Can Xolair (omalizumab) be used to treat patients with mast cell activation in a chronic flare and what is its effectiveness?

Omalizumab (Xolair) for Mast Cell Activation Syndrome in Chronic Flare

Omalizumab (Xolair) is an effective treatment option for patients with mast cell activation syndrome (MCAS) experiencing chronic flares, particularly when symptoms are insufficiently controlled by conventional therapies. 1

Mechanism of Action and Indications

• Omalizumab is a humanized monoclonal antibody that binds to circulating IgE, preventing it from binding to high-affinity receptors (FcεRI) on mast cells and basophils, thereby reducing mast cell degranulation and mediator release 2
• It is specifically indicated for patients with mast cell disorders who have symptoms insufficiently controlled by conventional therapy, including antihistamines and other antimediator agents 1
• Omalizumab is particularly recommended for patients with unprovoked anaphylaxis or those with hymenoptera or food-induced reactions 1

Effectiveness in MCAS

• In patients with mast cell disorders, omalizumab demonstrates an overall response rate of approximately 78%, with 54.5% achieving a major response 3
• Omalizumab is particularly effective for recurrent anaphylaxis and skin symptoms, though less effective for gastrointestinal, musculoskeletal, and neuropsychiatric symptoms 1
• The majority of patients with refractory MCAS (61%) achieve at least a partial response to omalizumab therapy, with some patients (18%) achieving complete symptom resolution 4
• Median time to first response is approximately 2 months, with best response typically achieved around 6 months of treatment 3

Dosing Considerations

• Dosing typically ranges from 150 mg every 4 weeks to 300 mg every 2-3 weeks, with higher doses (≥300 mg/month) associated with better complete response rates 4
• The most common effective dosing regimen is 150 mg every 2 weeks for patients with MCAS 4
• For allergic asthma, dosing is calculated based on body weight and baseline serum IgE levels (approximately 0.016 mg/kg/IgE [IU/mL] per 4 weeks) 2

Clinical Benefits

• Omalizumab can significantly reduce or eliminate anaphylactic episodes in patients with MCAS 1
• It may allow for discontinuation of systemic glucocorticoids in some patients, reducing steroid-related side effects 4
• The medication is particularly effective for vasomotor symptoms (flushing, urticaria), gastrointestinal symptoms, and urinary symptoms 3
• Low-dose omalizumab (150 mg monthly) has demonstrated sustained clinical response for up to 5 years in some patients with idiopathic MCAS 5

Safety Profile

• Omalizumab is generally well-tolerated with a safety profile similar to placebo in most studies 2
• Common side effects include injection site reactions, viral infections, upper respiratory tract infections, sinusitis, headache, and pharyngitis 2
• More serious adverse events are rare but may include laryngeal edema and dyspnea, particularly after the first injection 3
• Clinicians administering omalizumab should be prepared to identify and treat potential anaphylaxis 1

Treatment Algorithm for MCAS

1. First-line therapy: H1 and H2 antihistamines, often at higher than standard doses 1
2. Second-line therapy: Add cromolyn sodium for persistent symptoms, particularly for gastrointestinal manifestations 1
3. Third-line therapy: Consider leukotriene receptor antagonists (e.g., montelukast) or aspirin (if no NSAID sensitivity) 1
4. Fourth-line therapy: Consider omalizumab for patients with:
   • Persistent symptoms despite above therapies 1
   • Recurrent anaphylaxis 1
   • Severe skin manifestations 1
   • Need to reduce or eliminate systemic corticosteroids 4

Important Considerations and Caveats

• Response to omalizumab may vary based on symptom type, with better response for anaphylaxis and skin symptoms than for neuropsychiatric symptoms 1, 3
• Treatment should continue for at least 3-6 months to determine effectiveness, as best response may take time to achieve 3
• Patients should still carry emergency epinephrine autoinjectors even when on omalizumab therapy 1
• The response pattern does not appear to be influenced by sex or mast cell clonality (clonal vs. non-clonal MCAS) 4
• Cost considerations may impact treatment decisions, but low-dose regimens (150 mg monthly) may provide cost-effective benefits for some patients 5