Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial.

BACKGROUND: We assessed the efficacy, safety, and tolerability of ponesimod, an oral, selective, reversible modulator of sphingosine 1-phosphate receptor 1, in patients with moderate to severe chronic plaque psoriasis. METHODS: Between Sept 22, 2010, and Oct 24, 2012, patients with psoriasis area and severity index (PASI) scores higher than 10 were enrolled into this multicentre double-blind, phase 2 study. They received 20 mg or 40 mg ponesimod or placebo once daily for 16 weeks. Those with at least 50% reduction in PASI score at 16 weeks and who were receiving ponesimod were rerandomised to receive maintenance ponesimod therapy or placebo until week 28. The primary endpoint was reduction in PASI score from baseline of at least 75% (PASI75) at week 16. This study is registered with ClinicalTrials.gov, number NCT01208090. FINDINGS: Of 326 patients initially randomised (20 mg ponesimod n=126, 40 mg ponesimod n=133, and placebo n=67) PASI75 was achieved at week 16 in 58 (46·0%), 64 (48·1%), and nine (13·4%), respectively. The treatment effect was significant for the two ponesimod doses (both p<0·0001). Of 219 patients who entered the maintenance period, PASI75 was achieved by week 28 in 35 (71·4%) of 49 who continued on 20 mg ponesimod and 41 (77·4%) of 53 on 40 mg ponesimod, and in 19 (42·2%) of 45 who swapped from 20 mg to placebo and 19 (40·4%) of 47 from 40 mg to placebo. Ponesimod was associated with dyspnoea, raised liver enzyme concentrations, and dizziness. INTERPRETATION: Significant clinical benefit was seen at week 16 that increased with maintenance therapy. FUNDING: Actelion Pharmaceuticals.

Efficacy of two different methods of cold air analgesia for pain relief in PDT of actinic keratoses of the head region - a randomized controlled comparison study.

BACKGROUND: Photodynamic therapy (PDT) is an effective method for treating actinic keratosis (AK) with pain during illumination representing the major side effect. The efficacy of two different cooling methods for pain relief in PDT of AK in the head region was compared. METHODS: Randomized, assessor-blinded, half side comparison study in 20 patients with symmetrically distributed AK on the head. Conventional PDT was performed on both halves of the scalp or face by applying 20% aminolevulinic acid cream (ALA) and subsequent illumination with incoherent red light. During illumination one side was cooled with a cold air blower (CAB) and the other with a standard fan (FAN) in a randomized fashion. Pain and skin temperature were recorded during and after PDT. The phototoxic skin reaction was evaluated up to seven days after PDT. The clearance rate of AK was assessed at 3 and 6 months after PDT. RESULTS: Mean pain (VASmean), maximum pain intensity (VASmax) and the mean skin temperature during PDT were significantly lower with CAB as compared to FAN (VASmean: 2.7 ± 1.4 vs. 3.7 ± 2.1, p = 0.003; VASmax: 3.8 ± 2.0 vs. 4.8 ± 2.5, p = 0.002; 26.8 ± 2.0 °C vs. 32.1 ± 1.7 °C; p=<0.001). The severity of the phototoxic skin reaction and the clearance rate of AK did not differ between the two cooling methods. CONCLUSION: Cooling with CAB during PDT has a greater analgesic effect than cooling with FAN. Patients with a lower skin temperature during illumination tended to experience less pain, however, this effect did not reach the level of statistical significance.

Serum levels of glycoprotein Dickkopf-1 in patients with cutaneous malignant melanoma: a prospective pilot study.

BACKGROUND: Dickkopf-1 (Dkk-1) glycoprotein is an inhibitor of the canonical Wnt pathway. Recent studies have demonstrated elevated Dkk-1 serum levels in patients with diverse malignancies. In vitro studies with melanoma cell lines showed that loss of Dkk-1 expression may contribute to tumor progression. OBJECTIVE: The present study is the first in vivo investigation of Dkk-1 serum levels in patients with cutaneous malignant melanoma. METHODS: We analyzed serum levels of Dkk-1 protein in 82 patients with cutaneous melanoma. RESULTS: Serum levels were significantly increased (mean 83.01 pmol/l) in comparison to healthy controls (mean 29.36 pmol/l). No statistical difference in Dkk-1 serum levels neither between patients without or with lymph node metastases (p = 0.719) nor between patients with or without visceral metastases (p = 0.929) was found. Patients before excision had moderately higher Dkk-1 serum levels than after excision or with florid metastases. CONCLUSION: Our data suggest that increased Dkk-1 expression is an early event in melanoma, decreasing in later tumor stages. It was shown previously that Dkk-1 activates cell death in melanoma cells. Our in vivo data indicate that a decrease in Dkk-1 could be a sign of loss of tumor control.

