Publications

OBJECTIVE: To investigate the efficacy and safety of ABT-874, an interleukin 12/23 monoclonal antibody, in psoriasis.

DESIGN: Phase 2, 12-week, multicenter, randomized, double-blind, placebo-controlled trial.

SETTING: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Accurately determining the incidence and prevalence of dermatologic disease in most large populations has been challenging for reasons ranging from the lack of easily quantifiable tests and measures to imprecision around definitions of race, ethnicity, photo skin type, pigmentation, and population groups. Compounding the problems with these categorizations is the fact that skin disease and skin health are affected not just by inherent risk factors but also by habits and environment. Thus, a fundamental question remains as we evaluate the effects of cultural and environmental factors: do genetic factors account for most of the difference that we see in skin types? Is the primary influence the way the skin mediates the environmental insult of UV radiation or how inflammation is handled? Is melanization the primary characteristic that we should measure and consider? This article will provide an introduction to current knowledge and future directions researchers are taking in differentiating both the biological differences of skin and the clinical manifestations of skin disease among the groups described above. This discussion will be followed by a brief overview of cultural practices and environmental factors that are known to have significant impact on skin disease and a summary of the most common conditions that are encountered worldwide.

BACKGROUND: Submissions to the Journal of the American Academy of Dermatology (JAAD) undergo a rigorous peer-review process. However, little is known regarding the fate of manuscripts declined by the JAAD.

OBJECTIVE: We sought to: (1) determine the proportion of manuscripts declined by the JAAD that are subsequently published elsewhere; (2) identify the journals in which they were published; and (3) study whether the authors of declined manuscripts adopted in their final publications the changes suggested by the JAAD reviewers.

METHODS: We reviewed the outcomes of the 489 submissions declined by the JAAD during two 4-month periods: from March 1, 2004, to June 30, 2004, and from March 1, 2005, to June 30, 2005.

RESULTS: Of the 981 manuscripts submitted to JAAD during the two 4-month periods studied, 489 manuscripts (50%) were declined. Among the declined manuscripts, 201 (41%) had been subsequently published in other medical journals as of March 1, 2007. Among the 55 journals that published manuscripts declined by JAAD, 23 (42%) were nondermatology journals. The median impact factor for these 55 journals was 1.638, compared with the JAAD's impact factor of 2.402. Among the declined manuscripts, Case Reports comprised the largest proportion (n = 149, 31%), followed by Original Research Reports (n = 90, 18%). Overall, 46 (51%) rejected Original Research Reports were subsequently published, compared with 145 (36%) rejected submissions in other categories that were later published (P < .01). Among the 101 subsequently published manuscripts for which full texts were available, 82% of the authors incorporated at least one change suggested by the JAAD reviewers. The manuscripts that adopted JAAD-reviewer suggestions were published in journals with higher impact factors than those that did not incorporate any JAAD-reviewer suggestions (P = .0305).

LIMITATIONS: It is possible that the average lag time of 28 months in this study is not sufficient for some rejected manuscripts to reach subsequent publication.

CONCLUSIONS: Approximately half of the manuscripts rejected by the JAAD were subsequently published in other journals within 28 months, among which, roughly 40% went to nondermatology journals. The median impact factor of the journals that published JAAD-rejected manuscripts was lower than that of the JAAD. Rejected Original Research Reports have a significantly higher probability of being subsequently published than other category submissions. This may be a result of relative quality of Original Research Reports versus submissions for other sections of the journal (eg, Case Reports). Manuscripts that adopted JAAD-reviewer suggestions were subsequently published in journals with higher impact factors than those that did not incorporate JAAD-reviewer suggestions. This indicates that peer-reviewer comments can be useful and important for improving the quality of scientific publications.

INTRODUCTION: Erosive mucosal lichen planus is thought to be an autoimmune disease mediated by increased T-cell activation and proliferation. Alefacept is a biologic agent that selectively targets memory T cells.

OBJECTIVE: To evaluate the preliminary efficacy and safety of alefacept in the treatment of moderate to severe mucosal LP.

METHODS: Seven subjects were randomly selected to receive either alefacept 15 mg or placebo every week for 12 weeks. Endpoints of the case series were the Physician Global Assessment (PGA) of disease severity, mucosal pain (MP) severity, and itch severity (IS). Both subjects and investigators were blinded.

RESULTS: Two of the subjects receiving alefacept achieved significant improvement during the study. There were no serious adverse events during the course of the study period.

CONCLUSIONS: In this small case series, alefacept may have conferred a modest therapeutic response in erosive lichen planus (LP). Larger multicenter prospective studies will be needed to determine whether alefacept can improve erosive LP in a statistically significant way.

OBJECTIVE: The 24-week Etanercept Assessment of Safety and Effectiveness (EASE) study evaluated the effectiveness and tolerability of continuous versus interrupted etanercept treatment in patients with moderate to severe plaque psoriasis. The objective of this analysis was to assess patient-reported outcomes (PROs) and health-care resource utilization (HRU) data from the EASE study.

