News - June 2021

New FDA Approval to Treat Moderate to Severe Pediatric Psoriasis
The FDA announced approval of secukinumab, an IL-17 inhibitor, for the treatment of moderate to severe plaque psoriasis in patients aged 6 years and older.

The approved dosing is 75 mg or 150 mg, dependent on the child’s weight at dosing (<50kg and ≥50kg, respectively), and is administered by subcutaneous injection every 4 weeks following an initial loading regimen. Trained adult caregivers can administer secukinumab either by single-dose prefilled syringe or by autoinjector pen.

Approval is based on two phase 3 studies that evaluated secukinumab in patients aged 6 to less than 18 years. In a 52-week, randomized, double-blind, placebo- and active-controlled study, secukinumab reduced psoriasis severity at week 12 compared with placebo. Of the 162 included patients, 70% of patients receiving either dosing of secukinumab achieved Psoriasis Area Severity Index (PASI) 75. Similarly, 56% of patients receiving secukinumab achieved clear or almost clear skin responses on Investigator’s Global Assessment. The second trial, a randomized open-label, 208-week trial of 84 patients aged 6 years and older, demonstrated similar efficacy and safety.

Secukinumab is also indicated to treat moderate to severe plaque psoriasis in patients aged 18 years and older, active psoriatic arthritis, active ankylosing spondylitis, and active nonradiographic axial spondylarthritis and objective signs of inflammation.

Reference
Novartis Cosentyx receives FDA approval for treatment of children and adolescents with moderate to severe plaque psoriasis. News release. Novartis Pharmaceuticals Corporation; June 1, 2021. Accessed June 1, 2021. https://prnmedia.prnewswire.com/news-releases/novartis-cosentyx-receives-fda-approval-for-treatment-of-children-and-adolescents-with-moderate-to-severe-plaque-psoriasis-301303365.html

New JAK Inhibitor Shows Efficacy, Safety in Phase 3 Trials for Atopic Dermatitis
Upadacitinib, an oral Janus kinase (JAK) 1 inhibitor, was found to be safe and efficacious for the treatment of atopic dermatitis (AD) in two phase 3 clinical trials. The results of the trials were published in The Lancet.

The Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) trials were replicate multicenter, randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of upadacitinib. Patients aged 12 to 75 years with moderate to severe AD were randomly assigned to receive either upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily for 16 weeks.

In total, 1683 patients were included in the studies, with 557 patients in the 15-mg groups, 567 patients in the 30-mg groups, and 559 patients in the placebo groups. Primary endpoints were the proportion of patients who achieved at least a 75% improvement in Eczema Area and Severity Index (EASI) and the proportion of patients who achieved clear or almost clear on the validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD).

At the end of 16 weeks, the primary endpoints were met in both studies. In Measure Up 1, 70% of patients in the 15-mg group and 80% in the 30-mg group achieved EASI 75 or greater; similarly, in Measure Up 2, 60% receiving 15-mg upadacitinib and 73% receiving 30-mg upadacitinib achieved at least EASI 75. For vIGA-AD, 48% and 39% of patients who received 15-mg upadacitinib and 62% and 52% receiving 30-mg upadacitinib in Measure Up 1 and 2, respectively, achieved clear or almost clear at 16 weeks.

Treatment-emergent adverse events included

• Acne (54 patients receiving 15mg upadacitinib, 90 receiving 30mg);
• Upper respiratory tract infection (44 patients receiving 15mg upadacitinib, 55 receiving 30mg);
• Nasopharyngitis (38 patients receiving 15mg upadacitinib, 51 receiving 30mg);
• Headache (32 patients receiving 15mg upadacitinib, 39 receiving 30mg);
• Elevation in creatine phosphokinase levels (25 patients receiving 15mg upadacitinib, 28 receiving 30mg); and
• Atopic dermatitis (17 patients receiving 15mg upadacitinib, 8 receiving 30mg).

“Monotherapy with upadacitinib might be an effective treatment option and had a positive benefit–risk profile in adolescents and adults with moderate to severe AD,” concluded the study authors.

Reference
Guttman-Yassky E, Teixeira HD, Simpson EL, et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials. Lancet. Published online May 20, 2021. doi:10.1016/S0140-6736(21)00588-2

Treatment-Resistant Actinic Keratoses Characterized by Increased Pain, Acantholysis, and Distinct Histological Features
Treatment-resistant actinic keratoses (trAK) are painful and show acantholysis with distinct basal proliferation, according to a recent study published in Italian Journal of Dermatology and Venereology.

“This study aimed to investigate trAKs after field therapy compared to randomly chosen [actinic keratoses (AKs)] prior to treatment,” wrote the study authors.

Researchers clinically assessed AKs according to the hyperkeratosis grade and pain on palpation, prior to treatment. They were evaluated by histological severity (AKI-III), their basal growth grading (PROI-III), acantholysis, elastosis, follicular extension of atypical keratinocytes, and accompanying infiltrate.

