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Psoriasis: HELP
Articles by Lluís Puig
Based on 47 articles published since 2008
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Between 2008 and 2019, Ll Puig wrote the following 47 articles about Psoriasis.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Guidelines for the use of acitretin in psoriasis. Psoriasis Group of the Spanish Academy of Dermatology and Venereology. 2013

Carretero, G / Ribera, M / Belinchón, I / Carrascosa, J M / Puig, Ll / Ferrandiz, C / Dehesa, L / Vidal, D / Peral, F / Jorquera, E / González-Quesada, A / Muñoz, C / Notario, J / Vanaclocha, F / Moreno, J C / Anonymous1280765. ·Grupo de Psoriasis de la Academia Española de Dermatología y Venereología, Spain. gcarrete@aedv.es ·Actas Dermosifiliogr · Pubmed #23891453.

ABSTRACT: Phototherapy, classic systemic treatments (methotrexate, acitretin, and ciclosporin), and biologic agents (etanercept, infliximab, adalimumab, and ustekinumab) constitute a broad therapeutic arsenal that increases the likelihood of achieving control of severe and extensive disease in patients with psoriasis. Acitretin continues to be a very valuable tool in both monotherapy, in which it is combined with other systemic treatments (classic or biologic), and in sequential therapy. Thanks to its lack of a direct immunosuppressive effect and its ability to achieve a long-term response, acitretin has an important role in the treatment of psoriasis, although this has not always been acknowledged in relevant treatment guidelines. We present consensus guidelines for the use of acitretin in psoriasis drawn up by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology. These guidelines provide a detailed account of acitretin, including pharmacological properties, indications and contraindications, adverse effects, and factors that should be taken into account to enhance the safe use of this drug. They also propose treatment strategies for use in routine clinical practice. The overall aim of these guidelines is to define the criteria for the use and management of acetretin in psoriasis.

2 Review Cardiometabolic Comorbidities in Psoriasis and Psoriatic Arthritis. 2017

Puig, Lluís. ·Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Sant Quintí 89, 08041 Barcelona, Spain. lpuig@santpau.cat. ·Int J Mol Sci · Pubmed #29295598.

ABSTRACT: There is solid epidemiologic evidence linking psoriasis and psoriatic arthritis (PsA) to cardiovascular risk factors and an increased risk of developing cardiovascular disease. Chronic inflammation, with shared pathways and cytokines common to metabolic syndrome, atherosclerosis and psoriasis, might provide the basis for the cardiovascular and metabolic comorbidities of psoriasis and PsA. The purpose of this manuscript is to review recent evidence about the epidemiology and underlying mechanisms of cardiovascular risk factors and cardiovascular disease in patients with psoriasis and/or PsA; the use of analytical determinations, physiologic measures and imaging techniques as surrogate biomarkers of atherosclerosis, endothelial dysfunction and cardiovascular disease in these patients; and the epidemiological and clinical data, including results of clinical trials, supporting a cardioprotective role of anti-inflammatory and disease-modifying treatment in psoriasis and PsA.

3 Review The role of IL 23 in the treatment of psoriasis. 2017

Puig, Lluís. ·a Department of Dermatology, Hospital de la Santa Creu i Sant Pau , Universitat Autònoma de Barcelona , Barcelona , Catalonia , Spain. ·Expert Rev Clin Immunol · Pubmed #28165883.

ABSTRACT: INTRODUCTION: The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis. Human IL-23 is primarily produced by antigen-presenting cells and induces and maintains differentiation of Th17 cells and Th22 cells, a primary cellular source of proinflammatory cytokines such as IL-17 and IL-22, which mediate the epidermal hyperplasia, keratinocyte immune activation and tissue inflammation inherent in psoriasis. Agents that target the p40 subunit common to both IL-12 and IL-23 have shown robust clinical activity, but selectivity for IL-23p19 could offer advantages in efficacy and safety with respect to anti-p40 blockade. Areas covered: Relevant references regarding the role of the IL-23/IL-17 pathway in the pathogenesis of psoriasis/psoriatic arthritis and clinical trials with IL-23p40 and IL-23p19 blocking agents were obtained through a literature search in MEDLINE/Pubmed for articles published until November 2016. Moreover, ongoing registered clinical trials (RCTs) of moderate-to-severe psoriasis and psoriatic arthritis were searched through clinicaltrials.gov website, and a manual search was made for pertinent communications at the 2016 American Academy of Dermatology and European Academy of Dermatology and Venereology meetings. Expert commentary: There are potential advantages in selective blockade of the IL23-specific p19 subunit with respect to distal blockade of IL-17A or its receptor. Acting upstream in the IL-23/IL-17 cytokine pathway is likely to reduce the expression of multiple pro-inflammatory cytokines acting on keratinocytes -including IL-17F, IL-21 and IL-22-, in addition to IL-17A. On the other hand, safety data thus far suggest that these drugs might be devoid of some adverse effects of IL-17A blockade that seem to be class related, such as mucocutaneous Candida infections or triggering or worsening of inflammatory bowel disease. Specific IL-23p19 blockade with high-affinity monoclonal antibodies seems to be able to induce long-term remissions of the activity in psoriasis and might eventually represent a paradigm change in the treatment of psoriasis. The results of phase III and comparative head-to-head trials with these agents are eagerly awaited.

4 Review The role of biologics in the treatment of moderate-to-severe plaque psoriasis. 2017

Puig, Lluís. ·Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain - lpuig@santpau.cat. ·G Ital Dermatol Venereol · Pubmed #27627100.

ABSTRACT: Psoriasis is a chronic, relapsing, inflammatory skin disease requiring long-term treatment and in many cases involving a reduction in the quality of life. Treatment with biologics is indicated in patients with moderate-to-severe psoriasis who do not respond or cannot be treated with conventional systemic drugs, and the therapeutic goal is an improvement of 90% (or at least 75%) with respect to baseline PASi at the end of the induction phase, which should be maintained long-term in the mainternance phase of treatment. Before starting treatment with a biological agent it is necessary to review the contraindications and precautions, rule out latent tuberculosis infection and complete the pending immunizations. Biological agents have a more favorable safety profile than classical systemic treatments; the most common side effects are mild and rarely involve the discontinuation of treatment. The treatment decision will be based on individual characteristics and patient preferences, functional limitation, expected speed of onset of effect, adverse reactions, availability and cost of treatment.

5 Review Secukinumab (AIN457) for the treatment of psoriasis. 2015

López-Ferrer, Anna / Vilarrasa, Eva / Puig, Lluís. ·a Department of Dermatology, Hospital de la Santa Creu i Sant Pau. Universitat Autònoma de Barcelona, Campus de la UAB, Plaza Cívica, s/n, 08193 Bellaterra, Barcelona, Spain. ·Expert Rev Clin Immunol · Pubmed #26428036.