METHODS: Patients received open-label etanercept 50 mg twice weekly for 12 weeks and then received either continued or interrupted (single round of discontinuation and re-treatment with etanercept) etanercept 50 mg once weekly for the second 12 weeks. PROs included the following: 1) the patient global assessments of psoriasis, joint pain, and itching scores; 2) the Dermatology Life Quality Index; 3) the Medical Outcomes Study Short Form 36 vitality domain; 4) the Beck Depression Inventory; 5) the European Quality-of-Life Group Feeling Thermometer; and 6) a patient satisfaction survey. HRU was evaluated using the Economic Implications of Psoriasis patient questionnaire.

RESULTS: Continuous treatment with etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks produced sustained and clinically important improvements in PROs and reductions in HRU. Reductions in some outcome measures after treatment discontinuation at week 12 were observed in the interrupted group; however, most changes did not revert to baseline levels, consistent with some residual clinical effect, and re-treatment produced improvements similar to week 12 levels.

CONCLUSIONS: Continuous etanercept treatment provided greater sustained improvements in PROs than interrupted therapy; however, interrupting etanercept therapy, if needed, has predictable and manageable effects.

Oral contraceptives (OCs) have been shown to be safe and effective for the treatment of acne in most women of childbearing potential, and several have been approved by the Food and Drug Administration for this purpose. However, dermatologists have historically been reluctant to prescribe OCs for acne because of long-standing recommendations requiring a preliminary pelvic examination and Papanicolaou smear before initiation of therapy. In recent guideline shifts, expert panels and major health organizations have reached a consensus that OC provision no longer necessitates the performance of a pelvic examination and Papanicolaou smear. These new guideline revisions could change the way dermatologists treat acne in their healthy female patients of child-bearing age.

The diagnosis of thyroid disease can often first be identified by recognizing various cutaneous manifestations associated with an imbalance of circulating thyroid hormone. This article reviews the pathophysiology of thyroid disease, characteristic cutaneous findings of the hypothyroid and hyperthyroid states, and cutaneous conditions associated with thyroid disease.

BACKGROUND: Interleukins 12 and 23 have important roles in the pathophysiology of psoriasis. We assessed ustekinumab, a human monoclonal antibody directed against these cytokines, for the treatment of psoriasis.

METHODS: In this phase III, parallel, double-blind, placebo-controlled study, 766 patients with moderate-to-severe psoriasis were randomly assigned to receive ustekinumab 45 mg (n=255) or 90 mg (n=256) at weeks 0 and 4 and then every 12 weeks; or placebo (n=255) at weeks 0 and 4, with subsequent crossover to ustekinumab at week 12. Patients who were initially randomised to receive ustekinumab at week 0 who achieved long-term response (at least 75% improvement in psoriasis area and severity index [PASI 75] at weeks 28 and 40) were re-randomised at week 40 to maintenance ustekinumab or withdrawal from treatment until loss of response. Both randomisations were done with a minimisation method via a centralised interactive voice response system. The primary endpoint was the proportion of patients achieving PASI 75 at week 12. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00267969.

FINDINGS: All randomised patients were included in the efficacy analysis. 171 (67.1%) patients receiving ustekinumab 45 mg, 170 (66.4%) receiving ustekinumab 90 mg, and eight (3.1%) receiving placebo achieved PASI 75 at week 12 (difference in response rate vs placebo 63.9%, 95% CI 57.8-70.1, p<0.0001 for 45 mg and 63.3%, 57.1-69.4, p<0.0001 for 90 mg). At week 40, long-term response had been achieved by 150 patients in the 45 mg group and 172 patients in the 90 mg group. Of these, 162 patients were randomly assigned to maintenance ustekinumab and 160 to withdrawal. PASI 75 response was better maintained to at least 1 year in those receiving maintenance ustekinumab than in those withdrawn from treatment at week 40 (p<0.0001 by log-rank test). During the placebo-controlled phase, adverse events occurred in 278 (54.5%) of the 510 patients receiving ustekinumab and 123 (48.2%) of the 255 receiving placebo. Serious adverse events occurred in six (1.2%) of 510 patients receiving ustekinumab and in two (0.8%) of 255 receiving placebo in this phase. The pattern of adverse events was much the same in the placebo crossover and randomised withdrawal phases as it was in the placebo-controlled phase.

INTERPRETATION: Ustekinumab seems to be efficacious for the treatment of moderate-to-severe psoriasis; dosing every 12 weeks maintains efficacy for at least a year in most patients.

There have been several articles and reports in recent months about comorbidities and risks that affect psoriasis patients in addition to their underlying disease. This piece reviews the current literature and begins to address what should be done with this new information by updating the clinician about what health screening tests, preventative exams, and referrals should be considered in this population.