Effectiveness and clinical predictors of drug survival in psoriasis patients receiving apremilast: A registry analysis.

BACKGROUND: Little is known about the effectiveness and drug survival associated with apremilast under real-world conditions. OBJECTIVE: To investigate the influence of patient and disease characteristics on drug survival associated with apremilast and to elucidate clinical effectiveness with regard to the psoriasis area and severity index (PASI) reduction. METHODS: This was an observational, retrospective, multicenter analysis from the Austrian Psoriasis Registry. RESULTS: Data from 367 patients were eligible for analysis. The 12-month drug survival rate associated with apremilast (ie, the proportion of patients on the drug) was 57.3% and decreased significantly in patients younger than 40 years (relative hazard ratio = 1.49, P = .007918). Sex; concomitant arthritis; previous biologic therapy; obesity; and palmoplantar, scalp, nail, and intertriginous involvement did not significantly affect drug survival. At 12 months, the response rates in patients receiving apremilast per protocol with a PASI of 50, 75, 90, and 100 were 80.0%, 56.4%, 38.2%, and 22.7%, respectively. LIMITATIONS: Inclusion of a substantial number of patients with no record of absolute PASI at study entry and lack of PASI reduction follow-up data of 103 patients (28.1%) after starting apremilast treatment. CONCLUSION: Apremilast is a robust antipsoriatic drug for which the drug survival is not strongly influenced by most patient- or disease-related factors except age. Drug survival is significantly shorter in patients younger than 40 years.

Quality of Life, Anxiety, and Depression in Patients With Early-Stage Mycosis Fungoides and the Effect of Oral Psoralen Plus UV-A (PUVA) Photochemotherapy on it.

Background: Little is known about psychological discomfort and quality of life (QoL) in early stage mycosis fungoides (MF) and the effect of psoralen plus UV-A (PUVA) on it. Objective: To evaluate QoL, anxiety, and depression with validated instruments in early stage MF patients and whether PUVA treatment improves it. Methods: Patients with stage IA to IIA MF were treated with PUVA twice weekly for 12-24 weeks, followed by maintenance treatment or not, in a prospective randomized clinical trial. Patients completed a questionnaire on DLQI as well as the Hospital Anxiety and Depression Scale (HADS) prior to therapy, after their last PUVA exposure, and after the PUVA maintenance or observance phase. Results: For 24 patients with early stage MF, completed questionnaires were available and analyzed. Prior to treatment, 17% reported strong (DLQI > 10) and 29% moderate impairment (DLQI 6-10) in QoL; 33% of patients reported HADS scores indicating anxiety, and 21% reported scores indicating depression. PUVA significantly improved overall QoL by reducing mean DLQI scores by 58.6% (p = 0.003), HADS-A by 30% (p = 0.045), and HADS-D by 44% (p = 0.002). Improvements in QoL and psychological well-being seemed to be sustained, irrespective of maintenance treatment or not. Limitations: Small sample size. Conclusions: PUVA sustainably improves QoL and psychological well-being in patients with early stage MF. Clinical trial registration: ClinicalTrials.gov identifier: NCT01686594.

Secukinumab Use in Patients with Moderate to Severe Psoriasis, Psoriatic Arthritis and Ankylosing Spondylitis in Real-World Setting in Europe: Baseline Data from SERENA Study.

INTRODUCTION: Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin-17A, has demonstrated robust efficacy in the treatment of moderate to severe psoriasis (PsO), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), with a rapid onset of action, sustained long-term clinical responses and a consistently favourable safety profile across phase 3 trials. Here, we report the clinical data at enrolment from SERENA, designed to investigate the real-world use of secukinumab across all three indications. METHODS: SERENA is an ongoing, longitudinal, observational study conducted at 438 sites across Europe in patients with moderate to severe plaque PsO, active PsA or active AS. Patients should have received at least 16 weeks of secukinumab treatment before enrolment in the study. RESULTS: Overall 2800 patients were included in the safety set; patients with PsA (N = 541) were older than patients with PsO (N = 1799) and patients with AS (N = 460); patients with PsO had a higher mean body weight than patients with PsA and patients with AS; and patients with PsO and patients with AS were predominantly male. Time since diagnosis was longer in patients with PsO compared with patients with PsA and patients with AS, and about 40% of patients were either current or former smokers. The proportion of obese patients (body mass index ≥ 30 kg/m2) was similar across indications. Patients were treated with secukinumab for a mean duration of 1 year prior to enrolment (range 0.89-1.04). The percentages of patients with prior biologics exposure were 31.5% PsO, 59.7% PsA and 55% AS. The percentages of patients prescribed secukinumab monotherapy were 75% (n = 1349) in PsO, 48.2% (n = 261) in PsA and 48.9% (n = 225) in AS groups. CONCLUSION: Baseline demographics of the study population are consistent with existing literature. This large observational study across all secukinumab indications will provide valuable information on the long-term effectiveness and safety of secukinumab in the real-world setting.