ABSTRACT: Psoriasis is a chronic inflammatory disease with a multifactorial origin that appears in patients with genetic predisposition and is induced by environmental factors, and characterized by alterations in the innate and adaptive immunity. IL-17A is one of the specific cytokines involved in the pathogenesis of psoriasis and its inhibition is highly effective in the treatment of patients with moderate and severe psoriasis. Secukinumab is a monoclonal antibody that specifically binds to IL-17A and inhibits the interaction to its receptor, and it has demonstrated its efficacy and safety in the treatment of psoriasis. Phase II and III clinical trials indicate that > 80% of the patients receiving secukinumab achieve Psoriasis Area Severity Index (PASI) 75 at week 12. In the Phase III efficacy of response and safety of two fixed secukinumab regimens in psoriasis trial, PASI 75 rates were 81.6% with 300 mg secukinumab, 71.6% with 150 mg secukinumab and 4.5% with placebo, and responses were maintained up to 52 weeks in the majority of patients. In the Phase III Full Year Investigative Examination Of Secukinumab versus Etanercept Using Two Dosing Regimens To Determine Efficacy in Psoriasis study, the efficacy of secukinumab was compared to etanercept. The results indicate that both doses of secukinumab (150 and 300 mg) showed superior efficacy compared with etanercept throughout the study; PASI 75 rates at week 12 were 77.1% with 300 mg secukinumab, 67% with 150 mg of secukinumab, 44% with etanercept and 4.9% with placebo. PASI 90 and PASI 100 were 54 and 24% with secukinumab 300 mg and 21 and 4% with etanercept at week 12. At week 52, PASI 90 continued to be higher in the secukinumab group (65%) compared with the etanercept group (33%). Regarding safety, the most common side effects were nasopharyngitis and headache. The rate of infections was higher with secukinumab than placebo. This was especially the case for Candida infections, which were more common in the secukinumab group (4.7% with secukinumab 300 mg and 2.3% with secukinumab 150 mg), but all cases were resolved with conventional treatment. Secukinumab is a well-tolerated treatment that has demonstrated efficacy in treating moderate-to-severe plaque psoriasis. Nevertheless, long-term studies are necessary to confirm Phase II and Phase III data.

6 Review Systemic methotrexate for the treatment of psoriasis. 2015

Yélamos, Oriol / Puig, Lluís. ·Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, C/Sant Antoni Maria Claret 167, 08025 Barcelona, Spain. ·Expert Rev Clin Immunol · Pubmed #25779551.

ABSTRACT: In the era of biologic therapies, methotrexate (MTX), a classic immunomodulator, is still the cornerstone of systemic treatment of psoriasis. MTX has been used for many years, achieving good responses with a good safety profile. However, only a few randomized clinical trials have been performed involving MTX, and most of the current evidence comes from pivotal studies of biologic drugs. The aim of this article is to make an extensive review of the MTX mechanism of action, pharmacokinetics, efficacy, safety and tolerability, especially focusing on the future perspective of this old drug and recent advances in the field of pharmacogenetics.

7 Review Psoriasis beyond the skin: a review of the literature on cardiometabolic and psychological co-morbidities of psoriasis. 2014

Puig, Lluis / Kirby, Brian / Mallbris, Lotus / Strohal, Robert. ·Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Sant Antoni Maria Claret 167, 08025 Barcelona, Spain. · St Vincent's University Hospital, Elm Park, Dublin, Ireland. · Lotus Mallbris, Pfizer Global Medical Dermatology Lead, Philadelphia, USA. · Department of Dermatology, Federal Academic Teaching Hospital, Feldkirch, Austria. ·Eur J Dermatol · Pubmed #24752135.

ABSTRACT: Psoriasis is increasingly associated with a range of co-morbid diseases and risk factors. Patients with co-morbidities are more likely to need hospitalisation for non-dermatological conditions, and incur greater total costs than those without co-morbidities. A literature review was conducted on two of the most common co-morbidities of psoriasis (cardiovascular (CV) and psychological co-morbidities), to establish their incidence and impact and to raise awareness of unanswered questions and highlight knowledge gaps. A large number of small controlled or cross-sectional studies report increased prevalence of cardiometabolic and psychological co-morbidities in psoriasis patients. A number of large cohort studies documented the incidence of various cardiometabolic co-morbidities. Severe psoriasis is associated with increased mortality, and the most common cause of death is CV disease. Studies on the management of co-morbidities and their impact on psoriasis treatment are scarce. Many questions on the co-morbidities of psoriasis remain to be answered.

8 Review Ustekinumab treatment of TNF antagonist-induced paradoxical psoriasis flare in a patient with psoriatic arthritis: case report and review. 2012

Puig, Lluís / Morales-Múnera, Caridad E / López-Ferrer, Anna / Geli, Carme. ·Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. lpuig@santpau.cat ·Dermatology · Pubmed #22890275.

ABSTRACT: BACKGROUND: Therapy with tumour necrosis factor α (TNF) inhibitors can be associated with paradoxical reactions, namely the de novo development or flaring of conditions that usually respond to these therapeutic agents, such as arthritis, inflammatory bowel disease, sarcoidosis or psoriasis. They are considered a class effect of these drugs, and their incidence ranges from 1 to 5%, with paradoxical psoriasis (psoriasis vulgaris, palmoplantar pustulosis, scalp psoriasis and their combinations) being most frequently reported. Treatment of paradoxical psoriasis often requires withdrawal of the inducing drug and switching to another anti-TNF agent, but often this cannot avoid recurrence or persistence of the rash and/or loss of the therapeutic effect on the underlying condition. CASE REPORT: We report on a 47-year-old woman who developed incapacitating palmoplantar pustulosis and psoriasis vulgaris flare with severe scalp and nail involvement after 5 months of treatment with adalimumab for psoriatic arthritis. Several treatments, including topical corticosteroids, photochemotherapy, ciclosporin, acitretin and etanercept 50 mg twice a day for 1 month, were ineffective or not tolerated. Treatment with ustekinumab 45 mg provided complete resolution of skin lesions with acceptable therapeutic control of the arthritis, with a follow-up duration of 16 months. CONCLUSION: A review of the reported cases suggests that this may be a therapeutic option in patients who develop paradoxical psoriasis while under treatment for arthritis or Crohn's disease.

9 Review Treatment of acrodermatitis continua of Hallopeau with TNF-blocking agents: case report and review. 2010

Puig, Lluís / Barco, Didac / Vilarrasa, Eva / Alomar, Agustín. ·Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. lpuig@santpau.cat ·Dermatology · Pubmed #20110631.

ABSTRACT: Acrodermatitis continua of Hallopeau (ACH) is a rare acropustular eruption, characterized by sterile pustules, paronychia and atrophic skin changes, onychodystrophy and osteolysis of the distal phalanges of the fingers and toes. It is considered to be a variant of pustular psoriasis with a chronic relapsing course and frequent refractoriness to many therapeutic modalities, which can be amenable to successful treatment by tumor necrosis factor alpha antagonists. We report 1 patient with pustular psoriasis and ACH whom we have treated successfully with etanercept (for 30 months) and then adalimumab (for 13 months and ongoing). Blanching was initially achieved with etanercept 50 mg twice a week, but suppression of periungual inflammation then required combination therapy with etanercept 50 mg twice a week and methotrexate 10 mg weekly; lower doses of both drugs did not allow complete control of the disease. Eventually, adalimumab 40 mg every 2 weeks has provided the most cost-effective response in this patient, allowing maintenance of response with partial nail regrowth under monotherapy.

