Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks.

BACKGROUND: Remibrutinib (LOU064), an oral, highly selective Bruton tyrosine kinase inhibitor, offers fast disease control in patients with chronic spontaneous urticaria (CSU) who remain symptomatic despite treatment with second-generation H1 antihistamines. It is currently in phase 3 development for CSU. OBJECTIVE: We sought to evaluate long-term safety and efficacy of remibrutinib in patients with CSU inadequately controlled with H1 antihistamines. METHODS: In this phase 2b extension study, patients who completed the core study and had a weekly Urticaria Activity Score (UAS7) ≥16 at the beginning of the extension study received remibrutinib 100 mg twice daily for 52 weeks. The primary objective was to assess long-term safety and tolerability. Key efficacy end points included change from baseline in UAS7 and proportion of patients with complete response to treatment (UAS7 = 0) and well-controlled disease (UAS7 ≤6) at week 4 and over 52 weeks. RESULTS: Overall, 84.3% (194/230) of patients entered the treatment period and received ≥1 doses of remibrutinib. The overall safety profile of remibrutinib was comparable between the extension and core studies. Most treatment-emergent adverse events were mild to moderate and considered unrelated to remibrutinib by investigators. The 3 most common treatment-emergent adverse events by system organ class were infections (30.9%), skin and subcutaneous tissue (26.8%), and gastrointestinal disorders (16.5%). At week 4 and 52, mean ± SD change from baseline in UAS7 was -17.6 ± 13.40 and -21.8 ± 10.70; UAS7 = 0 (as observed) was achieved in 28.2% and 55.8% and UAS7 ≤6 (as observed) was achieved in 52.7% and 68.0% of patients, respectively. CONCLUSIONS: Remibrutinib demonstrated a consistent favorable safety profile with fast and sustained efficacy for up to 52 weeks in patients with CSU.

Randomized trial to assess the efficacy and safety of beclomethasone dipropionate breath-actuated inhaler in patients with asthma.

BACKGROUND: Breath-actuated inhalers (BAI) eliminate the need for the hand-breath coordination required with standard metered-dose inhalers (MDI). OBJECTIVE: To evaluate the efficacy and safety of beclomethasone dipropionate (BDP) administered via BAI. METHODS: This 6-week, phase III, double-blind study included patients aged ≥12 years with persistent asthma. During the single-blind run-in, patients discontinued asthma medications and received twice-daily placebo BAI or MDI. At randomization, BAI patients received BDP BAI 320 µg/day, BDP BAI 640 µg/day, or placebo BAI, and MDI patients received BDP MDI 320 µg/day or placebo MDI. Assessments included standardized baseline-adjusted trough morning forced expiratory volume in 1 second (FEV1) area under the effect curve from 0 to 6 weeks (AUEC[0-6 wk]) (obtained by clinic-based spirometry; the primary end point), morning peak expiratory flow (PEF), trough daily morning FEV1 (obtained by handheld spirometry), withdrawals, and tolerability. RESULTS: Of 425 patients randomized, most were white (81%) and female (61%). BDP BAI 320 and 640 µg/day significantly improved FEV1 AUEC(0-6 wk) versus placebo (p < 0.001). The BDP BAI treatment groups exhibited significantly improved morning PEF and daily morning FEV1 versus placebo (p < 0.001). Similar treatment effects were demonstrated for BDP MDI (p < 0.001). Fewer patients withdrew due to worsening asthma while taking BDP BAI 320 µg/day (n = 1), BDP BAI 640 µg/day (n = 0), and BDP MDI 320 µg/day (n = 1) versus placebo (n = 10). BDP BAI was well tolerated. CONCLUSION: BDP BAI demonstrated significant improvements in pulmonary function versus placebo, with results similar to BDP MDI. The safety profile of BDP BAI was comparable to BDP MDI, with no new safety signals.The study was registered on ClinicalTrials.gov (NCT02513160), www.clinicaltrials.gov.

Triamcinolone acetonide aqueous nasal spray and fluticasone propionate are equally effective for relief of nasal symptoms in patients with seasonal allergic rhinitis.

OBJECTIVE: We compared 220 microg daily intranasal aqueous triamcinolone acetonide (TAA AQ) with 200 microg daily fluticasone propionate (FP) for relief of seasonal allergic rhinitis symptoms. Study design and setting Randomized, parallel-group, investigator-blind study included patients with symptomatic seasonal allergic rhinitis. After a baseline period, TAA AQ or FP was taken for about 21 days. Nasal symptom (discharge, stuffiness, itching, sneezing) severity was recorded twice daily; total nasal symptom score was calculated. Health-related quality of life was assessed by Rhinoconjunctivitis Quality of Life Questionnaire. RESULTS: Reductions in individual symptoms and total nasal symptom score were statistically significant versus baseline and were equivalent between treatments: -3.15 +/- 0.19 with TAA AQ (n = 148) and approximately 3.17 +/- 0.18 with FP (n = 147) (95% confidence interval for the difference, -0.7391 to 0.3693). Clinically and statistically significant improvements in Rhinoconjunctivitis Quality of Life Questionnaire scores were comparable. CONCLUSION: TAA AQ and FP were equally efficacious in relieving seasonal allergic rhinitis symptoms and improving health-related quality of life. SIGNIFICANCE: Differences in molecular potency of intranasal steroids do not confer differences in efficacy.