Absolute and Relative Psoriasis Area and Severity Indices (PASI) for Comparison of the Efficacy of Ixekizumab to Etanercept and Placebo in Patients with Moderate-to-severe Plaque Psoriasis: An Integrated Analysis of UNCOVER-2 and UNCOVER-3 Outcomes.

Treatment goals defined by the absolute Psoriasis Area and Severity Index (PASI) scores offer certain advantages in the clinical setting. In order to investigate potential treatment targets, this study evaluated absolute PASI outcomes relative to other measures of response using data from two randomized clinical trials of patients with moderate-to-severe psoriasis treated with ixekizumab, etanercept, or placebo (n=2,567). Response was assessed throughout 12 weeks as the proportion of patients achieving absolute PASI band cut-offs who also reached established response criteria. Most PASI band ≤2 responders also achieved PASI 90 (70.1-100%), static Physician's Global Assessment (0,1) (91.3-96.1%), Dermatology Life Quality Index (0,1) (63.0-67.7%), Patient Global Assessment of Disease Severity (0,1) (80.3-86.7%), and Itch Numeric Rating Scale improvement ≥4 (87.2-87.6%). Agreement sharply decreased for less stringent PASI criteria. These data indicate that PASI ≤2 represents significantly meaningful clinical and health-related quality of life improvements and may be a suitable treatment target for moderate-to-severe plaque psoriasis.

Short- and long-term safety outcomes with ixekizumab from 7 clinical trials in psoriasis: Etanercept comparisons and integrated data.

BACKGROUND: Safety of biologics is important when treating patients with psoriasis. OBJECTIVE: We sought to determine the safety of ixekizumab in psoriasis. METHODS: Integrated safety data are presented from a 12-week induction period, a 12- to 60-week maintenance period, and from all ixekizumab-treated patients from 7 clinical trials. Exposure-adjusted incidence rates (IRs) per 100 patient-years are reported. RESULTS: Overall, 4209 patients received ixekizumab (total exposure: 6480 patient-years). During the induction period, the IRs of patients experiencing 1 or more treatment-emergent adverse event (AE) were 251 and 236 among ixekizumab- and etanercept-treated patients, respectively, and for serious AEs was 8.3 in both groups. During maintenance, for ixekizumab, the IRs of treatment-emergent AEs and serious AEs were 100.4 and 7.8, respectively. Among all ixekizumab-treated patients from 7 trials, the IR of Candida infections was 2.5. The IRs of treatment-emergent AEs of special interest (including serious infections, malignancies, major adverse cardiovascular events) were comparable for ixekizumab and etanercept during the induction period. LIMITATIONS: Additional long-term data are required. CONCLUSION: Ixekizumab had an acceptable safety profile with no unexpected safety findings during ixekizumab maintenance in psoriasis.

Costs and quality of life for psoriatic patients at different degrees of severity in southern Sweden - a cross-sectional study.

OBJECTIVES: Knowledge of the societal costs of psoriasis is limited. This study estimated the cost of care, psoriasis area and severity index (PASI), and quality of life in a defined patient population in Sweden. METHODS: A prevalence-based prospective recruitment of patients visiting two Swedish dermatology clinics between September and December 2009 was performed, collecting resource utilization for health care contacts, treatment, travelling, and productivity loss during 1 month. RESULTS: 164 patients were included. Mean total cost per patient-month was 994€. Main cost drivers were outpatient visits and light therapy (49%), biological drugs (20%) and productivity loss (22%). Total cost for topical treatment only (TT; 34%) was 369€, light therapy (LT; 24%) 1,274€, traditional systemic treatment (TST; 26%) 1,085€ and biological systemic treatment (BST; 16%) 1,709€ per patient-month. Main cost drivers were: outpatient visits (56%) in TT as well as for LT (78%), productivity loss (40%) in TST, and biological drugs (71%) among BST patients. There was no clear relationship between clinical (PASI) or subjective (DLQI) severity estimations and costs. CONCLUSIONS: The one-month cost-of-illness amounted to almost 1,000€/month, with great variations. Despite 1,190€ difference in drug cost for TST vs BST, total cost per month differed by 623€ because of offsets from improved productivity. A trend towards lower severity and reductions in outpatient and topical treatment costs was seen.

Psoriasis of the face and flexures.

