The Buzz by HIVE, Issue #10, December 2021
Issue #10, December 2021

We hope you have enjoyed and learned from the ten issues of The Buzz we provided in 2021, and we wish readers a happy and healthy New Year! This month, we feature two new randomized studies for monoclonal antibodies in CSU, a look at how Canadian parents view oral food challenge, Canadians' use of topical cannabinoids, and a scoping review for identifying drug culprits for adverse cutaneous drug reactions. View archived issues of The Buzz at


Ligelizumab Phase 2 extension study in CSU

Maurer and colleagues published the extension portion from a Phase 2 study of ligelizumab in patients with CSU. Ligelizumab is a humanized anti-IgE mAb under investigation for the treatment of CSU with inadequate control on standard therapies. The Phase 2 portion demonstrated a higher proportion of patients achieving a complete response when treated with ligelizumab compared to omalizumab or placebo. Patients in the extension study received 240 mg ligelizumab q4w for 52 weeks, and they were then followed for an additional 48 weeks. There were 226 patients enrolled in the extension study, comprising 95% of the original trial population, with a mean age of 44.5 years.

The primary outcome of the extension phase was safety, and no new safety signals were identified. The most frequently reported TEAEs were nasopharyngitis (25.2%), headache (12.8%), upper respiratory tract infection (10.2%), and urticaria (10.2%). Most of the events were classified as mild (41.6%) or moderate (35.8%). Minimal disease activity (UAS7 ≤ 6) was achieved in 54.4% (95% CI, 47.7, 61.0) of patients four weeks after the first dose of ligelizumab. At week 52, the rate was 61.1% (95% CI, 54.4, 67.5%) of patients. Complete response was observed in 53.1% (95% CI, 46.4, 59.7%) of patients at week 52. Ligelizumab is currently undergoing Phase 3 clinical trials in CSU.

Read more: [Sosido link] Maurer M, Giménez-Arnau A, Bernstein JA, et al. Sustained safety and efficacy of ligelizumab in patients with chronic spontaneous urticaria: A one-year extension study [published online ahead of print, 2021 Nov 13]. Allergy. 2021;10.1111/all.15175. doi:10.1111/all.15175


Phase 2 study of BTK inhibition in CSU

Despite highly active newer treatments such as omalizumab and ligelizumab, some patients with CSU do not respond and require alternative therapies. Those with type IIb autoimmune CSU appear to be more refractory to current treatments. Fenebrutinib an oral, potent, highly selective, reversible BTK inhibitor that blocks IgE-mediated histamine release from mast cells. The current publication details a randomized phase 2 study of fenebrutinib in CSU.

Enrolled patients had CSU for longer than six months and were symptomatic despite the use of up to 4x dose of H1 antihistamine. There were 94 patients randomized into the dose-ranging cohort of the study. Patients received placebo or fenebrutinib (50 or 150 mg daily or 200 mg twice daily). The primary end point (change from baseline in USAS7 at week 8) was met, with dose-dependent improvements in the 200 mg twice daily and 150 mg daily cohorts. Grade 2 and 3 liver transaminase elevations occurred in 2 patients in each of the fenebrutinib 150 mg daily and 200 mg twice daily groups. The results support further investigation of the use of BTK inhibitors in antihistamine-refractory CSU.

Read more: [Sosido link] Metz M, Sussman G, Gagnon R, et al. Fenebrutinib in H1 antihistaminerefractory chronic spontaneous urticaria: a randomized phase 2 trial. Nat Med. 2021;27(11):1961-1969. doi:10.1038/s41591-021-01537-w


Perceptions of oral food challenge among Canadian parents

To understand perceptions of oral food challenges (OFC), Correa and colleagues conducted extensive focus groups with Canadian parents of children with allergist-diagnosed food allergy. In total, 51 parents participated across six focus groups in British Columbia and Ontario. Most participants were of European descent, female, and of higher socioeconomic status. Half had children who had undergone OFCs and the median age of participants was 43 years.