Medium-dose is more effective than low-dose ultraviolet A1 phototherapy for localized scleroderma as shown by 20-MHz ultrasound assessment.

BACKGROUND: Recent studies suggest that ultraviolet (UV) A1 phototherapy is an effective treatment for localized scleroderma (LS); however, the optimum UVA1 dose remains to be determined. OBJECTIVE: We sought to compare the immediate and long-term efficacy of low- versus medium-dose UVA1 phototherapy for plaque-type LS. METHODS: Three comparable plaques in 16 patients were treated with 20 J/cm2 UVA1, 70 J/cm2 UVA1, or no irradiation. In total, 30 treatments were given. Skin thickness was determined by high-frequency ultrasound examination and clinical scoring. Assessments were done at baseline, immediately after treatment, and 3, 6, and 12 months thereafter. RESULTS: Ultrasound measurement showed a significantly greater reduction of skin thickness with 70 J/cm2 than with 20 J/cm2 at all time points of the study except immediately after UVA1 treatment. The clinical score of the irradiated plaques also decreased substantially but failed to detect a significant difference between the two dose regimens. LIMITATIONS: Our results only pertain to plaque-type LS and are limited by a small sample size. CONCLUSION: Medium-dose provides for better long-term results than low-dose UVA1 in LS as shown by ultrasound assessment. With clinical scoring, no significant difference between the two UVA1 dose regimens was detected, indicating that ultrasound measurement is a more sensitive method for quantifying treatment-induced skin changes in patients with LS.

Acrokeratosis paraneoplastica (Bazex's syndrome): association with liposarcoma.

Acrokeratosis paraneoplastica (Bazex's syndrome) is a rare obligate paraneoplastic dermatosis characterized by erythematosquamous lesions localized symmetrically at the acral sites. The condition almost exclusively affects Caucasian men older than 40 years. It is usually associated with primary malignant neoplasms of the upper aerodigestive tract. In most cases, the skin changes precede the clinical manifestation of the underlying neoplasm. The dermatosis can be cured only by removal of the underlying carcinoma. We describe a case of acrokeratosis paraneoplastica associated with a retroperitoneal liposarcoma in a 71-year-old Caucasian man. The liposarcoma was surgically removed but recurred several times, with acrokeratosis paraneoplastica showing a parallel development. We, therefore, add liposarcoma to the growing list of malignant neoplasms associated with acrokeratosis paraneoplastica.

Comparison of epidermal hydration and skin surface lipids in healthy individuals and in patients with atopic dermatitis.

BACKGROUND: The water content of the stratum corneum and skin surface lipids are important factors in the appearance and function of the skin. A disruption of the balance between the two may lead to the clinical manifestation of dryness of skin in patients with atopic dermatitis. OBJECTIVE: The aim of our study was to examine the so-called dry skin of patients with atopic dermatitis using objective parameters. We compared the epidermal hydration and the skin surface lipids, the so-called hydro-lipid film, of the clinically unaffected skin of patients suffering from atopic dermatitis with that of healthy subjects. METHODS: A total of 48 patients of either gender were included in this retrospective case-control study. We used the Corneometer CM 820 (Courage+Khazaka Electronic GmbH, Cologne, Germany) and the Sebumeter SM 810 (Courage+Khazaka Electronic GmbH) as noninvasive measuring methods. RESULTS: The results showed marked decreases in the atopic dermatitis group for both the Corneometer and Sebumeter measuring methods. CONCLUSION: Our results show that the dry skin of patients with atopic dermatitis, as previously shown, is due not only to a decrease in skin moisture but also to a reduction of skin lipids. This finding gives rise to a new understanding of the condition, and therefore one should always speak of a hydro-lipid film.