A Prospective Study Evaluating the Use of Helium Plasma for Dermal Resurfacing.

BACKGROUND AND OBJECTIVES: A novel helium plasma device was evaluated for efficacy and safety for dermal resurfacing (ClinicalTrials.gov Identifier: NCT03286283). The helium plasma device delivers energy in a controlled, bimodal fashion that when compared with the nitrogen plasma predicate device in a porcine animal model demonstrated a more limited depth of thermal effect but a greater skin tissue contraction. STUDY DESIGN/MATERIALS AND METHODS: Fifty-five eligible subjects seeking improvement in facial rhytids were enrolled for study at one of three investigational sites. Most subjects underwent full-face treatment. Power levels were limited to 20% at peri-oral and peri-orbital areas-a level that correlates to an energy density 40% lower than the highest setting on the predicate device. Three-month post-treatment Fitzpatrick Wrinkle and Elastosis Scale (FWS) scores were compared with baseline scores as determined by blinded independent photographic reviewers (IPRs) and study investigators. RESULTS: Blinded IPRs observed a ≥1-point FWS improvement in 63.64% of subjects whereas study investigators noted a ≥1-point FWS improvement in 54 of 55 subjects (98.18%) of subjects. 90.9% of subjects indicated "improvement" in appearance utilizing the modified Global Aesthetic Improvement Scale. Subgroup analysis showed 1-point (±0.05) FWS improvement by IPRs and study investigators for Fitzpatrick Skin Types II and III, age≥62, two of three study sites, and post-treatment oral steroid use. Eighty Non-Serious Adverse Events in 39 subjects were reported, most of which resolved within 14 days or less. There were no Serious Adverse Events or Unanticipated Device Effects reported. CONCLUSION: At the modest power level studied, a significant improvement from a single pass helium plasma dermal resurfacing treatment was observable in most subjects by IPRs and investigators, and no serious adverse events were reported. The discrepancy between IPR and study investigator FWS improvement may be explained in part by the limitations of assessing two-dimensional photographs versus live in-person evaluation of subjects. Studies evaluating higher energy levels and/or multiple treatment passes are ongoing. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

A phase II, multicenter, open-label, 3-cohort trial evaluating the efficacy and safety of vismodegib in operable basal cell carcinoma.

BACKGROUND: Vismodegib is approved for treatment of advanced basal cell carcinoma. OBJECTIVE: We sought to characterize vismodegib efficacy and safety in operable basal cell carcinoma. METHODS: Patients with new, operable, nodular basal cell carcinoma received vismodegib (150 mg/d) followed by excision and Mohs micrographic surgery to ensure clear margins. Cohort 1 received vismodegib for 12 weeks; cohort 2 received vismodegib for 12 weeks, then 24 weeks of observation before excision; and cohort 3 received vismodegib for 8 weeks on/4 weeks off/8 weeks on. RESULTS: In all, 24 patients enrolled in cohort 1, and 25 in cohorts 2 and 3. Complete histologic clearance was achieved by 42%, 16%, and 44% of patients in cohorts 1, 2, and 3, respectively. Muscle spasms (76%), alopecia (58%), and dysgeusia (50%) were the most frequent adverse events (AEs). Five (7%) patients discontinued treatment because of an AE. AE reversibility was evaluated in cohort 2 with 24 weeks of observation after treatment discontinuation. LIMITATIONS: Nonrandomized, small cohort sizes, and short observation durations for some patients are limitations. CONCLUSION: Primary efficacy end points were not met (predefined complete histologic clearance rate: >50% in cohorts 1 and 3; >30% in cohort 2). Safety was comparable when dosed continuously versus intermittently. Posttreatment reversibility of vismodegib-related AEs was demonstrated.

Considerations for the use of injectable poly-L-lactic acid in people of color.

With demand for minimally invasive cosmetic procedures rising in patients of color, it is becoming increasingly important for clinical dermatologists to be aware of specific needs of these patients. This article therefore reviews considerations for using cosmetic procedures on skin of color, and reports the authors' clinical experience with the use of injectable poly-L-lactic acid (PLLA, Sculptra, Dermik Laboratories, a business of sanofi-aventis U.S. LLC) in this patient population. The authors' experience indicates that patients with skin of color may require an increased interval between treatments; however, with proper attention to patient selection and administration technique, injectable PLLA can be used effectively in this patient group. Controlled clinical studies that include more patients of color are needed to fully assess the benefits and risks of cosmetic products, such as injectable PLLA, in these populations.

