Jashin J. Wu

Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis

BACKGROUND Early clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis. METHODS In two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physicians global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the superiority of brodalumab over ustekinumab at week 12 with respect to a 100% reduction in PASI score (PASI 100). RESULTS At week 12, the PASI 75 response rates were higher with brodalumab at the 210-mg and 140-mg doses than with placebo (86% and 67%, respectively, vs. 8% [AMAGINE-2] and 85% and 69%, respectively, vs. 6% [AMAGINE-3]; P<0.001); the rates of sPGA scores of 0 or 1 were also higher with brodalumab (P<0.001). The week 12 PASI 100 response rates were significantly higher with 210 mg of brodalumab than with ustekinumab (44% vs. 22% [AMAGINE-2] and 37% vs. 19% [AMAGINE-3], P<0.001). The PASI 100 response rates with 140 mg of brodalumab were 26% in AMAGINE-2 (P=0.08 for the comparison with ustekinumab) and 27% in AMAGINE-3 (P=0.007). Rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo. Mild or moderate candida infections were more frequent with brodalumab than with ustekinumab or placebo. Through week 52, the rates of serious infectious episodes were 1.0 (AMAGINE-2) and 1.3 (AMAGINE-3) per 100 patient-years of exposure to brodalumab. CONCLUSIONS Brodalumab treatment resulted in significant clinical improvements in patients with moderate-to-severe psoriasis. (Funded by Amgen; AMAGINE-2 and AMAGINE-3 ClinicalTrials.gov numbers, NCT01708603 and NCT01708629.).

Association Between Tumor Necrosis Factor Inhibitor Therapy and Myocardial Infarction Risk in Patients With Psoriasis

OBJECTIVE To assess whether patients with psoriasis treated with tumor necrosis factor (TNF) inhibitors have a decreased risk of myocardial infarction (MI) compared with those not treated with TNF inhibitors. DESIGN Retrospective cohort study. SETTING Kaiser Permanente Southern California health plan. PATIENTS Patients with at least 3 International Classification of Diseases, Ninth Revision, Clinical Modification, codes for psoriasis (696.1) or psoriatic arthritis (696.0) (without antecedent MI) between January 1, 2004, and November 30, 2010. MAIN OUTCOME MEASURE Incident MI. RESULTS Of 8845 patients included, 1673 received a TNF inhibitor for at least 2 months (TNF inhibitor cohort), 2097 were TNF inhibitor naive and received other systemic agents or phototherapy (oral/phototherapy cohort), and 5075 were not treated with TNF inhibitors, other systemic therapies, or phototherapy (topical cohort). The median duration of follow-up was 4.3 years (interquartile range, 2.9, 5.5 years), and the median duration of TNF inhibitor therapy was 685 days (interquartile range, 215, 1312 days). After adjusting for MI risk factors, the TNF inhibitor cohort had a significantly lower hazard of MI compared with the topical cohort (adjusted hazard ratio, 0.50; 95% CI, 0.32-0.79). The incidence of MI in the TNF inhibitor, oral/phototherapy, and topical cohorts were 3.05, 3.85, and 6.73 per 1000 patient-years, respectively. CONCLUSIONS Use of TNF inhibitors for psoriasis was associated with a significant reduction in MI risk and incident rate compared with treatment with topical agents. Use of TNF inhibitors for psoriasis was associated with a non-statistically significant lower MI incident rate compared with treatment with oral agents/phototherapy.

Thalidomide: dermatological indications, mechanisms of action and side-effects.

Thalidomide was first introduced in the 1950s as a sedative but was quickly removed from the market after it was linked to cases of severe birth defects. However, it has since made a remarkable comeback for the U.S. Food and Drug Administration‐approved use in the treatment of erythema nodosum leprosum. Further, it has shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell histiocytosis, aphthous stomatitis, Behçets syndrome, graft‐versus‐host disease, cutaneous sarcoidosis, erythema multiforme, Jessner–Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and uraemic pruritus. This article reviews the history, pharmacology, mechanism of action, clinical uses and adverse effects of thalidomide.

Effects of tumor necrosis factor‐α blockade on metabolic syndrome components in psoriasis and psoriatic arthritis and additional lessons learned from rheumatoid arthritis

Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic T cell‐mediated inflammatory diseases that manifest not only in the skin and joints but also in the form of cardiometabolic disturbances, which include insulin resistance, dyslipidemia, and obesity. Thus, PsO and PsA patients are predisposed to metabolic syndrome (MetS), diabetes, and cardiovascular disease. In recent years, the introduction of targeted therapy in the form of tumor necrosis factor‐α (TNF‐α) antagonists, such as infliximab, etanercept, and adalimumab has been an important and effective addition to the treatment armamentarium for PsO and PsA. Although TNF‐α antagonists have produced promising results clinically in reducing cutaneous and joint manifestations of PsO and PsA, their effects on MetS components in these patients are presently unclear. This review summarizes the current limited evidence on the effects of TNF‐α antagonists on MetS components in PsO and PsA patients and extrapolates from related literature in rheumatoid arthritis, which is also a T cell‐mediated inflammatory disease, for additional information.

