REMIBRUTINIB TAB,ORAL

Clinical Criteria Summary

Indicated for treatment of chronic spontaneous urticaria (CSU) in adult patients who remain symptomatic despite use of H1 AH treatment.
Patients must have CSU diagnosed > 6 months that remained symptomatic despite H1 AH use.
Symptomatic disease on H1 AH requires itch and hives for at least 6 consecutive weeks prior to screening, with UAS7 > 16, ISS7 > 6, and HSS7 > 6 during the 7 days prior to randomization.

Monitor for signs and symptoms of bleeding; discontinue remibrutinib if bleeding occurs.
Temporarily interrupt therapy 3–7 days before and after surgery, depending on surgery type and bleeding risk.
Avoid use of live or live-attenuated vaccines due to lack of data on effect.

No boxed warnings or contraindications listed.
Avoid concomitant use with strong or moderate CYP3A4 inhibitors or inducers; remibrutinib is a CYP3A4 substrate.
Remibrutinib is a P-gp inhibitor; closer monitoring recommended for P-gp substrates where minimal concentration changes may cause serious ADEs (e.g., digoxin).
Concomitant use with antithrombotic drugs may increase bleeding risk; risks and benefits should be considered. Lack of data on anticoagulant concomitant use due to patient exclusion in trials.

Considered an alternative to omalizumab or dupilumab for patients remaining symptomatic despite maximized H1 AH (up to 4 times the approved daily dose).
Omalizumab is the preferred second-line agent after inadequate response to H1 AH up to 4x dose.
Maximum doses of H1 AH should be continued in combination with second-line therapies.
Low-dose cyclosporine may be considered as a third-line agent for more refractory symptoms/disease.
Therapy can be stepped down by reducing doses or extending dosing intervals when the urticaria control test (UCT) score equals 16.

Hepatic impairment: Avoid use in patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, and C); exposure is increased in any degree of liver impairment.
Renal impairment: No clinically significant effect on pharmacokinetics in mild, moderate, or severe renal impairment.
Pregnancy: Data lacking to evaluate risk of major birth defects, miscarriage, or other adverse maternal/fetal outcomes; pregnancy exposure registry available.
Lactation: No data; consider developmental/health benefits of breastfeeding alongside mother’s clinical need and potential ADEs on the breastfed child.

Provider must be a VA or VA Community Care allergy specialist, dermatologist, or designated expert in the management of allergic conditions
Diagnosis of severe chronic spontaneous urticaria (e.g., UAS7 >28 and/or UCT <12)
Unacceptable symptoms despite a therapeutic trial of 1 non-sedating H antihistamine titrated up to 4 times the usual daily dose
Inadequate response to a 3-month trial of omalizumab 300 mg every 4 weeks (minimum of 3 doses), unable to tolerate, or not a candidate for omalizumab
Inadequate response to a 6-month trial of dupilumab 300 mg every 2 weeks (minimum of 12 doses), unable to tolerate, or not a candidate for dupilumab

For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy; pregnancy register enrollment recommended if pregnancy occurs