10 Review Treatment of psoriasis with anti-TNF drugs during pregnancy: case report and review of the literature. 2010

Puig, Lluís / Barco, Didac / Alomar, Agustín. ·Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. lpuig@santpau.cat ·Dermatology · Pubmed #19940453.

ABSTRACT: Published experiences of TNF-alpha inhibition during pregnancy consist of a limited number of case reports, series and ongoing registry data in patients with arthritis and inflammatory bowel disease. A 28-year-old woman - with psoriasis vulgaris since she was 8 years of age and generalized pustular psoriasis during her first pregnancy (partially controlled with ciclosporin, oral prednisone and topical corticosteroids, when lupus anticoagulant was detected at another hospital) - presented 4 months after delivery with severe psoriasis (PASI = 15.4) that did not respond to ciclosporin (3 mg/kg/day). Ten days after the first infusion of infliximab (5 mg/kg), when the patient became aware that she was pregnant again, there was PASI75 response, and the patient wished to continue this treatment after being fully informed. Complete blanching was achieved by week 6 of treatment, and was maintained thereafter until the moment of writing (19 months after the start of treatment). She gave birth by caesarean delivery to a healthy female baby, who was breastfed for 1 month and has developed normally. The current report extends the available evidence on successful infliximab treatment in pregnant women, with the first case of a patient with psoriasis who presented impetigo herpetiformis during her previous pregnancy. No detectable adverse effects were detected in the neonate, despite potential exposure to infliximab throughout gestation and breastfeeding. Even though absolute safety is difficult to prove, available data suggest that women who become pregnant while taking infliximab or other anti-TNFalpha agents can be reassured regarding the continuation of pregnancy.

11 Clinical Trial Ixekizumab provides superior efficacy compared with ustekinumab over 52 weeks of treatment: Results from IXORA-S, a phase 3 study. 2019

Paul, Carle / Griffiths, Christopher E M / van de Kerkhof, Peter C M / Puig, Lluís / Dutronc, Yves / Henneges, Carsten / Dossenbach, Martin / Hollister, Kristin / Reich, Kristian. ·Dermatology Department, CHU, Paul Sabatier University, Toulouse, France. Electronic address: paul.c@chu-toulouse.fr. · Dermatology Centre, Salford Royal Hospital, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom. · Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. · Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. · Eli Lilly and Company, Indianapolis, Indiana. · Dermatologikum Berlin and Georg-August-University Göttingen, Göttingen, Germany. ·J Am Acad Dermatol · Pubmed #29969700.

ABSTRACT: BACKGROUND: Biologics targeting interleukin 17A (IL-17A) allow for rapid clearance of psoriatic plaques, with a clinically favorable safety profile. OBJECTIVES: To compare the safety and efficacy of ixekizumab, an IL-17A antagonist, with the safety and efficacy of the IL-12/23 inhibitor ustekinumab through 52 weeks of treatment in the head-to-head trial IXORA-S. METHODS: Patients were randomized to ixekizumab (n = 136) or ustekinumab (n = 166) and dosed per the approved labels. After 1 year, efficacy was assessed via improvements in Psoriasis Area and Severity Index (PASI) score (with PASI 90 indicating a 90% or greater improvement from baseline PASI score) and a static Physician's Global Assessment (sPGA) response of either 0 or 0 or 1, with dropouts counted as nonresponders. Safety analyses included treatment-emergent adverse events (AEs). RESULTS: At week 52, significantly more ixekizumab-treated patients (P < .01) reported PASI 90 (104 [76.5%]), an sPGA response of 0 (72 [52.9%]), or an sPGA response of 0 or 1 (110 [82.1%]) responses than did ustekinumab-treated patients (PASI 90, 98 [59.0%]; sPGA response of 0, 60 [36.1%]; and sPGA response of 0 or 1, 108 [65.1%]). Treatment-emergent AEs, serious AEs, and discontinuation rates were not different between the treatment groups. Injection site reactions occurred more frequently in the ixekizumab-treated group (ixekizumab, 22 [16.3%]; ustekinumab, 2 [1.2%]) (P < .001). LIMITATIONS: This study was not designed to compare safety end points related to rare events. CONCLUSIONS: Compared with ustekinumab, ixekizumab showed superior efficacy and comparable safety outcomes through 52 weeks of treatment.

12 Clinical Trial Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. 2018

Gordon, Kenneth B / Strober, Bruce / Lebwohl, Mark / Augustin, Matthias / Blauvelt, Andrew / Poulin, Yves / Papp, Kim A / Sofen, Howard / Puig, Lluís / Foley, Peter / Ohtsuki, Mamitaro / Flack, Mary / Geng, Ziqian / Gu, Yihua / Valdes, Joaquin M / Thompson, Elizabeth H Z / Bachelez, Hervé. ·Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: kegordon@mcw.edu. · University of Connecticut Health Center and Probity Medical Research, Farmington, CT, USA. · Icahn School of Medicine at Mount Sinai, New York, NY, USA. · University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Oregon Medical Research Center, Portland, OR, USA. · Centre Dermatologique du Québec Métropolitain, Québec, QC, Canada. · K Papp Clinical Research and Probity Medical Research, Waterloo, ON, Canada. · University of California, Los Angeles, CA, USA; School of Medicine, Los Angeles, CA, USA. · Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. · University of Melbourne, Parkville, Skin & Cancer Foundation Inc, Carlton, Probity Medical Research, Carlton, and St Vincent's Hospital Melbourne, Fitzroy VIC, Australia. · Jichi Medical University, Shimotsuke, Japan. · Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA. · AbbVie, North Chicago, IL, USA. · AbbVie, Redwood City, CA, USA. · Saint-Louis Hospital, AP-HP, Sorbonne Paris Cité Université Paris Diderot, INSERUM UMR 1163, Institut Imagine, Paris, France. Electronic address: herve.bachelez@aphp.fr. ·Lancet · Pubmed #30097359.

