Palmoplantar psoriasis is a chronic (long term) and difficult-to-treat form of psoriasis that affects the palms of the hands and the soles of the feet. The disease causes reddish, scaly plaques on the palms and/or soles with or without the presence of such scales elsewhere on the body. Since palms and soles are affected, the patient can have serious issues in carrying out tasks of daily life such as walking, bathing and eating. This can lead to severe disturbance of their quality of life, and such patients may withdraw socially or suffer from depression and lack of confidence. A drug called secukinumab has been shown to offer rapid and long-lasting effectiveness in treating patients with plaque psoriasis (psoriasis with scales on back, trunk, hands and legs); however, its effect on palmoplantar psoriasis had not been exclusively studied. A randomized control trial is a type of clinical trial in which patients are randomly assigned to a treatment group, and there is also a control group who do not receive any of the treatments being studied. GESTURE, the largest and longest duration randomized controlled study, was conducted to assess the efficacy and safety of secukinumab in people with palmoplantar psoriasis. Both the immediate (16 weeks) and long-term (2.5 years) results were evaluated. Treatment with secukinumab resulted in quick improvements (starting as early as Week 2) in these patients and the Week 16 results proved the efficacy of secukinumab in palmoplantar psoriasis. The patients were further treated and followed-up until 2.5 years to understand if the effects are continued or if the disease returns (known as relapse). The 2.5-year results confirmed that secukinumab treatment resulted in long-lasting effectiveness in patients with palmoplantar psoriasis. Patients experienced improved hand and feet functioning and therefore improved quality of life. No safety issues were identified. This is a summary of the study: Sustained efficacy of secukinumab in patients with moderate-to-severe palmoplantar psoriasis: 2.5-year results from GESTURE, a randomized, double-blind, placebo-controlled trial

Background Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A, a cornerstone cytokine in psoriasis, has shown long-lasting efficacy and safety in the complete spectrum of psoriasis manifestations. Objectives To report the long-term (2 center dot 5-year) efficacy and safety of secukinumab in nail psoriasis. Methods TRANSFIGURE, a double-blind, randomized, placebo-controlled, parallel-group, multicentre phase IIIb study in 198 patients, investigated secukinumab 150 mg and 300 mg in patients with moderate-to-severe nail psoriasis. Results At week 16, the primary endpoint Nail Psoriasis Severity Index (NAPSI) was met, demonstrating superiority of secukinumab to placebo. The effect was sustained over 2 center dot 5 years with a large benefit for nail clearance, with mean NAPSI improvement of -73 center dot 3% and -63 center dot 6% with secukinumab 300 mg and 150 mg, respectively. At 2 center dot 5 years, secukinumab demonstrated sustained clinically significant reductions in total mean Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) quality-of-life (QoL) scores of -52 center dot 4% and -18 center dot 1%, and 70% and 71% of patients achieved a weighted NAPPA Patient Benefit Index global score of >= 2 with secukinumab 300 mg and 150 mg, respectively. Patients showed considerable improvements in the EuroQol 5-Dimension health status questionnaire at 2 center dot 5 years, reporting a decrease in pain and discomfort. No new safety findings were observed. Conclusions Secukinumab demonstrated strong and clinically meaningful efficacy for up to 2 center dot 5 years in nail psoriasis, with significant sustained QoL improvements and a favourable safety profile.

Background::Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis.Methods::This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator’s Global Assessment (IGA) 0/1 at Week 12.Results::A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. Conclusion: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. Trial Registration::ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.

掌跖银屑病是一种慢性(长期)、难以治疗的银屑病,累及手掌和足底。该病引起手掌和/或足底淡红色、鳞屑性斑块,伴或不伴身体其他部位的此类鳞屑。由于手掌和脚掌受累,患者在执行日常生活任务如行走、洗澡和进食时可能会出现严重问题。这会导致其生活质量严重紊乱,这类患者可能会社交退缩或患有抑郁症和信心不足。 一种名为苏金单抗的药物已被证明在治疗斑块状银屑病(背部、躯干、手部和腿部有鳞屑的银屑病)患者方面具有快速和持久的有效性;然而,尚未专门研究其对掌跖银屑病的作用。 随机对照试验是将患者随机分配到治疗组的一类临床试验,也有不接受任何研究中治疗的对照组。GESTURE 是规模最大、持续时间最长的随机对照研究,旨在评估苏金单抗在掌跖银屑病患者中的疗效和安全性。对即刻(16 周)和长期(2·5 年)结果进行了评估。 苏金单抗治疗使这些患者快速改善(最早从第 2 周开始),第 16 周的结果证明了苏金单抗治疗掌跖银屑病的疗效。对患者进行进一步治疗并随访至 2·5 年,以了解疗效是否持续或疾病是否再次出现(称为复发)。 2·5 年的结果证实苏金单抗治疗掌跖银屑病患者可产生持久的疗效。患者的手足功能得到改善,因此生活质量得到改善。未发现安全性问题。 本摘要涉及研究:苏金单抗对中重度掌跖银屑病患者的持续疗效:来自一项随机、双盲、安慰剂对照试验 GESTURE 的 2·5 年结果

