Publications

BACKGROUND: Psoriasis significantly impairs work productivity and daily activities.

OBJECTIVES: We sought to examine the effects of adalimumab on psoriasis-related work productivity and activity impairment and associations between the impairment and psoriasis severity in patients with moderate to severe psoriasis.

METHODS: Data were from the first 16 weeks of the Randomized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis TriAL (REVEAL). Outcomes as measured by the Work Productivity and Activity Impairment Questionnaire for Psoriasis (WPAI-Psoriasis) included employment status, total work productivity impairment, and total activity impairment. Logistic regression and analyses of covariance were used to assess the effects of adalimumab and treatment response (≥ 75% improvement in Psoriasis Area and Severity Index responders) on WPAI-Psoriasis outcomes. Longitudinal generalized estimating equations and Pearson correlation coefficients were used to assess associations between WPAI outcomes and psoriasis severity.

RESULTS: Greater improvements in total work productivity impairment and total activity impairment were observed with adalimumab treatment versus placebo (15.5 and 11.1 percentage points, respectively; P < .001). Unemployment rate, total work productivity impairment, and total activity impairment were significantly associated with greater baseline psoriasis severity. Changes in WPAI outcomes were significantly correlated with greater psoriasis severity. The Dermatology Life Quality Index had stronger associations with changes in WPAI outcomes compared with clinical severity measures (Psoriasis Area and Severity Index and Physician Global Assessment).

LIMITATIONS: REVEAL only included WPAI data for 16 weeks. Therefore, long-term impact of adalimumab treatment on productivity outcomes could not be assessed. In addition, information on occupational job title or industry was not collected and data were not adjusted for psoriatic arthritis.

CONCLUSIONS: Adalimumab reduced psoriasis-related work productivity and activity impairment in patients with moderate to severe psoriasis.

Treatment with tumor necrosis factor-alfa inhibitors and other systemic medications increases the risk of reactivating a latent tuberculosis (TB) infection. Therefore, screening for latent TB infection is important in dermatology patients eligible for treatment with these medications. Although the tuberculin skin test (TST) has its limitations, it has been the standard choice for diagnosis of latent TB infection. Since the development of interferon gamma release assays (IGRAs), the role of the TST has been re-evaluated and IGRAs have increasingly been incorporated into national guidelines. Although there are situations when either test may be performed, in individuals who have received a BCG vaccination and in those who are unlikely to return for a TST reading, IGRAs may be particularly helpful in distinguishing patients at risk for TB. This article discusses the advantages and disadvantages of both the TST and the IGRA and presents a summary of the Centers for Disease Control and Prevention 2010 guidelines for using IGRAs.

BACKGROUND: Although there are many psoriasis assessment tools currently published, one of the unmet needs in psoriasis research remains consensus about the single best validated and reproducible assessment tool.

OBJECTIVES: In this systematic review we sought to determine the degree of correlation between two commonly used psoriasis assessment tools, the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA).

METHODS: Randomized controlled systemic trials in moderate to severe psoriasis were reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We recorded and compared the percent of patients achieving both 75% reduction in PASI score (PASI 75) and PGA 0 or 1 (clear or almost clear) at 8 to 16 weeks, 17 to 24 weeks, and greater than 24 weeks of treatment with the investigational drug.

RESULTS: Our literature review yielded 30 randomized controlled trials using biologic agents in moderate to severe psoriasis. We found that the two assessment tools correlate very tightly except at the lower bounds of therapeutic efficacy. The r(2) values for the correlation between PASI 75 and a score of clear or almost clear on the PGA were 0.9157 at 8 to 16 weeks and 0.892 at 17 to 24 weeks.

LIMITATIONS: Limitations of our study include the small number of randomized controlled trials publishing the percent of patients achieving 75% reduction in PASI score and a score of clear or almost clear on the PGA after 24 weeks of therapy. In addition, our results are not generalizable beyond the patients with moderate to severe plaque psoriasis.

CONCLUSION: The two assessment tools are substantially redundant and either alone is a sufficient tool for assessing psoriasis severity in patients with moderate to severe disease. Because the PASI is better validated and more detailed, it remains the score of choice for clinical trials, but the simpler PGA may be well suited for community-based outcomes projects.

