BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, painful skin disease characterized by abscesses, nodules, and draining fistulas in the axilla and groin of young adults.
OBJECTIVE: To evaluate the efficacy and safety of adalimumab, an anti-tumor necrosis factor-α antibody, in patients with moderate to severe HS.
DESIGN: Phase 2, parallel, randomized, placebo-controlled trial consisting of a blinded 16-week period (period 1) and an open-label 36-week period (period 2). All study personnel, investigators, and patients remained blinded to treatment group throughout the study. (ClinicalTrials.gov: NCT00918255)
SETTING: 26 academic and private practice medical centers in the United States and Europe.
PATIENTS: 154 adult patients with moderate to severe HS who were unresponsive or intolerant to oral antibiotics.
INTERVENTION: Patients were assigned in a 1:1:1 ratio to adalimumab, 40 mg/wk; adalimumab, 40 mg every other week (EOW); or placebo. All patients received adalimumab, 40 mg EOW, at the beginning of period 2 but switched to weekly dosing if the response was suboptimal (HS Physician's Global Assessment [PGA] score of moderate or worse) at weeks 28 or 31.
MEASUREMENTS: The primary outcome measure (clinical response) was the proportion of patients achieving an HS-PGA score of clear, minimal, or mild with at least a 2-grade improvement relative to baseline at week 16.
RESULTS: At week 16, 3.9% of placebo patients (2 of 51), 9.6% of EOW patients (5 of 52), and 17.6% of weekly patients (9 of 51) achieved clinical response (EOW vs. placebo strata-adjusted difference, 5.6% [95% CI, -4.0% to 15.3%]; P = 0.25; weekly vs. placebo strata-adjusted difference, 13.7% [CI, 1.7% to 25.7%]; P = 0.025). Serious adverse event rates were 3.9%, 5.8%, and 7.8% for placebo, EOW, and weekly patients, respectively (EOW vs. placebo difference, 1.8% [CI, -6.4% to 10.1%]; weekly vs. placebo difference, 3.9% [CI, -5.2% to 13.0%]). Significantly greater improvements in patient-reported outcomes and pain were seen in the weekly dosing group than in the placebo group. A decrease in response was seen after the switch from weekly to EOW dosing in period 2.
LIMITATIONS: Weeks 16 to 52 of the study were open-label. The study was not powered to assess the risk for known serious adverse effects of adalimumab, such as tuberculosis, other serious infections, and demyelinating disorders.
CONCLUSION: Adalimumab dosed once per week alleviates moderate to severe HS.
PRIMARY FUNDING SOURCE: Abbott Laboratories.
BACKGROUND: Psoriasis is associated with a variety of major physical and mental co-morbidities.
OBJECTIVE: To assess the incremental burden of co-morbidities on patient-reported outcomes and evaluate the efficacy and safety of adalimumab in psoriasis patients with co-morbidities.
STUDY DESIGN: Data were obtained from the initial 16-week, double-blind treatment period of REVEAL (Randomized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis triAL), a randomized, multicenter, phase III clinical trial.
INTERVENTION: Patients with moderate to severe psoriasis were randomized in a 2 : 1 ratio to receive adalimumab 80 mg (two 40 mg injections administered subcutaneously) at baseline followed by one 40 mg injection every other week from week 1 to week 15 or placebo.
MAIN OUTCOME MEASURES: Clinical severity (Psoriasis Area and Severity Index [PASI]) and patient-reported outcomes (Dermatology Life Quality Index [DLQI], Short Form 36 [SF-36] health survey, Work Productivity and Activity Impairment [WPAI] questionnaire) were assessed during the trial. The effect of selected co-morbidities (i.e. hypertension, psoriatic arthritis, hyperlipidemia, obesity, depression, other forms of arthritis, diabetes mellitus, and other cardiovascular diseases) on patient-reported outcomes was evaluated using multivariate analysis of covariance models. Subgroup analyses were performed by co-morbidity type to statistically compare the clinical efficacy, patient-reported outcome benefits, and safety of adalimumab with placebo in the presence of these conditions.
