Patients with idiopathic angioedema show improvement with omalizumab

Patients with chronic spontaneous urticaria demonstrated improved outcomes related to idiopathic angioedema after taking omalizumab, according to a study presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting.

“The study was prompted by the observations that patients with idiopathic angioedema (IAE) tended to respond to omalizumab, but there were no prospective trials that we could point or refer to,” Vinay P. Goswamy, MD, an allergy and immunology fellow at University of Wisconsin School of Medicine and Public Health, told Healio.

“Additionally, we hypothesized that most patients with IAE had an underlying histaminergic mechanism involved, as opposed to a bradykinin-mediated mechanism that would not be responsive to omalizumab,” Goswamy said.

Current recommended therapy for IAE includes high-dose antihistamines at up to four times the daily dose; leukotriene-modifying medications such as montelukast; and H2 antagonists, which act on histaminergic pathways and are commonly used to treat gastric reflux and ulcers .

“For those with refractory symptoms, options are much more limited. Omalizumab is a relatively safe medication,” Goswamy said. “We have seen in the past, and found with this study, that it can be effective in patients with IAE.”

The study involved 10 adults with chronic spontaneous urticaria (CSU) who had been diagnosed with at least two episodes of IAE during the previous 6 months despite maintaining a stable H1-antagonist regimen.

Five (mean age, 53.8 years; 60% men) of these patients received 300 mg subcutaneous omalizumab (Xolair; Genentech, Novartis) and five (mean age, 53 years; 60% men) received placebo every 4 weeks for 24 weeks with a 12-week follow-up period.

The 6-month mean number of angioedema episodes was 10.6 among patients assigned omalizumab and 15.2 among patients assigned placebo.

Researchers recorded baseline scores for patients in the omalizumab and placebo groups for angioedema activity (AAS7; omalizumab, 1.6; placebo, 2.8), visual analog scale (VAS; 84; 91) and an angioedema quality-of-life questionnaire (AE-QOL; 21.5; 28.23).

After 24 weeks, patients who received omalizumab experienced fewer angioedema episodes per month compared with those on placebo (–1.93 in count; 95% CI, –3.23 to –0.63).

The patients on omalizumab also saw improvements in AAS7 scores (–2.93 in odds; 95% CI, –4.84 to –1.02), VAS (–3.49 in odds; 95% CI, –6.58 to –0.4) and AE-QOL (–9.43 score; 95% CI, –17.63 to –1.24).

There were no serious adverse events.

The researchers called the rapid improvement in IAE outcomes consistent with the rapid improvements that patients with CSU see with omalizumab treatment.

In fact, four of the five patients receiving omalizumab achieved AAS7 scores of 0 and VAS scores of 100 during the treatment period, suggesting apparent disease remission.

“Although we anticipated that omalizumab would be effective to reduce symptoms in these patients, we were surprised to see that four out of five patients in the treatment group had an apparent remission of disease activity throughout the treatment course,” Goswamy said.

Noting that IAE refers to unexplained episodes of angioedema without urticaria, the researchers said these findings support the hypothesis that IAE is a form of urticaria isolated to deeper layers of the skin.

However, Goswamy cautioned that the sample size was small and that the natural course of the disease includes periods when patients will remain asymptomatic spontaneously, which confounds the observation that four of five patients remained asymptomatic through the treatment period.

“Additionally, the patients in the study represented the entire spectrum of disease, from mild to severe, which also confounded this observation,” Goswamy said.

Prior to this study, the researchers noted that most patients had significant improvement in symptoms after being placed on omalizumab. However, achieving an 80% remission rate would be difficult for almost any medication if future studies were to only include severe cases, Goswamy said.

Still, he continued, this is the initial prospective evidence showing that omalizumab is safe and effective in treating patients with IAE.

“Physicians can use this evidence to counsel patients that omalizumab is likely to be effective for refractory symptoms in addition to citing it in order to obtain approval to use this medication,” Goswamy said.

Omalizumab also can serve as a diagnostic tool to help delineate between patients with histaminergic and bradykinin-mediated angioedema, Goswamy said, because there would be at least some response to omalizumab with histaminergic angioedema.

“This could have management implications if no response was noted, such as having a discussion about genetic testing for bradykinin-mediated angioedema or starting treatment for it,” he said.

Currently, no FDA-approved medication exists for histaminergic IAE, he said.

“Larger trials will be needed to confirm the results of any proof-of-concept studies such as this one,” Goswamy said. “I would suspect that those trials would include patients with moderate to severe histaminergic angioedema and exclude patients who have obtained remission with antihistamines, leukotriene-modifying medications and H2 antagonist alone.”

For more information:

Vinay P. Goswamy, MD, can be reached at vgoswamy@wisc.edu.