Treatment of psoriatic arthritis and recalcitrant skin disease with combination therapy.

Psoriasis and psoriatic arthritis (PsA) are chronic inflammatory disorders. Efalizumab targets several T-cell interactions central to psoriasis immunopathogenesis. Etanercept and infliximab are antitumor necrosis factor (anti-TNF) agents that modify the inflammatory and cell-mediated immune responses involved in the pathogenesis of psoriasis and PsA. All 3 agents are approved for the treatment of plaque psoriasis, and etanercept and infliximab are also approved for the treatment of PsA. Twenty patients with psoriasis and PsA have been successfully treated with a combination of efalizumab (1 mg/kg/wk) and etanercept (25 mg or 50 mg/wk) or infliximab (5 to 6 mg/kg). To date, no serious adverse events have been reported. Combination therapy was well tolerated and effectively controlled both skin disease and arthritis. The complementary activity of efalizumab with an anti-TNF agent is most likely attributable to their differing mechanisms of action. Further investigation is warranted.

Transitioning patients from efalizumab to alternative psoriasis therapies: findings from an open-label, multicenter, Phase IIIb study.

BACKGROUND: Rebound in psoriasis is, by definition, a rapid worsening of disease following the discontinuation of therapy for psoriasis; it occurs following the abrupt discontinuation of many therapies. To prevent rebound on discontinuation of efalizumab, this study evaluated the effectiveness of transitioning patients to an alternative psoriasis therapy. METHODS: Patients (n = 130) received subcutaneous efalizumab 1 mg/kg/week for 12 weeks. Efalizumab was discontinued at 12 weeks; patients were evaluated for improvement from baseline in the Psoriasis Area and Severity Index (PASI) and a 12-week transition period was begun. Patients who achieved PASI improvement of 75% or more (PASI-75) at week 12 of efalizumab treatment were observed during the transition period and treated only if psoriasis recurred. Patients who did not attain PASI-75 at week 12 of efalizumab treatment were immediately transitioned to an alternative psoriasis therapy at the physician's discretion. All patients were evaluated for signs of rebound following efalizumab discontinuation. RESULTS: Rebound was not observed in any PASI-75 responder (n = 46). Rebound was observed in two of 32 patients who achieved between PASI-50 and PASI-75, and was more common in nonresponders (14/49). Rebound was observed in none of the eight patients treated with cyclosporine and in two of the 12 patients treated with methotrexate during the transition period. CONCLUSIONS: These results suggest that efalizumab-responsive patients are less likely to experience rebound than nonresponders and may not require treatment until disease recurrence following efalizumab discontinuation. Efalizumab nonresponders are at higher risk of developing rebound and thus should be considered for transition to an appropriate psoriasis therapy immediately following efalizumab discontinuation.

Assessing nonsurgical options for facial restoration.

In this article, the readily available nonsurgical options for facial restoration are reviewed and compared as the first step in treatment selection following careful facial evaluation.

Clinical considerations of efalizumab therapy in patients with psoriasis.

Psoriasis is a chronic, incurable disease that often requires decades of therapy to maintain disease control. Efalizumab is a recombinant monoclonal IgG1 antibody approved for use in patients with chronic moderate-to-severe plaque psoriasis. To date, efalizumab has been evaluated extensively in more than 3500 patients, including in studies that have evaluated its efficacy and safety during extended use. Just as psoriasis fluctuates in severity, the response to treatment with efalizumab can vary among patients. On the basis of my personal experience managing patients in and out of clinical trials, most patients benefit from efalizumab. The possibility exists of intercurrent events during efalizumab therapy, such as the development of a transient localized papular eruption or mild arthralgia or, in a few patients, a generalized inflammatory flare or severe arthralgia. However, there are techniques to potentially manage these events in a manner that maximizes patient comfort and compliance. If dermatologists become comfortable recognizing the subset of patients who are overall excellent responders but develop a papular eruption or mild and manageable arthralgia, they will be able to readily incorporate this effective biologic into their daily practice. In this article, clinical trial data and case reports illustrate recommended patient management techniques and the substantial long-term benefits that psoriasis patients may realize with efalizumab therapy.

Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial.

CONTEXT: Because T-cell interactions are involved in the pathophysiology of psoriasis, therapy with a T-cell modulator may have beneficial effects on psoriasis severity and health-related quality of life (HRQL). OBJECTIVE: To assess the efficacy and safety of efalizumab, a T-cell modulator, in patients with plaque psoriasis. DESIGN, SETTING, AND PATIENTS: Phase 3 randomized, double-blind, parallel-group, placebo-controlled trial involving 556 adult patients with stable, moderate to severe plaque psoriasis and conducted at 30 study centers in the United States and Canada between January and July 2002. INTERVENTIONS: Patients were randomly assigned in a 2:1 ratio to receive 12 weekly doses of subcutaneous efalizumab, 1 mg/kg (n = 369), or placebo equivalent (n = 187). MAIN OUTCOME MEASURES: At least 75% improvement on the Psoriasis Area and Severity Index (PASI-75); improvement on the overall Dermatology Life Quality Index (DLQI), Itching Visual Analog Scale (VAS), and Psoriasis Symptom Assessment (PSA) at week 12 vs baseline. RESULTS: Efalizumab-treated patients experienced significantly greater improvement on all end points than placebo-treated patients. Twenty-seven percent of efalizumab-treated patients achieved PASI-75 vs 4% of the placebo group ( P<.001). Efalizumab-treated patients exhibited significantly greater mean percentage improvement than placebo-treated patients on the overall DLQI (47% vs 14%; P<.001), Itching VAS (38% vs -0.2%; P<.001), and PSA frequency and severity subscales (48% vs 18% and 47% vs 17%, respectively; P<.001 for both) at the first assessment point. Efalizumab was safe and well tolerated, with primarily mild to moderate adverse events. CONCLUSION: In this 12-week study, efalizumab resulted in significant improvements in clinical end points, including physician-assessed and dermatology-specific patient-reported HRQL measures, in patients with moderate to severe plaque psoriasis.

A novel targeted T-cell modulator, efalizumab, for plaque psoriasis.

BACKGROUND: Interactions between leukocyte-function-associated antigen type 1 (LFA-1) and intercellular adhesion molecules are important in the pathogenesis of psoriasis. Efalizumab, a humanized monoclonal antibody, binds to the alpha subunit (CD11a) of LFA-1 and inhibits the activation of T cells. METHODS: In a phase 3, multicenter, randomized, placebo-controlled, double-blind study, we assign 597 subjects with psoriasis to receive subcutaneous efalizumab (1 or 2 mg per kilogram of body weight per week) or placebo for 12 weeks. Depending on the response after 12 weeks, subjects received an additional 12 weeks of treatment with efalizumab or placebo. Study treatments were discontinued at week 24, and subjects were followed for an additional 12 weeks. RESULTS: At week 12, there was an improvement of 75 percent or more in the psoriasis area-and-severity index in 22 percent of the subjects who had received 1 mg of efalizumab per kilogram per week and 28 percent of those who had received 2 mg of efalizumab per kilogram per week, as compared with 5 percent of the subjects in the placebo group (P<0.001 for both comparisons). Efalizumab-treated subjects had greater improvement than those in the placebo group as early as week 4 (P<0.001). Among the efalizumab-treated subjects who had an improvement of 75 percent or more at week 12, improvement was maintained through week 24 in 77 percent of those who continued to receive efalizumab, as compared with 20 percent of those who were switched to placebo (P<0.001 for both comparisons). After the discontinuation of efalizumab at week 24, an improvement of 50 percent or more in the psoriasis area-and-severity index was maintained in approximately 30 percent of subjects during the 12 weeks of follow-up. Efalizumab was well tolerated, and adverse events were generally mild to moderate. CONCLUSIONS: Efalizumab therapy resulted in significant improvements in plaque psoriasis in subjects with moderate-to-severe disease. Extending treatment from 12 to 24 weeks resulted in both maintenance and improvement of responses.