ABSTRACT: BACKGROUND: Risankizumab is a humanised IgG1 monoclonal antibody that binds to the p19 subunit of interleukin-23, inhibiting this key cytokine and its role in psoriatic inflammation. We aimed to assess the efficacy and safety of risankizumab compared with placebo or ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. METHODS: UltIMMa-1 and UltIMMa-2 were replicate phase 3, randomised, double-blind, placebo-controlled and active comparator-controlled trials done at 139 sites in Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Japan, Mexico, Poland, Portugal, South Korea, Spain, and the USA. Eligible patients were 18 years or older, with moderate-to-severe chronic plaque psoriasis. In each study, patients were stratified by weight and previous exposure to tumour necrosis factor inhibitor and randomly assigned (3:1:1) by use of interactive response technology to receive 150 mg risankizumab, 45 mg or 90 mg ustekinumab (weight-based per label), or placebo. Following the 16-week double-blind treatment period (part A), patients initially assigned to placebo switched to 150 mg risankizumab at week 16; other patients continued their originally randomised treatment (part B, double-blind, weeks 16-52). Study drug was administered subcutaneously at weeks 0 and 4 during part A and at weeks 16, 28, and 40 during part B. Co-primary endpoints were proportions of patients achieving a 90% improvement in the Psoriasis Area Severity Index (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16 (non-responder imputation). All efficacy analyses were done in the intention-to-treat population. These trials are registered with ClinicalTrials.gov, numbers NCT02684370 (UltIMMa-1) and NCT02684357 (UltIMMa-2), and have been completed. FINDINGS: Between Feb 24, 2016, and Aug 31, 2016, 506 patients in UltIMMa-1 were randomly assigned to receive 150 mg risankizumab (n=304), 45 mg or 90 mg ustekinumab (n=100), or placebo (n=102). Between March 1, 2016, and Aug 30, 2016, 491 patients in UltIMMa-2 were randomly assigned to receive 150 mg risankizumab (n=294), 45 mg or 90 mg ustekinumab (n=99), or placebo (n=98). Co-primary endpoints were met for both studies. At week 16 of UltIMMa-1, PASI 90 was achieved by 229 (75·3%) patients receiving risankizumab versus five (4·9%) receiving placebo (placebo-adjusted difference 70·3% [95% CI 64·0-76·7]) and 42 (42·0%) receiving ustekinumab (ustekinumab-adjusted difference 33·5% [22·7-44·3]; p<0·0001 vs placebo and ustekinumab). At week 16 of UltIMMa-2, PASI 90 was achieved by 220 (74·8%) patients receiving risankizumab versus two (2·0%) receiving placebo (placebo-adjusted difference 72·5% [95% CI 66·8-78·2]) and 47 (47·5%) receiving ustekinumab (ustekinumab-adjusted difference 27·6% [16·7-38·5]; p<0·0001 vs placebo and ustekinumab). In UltIMMa-1, sPGA 0 or 1 at week 16 was achieved by 267 (87·8%) patients receiving risankizumab versus eight (7·8%) receiving placebo (placebo-adjusted difference 79·9% [95% CI 73·5-86·3]) and 63 (63·0%) receiving ustekinumab (ustekinumab-adjusted difference 25·1% [15·2-35·0]; p<0·0001 vs placebo and ustekinumab). In UltIMMa-2, 246 (83·7%) patients receiving risankizumab versus five (5·1%) receiving placebo (placebo-adjusted difference 78·5% [95% CI 72·4-84·5]) and 61 (61·6%) receiving ustekinumab achieved sPGA 0 or 1 at week 16 (ustekinumab-adjusted difference 22·3% [12·0-32·5]; p<0·0001 vs placebo and ustekinumab). The frequency of treatment-emergent adverse events in UltIMMa-1 and UltIMMa-2 was similar across risankizumab (part A: 151 [49·7%] of 304 and 134 [45·6%] of 294; part B: 182 [61·3%] of 297 and 162 [55·7%] of 291), placebo (part A: 52 [51·0%] of 102 and 45 [45·9%] of 98), ustekinumab (part A: 50 [50·0%] of 100 and 53 [53·5%] of 99; part B: 66 [66·7%] of 99 and 70 [74·5%] of 94), and placebo to risankizumab (part B: 65 [67·0%] of 97 and 61 [64·9%] of 94) treatment groups throughout the study duration. INTERPRETATION: Risankizumab showed superior efficacy to both placebo and ustekinumab in the treatment of moderate-to-severe plaque psoriasis. Treatment-emergent adverse event profiles were similar across treatment groups and there were no unexpected safety findings. FUNDING: AbbVie and Boehringer Ingelheim.

13 Clinical Trial Psoriasis patients with psoriasis Area and Severity Index (PASI) 90 response achieve greater health-related quality-of-life improvements than those with PASI 75-89 response: results from two phase 3 studies of secukinumab. 2017

Elewski, Boni E / Puig, Lluís / Mordin, Margaret / Gilloteau, Isabelle / Sherif, Bintu / Fox, Todd / Gnanasakthy, Ari / Papavassilis, Charis / Strober, Bruce E. ·a University of Alabama at Birmingham , Birmingham , AL , USA. · b Department of Dermatology , Hospital de la Sanat Creu i Sant Pau , Barcelona , Spain. · c RTI Health Solutions , Ann Arbor , MI , USA. · d Novartis Pharma AG , Basel , Switzerland. · e RTI Health Solutions , Research Triangle Park , NC , USA. · f University of Connecticut Health Center , Farmington , CT , USA. · g Probity Medical Research , Waterloo , Canada. ·J Dermatolog Treat · Pubmed #28266243.

ABSTRACT: BACKGROUND: The emergence of new biological therapies showing high and sustained level of Psoriasis Area and Severity Index (PASI) 90 response has provided the possibility of both greater skin clearance and increased quality of life (QOL). OBJECTIVE: To evaluate the association of greater response in skin clearance with improvements in skin-related QOL up to 52 weeks. METHODS: Subjects achieving various levels of skin clearance (PASI 90-100 or PASI 75-89) and Dermatology Life Quality Index (DLQI) (0/1) response were compared using ERASURE and FIXTURE trial data. Similar analyses with IGA ratings of Clear or Almost Clear were performed. RESULTS: Significantly more PASI 90-100 responders at week 12 had DLQI 0/1 response than PASI 75-89 (69.4% vs. 47.1%; p < .001) and sustained DLQI 0/1 response at week 52 (74.0% vs. 56.7%; p < .001). IGA results were similar. CONCLUSIONS: These results show that PASI 90-100 is a relevant therapeutic goal in moderate to severe psoriasis compared to PASI 75-89 when considering patients' QOL.

14 Clinical Trial Ustekinumab Treatment and Improvement of Physical Function and Health-Related Quality of Life in Patients With Psoriatic Arthritis. 2016

Rahman, Proton / Puig, Lluis / Gottlieb, Alice B / Kavanaugh, Arthur / McInnes, Iain B / Ritchlin, Christopher / Li, Shu / Wang, Yuhua / Song, Michael / Mendelsohn, Alan / Han, Chenglong / Anonymous70877. ·Memorial University, Newfoundland, Canada. · Hospital de la Santa Creu i Sant Pau, Universitat Autònoa de Barcelona, Barcelona, Spain. · Tufts University School of Medicine, Boston, Massachusetts. · University of California, San Diego. · University of Glasgow, Glasgow, Scotland. · University of Rochester, Rochester, New York. · Janssen Research & Development, LLC, Spring House, Pennsylvania. · Janssen Global Services, LLC, Malvern, Pennsylvania. ·Arthritis Care Res (Hoboken) · Pubmed #27483458.

