Super-response to guselkumab treatment in patients with moderate-to-severe psoriasis: age, body weight, baseline Psoriasis Area and Severity Index, and baseline Investigator's Global Assessment scores predict complete skin clearance.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease that often leads to a diminished quality of life. Goals of treating patients with psoriasis have shifted with more focus on achieving near or complete clearance of the skin. Guselkumab, a fully human monoclonal antibody targeting interleukin-23, is effective in treating moderate-to-severe psoriasis. OBJECTIVE: To describe the baseline characteristics of patients with moderate-to-severe psoriasis achieving super-response (Psoriasis Area and Severity Index [PASI] 100 response at Weeks 20 and 28) after commencing guselkumab treatment. METHODS: Pooled data from VOYAGE 1 and VOYAGE 2 studies identified super-response; baseline demographic, disease and pharmacokinetic characteristics were compared with non-super-response. A stepwise logistic regression analysis identified which factors were potentially predictive of super-response status, with significance level of 0.1. RESULTS: A subset of patients randomized to guselkumab comprised this post hoc analysis (n = 664); 271 patients achieved super-response vs. 393 with non-super-response. Patient age at study entry and baseline body weight (≤90 kg vs. >90 kg), PASI, and Investigator's Global Assessment (IGA) score were significant predictors of super-response status, with odds ratios (95% confidence intervals) of 0.98 (0.967-0.993; P = 0.003), 1.42 (1.026-1.977; P = 0.034), 0.97 (0.955-0.993; P = 0.007) and 0.66 (0.433-0.997; P = 0.048), respectively. More patients with super-response achieved an early response: Week 2 PASI 75 (5.5% vs. 1.8%) and Week 8 PASI 100 (22.5% vs. 3.3%) vs. non-super-response. Median serum guselkumab concentrations through Week 28 were slightly greater in patients with super-response vs. non-super-response. CONCLUSION: Guselkumab was more likely to achieve early clinical responses (complete skin clearance) in younger patients, less obese patients and patients with less severe psoriasis.

Guidelines for the peri-operative management of people with cardiac implantable electronic devices: Guidelines from the British Heart Rhythm Society.

This document provides practical guidance for the management of people with cardiac implantable electronic devices who are undergoing surgical intervention. Increasing numbers of people have cardiac device implants including pacemakers, implantable defibrillators and cardiac resynchronisation devices. During surgical procedures, exposure to electromagnetic interference may lead to inappropriate device function including withholding of pacing function or shock therapies. The guideline summarises key aspects of pre-operative assessment protocols to ensure that all people have their device clearly identified and have had appropriate device follow-up pre-operatively. It outlines general measures which can minimise the risk of potentially problematic electromagnetic interference in the surgical environment. It also includes detailed guidance according to the type of device, whether individuals are dependent on the pacing function of the device and the nature of the procedure they are undergoing. People identified as being at significant risk of harmful procedure-related inappropriate device function may require temporary alteration to the device programming. This may be carried out by a trained cardiac physiologist using a device programmer or, in some cases, can be achieved by clinical magnet application. Guidance on the safe use of magnets and emergency situations is included. Common diagnostic procedures and dental interventions are covered. The guidance aims to provide specific and pragmatic advice which can be applied to provide safe and streamlined care for people with cardiac implantable devices.

Five-year maintenance of clinical response and health-related quality of life improvements in patients with moderate-to-severe psoriasis treated with guselkumab: results from VOYAGE 1 and VOYAGE 2.

