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Issue #4, June 2021
Welcome back to The Surface, a monthly feature of the PSOLVE+ community where we summarize recent publications with high clinical relevance for Canadian dermatologists. View archived issues of The Surface at psolve.org/the-surface.
Safety and efficacy of secukinumab in a single, 300mg/2mL pre-filled syringe
In Canada, secukinumab is currently available in two devices: a pre-filled syringe (PFS) or an autoinjector, both of which contain 150mg of active agent in a 1mL solution. Two injections are required to deliver the approved adult PsO dose of 300mg. The ALLURE study is a phase 3, randomized, double-blind, placebo-controlled trial that measured efficacy, pharmacokinetics, tolerability, patient usability, and satisfaction with a larger volume PFS (300mg/2mL). This would allow the full adult PsO dose to be delivered in a single injection. Comparator arms were placebo and the standard two 150mg/1mL secukinumab PFS injections.
At week 12, the secukinumab 300mg/2mL PFS was superior to placebo for PASI 75 (88.9% vs 1.7%; p<0.0001), and IGA 0/1 (76.4% vs 1.4%; p<0.0001). Risk differences were 65.09 (95% CI, 53.77 to 76.41) for PASI 90, and 38.75 (95% CI, 27.41 to 50.09) for PASI 100 endpoints. A single 300mg injection showed comparable efficacy to the established two 150mg injections at week 52. Pharmacokinetics were measured at week 4 and were similar between the two dosing devices. Exposure and time to reach peak concentration were also similar, and there were no new or specific safety findings with the 300mg/2mL PFS. The proportion of patients either “satisfied” or “very satisfied” with self-injecting the 300mg2mL PFS reached over 90% at week 28.
The study demonstrated a rapid onset of response with superior efficacy compared to placebo in the treatment of patients with moderate-to-severe chronic plaque PsO and favorable safety profile with a single, 300mg injection of secukinumab delivered by PFS.
Read more: [Sosido link] Sigurgeirsson B, Schäkel K, Hong CH, et al. Efficacy, tolerability, patient usability, and satisfaction with a 2 mL pre-filled syringe containing secukinumab 300 mg in patients with moderate to severe plaque psoriasis: results from the phase 3 randomized, double-blind, placebo-controlled ALLURE study [published online ahead of print, 2021 Apr 26]. J Dermatolog Treat. 2021;1-9. doi:10.1080/09546634.2021.1902925
Risk of malignancy with up to five years of secukinumab treatment
Chronic inflammatory diseases are associated with higher risk for malignancy owing both to the disease itself as well as some immunosuppressive and immunomodulatory therapies. The secukinumab clinical studies reported low exposure-adjusted incidence rates (EAIR) of malignancy. The current study aims to evaluate the risk of malignancy with secukinumab over a longer treatment period. The authors conducted an integrated safety analysis from the secukinumab clinical trial program and post-marketing safety surveillance data. Included in the analysis were data from a total of 14,519 patients (10,685 PsO, 2,523 PsA, and 1,311 axSpA) treated with secukinumab for up to five years.
The EAIR of malignant or unspecified tumor was 0.85 (95% CI, 0.74 to 0.98) per 100 patient treatmentyears (PTY), and the risk for malignancy did not increase over time with secukinumab treatment. The two most common malignancies were both non-melanoma skin cancers: basal cell carcinoma followed by squamous cell carcinoma. No cases of lymphoma were reported. Using the SEER database as a comparison, the pooled standardized incidence rate (SIR) was 0.99 (95% CI, 0.82 to 1.19) for secukinumab-treated patients, indicating no difference in the observed rate compared to the expected rate. No difference was found as well when considering different doses of secukinumab (150mg and 300mg), or the individual indications. The authors conclude that the risk of malignancy events does not appear to be increased compared to the reference population for up to five years of secukinumab treatment.
Readers are reminded that in Issue #1 of The Surface (psolve.org/the-surface) we highlighted an Ontario database analysis of malignancy risk in the psoriasis population.
Read more: [Sosido link] Lebwohl M, Deodhar A, Griffiths CEM, et al. The risk of malignancy in secukinumab-treated psoriasis, psoriatic arthritis and ankylosing spondylitis patients: analysis of up to five-year clinical trial and post-marketing surveillance data [published online ahead of print, 2021 Apr 8]. Br J Dermatol. 2021;10.1111/bjd.20136. doi:10.1111/bjd.20136
Reviewing the evidence for over-the-counter supplements in dermatology
Thompson and Kim provide a review of the limited evidence supporting use of over-the-counter supplements in dermatology, including zinc, biotin, vitamin D, nicotinamide and Polypodium. There are few randomized controlled studies evaluating the efficacy and safety of these supplements, but the review provides, in helpful table format, a summary of the evidence for each product. The authors suggest there is some evidence for clinical uses of vitamin D, nicotinamide and Polypodium, but insufficient evidence exists for biotin and zinc.