RESULTS: Study co-morbidities were each independently associated with significantly greater impairment on at least one general patient-reported outcome measured at baseline (all p < 0.05), with the exception of hyperlipidemia. During the 16-week study, adalimumab patients demonstrated significantly greater PASI 75 response rates (defined as a reduction of at least 75% in PASI scores from baseline) compared with placebo patients for all co-morbidity subgroups. Adalimumab provided consistent improvements in DLQI, SF-36 Physical Component Summary and Mental Component Summary scores, and WPAI total scores from baseline to week 16 within co-morbidity subgroups. Rates of serious adverse events (AEs), serious infectious AEs, and AEs leading to discontinuation were comparable between adalimumab and placebo for patients with co-morbidities.
CONCLUSIONS: Co-morbidities were associated with additionally impaired health-related quality of life and work productivity in patients with psoriasis. Adalimumab significantly improved efficacy and patient-reported outcomes and was well tolerated in patients with co-morbidities.
BACKGROUND: Psoriasis is frequently associated with comorbidities.
OBJECTIVE: To estimate the incremental economic burden associated with comorbidities in patients with psoriasis, accounting for psoriasis severity.
METHODS: Patients continuously enrolled ≥6 months after a randomly selected psoriasis diagnosis date were selected from the Ingenix Impact National Managed Care Database (1999-2004). Comorbidities identified during the 6-month study included: psoriatic arthritis, cardiovascular disease, depression, diabetes, hyperlipidemia, hypertension, obesity, cerebrovascular diseases and peripheral vascular disease. Resource utilization and costs during the 6-month follow-up period were compared for patients with ≥1 comorbidity vs. those without and for patients with a specific comorbidity vs. those without. Adjusted incidence rate ratios (IRRs) and odds ratios (ORs) were estimated for resource utilization using negative binomial and logistic regression models, respectively. Adjusted incremental costs associated with comorbidities were reported using general linear models with log-link and gamma distributions or two-part models. Models controlled for age, sex and psoriasis severity.
RESULTS: A total of 114,512 patients were included; 51% had ≥1 comorbidity. Hyperlipidemia (27%) and hypertension (25%) were most prevalent. Patients with comorbidities were more likely to experience urgent care [OR (95% confidence interval (CI))=1.58 (1.51-1.65)] than patients without comorbidities. They also had significantly greater hospitalization rates [IRR (95% CI)=2.27 (2.13-2.42)] and outpatient visits [IRR (95% CI)=1.53 (1.52-1.55)]. Compared with patients who did not have comorbidities, patients with comorbidities incurred $2184 (P<0.001) greater total costs.
CONCLUSION: Comorbidities present a significant economic burden in patients with psoriasis.
BACKGROUND: ABT-874, an anti-interleukin-12 and -23 antibody, was previously shown to be significantly more effective compared with placebo during a 12-week phase II study of psoriasis. We report here safety and efficacy data of ABT-874 during subsequent phases of this study.
OBJECTIVE: We sought to examine the preliminary efficacy and safety of ABT-874 for moderate to severe psoriasis beyond 12 weeks.
METHODS: Patients with chronic plaque psoriasis who responded to ABT-874 during the initial randomized, placebo-controlled, 12-week study phase were eligible for a 36-week observation/retreatment phase. During the subsequent 60-week, open-label extension phase, eligible patients were retreated with one of two ABT-874 dosages. Efficacy was measured using Psoriasis Area and Severity Index and physician global assessment scores; safety was monitored by adverse events (AEs), laboratory parameters, and vital signs.