BACKGROUND:Nail psoriasis is associated with functional impairment, pain and reduced quality of life.OBJECTIVES:To demonstrate the superiority of secukinumab over placebo in clearing nail psoriasis as assessed by the Nail Psoriasis Severity Index (NAPSI) at week 16 and over time up to week 132. Presented here is the week 32 interim analysis. Impact on quality of life was assessed by Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) patient questionnaires.METHODS:TRANSFIGURE is a double-blind, randomized, placebo-controlled study in patients with moderate-to-severe plaque and nail psoriasis.RESULTS:The primary objective of this study was met: both doses of secukinumab were superior to placebo at week 16 (NAPSI improvements of -45·3%, -37·9% and -10·8% for secukinumab 300 mg and 150 mg and placebo, respectively, P < 0·001). Significant improvements were seen in patients' quality of life: the NAPPA-Quality of Life total score median decreases at week 16 were 60·9%, 49·9% and 15·8% for secukinumab 300 mg and 150 mg and placebo, respectively (P < 0·001). Improvement in nail psoriasis continued to week 32: NAPSI percentage change reached -63·2% and -52·6% for secukinumab 300 mg and 150 mg, respectively. Skin clearance measured by ≥ 90% improvement in Psoriasis Area and Severity Index was significant (rates of 72·5%, 54·0% and 1·7% for secukinumab 300 mg and 150 mg and placebo at week 16, respectively, P < 0·001) and was sustained to week 32. The most common adverse events were nasopharyngitis, headache and upper respiratory tract infections.CONCLUSIONS:Secukinumab demonstrated significant and clinically meaningful efficacy and quality-of-life improvements for patients with nail psoriasis up to week 32. What's already known about this topic? Nail psoriasis is understudied and there is a lack of effective treatment options. Nail psoriasis is correlated with more severe psoriatic disease and the development of psoriatic arthritis. What does this study add? TRANSFIGURE is one of the few prospective placebo-controlled trials specifically in nail psoriasis and includes nail-specific quality-of-life measures such as Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA)-Quality of Life and NAPPA-Patient Benefit Index. In this trial, secukinumab demonstrates significant efficacy and quality-of-life improvements in this difficult-to-treat population.

BACKGROUND:Secukinumab has shown sustained efficacy and safety in several manifestations of psoriasis.OBJECTIVES:GESTURE investigated the long-term (2·5-year) safety and efficacy of 150 mg and 300 mg subcutaneous secukinumab in 205 patients with moderate-to-severe palmoplantar psoriasis.METHODS:GESTURE was a randomized, double-blind, placebo-controlled, multicentre, phase IIIb trial conducted across 15 countries. The study was 140 weeks long and consisted of four periods: screening (up to 4 weeks), treatment period 1 (16 weeks), treatment period 2 (116 weeks) and post-treatment follow-up (8 weeks). Eligible patients were aged ≥ 18 years with moderate-to-severe palmoplantar psoriasis and at least one plaque outside of the palms and soles. Efficacy was assessed via a palmoplantar Investigator's Global Assessment (ppIGA) and the palmoplantar Psoriasis Area and Severity Index (PASI).RESULTS:The primary end point, a ppIGA score of 0 or 1, was met at week 16. The effect was sustained over 2·5 years with 59% [95% confidence interval (CI) 43·5-74·1] and 53% (95% CI 35·1-69·6) of patients in the secukinumab 300 mg and 150 mg groups, respectively, achieving clear or almost clear palms and soles (ppIGA 0 or 1). At 2·5 years, the mean palmoplantar PASI percentage was reduced in both the secukinumab 300 mg group (-74·7%) and the secukinumab 150 mg group (-61·6%). A total of 17% (secukinumab 300 mg group) and 18% (secukinumab 150 mg group) of patients experienced no difficulty in hands and feet functionality, as indicated by the palmoplantar quality of life instrument overall scores. The safety profile was favourable.CONCLUSIONS:GESTURE revealed that secukinumab provides a strong and sustained response over 2·5 years in challenging-to-treat palmoplantar psoriasis.

