Chronic spontaneous urticaria symptoms improve in 1 week with remibrutinib
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Key takeaways:
- Remibrutinib is a highly selective Bruton’s tyrosine kinase inhibitor.
- H1 antihistamines inadequately controlled disease.
- Patients experienced improvements in urticaria activity and itch and hives severity.
BOSTON — Chronic spontaneous urticaria symptoms improved with 1 week of remibrutinib treatment, according to a poster presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.
These improvements persisted through week 24, Robert Szalewski, MD, a physician with Allergy, Asthma and Immunology Associates in Lincoln, Nebraska, and colleagues wrote.
Drug mechanics
“It’s incredible, absolutely incredible, because you’re seeing a huge change,” Szalewski told Healio, adding that more than 50% of patients with chronic spontaneous urticaria (CSU) do not get relief for their symptoms with H1 antihistamines alone, which is first-line treatment.
“A lot of these patients are really struggling for a long time despite appropriate therapy,” Szalewski said.
Remibrutinib (Novartis) is a novel, oral highly selective Bruton’s tyrosine kinase, or BTK, inhibitor that prevents mast cell release as well as histamine and other pro-inflammatory mediators, Szalewski said.
Unlike other treatments such as omalizumab (Xolair; Genentech, Novartis) that bind with IgE antibodies, Szalewski said, remibrutinib works within the mast cell.
“It’s post-IgE binding. And then you go through this inflammatory pathway. BTK leads to mast cell release of histamine and other mediators,” Szalewski said. “It’s actually blocking the BTK [molecule] itself inside of the mast cell after the binding of the IgE molecule.”
Remibrutinib also has shown superior efficacy and symptom improvement after 12 weeks without any impact on immunoglobulin levels, he continued.
Study design, results
The REMIX-1 and REMIX-2 multicenter, randomized, double-blind, placebo-controlled, phase 3 studies assessed the efficacy of remibrutinib among patients who had CSU for 6 months or more that was inadequately controlled with H1 antihistamines.
“Patients were required to have that background antihistamine use, and they could use additional antihistamines as acute hive controllers or to control flares as needed,” Szalewski said. “Usually patients with CSU, especially if they’ve had it for this long, we’re seeing them on up to four-times-daily antihistamines.”
Mean durations of CSU included 6.6 years for the REMIX-1 group (n = 470; mean age = 45 years; 68.3% women) and 5.2 years for REMIX-2 (n = 455; mean age = 41.7 years; 65.3% women).
“The duration of CSU for a lot of these patients was in years,” Szalewski said.
The patients in the REMIX-1 and REMIX-2 groups both received 25 mg of remibrutinib twice a day or a placebo for 24 weeks in a 2:1 ratio.
Compared with the group on placebo (n = 157), patients on remibrutinib (n = 313) experienced least squares (LS) mean changes from baseline in Urticaria Activity Score (CFB-UAS7) of –11.3 at week 1, –15.6 at week 2, –18.6 at week 4, –20.1 at week 12 and –20.7 at week 24 in REMIX-1.
The remibrutinib group in REMIX-1 also experienced LS mean changes from baseline in Itch Severity Score (CFB-ISS7) of –5.2 of week 1, –7.2 at week 2, –8.6 at week 4, –9.6 at week 12 and –9.8 at week 24.
LS mean changes from baseline in Hives Severity Score (CFB-HSS7) for the REMIX-1 remibrutinib group included –6 at week 1, –8.3 at week 2, –9.9 at week 4, –10.5 at week 12 and –10.9 at week 24.
Results were similar in REMIX-2, including LS mean CFB-UAS7 of –11.3 at week 1, –15.1 at week 2, –17.4 at week 4, –19.5 at week 12 and –20.4 at week 24 for the remibrutinib group (n = 300) compared with the placebo group (n = 155).
LS mean CFB-ISS7 for the remibrutinib group in REMIX-2 included –5 at week 1, –6.7 at week 2, –7.9 at week 4, –9 at week 12 and –9.5 at week 24. Also, LS mean CFB-HSS7 included –6.3 at week 1, –8.5 at week 2, –9.6 at week 4, –10.5 at week 12 and –10.9 at week 24 for the remibrutinib group in REMIX-2.
The researchers called all these changes significant, with P values of less than .001, as well as fast.
Additionally, at week 1, 50.7% of those on remibrutinib and 14.5% of those on placebo achieved minimal important differences (MIDs) in their UAS7 scores; 50.4% of those on remibrutinib and 17.2% of those on placebo achieved MIDs in their ISS7 scores; and 52.1% of those on remibrutinib and 17.2% of those on placebo achieved MIDs in their HSS7 scores.
“Over 50% had a UAS7 of zero, which indicates no hives, no itching whatsoever, and that response was sustained,” Szalewski said.
The safety profiles for the remibrutinib and placebo groups were about equal as well, Szalewski said.
“This is a BTK inhibitor. We use this for cancers. We use this for rheumatoid arthritis,” he said. “Given what we know from this medication and how selective it is and what the safety profile looks like in the studies, I’m very comfortable with using it.”
Szalewski also noted patient adherence, with few patients who dropped out.
“Twice daily may be a little difficult for some people. I would probably find that difficult myself, because I sometimes forget to take medicine once a day,” Szalewski said. “But I think when it comes to how much this impacts people’s quality of life, from what we’ve seen here, they’re very adherent.”
Based on these findings, the researchers said remibrutinib has the potential to be an effective treatment option with early onset response for patients whose H1 antihistamines have not adequately controlled their CSU.
“People in this study were very, very happy,” Szalewski said. “To see how safe this is and how quick the response is, I think it’s going to be a great option for people.”
For more information:
Robert Szalewski, MD, can be reached at rszalewski@allergynebraska.com.