ABSTRACT: OBJECTIVE: To examine the effects of ustekinumab on patient-reported outcomes (PROs) in PSUMMIT 1 and PSUMMIT 2 patients with active psoriatic arthritis (PsA) who were methotrexate (MTX) naive, MTX experienced, or anti-tumor necrosis factor (TNF) experienced. METHODS: Patients in the phase 3, PSUMMIT 1 (n = 615) and PSUMMIT 2 (n = 312) studies randomly (1:1:1) received placebo, ustekinumab 45-mg, or ustekinumab 90-mg subcutaneous injections at weeks 0, 4, 16, 28, 40, and 52. The PROs (Health Assessment Questionnaire [HAQ] disability index [DI], Dermatology Life Quality Index [DLQI], 36-Item Short Form [SF-36] health survey physical (PCS) and mental component summary scores, patient assessments of pain and disease activity, and impact of disease on productivity) were assessed at weeks 0, 24, and 52. In these post hoc analyses, outcomes were compared between the ustekinumab and placebo groups for 3 mutually exclusive antecedent-exposure populations from the combined studies: MTX/anti-TNF naive (placebo, n = 56; 45 mg, n = 58; and 90 mg, n = 66), MTX experienced, biologic agent naive (placebo, n = 192; 45 mg, n = 190; and 90 mg, n = 185), and anti-TNF experienced with or without MTX (placebo, n = 62; 45 mg, n = 60; and 90 mg, n = 58). RESULTS: At week 24, mean improvements from baseline in HAQ DI, DLQI, and SF-36 PCS scores were significantly greater in both ustekinumab groups versus placebo across antecedent-exposure groups. Greater proportions of ustekinumab-treated than placebo-treated patients (all P < 0.05) had clinically meaningful improvements in HAQ DI (≥0.3), DLQI (≥5), and SF-36 (≥5) scores at week 24, irrespective of drug exposure. Improvements in pain, disease activity, and impact of disease on productivity were similar, and benefits were maintained through week 52. CONCLUSION: Significant improvements in PROs with ustekinumab versus placebo were observed in 3 antecedent-exposure populations of PsA patients, including those with prior MTX and anti-TNF use.

15 Clinical Trial Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (PSUMMIT-1/PSUMMIT-2). 2016

Kavanaugh, Arthur / Puig, Lluis / Gottlieb, Alice B / Ritchlin, Christopher / You, Yin / Li, Shu / Song, Michael / Randazzo, Bruce / Rahman, Proton / McInnes, Iain B. ·Division of Rheumatology, Allergy, and Immunology, University of California-San Diego, La Jolla, California, USA. · Department of Dermatology, Hospital de la Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain. · Department of Dermatology, Tufts Medical Center, Boston, Massachusetts, USA. · Department of Dermatology, University of Rochester, Rochester, New York, USA. · Department of Biostatistics, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA. · Department of Immunology, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA. · Department of Immunology, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Department of Dermatology, Memorial University, St. Johns, Newfoundland, Canada. · College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. ·Ann Rheum Dis · Pubmed #27098404.

ABSTRACT: OBJECTIVE: To evaluate ustekinumab efficacy and safety in psoriatic arthritis (PsA) patients with peripheral arthritis and physician-reported spondylitis (termed the 'spondylitis subset'). METHODS: Adults with active PsA (PSUMMIT-1/PSUMMIT-2, n=615/312) were randomised to ustekinumab 45 mg, 90 mg or placebo at week 0/week 4/q12 week. At week 16, patients with <5% improvement in tender and swollen joints entered blinded early escape. A subset of patients with physician-identified spondylitis was evaluated with spondylitis-specific assessments, including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score employing C reactive protein (ASDAS-CRP), through week 24. RESULTS: 256/927 (27.6%) PSUMMIT-1/PSUMMIT-2 patients (placebo/ustekinumab, n=92/164) comprised the evaluable spondylitis subset. At week 24, in this analysis subset, significantly more patients achieved BASDAI20/50/70 responses (54.8%/29.3%/15.3% vs 32.9%/11.4%/0%; p≤0.002), improvement in BASDAI question 2 concerning axial pain (1.85 vs 0.24; p<0.001) and mean per cent ASDAS-CRP improvements (27.8% vs 3.9%; p<0.001) for ustekinumab versus placebo recipients, respectively. Comparable to the overall study population, significant improvements were also achieved in psoriasis, peripheral arthritis, enthesitis, dactylitis, physical function and peripheral joint radiographs in the spondylitis subset. CONCLUSIONS: In this post-hoc analysis of PsA patients with baseline peripheral arthritis and physician-reported spondylitis, ustekinumab-treated patients demonstrated significant improvements in axial signs and symptoms through week 24. TRIAL REGISTRATION NUMBER: PSUMMIT-1 (NCT01009086, EudraCT 2009-012264-14) and PSUMMIT-2 (NCT01077362, EudraCT 2009-012265-60); post-study results.

16 Clinical Trial Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis. 2015

Lebwohl, Mark / Strober, Bruce / Menter, Alan / Gordon, Kenneth / Weglowska, Jolanta / Puig, Lluis / Papp, Kim / Spelman, Lynda / Toth, Darryl / Kerdel, Francisco / Armstrong, April W / Stingl, Georg / Kimball, Alexa B / Bachelez, Herve / Wu, Jashin J / Crowley, Jeffrey / Langley, Richard G / Blicharski, Tomasz / Paul, Carle / Lacour, Jean-Philippe / Tyring, Stephen / Kircik, Leon / Chimenti, Sergio / Callis Duffin, Kristina / Bagel, Jerry / Koo, John / Aras, Gary / Li, Joanne / Song, Wenjie / Milmont, Cassandra E / Shi, Yifei / Erondu, Ngozi / Klekotka, Paul / Kotzin, Brian / Nirula, Ajay. ·From the Icahn School of Medicine at Mount Sinai, New York (M.L., L.K.) · University of Connecticut School of Medicine, Farmington (B.S.) · Probity Medical Research (B.S., L.S., D.T.) and XLR8 Medical Research (D.T.), Windsor, ON, K Papp Medical Research (K.P.), Waterloo, ON, and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada · Baylor University Medical Center, Dallas (A.M.) · Northwestern University, Feinberg School of Medicine, Chicago (K.G.) · Niepubliczny Zakład Opieki Zdrowotnej multiMedica, Wrocław (J.W.), and Lubelskie Centrum Diagnostyczne, Świdnik (T.B.) - both in Poland · Hospital de la Santa Creu i Sant Pau, Barcelona (L.P.) · Veracity Clinical Research, Woolloongabba, QLD, Australia (L.S.) · Florida Academic Dermatology Center, Miami (F.K.) · University of Colorado, Denver (A.W.A.) · Medizinische Universität Wien, Vienna, Austria (G.S.) · Massachusetts General Hospital and Harvard Medical School, Boston (A.B.K.) · Sorbonne Paris Cité Université Paris Diderot, Assistance Publique-Hôpitaux de Paris Hôpital Saint Louis, Paris (H.B.), Paul Sabatier University, Toulouse (C.P.), and University Hospital of Nice, Nice (J.-P.L.) - all in France · Kaiser Permanente Los Angeles Medical Center, Los Angeles (J.J.W.), Bakersfield Dermatology and Skin Cancer Medical Group, Bakersfield (J.C.), University of California, San Francisco, San Francisco (J.K.), and Amgen, Thousand Oaks (G.A., J.L., W.S., C.E.M., Y.S., N.E., P.K., B.K., A.N.) - all in California. · University of Texas Health Science Center, Houston (S.T.) · DermResearch, Louisville, KY (L.K.) · University of Rome Tor Vergata, Rome (S.C.) · University of Utah Medical Center, Salt Lake City (K.C.D.) · and the Psoriasis Treatment Center of Central New Jersey, East Windsor (J.B.). ·N Engl J Med · Pubmed #26422722.

ABSTRACT: 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 physician's 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.).