BACKGROUND: Fixed combinations are commonplace in dermatology, providing significant efficacy and tolerability benefits. In some cases, two active ingredients complement each other providing a cumulative or additive effect. In rarer cases, a synergistic effect may be seen where the sum of the two active ingredients combined action is greater than the sum of the efficacy of the constituent parts. Being able to demonstrate synergy is important in situations where the two active ingredients may be used individually to provide layering. OBJECTIVE: To determine whether a novel halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) fixed combination lotion provides a synergistic effect in the treatment of moderate-to-severe plaque psoriasis. MATERIALS/METHODS: Post hoc analysis of 212 patients with moderate-to-severe plaque psoriasis randomized (2:2:2:1) to HP/TAZ lotion, HP, TAZ or vehicle once-daily for 8 weeks, with a 4-week posttreatment follow-up. Treatment success was evaluated based on two outcomes: percent of patients achieving at least a 2-grade improvement in Investigator Global Assessment (IGA) and IGA score equating to ‘clear’ or ‘almost clear’; and percent change from baseline in the IGA multiplied by Body Surface Area (BSA) composite score, a simple validated alternative to assessing response to therapy that correlates well with the Psoriasis Area Severity Index (PASI). Synergy was calculated by summing up the contribution of the individual active ingredients (HP and TAZ) to overall efficacy and comparing to the efficacy achieved with HP/ TAZ lotion relative to vehicle. RESULTS: At Week 8, treatment success with HP/TAZ lotion, relative to vehicle was 42.8% compared with 23.6% and 9.0% for HP and TAZ. Percent change from baseline in IGAxBSA score, relative to vehicle was 51.6% compared with 37.3% and 3.3% for HP and TAZ. In both cases the synergy ratios were 1.3. At Week 12, treatment success with HP/TAZ lotion, relative to vehicle was 31.3% compared with 14.1% and 5.9% for HP and TAZ. Percent change from baseline in IGAxBSA score, relative to vehicle was 47.3% compared with 25.7% and 8.6% for HP and TAZ. Synergy ratios were 1.6 and 1.4 respectively. CONCLUSIONS: Halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) fixed combination lotion provides a synergistic effect in the treatment of moderate-to-severe plaque psoriasis. In addition, by combining two agents into one once-daily formulation, this novel formulation reduces the number of product applications and may help patient adherence. CORRESPONDENCE: brian.bulley@btinternet.com DISCLOSURES: Tina Lin, is an employee of Bausch Health; Leon Kircik: has been a consultant and investigator for Valeant Pharmaceuticals.