BACKGROUND: Acne vulgaris is a common skin disease with a large quality of life impact, characterized by comedones, inflammatory lesions, secondary dyspigmentation, and scarring. Although traditionally considered a disease of adolescence, reports suggest it is also a disease of adults, especially adult women. Our objectives were to determine acne prevalence in a large, diverse group of women and to examine acne by subtype and in relation to other skin findings, measurements, and lifestyle factors.

METHODS: We recruited 2895 women aged 10-70 from the general population. Photographs were graded for acne lesions, scars, and dyspigmentation. Measurements were taken of sebum excretion and pore size, and survey data were collected.

RESULTS: Of the women studied, 55% had some form of acne: 28% had mild acne, and 27% had clinical acne, 14% of which was primarily inflammatory and 13% of which was primarily comedonal. Acne peaked in the teenage years, but 45% of women aged 21-30, 26% aged 31-40, and 12% aged 41-50 had clinical acne. Women with inflammatory acne were younger than those with comedonal acne (p≤0.001), and postmenopausal women had less acne than age-matched peers (p<0.0001). Acne was associated with facial hirsutism (p=0.001), large pores (p=0.001), and sebum excretion (p=0.002). Smokers had more, primarily comedonal, acne than nonsmokers.

CONCLUSIONS: The cross-sectional design precludes conclusions about progression of acne with age. Participation was restricted to women. The photographic nature of the study imposes general limitations. Techniques used in this study were not sufficiently sensitive to identify cases of subclinical acne. More than a quarter of women studied had acne, which peaked in the teens but continued to be prevalent through the fifth decade.

BACKGROUND: An unmet need remains for safe and effective long-term treatments of psoriasis.

OBJECTIVES: To evaluate ustekinumab efficacy and safety for up to 3 years in the PHOENIX 1 trial.

METHODS: Patients (n = 766) with moderate-to-severe psoriasis were randomized to ustekinumab 45 mg or 90 mg at weeks 0 and 4, and then every 12 weeks, or placebo at weeks 0 and 4, with crossover to ustekinumab at week 12. Ustekinumab responders [≥ 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at weeks 28 and 40] were re-randomized at week 40 to continue or withdraw from treatment until psoriasis recurrence. Partial responders (week 28: PASI 50-74; week 40: < PASI 75) switched to dosing every 8 weeks. Clinical efficacy was assessed by PASI, the Physician's Global Assessment (PGA), and the Dermatology Life Quality Index (DLQI) measures.

RESULTS: Overall, 79·8% of the ustekinumab-treated patients remained in the study for 3 years. PASI 75 response rates (45 mg: 61·2%; 90 mg: 72·4%) at week 76 were maintained through year 3 (45 mg: 62·7%; 90 mg: 72·2%); PGA response was similarly durable. At year 3, 80·9% (45 mg) and 82·7% (90 mg) of week 40 responders continuing treatment every 12 weeks achieved a PASI 75 response, while 42·6% (45 mg) and 58·0% (90 mg) achieved a PASI 90 response. Among partial responders adjusted to dosing every 8 weeks, 50·9% (45 mg) and 52·0% (90 mg) had a PASI 75 response at year 3. DLQI responses paralleled the PASI responses. Through year 3, no dose response was observed in rates of adverse events (AEs), overall infections, serious AEs, or AEs leading to discontinuation; nor was there evidence of cumulative organ toxicity. CONCLUSIONS; Continuous, stable, maintenance dosing with ustekinumab was generally well tolerated and sustained durable efficacy for up to 3 years of treatment.

BACKGROUND: Papulopustular acne rosacea is a chronic inflammatory condition which can be difficult to treat. Many patients are unwilling to use systemic medications, and single topical agents alone may not address all the symptoms of rosacea. A combination topical clindamycin phosphate 1.2% and tretinoin 0.025% gel is efficacious for acne vulgaris, and may be helpful for rosacea, since acne vulgaris and rosacea shares many similar clinical and histologic features.

OBJECTIVE: To assess the preliminary efficacy and safety of a combination gel consisting of clindamycin phosphate 1.2% and tretinoin 0.025% on papulopustular rosacea after 12 weeks of usage.

