-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Few clinical trials have evaluated the combination of topical corticosteroids plus systemic therapies for psoriasis. OBJECTIVE: We sought to evaluate efficacy and safety of etanercept plus topical clobetasol propionate (CP) foam versus etanercept monotherapy for treatment of moderate to severe plaque psoriasis. METHODS: Adults with Psoriasis Area and Severity Index (PASI) score greater than or equal to 10 and psoriasis-affected body surface area greater than or equal to 10% were randomized to etanercept with CP as needed to clear (2 up-to-2-week courses, weeks 11-12 and 23-24) or etanercept alone (each arm at 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks). RESULTS: A total of 592 patients enrolled (295 etanercept + CP arm; 297 etanercept arm). At week 12, significant differences were observed for response of 75% improvement in PASI score (primary end point, 65.2% vs 48.3% in the etanercept + CP vs etanercept arms, respectively; P < .001), response of 90% improvement in PASI score (29.7% vs 19.4%; P = .009), percentage PASI score improvement (76.5% vs 68.2%; P < .001), static physician global assessment of clear/almost clear (63.1% vs 47.3%; P < .001), and patient satisfaction with treatment (P = .006). Response of 75% improvement in PASI score and static physician global assessment of clear/almost clear were not significantly different between arms at week 24. Patient satisfaction with treatment (P = .001) and percentage improvement in PASI score (P = .031) were also greater in the etanercept + CP arm compared with etanercept only at week 24. Comparable numbers of adverse events occurred in each arm. LIMITATIONS: No placebo for CP foam was provided in the etanercept arm. CONCLUSIONS: Addition of CP to etanercept yielded increased efficacy compared with etanercept alone at week 12 without an increase in treatment-related adverse events.
Journal of the American Academy of Dermatology 05/2013; · 3.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: No systemic therapies are approved by the US Food and Drug Administration for the treatment of psoriasis in children and adolescents.
We sought to evaluate the long-term safety and efficacy of etanercept in pediatric patients (aged 4-17 years) with moderate to severe plaque psoriasis.
Patients who completed or received substantial treatment benefit in a 48-week, randomized, double-blind, placebo-controlled study (N = 211) evaluating the efficacy and safety of once-weekly etanercept (0.8 mg/kg) were enrolled in this 264-week open-label extension study. The primary end point was the occurrence of adverse events. Secondary end points included Psoriasis Area and Severity Index 50%, 75%, and 90% responses compared with baseline; static Physician Global Assessment; and clear and clear/almost clear static Physician Global Assessment status. Results from a 96-week interim analysis are presented.
Of 182 enrolled patients, 181 received treatment and 140 (76.9%) completed week 96. A total of 145 patients (80.1%) reported adverse events; 5 serious adverse events occurred in 3 patients, none of which were treatment related. Observed Psoriasis Area and Severity Index 50% (89%), 75% (61%), and 90% (30%) responses compared with baseline at week 96 were similar to those observed in the double-blind trial. The static Physician Global Assessment was maintained through week 96, when 47% of patients achieved clear/almost clear status.
This is an interim analysis from an open-label study.
Extended treatment with etanercept in pediatric patients with moderate to severe plaque psoriasis was generally well tolerated, and efficacy was maintained through 96 weeks.
Journal of the American Academy of Dermatology 11/2010; 63(5):762-8. · 3.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Psoralen plus ultraviolet A (PUVA) for the treatment of psoriasis has never been evaluated using the Psoriasis Area Severity Index (PASI) in a randomized, double-blind, placebo-controlled trial. The lack of such data limits our capacity to estimate PUVA's efficacy relative to other treatment options that are available today.
The purpose of this study was to evaluate the efficacy of PUVA therapy for patients with plaque-type psoriasis.
This study involved 40 patients with psoriasis; 30 received PUVA and 10 received UVA with placebo. PASI scores were assessed at baseline and every 4 weeks thereafter for 12 weeks.
By nonresponder imputation, 60% (18 of 30) in the PUVA group achieved 75% or more improvement in PASI score after 12 weeks of treatment compared with 0% (0 of 10) in the UVA plus placebo group (P < .0001). Using intent to treat with last observation carried forward analysis, 63% (19 of 30) in the PUVA group achieved 75% or more improvement in PASI score compared with 0% (0 of 10) in the UVA plus placebo group (P < .0001). By per protocol analysis, 86% (18 of 21) in the PUVA group as compared with 0% (0 of 7) in the UVA plus placebo group reached 75% or more improvement in PASI score after 12 weeks (P < .0001).
The study was relatively small with only 40 patients enrolled and 28 patients who completed the protocol. Further studies that involve head-to-head comparison of PUVA with other treatment modalities are needed. Nonresponder imputation, last observation carried forward with intent to treat, and per protocol analyses each have separate advantages and limitations when determining clinical significance.
This study supports the observation that PUVA is a highly efficacious treatment for chronic plaque psoriasis.
