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To investigate the efficacy and safety of ABT-874, an interleukin 12/23 monoclonal antibody, in psoriasis.Phase 2, 12-week, multicenter, randomized, double-blind, placebo-controlled trial.Outpatient dermatology clinics. Patients One hundred eighty patients with clinically stable moderate to severe chronic plaque psoriasis. Interventions Patients were randomized in groups of 30 to receive 1 of 6 treatments with ABT-874 provided as a subcutaneous injection: one 200-mg dose at week 0; 100 mg every other week for 12 weeks; 200 mg weekly for 4 weeks; 200 mg every other week for 12 weeks; 200 mg weekly for 12 weeks; or placebo. Main Outcome Measure At least a 75% reduction in the Psoriasis Area and Severity Index.The percentage of patients achieving a 75% reduction in the Psoriasis Area and Severity Index at week 12 was statistically significantly greater in all of the ABT-874 treatment groups than in the placebo group (200 mg once, 63% [19 of 30]; 100 mg every other week for 12 weeks, 93% [28 of 30]; 200 mg weekly for 4 weeks, 90% [27 of 30]; 200 mg every other week for 12 weeks, 93% [28 of 30]; 200 mg weekly for 12 weeks, 90% [27 of 30]; placebo, 3% [1 of 30]; P.001). Treatment with ABT-874 was well tolerated. The most common adverse event was injection-site reaction, and the most common infectious adverse events were nasopharyngitis and upper respiratory tract infection. There were no serious infectious adverse events.ABT-874, an interleukin 12/23 monoclonal antibody, was highly effective and well tolerated in the treatment of psoriasis. Longer-term studies are required to confirm these findings.

Objective To evaluate the safety and efficacy of long-term treatment of psoriasis with etanercept, 50 mg twice weekly. Design, Setting, and Patients A phase 3, randomized, double-blind trial with an open-label extension. A total of 618 adult patients with moderate to severe plaque psoriasis were studied at 39 medical centers in the United States and Canada from May 23, 2003, through June 22, 2005. Interventions Patients were randomized to receive placebo or etanercept for 12 weeks. Beginning with week 13, all patients (N = 591) received etanercept. Main Outcome Measures Exposure-adjusted adverse event rates were calculated. Efficacy measures included efficacy and patient global assessment of psoriasis. Results Exposure-adjusted rates of adverse events, serious adverse events, infections, and serious infections were similar for placebo and etanercept treatments. Nonneutralizing antibodies to etanercept, observed in 18.3% of patients, had no apparent effect on safety or efficacy. Patients responded within 2 weeks to etanercept, with statistically significant differences in the Psoriasis Area and Severity Index and Dermatology Life Quality Index between the etanercept and placebo groups at week 12. At week 24, after 12 weeks of open-label etanercept treatment, patients in the original placebo group had clinical benefits comparable to those of patients in the original etanercept group. As both groups progressed through the open-label period, the Psoriasis Area and Severity Index response peaked at week 48. At week 96, 51.6% of the original placebo-treated patients and 51.1% of the original etanercept-treated patients had improvements from baseline in the Psoriasis Area and Severity Index of at least 75%. Conclusions Extended exposure to 50 mg of etanercept twice weekly resulted in exposure-adjusted rates of adverse events and infections similar to those in patients receiving placebo. Improvements in physician- and patient-reported measures of psoriasis severity were observed for up to 96 weeks of continuous etanercept therapy. Trial Registration clinicaltrials.gov IdentifierNCT00111449.