17 Clinical Trial Maintenance of Clinical Efficacy and Radiographic Benefit Through Two Years of Ustekinumab Therapy in Patients With Active Psoriatic Arthritis: Results From a Randomized, Placebo-Controlled Phase III Trial. 2015

Kavanaugh, Arthur / Puig, Lluís / Gottlieb, Alice B / Ritchlin, Christopher / Li, Shu / Wang, Yuhua / Mendelsohn, Alan M / Song, Michael / Zhu, Yaowei / Rahman, Proton / McInnes, Iain B / Anonymous350834. ·University of California, San Diego, La Jolla, California. · Universitat Autònoma de Barcelona, Barcelona, Spain. · Tufts Medical Center, Boston, Massachusetts. · University of Rochester, Rochester, New York. · Janssen Research & Development, Spring House, Pennsylvania. · Memorial University, St. John's, Newfoundland and Labrador, Canada. · University of Glasgow, Glasgow, Scotland. ·Arthritis Care Res (Hoboken) · Pubmed #26097039.

ABSTRACT: OBJECTIVE: To evaluate the efficacy and safety of ustekinumab through 2 years in adult patients with active psoriatic arthritis (PsA). METHODS: A total of 615 adult patients with active PsA were randomized to placebo, ustekinumab 45 mg, or ustekinumab 90 mg, at weeks 0, 4, and every 12 weeks through week 88 (last dose). At week 16, patients with <5% improvement in both tender and swollen joint counts entered blinded early escape (placebo to 45 mg, 45 mg to 90 mg, and 90 mg to 90 mg). All remaining placebo patients crossed over to ustekinumab 45 mg at week 24. Clinical efficacy measures included American College of Rheumatology criteria for 20% improvement (ACR20), Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP), and ≥75% improvement in the Psoriasis Area and Severity Index (PASI75). Radiographic progression was evaluated using the modified Sharp/van der Heijde score (SHS). RESULTS: At week 100, ACR20, DAS28-CRP moderate/good response, and PASI75 rates ranged from 56.7-63.6%, 71.9-76.7%, and 63.9-72.5%, respectively, across the 3 treatment groups. In both ustekinumab groups, the median percent improvement in dactylitis and enthesitis was 100% at week 100. The mean changes in SHS score from week 52 to week 100 were similar to those observed from week 0 to week 52 in the ustekinumab groups. Through week 108, 70.7% and 9.7% of patients had an adverse event (AE) or serious AE, respectively. The rates and type of AEs were similar between the dose groups. CONCLUSION: Clinical and radiographic benefits from ustekinumab treatment were maintained through week 100 in the PSUMMIT 1 study. No unexpected safety events were observed; the safety profile of ustekinumab in this population was similar to that previously observed in psoriasis patients treated with ustekinumab.

18 Clinical Trial Secukinumab in plaque psoriasis--results of two phase 3 trials. 2014

Langley, Richard G / Elewski, Boni E / Lebwohl, Mark / Reich, Kristian / Griffiths, Christopher E M / Papp, Kim / Puig, Lluís / Nakagawa, Hidemi / Spelman, Lynda / Sigurgeirsson, Bárður / Rivas, Enrique / Tsai, Tsen-Fang / Wasel, Norman / Tyring, Stephen / Salko, Thomas / Hampele, Isabelle / Notter, Marianne / Karpov, Alexander / Helou, Silvia / Papavassilis, Charis / Anonymous6380799 / Anonymous6390799. ·From Dalhousie University, Halifax, NS (R.G.L.), Clinical Research (K.P.) and Probity Medical Research (K.P., L.S.), Waterloo, ON, and Stratica Medical and Probity Medical Research, Edmonton, AB (N.W.) - all in Canada · University of Alabama, Birmingham (B.E.E.) · Mount Sinai Hospital, New York (M.L.) · Dermatologikum Hamburg and Georg-August-Universität, Göttingen, Germany (K.R.) · Dermatology Centre, Salford Royal Hospital, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom (C.E.M.G.) · Hospital de Sant Pau, Barcelona (L.P.) · Jikei University School of Medicine, Tokyo (H.N.) · Veracity Clinical Research, Woolloongabba, QLD, Australia (L.S.) · Faculty of Medicine, Department of Dermatology, University of Iceland, Reykjavik (B.S.) · Dermos, Guatemala City, Guatemala (E.R.) · Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei (T.-F.T.) · University of Texas Health Science Center and Center for Clinical Studies, Houston (S.T.) · and Novartis Pharma, Basel, Switzerland (T.S., I.H., M.N., A.K., S.H., C.P.). ·N Engl J Med · Pubmed #25007392.

ABSTRACT: BACKGROUND: Interleukin-17A is considered to be central to the pathogenesis of psoriasis. We evaluated secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. METHODS: In two phase 3, double-blind, 52-week trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), we randomly assigned 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) to subcutaneous secukinumab at a dose of 300 mg or 150 mg (administered once weekly for 5 weeks, then every 4 weeks), placebo, or (in the FIXTURE study only) etanercept at a dose of 50 mg (administered twice weekly for 12 weeks, then once weekly). The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (coprimary end points). RESULTS: The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300 mg of secukinumab, 71.6% with 150 mg of secukinumab, and 4.5% with placebo; in the FIXTURE study, the rates were 77.1% with 300 mg of secukinumab, 67.0% with 150 mg of secukinumab, 44.0% with etanercept, and 4.9% with placebo (P<0.001 for each secukinumab dose vs. comparators). The proportion of patients with a response of 0 or 1 on the modified investigator's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 65.3% with 300 mg of secukinumab, 51.2% with 150 mg of secukinumab, and 2.4% with placebo; in the FIXTURE study, the rates were 62.5% with 300 mg of secukinumab, 51.1% with 150 mg of secukinumab, 27.2% with etanercept, and 2.8% with placebo (P<0.001 for each secukinumab dose vs. comparators). The rates of infection were higher with secukinumab than with placebo in both studies and were similar to those with etanercept. CONCLUSIONS: Secukinumab was effective for psoriasis in two randomized trials, validating interleukin-17A as a therapeutic target. (Funded by Novartis Pharmaceuticals; ERASURE and FIXTURE ClinicalTrials.gov numbers, NCT01365455 and NCT01358578, respectively.).

19 Clinical Trial Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials. 2014

Kavanaugh, Arthur / Ritchlin, Christopher / Rahman, Proton / Puig, Lluis / Gottlieb, Alice B / Li, Shu / Wang, Yuhua / Noonan, Lenore / Brodmerkel, Carrie / Song, Michael / Mendelsohn, Alan M / McInnes, Iain B / Anonymous9310785. ·Rheumatology Allergy and Immunology Division, University of California-San Diego, , La Jolla, California, USA. ·Ann Rheum Dis · Pubmed #24553909.