For vitamin D, there are a few randomized trials that demonstrated a reduction in Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, S aureus colonization and erythema index in atopic dermatitis. Data in PsO is scarcer, and data in melanoma and non-melanoma skin cancers (NMSC) is likely confounded by sun exposure. Nicotinamide, a precursor involved in the PARP DNA repair pathway, has some weak evidence to suggest reduced actinic keratosis counts and lower rates of NMSC while taking the supplement, but these effects do not persist after discontinuation. Preliminary, small, randomized studies suggest a role for Polypodium leucotomos extract as an adjunct in photodermatoses, melasma and actinic damage.
Read more: [Sosido link] Thompson KG, Kim N. Dietary supplements in dermatology: A review of the evidence for zinc, biotin, vitamin D, nicotinamide, and Polypodium. J Am Acad Dermatol. 2021;84(4):1042-1050. doi:10.1016/j.jaad.2020.04.123
Telogen effluvium patient demographics during the pandemic
Cline and colleagues present demographic information on a series of telogen effluvium (TE) cases at 8 hospitals in New York City. They found a nearly 3-fold increase in the incidence of TE in the seven months after March 1, 2020 (COVID-19 pandemic) compared with the prior seven months (pre-pandemic). In the pandemic cohort, 10 patients tested positive for COVID-19, while 98 patients were either negative or untested. Of those testing positive, 90% had at least one underlying medical condition that is associated with poorer outcomes of SARS-CoV-2 infection.
Interestingly, while the number of Caucasian patients identified during the pandemic was similar to the pre-pandemic period (9 cases vs 8 cases, respectively), the incidence of TE was significantly increased in Hispanic (65 vs 19 cases) and other non-White individuals (31 vs 8 cases). Cases in Blacks were much less frequently identified both before (n=4) and during (n=3) the pandemic. The authors hypothesize that hair loss disorders may have ethnic and racial disparities, and suggest further study is needed.
Read more: [Sosido link] Cline A, Jacobs AK, Fonseca M, et al. Race, ethnicity, and comorbidities are critical factors in the diagnosis of telogen effluvium during the COVID-19 pandemic [published online ahead of print, 2021 Apr 8]. J Am Acad Dermatol. 2021;S0190-9622(21)00667-8. doi:10.1016/j.jaad.2021.03.099
North American Contact Dermatitis Group patch testing with sodium disulfite
Sodium disulfite (SD), like other sulfites, has been used as an antioxidant, preservative, and bleaching agent in the food, drug, and cosmetic industries. It has been associated with Type I and allergic contact dermatitis (ACD) reactions. The current study aimed to characterize the profile of ACD using the North American Contact Dermatitis Group (NACDG) patch test data. The study examined 4885 patients who were tested, of whom 132 (2.7%) had a positive reaction.
Compared to SD-negative patients, SD-positive patients were more likely to be male (51.9% vs 27.8%, p<0.0001) and over 40 years of age (78.0% vs 64.5%, p=0.0011). Three cases were related to occupational exposure. Personal care products (especially hair dyes) and topical medications (especially antifungals) were the two most commonly found sources of primary exposure to SD.
Read more: [Sosido link] Warshaw EM, Buonomo M, DeKoven JG, et al. Patch testing with sodium disulfite: North American Contact Dermatitis Group experience, 2017 to 2018 [published online ahead of print, 2021 Apr 11]. Contact Dermatitis. 2021; 10.1111/cod.13860. doi:10.1111/cod.13860
Hereditary angioedema in the emergency department
Data from the US indicate approximate 100,000 emergency department visits per year are due to hereditary angioedema (HAE) or acquired angioedema (AAE), which can cause fatal asphyxiation if the larynx is involved. The attacks can be mediated by either histamine or bradykinin – and treatment will differ based on the mediator. Urticaria with angioedema suggests a histamine-mediated mechanism, which can be treated with removal of the trigger and treatment with antihistamines, corticosteroids, or epinephrine. In bradykinin-mediated angioedema, urticaria are generally not present and attacks do not respond to conventional treatment. The authors describe warning signs that emergency physicians should be aware of and review several new classes of agents for treatment of HAE, including plasmaderived and human recombinant C1 inhibitors, bradykinin B2 receptor antagonists, and kallikrein inhibitors.
While the article is interesting, readers of The Surface are also directed to the International/Canadian Hereditary Angioedema Guideline published in 2019.
Read more:
[Sosido Link] Serpa FS, Mansour E, Aun MV, et al. Hereditary angioedema: how to approach it at the emergency department? Einstein (Sao Paulo). 2021;19:eRW5498. Published 2021 Apr 9. doi:10.31744/einstein_journal/2021RW5498
[Sosido Link] Betschel S, Badiou J, Binkley K, et al. The International/Canadian Hereditary Angioedema Guideline [published correction appears in Allergy Asthma Clin Immunol. 2020 May 6;16:33]. Allergy Asthma Clin Immunol. 2019;15:72. Published 2019 Nov 25. doi:10.1186/s13223-019-0376-8
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