Background Nail psoriasis is associated with decreased finger mobility, functional impairment, pain and reduced quality of life [1] and is often resistant to available therapies.[2] It correlates with more severe psoriatic disease and is an important predictor of psoriatic arthritis (PsA).[3] The incidence of nail psoriasis in PsA patients is up to 80%.[4] Objectives We assessed superiority of secukinumab 300 mg and/or 150 mg vs. placebo (PBO) in treating subjects with moderate to severe psoriasis and significant nail involvement, as assessed by NAil Psoriasis Severity Index (NAPSI) at Week (Wk) 16 and Wk 32 and Psoriasis Area and Severity Index (PASI) at Wk 32. Impact on quality of life was assessed by Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) Patient Benefit Index (-PBI) and Quality of Life (-QOL) at Wk 16. Methods TRANSFIGURE is a double-blind, randomized, PBO-controlled, parallel-group multicentre phase 3b study. Subjects (N=198) were randomized 1:1:1 to receive either secukinumab 300 mg, secukinumab 150 mg or PBO subcutaneously up to Wk 128. At Wk 16, all subjects receiving PBO were re-randomized 1:1 to receive 300 mg or 150 mg secukinumab. Results The primary objective of this study was met. Both doses of secukinumab were superior to PBO at Wk 16 with a mean percentage NAPSI improvement from Baseline of -45.3%, -37.9%, and -10.8%, for secukinumab 300 mg, 150 mg and PBO, respectively (P <0.0001). Responses improved further by Wk 32 with a NAPSI change of -63.2% and -52.6%, for secukinumab 300 mg and 150 mg, respectively. At Wk 32, PASI 90 responses were achieved in 72.1% and 61.4% of subjects, and PASI 100 responses in 36.9% and 28.1% for secukinumab 300 mg and 150 mg, respectively. At Wk 16, subjects on secukinumab showed significant improvements in NAPPA-QOL with a median decrease in total score of 60.9%, 49.9% and 15.8% for secukinumab 300 mg, 150 mg and PBO, respectively. The percentage of subjects achieving a weighted NAPPA-PBI global score of 2 and above (i.e. at least moderate benefits) was 75.4%, 61.3% and 8.6% for secukinumab 300 mg, 150 mg and PBO, respectively. The most common adverse events were nasopharyngitis, headache and upper respiratory tract infections, similar to previous studies. Conclusions In the prospective, placebo-controlled TRANSFIGURE trial, secukinumab demonstrated significant and clinically meaningful efficacy, quality of life improvement and patient-reported benefit in nail psoriasis. References Baran R. Dermatology. 2010;221 Suppl 1:1–5 Thaci D, Unnebrink K, Sundaram M, et al. JEADV. 2015 Feb; 29(2):353–360 Langenbruch A, Radtke MA, Krensel M, et al. Br J Dermatol. 2014 Nov; 171(5):1123–8 Reich K. JEADV. 2009 Sep; 23 Suppl 1:15–21 Acknowledgement This investigation was sponsored by Novartis Pharma AG, Basel, Switzerland. Medical writing assistance was provided by Gillian Brodie, Novartis Ireland Ltd. Disclosure of Interest K. Reich Grant/research support from: K Reich has participated in clinical trials sponsored by AbbVie, Amgen, Biogen-Idec, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo, Lilly, Medac, MSD, Novartis, Pfizer, Takeda, and Vertex, Consultant for: K Reich has served as a consultant for AbbVie, Amgen, Biogen-Idec, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo, Lilly, Medac, MSD, Novartis, Pfizer, Takeda, and Vertex, J. Sullivan Grant/research support from: J Sullivan has received educational grants from Novartis, Abbvie and Pfizer., Consultant for: J Sullivan has received consultancy fees from Novartis, Abbvie, Pfizer and Eli Lilly. P. Arenberger Grant/research support from: P Arenberger has received grants from Novartis. U. Mrowietz Grant/research support from: U Mrowietz has received grants and/or participated in clinical trials for Abbott/AbbVie, Almirall, Amgen, BASF, Biogen Idec, Celgene, Centocor, Eli Lilly, Forward Pharma, Galderma, Janssen, Leo Pharma, Medac, MSD, Miltenyi Biotech, Novartis, Pfizer, Teva, VBL, and Xenoport. Consultant for: U Mrowietz has served as advisor and/or received speaker honoraria and/or received grants for Abbott/AbbVie, Almirall, Amgen, BASF, Biogen Idec, Celgene, Centocor, Eli Lilly, Forward Pharma, Galderma, Janssen, Leo Pharma, Medac, MSD, Miltenyi Biotech, Novartis, Pfizer, Teva, VBL, and Xenoport. S. Jazayeri Grant/research support from: S Jazayeri has received a grant from Novartis and personal fees outside of the submitted work., M. Augustin Grant/research support from: M Augustin has received grants and/or participated in clinical trials for Abbvie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, Janssen-Cilag, Leo, Medac, MSD (formerly Essex, Schering-Plough), Mundipharma, Novartis, Pfizer (formerly Wyeth), Pohl Boskamp, Sandoz, Xenoport. Consultant for: M Augustin has served as advisor and/or received speaker honoraria from Abbvie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, Janssen-Cilag, Leo, Medac, MSD (formerly Essex, Schering-Plough), Mundipharma, Novartis, Pfizer (formerly Wyeth), Pohl Boskamp, Sandoz, Xenoport. A. Parneix Employee of: A Parneix is a full time employee of Novartis, P. Regnault Employee of: P Regnault is a full time employee of Novartis, R. You Employee of: R You is a full time employee of Novartis, M. Milutinovic Employee of: M Milutinovic is a full time employee of Novartis

Background: Secukinumab has demonstrated high, sustained efficacy in psoriasis to 52 weeks on a fixed-interval regimen.Objective: We sought to compare a retreatment-as-needed versus a fixed-interval regimen.Methods: In this double-blind study, adults with moderate to severe plaque psoriasis were randomized 1: 1 to subcutaneous secukinumab at 300 mg (n = 484) or 150 mg (n = 482) weekly from baseline until week 4, and at week 8. At week 12, patients achieving 75% or more improvement from baseline Psoriasis Area and Severity Index score (PASI 75) were rerandomized to 2 dose levels of secukinumab retreatment as needed (n = 217, 300 mg; n = 206, 150 mg) or fixed interval (n = 217; n = 203). Primary end point was noninferiority of retreatment as needed versus fixed interval for maintaining PASI 75 to week 52.Results: Secukinumab induced high responses by week 12 (84.4%-91.1% PASI 75 responders). From week 12 to week 52, more patients on fixed interval (78.2%, 300 mg; 62.1%, 150 mg) maintained PASI 75 versus retreatment as needed (67.7%; 52.4%); statistical noninferiority of retreatment as needed was not established. Overall safety, including very low incidences of treatment-emergent anti-drug antibodies (<0.5%), was similar between regimens.Limitations: The primary end point was developed without any known precedent.Conclusion: Secukinumab fixed interval showed clear benefit versus the study-specified retreatment-as-needed regimen for maintaining efficacy. Both regimens exhibited safety consistent with previous trials. The potential of retreatment as needed with secukinumab warrants further investigation.