171 research outputs found
Tofacitinib in Patients With Psoriatic Arthritis and Metabolic Syndrome: A Post hoc Analysis of Phase 3 Studies
Objective:
Metabolic syndrome (MetS) is a cluster of concurrent risk factors for cardiovascular disease and type 2 diabetes. This post hoc analysis explored key efficacy and safety endpoints in patients with psoriatic arthritis (PsA) and MetS treated with tofacitinib.
Methods:
Tofacitinib 5 and 10 mg twice daily and placebo data were pooled from two Phase 3 studies (OPAL Broaden [12 months; ClinicalTrials.gov identifier NCT01877668]; OPAL Beyond [6 months; ClinicalTrials.gov identifier NCT01882439]); patients received one background conventional synthetic diseaseâmodifying antirheumatic drug. Patients were stratified by baseline presence/absence of MetS. Efficacy and safety were reported to month 3 (tofacitinib and placebo) and 6 (tofacitinib only). Efficacy outcomes included: American College of Rheumatology (ACR)20/50/70, Health Assessment QuestionnaireâDisability Index (HAQâDI) response, Psoriasis Area Severity Index (PASI)75 response, and enthesitis/dactylitis resolution rates; and changes from baseline (Î) in Câreactive protein, HAQâDI, Patientâs/Physicianâs Global Assessment of Arthritis, and patientâreported outcomes. Safety outcomes included treatmentâemergent allâcausality adverse events (AEs), Î in lipid/hepatic values, and liver parameter increases.
Results:
Of 710 patients, 41.4% (n = 294) had baseline MetS. All efficacy outcomes improved with both tofacitinib doses versus placebo, to month 3; tofacitinib efficacy was consistent to month 6, regardless of MetS status. MetS did not appear to affect the incidence of AEs or Î in lipid/hepatic values with tofacitinib up to month 3 or 6. Arterial thromboembolism and myocardial infarction (adjudicated major adverse cardiovascular events) were each reported once in tofacitinibâtreated patients with MetS.
Conclusion:
Regardless of baseline MetS status, tofacitinib showed greater efficacy versus placebo in patients with active PsA. The tofacitinib safety profile appeared similar in patients with versus without MetS
Etanercept and Methotrexate as Monotherapy or in Combination for Psoriatic Arthritis: Primary Results From a Randomized, Controlled Phase III Trial
Objective: To examine the efficacy of methotrexate monotherapy relative to etanercept monotherapy and the value of combining methotrexate and etanercept for the treatment of patients with psoriatic arthritis (PsA).
Methods: In this doubleâblind study, 851 patients with PsA were randomized to 1 of 3 treatment arms, as follows: oral methotrexate (20 mg) plus subcutaneous placebo given weekly (n = 284), subcutaneous etanercept (50 mg) plus oral placebo given weekly (n = 284), or subcutaneous etanercept (50 mg) plus oral methotrexate (20 mg) given weekly (combination therapy; n = 283). The American College of Rheumatology 20% improvement (ACR20) response and Minimal Disease Activity (MDA) response at week 24 were the primary end point and key secondary end point, respectively. Other measures of inflammatory arthritis, radiographic progression, and nonarticular disease manifestations were also assessed.
Results: Patients with PsA had a mean ± SD age of 48.4 ± 13.1 years, and the mean ± SD duration of PsA was 3.2 ± 6.3 years (median 0.6 years). ACR20 and MDA response rates at week 24 were significantly greater in patients who received etanercept monotherapy compared with those who received methotrexate monotherapy (ACR20, 60.9% versus 50.7% of patients [P = 0.029]; MDA, 35.9% versus 22.9% of patients [P = 0.005]), and both were significantly greater in the combination therapy group compared with the methotrexate monotherapy group at week 24 (ACR20, 65.0% versus 50.7% of patients [P = 0.005]; MDA, 35.7% versus 22.9% of patients [P = 0.005]). Other secondary outcomes (ACR50 and ACR70 response rates, proportions of patients achieving a Very Low Disease Activity score, and PsA disease activity scores) showed betweenâgroup differences that were consistent with the primary and key secondary end point results. Furthermore, patients in both etanercept treatment arms showed less radiographic progression at week 48 compared with patients who received methotrexate monotherapy. Outcomes were similar in the combination therapy and etanercept monotherapy groups, except for some skin end points. No new safety signals were seen.
