Creation and Validation of a Photonumeric Scale for Assessment of Infraorbital Hollows.

BACKGROUND: Validated clinical scales are needed to assess aesthetic improvement of the infraorbital hollows (IOHs) after treatment with dermal fillers. OBJECTIVE: To develop an IOHs scale and establish its reliability and sensitivity for grading subjects in clinical trials or routine practice. METHODS AND MATERIALS: The Teoxane IOHs Scale (TIOHS), a 5-grade photonumeric scale, was developed based on real-subject photographs and validated through photographic and live subjects' evaluation. RESULTS: Clinician intra- and inter-rater agreements during the TIOHS validation were excellent. The mean intrarater-weighted Kappa score between the 2 sessions of photographic validation was 0.92, while inter-rater interclass correlation coefficient (ICC) was 0.92 for the combined sessions. The average intrarater-weighted Kappa score and inter-rater ICC for the live validation reached 0.80 and 0.76, respectively. In addition, evaluators identified clinically significant differences between photographs of subjects presenting a 1-grade or 2-grade difference in 82% and 86% of cases, respectively. CONCLUSION: The intrarater Kappa scores and inter-rater ICCs met their predetermined acceptance criteria of >0.70. The TIOHS is a repeatable and reproducible clinician-reported outcome for health care providers to classify IOHs in clinical trials and routine patient care. A 1-grade difference on the TIOHS can detect a clinically meaningful difference in infraorbital hollowing.

Creation and validation of a photonumeric scale for assessment of lip fullness.

BACKGROUND: Validated, objective clinical scales are needed to assess aesthetic improvement of the lips after augmentation with dermal fillers. OBJECTIVE: To develop a lip fullness rating scale and establish its reliability for grading subjects in clinical trials or routine practice, and sensitivity for detecting clinically meaningful changes. METHODS: The Teoxane Lip Fullness Scale (TLFS), a proprietary, 5-grade photonumeric scale, was developed by clinical experts based on real subject photographs and was validated through both photographic and live subjects' evaluation. RESULTS: Clinician intra- and inter-rater agreement for the TLFS was substantial to almost perfect. Mean intra-rater weighted Kappa score between the two rounds of photographic validation was 0.92, and inter-rater agreement was substantial with an ICC of 0.93 for the combined rounds. Average intra-rater weighted Kappa score and inter-rater ICC for the live validation were equally high, reaching 0.91 and 0.89 respectively. Additionally, evaluators identified clinically significant differences between photographs of subjects presenting a 1-grade or 2-grade difference on the scale in 90% and 98% of cases, respectively. CONCLUSIONS: The intra-rater Kappa scores and inter-rater ICC met their pre-determined acceptance criteria of >0.70 in the photographic and live validation. The TLFS was shown to be a repeatable and reproducible Clinician Reported Outcome (Clin-RO) for healthcare providers to classify lip fullness both in clinical trials and in routine patient care. A 1-grade difference on the TLFS can detect a clinically meaningful difference in lip fullness.

Efficacy and Safety of a New Resilient Hyaluronic Acid Filler in the Correction of Moderate-to-Severe Dynamic Perioral Rhytides: A 52-Week Prospective, Multicenter, Controlled, Randomized, Evaluator-Blinded Study.

BACKGROUND: The perioral region is highly mobile and subject to multifactorial changes during aging. Resilient Hyaluronic Acid Redensity (RHAR), an RHA filler, was developed with the aim of optimizing outcomes in dynamic facial areas. OBJECTIVE: This randomized, blinded, multicenter clinical study aimed to demonstrate superiority of RHAR over no-treatment control for correction of moderate-to-severe dynamic perioral rhytides. MATERIALS AND METHODS: Blinded live evaluator assessments of efficacy included improvement in perioral rhytides severity using a proprietary scale (Perioral Rhytids Severity Rating Scale [PR-SRS]) and the Global Aesthetic Improvement Scale. Subjects self-assessed their results with FACE-Q, a validated patient-reported outcome measure, and satisfaction scales. Safety was monitored throughout the study based on common treatment responses (CTRs) and adverse events (AEs). RESULTS: The primary efficacy end point was achieved, with the treatment group showing statistically significant superiority over the control group at Week 8 (80.7% vs 7.8% responder rate by PR-SRS, p < .0001). Most patients (66%) were still responders at Week 52 (study completion). Most AEs were CTRs after perioral injection of a dermal filler, and none was a clinically significant treatment-related AE. CONCLUSION: Resilient Hyaluronic Acid Redensity is effective and safe for the correction of dynamic perioral rhytides in all Fitzpatrick phototypes, with marked durability.