Upon analysis, trAKs were more painful and showed acantholysis with distinct basal proliferation compared with the control group. Pain and PROIII-graded lesions were predictors for trAKs. AKs with grade AKIII, PROIII or follicular extension reaching the sebaceous gland were the most common histological findings.

“TrAKs are often painful, showing a distinct basal proliferation (PROIII) and acantholysis,” concluded the study authors. “As these features are also seen in invasive [cutaneous squamous cell carcinomas], trAKs may represent a subgroup of AKs and, for this reason, it requires further evaluations,” they continued. 

Reference
Schmitz L, Brehmer A, Falkenberg C, et al. Treatment-resistant actinic keratoses are characterized by distinct clinical and histological features. Ital J Dermatol Venerol. 2021;156(2):213-219. doi:10.23736/S2784-8671.21.06892-9

Alopecia Areata Not Associated With Increased Risk for Heart Disease
Chronic inflammatory skin diseases can increase the risk for cardiovascular diseases, but alopecia areata (AA) is not a risk factor for heart diseases, according to a recent publication in PLoS One.

“The objective of this study was to determine the risk of heart diseases in Korean patients [with AA],” explained the study authors.

Researchers conducted a retrospective cohort study to evaluate the risk of heart diseases in patients with AA using the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2013. A total of 3770 cases of AA from 18,850 age-, sex-, and income level-matched controls were reviewed.

The risk of developing at least one heart disease was higher in the AA group, but the difference was not statistically significant. The severity or duration of AA was not related to an increased risk of heart diseases. Patients with AA did not show a significantly higher cumulative incidence of heart diseases than controls during the study period.

“In this retrospective cohort study, we found that AA was not related to an increased risk of [heart disease],” concluded the study authors.

Reference
Lee H, Kim YC, Choi JW. Alopecia areata is not a risk factor for heart diseases: A 10-year retrospective cohort study. PLoS One. 2021;16(5):e0250216. doi:10.1371/journal.pone.0250216

Four Different Options Considered Most Efficacious Nonsurgical Monotherapies for Hidradenitis Suppurativa
Monotherapies infliximab, bimekizumab, onabotulinumtoxinA, and oral tetracycline for hidradenitis suppurativa (HS) are more efficacious than placebo in pain reduction, occurrence of clinical response, quality of life, and reduction in abscess count, respectively.

“We determined the relative efficacy of nonsurgical monotherapies for [HS],” explained the study authors.

Researchers conducted a systematic review and network meta-analysis of randomized trials to rank their treatment efficacy using the cumulative ranking curve (SUCRA) value.

Infliximab had the highest SUCRA score for pain reduction compared with bermekimab, anakinra, and placebo. Bimekizumab had the highest SUCRA relative to adalimumab, anakinra, and placebo for occurrence of clinical response. OnabotulinumtoxinAhad the highest SUCRA compared with adalimumab and placebo for quality of life in mild HS. Oral tetracycline had the highest SUCRA (48%) compared with topical clindamycin and vehicle for reduction in abscess count.

“Our work-being the first [network meta-analysis] study on non-surgical HS monotherapies contributes to the comparative effectiveness literature for this condition,” concluded the study authors.

Reference
Gupta AK, Shear NH, Piguet V, Bamimore MA. Efficacy of non-surgical monotherapies for hidradenitis suppurativa: a systematic review and network meta-analyses of randomized trials. J Dermatolog Treat. Published May 7, 2021. doi:10.1080/09546634.2021.1927949

Patients With Rosacea Report Higher Tolerability With Azelaic Acid Foam Than Metronidazole Cream or Metronidazole Gel
Patients with rosacea treated with metronidazole cream (MC) and metronidazole gel (MG) more frequently reported treatment concerns and side effects than patients treated with azelaic acid 15% foam (AAF).

Researchers aimed to assess the differences in patient-reported safety and tolerability of AAF vs MC and MG using matching-adjusted indirect comparison to compare patient-reported outcomes from survey data.

Survey results showed that patients treated with MG reported concerns with treatment efficacy, application, and treatment side effects more frequently compared with AAF. Patients with MC more frequently reported concerns with treatment efficacy and dryness. Further, patients treated with AAF reported concerns with cost of treatment compared with those who were treated with MG and MC.

“MG- and MC-treated patients more frequently reported treatment concerns and side effects than AAF-treated patients, and tolerability of those side effects was higher for patients treated with AAF,” concluded the study authors. “While treatment cost is a more frequent concern in patients treated with AAF, these patients less frequently reported concerns with treatment efficacy and reported similar or greater tolerance to side effects than patients treated with either MC or MG,” they continued.

Reference
Williamson T, LaRose A, Cameron J, et al. Rosacea treatment satisfaction: matching adjusted indirect treatment comparison analysis of metronidazole gel or cream vs azelaic acid foam. J Drugs Dermatol. 2020;19(3):295-304.