ABSTRACT: OBJECTIVE: Evaluate ustekinumab, an anti-interleukin (IL)-12 and IL-23 antibody, effects on radiographic progression in psoriatic arthritis (PsA). METHODS: We conducted preplanned integrated analyses of combined radiographic data from PSUMMIT-1 and PSUMMIT-2 phase 3, randomised, controlled trials. Patients had active PsA despite prior conventional and/or biologic disease-modifying antirheumatic drugs (≥5/66 swollen, ≥5/68 tender joints, C-reactive protein ≥3.0 mg/L, documented plaque psoriasis). Patients (PSUMMIT-1, n=615; PSUMMIT-2, n=312) were randomised to ustekinumab 45 mg, 90 mg, or placebo, at weeks (wk) 0, 4 and every (q) 12 wks. At wk 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape. All other placebo patients received ustekinumab 45 mg at wk 24 and wk 28, then q 12 wks. Radiographs of hands/feet at wks 0/24/52 were assessed using PsA-modified van der Heijde-Sharp (vdH-S) scores; combined PSUMMIT-1 and PSUMMIT-2 changes in total vdH-S scores from wk 0 to wk 24 comprised the prespecified primary radiographic analysis. Treatment effects were assessed using analysis of variance on van der Waerden normal scores (factors=treatment, baseline methotrexate usage, and study). RESULTS: Integrated data analysis results indicated that ustekinumab-treated patients (regardless of dose) demonstrated significantly less radiographic progression at wk 24 than did placebo recipients (wk 0-24 total vdH-S score mean changes: 0.4-combined/individual ustekinumab dose groups, 1.0-placebo; all p<0.02). From wk 24 to wk 52, inhibition of radiographic progression was maintained for ustekinumab-treated patients, and progression was substantially reduced among initial placebo recipients who started ustekinumab at wk 16 or wk 24 (wk 24 - wk 52, total vdH-S score mean change: 0.08). CONCLUSIONS: Ustekinumab 45 and 90 mg treatments significantly inhibited radiographic progression of joint damage in patients with active PsA.

20 Clinical Trial Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial. 2014

Ritchlin, Christopher / Rahman, Proton / Kavanaugh, Arthur / McInnes, Iain B / Puig, Lluis / Li, Shu / Wang, Yuhua / Shen, Yaung-Kaung / Doyle, Mittie K / Mendelsohn, Alan M / Gottlieb, Alice B / Anonymous3430783. ·Allergy, Immunology & Rheumatology Division, University of Rochester Medical Center, , Rochester, New York, USA. ·Ann Rheum Dis · Pubmed #24482301.

ABSTRACT: OBJECTIVE: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. METHODS: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. RESULTS: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change -0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change -0.13). No unexpected adverse events were observed through week 60. CONCLUSIONS: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients.

21 Clinical Trial Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. 2013

McInnes, Iain B / Kavanaugh, Arthur / Gottlieb, Alice B / Puig, Lluís / Rahman, Proton / Ritchlin, Christopher / Brodmerkel, Carrie / Li, Shu / Wang, Yuhua / Mendelsohn, Alan M / Doyle, Mittie K / Anonymous2900761. ·Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK. iain.mcinnes@glasgow.ac.uk ·Lancet · Pubmed #23769296.

ABSTRACT: BACKGROUND: Many patients with psoriasis develop psoriatic arthritis, a chronic inflammatory disease that afflicts peripheral synovial, axial, and entheseal structures. The fully human monoclonal antibody ustekinumab is an efficacious treatment for moderate-to-severe plaque psoriasis. We did a randomised, placebo-controlled, phase 3 trial to assess the safety and efficacy of ustekinumab in patients with active psoriatic arthritis. METHODS: In this phase 3, multicentre, double-blind, placebo-controlled trial at 104 sites in Europe, North America, and Asia-Pacific, adults with active psoriatic arthritis (≥5 tender and ≥5 swollen joints, C-reactive protein ≥3·0 mg/L) were randomly assigned (1:1:1, by dynamic central randomisation based on an algorithm implemented by an interactive voice-web response system) to 45 mg ustekinumab, 90 mg ustekinumab, or placebo at week 0, week 4, and every 12 weeks thereafter. At week 16, patients with less than 5% improvement in both tender and swollen joint counts entered masked early-escape and were given 45 mg ustekinumab (if in the placebo group) or 90 mg ustekinumab (if in the 45 mg group). At week 24, all remaining patients in the placebo group received ustekinumab 45 mg, which they continued at week 28 and every 12 weeks thereafter. Our primary endpoint was 20% or greater improvement in American College of Rheumatology (ACR20) criteria at week 24. This trial is registered with ClinicalTrials.gov (NCT01009086) and EudraCT (2009-012264-14). FINDINGS: Between Nov 30, 2009, and March 30, 2011, 615 patients were randomly assigned-206 to placebo, 205 to 45 mg ustekinumab, and 204 to 90 mg ustekinumab. More ustekinumab-treated (87 of 205 [42·4%] in the 45 mg group and 101 of 204 [49·5%] in the 90 mg group) than placebo-treated (47 of 206 [22·8%]) patients achieved ACR20 at week 24 (p<0·0001 for both comparisons); responses were maintained at week 52. At week 16, proportions of patients with adverse events were similar in the ustekinumab and placebo groups (171 of 409 [41·8%] vs 86 of 205 [42·0%]). INTERPRETATION: Ustekinumab significantly improved active psoriatic arthritis compared with placebo, and might offer an alternative therapeutic mechanism of action to approved biological treatments. FUNDING: Janssen Research & Development.

22 Clinical Trial Influence of psoriatic arthritis on the efficacy of adalimumab and on the treatment response of other markers of psoriasis burden: subanalysis of the BELIEVE study. 2012

Paul, Carle / van de Kerkhof, Peter / Puig, Lluis / Unnebrink, Kristina / Goldblum, Orin / Thaçi, Diamant. ·Paul Sabatier University and Larrey Hospital, 24 Chemin de Pouvourville, 31000 Toulouse, France. paul.c@chu-toulouse ·Eur J Dermatol · Pubmed #23178916.

ABSTRACT: BACKGROUND: Adalimumab is a fully human anti-TNF monoclonal antibody with demonstrated efficacy and safety in patients with moderate to severe psoriasis and psoriatic arthritis (PsA). OBJECTIVE: This study examined the effect of PsA on adalimumab treatment response in patients from the Phase IIIb BELIEVE trial (NCT00574249, ClinicalTrials.gov registry), and response of other markers of disease burden to adalimumab treatment. METHODS: In this post hoc analysis, patients with or without a history of PsA and with moderate to severe psoriasis were randomized to adalimumab plus adjunctive topical therapy (calcipotriol/betamethasone dipropionate) or monotherapy (adalimumab plus matching topical vehicle). RESULTS: Regardless of baseline PsA, improvement at Week 16 was seen in PASI 75, pruritus, PSSI, and DLQI (all patients), and mean NAPSI scores. Patients with PsA had HAQ improvement at Week 16, and compared to patients without PsA, had higher VAS pain scores. This analysis represents the first publication of the influence of PsA and PsA plus body weight on patient response to adalimumab, and response of scalp psoriasis, nail psoriasis, and patient-reported outcomes to adalimumab. The incidence of AEs was similar among all patients (62%), those with PsA (65%) and without PsA (60%). The most common AEs were infections (27%); 4.2% of all patients reported serious AEs. CONCLUSION: Adalimumab treatment resulted in comprehensive, clinically relevant improvements from baseline PsA status, in skin, nails, quality of life, pain and pruritus. Despite having more severely affected disease and quality of life, patients with PsA did not respond to adalimumab significantly differently from patients without PsA.

