Dermatology

Strober, B., A. Menter, C. Leonardi, K. Gordon, J. Lambert, L. Puig, H. Photowala, M. Longcore, T. Zhan and P. Foley (2020). “Efficacy of Risankizumab in Patients with Moderate-to-Severe Plaque Psoriasis by Baseline Demographics, Disease Characteristics and Prior Biologic Therapy: An Integrated Analysis of the Phase III UltIMMa-1 and UltIMMa-2 Studies.” J Eur Acad Dermatol Venereol Apr 22. [Epub ahead of print].

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BACKGROUND: Risankizumab is a humanized IgG monoclonal antibody that selectively inhibits interleukin-23 through binding the p19 subunit. In Phase 3 trials, risankizumab demonstrated superior efficacy compared with adalimumab and ustekinumab in patients with moderate-to-severe plaque psoriasis. Here, we evaluated the impact of baseline characteristics on efficacy of risankizumab compared with ustekinumab in patients with moderate-to-severe plaque psoriasis. METHODS: This analysis included all patients initially randomized to risankizumab or ustekinumab from the replicate, double-blinded, randomized, placebo-controlled phase 3 trials, UltIMMa-1 (NCT02684370) and UltIMMa-2 (NCT02684357). Patients received either risankizumab (150 mg) or ustekinumab (weight-based; 45 or 90 mg per label) at weeks 0, 4, 16, 28, and 40. Efficacy was assessed as the proportion of patients achieving >/=90% improvement in Psoriasis Area and Severity Index (PASI 90) at weeks 16 and 52 by baseline patient demographics, disease characteristics, and prior biologic exposure. Mean percent improvement in PASI was calculated by body weight and body mass index at week 52. Missing efficacy data were imputed as non-responders for categorical variables and last observation carried forward for continuous variables. Logistic regression analyses assessed for interactions between treatment and five independent variables (age, sex, weight, baseline PASI score, and presence of psoriatic arthritis) at both weeks 16 and 52. RESULTS: Baseline patient demographics, disease characteristics and prior biologic exposure were similar between patients randomized to risankizumab (n=598) and ustekinumab (n=199). At weeks 16 and 52, risankizumab demonstrated superior efficacy compared with ustekinumab across these patient characteristics (P<0.01). Logistic regression analyses demonstrated that risankizumab was superior to ustekinumab at weeks 16 and 52 in all models tested (P<0.0001 for all). CONCLUSIONS: Risankizumab demonstrated consistent and superior efficacy compared with ustekinumab regardless of patient demographics, disease characteristics, or prior biologic exposure.

Simpson, E., R. Bissonnette, L. F. Eichenfield, E. Guttman, B. King, J. I. Silverberg, L. A. Beck, T. Bieber, K. Reich, K. Kabashima, M. Seyger, E. Siegfried, G. Stingl, S. R. Feldman, A. Menter, P. van de Kerkhof, G. Yosipovitch, C. Paul, P. Martel, A. Dubost-Brama, J. Armstrong, R. Chavda, S. Frey, Y. Joubert, M. Milutinovic, A. Parneix, H. D. Teixeira, C. Y. Lin, L. Sun, P. Klekotka, B. Nickoloff, Y. Dutronc, L. Mallbris, J. M. Janes, A. M. DeLozier, F. Nunes and A. S. Paller (2020). “The validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): The development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis.” J Am Acad Dermatol Apr 25. pii: S0190-9622(20)30720-9. [Epub ahead of print].

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BACKGROUND: An Investigator Global Assessment (IGA) is recommended by health agencies for drug registration in atopic dermatitis (AD). Current IGA scales lack standardization. OBJECTIVES: To develop an IGA scale, training module, and clinical certification exam for use in AD trials, and establish content validity and assess reliability. METHODS: Expert dermatologists participated in the development of the validated IGA for AD (vIGA-AD). Reliability (inter-rater and intra-rater) was assessed by 2 web-based surveys. Clinical certification for investigators consisted of a training module and exam. RESULTS: Expert consensus was achieved around a 5-point IGA scale including morphological descriptions, and content validity was established. Survey 1 showed strong inter-rater reliability (Kendall’s coefficient of concordance W [Kendall’s W] = 0.809, intra-class correlation [ICC] = 0.817) and excellent agreement (weighted Kappa = 0.857). Survey 2, completed 5 months after training of dermatologists, showed improvements in scale reliability (Kendall’s W = 0.819, ICC = 0.852, weighted Kappa = 0.889). In this study 627 investigators completed vIGA-AD training and certification. LIMITATIONS: Ratings were assessed on photographs. CONCLUSION: A validated IGA scale and training module were developed with the intent of harmonizing assessment of disease severity in AD trials. Strong reliability and excellent agreement between assessments were observed.