BACKGROUND: Psoriasis is a chronic disease requiring long-term therapy. OBJECTIVES: Physician- and patient-reported outcomes were evaluated through week 252 in VOYAGE 1 and VOYAGE 2. METHODS: In total, 1829 patients were randomized at baseline to receive guselkumab 100 mg every 8 weeks, placebo or adalimumab. Patients receiving placebo crossed over to guselkumab at week 16. Patients receiving adalimumab crossed over to guselkumab at week 52 in VOYAGE 1, and randomized withdrawal and retreatment occurred at weeks 28-76 in VOYAGE 2; all patients then received open-label guselkumab through week 252. Efficacy and health-related quality of life (HRQoL) endpoints were analysed through week 252. Safety was monitored through week 264. RESULTS: The proportions of patients in the guselkumab group who achieved clinical responses at week 252 in VOYAGE 1 and VOYAGE 2, respectively, were 84·1% and 82·0% [≥ 90% improvement in Psoriasis Area and Severity Index (PASI)]; 82·4% and 85·0% [Investigator's Global Assessment (IGA) 0 or 1]; 52·7% and 53·0% (100% improvement in PASI) and 54·7% and 55·5% (IGA 0). HRQoL endpoints were achieved as follows: 72·7% and 71·1% of patients (Dermatology Life Quality Index 0 or 1: no effect on patient's life); 42·4% and 42·0% [Psoriasis Symptoms and Signs Diary (PSSD) symptom score = 0] and 33·0% and 31·0% (PSSD sign score = 0). As measured in VOYAGE 2 only, approximately 45% of patients achieved ≥ 5-point reduction in Short Form-36 physical and mental component scores, and 80% reported no anxiety or depression (Hospital Anxiety and Depression Scale scores < 8). Similar findings were reported for adalimumab crossovers. These effects were maintained from week 52 in VOYAGE 1 and week 100 in VOYAGE 2. No new safety signals were identified. CONCLUSIONS: Guselkumab maintains high levels of clinical response and improvement in patient-reported outcomes through 5 years in patients with moderate-to-severe psoriasis.

Five-year efficacy and safety of tildrakizumab in patients with moderate-to-severe psoriasis who respond at week 28: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2).

BACKGROUND: The phase III reSURFACE 1 and reSURFACE 2 (NCT01722331/NCT01729754) trials of the anti-interleukin-23p19 monoclonal antibody tildrakizumab (TIL) for psoriasis treatment are complete. OBJECTIVES: We present 5-year pooled data from reSURFACE 1 and reSURFACE 2. METHODS: reSURFACE 1 and reSURFACE 2 were double-blind, randomized, controlled studies with optional long-term extensions. Adults with moderate-to-severe chronic plaque psoriasis were randomized 2 : 2 : 1 to TIL 100 mg (TIL 100) or 200 mg (TIL 200) or placebo at weeks 0 and 4, and every 12 weeks thereafter [reSURFACE 2 included an etanercept (ETN) arm]. Efficacy outcomes included proportions of patients achieving absolute and relative improvement from baseline Psoriasis Area and Severity Index (PASI) score through week 244 in TIL responders (≥ 75% improvement from baseline PASI; PASI 75 response) continuously receiving the same dose and ETN partial responders and nonresponders (PASI < 75 response) switched to TIL 200 at week 28. Safety was assessed from adverse events (AEs) in all patients as treated. RESULTS: Efficacy analyses included 329 and 227 week 28 responders to TIL 100 and TIL 200, respectively, and 121 ETN partial responders/nonresponders switched to TIL 200 at week 28. Of TIL 100 or TIL 200 responders and ETN partial responders/nonresponders entering the extensions, 235/302, 176/213 and 85/107, respectively, were evaluated at week 244, and 88·7%, 92·5% and 81·3%, respectively, achieved PASI 75 response. Exposure-adjusted rates of serious AEs were 6·3 and 6·0 patients with events per 100 patient-years of TIL 100 and TIL 200, respectively. CONCLUSIONS: TIL treatment provided sustained disease control over 5 years in week 28 TIL responders and ETN partial responders/nonresponders, with a reassuring safety profile.

Efficacy of risankizumab in patients with moderate-to-severe plaque psoriasis by baseline demographics, disease characteristics and prior biologic therapy: an integrated analysis of the phase III UltIMMa-1 and UltIMMa-2 studies.

