Effectiveness and Safety of Sculptra Poly-L-Lactic Acid Injectable Implant in the Correction of Cheek Wrinkles.

BACKGROUND: The current study evaluated the effectiveness and safety of Sculptra injectable poly-L-lactic acid (PLLA-SCA) treatment in correcting cheek wrinkles compared with a no-treatment control. METHODS: Male/female immune-competent adults (aged >21 years) with moderate/severe cheek wrinkles, graded using the Galderma Cheek Wrinkle Scale (GCWS) at rest, were randomized 2:1 to receive PLLA-SCA injections (150 mg; 8 mL reconstitution in sterile water for injection) + 1 mL lidocaine hydrochloride (2%), administered immediately after reconstitution, or no treatment (control). Up to 3 additional treatments were allowed at monthly intervals, and follow-up was at months 7, 9, and 12. The primary endpoint was 1-grade or greater improvement in GCWS at rest for both cheeks at month 12. RESULTS: GCWS at rest responder rate was significantly higher with PLLA-SCA treatment versus the no-treatment control at months 7 (66.2% versus 38.6%; P=0.0043), 9 (70.6% versus 31.1%; P<0.0001), and 12 (71.6% versus 26.1%; P<0.0001). Treating investigators reported improvements in skin radiance (>95%), tighter appearance (>88%), and jawline contour (>85%). PLLA-SCA recipients reported high satisfaction levels regarding improvements in skin radiance (90% or greater), sagging (84% or greater), and firmness (91% or greater) as well as natural-looking results (85% or greater) and a desire for repeat treatment (84% or greater). Treatment-related adverse events were mostly mild in severity with no serious events related to PLLA-SCA injections. CONCLUSION: Injectable PLLA-SCA treatments were well tolerated and significantly reduced the severity of moderate/severe cheek lines and wrinkles, while improving skin quality. Effectiveness was durable over the 12-month study period with high subject-reported satisfaction, natural-looking appearance, and enthusiasm for repeat treatments. CLINICALTRIALS: gov registry number: NCT04124692J Drugs Dermatol. 2024;23(1):1297-1305.        doi:10.36849/JDD.7729.

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.

Injectable poly-L-lactic acid for human immunodeficiency virus-associated facial lipoatrophy: cumulative year 2 interim analysis of an open-label study (FACES).

BACKGROUND: Studies of injectable poly-L-lactic acid (PLLA) in human immunodeficiency virus (HIV)-associated facial lipoatrophy have predominantly included male Caucasians. OBJECTIVE: To report cumulative year 2 interim study results examining the safety and efficacy of injectable PLLA in subjects with HIV categorized according to Fitzpatrick skin type and sex. MATERIALS AND METHODS: This is an ongoing open-label, multicenter, 5-year study of 290 treated subjects. After correction with injectable PLLA, subjects are being followed annually. Primary end points include incidence and severity of treatment-emergent adverse events (TEAEs). Secondary end points include mean change from baseline of James scale severity grade and treatment satisfaction. RESULTS: At 2 years, TEAE incidences were: potentially related to study product (n = 53,18.3%) or injection procedure (n = 71, 24.5%), injection-site nodules (n = 24, 8.3%) and papules (n = 25, 8.6%). No hypertrophic scars, keloids, or product-related serious TEAEs were reported. Mean improvement in James scale grade for all groups was 1.4 (p < .001), and 89.4% of subjects and 95.5% of physicians rated treatment satisfaction as very good or excellent. CONCLUSION: At 2 years, injectable PLLA is a safe and effective long-term treatment for HIV-associated facial lipoatrophy regardless of Fitzpatrick skin type; confirmation of these results will be needed at the completion of this 5-year study.

A calcipotriene/betamethasone dipropionate two-compound scalp formulation in the treatment of scalp psoriasis in Hispanic/Latino and Black/African American patients: results of the randomized, 8-week, double-blind phase of a clinical trial.

The calcipotriene/betamethasone dipropionate two-compound scalp formulation has been shown to be safe and effective in the treatment of scalp psoriasis over 8 weeks, but the patients studied were mainly White and non-Hispanic. The aim of this study was to evaluate the efficacy and safety of the two-compound scalp formulation in the treatment of scalp psoriasis in Hispanic/Latino and Black/African American patients. A total of 99 Hispanic/Latino and 78 Black/African American patients were randomized double-blind in a 3:1 ratio to 8 weeks of once daily treatment of scalp psoriasis with either the two-compound scalp formulation (n=135) or its vehicle (n=42). In the two-compound group, 71.9% of patients had cleared or minimal disease at week 8 by the investigator's global assessment compared to 40.5% in the vehicle group (odds ratio 3.30; 95% CI 1.62-6.72; P<0.001). For the five secondary efficacy response criteria, three (total sign score, thickness of scalp psoriasis, patient's global assessment) showed that two-compound scalp formulation was statistically significantly more effective than its vehicle, and the other two (redness and scaliness of scalp psoriasis) approached statistical significance in favor of the two-compound scalp formulation. There was no statistically significant difference (P=1.00) between the percentage of patients with adverse reactions in the two-compound group (7.0%) and the vehicle group (7.9%). The two-compound scalp formulation is safe and effective in the treatment of scalp psoriasis over 8 weeks in Hispanic/Latino and Black/African American patients.

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.

Safety of efalizumab therapy in patients with moderate to severe psoriasis: an open-label extension of a phase IIIb trial.