Papp, K., A. Menter, C. Leonardi, J. Soung, S. Weiss, R. Pillai and A. Jacobson (2020). “Long-term efficacy and safety of brodalumab in psoriasis through 120 weeks and after withdrawal and retreatment: subgroup analysis of a randomised phase 3 trial (AMAGINE-1).” Br J Dermatol Apr 14. [Epub ahead of print].

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BACKGROUND: Brodalumab is efficacious for the treatment of moderate-to-severe plaque psoriasis through 52 weeks. OBJECTIVE: To evaluate the efficacy and safety of brodalumab through 120 weeks, including following withdrawal and retreatment. METHODS: At baseline, patients were randomized to brodalumab (n=222) or placebo (n=220). At week 12, patients achieving static physician’s global assessment score of 0 or 1 (sPGA 0/1) with brodalumab were re-randomized to brodalumab (n=83) or placebo (n=84; later re-treated with brodalumab if sPGA >/=3 occurred), and patients receiving placebo switched to brodalumab (n=208). Safety was assessed by treatment-emergent adverse events. RESULTS: Among those who achieved sPGA 0/1 at week 12 and were re-randomized to brodalumab, 95.7% and 79.5% using observed data, respectively, and 73.9% and 61.4% using nonresponder imputation, respectively, achieved 75% improvement in psoriasis area and severity index (PASI 75) and PASI 100 at week 120. Following withdrawal from brodalumab, return of disease occurred after a mean (standard deviation) of 74.7 (50.5) days. Among those who switched from brodalumab to placebo at week 12, PASI 75 rates using observed data and nonresponder imputation were 55.1% and 51.2% at week 20, respectively, and 94.0% and 75.0% at week 120, respectively; PASI 100 rates at week 120 were 74.6% and 59.5%, respectively. Efficacy was maintained through week 120 in those receiving brodalumab after placebo. No new safety signals were observed. CONCLUSIONS: These findings indicate that brodalumab is efficacious and safe for continuous long-term treatment of psoriasis and support potential for response after discontinuation and retreatment.

Minzenmayer, A., R. N. Miranda, P. Powell and P. Parekh (2020). “An unusual case of cutaneous Waldenstrom macroglobulinemia with the MYD88 L265P mutation.” J Cutan Pathol Apr 26. [Epub ahead of print].

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Waldenstrom macroglobulinemia is a lymphoplasmacytic lymphoma with bone marrow involvement and a monoclonal IgM gammopathy. Infiltration of the skin by neoplastic cells is very rare, and it can be difficult to distinguish from marginal zone lymphoma. The MYD88 L265P mutation is strongly associated with Waldenstrom macroglobulinemia, and it may be helpful in differentiating the two disorders, although the presence of this mutation is not specific, and other factors must be considered when making the final diagnosis. We present a diagnostically challenging case of cutaneous Waldenstrom macroglobulinemia in which the MYD88 L265P mutation was identified in the skin but not in the bone marrow, due to a low tumor burden. This article is protected by copyright. All rights reserved.

Amin, S. D., K. B. Homan, M. Assar, M. Lee and C. D. Housewright (2020). “Hyfrecation and Interference With Implantable Cardiac Devices.” Dermatol Surg 46(5): 612-615.

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BACKGROUND: Mohs micrographic surgery, excisional surgery, and electrodessication and curettage (ED&C) are common dermatologic procedures that often use electrodessication through hyfrecators to achieve hemostasis. According to in vitro studies, electrodessication is considered safe in patients with implanted cardiac devices. To the authors’ knowledge, there are no in vivo data to support this claim. OBJECTIVE: In this study, the authors aim to describe the outcomes of hyfrecation during dermatologic procedures in patients with pacemakers and implantable cardiac devices. METHODS: Retrospective chart review was completed from March 2014 to April 2018 at a single center. Forty-five patients met criteria of having a cardiac device and having undergone an electrosurgery procedure using the Conmed 2000 Hyfrecator (Utica, NY). Adverse perioperative and postoperative outcomes, as well as device malfunction, were evaluated. RESULTS: No adverse perioperative effects were reported. Device reports were examined for inappropriate firing of the defibrillator, loss of capture, temporary inhibition of pacing, battery drainage, pacing at an elevated or erratic rate, failure to deliver antitachycardia, reversion to asynchronous pacing, induction of arrhythmias, or tissue damage at lead tissue, but no such issues were found. CONCLUSION: The lack of complications associated with cardiac devices with hyfrecation is reassuring. However, prospective and larger retrospective studies are warranted.