BACKGROUND: Risankizumab is a humanized IgG monoclonal antibody that selectively inhibits interleukin-23 through binding the p19 subunit. In Phase 3 trials, risankizumab demonstrated superior efficacy compared with adalimumab and ustekinumab in patients with moderate-to-severe plaque psoriasis. Here, we evaluated the impact of baseline characteristics on efficacy of risankizumab compared with ustekinumab in patients with moderate-to-severe plaque psoriasis. METHODS: This analysis included all patients initially randomized to risankizumab or ustekinumab from the replicate, double-blinded, randomized, placebo-controlled phase 3 trials, UltIMMa-1 (NCT02684370) and UltIMMa-2 (NCT02684357). Patients received either risankizumab (150 mg) or ustekinumab (weight-based; 45 or 90 mg per label) at weeks 0, 4, 16, 28 and 40. Efficacy was assessed as the proportion of patients achieving ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) at weeks 16 and 52 by baseline patient demographics, disease characteristics and prior biologic exposure. Mean per cent improvement in PASI was calculated by body weight and body mass index at week 52. Missing efficacy data were imputed as non-responders for categorical variables and last observation carried forward for continuous variables. Logistic regression analyses assessed for interactions between treatment and five independent variables (age, sex, weight, baseline PASI score and presence of psoriatic arthritis) at both weeks 16 and 52. RESULTS: Baseline patient demographics, disease characteristics and prior biologic exposure were similar between patients randomized to risankizumab (n = 598) and ustekinumab (n = 199). At weeks 16 and 52, risankizumab demonstrated superior efficacy compared with ustekinumab across these patient characteristics (P < 0.01). Logistic regression analyses demonstrated that risankizumab was superior to ustekinumab at weeks 16 and 52 in all models tested (P < 0.0001 for all). CONCLUSIONS: Risankizumab demonstrated consistent and superior efficacy compared with ustekinumab regardless of patient demographics, disease characteristics or prior biologic exposure.

Anxiety and depression in patients with moderate-to-severe psoriasis and comparison of change from baseline after treatment with guselkumab vs. adalimumab: results from the Phase 3 VOYAGE 2 study.

BACKGROUND: Anxiety and depression are clinically significant comorbidities associated with psoriasis. Improvements in psoriasis are known to decrease anxiety and depression. Guselkumab, an anti-interleukin-23 monoclonal antibody, has demonstrated efficacy and safety for the treatment of moderate-to-severe psoriasis. OBJECTIVE: Assess improvements in anxiety and depression with guselkumab vs. placebo and adalimumab using the Hospital Anxiety and Depression Scale (HADS). METHODS: In VOYAGE 2, a Phase 3, randomized, double-blind, placebo- and adalimumab-controlled study, patients received placebo (through week 16 followed by crossover to guselkumab), guselkumab, or adalimumab through week 24. HADS consists of two subscales measuring anxiety (HADS-A) and depression (HADS-D), with scores ranging from 0 to 21 and higher scores indicating more severe symptoms. Scores ≥8 indicate instrument-defined anxiety or depression. Severity of psoriasis was assessed using the Psoriasis Area and Severity Index (PASI). RESULTS: Among 989 patients randomized (with baseline HADS measurements), mean HADS-A and HADS-D scores were 6.8 ± 4.2 and 5.3 ± 4.2, respectively; 38.6% of patients reported HADS-A ≥8 and 27.7% HADS-D ≥8 at baseline. At week 16, a significantly greater proportion of guselkumab patients with baseline HADS-A or HADS-D ≥8 reported HADS-A <8 (51.4% vs. 25.9%; P < 0.001) or HADS-D <8 (59.2% vs. 27.0%; P < 0.001) vs. placebo patients. At week 24, a greater proportion of guselkumab patients with baseline HADS-A or HADS-D ≥8 reported HADS-A <8 (58.4% vs. 42.9%; P = 0.028) or HADS-D <8 (59.8% vs. 46.4%; P = 0.079) vs. adalimumab patients. PASI improvements correlated with improvement in anxiety (r = 0.27; P < 0.0001) and depression (r = 0.25; P < 0.0001) scores in patients with baseline HADS-A or HADS-D ≥8. Greater improvements in HADS were also observed at week 16 in guselkumab-treated patients vs. placebo using a more stringent cut-off of HADS ≥11. CONCLUSION: Guselkumab treatment was associated with greater improvements in symptoms of anxiety and depression scores in patients with psoriasis compared with placebo and adalimumab.

Efficacy and safety of continuous every-2-week dosing of ixekizumab over 52 weeks in patients with moderate-to-severe plaque psoriasis in a randomized phase III trial (IXORA-P).