Intralesional Hyaluronic Acid Injection for Chondrodermatitis Nodularis Helicis: A Novel Treatment for Rapid Relief of Pain and Healing of Ulcerations.

BACKGROUND: Chondrodermatitis nodularis helicis (CNH) is a common chronic condition characterized by a tender nodule on the helix or antihelix of the ear which may or may not have accompanying crusting, scaling, or ulceration and that is often difficult to treat. OBJECTIVE: Develop an easy, effective, and durable treatment to reduce the pain and clinical signs including ulcerations associated with CNH using injectable hyaluronic acid (HA). MATERIALS AND METHODS: Twenty-four patients were injected and followed up in 2 to 4 weeks intervals using 0.2 to 0.3 mL of various HA with a high G-Prime. RESULTS: Injectable HA significantly improved the symptoms and also the clinical appearance of all patients treated after 1 or 2 injections except 1 patient. Extrusion of the material through a preexisting ulcer usually required a second follow-up injection 2 weeks later. No adverse events were noted with the injections other than the intentional visible bulging of the injected region with HA. CONCLUSION: Injectable HA provides almost immediate relief from the discomfort of CNH in most cases in less than 1 or 2 weeks, significantly improves the clinical appearance over time and resolves accompanying ulcerations.

Retraction of the Plunger on a Syringe of Hyaluronic Acid Before Injection: Are We Safe?

BACKGROUND: Controversy exists concerning the need for aspiration before injection with hyaluronic acid (HA) fillers. OBJECTIVE: The authors undertook a study of HA products to determine if blood could be aspirated back into a syringe of HA when the needle has been primed or filled with HA. METHODS AND MATERIALS: Two studies were set up to determine if or when blood could be withdrawn from a heparinized fresh tube of blood into the HA syringe. Two different techniques were tested; one using a slow-pull retraction of the plunger and up to a 5-second waiting time before release versus a rapid pullback and quick release. RESULTS: Review of these data demonstrates that the usual clinical method, which involves quick withdrawal and instant release of the syringe plunger does not allow for sufficient removal of the filler found intraluminal in the needle and may give rise to false negative results in vitro and likely in vivo with the exception being the Galderma/Medicis products. CONCLUSION: In summary, withdrawal of the syringe plunger with no visible blood in the syringe does not eliminate the possibility of intravascular placement of the syringe needle.

Incorrect reconstitution of incobotulinumtoxinA leads to loss of neurotoxin.

BACKGROUND: IncobotulinumtoxinA (INCO) was approved for aesthetic use in the United States in 2011. When reconstituted per manufacturer's instructions, diminished delivery of INCO in US may result. OBJECTIVE: Investigators sought to determine whether potential loss of decreased motor activity could be demonstrated, using a simple reconstitution technique. METHODS AND MATERIALS: In this 5-patient study, investigators added 2.0 mL of saline to INCO powder at the bottom of the first of 5 vials, swirling gently to dissolve INCO powder at the bottom. Reconstituted INCO was discarded and the cap was replaced. The "empty" vial then received 0.6 mL of saline, and was swirled and inverted 3 times to ensure dissolution. The 0.6 mL from the first vial was added to the second "empty" vial and the process was repeated for the remaining 3 vials (5 vials per patient). Patients were injected from reconstitution of "empty" vials to determine neuromodulatory activity. Pre- and post-treatment patient photographs of maximal contraction were taken. RESULTS: Markedly diminished maximal frown could be observed in all 5 patients. CONCLUSION: Improper reconstitution of INCO, or swirling without inversion of the vial following saline injection, can result in significant loss of units of the neurotoxin in the clinical setting.

Quality of life in plaque psoriasis patients treated with voclosporin: a Canadian phase III, randomized, multicenter, double-blind, placebo-controlled study.

