Ligelizumab improves symptoms, QoL in patients with urticaria

In patients with chronic spontaneous urticaria (CSU) who remained symptomatic despite treatment, the monoclonal anti-immunoglobulin E antibody ligelizumab improved symptom control regardless of BHRA* status, as well as dermatology quality of life (QoL) regardless of angioedema status, findings from a phase IIb study have shown.

In this trial, individuals with moderate-to-severe (ie, weekly UAS7** ≥16) CSU were randomized 1:2:2:2:2 to receive SC ligelizumab 24, 72, or 240 mg, omalizumab 300 mg, or placebo Q4W for 20 weeks. After which, patients who continued to have active disease (ie, UAS7 ≥12) may enter the open-label extension (OLE) phase wherein they received ligelizumab 240 mg Q4W from week 32 onwards.

Improved symptoms regardless of BHRA status

This analysis included patients on ligelizumab 72 mg, ligelizumab 240 mg, and omalizumab 300 mg (n=253). Of these, 60 percent were BHRA-negative (BHRA–). [AAAAI 2022, abstract 538]

At baseline, mean UAS7 among ligelizumab recipients were 31.1 and 29.6 for the respective 72 and 240-mg doses in the BHRA– subgroup. Similar values were seen in the BHRA+ cohort (mean UAS7, 32.7 and 31.3, respectively). By week 12, absolute mean changes from baseline UAS7 were –22.7 (72 mg) and –22.3 (240 mg) in the BHRA– subgroup. In the BHRA+ subset, the corresponding values were –21.0 and –21.1.

“[These imply that] baseline BHRA status of CSU patients did not impact response to ligelizumab,” said Dr Karl Sitz from Little Rock Allergy and Asthma Clinic, Little Rock, Arkansas, US, during his presentation.

UAS7=0** responder rates at week 12 for the respective ligelizumab 72- and 240-mg doses were 46 percent and 42 percent (BHRA–) and 41 and 37 percent (BHRA+).

Compared with patients on omalizumab, those on ligelizumab 72 mg were more likely to achieve UAS7=0 response at week 12 (odds ratios [ORs], 1.43 [BHRA–] and 6.00 [BHRA+]). A similar effect was seen in the comparison between ligelizumab 240 mg and omalizumab (ORs, 1.21 and 5.21, respectively).

“[These findings support the] therapeutic benefit [of ligelizumab] in CSU patients, with high rates of complete response, regardless of their BHRA status,” said Sitz.

Better QoL irrespective of angioedema

This analysis used data from the core*** and OLE studies (n=297 and 226, respectively). Among participants with angioedema (n=165 and 84, respectively), mean baseline AAS7^# ranged between 30.6 and 42.2 in the core study and was 30.9 in the OLE study. [AAAAI 2022, abstract 539]

“The least squares mean change from baseline in AAS7 evaluated for patients with angioedema, by treatment groups, was larger with ligelizumab compared with omalizumab or placebo,” noted Dr Weily Soong from AllerVie Health, Birmingham, Alabama, US.

Patients with angioedema had higher mean DLQI^## at baseline compared with angioedema-free patients, both in the core (range, 14.9–16.1 vs 10.6–12.0) and OLE studies (15.7 vs 12.6). The higher DLQI at baseline among patients with angioedema indicates a more severe impact of the disease on dermatology QoL vs those without angioedema, noted Soong.

Following ligelizumab treatment, mean DLQI were comparable between patients with and without angioedema by week 12 (5.1 vs 2.7 [72 mg] and 4.4 vs 3.4 [240 mg]).

“Overall data from the core and OLE studies showed that lower AAS7 were significantly associated with better dermatology QoL outcomes,” said Soong.

“Complete control of symptoms of urticaria and angioedema may normalize patients’ health-related QoL … [Our finding suggest that] ligelizumab may provide an effective therapeutic option for CSU patients with angioedema,” Soong concluded.

The phase III PEARL studies are underway to further shed light on the benefit of ligelizumab for CSU, a distressing and unpredictable disease characterized by spontaneous occurrence of itchy hives, angioedema, or both, for >6 weeks without specific external stimuli. [Allergy 2018;73:1393-1414; N Engl J Med 2019;381:1321-1332; Allergy 2022:77;734-766]