BACKGROUND: Ixekizumab is an interleukin-17A antagonist approved for treatment of moderate-to-severe plaque psoriasis with a recommended 160-mg starting dose, then 80 mg every 2 weeks (Q2W) to week 12, and every 4 weeks (Q4W) thereafter. OBJECTIVE: To evaluate continuous Q2W dosing over 52 weeks. METHODS: In this phase III, multicentre, double-blinded, parallel-group trial, three ixekizumab dosing regimens were assessed for efficacy and safety at week 52 in patients with moderate-to-severe plaque psoriasis randomized at a 2 : 1 : 1 ratio to continuous Q2W (n = 611), continuous Q4W (n = 310) or dose adjustment per protocol (Q4W/Q2W, n = 306), each with a 160-mg starting dose. Dose adjustment was determined by predefined criteria to which investigators were blinded; 72 (23?5%) patients in the Q4W/Q2W group adjusted dose. Efficacy outcomes were evaluated using logistic regression. RESULTS: Co-primary end points were met at week 52: Psoriasis Area and Severity Index 75 responses for Q2W and Q4W dose groups were 85·9% and 79·0%, respectively (P = 0·006), and static patient global assessment 0/1 responses for Q2W and Q4W dose groups were 78·6% and 70·6%, respectively (P = 0·005). Treatment-emergent and serious adverse events were comparable across dose groups. CONCLUSIONS: Ixekizumab Q2W had higher efficacy at week 52 than ixekizumab Q4W, with no increase in safety events.

Efficacy of guselkumab in subpopulations of patients with moderate-to-severe plaque psoriasis: a pooled analysis of the phase III VOYAGE 1 and VOYAGE 2 studies.

BACKGROUND: Significant advances have been made in the treatment of moderate-to-severe plaque psoriasis with biological therapies; however, these agents may not work equally in all populations. OBJECTIVES: To evaluate the efficacy of guselkumab in patient subgroups with moderate-to-severe psoriasis from the pooled guselkumab VOYAGE 1 and VOYAGE 2 phase III studies. METHODS: Using data from the pooled VOYAGE 1 and VOYAGE 2 psoriasis studies, analyses were performed to evaluate the consistency of efficacy [Investigator's Global Assessment (IGA) 0/1 (cleared or minimal psoriasis) and IGA 0 (cleared)] across subpopulations defined by demographics, baseline disease characteristics and previous psoriasis treatment. RESULTS: A total of 1829 patients were randomized. Baseline demographics, disease characteristics and previous psoriasis treatment were comparable across treatment groups in the pooled population. Guselkumab, an anti-interleukin (IL)-23 monoclonal antibody that binds to the p19 subunit of IL-23, provided substantial benefit across almost all subpopulations, with greater proportions of patients achieving IGA 0/1 vs. placebo at week 16, and vs. adalimumab (an antitumour necrosis factor monoclonal antibody) at week 24. Patients treated with guselkumab achieved greater efficacy (IGA 0/1 and IGA 0) compared with adalimumab at week 24 across all weight quartiles, most notably among patients weighing ≥ 100 kg. CONCLUSIONS: This analysis demonstrates a high degree of efficacy with guselkumab treatment compared with placebo at week 16 and with adalimumab at week 24 among broad subpopulations of patients with varying baseline demographics, disease characteristics and previous psoriasis treatments.

Outcomes of type 2 endoleaks detected on venous phase CT arteriography.

PURPOSE: The majority of type 2 endoleaks (T2EL) are identified on computed tomography angiography (CTA) both on arterial and venous phase. There is a subset of T2EL that are demonstrated only on venous phase CTA. This study was done to report the outcomes of T2EL detected only on venous phase CTA. MATERIALS AND METHODS: A total of 261 consecutive T2EL treated via embolization were reviewed for the presence of endoleak demonstrated only on venous phase CTA. A group of 16 patients (12 men, 4 women; mean age, 80.1 years) was identified who had pre-embolization venous phase T2EL. Patients were evaluated for presence of T2EL after embolization, change in aneurysm diameter, and need for further intervention. RESULTS: The prevalence of venous phase T2EL was 6.1% (16/261; 95%CI: 3.2%-9.0%). On post-embolization CTA, the rate of successful embolization at 6 months was 2/12 (17%; 95%CI: 0%-38%). At 6-month follow-up, mean change in aneurysm diameter was +2.3mm (n=12; 95%CI: -0.5mm to +5.0mm). In total, 4/16 (25%; 95%CI: 4%-46%) underwent re-embolization and 4/16 (25%, 95%CI: 4%-46%) underwent conversion to open repair. There was one aneurysm rupture, which was successfully treated surgically. CONCLUSION: These results suggest that venous phase T2EL are not as responsive to embolization as standard T2EL and emphasize the need to follow patients with venous phase T2EL closely.