RESULTS: During the observation/retreatment phase, 130 of 180 patients were eligible for retreatment. After 12-week retreatment with ABT-874, 55% to 94% of retreated patients (n = 58) achieved a 75% or greater reduction in Psoriasis Area and Severity Index score. Among patients receiving ABT-874 through the first 48 weeks, there were no deaths and 4 patients with serious AEs; one patient discontinued because of an AE. During the open-label extension (N = 105), there were no deaths or serious infections, and 3 serious AEs.
LIMITATIONS: Lack of placebo or active comparator groups limited statistical analysis in later study phases. Dosing differences existed between groups, and only week-12 responders were eligible for retreatment.
CONCLUSION: ABT-874 continued to show good efficacy and safety during withdrawal and reinitiation of therapy.
BACKGROUND: Psoriasis is an inflammatory disease that not only affects the skin but can also have systemic implications such as obesity and nutritional deficiencies. Carotenoids are vitamin A provitamins with anti-oxidant properties that are present in human tissues including skin.
OBJECTIVES: To determine whether psoriasis is associated with lower levels of skin carotenoid levels.
METHODS: In this cross-sectional study, skin carotenoid levels were measured on the palms of 44 patients with psoriasis and 72 patients without psoriasis. A linear regression model was used to evaluate the relationship between psoriasis and carotenoid levels (primary aim) and to determine if severity of disease was associated with carotenoid levels (secondary aim). Potential confounders included demographic factors, smoking status, body mass index and multivitamin intake.
RESULTS: The mean carotenoid levels in the psoriasis and no psoriasis groups were respectively 22,099 and 29,180 and presence of psoriasis was found to be significantly related to lower levels of carotenoids in both univariable and multivariable analysis (P < 0.05). In the psoriasis group, the Psoriasis Area and Severity Index score was not significantly related to carotenoid levels (P = 0.07).
CONCLUSIONS: Patients with psoriasis appear to have lower skin carotenoid counts than patients without psoriasis.
BACKGROUND: The prevalence of physician extenders (PEs) has increased significantly in dermatologic surgery over the last decade.
METHODS: An analysis was performed of the staff in dermatologic surgery practices, roles of PEs, and level of supervision.
RESULTS: Mohs fellowship-trained (MMSFT) dermatologic surgeons were more likely to employ registered nurses (n=85, 73.9%) than non-fellowship-trained (NMMSFT) surgeons (n=65, 50.0%, p<.05) (dermatologists who reported performing Mohs without having completed a Mohs College fellowship). NMMSFT surgeons (n=46, 35.4%) were 33% more likely to employ physician assistants than MMSFT surgeons (n=30, 26.1%, p=.05). Both surgeon types reported that their physician assistants and nurse practitioners spent the majority of their time treating medical dermatology patients, but NMMSFT surgeons were twice as likely as MMSFT surgeons to have their PEs involved in performing or assisting with cosmetic procedures. MMSFT surgeons (38.5%) were twice as likely to have direct supervision of their PEs as NMMSFT surgeons (16.1%, p=.01).
CONCLUSIONS: PEs are highly prevalent in dermatologic surgery practices and are playing direct roles in the delivery of dermatologic care. Promoting patient safety through appropriate extender supervision and reporting of patient outcomes are highly needed as this sector of the dermatologic surgery workforce continues to expand.
CONTEXT: Ustekinumab and briakinumab, monoclonal antibodies to the shared p40 subunit of interleukin (IL)-12 and IL-23, have shown efficacy in treating chronic plaque psoriasis (CPP). Preliminary reports of major adverse cardiovascular events (MACEs) in psoriasis patients receiving anti-IL-12/23 agents have prompted concern.
OBJECTIVE: To evaluate a possible association between biologic therapies for CPP and MACEs via meta-analysis.
DATA SOURCES: Randomized controlled trials (RCTs) of anti-IL-12/23 (ustekinumab and briakinumab) agents and anti-tumor necrosis factor α (TNF-α) agents (adalimumab, etanercept, and infliximab) used in treating CPP were reviewed using the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Ovid MEDLINE from database inception to May 2011. The results of registered nonpublished completed studies were procured through abstract publications or poster presentations.