23 Clinical Trial Validation of a new tool to assess health-related quality of life in psoriasis: the PSO-LIFE questionnaire. 2012

Dauden, Esteban / Herrera, Enrique / Puig, Lluis / Sánchez-Carazo, José Luis / Toribio, Jaime / Caloto, Ma Teresa / Nocea, Gonzalo / Roset, Montse / Lara, Nuria. ·Outcomes Research, MSD, Madrid, Spain. ·Health Qual Life Outcomes · Pubmed #22624984.

ABSTRACT: BACKGROUND: Several questionnaires have been used to measure health related quality of life (HRQoL) in patients with psoriasis, few have been adapted for use in Spain; none of them was developed specifically for the Spanish population. The purpose of the study was to validate and assess the sensitivity to change of a new questionnaire to measure HRQOL in patients with psoriasis (PSO-LIFE). METHODS: Observational, prospective, multicenter study performed in centers around Spain. Patients with active or inactive psoriasis completed the PSO-LIFE together with other Dermatology Quality of Life Index (DLQI) and Psoriasis Disability Index (PDI). A control group of patients with urticaria or atopic dermatitis was also included. Internal consistency and test-retest reliability of the PSO-LIFE were assessed by calculating Cronbach's alpha and Intraclass Correlation Coefficient (ICC). Validity was assessed by examining factorial structure, the capacity to discriminate between groups, and correlations with other measures. Sensitivity to change was measured using effect sizes. RESULTS: The final sample included for analysis consisted of 304 patients and 56 controls. Mean (SD) age of psoriasis patients was 45.3 (14.5) years compared to 38.8 (14) years for controls (p < 0.01). Cronbach's alpha for the PSO-LIFE was 0.95 and test-retest reliability using the ICC was 0.98. Factor analysis showed the questionnaire to be unidimensional. Mean (SD) PSO-LIFE scores differed between patients with psoriasis and controls (64.9 [22.5] vs 69.4 [17.3]; p < 0.05), between those with active and inactive disease (57.4 [20.4] vs 76.4 [20.6]; p < 0.01), and between those with visible and non-visible lesions (63.0 [21.9] vs. 74.8 [23.9]; p < 0.01). The correlation between PSO-LIFE and PASI scores was moderate (r = -0.43) while correlations with DLQI and PDI dimensions ranged from moderate to high (between 0.4 and 0.8). Effect size on the PSO-LIFE in patients reporting 'much improved' health status at study completion was 1.01 (large effect size). CONCLUSIONS: The present results provide substantial support for the reliability, validity, and responsiveness of the PSO-LIFE questionnaire in the population for which it was designed.

24 Article Paradoxical Reactions: Anti-Tumor Necrosis Factor Alpha Agents, Ustekinumab, Secukinumab, Ixekizumab, and Others. 2018

Puig, Lluís. ·Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. ·Curr Probl Dermatol · Pubmed #29131037.

ABSTRACT: Paradoxical reactions during treatment with a biologic agent can be defined as the appearance or exacerbation of a pathological condition that usually responds to this class of drug while treating a patient for another condition, which usually remains under control (even though there may be a change in morphology or phenotype). Paradoxical reactions were initially described as isolated case reports or case series in patients treated with anti-tumor necrosis factor (TNF) α agents, first in inflammatory rheumatic diseases, later in psoriasis and inflammatory bowel disease. Paradoxical reactions have subsequently been reported with other biological drugs or classes (e.g., tocilizumab), even though in some cases insufficient efficacy or phenotype switch may be difficult to differentiate from true paradoxical reactions. This chapter will deal with the most frequently reported variants of paradoxical reactions: palmoplantar pustular and psoriasiform reactions, psoriatic arthritis, hidradenitis, inflammatory bowel disease, uveitis, pyoderma gangrenosum, granulomatous reactions, and vasculitis. The underlying pathomechanism in these complex diseases with involvement of multiple immunological pathways is most likely a cytokine imbalance, and substitution of the anti-TNFα agent by an alternative anti-p40 or anti-IL-17A biologic may be extremely helpful. Paradoxical reactions can cause serious handicap, and early recognition and treatment of these drug class effects is of paramount importance, especially when the primary disease is relatively devoid of therapeutic alternatives and its reactivation may have catastrophic consequences. Close surveillance of patients treated with newly available biologic drugs is necessary to detect and describe new paradoxical reactions.

25 Article Effect of secukinumab on quality of life and psoriasis-related symptoms: A comparative analysis versus ustekinumab from the CLEAR 52-week study. 2018

Puig, Lluís / Augustin, Matthias / Blauvelt, Andrew / Gottlieb, Alice B / Vender, Ron / Korman, Neil J / Thaçi, Diamant / Zhao, Yang / Gilloteau, Isabelle / Sherif, Bintu / Williams, Nicole / Guana, Adriana / Lebwohl, Mark G. ·Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. · Institute for Health Services Research in Dermatology and Nursing University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Oregon Medical Research Center, Portland, Oregon. · New York Medical College at Metropolitan Hospital, New York, New York. · Dermatrials Research Inc., Hamilton, Ontario, Canada. · University Hospitals Cleveland Medical Center, Cleveland, Ohio. · Comprehensive Center for Inflammation Medicine, University Hospital Schleswig-Holstein, Lübeck, Germany. · formerly with Novartis Pharmaceuticals Corporation, East Hanover, New Jersey. · Novartis Pharma AG, Basel, Switzerland. · RTI Health Solutions, Research Triangle Park, North Carolina. Electronic address: bsherif@rti.org. · RTI Health Solutions, Research Triangle Park, North Carolina. · Icahn School of Medicine at Mount Sinai, New York, New York. ·J Am Acad Dermatol · Pubmed #29066271.

ABSTRACT: BACKGROUND: Secukinumab has demonstrated greater sustained skin clearance than ustekinumab through week 52, greater improvement in symptoms and health-related quality of life, and comparable safety profile. OBJECTIVE: To assess the impact of secukinumab versus that of ustekinumab on complete relief from psoriasis-related symptoms, time to response in terms of health-related quality of life, and cumulative benefit among patients with moderate-to-severe plaque psoriasis. METHODS: Psoriasis-related pain, itching, and scaling and the Dermatology Life Quality Index (DLQI) score were compared between treatments on the basis of time to complete relief of symptoms and time to DLQI response in the CLEAR trial. Cumulative benefit over 52 weeks based on Psoriasis Area and Severity Index score, symptom relief, and DLQI response were evaluated by area under the curve analysis. RESULTS: Significantly more patients treated with secukinumab achieved complete relief of pain at weeks 16 and 52 (all P < .05). Complete relief of itching and scaling occurred significantly faster with secukinumab (median, 4 weeks faster for itching and 8 weeks faster for scaling [P < .001]). Response as measured by the DLQI was 4 weeks faster with secukinumab (P < .0001). Cumulative benefits were greater with secukinumab (all P < .05). LIMITATIONS: Analyses were post hoc. CONCLUSION: This patient-reported outcome analysis confirms greater and sustained benefits of secukinumab versus those of ustekinumab treatment on patients' lives.

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