Clinical similarity of the biosimilar ABP 501 compared with adalimumab after single transition: long-term results from a randomized controlled, double-blind, 52-week, phase III trial in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: ABP 501, a U.S.A. Food and Drug Administration- and European Medicines Agency-approved biosimilar, is highly similar to adalimumab in structure, function and pharmacokinetics. OBJECTIVES: To demonstrate similarity in efficacy, safety and immunogenicity of ABP 501 vs. adalimumab for moderate-to-severe plaque psoriasis (clinical trial: NCT01970488). METHODS: Patients were randomized (1 : 1) to receive ABP 501 or adalimumab 40 mg every 2 weeks for 16 weeks. At week 16, patients with ≥ 50% improvement from baseline in Psoriasis Area and Severity Index (PASI) score were eligible to continue to week 52. Patients receiving ABP 501 continued; adalimumab patients were rerandomized (1 : 1) to continue adalimumab or undergo a single transition to ABP 501. Key efficacy assessments included percentage PASI improvement from baseline, PASI responders and mean change in affected body surface area from baseline to weeks 16, 32 and 50. Safety was monitored via adverse events (AEs) and antidrug antibodies (ADAs) were assessed. RESULTS: A total of 308 patients were rerandomized at week 16 (ABP 501/ABP 501, n = 152; adalimumab/adalimumab, n = 79; adalimumab/ABP 501, n = 77). PASI percentage improvements from baseline were similar across groups for weeks 16, 32 and 50 (range: 85·8-88·2%), with no significant differences detected across groups in percentages of PASI 50, 75, 90 and 100 responders. Changes from baseline in percentage body surface area affected were similar across groups and time points. No new safety signals were detected. AEs were balanced between groups. Percentages of patients with binding and neutralizing ADAs were similar across treatments. CONCLUSIONS: ABP 501 and adalimumab have similar clinical efficacy, safety and immunogenicity profiles over 52 weeks, including after single transition, in this patient population.

Biosimilars for psoriasis: worldwide overview of regulatory guidelines, uptake and implications for dermatology clinical practice.

The introduction of biological drugs for the treatment of patients with psoriasis has revolutionized treatment paradigms and enabled numerous patients to achieve disease control with an acceptable safety profile. However, the high cost of biologics limits access to these medications for the majority of patients worldwide. In recent years, the introduction of biosimilars for inflammatory diseases has become a fast evolving field. The future use of biosimilars offers the potential for decreased cost and increased access to biologics for patients with psoriasis. For approval of biosimilars, different regulatory agencies use highly variable methods for definition, production, approval, marketing and postmarketing surveillance. Due to potential interchangeability between biologics and biosimilars, traceability and pharmacovigilance are required to collect accurate data about adverse events in patients with psoriasis; spontaneous reporting, registries and use of 'big data' should facilitate this process on a global basis. The current article describes biosimilar regulatory guidelines and examples of biosimilar uptake in clinical practice in several countries around the world. As it is apparent that biological therapy treatment decisions may become more physician independent, the International Psoriasis Council recommends that dermatologists should take an active role in the development of biosimilar prescribing policies with their respective healthcare settings and government agencies.

Diversity of Flea (Siphonaptera) Parasites on Red Foxes (Vulpes vulpes) in Romania.

