Remibrutinib confers fast symptom improvement in chronic spontaneous urticaria
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Key takeaways:
- More patients assigned remibrutinib vs. placebo showed improvements in UAS7, ISS7 and HSS7.
- Remibrutinib led to well-controlled disease as early as week 2, with proportions increasing by week 12.
ANAHEIM, Calif. — Patients with inadequately controlled chronic spontaneous urticaria experienced relief of symptoms after only 2 weeks of treatment with remibrutinib, according to data from the ongoing REMIX-1 and REMIX-2 studies.
Study results, presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting, also showed the oral Burton tyrosine kinase inhibitor remibrutinib (Novartis) had a favorable safety profile.
If approved for chronic spontaneous urticaria (CSU), remibrutinib could offer an effective oral treatment option for the more than 50% of people who experience inadequate disease control with H1 antihistamines, Marcus Maurer, MD, professor of dermatology and allergy, executive director of the Institute of Allergology at Charité – Universitätsmedizin Berlin and co-director of immunology and allergy at the Fraunhofer Institute for Translational Medicine and Pharmacology in Berlin, Germany, told Healio.
“These findings could be significant for the millions of people globally who suffer from CSU and are still symptomatic despite treatment with antihistamines,” Maurer said. “CSU is a very debilitating disease; it often takes a tremendous emotional toll on those who live with it, and it is psychologically extremely difficult as it impacts on many aspects of people’s lives such as sleep, sexual health and ability to work. Having another option that could potentially provide effective relief as early as 2 weeks, after trying antihistamines alone, could be transformative for these people.”
Researchers evaluated data from the global, double-blind, placebo-controlled phase 3 REMIX-1 (n = 470; mean age, 45 years; 68.3% women) and REMIX-2 trials (n = 455; mean age, 41.7 years; 65.3% women), which included patients aged at least 18 years with CSU that had been inadequately controlled by second-generation H1 antihistamines.
During his presentation at ACAAI, Sarbjit Singh Saini, MD, professor of medicine at Johns Hopkins Medicine, noted that about half of the patients in both studies had previously experienced angioedema (REMIX-1, 51.7%; REMIX-2, 47%) and less than one-third had previous exposure to anti-IgE biologics (REMIX-1, 31.9%; REMIX-2, 30.8%).
Treatment consisted of 25 mg twice-daily remibrutinib (REMIX-1, n = 313; REMIX-2, n = 300) or placebo (REMIX-1, n = 157; REMIX-2, n = 155) for 24 weeks, followed by open-label treatment with remibrutinib for 28 weeks, which is currently ongoing.
Change from baseline in weekly Urticaria Activity Score (UAS7), Itch Severity Score (ISS7) and Hives Severity Score (HSS7) at week 12 served as the study’s primary endpoints.
Eighty-six percent of patients from REMIX-1 and 85.3% from REMIX-2 completed the double-blind treatment period, with comparable rates of discontinuation between patients assigned remibrutinib and placebo and 2.6% of patients from each group discontinuing due to an adverse event.
Overall, researchers found that remibrutinib led to significantly greater changes from baseline in UAS7 vs. placebo at week 12 in both REMIX-1 (least-square mean change, –20.1 vs. –13.8; treatment difference, –6.32; 95% CI, –8.52 to –4.13; P < .001) and REMIX-2 (least-square mean change, –19.6 vs. –11.7; treatment difference, –7.86; 95% CI, –10.06 to –5.66; P < .001).
Similarly, patients assigned remibrutinib showed about a 10-point change in itch and hives severity across studies, with significant improvements as demonstrated by the treatment difference in least-squares mean change from baseline compared with placebo for both ISS7 (REMIX-1, –2.68; 95% CI, –3.73 to –1.63; REMIX-2, –3.32; 95% CI, –4.37 to –2.26) and HSS7 (REMIX-1, –3.65; 95% CI, –4.89 to –2.42; REMIX-2, –4.55; 95% CI, –5.78 to –3.32; P < .001 for all).
“Looking at the improvement over time, we see the change in US7,” Saini said. “What should catch your eye is the dramatic reduction in US7 that occurs in the early weeks of therapy relative to the placebo.”
Also, a significantly greater proportion of patients achieved well-controlled disease, defined a UAS7 of 6 of less, at week 2 in both REMIX-1 (33.3% vs. 3.3%) and REMIX-2 (30% vs. 5.9%; P < .001 for both), with sustained results at week 12 again in REMIX-1 (50.2% vs. 24.8%) and REMIX-2 (47.5% VS. 19.6%; P < .001 for both).
Lastly, the complete response rate, defined as a UAS7 score of 0, at week 12 appeared higher in the remibrutinib arm in both REMIX-1 (31.1% vs. 11.1%) and REMIX-2 (27.9% vs. 6.5%; P < .001 for both).
Pooled data from both studies showed comparable incidence among the remibrutinib and placebo groups in terms of overall adverse events (64% vs. 64.7%), serious adverse events (3.3% vs. 2.3%) and adverse events leading to treatment continuation (2.6% for both) during the 24-week double-blind period.
“None of the serious adverse events are considered related to the study medication,” Saini said.
The most common adverse events that occurred in the remibrutinib and placebo groups included COVID-19 (10.7% vs. 11.4%), nasopharyngitis (6.6% vs. 4.6%) and headache (6.1% vs. 5.9%), with more patients in the treatment group experiencing petechiae (3.8% vs. 0.3%), which Saini noted was mostly mild or moderate.
Liver transaminase elevations occurred among 1.3% of both study groups and were largely asymptomatic, transient and reversible, Saini added.
Next, the researchers will conduct the final 52-week analysis, and they plan to file for FDA approval next year, Maurer said.
“In addition to CSU, remibrutinib is being investigated in other immune-mediated conditions, such as multiple sclerosis, hidradenitis suppurativa, food allergy, chronic inducible urticaria and Sjögren’s,” he told Healio.