Role of Substance P and Its Receptor Neurokinin 1 in Chronic Prurigo: A Randomized, Proof-of-Concept, Controlled Trial with Topical Aprepitant.

Substance P (SP) and its receptor neurokinin 1 (NK1R) are thought to be involved in the pathogenesis of chronic prurigo. Here, we assessed SP serum levels, cutaneous NK1R expression, and the effects of topical aprepitant, an NK1R antagonist, in patients with chronic prurigo. SP and NK1R were increased, compared with controls, in the serum and in lesional vs. non-lesional skin of the patients, respectively. Aprepitant, in a randomized, placebo-controlled, split-sided, doubleblind trial, reduced the intensity of pruritus as assessed by visual analogue scale by >50% from baseline to day 28 (-35.2), but so did placebo vehicle (-38.1, p= 0.76). Overall clinical scores improved significantly by day 28 in both treatment groups, with no significant difference between the 2 groups (p=0.32). Our findings imply that both SP and NK1R are involved in the pathogenesis of chronic prurigo. Parallel groupdesigned trials are needed to assess the efficacy of topical aprepitant treatment in this condition.

The Urticaria Activity Score-Validity, Reliability, and Responsiveness.

BACKGROUND: Chronic spontaneous urticaria is characterized by fluctuating symptoms. Its activity is assessed with the urticaria activity score (UAS). Two versions of the urticaria activity score used for 7 consecutive days (UAS7) are available: (1) The guideline-recommended UAS7, with once-daily documentation, and (2) the UAS7TD, with twice-daily documentation. OBJECTIVE: To better characterize both UAS7 versions with regard to their validity, reliability, sensitivity to change, minimal important difference (MID), and smallest detectable change (SDC). METHODS: One hundred thirty adult patients with chronic spontaneous urticaria completed both UAS7 versions, the Patients Global Assessment (PatGA) of disease activity, the Urticaria Control Test (UCT), the Chronic Urticaria Quality of Life Questionnaire, and the Dermatology Life Quality Index before and after the initiation of omalizumab therapy. Physicians completed a Physician Global Assessment of disease activity. RESULTS: The UAS7 and the UAS7TD showed high correlation with the activity anchor PatGA (r = 0.568, P < .001 and r = 0.605, P < .001) and the UCT (r = -0.580, P < .001 and r = -0.585, P < .001). The wheal and pruritus scores of the UAS7 and the UAS7TD exhibited respectable internal consistency and, in each UAS7 version, correlated well with each other (Cronbach α = 0.78, r = 0.640, P < .001, and Cronbach α = 0.77, r = 0.626, P < .001). Changes in the UAS7 and UAS7TD correlated well with PatGA changes (r = 639, P < .001, and r = .763, P < .001) and with UCT changes (r = -0.642, P < .001, and r = -0.703, P < .001). The MID was 11 for the UAS7 (SDC = 12) and 12 for the UAS7TD (SDC = 11). CONCLUSIONS: The UAS7 and UAS7TD show good and comparable clinimetric properties, including good sensitivity to change, and similar MIDs.

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.

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.