Red foxes (Vulpes vulpes (L.)) are widespread across Europe, tolerant of synanthropic ecosystems, and susceptible to diseases potentially shared with humans and other animals. We describe flea fauna on red foxes in Romania, a large, ecologically diverse country, in part because fleas may serve as an indicator of the risk of spillover of vector-borne disease. We found 912 individual fleas of seven species on the 305 foxes assessed, for an infestation prevalence of 49.5%. Mean flea load per fox was 5.8 (range 0-44 fleas), and flea detections were most abundant in fall and early spring. Fleas included generalists (Ctenocephalides canis (Curtis), 32.6% of all fleas), Ct. felis (Bouché, 0.1%), and Pulex irritans L. (29.9%), the fox specialist Chaetopsylla globiceps (Taschenberg, 32.5%), mesocarnivore fleas Paraceras melis Walker (3.2%) and Ch. trichosa Kohaut (1.5%), and the small mammal flea Ctenophthalmus assimilis (Taschenberg, 0.1%), which is rarely or never reported from carnivores. There were significantly more female than male Ch. globiceps, Ct. canis, and Pu. irritans, and these three species were the most broadly distributed geographically. Diversity indices suggested reduced diversity in mountainous areas above 700 m. When compared to other flea studies on foxes in Europe, Romania had flea diversity near the median of reports, which was unexpected given Romania's high ecological diversity. Notably absent prey specialists, compared to other studies, include Archaeopsylla erinacei (Bouché) and Spilopsyllus cuniculi (Dale). Further studies of possible disease agents in fox fleas could help elucidate possible risks of vector-borne disease in foxes, domestic animals, and humans as well.

Management of thyroid eye disease in the United Kingdom: A multi-centre thyroid eye disease audit.

This article aims to provide baseline data and highlight any major deficiencies in the current level of care provided for adult patients with thyroid eye disease (TED). We undertook a prospective, nonrandomized cross-sectional multicenter observational study. During a 3-month period June-August 2014, consecutive adult patients with TED who presented to nominated specialist eye clinics in the United Kingdom, completed a standardized questionnaire. Main outcome measures were: demographics, time from diagnosis to referral to tertiary centre, time from referral to review in specialist eye clinic, management of thyroid dysfunction, radioiodine and provision of steroid prophylaxis, smoking, and TED classification. 91 patients (mean age 47.88 years) were included. Female-to-male ratio was 6:1. Mean time since first symptoms of TED = 27.92 (73.71) months; from first visit to any doctor with symptoms to diagnosis = 9.37 (26.03) months; from hyperthyroidism diagnosis to euthyroidism 12.45 (16.81) months. First, 13% had received radioiodine. All those with active TED received prophylactic steroids. Seven patients who received radioiodine and did not have TED at the time went on to develop it. Then, 60% patients were current or ex-smokers. 63% current smokers had been offered smoking cessation advice. 65% patients had active TED; 4% had sight-threatening TED. A large proportion of patients (54%) were unaware of their thyroid status. Not enough patients are being provided with smoking cessation advice and information on the impact of smoking on TED and control of thyroid function.

Ixekizumab treatment improves fingernail psoriasis in patients with moderate-to-severe psoriasis: results from the randomized, controlled and open-label phases of UNCOVER-3.

BACKGROUND: Fingernail psoriasis is difficult to treat. OBJECTIVE: The objective was to evaluate the effect of ixekizumab, a monoclonal antibody selectively targeting IL-17A, on fingernail psoriasis. METHODS: This Phase 3, double-blind trial (UNCOVER-3) randomized patients to placebo, etanercept (50-mg twice weekly), or 80 mg ixekizumab as one injection every 4 (IXE Q4W) or 2 weeks (IXE Q2W) after a 160-mg starting dose. At Week 12, ixekizumab patients received open-label IXE Q4W through Week 60; placebo patients received a 160-mg starting ixekizumab dose and etanercept patients a 4-week placebo washout before starting IXE Q4W. Efficacy was assessed by mean per cent Nail Psoriasis Severity Index (NAPSI) improvement at Weeks 12 and 60. RESULTS: Of 1346 patients in the UNCOVER-3 trial, this subgroup analysis included only patients with baseline fingernail psoriasis: 116 (60.1%) placebo, 236 (61.8%) etanercept, 228 (59.1%) IXE Q4W and 229 (59.5%) IXE Q2W. At Week 12, greater mean per cent NAPSI improvements were achieved in IXE Q4W (36.7%) and IXE Q2W (35.2%) vs. placebo (-34.3%, P < 0.001 each comparison) and etanercept (20.0%, P = 0.048 vs. Q4W, P = 0.072 vs. Q2W). At Week 60, mean per cent NAPSI improvement was >80% regardless of initial treatment. At Week 12 (nonresponder imputation), complete resolution (NAPSI = 0) was achieved in 19.7% (IXE Q4W), 17.5% (IXE Q2W), 4.3% (placebo, P < 0.001 each comparison) and 10.2% (etanercept, P < 0.05 each comparison) of patients. By Week 60, >50% of patients achieved complete resolution. CONCLUSIONS: At Week 12, significant improvements in fingernail psoriasis were achieved with ixekizumab therapy. With IXE Q4W maintenance dosing, additional improvement was demonstrated through 60 weeks, and >50% of patients achieved complete resolution. Registered at clinicaltrials.gov: NCT01646177.