The association of psoriasis with autoimmune diseases

BACKGROUND Previous studies provide evidence that there is a greater frequency of autoimmune diseases among patients with psoriasis than in the general population. OBJECTIVE This study examined the association between psoriasis and 21 common autoimmune diseases, specified a priori. METHODS A retrospective cohort study was conducted among persons who were members of Kaiser Permanente Southern California from 2004 to 2011. A total of 25,341 patients with 2 or more diagnosis codes for any psoriatic disease were evaluated. Five persons not meeting this case definition were matched to each psoriatic patient based on age, sex, and length of enrollment. RESULTS Patients with psoriasis were more likely to have at least 1 other autoimmune disease (odds ratio [OR] 1.6; 95% confidence interval [CI] 1.5-1.7) and to have at least 2 other autoimmune diseases (1.9; 95% CI 1.6-2.4). Of the 17 conditions evaluated, associations with 14 were found to be statistically significant. The strongest association was with rheumatoid arthritis (3.6; 95% CI 3.4-3.9). LIMITATIONS Patients with autoimmune conditions are likely to have a greater number of health care encounters, which may result in overascertainment and misascertainment of immune-mediated conditions, although the patients included in the study averaged 5.2 years of observation and the comparison subjects were matched on length of enrollment. CONCLUSIONS The study suggests a genetic or environmental cause common across autoimmune diseases. Further investigation of individuals with multiple autoimmune diseases may yield important clues about the origin and pathogenesis of the disease.

Subcutaneous fungal infections

ABSTRACT:  Subcutaneous mycoses are caused by a variety of mostly tropical organisms, usually when they are implanted into the dermis or the subcutaneous tissue. They rarely disseminate or become systemic. Sporotrichosis, mycetoma, and chromoblastomycosis are more common subcutaneous mycoses than are rhinosporidiosis, zygomycosis, pheohyphomycosis, and lobomycosis.

The association of psoriasis and elevated blood lipids in overweight and obese children.

OBJECTIVE To investigate whether obesity and cardiovascular risk factors are associated with psoriasis in children and adolescents. STUDY DESIGN For this population-based, cross-sectional study, measured weight and height, laboratory data, and psoriasis diagnoses were extracted from electronic medical records of 710,949 patients age 2 to 19 years enrolled in an integrated health plan. Weight class was assigned on the basis of body mass index-for-age. RESULTS The OR for psoriasis was 0.68, 1.00, 1.31, 1.39, and 1.78 (95% CI, 1.49 to 2.14) for underweight, normal-weight, overweight, moderately obese, and extremely obese children, respectively (P for trend < .001). The OR for psoriasis treated with systemic therapy or phototherapy as an indicator of severe or widespread psoriasis was 0.00, 1.00, 2.78, 2.93, and 4.19 (95% CI, 1.81 to 9.68) for underweight, normal-weight, overweight, moderately obese, and extremely obese children, respectively (P for trend < .003). In adolescents, mean total cholesterol, low-density lipoprotein cholesterol, triglycerides, and alanine aminotransferase were significantly higher in children with psoriasis compared with children without psoriasis after adjustment for body mass index. CONCLUSION Overweight and obesity are associated with higher odds of psoriasis in youths. Independent of body weight, adolescent patients with psoriasis have higher blood lipids. These data suggest that pediatricians and dermatologists should screen youths with psoriasis for cardiovascular disease risk factors.

Validity of diagnostic codes and prevalence of psoriasis and psoriatic arthritis in a managed care population, 1996-2009

Few population‐based studies have reported the prevalence of psoriatic disease.

Treatment of Nail Psoriasis Best Practice Recommendations From the Medical Board of the National Psoriasis Foundation

IMPORTANCE Nail psoriasis can be difficult to treat and has a significant effect on quality of life. Relatively few controlled trials evaluating treatments for nail psoriasis have been published. There is an unmet need for treatment recommendations to guide therapeutic decisions. OBJECTIVE To develop treatment recommendations for nail psoriasis from the Medical Board of the National Psoriasis Foundation. EVIDENCE REVIEW A PubMed search for publications on nail psoriasis treatments was performed from January 1, 1947, through May 11, 2014, without language restrictions. FINDINGS Treatment recommendations for 4 clinical nail psoriasis scenarios were developed based on the evidence reviewed in this study and expert opinion of the Medical Board of the National Psoriasis Foundation. Treatment of nail psoriasis should balance consideration of the extent of skin disease, psoriatic arthritis, and severity of nail disease with concomitant impairment of quality of life. All patients should be evaluated for onychomycosis because this may complicate psoriatic nail disease. For disease limited to the nails, high-potency topical corticosteroids with or without calcipotriol are initial options. For patients with significant nail disease for whom topical therapy has failed, treatment with adalimumab, etanercept, intralesional corticosteroids, ustekinumab, methotrexate sodium, and acitretin are recommended. For patients with significant skin and nail disease, adalimumab, etanercept, and ustekinumab are strongly recommended, and methotrexate, acitretin, infliximab, and apremilast are recommended. Finally, for a patient with significant nail, skin, and joint disease, adalimumab, etanercept, ustekinumab, infliximab, methotrexate, apremilast, and golimumab are recommended. CONCLUSIONS AND RELEVANCE Treatment of nail psoriasis poses a clinical challenge. Clinical trial data are limited, and results are reported inconsistently, making comparisons among treatment options difficult. The treatment recommendations from the Medical Board of the National Psoriasis Foundation will help guide treatment decisions for clinicians who are treating patients with nail psoriasis.

Prevalence and incidence rates of cardiovascular, autoimmune, and other diseases in patients with psoriatic or psoriatic arthritis: a retrospective study using Clinical Practice Research Datalink

Previous studies have demonstrated that patients with psoriasis have higher rates of comorbidities compared to the general population. Despite the clinical and economic burden of psoriatic disease, there have been few large‐scale observational studies focused on this condition.