BACKGROUND: Quality of life assessments are important in the evaluation of new therapies for psoriasis. OBJECTIVE: To determine the effect of voclosporin (VCS) treatment on quality of life in patients with psoriasis. PATIENTS AND METHODS: 451 plaque psoriasis patients with ≥  10% body surface area involvement were randomly assigned in a double-blind fashion to 1 of 4 treatment groups (placebo, VCS 0.2 mg kg(-1) BID, VCS 0.3 mg kg(-1) BID, and VCS 0.4 mg kg(-1) BID) for up to 12 weeks of treatment. Quality of life was assessed using the Dermatology Life Quality Index (DLQI) and the Psoriasis Disability Index (PDI). RESULTS: At 12 weeks, patients treated with VCS 0.4 mg kg(-1) BID had statistically significantly more favourable assessments than placebo-treated patients in all domains of the DLQI and the PDI. Patients treated with VCS 0.3 mg kg(-1) BID had statistically significant improvements in 5 of 10 domains of the DLQI and all domains of the PDI. Patients treated with VCS 0.2 mg kg(-1) BID had statistically significant improvements in 4 of 10 domains of the DLQI and 2 of 4 domains of the PDI. CONCLUSION: Treatment with VCS 0.4 mg kg(-1) BID significantly improves the quality of life of patients with psoriasis.

Psoriasis care: new and emerging pharmacologic trends.

BACKGROUND: The first Canadian Guidelines for the Management of Plaque Psoriasis were recently published, reflecting an evidence-based analysis of psoriasis therapies available in Canada. The guidelines advocate patient-centered psoriasis care in which physicians explore appropriate options to find safe therapies that patients will adhere to and be satisfied with over the long term. OBJECTIVE: To update the discussion in the guidelines regarding new and emerging therapies and trends in psoriasis clinical research. METHODS: Searches of Medline and clinicaltrials.gov were undertaken to identify new and emerging psoriasis therapies as of March 2009. RESULTS: Since May 2008, when published evidence was evaluated for the guidelines, one new drug, ustekinumab, has been approved for moderate to severe psoriasis. New formulations and combinations of existing drugs are expected to reach the Canadian market shortly. Novel agents continue to move through clinical development. CONCLUSION: With the introduction and removal of antipsoriatic therapies from the Canadian market, the therapeutic landscape continues to shift. An increasing number of head-to-head comparisons and the reporting of ambitious treatment outcomes will simplify physicians' evaluation of treatment options. Recognition of quality of life as a key goal of psoriasis treatment is another hopeful trend, consistent with the principles of patient-centered care.

A favourable benefit/risk ratio with efalizumab: a review of the clinical evidence.

Moderate to severe plaque psoriasis has traditionally been treated with agents that have toxicities associated with long-term use. Many patients therefore cannot be treated safely, conveniently or effectively with traditional therapies. Recent phase 3 clinical trials for efalizumab, a biological agent targeted specifically at the T-cell-based pathology of psoriasis, have demonstrated its short- and long-term efficacy and safety for the treatment of psoriasis. This article reviews results from 12-week, six-month, and three-year trials, focusing on the drug's safety, efficacy, and therapeutic response time, as well as the phenomenon of rebound in non-responding patients. Efalizumab emerges as an important addition to the dermatological pharmacopeia for the long-term treatment of psoriasis.

Relapse, rebound, and psoriasis adverse events: an advisory group report.

Psoriasis is a chronic disease, the severity of which varies among patients and changes unpredictably over time in individual patients. Psoriasis can be exacerbated during treatment by infection, endocrine factors, hypocalcemia, medications, psychologic stress, skin trauma, or other factors. Patients who discontinue treatments may experience a return of disease--relapse--or worsening of disease--rebound. The National Psoriasis Foundation (NPF) proposed standardized definitions of relapse and rebound. Efalizumab, a recombinant humanized immunoglobulin G-1 monoclonal antibody, is approved for the management of psoriasis. During efalizumab clinical trials, a small percentage of patients experienced protocol-defined adverse events related to psoriasis. After publication of the NPF definition of rebound, post hoc exploratory analyses of the efalizumab clinical trial data were performed. The efalizumab clinical trial investigators discussed their observations, the analyses, and their individual approaches to the treatment of patients receiving or discontinuing efalizumab therapy, the conclusions of which are described herein.

Incidence of infection during efalizumab therapy for psoriasis: analysis of the clinical trial experience.