Facial and flexural psoriasis may impair the quality of life of psoriatic patients considerably. For the adequate management of psoriasis it is important to pay attention to lesions at these sensitive sites, which require an approach different to that for lesions on other sites in several respects. An extensive literature search was carried out to collect evidence-based data on facial and flexural psoriasis with respect to epidemiology, clinical aspects, pathogenetic factors and various treatments. Subsequently, a panel of experts, the Copenhagen Psoriasis Working Group (CPWG), discussed these aspects and several recommendations were formulated reconciling the evidence-based data. Facial psoriasis occurs in 17-46% of psoriatics and flexural psoriasis is experienced by 6.8-36% of patients with psoriasis. Therefore, psoriasis at these sites cannot be regarded as a rare manifestation. Facial psoriasis is a prognostic marker indicating a poor prognosis of psoriasis. Facial and flexural psoriasis cannot be regarded as distinct disease entities but rather as site variations. The clinical features of facial psoriasis suggest that there are three subtypes: hairline psoriasis, sebo-psoriasis and true facial psoriasis. Otitis externa and ocular manifestations should not be neglected. Evidence that microbiological factors may be relevant to facial and flexural psoriasis is virtually absent. For facial psoriasis the response to UV radiation is variable. At least 5% of psoriatics have photosensitive psoriasis. In these patients photosensitive diseases such as lupus erythematodes and polymorphic light eruption have to be excluded. Based on the literature assessment and working group discussions the CPWG concluded the following. (1) Low-potency topical corticosteroids, vitamin D3 analogues and calcineurin inhibitors are first choice treatments in facial and flexural psoriasis. Evidence for the efficacy of the first two modalities is at level 3 while it is at level 1 for the third one. An individualized approach is indicated; for example, in case of corticosteroid side effects in the past the other two modalities should be selected and in unstable psoriasis prone to irritation, monotherapy with vitamin D3 analogues should be avoided. (2) Antimicrobial treatments are not indicated for facial and flexural psoriasis. (3) Dithranol and tar treatment are not indicated as first-line treatment but only if the first-line options fail. (4) In case topical therapies are not effective, phototherapy and systemic treatments are indicated. (5) For future drug development the combination of vitamin D3 analogues with low strength corticosteroids is recommended.

Psoriasis: severity assessment in clinical practice. Conclusions from workshop discussions and a prospective multicentre survey of psoriasis severity.

Psoriasis treatment is highly individualized. Although a standardized assessment of psoriasis severity for clinical practice may be theoretically advantageous for the purposes of determining treatment, the relevance of currently available research tools in clinical practice is uncertain. Our objectives were to ascertain in workshop discussions and through a prospective survey the relevance of standard severity measures in clinical practice with regard to choice of treatment. Although there was agreement on the possible structure of an algorithm for the treatment-related definition of psoriasis severity, consensus on the cut-off levels for the PASI and %BSA that would indicate a switch in treatment mode could not be reached. The lack of agreement prompted a prospective survey of 112 patients with psoriasis from 10 countries. This survey used a formal questionnaire asking for the PASI and %BSA scores, the patient's self assessment score (VAS ranging from 0 to 10), location of the psoriatic lesions and disease phase. Severity scores from 20 patients pre-selected for inclusion in a trial of a biological agent were included for comparison. Severity scores were analysed in relation to the choice of treatment (topical or systemic, which included phototherapy and combination) suggested by the treating physician.PASI scores differed significantly between the treatment groups (topical vs systemic, p=0.009); however, there was large overlap in the range of PASI scores between the groups. The same was true for VAS scores (topical vs systemic, p=0.035). %BSA scores were not significantly different between treatment groups. There was a large overlap for both the topical and systemic treatment groups with the biologicals group for the range of both the PASI and %BSA scores. A standardized protocol for the evaluation of psoriasis severity based on established severity scores (PASI, %BSA) appears to be unrealistic in day-to-day clinical practice. In clinical practice, a host of factors must be evaluated alongside possible metric measures. This requires experience and the specialized medical education of those involved in the treatment of patients with psoriasis.

Progressive cutaneous sarcoidosis responding to anti-tumor necrosis factor-alpha therapy.

We describe a patient with widespread and progressive cutaneous sarcoidosis who was successfully treated with anti-tumor necrosis factor-alpha monoclonal antibody, infliximab, suggesting that inhibition of tumor necrosis factor-alpha may be useful as targeted treatment in cutaneous sarcoidosis.