Tatevik Ohanyan

Omalizumab is an effective and rapidly acting therapy in difficult-to-treat chronic urticaria: A retrospective clinical analysis

BACKGROUND Omalizumab (anti-IgE) therapy is effective and safe in chronic urticaria (CU) in placebo-controlled clinical trials but real life clinical data are scarce. OBJECTIVE To better understand the effects of omalizumab in CU patients treated outside of clinical trials. METHODS In this retrospective clinical analysis, we assessed responder rates, optimal dosage, response to up-/downdosing, time to relief of symptoms, rates of return and time of relapse after omalizumab administration, and safety in 51 CU patients, 20 with chronic spontaneous urticaria (CSU) alone, 21 with different forms of chronic inducible urticaria (CindU) and 10 with both. RESULTS Omalizumab treatment led to complete remission in 83% of CSU and 70% of CindU patients. When starting with 150mg omalizumab 4 weekly, only 2/15 CSU and 7/17 CindU patients required updosing to achieve complete remission. In CSU, 57% of complete responses occurred within week one, all on the first day. Relapses were 2-8 weeks in all but six patients, where they were <4 months. Omalizumab was safe. Efficacy was not correlated to baseline IgE levels. CONCLUSION Clinical experience from more than 1250 injections in 51 patients over four years indicates that omalizumab is a rapidly acting, highly effective and safe drug in CSU and CindU patients. Our observations in a real life clinical setting support the recommendation of current EAACI/GA(2)LEN/EDF/WAO guideline for the management of urticaria to use omalizumab to treat urticaria patients.

Retreatment With Omalizumab Results in Rapid Remission in Chronic Spontaneous and Inducible Urticaria

IMPORTANCE Omalizumab has emerged as a novel and effective treatment option for patients with antihistamine-resistant chronic urticaria. It is unclear whether patients with recurrent urticaria symptoms after discontinuation of omalizumab treatment can benefit from retreatment. OBJECTIVE To assess the response of patients with chronic urticaria who receive omalizumab retreatment. DESIGN, SETTING, AND PARTICIPANTS Retrospective analyses were conducted of outpatients treated at an urticaria specialist center of a university hospital. Participants included 25 consecutive patients (aged 18-74 years; 18 women) with chronic spontaneous urticaria, chronic inducible urticaria, or both who showed complete response to omalizumab treatment, experienced relapse after discontinuation of treatment, and received retreatment with omalizumab. INTERVENTIONS Subcutaneous treatment with omalizumab (150-600 mg/mo). MAIN OUTCOMES AND MEASURES Response after retreatment was assessed by the urticaria activity score in patients with chronic spontaneous urticaria and by trigger threshold testing (in patients with cold urticaria or symptomatic dermographism) and/or a carefully determined history (in patients with cholinergic urticaria, solar urticaria, or pressure urticaria). Adverse events were documented. RESULTS All patients experienced complete response after retreatment. None of the patients reported relevant adverse events during omalizumab treatment and retreatment. CONCLUSIONS AND RELEVANCE Omalizumab retreatment is effective and safe in patients with chronic urticaria who have benefited from initial omalizumab treatment.

Responsiveness and minimal important difference of the urticaria control test

This study demonstrates the responsiveness of the Urticaria Control Test (UCT). Changes of its score by 3 points or more reflect a clinically relevant change of disease control (minimal important difference).

Omalizumab may not inhibit mast cell and basophil activation in vitro

In March 2014, omalizumab, a monoclonal anti‐IgE antibody, was approved for the treatment of chronic spontaneous urticaria (CSU). The primary mode of action of omalizumab is considered to be the reduction in free IgE serum levels and the subsequent down‐regulation of FcεRI, the high affinity receptor for IgE, on mast cells and basophils. Recently, it has been suggested that most CSU patients have an autoimmune aetiology which may lead to chronic activation of mast cells and basophils.

