Omalizumab in chronic urticaria: Dr. Kiran Godse & Dr. Anant Patil
M3 India Newsdesk Dec 11, 2019
Here is an expert analysis from Dr. Kiran Godse and Dr. Anant Patil, of the recently (2019) published studies on omalizumab for their relevance and usefulness in clinical practice for Indian doctors.
Chronic spontaneous urticaria (CSU) is a complex heterogeneous disease characterised by repeated occurrence of wheals and/or angioedema without specific external stimulus for more than 6 weeks. The international guideline [1] and Indian consensus statement [2] recommend use of second generation H1-antihistamines as first-line treatment in these patients. In patients not responding to the licensed dose of H1 antihistamine, up-dosing up to 4-fold is recommended. [1,2] However, many patients do not respond to the higher doses of non-sedating H1-antihistamines either. In these patients, omalizumab is a promising treatment and is recommended by international guideline as third-line treatment. [1,2]
Omalizumab is well studied, effective and well tolerated treatment option for patients with chronic spontaneous urticaria not responding to up-dosing (up to 4 times) of second generation non-sedating antihistamines. Omalizumab has been extensively studied for its use in the treatment of chronic urticaria. Several studies evaluating effects of omalizumab on blood and clinical parameters have been published in last few years. Increasing number of reports on omalizumab has helped dermatologists to better understand the place of omalizumab in clinical practice for the management of chronic urticaria. The published literature also provides insights on prediction of responders and patients who are likely to show resistance to omalizumab.
In this article, we analyse recently (2019) published studies on omalizumab for their relevance and usefulness in clinical practice.
Studies evaluating effects of omalizumab on immunoinflammatory cells
- A retrospective study [3] evaluating effect of omalizumab on immunoinflammatory cells in patients (n=74) with chronic spontaneous urticaria reported 12 weeks treatment results of significant reduction in neutrophil count, neutrophil/lymphocyte ratio and neutrophil/monocyte ratio.
- The results of another retrospective study [4] involving 74 patients showed rapid reduction in mean serum C-reactive protein and percentage of peripheral neutrophils within 3 months. Even at 12 months, the levels were significantly lower than baseline. The percentage of peripheral basophils increased significantly at third month and remained higher even at the 12th month.
- In a small retrospective study (n=11), [5] there was reduction serum eosinophil levels and increase in basophil percentage with omalizumab treatment.
Evidence from the randomised trials
The XTEND-CIU study [6] reported omalizumab treatment significant and early (at 12 weeks) and sustained improvement in symptoms and impairment in health related quality of life in patients with chronic idiopathic urticaria. In another randomised trial, [7] omalizumab in treatment responders normalised the gene expression of lesional skin in chronic spontaneous urticaria. A multicentre randomised, placebo controlled trial (n=22) [8] reported efficacy and safety of omalizumab in patients with cholinergic urticaria.
Although randomised clinical trials (RCTs) are considered gold standard in terms of evidence, real-life data is more relevant in clinical practice considering non-controlled situations unlike in clinical trials. In 2019, retrospective studies from different parts of the world have been published providing significant insights regarding the use of omalizumab.
Prediction of response to omalizumab
The results of a retrospective study (n=42) [9] reported that a better urticaria activity score over 7 days (UAS7), Urticaria Control Test, Dermatology Life Quality Index (DLQI), and Chronic Urticaria Quality of Life questionnaire score at the baseline might be the predictors of a better response to omalizumab and more improvement in QoL.
Other evidence from real world studies with omalizumab
A real world retrospective study [10] from Belgium involving 235 patients showed median time for initiation of omalizumab from the time of diagnosis was 6.7 months whereas mean interval between two injections of omalizumab was 4.8 (+1.7) weeks. Mean 7-day Urticaria Activity Score (UAS7) improved from 32 (+6.05) at baseline to 12.6 (+11.2) after one month of treatment with omalizumab. A total of 67.2% patients were well controlled (defined as UAS7 of 6 or lower). Patients who received omalizumab had severe disease at baseline.
A single centre retrospective real-life study (n=23) [11] from France reported effectiveness and safety of omalizumab (300 mg every 4 weeks) in patients refractory patients with chronic urticaria. A total of 13 (83%) patients reported either complete or significant remission. Interestingly, 9 (47%) patients showed complete/significant remission within 72 hours of first injection. Non-serious adverse events were reported by 52% patients.
A study [12] involving patients (n=1096) from the USA reported long term effectiveness of omalizumab. According to the results of this study, patients receiving mean of 15 injections over mean of 14.2 months show improved control of symptoms
In a retrospective study, Salman A and colleagues [13] evaluated effectiveness and safety of omalizumab 450 mg in patients (n=13) with chronic spontaneous urticaria. The mean UAS7 score reduced from 18.6 to 5.1 whereas mean UCT score increased from 8.6 to 12 after a mean 4.3 courses of 450 mg omalizumab treatment. The author concluded that omalizumab 450 mg is effective and well tolerated in patients nor responding to omalizumab 300 mg. A single-centre retrospective study [14] involving West Australian outpatients reported overall response rate of 67% in patients with treatment-resistant cases of chronic spontaneous urticaria.
Another retrospective study (n=106) [15] reported rapid and consistent improvement with omalizumab. Monotherapy or combination of omalizumab with antihistamines did not differ in the response. Its use with immunomodulatory agents was useful in some patients.
Results of another small (n=32) real life study [16] suggested that omalizumab may be considered as well-tolerated option even in patients with chronic spontaneous urticaria with comorbidities (cardio-metabolic, oncologic, infections, allergy, immunologic). Larger studies are needed to confirm these results.
Predicting resistance to omalizumab
Results of a retrospective observational study [17] suggested that presence of obesity, arterial hypertension, high plasma C3 level, and high-CRP level is associated with omalizumab resistance in patients with severe CSU.
A study from Spain (n=48) [18] reported results of omalizumab in patients with moderate to severe chronic spontaneous urticaria (defined as UAS >16) after at least 24 weeks of treatment and follow up. After 24 weeks, clinical response rate and complete response rate was 64.6% and 52.1% respectively. In this study, long duration of urticaria and prior immunosuppression use were associated with less likely to provide satisfactory clinical response at 12 weeks. Similarly, H1 antihistamine treatment was associated with less chances of response at 24 weeks.
In a retrospective Italian study (n=470), [19] total IgE correlated good response to omalizumab. The levels of IgE in responders were significantly higher as compared to those with non-responders. However, there was no correlation with levels of d-dimer.
Indian perspective
The experience on usage of omalizumab suggests its effectiveness and well-tolerated profile in patients with chronic spontaneous urticaria.
- It can be effectively use as third-line agent i.e. for those patients who do not respond to up to 4 times higher dosage of second generation non-sedating antihistamines.
- Cost of omalizumab treatment is an important factor which limits widespread usage of omalizumab in Indian patients.
- Patient counselling and setting the expectation of patients are important while using omalizumab in clinical practice for the treatment of chronic urticaria.
Webinar on "Urticaria Management" by Dr. Kiran Godse is scheduled on 20.12.19.Free registrations available here
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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.
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