Parents were asked what “oral food challenge” meant, why someone would need it, their experience with OFC and barriers to OFC. Parents frequently misunderstood the purpose of OFC, confusing it with desensitization or as a way to prevent future anaphylactic reactions. They perceived limited access to
OFC, push-back from primary care physicians against allergist referral, and that OFC was rarely offered by allergists. They preferred OFCs to take place in a hospital setting in case of emergency. The letter offers several potential solutions to the identified barriers.

Read more: [Sosido link] Correa N, L P Protudjer J, Hsu E, et al. Canadian parent perceptions of oral food challenges: A qualitative analysis [published online ahead of print, 2021 Nov 22]. Pediatr Allergy Immunol. 2021;10.1111/pai.13698. doi:10.1111/pai.13698


Topical cannabis use in Canada

Since legalization in 2018, cannabis use has expanded to include topical formations including various patches, creams, ointments, salves, soaps, and more. Many scientifically unsupported claims regarding therapeutic benefits of topical cannabis have been made, with dispensaries advertising dermatologic and non-dermatologic indications. The potential for benefit is based on cannabinoid binding to CB1 and CB2 receptors in skin cells. The authors conducted a survey to understand the use of topical cannabis in Canada. A total of 100 participants reported topical cannabis use and completed the full survey.

Participants were predominantly White (70%), and over half were university- or college-educated (55%). Most respondents were between the ages of 30-44 years. Creams were the most commonly used for of topical cannabis. The most common dermatologic conditions being treated included atopic dermatitis
(25%), acne (19%), anti- aging (16%), sunburn (15%), and pruritus (10%); for non-dermatologic conditions, common uses were for joint stiffness or tendonitis (30%), and headaches and migraines (27%). Twelve percent of participants had the topical cannabis medically prescribed, and 70% of respondents reported no side effects. Local side effects were reported in 30% of participants, most commonly skin erythema, irritation and pain, blistering, rash, and abnormal skin peeling. It is not clear if these events were due to the cannabinoids or the vehicle. Respondents reported receiving information from cannabis dispensaries (41%), website or blogs (37%), friend/family members (36%), or a doctor (32%). Clinical studies are needed to formally evaluate safety and efficacy. Patients should be screened for topical cannabis use.

Read more: [Sosido link] Mahmood F, Lim MM, Kirchhof MG. A Survey of Topical Cannabis Use in Canada [published online ahead of print, 2021 Nov 19]. J Cutan Med Surg. 2021; 12034754211059025. doi:10.1177/12034754211059025


Scoping review of methods to identify the causative agent in adverse cutaneous drug reactions 

Adverse drug reactions commonly involve the skin, pose significant risks, and are costly to the healthcare system. Bose and colleagues recognized there are no consensus guidelines on how to identify the culprit drug for cutaneous drug eruptions, so they conducted a scoping review. They searched the published literature for publications describing culprit drug identification methods, and categorized them by operational algorithms, probabilistic approaches, and expert judgement. There were 109 peer-reviewed studies included comprising 656,635 case events of adverse drug events. Thirty-three types of cutaneious drug eruptions were identified. More than 75% of studies reported the time from drug exposure to rash onset as a criterion for identification of culprit drugs.

Algorithms had higher sensitivity and positive predictive value, but lower specificity and negative predictive value. Probabilistic approaches had lower sensitivity and positive predictive value, but higher specificity and negative predictive value. Expert judgment was subjective, less reproducible, but the most frequently used to validate other methods. The authors state that their scoping review should lead to more studies and contribute to the development of consensus guidelines.

Read more: [Sosido link] Bose R, Ogbalidet S, Boshra M, et al. Methods for Identifying Culprit Drugs in Cutaneous Drug Eruptions: A Scoping Review [published online ahead of print, 2021 Nov 19]. J Cutan Med Surg. 2021;12034754211027509. doi:10.1177/12034754211027509


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