METHODS: Randomized, double-blind, placebo controlled two site study of 79 participants with moderate to severe papulopustular acne rosacea using both physician and subjects' validated assessment tools. Primary endpoint consisted of statistically significant reduction in absolute papule or pustule count after 12 weeks of usage.

RESULTS: There was no significant difference in papule/pustule count between placebo and treated groups after 12 weeks (P=0.10). However, there was nearly significant improvement in physicians' assessments of the telangiectasia component of rosacea (P=0.06) and erythematotelangiectatic rosacea subtype (P=0.05) in treated versus placebo group after 12 weeks. The only significant adverse event different was facial scaling, which was significantly increased in treated group (P=0.01), but this did not result in discontinuation of study drug.

CONCLUSIONS: A combination gel of clindamycin phosphate 1.2% and tretinoin 0.025% may improve the telangiectatic component of rosacea and appears to better treat the erythemotelangiectatic subtype of rosacea rather than papulopustular subtype. Our preliminary study suggests that future studies with much larger sample size might confirm our findings.

BACKGROUND: Ingestion of multiple antioxidants may result in synergistic increases in skin protection.

METHODS: In a double-blind, randomized, controlled study, the authors evaluated the effect of an antioxidant combination product in women with mild-to-moderate photoaging over 20 weeks. Changes on Oxygen Radical Absorbance Capacity levels and Minimal Erythema Dose were measured throughout the study.

RESULTS: Both Minimal Erythema Dose and Oxygen Radical Absorbance Capacity levels increased in women receiving the antioxidant combination product, with the difference from baseline being statistically significant as early as Week 4. Similar findings were observed in women who received the control product, which had modest antioxidant activity. The comparisons between the two groups were not statistically significant.

CONCLUSION: Oral ingestion of a combination of antioxidants can lead to improvement on objective measurements, such as Minimal Erythema Dose and Oxygen Radical Absorbance Capacity levels, when compared to baseline values.

BACKGROUND: Ustekinumab targets interleukin (IL)-12 and IL-23 in the treatment of moderate to severe psoriasis.

OBJECTIVE: We sought to evaluate the impact of ustekinumab on infections and malignancies, both theoretical risks of blocking IL-12 and IL-23, in patients exposed up to 3 years.

METHODS: Rates of infections and malignancies were evaluated in cumulative safety data from 3117 ustekinumab-treated patients across 4 studies.

RESULTS: During the placebo-controlled periods, rates of overall infections per 100 patient-years were similar among placebo (121.0), ustekinumab 45-mg (145.7), and ustekinumab 90-mg (132.2) groups, with overlapping confidence intervals, and remained stable through 3 years in ustekinumab groups. Rates of serious infections during the placebo-controlled periods were similar between placebo (1.70) and 90-mg (1.97) groups, yet lower in the 45-mg group (0.49). Rates remained stable (90 mg) or decreased (45 mg) over time, and were comparable with those for the US psoriasis population based on a managed care database. Rates of malignancies during the placebo-controlled periods were comparable among groups (placebo: 1.70; 45 mg: 0.99; 90 mg: 0.98) and remained stable over time in ustekinumab groups. Rates of malignancies, excluding nonmelanoma skin cancer, were comparable with rates expected in the general US population based on the Surveillance, Epidemiology, and End Results database.

LIMITATIONS: Controlled periods do not extend beyond 12 to 20 weeks. Only 1247 patients were treated for at least 2 years, to date. Comparator database populations may not fully represent the clinical trial population.

CONCLUSIONS: The emerging safety profile of ustekinumab remains favorable and does not suggest increased rates of infection or malignancy through 3 years.

The skin has an amazing array of complex interacting biological processes. Recent advances in investigational techniques now allow evaluation of these processes at the level of the gene, protein and metabolite. Sometimes collectively known as the omics, these fields of inquiry, known as genomics, proteomics and metabolomics, respectively, are yielding new and important insights into skin structure and processes, its responses to injury and age, and the mechanisms by which new interventions and compounds may work to improve the health and integrity of this crucial organ.