Journal of the American Academy of Dermatology 09/2009; 61(5):793-8. · 3.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Five percent 5-fluorouracil (5-FU) cream is approved by the FDA for the treatment of superficial basal cell carcinomas but has been underutilized.
The objective was to evaluate the efficacy, tolerability, cosmetic outcome, and patient satisfaction of 5% 5-FU in the treatment of superficial basal cell carcinomas.
A total of 29 patients with 31 biopsy-proven superficial basal cell carcinoma lesions on the trunk or limbs were treated with 5% 5-FU cream twice daily for up to 12 weeks. Treatment could be stopped sooner if the lesion was clinically resolved. The lesional site was surgically excised 3 weeks after the end of treatment for histologic evaluation of cure. RESULTS The histologic cure rate was 90% (28/31 lesions cured) and the mean time to clinical cure was 10.5 weeks. 5-FU was generally well tolerated with a good cosmetic outcome-the majority of patients had no pain or scarring and only mild erythema. Patients were generally very satisfied with their treatment.
Five percent 5-FU is a highly effective and well-tolerated treatment option for superficial basal cell carcinomas offering a generally good cosmetic outcome and high levels of patient satisfaction.
Dermatologic Surgery 05/2007; 33(4):433-9; discussion 440. · 1.80 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Patients receiving levodopa for Parkinson's disease experience motor fluctuations and immobility ('off' episodes) between doses. This study assessed adjunctive Zelapar (selegiline orally disintegrating tablet (ODT)) for managing off episodes and for long-term safety.
This open-label extension evaluated long-term safety, efficacy, and tolerability of adjunctive selegiline ODT 2.5 mg in patients who completed either of two large phase 3 double-blind studies. The study was to end after 12 months but was amended to be open-ended. Investigators could increase levodopa doses and introduce controlled-release formulations of levodopa or dopamine agonists if warranted. Additionally, results of a small randomized trial of open-label selegiline ODT 1.25 mg in comparison to conventional selegiline was added only to the safety analysis. Efficacy variables included changes in daily off time and Patient's Global Impression of Improvement (PGI-I) and Clinical Global Impressions Severity of Disease (CGI-S) ratings. Safety assessments included adverse events and oropharyngeal findings.
This study enrolled 254 patients: 248 from the large phase 3 studies (efficacy analysis) and an additional six from the prior open-label comparison (safety analysis) in order to evaluate a larger population for safety purposes. Mean reduction from baseline in daily off time was 9.4% (1.6 h) for patients previously given selegiline ODT, 6.0% (1.2 h) for those switched from placebo, and 8.1% (1.4 h) overall. PGI-I and CGI-S ratings indicated little or no change from baseline. Treatment-related adverse events occurred in 132 (52%) patients. No severe oral irritations were attributed to selegiline ODT or prompted discontinuation.
Long-term selegiline ODT 2.5 mg/day was effective, safe, and well tolerated in patients with Parkinson's disease experiencing off episodes during levodopa therapy.
Current Medical Research and Opinion 05/2007; 23(4):741-50. · 2.38 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Treatment options for basal cell carcinoma include surgical excision, cryotherapy, radiation, photodynamic therapy, Moh's micrographic surgery, and topical treatment with 5-fluorouracil and immunomodulators such as imiquimod. Resurfacing and ablation with a CO(2) laser (UltraPulse, Coherent Inc.) may present an attractive and effective treatment option in the management of these cutaneous cancers. We demonstrate the efficacy and safety of the UltraPulse CO(2) in the treatment of basal cell carcinomas of the skin.
We performed a retrospective chart review of 23 patients treated with the UltraPulse CO(2) laser. A total of 61 biopsy-proven superficial and nodular basal cell carcinomas without prior treatment were included in the study. The patients were followed postoperatively for a period of 15 to 85 months (mean 41.7 months) and assessed for clinical recurrence.
Of the 61 tumors treated, clinical recurrence was observed in two cases (3.2%). Adverse effects included significant hypertrophic scarring in one patient and hypopigmentation in one patient.
Destruction of superficial and nodular basal cell carcinomas may be accomplished successfully and safely with the UltraPulse CO(2) laser with a cure rate of 97%.
Dermatologic Surgery 10/2004; 30(9):1214-8. · 1.80 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although there are many effective treatment modalities for individual actinic keratoses (AKs), widespread lesions on the photoaged face pose a challenge due to inefficient and ineffective therapy resulting in high rates of recurrence after local destruction. Full face laser resurfacing offers an effective and efficient treatment option that successfully reduces the number of AK's on diffusely damaged skin and may show a prophylactic benefit for preventing non-melanoma skin cancers.
To assess the efficacy of full face laser resurfacing in reducing the number of facial AK's by comparing preoperative and postoperative numbers of lesions present and to observe the incidence of non-melanoma skin cancer after full face laser resurfacing.
A retrospective chart review of 24 patients with widespread facial AK's (greater than 30) treated with full face UPCO(2) and/or Er:Yag laser resurfacing was performed. All patients were a minimum of 1 year post-operative following facial laser resurfacing. The recurrence of AK's and the occurrence of facial non-melanoma skin cancers in these patients was assessed through chart analysis.
