Issue #10, December 2021
In this issue of The Surface, we bring you information on third doses of the COVID-19 vaccines in dermatology patients, a cost-per-response analysis of biologic therapy, information on psoriasiform eruptions in pediatric AD patients, the risk of PsO in patients on antihypertensives, and a single-institution study of the frequency of upstaging in melanoma. View archived issues of The Surface at psolve.org/the-surface.
Third doses of COVID-19 mRNA vaccine in dermatology patients
Our first featured publication reviews the ACIP recommendation made in Augusts for third doses (“boosters”) of mRNA COVID-19 vaccines in immunocompromised patients, and makes recommendations for dermatology. The article was written when third doses were authorized in the USA only for certain “immunocompromised” individuals. This included patients treated for solid malignancy, those on chronic prednisone, transplant medications, methotrexate, TNFi, and other immunomodulatory biologic agents.
The article reviews the data for antibody responses in patients receiving various immunomodulatory therapies. The article notes that about half of transplant and hemodialysis patients who did not mount a detectible antibody response following doses 1 and 2 responded to the third dose.
Third doses are now rolling out across Canada with the highly transmissible omicron variant displacing delta. At the time of writing, NACI had recommended that adult patients taking chronic steroids, JAKi, TNFi, anti-IL12/23, anti-IL23, anti-IL17(R), and PDE4i be offered a third dose. Many provinces are rolling out third doses to all adults in the face of omicron. Readers are encouraged to check NACI for the latest Canadian recommendations.
Read more: [PubMed link] Waldman RA, Grant-Kels JM. Dermatology patients on biologics and certain other systemic therapies should receive a "booster" messenger RNA COVID-19 vaccine dose: A critical appraisal of recent Food and Drug Administration and Advisory Committee on Immunization Practices recommendations. J Am Acad Dermatol. 2021;85(5):1113-1116. doi:10.1016/j.jaad.2021.08.031
Italian economic analysis of biologic therapy for PsO
Zagni and colleagues used the Italian CANOVA study to evaluate biologic drug costs in plaque psoriasis (PsO). CANOVA is a multicentre, non-interventional longitudinal study conducted at Italian hospital dermatology clinics. There were 669 eligible patients in the study. The most commonly prescribed agents were secukinumab (41% of patients), ustekinumab (25%), adalimumab originator (13%), and ixekizumab (12%). The analysis included only direct resource costs borne by the Italian national healthcare system, including biologic drug costs, administration setting, concomitant PsO medications, biologic treatmentrelated adverse events, treatment follow-up and monitoring, and other interventions. A key limitation of the analysis is that indirect costs, including reduced productivity, were not included in the study.
Median treatment duration was 17.9 months and 52.1% of the sample were on their first biologic therapy for PsO. The average annualized management cost was €15,001, most of which was attributed to biologic acquisition. Adalimumab originator was associated with the lowest cost, while ixekizumab was
associated with the highest cost. At PASI 90, cost per response at 52 weeks was €22,755 for adalimumab originator, €23,978 for secukinumab, €24,743 for ixekizumab, and €27,522 for ustekinumab. A similar pattern held for PASI 100 responses. PASI 75 response rates at week 52 were observed in > 85% for all the treatment groups, demonstrating remarkable clinical benefit at one year. Costs were not adjusted for baseline characteristics, so it is possible that patients with more challenging disease were offered highercost therapies.
Read more: [Sosido link] Zagni E, Bianchi L, Fabbrocini G, et al. A real-world economic analysis of biologic therapies for moderate-to-severe plaque psoriasis in Italy: results of the CANOVA observational longitudinal study. BMC Health Serv Res. 2021;21(1):924. Published 2021 Sep 6. doi:10.1186/ s12913-021-06866-7
Psoriasiform eruptions in children taking dupilumab for atopic dermatitis
Parker and colleagues present a retrospective analysis of psoriasiform eruptions in children taking dupilumab for atopic dermatitis (AD). They found six cases in children from ages 4-18 years who developed psoriasiform dermatitis, and one additional case of undiagnosed psoriasis that had been masked by the AD. All of the children had severe AD at baseline and five of six experienced a 3-point improvement in IGA with dupilumab treatment. None had a known family history of psoriasis. The newonset psoriasiform plaques appeared at a median treatment duration of eight months (range, 6- 12 months), at sites typically observed with psoriasis. Lesions were visually distinct from the AD lesions.