To identify histologic criteria and prognostic significance in patients with toxic epidermal necrolysis (TEN), a frequently lethal disease that usually represents an adverse drug reaction.Retrospective analysis of clinical records and histologic material from a 10-year period (1994-2004). Two investigators blinded to clinical data reviewed hematoxylin-eosin-stained sections.North American tertiary care, university-based burn unit. Patients Thirty-seven patients treated for TEN between 1994 and 2004 who had sloughing of 30% or more of their total body surface area and who underwent skin punch biopsies immediately following admission. Main Outcome Measure The degree of dermal mononuclear (DM) inflammation was graded (sparse, moderate, or extensive) at least 2 high-power fields (HPF) away from the perimeter of epidermal detachment, and the mean number of DM cells/5 HPF was quantified for each patient. Clinical records were reviewed and the following data extracted: age, history of cancer, percentage of total body surface area slough, heart rate, and serum glucose, bicarbonate, and serum urea nitrogen values on admission. Severity scores for TEN (SCORTEN) were calculated, and clinical outcome was recorded as survived or died during hospitalization.Extent of inflammation was assessed by categorizing the mean +/- SD DM cell counts as follows: sparse, 161 +/- 36 cells/HPF (n = 15); moderate, 273 +/- 76 cells/HPF (n = 15); and extensive, 392 +/- 124 cells/HPF (n = 7). There was good concordance between observer ratings (P.001). While 73% of patients (n = 11) with sparse inflammation survived, only 47% (n = 7) with moderate and 29% (n = 2) with extensive inflammation survived. The accuracy in predicting patient outcome was 65% using grade of inflammation, 68% with mean cell count, and 71% with SCORTEN.There is a histologic spectrum with TEN that ranges from sparse to extensive DM inflammation, and degree of inflammation predicts clinical outcome approximately as well as SCORTEN. Future clinical trials should consider the possibility that various patient subsets exist within the TEN population, and a role for immunocytes needs to be critically reevaluated in this devastating disease.

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.

To determine safety and efficacy of monotherapy with etanercept.Randomized, double-blind, placebo-controlled, multicenter study.Outpatient, ambulatory; private practice and university dermatology research centers.Patients aged at least 18 years, with plaque psoriasis involving 10% or more of body surface area; 148 were screened and 112 were randomly assigned to treatment groups and received study drug.Patients received placebo or etanercept, 25 mg, subcutaneously twice a week for 24 weeks. Other psoriasis therapies were limited during the study.Safety measurements included tracking of adverse events and laboratory values. Efficacy was evaluated using the Psoriasis Area and Severity Index (PASI); the primary end point was a 75% improvement in PASI. Other efficacy measurements included patient and physician global assessments and quality-of-life measures.After 12 weeks of treatment, 17 (30%) of the 57 etanercept-treated patients and 1 (2%) of the 55 placebo-treated patients had achieved PASI 75%, and after 24 weeks, 32 (56%) of etanercept-treated patients and 3 (5%) of placebo-treated patients had reached this level (P.001 for both time points). By 24 weeks, psoriasis was clear or minimal by physician's global assessment in more than 50% of patients who received etanercept. Treatment failure (PASI response50) occurred in 23% of patients at week 24. All other measures confirmed the efficacy of etanercept. Adverse events were similar among etanercept and placebo groups.Etanercept monotherapy provided significant benefit to patients with psoriasis and had a favorable safety profile.

REPORT OF A CASE A 77-year-old white woman presented with multiple (>50) erythematous, keratotic papules and plaques distributed diffusely on her trunk and extremities, including the sole of her left foot. These lesions varied in size from 2 mm to 6 cm in diameter (Figure). The patient noted an increasing number of lesions at a rate of approximately 2 to 3 new plaques per month. An excisional biopsy specimen of the largest and most irregular lesion on her back demonstrated invasive squamous cell carcinoma (SCC). Three more biopsies were performed, specimens of which showed full-thickness epidermal cell atypia and disorder consistent with Bowen disease (SCC in situ). The patient had 1 slightly pearly nodule on her neck that was clinically and histologically consistent with basal cell carcinoma. The patient grew up in rural Montana and had been exposed to arsenic in the well water and had also been given an

REPORT OF A CASE A 57-year-old man presented with a 5-year history of a crusting area on the left index finger. He was right handed and used the right hand to hold cigarettes. He had no history of arsenic ingestion or grenz ray treatments but had significant amounts of sun exposure. The area was not previously treated. An erythematous scaling plaque with sharply defined borders covered the dorsum of the left index finger and extended around to the palmar aspect of the digit. It also involved a portion of the web space between the first and second fingers. The dorsal and palmar surfaces of the digit were involved from a point 10 mm distal to the proximal interphalangeal joint to the base of the digit. However, a portion of the lateral aspect of the ir was spared. The plaque was 3.4×2.1 cm in diameter and had heaped up central crusting