Widespread AK's were effectively eliminated in all patients. Twenty-one patients (87%) remained lesion free for at least 1 year. Fourteen of the 24 patients (58.3%) showed no new lesions during a 2-year follow-up. There was an overall 94% reduction in total number of AK's. Adverse effects included transient perioral scarring in one patient, S. aureus infection in two patients, and dyschromia in two patients.
Full face laser resurfacing provides long-term effective prophylaxis against AKs and may reduce the incidence of AK related squamous cell carcinoma.
Lasers in Surgery and Medicine 02/2004; 34(2):114-9. · 2.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Tolcapone, administered with levodopa/carbidopa to patients with Parkinson disease, is an effective and generally well-tolerated adjunctive therapy. However, 4 early cases of hepatotoxicity causing 3 deaths in patients not properly monitored gave rise to more rigorous liver function test monitoring guidelines and a liver function test monitoring program in which blood samples from tolcapone-treated patients were tested and results were collected in a central database. We analyzed these results to determine the percentages of patients with at least 1 aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation above the upper limit of normal (ULN) and at least 1 elevation greater than 2 times the ULN.
This retrospective, observational analysis included all AST and ALT values recorded in the database from 11,883 samples from patients who received tolcapone for up to 2 years or longer (January 1999-January 2001).
Of 1725 patients who had at least 1 AST or ALT measurement, 3.9% (n = 67) had elevations above the ULN. Less than 1% (15/1725) of patients had AST or ALT elevations greater than 2 times the ULN. Most values returned to normal during continued tolcapone treatment. In 472 patients monitored biweekly while receiving tolcapone for 20 to 114 consecutive weeks, only 0.6% (n = 3) had an AST or ALT value greater than 2 times the ULN; no significant elevations occurred in the remaining 469 (99.4%).
This analysis of results from the central monitoring program suggests that significant transaminase elevations are rare, typically transient, and may return to normal in the face of continued tolcapone therapy in most patients.
Clinical Neuropharmacology 30(5):281-6. · 2.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Selegiline orally disintegrating tablet (ODT; Zelapar) is a selective monoamine oxidase B inhibitor developed as an adjunct to levodopa (LD) for Parkinson disease. Most patients on long-term LD therapy eventually experience deterioration at the end of the LD dosing interval, with predictable "wearing off" and "on-off" fluctuations.
We conducted a 12-week, double-blind, placebo-controlled, parallel-design trial of selegiline ODT. The primary efficacy point was reduction in the percentage of average daily "off" time. Secondary measures included reductions in daily off hours and total daily off time, Clinical Global Impressions-Improvement (CGI-I), and Patient Global Impression-Improvement (PGI-I). Patients on LD received selegiline ODT (1.25 mg/d for 6 weeks, then 2.5 mg/d for 6 weeks) or placebo. Safety and tolerability were measured.
The intent-to-treat population included 98 patients receiving selegiline ODT and 50 patients receiving placebo. Combined efficacy results for weeks 10 and 12 revealed an 11.6% reduction in percentage of daily off time for selegiline ODT versus a 9.8% reduction for placebo (NS). PGI-I detected a statistically significant difference between treatment groups in favor of selegiline ODT (P = 0.02), whereas CGI-I detected a strong trend toward improvement (P = 0.06). Selegiline ODT was safe and well tolerated.
This study showed no significant difference in improvement in percentage of off time with selegiline ODT versus placebo. Some clinical impressions (e.g., PGI-I, CGI-I) improved. This result contrasts with an identically designed study that showed a significant improvement in off time with selegiline ODT. A combined analysis of both studies suggested overall efficacy.
Clinical Neuropharmacology 30(5):295-300. · 2.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Warts are a common pediatric skin disease. Most treatments show only modest benefit, and some are poorly tolerated because of pain. 5-fluorouracil interferes with deoxyribonucleic acid and ribonucleic acid synthesis, and is used to treat genital warts in adults. Efficacy, safety, and tolerability of topical 5% 5-fluorouracil for treatment of common warts were examined in an open-label pilot study with pediatric patients. Thirty-nine children who have at least two hand warts applied 5% 5-fluorouracil cream (Efudex, Valeant Pharmaceuticals International) once or twice daily, under occlusion for 6 weeks. Assessment of treatment response and side effects was performed at baseline, treatment completion, and 3- and 6-month follow-ups. Hematology measures, liver function tests, and medication blood levels were reassessed at treatment completion. Eighty-eight percent of treated warts improved after 6 weeks of treatment, and 41% of subjects had complete resolution of at least one wart. Treatment response did not differ between once or twice daily applications. Tolerability and patient satisfaction were excellent. No subject had clinically significant blood levels of 5-fluorouracil. At 6 month follow-up, 87% of complete responders had no wart recurrence. Topical 5% 5-fluorouracil is a safe, effective, and well-tolerated treatment for warts in children.
Pediatric Dermatology 26(3):279-85. · 1.07 Impact Factor