Biopsies were not performed, therefore the mechanism for dupilumab-associated psoriasiform lesions in the children in unknown. One patient had inadequate AD response to dupilumab, switched to ustekinumab to control the psoriasis with tofacitinib and IVIG for the AD. The other patients continued
dupilumab while using topical corticosteroid to control the psoriasiform lesions.
Read more: [Sosido link] Parker JJ, Sugarman JL, Silverberg NB, et al. Psoriasiform dermatitis during dupilumab treatment for moderate-to-severe atopic dermatitis in children [published online ahead of print, 2021 Oct 14]. Pediatr Dermatol. 2021;10.1111/pde.14820. doi:10.1111/pde.14820
Risk of PsO in patients taking beta-blockers for hypertension
A retrospective cohort study was undertaken to evaluate if there is an association between beta-blocker use and development of de novo psoriasis in patients with hypertension. The study leveraged the National Health Insurance Service database in South Korea, and included patients diagnosed with hypertension between 2004 and 2013. The exposed group included patient treated with beta-blockers for at least 90 consecutive days. 105,529 patients were included, with equal numbers of men and women.
In total, 2905 patients (1698 males and 1207 females) developed psoriasis during the study period. The group that developed psoriasis had a significantly higher proportion of current or previous smokers and BMI ≥ 18.5. Diabetes and hyperlipidemia were significantly higher in the psoriasis group. When the exposed and unexposed groups were compared, there were no statistical differences found in the rate of de novo PsO (P = 0.77 at year 1 and P = 0.96 at year 2), and the odds ratio demonstrated no increased risk (OR, 0.95, 95% CI 0.61-1.48)). One major limitation of the study was that only the first antihypertensive used was evaluated, and only at the one- and two-year timepoints.
Read more: [PubMed link] Duncan JR, Beal LL, Daugherty A, et al. Management of Transected Invasive Melanoma: A Single Institution Retrospective Review. Dermatol Surg. 2022;48(1):47-50. doi:10.1097/ DSS.0000000000003283
Upstaging of transected invasive melanoma
Prior studies have demonstrated deep transection of invasive melanoma during initial biopsy can lead to inaccurate staging. A search of a single institution’s biopsy reports for melanoma during 2017 to 2019 was conducted. Biopsy reports for primary cutaneous invasive melanomas were included. Tumors were excluded if they were in situ, non-cutaneous, metastases, recurrences, or if the biopsy report did not include a deep margin status. Included biopsy reports were then further analyzed to identify cases in which the initial biopsy was deeply transected. These reports were compared to excisional pathology reports for an increase in Breslow depth compared to initial biopsy, upstaging based on AJCC criteria, and upstaging that would have changed the NCCN-recommended management.
A total of 726 tumors met the inclusion criteria, with a median patient age of 62.9 years. There were 360 (47.2%) deeply transected tumours in the sample. Among the transected cases, 86 (23.9%) had an increase in Breslow depth and 58 (16.1%) were upstaged based on excisional pathology. 49 (13.6%) of
the transected cases had upstaging that would have resulted in a change in initial NCCN-recommended management. Broad transection and gross residual tumor or pigment after biopsy predicted higher likelihood of upstaging.
Read more: [PubMed link] Kim YE, Cho Y, Jo SJ. Risk of de novo psoriasis in hypertension patients initially treated with beta-blockers: Nationwide population-based cohort study in Korea [published online ahead of print, 2021 Oct 9]. J Eur Acad Dermatol Venereol. 2021;10.1111/jdv.17733. doi:10.1111/jdv.17733
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