The Surface by PSOLVE+, Issue #2, April 2021
Issue #2, April 2021

Welcome back to Issue #2 of The Surface, a monthly feature of the PSOLVE+ community where we summarize recent publications with high clinical relevance for Canadian dermatologists.
 

Vaccine literacy amongst patients with psoriasis

To understand vaccine literacy amongst patients with psoriasis, a short survey was conducted at one community-based dermatology practice in Ontario. The Canadian Immunization Guide recommends patients avoid live, attenuated vaccines while taking immunosuppressive therapies, including many biologics. Inactivated vaccines may be given during therapy if needed.

In this study, patients were assigned to the control group if they had never received a biologic, while those who were currently or previously on a biologic were assigned to the study group. The response rate for this survey was high, at over 80%. The percent of patients indicating that they understood the difference between live and killed virus vaccines was 32.7% in the control group and 37.5% in the study group. Importantly, 56% of patients in the study group were unsure if they could receive a live vaccine while on biologic therapy, and 64% were unsure if they could receive a killed vaccine. The results of this survey indicate a high need for education on the types of vaccines and their use in patients on chronic biologic treatment. Manufacturers of biologics should create patient education materials on vaccine safety with biologics as the SARS-CoV-2 vaccination program moves forward.

Read more: [Sosido link] Le H, Vender RB. A Psoriatic Patient-Based Survey on the Understanding of the Use of Vaccines While on Biologics During the COVID-19 Pandemic [published online ahead of print, 2021 Jan 27]. J Cutan Med Surg. 2021;1203475421991126. doi:10.1177/1203475421991126

Canadian Immunization Guide: Immunization of immunocompromised persons. Available at: [CIG Link] 

 

Pregnancy outcomes from the PSOLAR registry

A previous report on pregnancy outcomes from the Psoriasis Longitudinal Assessment and Registry (PSOLAR) registry (n=83 pregnancies) was presented at the AAD congress in 2014, before many of the newer biologic agents used in psoriasis were available. In an updated analysis of the PSOLAR registry, Kimball and colleagues present data on 298 pregnancies in 220 women. Biologic exposure before or during pregnancy was associated with 252 of the pregnancies. The results of the current study are reassuring and consistent with other publications reporting no significant differences in the number of live-born infants, spontaneous abortions, elective terminations, or congenital abnormalities among women with psoriasis exposed to biologics during pregnancy and the general population. Pregnancy data are also consistent with observations from women with rheumatic diseases and inflammatory bowel disease.

Read more: [Sosido link] Kimball AB, Guenther L, Kalia S, et al. Pregnancy Outcomes in Women With Moderate-to-Severe Psoriasis From the Psoriasis Longitudinal Assessment and Registry (PSOLAR) [published online ahead of print, 2021 Feb 3]. JAMA Dermatol. 2021;e205595. doi:10.1001/jamadermatol.2020.5595

 

Bimekizumab phase 3 results in moderate-to-severe plaque psoriasis

Two phase 3 studies with bimekizumab in patients with moderate-to-severe plaque psoriasis were published this month in the Lancet. Bimekizumab is a biologic targeting IL-17A and IL-17F. 

The first study, BE READY, was placebo-controlled and consisted of 16 weeks of initial treatment, followed by a 40-week randomized withdrawal study investigating two maintenance dosing schedules. The co-primary endpoints at week 16 were met: Percent of patients with PASI90 (90.8% vs 1.2%); and IGA response (92.6% vs 1.2%). As well, 68.2% of patients on bimekizumab achieved PASI100. Both q4w and q8w dosing was found to maintain response in over 85% of patients over the 40 weeks of maintenance dosing.

The second study, BE VIVID, compared bimekizumab to both placebo and ustekinumab during the initial 16 weeks. During the maintenance phase patients originally randomized to placebo were switched to bimekizumab. While bimekizumab was dosed at q4w in this study, ustekinumab dosing was held at q12w through the trial with no allowance for up-dosing, which may not reflect clinical use of this agent. Bimekizumab appeared to result in faster clearance and higher PASI than ustekinumab, and response was maintained with q4w dosing during the maintenance phase.

