Omalizumab for Chronic Idiopathic or Spontaneous Urticaria
Omalizumab for Chronic Idiopathic or Spontaneous Urticaria
Aim Maurer et al. (N Engl J Med 2013; 368: 924–35) aimed to evaluate the efficacy and safety of omalizumab (an IgE monoclonal antibody) in patients with moderate-to-severe chronic idiopathic urticaria who remain symptomatic despite H1-antihistamine therapy at licensed doses.
Setting and design Phase 3 international, multicentre, randomized, double-blinded study (ratio 1:1:1:1).
Study exposure Adults and adolescents aged over 12 years (or over 18 years in Germany) with chronic idiopathic urticaria, assigned to receive three subcutaneous injections of omalizumab 75, 150 or 300 mg, or placebo, over 12 weeks followed by a 16-week observation period.
Outcomes Outcome measures comprised scoring tools for itch and urticarial activity, including itch severity scores, 7-day Urticaria Activity Score (UAS7), size of largest hives, Dermatology Life Quality Index (DLQI) and proportion of angio-oedema-free days. Additional outcomes included Chronic Urticaria Quality of Life Questionnaire scores, interference with sleep and daily activities, use of rescue medications and any contact with a healthcare professional.
Primary outcome measure Change in the weekly itch severity scores (range 0–21) from baseline to week 12.
Results Overall, 323 patients were included in the trial. At week 12, the mean ± SD changes from baseline in the weekly itch severity score were −5·1 ± 5·6 in the placebo group, −5·9 ± 6·5 in the 75-mg group (P = 0·46), −8·1 ± 6·4 in the 150-mg group (P = 0·001) and −9·8 ± 6·0 in the 300-mg group (P < 0·001). During the follow-up period, the mean weekly itch severity scores for all treatment groups reached similar values to those in the placebo group. With respect to the secondary end points, a statistically significant difference was demonstrated between the placebo group and the 150-mg and 300-mg groups in all aspects: changes from baseline in UAS7 and weekly score for number of hives, time until reduction from baseline of > 5 points in the weekly itch severity score (referred to as minimally important difference, MID), proportion of patients with UAS7 of ≤ 6, the proportion of patients with the MID response in weekly itch severity scores, the change from baseline in score for size of largest hive, change from baseline in overall DLQI and proportion of angio-oedema-free days from weeks 4–12. Statistical significance was reached for one secondary outcome in the 300-mg group alone – difference in angio-oedema-free days from weeks 4–12. Most prespecified secondary outcomes at week 12 showed similar dose-dependent effects. The frequency of adverse events was similar across groups. The frequency of serious adverse events was low, although the rate was higher in the 300-mg group (6%) than in the placebo group (3%) or in either the 75-mg or 150-mg groups (1% for each).
Conclusions Maurer et al. conclude that omalizumab administered as 150-mg and 300-mg doses at 4-week intervals significantly reduced symptoms, compared with placebo, in patients with chronic idiopathic urticaria. The small sample size prevents definitive safety conclusions being drawn, although serious adverse events were more commonly observed in the group treated with the highest dose of omalizumab.
Abstract and Introduction
Abstract
Aim Maurer et al. (N Engl J Med 2013; 368: 924–35) aimed to evaluate the efficacy and safety of omalizumab (an IgE monoclonal antibody) in patients with moderate-to-severe chronic idiopathic urticaria who remain symptomatic despite H1-antihistamine therapy at licensed doses.
Setting and design Phase 3 international, multicentre, randomized, double-blinded study (ratio 1:1:1:1).
Study exposure Adults and adolescents aged over 12 years (or over 18 years in Germany) with chronic idiopathic urticaria, assigned to receive three subcutaneous injections of omalizumab 75, 150 or 300 mg, or placebo, over 12 weeks followed by a 16-week observation period.
Outcomes Outcome measures comprised scoring tools for itch and urticarial activity, including itch severity scores, 7-day Urticaria Activity Score (UAS7), size of largest hives, Dermatology Life Quality Index (DLQI) and proportion of angio-oedema-free days. Additional outcomes included Chronic Urticaria Quality of Life Questionnaire scores, interference with sleep and daily activities, use of rescue medications and any contact with a healthcare professional.
Primary outcome measure Change in the weekly itch severity scores (range 0–21) from baseline to week 12.
Results Overall, 323 patients were included in the trial. At week 12, the mean ± SD changes from baseline in the weekly itch severity score were −5·1 ± 5·6 in the placebo group, −5·9 ± 6·5 in the 75-mg group (P = 0·46), −8·1 ± 6·4 in the 150-mg group (P = 0·001) and −9·8 ± 6·0 in the 300-mg group (P < 0·001). During the follow-up period, the mean weekly itch severity scores for all treatment groups reached similar values to those in the placebo group. With respect to the secondary end points, a statistically significant difference was demonstrated between the placebo group and the 150-mg and 300-mg groups in all aspects: changes from baseline in UAS7 and weekly score for number of hives, time until reduction from baseline of > 5 points in the weekly itch severity score (referred to as minimally important difference, MID), proportion of patients with UAS7 of ≤ 6, the proportion of patients with the MID response in weekly itch severity scores, the change from baseline in score for size of largest hive, change from baseline in overall DLQI and proportion of angio-oedema-free days from weeks 4–12. Statistical significance was reached for one secondary outcome in the 300-mg group alone – difference in angio-oedema-free days from weeks 4–12. Most prespecified secondary outcomes at week 12 showed similar dose-dependent effects. The frequency of adverse events was similar across groups. The frequency of serious adverse events was low, although the rate was higher in the 300-mg group (6%) than in the placebo group (3%) or in either the 75-mg or 150-mg groups (1% for each).
Conclusions Maurer et al. conclude that omalizumab administered as 150-mg and 300-mg doses at 4-week intervals significantly reduced symptoms, compared with placebo, in patients with chronic idiopathic urticaria. The small sample size prevents definitive safety conclusions being drawn, although serious adverse events were more commonly observed in the group treated with the highest dose of omalizumab.