Comparison and Interpretability of the available Urticaria Activity Scores

The urticaria activity score (UAS) is the gold standard for assessing disease activity in patients with chronic spontaneous urticaria (CSU). Two different versions, the UAS7 and UAS7TD, are currently used in clinical trials and routine care. To compare both versions and to obtain data on their interpretability, 130 CSU patients applied both versions and globally rated their disease activity as none, mild, moderate, or severe. UAS7 and UAS7TD values correlated strongly (r = .90, P < .001). Interquartile ranges for UAS7 and UAS7TD values for mild, moderate, and severe CSU were 11‐20 and 10‐24, 16‐30 and 16‐32, and 27‐37 and 28‐40. UAS7 values were slightly, but significantly lower as compared to UAS7TD values (mean difference: 1.6 ± 4.6, P < .001). This difference was driven by lower wheal subscores (2.1 ± 3.5, P < .001) and was most pronounced in patients with severe CSU (2.5 ± 5.6, P < .01). The UAS7/UAS7TD ratio was 0.96 ± 0.21 and did not differ significantly between mild, moderate, and severe CSU. Since the results of both UAS versions are comparable, we recommend the use of the UAS7, which is less burdensome in administration and scoring.

Increased angiogenesis and VEGF expression correlates with disease severity in prurigo patients

Vascular endothelial growth factor‐A (VEGF‐A) is known as the major skin angiogenesis factor and can be produced by various resident skin cells including keratinocytes.

Real life treatment of Cholinergic Urticaria with Omalizumab

BACKGROUND Cholinergic urticaria (CholU), a frequent type of chronic inducible urticaria, presents with small itchy wheals upon physical exercise or passive warming. Omalizumab has been shown to be very effective in patients with chronic spontaneous urticaria. Whether or not omalizumab is also effective in CholU is largely unknown. AIM To assess the effectiveness of omalizumab treatment in CholU METHOD: We assessed the effects of real life omalizumab treatment at standard and higher than standard doses in CholU patients including their time to response, the effects on concomitant urticaria forms and links to clinical features. RESULTS Of 16 CholU patients treated with omalizumab, 11 (68%) reported a major or complete response, 2 patients reported a minor effect (13 %) and 3 patients (19%) showed no benefit. Omalizumab updosing led to complete response in 4 of 6 patients, who did not achieve controlled disease on standard dosed omalizumab therapy, i.e. 300 mg/4wks. Time to onset of benefit was fast, and concomitant urticaria forms showed similar response patterns. Treatment effects were linked to patient gender, with better responses in female patients (p < 0.05), but not patient age, age at onset of disease, duration of disease, or total IgE serum levels. CONCLUSION Omalizumab treatment is effective in the majority of CholU patients, especially in female patients. Most non-responders to standard-dosed omalizumab benefit from updosing. Our findings call for controlled clinical trials of omalizumab and other IgE-targeted treatments in CholU.

Development of tripe palms and soles in a patient with long pre‐existing systemic mastocytosis and newly developed non‐small cell lung cancer

Israel: clinical and genetic features. Arch Dermatol 2003; 139: 498–505. 4 Rugg EL, McLean WH, Lane EB et al. A functional “knockout” of human keratin 14. Genes Dev 1994; 8: 2563–2573. 5 Jonkman MF, Heeres K, Pas HH et al. Effects of keratin 14 ablation on the clinical and cellular phenotype in a kindred with recessive epidermolysis bullosa simplex. J Invest Dermatol 1996; 107: 764–769. 6 Batta K, Rugg EL, Wilson NJ et al. A keratin 14 ‘knockout’ mutation in recessive epidermolysis bullosa simplex resulting in less severe disease. Br J Dermatol 2000; 143: 621–627. 7 Lanschuetzer CM, Klausegger A, Pohla-Gubo G et al. A novel homozygous nonsense deletion/insertion mutation in the keratin 14 gene (Y248X; 744delC/insAG) causes recessive epidermolysis bullosa simplex type K€ obner. Clin Exp Dermatol 2003; 28: 77–79. 8 Has C, Chang YR, Volz A, Hoeping D, Kohlhase J, Bruckner-Tuderman L. Novel keratin 14 mutations in patients with severe recessive epidermolysis bullosa simplex. J Invest Dermatol 2006; 126: 1912–1914. 9 Yiasemides E, Trisnowati N, Su J et al. Clinical heterogeneity in recessive epidermolysis bullosa due to mutations in the keratin 14 gene, KRT14. Clin Exp Dermatol 2008; 33: 689–697. 10 Garc ıa M, Santiago JL, Terr on A et al. Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex. Br J Dermatol 2011; 165: 683–692.