STUDY SELECTION: Randomized, placebo-controlled, double-blind, monotherapy studies (with safety outcome data for MACE) of IL-12/23 antibodies and anti-TNF-α agents in adults. Studies of psoriatic arthritis were excluded.
DATA EXTRACTION: Two investigators independently searched data while 6 investigators reviewed the abstracted data.
RESULTS: A total of 22 RCTs comprising 10 183 patients met the predefined inclusion criteria. The primary outcome measure was MACE, a composite end point of myocardial infarction, cerebrovascular accident, or cardiovascular death during the placebo-controlled phase of treatment in patients receiving at least 1 dose of study agent or placebo. Absolute risk differences were used as an effect measure. There was no evidence of statistical heterogeneity across the studies using the I(2) statistic (I(2) = 0), allowing for combination of trial results using the Mantel-Haenszel fixed-effects method. During the placebo-controlled phases of the anti-IL-12/23 studies, 10 of 3179 patients receiving anti-IL-12/23 therapies experienced MACEs compared with zero events in 1474 patients receiving placebo (Mantel-Haenszel risk difference, 0.012 events/person-year; 95% confidence interval [CI], -0.001 to 0.026; P =.12). In the anti-TNF-α trials, only 1 of 3858 patients receiving anti-TNF-α agents experienced a MACE compared with 1 of 1812 patients receiving placebo (Mantel-Haenszel risk difference, -0.0005 events/person-year; 95% CI, -0.010 to 0.009; P = .94).
CONCLUSIONS: Compared with placebo, there was no significant difference in the rate of MACEs observed in patients receiving anti-IL-12/IL-23 antibodies or anti-TNF-α treatments. This study may have been underpowered to identify a significant difference.
BACKGROUND: Acne vulgaris is a common skin disease with a large quality of life impact, characterized by comedones, inflammatory lesions, secondary dyspigmentation and scarring. There are few large objective studies comparing acne epidemiology between racial and ethnic groups.
OBJECTIVE: This study aimed to define the prevalence and subtypes of acne in women of different racial groups from four ethnicities.
METHODS: The sample consisted of 2895 (384 African American, 520 Asian, 1295 Caucasian, 258 Hispanic and 438 Continental Indian) women ranging in age from 10 to 70 years. Photographs of subjects were graded for acne lesions, scars, dyspigmentation, and measurements taken of sebum excretion and pore size.
RESULTS: Clinical acne was more prevalent in African American and Hispanic women (37%, 32% respectively) than in Continental Indian, Caucasian and Asian (23%, 24%, 30% respectively) women. All racial groups displayed equal prevalence of both subtypes of acne with the exception of Asians, for whom inflammatory acne was more prevalent than comedonal (20% vs. 10%) acne, and in Caucasians, for whom comedonal acne was more prevalent than inflammatory (14% vs. 10%) acne. Hyperpigmentation was more prevalent in African American and Hispanic (65%, 48% respectively) than in Asian, Continental Indian and Caucasian (18%, 10%, 25% respectively) women. Dyspigmentation and atrophic scarring were more common in African American and Hispanic women than in all other ethnicities. There was a negative correlation between pore size and skin lightness for all ethnicities. Sebum production was positively correlated with acne severity in African American, Asian and Hispanic women, and pore size was positively correlated with acne in African American, Asian and Continental Indian women, (for all above results, P<0.05).
LIMITATIONS: Only female participants were recruited. Data collection was restricted to four cities, with some ethnicities from single cities. Acne was evaluated only on the left side of the face and the two-dimensional nature of photography may not capture all skin surface changes.
CONCLUSION: Acne prevalence and sequelae were more common in those with darker skin types, suggesting that acne is a more heterogeneous condition than previously described and highlight the importance of skin-colour tailored treatment.