BACKGROUND: Psoriasis is a chronic autoimmune disease characterized by infiltration of the dermis and epidermis by activated T cells and the hyperproliferation and abnormal differentiation of keratinocytes. It is a life-long disease with alternating periods of remission and recurrence. Efalizumab is a humanized, recombinant, T-cell targeting monoclonal antibody, approved for use in adults with chronic moderate to severe plaque psoriasis. OBJECTIVE: To assess the safety of continued or newly initiated treatment with efalizumab for up to 48 weeks in patients with psoriasis who were treated previously with efalizumab or placebo. METHODS: This study was an open-label, 48-week extension of a previously published 12-week, randomized, double-blind, parallel-group, placebo-controlled, multicentre, phase IIIb study, carried out in the US and Canada between 24 October 2002 and 2 July 2004. Patients were followed and treated at the study clinic in an outpatient setting and also were trained to self-administer the drug at home. Patients comprising individuals with chronic moderate to severe plaque psoriasis who had completed the 12-week, placebo-controlled segment of the study were eligible for enrolment in the extension phase. Of the 686 patients enrolled in the study, 636 (92.7%) enrolled in the open-label extension of the study, 418 of whom had received 12 weeks of efalizumab therapy and 218 of whom had received 12 weeks of placebo. All patients entering the open-label phase of the study received efalizumab 1 mg/kg/wk for an additional 48 weeks, for a maximum exposure of up to 60 weeks. Safety was evaluated by an assessment of adverse events, including infections and serious adverse events. RESULTS: The rate of withdrawal due to adverse events remained low throughout the trial, ranging from 1.2% to 6.6% during the 12-week segments of the open-label extension phase of the trial. The incidence of adverse events decreased with increased exposure to efalizumab; the incidence during the initial 12 weeks of exposure to efalizumab was 79.0% compared with 72.9% for patients exposed to placebo. Patients treated with efalizumab for 13-24 weeks, 25-36 weeks, 37-48 weeks and 49-60 weeks experienced adverse events at an incidence of 66.8%, 54.3%, 49.6% and 48.5%, respectively. The incidence of serious adverse events ranged from 1.6% to 3.5% during the 12-week segments of efalizumab therapy, compared with an incidence of 3.4% for placebo-treated patients. The incidence of infection ranged from 9.9% to 14.7% during the 12-week segments of efalizumab therapy, compared with an incidence of 19.1% for placebo-treated patients. Malignancies were reported with an incidence of

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.

Long-term continuous efalizumab therapy in patients with moderate to severe chronic plaque psoriasis: updated results from an ongoing trial.

BACKGROUND: Efalizumab is a T cell-targeted therapy for psoriasis. OBJECTIVE: We sought to evaluate the efficacy and safety of long-term, continuous efalizumab therapy. METHODS: Of 339 patients enrolled in this ongoing, open-label, phase III study, after 3 months 290 qualified for and entered the maintenance treatment phase. RESULTS: Results for the first 27 months of this 36-month continuous therapy trial are available. At month 3, 41% of patients achieved at least a 75% reduction in Psoriasis Area and Severity Index (PASI) score; at month 27, 47% achieved at least a 75% reduction in PASI score (intent to treat, n = 339). Among patients eligible for maintenance therapy (n = 290), 56% achieved at least a 75% reduction in PASI score at month 27. Moreover, the at least 90% reduction in PASI score rate increased through 18 months (33%). The safety profile with efalizumab was sustained throughout 27 months of continuous treatment with no new common events over time. LIMITATIONS: Because the extended treatment period was not a randomized clinical trial, no formal comparative analyses versus placebo were conducted. Three-month placebo data from randomized, parallel, placebo-controlled studies are briefly discussed. CONCLUSIONS: These results suggest that efalizumab maintains, and in some patients continues to improve, efficacy during long-term therapy.

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.

Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis.

OBJECTIVE: To assess the efficacy and safety of a 24-week course of efalizumab. DESIGN: Phase 3, randomized, double-blind, parallel-group, placebo-controlled 12-week study followed by a 12-week open-label study. SETTING: Outpatient dermatology clinics. Patients A total of 556 patients with moderate to severe chronic plaque psoriasis who were seeing an outpatient dermatologist were included in the study. Intervention For weeks 1 to 12, the 556 patients were randomized to receive 1 mg/kg of efalizumab weekly or placebo subcutaneously. For weeks 13 to 24, 516 of these patients received 1 mg/kg of efalizumab weekly. MAIN OUTCOME MEASURES: Proportion of patients with a 75% or greater improvement in Psoriasis Area and Severity Index (PASI-75), a 50% or greater improvement in PASI (PASI-50), static Physician's Global Assessment (sPGA) rating of minimal or clear, and improvements in Dermatology Life Quality Index (DLQI), itching scale, and Psoriasis Symptom Assessment (PSA) frequency and severity scores at weeks 12 and 24. Safety was evaluated by reviewing adverse events, laboratory parameters, vital signs, and anti-efalizumab antibodies. RESULTS: At week 12, 26.6% of efalizumab-treated patients achieved PASI-75 and 58.5% achieved PASI-50. After 24 weeks of continuous efalizumab therapy, PASI responses increased: 43.8% of patients achieved PASI-75 and 66.6% achieved PASI-50. The percentage of patients who achieved an sPGA rating of minimal or clear increased from 25.7% to 35.9%. The mean percentage of improvement in all patient-reported outcomes (DLQI, itching scale, and PSA frequency and severity scores) at week 12 was maintained at week 24 (DLQI, 49.2%; itching scale, 42.2%; PSA frequency, 47.6%; PSA severity, 47.3%). There was a decline in overall reported adverse events from weeks 1 to 12 (80.4%) to weeks 13 to 24 (63.2%) without evidence of cumulative toxic effects. Conclusion Extending efalizumab treatment from 12 to 24 weeks leads to improved efficacy and maintenance of quality of life with no evidence of cumulative toxic effects noted in patients with moderate to severe chronic plaque psoriasis.

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.