From the Guidelines
For patients with elevated IgE who fail treatment with Xolair (omalizumab), I strongly recommend considering mepolizumab (Nucala, 100mg subcutaneously every 4 weeks) as the preferred alternative biologic therapy, based on recent guideline recommendations. This recommendation is supported by the 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis, which conditionally recommends adding mepolizumab over adding omalizumab for patients with EGPA and high serum IgE levels who have experienced relapse with non-severe disease manifestations 1.
The rationale behind this recommendation is that mepolizumab has shown efficacy in targeting IL-5 pathways, which are involved in eosinophilic inflammation, a common feature in patients with elevated IgE. In contrast, the published evidence on omalizumab, an anti-IgE antibody, in EGPA has been limited 1.
Before switching to mepolizumab, it is essential to ensure that optimal dosing of Xolair was achieved and adherence was maintained. Additionally, reassessing the underlying condition causing elevated IgE is crucial, as conditions like allergic bronchopulmonary aspergillosis may require antifungal therapy, and atopic dermatitis might respond to topical treatments alongside biologics. Combination approaches with medium-dose inhaled corticosteroids plus long-acting beta-agonists for asthma patients, or antihistamines for those with chronic urticaria, should also be considered. Treatment response should be evaluated after 3-6 months, and therapy adjusted accordingly.
Key points to consider when switching to mepolizumab include:
- Ensuring optimal dosing and adherence to previous treatment
- Reassessing the underlying condition causing elevated IgE
- Considering combination approaches with other therapies
- Evaluating treatment response after 3-6 months and adjusting therapy as needed.
From the Research
Treatment Options for Patients with Elevated IgE who Fail Treatment with Xolair
- For patients with elevated IgE who fail treatment with Xolair (omalizumab), several alternative treatment options are available, as discussed in studies 2, 3.
- These options include the use of other anti-IgE monoclonal antibodies, such as ligelizumab and UB-221, which have shown promise in clinical trials for the treatment of chronic spontaneous urticaria (CSU) and other IgE-mediated diseases 2, 3.
- Additionally, other treatments such as dupilumab, reslizumab, mepolizumab, and benralizumab may be effective in certain cases of chronic urticaria, as reported in study 2.
Mechanisms of Action and Efficacy
- The mechanisms of action of these alternative treatments vary, with some targeting specific receptors or pathways involved in IgE-mediated inflammation, as discussed in study 3.
- For example, UB-221 has been shown to exhibit CD23-mediated IgE downregulation and relieve urticaria symptoms, making it a potentially effective treatment option for patients who fail Xolair treatment 3.
- The efficacy of these treatments has been demonstrated in clinical trials, with some showing superior results compared to Xolair, as reported in studies 2, 3.
Safety and Potential Side Effects
- As with any treatment, potential side effects and safety concerns must be considered, as discussed in studies 4, 5, 6.
- For example, omalizumab has been associated with adverse reactions, including anaphylaxis, as reported in study 4.
- Additionally, the use of Xolair has been linked to increased blood glucose levels in patients with diabetes mellitus, as reported in study 5.
- However, the safety profiles of alternative treatments, such as UB-221, have not been fully established, and further research is needed to determine their potential side effects and risks, as discussed in study 3.