BACKGROUND: Because many therapies for psoriasis disrupt the normal inflammatory cascade and could theoretically impair the body's ability to respond to external pathogens, a possible increase in the incidence of infection is a concern with any new psoriasis therapy that affects the immune system. Efalizumab is a biologic therapy targeted to inhibit T cells. Its efficacy has been shown in clinical trials encompassing >3500 patients with psoriasis. OBJECTIVES: The aims of this article were to review the incidence of infection observed in efalizumab-treated patients during 12-week, Phase III clinical trials, compare the incidence rate with that in patients receiving placebo, and evaluate the incidence of infection observed in patients with extended (>12-week) efalizumab use. METHODS: Adverse events (AEs) of infection were tabulated from a pooled data set of 2335 patients enrolled to receive 12 weeks of subcutaneous (SC) efalizumab 1 or 2 mg/kg . wk or placebo in 4 randomized, double-blind, placebo-controlled, Phase III efalizumab clinical studies. The incidence of infection was further evaluated using pooled data from 1115 patients who received up to 24 weeks of efalizumab therapy during 5 clinical trials with treatment extension arms and from 170 patients who received up to 108 weeks (27 months) of continuous therapy in an open-label, Phase III efalizumab trial of 36 months' total duration. RESULTS: The incidence and severity of AEs of infection during 12 weeks of efalizumab therapy were comparable to those observed in patients receiving placebo (overall, 28.6% vs 26.3%). Infections did not appear to increase with extended therapy of up to 27 months. Serious infections requiring hospitalization occurred in 1.1% of efalizumab-treated patients. CONCLUSION: The present review of the available Phase III clinical trial suggests that efalizumab is not associated with an increased risk for infection in patients receiving initial or long-term (27-month) treatment for moderate to severe chronic plaque psoriasis.

Dermatologic surgery practice and skin cancer treatment in Canada: results of a national survey.

BACKGROUND: Although traditionally considered a medical subspecialty, dermatology has rapidly evolved over the past two decades to encompass a wide variety of cutaneous surgical procedures. OBJECTIVE: The study was carried out to evaluate the status of dermatologic surgery practice and skin cancer treatment in Canada. METHODS: In 2003, 550 practicing Canadian dermatologists were surveyed. RESULTS: Two hundred fifty-one dermatologists responded to the questionnaire, with the majority practicing in an urban part-time academic, part-time private setting. Statistics are presented on the types and demographics of dermatosurgical and cosmetic procedures performed, as well as on the specific dermatosurgical therapies used in the treatment of various cutaneous malignancies. CONCLUSIONS: The survey provides a current picture of dermatologic surgery practice and skin cancer treatment in Canada. The data suggest that Canadian dermatologists are further embracing surgical and cosmetic procedures.

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.

Randomized, double-blind comparison of the efficacy of two hyaluronic acid derivatives, restylane perlane and hylaform, in the treatment of nasolabial folds.

BACKGROUND: Cross-linked hyaluronic acid gels may offer longer-lasting cosmetic correction and a lower risk of immunogenicity than other soft tissue augmentation agents. OBJECTIVE: To compare the efficacy and safety of a non-animal-stabilized hyaluronic acid gel (Restylane Perlane, Q-Med, Uppsala, Sweden) with that of a hylan B gel (Hylaform, Genzyme Corp., Cambridge, MA, USA), a cross-linked hyaluronic acid from chicken combs, for treatment of nasolabial folds. METHODS: One hundred fifty patients with moderate or severe nasolabial folds were randomized to contralateral treatment with Restylane Perlane and Hylaform. Efficacy was assessed using semi-objective outcome instruments at 3, 4.5, and 6 months after achievement of an "optimal cosmetic result". Patients subsequently underwent open-label bilateral retreatment with Restylane Perlane (if required) and were followed up for a further 6 months. RESULTS: The two products were equally effective in producing an optimal cosmetic result, although fewer treatment sessions were required with Restylane Perlane. At 6 months post-treatment, a higher proportion of patients showed a > or = 1-grade improvement in Wrinkle Severity Rating Scale (WSRS) score with Restylane Perlane (75%) than with Hylaform (38%). Restylane Perlane was considered superior in 64% of patients, whereas Hylaform was superior in 8% of patients. Treatment-related adverse events tended to be more frequent with Restylane Perlane. Local injection-site reactions were generally transient and mild or moderate in intensity and were no more frequent after Restylane Perlane retreatment. CONCLUSIONS: Restylane Perlane provides a more durable esthetic improvement than Hylaform and offers acceptable tolerability.