Effectiveness and safety of omalizumab in chronic spontaneous or inducible urticaria: evaluation of 154 patients

Dear Editor, Out‐of‐trial data on long‐term safety and predictors of effectiveness of omalizumab (anti‐IgE) in chronic urticaria are lacking. We evaluated the outcome of treatment with omalizumab in a large cohort of patients with chronic spontaneous or chronic inducible urticaria (CSU and CINDU, respectively). Data were retrieved via retrospective review of patient records from a tertiary dermatological referral centre (Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark). Complete ascertainment of patient records was possible as the department keeps track of all administered biological therapy. A consultant dermatologist (S.F.T.) verified the urticaria diagnosis and assessed response to treatment. Two authors (M.N.G. and S.F.T.) extracted the data and, in cases of disagreement, consensus was obtained by discussion with all the authors. According to Danish law, scientific ethics approval is not needed for retrospective chart reviews. Approval for the study was obtained from the National Board of Health (to examine patient records) and from the Data Protection Agency (to save patient data on file). All patients diagnosed with CSU or CINDU who had received at least one injection of omalizumab from 30 June 2010 to 31 December 2014 were included in the study. Response to omalizumab treatment was graded according to the degree of relief of symptoms reported by the patient and according to the physician's assessment. It was possible to score the clinical response to treatment with omalizumab for each patient as a ‘complete or almost complete response’, ‘partial response’ and ‘no/limited response’ after 3–6 months of treatment. This grading is in accordance with the modified physician global assessment used in other dermatological diseases, where a complete or almost complete response corresponds to ≥ 90% reduction of symptoms; partial response is reduction in symptoms of between 30% and 89%; and no response or a limited response is a reduction in symptoms of 85% of patients. There was a statistically nonsignificant tendency for a better response to treatment among patients with a late age at onset and a shorter duration of urticaria. There was no significant effect of sex or smoking on treatment response. Also, the effect of omalizumab was not significantly different in patients receiving 300 mg every 4 weeks compared with patients receiving 150 mg every 2 weeks (65·8% vs. 68·9%; OR 1·15, 95% CI 0·56–2·38 (P = 0·70)]. Of the 17 patients with CINDU, nine (53%) had a complete or almost complete response to treatment: three of the five patients with delayed pressure urticaria; two of the five patients with cold urticaria; three of the four patients with cholinergic urticaria; and one of the two patients with symptomatic dermographism. The patient with solar urticaria had no response to treatment. Fourteen percent reported adverse effects during treatment with omalizumab. Reported adverse effects were, in descending order of frequency, suspected allergic reactions, gastrointestinal symptoms, injection site reactions, worsening urticaria, headache, dizziness, arthritis and fatigue. The drug was administered in the outpatient clinic, with the exception of a few patients who were treated at home by autoinjection. Patients were monitored 30 min after each injection. The suspected allergic reactions occurred during or immediately after administration of the drug but after retrospective evaluation were probably vasovagal syncopes and not suspected to be anaphylaxis. Worsening urticaria was only observed in two patients in the weeks after one of the two‐first injections, and was probably related to slow or absence of response to treatment rather than to genuine worsening of urticaria. All observed suspected side‐effects were reversible. One year after initiation of omalizumab, 56% of the patients with CSU were still on continuous treatment, while 44% had discontinued treatment owing to any cause. The median overall drug survival for the first round of treatment (discontinuation owing to any cause) in patients with CSU was 406 days (range 325–487); 462 days (range 305–619) for women and 364 days (range 332–496) for men (P = 0·41 for the difference between men and women). The most common causes of discontinuation were symptomatic remission or lack of effect, whereas a smaller proportion discontinued because of nonadherence to scheduled ambulatory visits, adverse effects or pregnancy (Table 2). Of the patients who discontinued treatment with omalizumab owing to symptomatic remission, 58% (n = 14/24) resumed treatment one or more times at a later stage owing to recurrence of symptoms. Among these, the effect of omalizumab was comparable with the first round of treatment. Of interest, 10 patients with CSU did not resume treatment with omalizumab owing to long‐term symptomatic remission and were eventually discontinued from the department. This corresponds to an overall remission rate of 7% out of the 137 patients with CSU, which is lower than the inferred 1‐year remission rates observed in most but not in all previous studies of the natural history of CSU.11 12 13 14 Outcome of treatment 1 year after initiation of omalizumab in 154 patients with chronic spontaneous urticaria (CSU) or chronic inducible urticaria (CINDU) aOf the patients on continuous treatment (n = 20), 17 with CSU and three with CINDU had been on treatment for 85% of the cases. It is of novel interest that response to omalizumab is better in patients with a negative HR test, i.e. in patients with nonautoreactive CSU. However, this finding is in accordance with previous studies that have associated longer duration and severity of CSU, with the presence of a positive autologous serum test.12 In a clinical setting, documentation of autoreactivity in CSU should therefore be accommodated in the decision of when to deem a patient a nonresponder. This study was retrospective and examined the effect of omalizumab in a single dermatological centre. Furthermore, no validated instruments for measuring urticaria severity, such as the Urticaria Activity Score or the Urticaria Control Test,15 16 were employed to more objectively estimate the effect of omalizumab treatment. Future prospective studies of chronic urticaria should examine in more detail the clinical and paraclinical predictors of response, and the adverse effects of omalizumab. Funding sources: none. Conflicts of interest: none declared.