Apremilast, an oral phosphodiesterase 4 inhibitor, improves patient-reported outcomes in the treatment of moderate to severe psoriasis: results of two phase III randomized, controlled trials.

BACKGROUND: Apremilast, an oral phosphodiesterase 4 inhibitor, has an acceptable safety profile and is effective for treatment of plaque psoriasis and psoriatic arthritis. OBJECTIVES: To evaluate the impact of apremilast on health-related quality of life (HRQOL), general functioning and mental health using patient-reported outcome (PRO) assessments among patients with moderate to severe plaque psoriasis in the ESTEEM 1 and 2 trials. METHODS: A total of 1255 patients were randomized (2 : 1) to apremilast 30 mg BID or placebo for 16 weeks; all received apremilast through Week 32. PRO assessments included the Dermatology Life Quality Index (DLQI), 36-Item Short-Form Health Survey version 2 mental/physical component summary scores (SF-36v2 MCS/PCS), Patient Health Questionnaire-8 (PHQ-8), EuroQol-5D (EQ-5D) and Work Limitations Questionnaire-25 (WLQ-25). Post hoc analyses examined relationships between Psoriasis Area and Severity Index (PASI) scores and PHQ-8 in the apremilast-treated population at Week 16. RESULTS: Treatment with apremilast improved all HRQOL PROs at Week 16 (vs. placebo), except the SF-36v2 PCS, and improvements were sustained through Week 32. Mean DLQI and SF-36v2 MCS improvements exceeded minimal clinically important differences. Changes at Week 16 in PHQ-8 and PASI were weakly correlated, and only 35.8% of patients who achieved a ≥75% reduction from baseline in PASI score (PASI-75) with apremilast treatment also achieved PHQ-8 scores of 0-4. CONCLUSIONS: Apremilast led to improvements in HRQOL PROs vs. placebo in patients with moderate to severe plaque psoriasis.

Evidence and consensus-based (S3) guidelines for the treatment of actinic keratosis: International League of Dermatological Societies in cooperation with the European Dermatology Forum: short version

BACKGROUND: Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. OBJECTIVES: The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. METHODS: The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies.RESULTS: Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. CONCLUSIONS: International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).(AU)

Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version.

BACKGROUND: Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. OBJECTIVES: The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. METHODS: The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies. RESULTS: Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. CONCLUSIONS: International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).

Proximal Versus Distal Splenic Artery Embolisation for Blunt Splenic Trauma: What is the Impact on Splenic Immune Function?

PURPOSE: To compare the impact of proximal or distal splenic artery embolisation versus that of splenectomy on splenic immune function as measured by IgM memory B cell levels. MATERIALS AND METHODS: Patients with splenic trauma who were treated by splenic artery embolisation (SAE) were enrolled. After 6 months splenic volume was assessed by CT, and IgM memory B cells in peripheral blood were measured and compared to a local normal reference population and to a post-splenectomy population. RESULTS: Of the 71 patients who underwent embolisation, 38 underwent proximal embolisation, 11 underwent distal embolisation, 22 patients were excluded, 1 had both proximal and distal embolisation, 5 did not survive and 16 did not return for evaluation. There was a significant difference between splenectomy and proximal or distal embolisation and a trend towards greater preservation of IgM memory B cell number in those with distal embolisation-a difference that could not be attributed to differences in age, grade of injury or residual splenic volume. CONCLUSION: IgM memory B cell levels are significantly higher in those treated with SAE compared to splenectomy. Our data provide evidence that splenic embolisation should reduce immunological complications of spleen trauma and suggest that distal embolisation may maintain better function.