 
  IL-17-targeted agents   Inhibits
  Bimekizumab   IL-17A, IL-17F
  Secukinumab and ixekizumab   IL-17A
  Brodalumab   IL-17A, IL-17C, IL-17E, IL-17F
  (by inhibiting a common receptor subunit IL-17RA)

Read more: [Sosido Link] Gordon KB, Foley P, Krueger JG, et al. Bimekizumab efficacy and safety in moderate to severe plaque psoriasis (BE READY): a multicentre, double-blind, placebo-controlled, randomised withdrawal phase 3 trial. Lancet. 2021;397(10273):475-486. doi:10.1016/S0140-6736(21)00126-4

Read more: [Sosido Link] Reich K, Papp KA, Blauvelt A, et al. Bimekizumab versus ustekinumab for the treatment of moderate to severe plaque psoriasis (BE VIVID): efficacy and safety from a 52-week, multicentre, double-blind, active comparator and placebo controlled phase 3 trial [published correction appears in Lancet. 2021 Feb 20;397(10275):670]. Lancet. 2021;397(10273):487-498. doi:10.1016/S0140-6736(21)00125-2

 

Targeting the IL-23/IL-17 pathway in plaque psoriasis

This review focuses on the therapeutics targeting the interleukin (IL)-23/IL-17 pathway that are approved or in development for the treatment of psoriasis. Biologics that specifically target IL-23, IL-17 and IL-17RA have shown dramatically better skin clearance over the first-generation anti-TNF biologics. The review provides an algorithm that can be used to select the most appropriate biologic for patients with moderate-to-severe plaque psoriasis. It notes that IL-23 inhibitors may be preferred in patients with considerable skin involvement but without spondylarthritis, those that favour longer dosing intervals, and patients pre-disposed to Candida infections. IL-17 inhibitors should be the first choice in patients with extensive skin involvement and psoriatic arthritis or spondylarthritis, and when fast responses are needed. IL-17 treatments should be avoided in patients with inflammatory bowel disease. Therapeutic blockade of IL-23 or IL-17 translates into substantial reduction or complete disappearance of psoriatic lesions and improves the quality of life of most patients with psoriasis. Further research is needed on whether early intervention with these targeted agents can alter the natural course of psoriasis, and perhaps prevent the emergence of long-lived pathogenetic cells, signalling a potential cure for psoriasis.

Read more: [Sosido Link] Ghoreschi K, Balato A, Enerbäck C, Sabat R. Therapeutics targeting the IL-23 and IL-17 pathway in psoriasis. Lancet. 2021;397(10275):754-766. doi:10.1016/S0140-6736(21)

 

Compassionately addressing teratogenic risk factors in the transgender population

Kuritzky and Richer initially published their letter, “Considerations in Treating Severe Acne With Isotretinoin in Transgender Men” in the May 2020 edition of JCMS, and highlighted the need to compassionately counsel patients on the teratogenic risks associated with isotretinoin if they retained functional female reproductive organs. Haber responded by noting that amongst a small survey of transgender men, 20% reported conceiving while amenorrheic from testosterone therapy, and references the ethical considerations in the American iPLEDGE program. 

In their most recent response, the original authors note that Canadian practitioners are not bound by the American program. iPLEDGE strictly classifies patients according to their sex assigned at birth, coming in conflict with the patient’s right to self-identification. Physicians have a responsibility to thoughtfully manage risk factors for teratogenicity with isotretinoin therapy.

Read more: [Sosido Link] Kuritzky LA, Richer V. Response to Reader Comment on “Considerations in Treating Severe Acne With Isotretinoin in Transgender Men.” Journal of Cutaneous Medicine and Surgery. February 2021. doi:10.1177/1203475421994564

 

Real-world safety profile of acitretin in psoriasis patients

The authors of this study aimed to characterize the real-world safety profile of the synthetic retinoid acitretin using data from six outpatient dermatology clinics in Turkey, with doses between 10-50mg/day with no median dose stated in the manuscript. Adverse effects were observed in 93% of 412 patients, with cheilitis (71.4%), dry skin (62.5%), and palmoplantar skin peeling (37.2%) the most common. High triglyceride and high total cholesterol levels were observed in 50.0% and 49.5% of patients, respectively, and hepatoxicity rates were aligned with other reports in the literature. The median time on therapy was 18 months, with 55% of patients discontinuing treatment. By three years, 32% of patients remained on treatment.

Read more: [Sosido Link] Kara Polat A, Oguz Topal I, Aslan Kayıran M, et al. Drug survival and safety profile of acitretin monotherapy in patients with psoriasis: A multicenter retrospective study [published online ahead of print, 2021 Feb 1]. Dermatol Ther. 2021;e14834. doi:10.1111/dth.14834


 

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