monoclonal antibody that blocks both interleukin‐4 and interleukin‐13 signaling. Its effectiveness in reducing oral glucocorticoid use in patients with severe asthma while maintaining asthma control is unknown. METHODS We randomly assigned 210 patients with oral glucocorticoid–treated asthma to receive add‐on dupilumab (at a dose of 300 mg) or placebo every 2 weeks for 24 weeks. After a glucocorticoid dose‐adjustment period before randomization, glucocorticoid doses were adjusted in a downward trend from week 4 to week 20 and then maintained at a stable dose for 4 weeks. The primary end point was the percentage reduction in the glucocorticoid dose at week 24. Key secondary end points were the proportion of patients at week 24 with a reduction of at least 50% in the glucocorticoid dose and the proportion of patients with a reduction to a glucocorticoid dose of less than 5 mg per day. Severe exacerbation rates and the forced expiratory volume in 1 second (FEV1) before bronchodilator use were also assessed. RESULTS The percentage change in the glucocorticoid dose was ‐70.1% in the dupilumab group, as compared with ‐41.9% in the placebo group (P<0.001); 80% versus 50% of the patients had a dose reduction of at least 50%, 69% versus 33% had a dose reduction to less than 5 mg per day, and 48% versus 25% completely discontinued oral glucocorticoid use. Despite reductions in the glucocorticoid dose, in the overall population, dupilumab treatment resulted in a severe exacerbation rate that was 59% (95% confidence interval [CI], 37 to 74) lower than that in the placebo group and resulted in an FEV1 that was 0.22 liters (95% CI, 0.09 to 0.34) higher. Injection‐site reactions were more common with dupilumab than with placebo (9% vs. 4%). Transient blood eosinophilia was observed in more patients in the dupilumab group than in the placebo group (14% vs. 1%). CONCLUSIONS In patients with glucocorticoid‐dependent severe asthma, dupilumab treatment reduced oral glucocorticoid use while decreasing the rate of severe exacerbations and increasing the FEV1. Transient eosinophilia was observed in approximately 1 in 7 dupilumab‐treated patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA VENTURE ClinicalTrials.gov number, NCT02528214.)

Mometasone furoate nasal spray for moderate-to-severe nasal congestion in subjects with seasonal allergic rhinitis.

Nasal congestion is a frequent, bothersome symptom of seasonal allergic rhinitis (SAR). Mometasone furoate nasal spray (MFNS) has established efficacy in treating nasal allergy symptoms, but no study has been conducted with the primary purpose of evaluating MFNS for relief of congestion. This study assessed MFNS for congestion and other nasal symptoms in SAR. Two double-blind, placebo-controlled studies randomized symptomatic SAR patients to 15 days of MFNS, 200 micrograms, or placebo q.d. each morning. Participants scored individual components of total nasal symptom score (TNSS; congestion, rhinorrhea, sneezing, and itching) on a 4-point scale in the morning (A.M.) and evening (P.M.). Symptoms were scored for the time of assessment (NOW) and for the previous 12 hours (PRIOR). The pooled population comprised 684 patients randomized to MFNS (n = 344) or placebo (n = 340). Change from baseline in A.M./P.M. PRIOR nasal congestion score averaged over days 1-15, the primary end point, was significantly (p < 0.001) greater with MFNS than with placebo (0.68-point [25.2%] reduction versus 0.45-point [16.0%] reduction, respectively). Reduction in A.M./P.M. PRIOR TNSS averaged over days 1-15, a key secondary end point, was also superior with MFNS (2.83 points [28.5%] versus 1.79 points [17.6%]; p < 0.001). Predose A.M. NOW congestion, other nasal symptoms, and TNSS improved significantly more with MFNS, indicating 24-hour efficacy. Adverse events were infrequent and localized; the most common (epistaxis and pharyngolaryngeal pain) occurred in 1.0% of MFNS patients. MFNS q.d. provides sustained relief for nasal congestion and other SAR symptoms.