Conclusion: Etanercept monotherapy and combination therapy with etanercept and methotrexate showed greater efficacy than methotrexate monotherapy in patients with PsA, according to the ACR and MDA response rates and extent of radiographic progression at followâup. Overall, combining methotrexate and etanercept did not improve the efficacy of etanercept
Bone mineral density and body composition in postmenopausal women with psoriasis and psoriatic arthritis
Introduction: the aim of the present study was to compare bone mineral density (BMD) and body composition (BC) measurements as well as identify risk factors for low BMD and osteoporotic fractures in postmenopausal women with psoriasis (Ps) and psoriatic arthritis (PsA).Methods: A cross-sectional study was carried out in 45 PsA women, 52 Ps women and 98 healthy female controls (HC). Clinical risk factors for low bone density and osteoporotic fracture were evaluated by a specific questionnaire. An X-ray absorptiometry (DXA) at the lumbar spine, total femur and total body was performed on all patients. Skin and joint outcomes were measured by specific tools (PASI, HAQ and DAS28). Morphometric vertebral fractures were evaluated by lumbar and thoracic spine X-ray, according to Genant's method.Results: There were no significant differences in age, body mass index (BMI), total lean mass and bone mineral density among the groups. However, the PsA group had a significantly higher body fat percentage (BF%) than the Ps and HC groups. Osteoporotic fractures were more frequently observed in PsA and Ps groups than in the HC group (P = 0.01). Recurrent falls and a longer duration of disease increased the risk of fracture (odds ratio (OR) = 18.3 and 1.08, respectively) in the PsA group (P = 0.02). Disability was the main factor related to osteoporotic fracture in the Ps group (odds ratio (OR) = 11.1) (P = 0.02).Conclusions: Ps and PsA patients did not present lower BMD. However, they had a higher prevalence of osteoporotic fractures and higher risk of metabolic syndrome. Patients with a longer duration of disease, disability and recurrent falls need preventive measures.Rheumatology Division at UNIFESP/EPMUniversidade Federal de SĂŁo Paulo, UNIFESP Paulista Sch Med, Div Rheumatol, EPM, BR-04023900 SĂŁo Paulo, BrazilUniversidade Federal de SĂŁo Paulo, UNIFESP Paulista Sch Med, Div Rheumatol, EPM, BR-04023900 SĂŁo Paulo, BrazilWeb of Scienc
GRAPPA 2019 Project Report
At the 2019 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members received updates on several ongoing efforts. Among them were updates on research, including the trainee symposium, pilot research grants, and the Collaborative Research Network; GRAPPAâs patient research partners; education, including the slide collection; treatment recommendations; and additional work related to advancing the understanding of disease aspects, including the Outcome Measures in Rheumatology (OMERACT)-GRAPPA outcome measure, axial involvement, and ultrasound enthesitis projects; as well as the early psoriatic disease systematic literature review and magnetic resonance imaging
A sonographic spectrum of psoriatic arthritis: âthe five targetsâ
Ultrasound is a rapidly evolving technique that is gaining an increasing success in the assessment of psoriatic arthritis. Most of the studies have been aimed at investigating its ability in the assessment of joints, tendons, and entheses in psoriatic arthritis patients. Less attention has been paid to demonstrate the potential of ultrasound in the evaluation of skin and nail. The aim of this pictorial essay was to show the main high-frequency grayscale and power Doppler ultrasound findings in patients with psoriatic arthritis at joint, tendon, enthesis, skin, and nail level
Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years
Ankylosing spondylitis (AS) is a chronic rheumatic disease associated with spinal inflammation that subsequently leads to progression of structural damage and loss of function. The fully human anti-tumor necrosis factor (anti-TNF) antibody adalimumab reduces the signs and symptoms and improves overall quality of life in patients with active AS; these benefits have been maintained through 2 years of treatment. Our objective was to compare the progression of structural damage in the spine in patients with AS treated with adalimumab for up to 2 years versus patients who had not received TNF antagonist therapy. Radiographs from patients with AS who received adalimumab 40 mg every other week subcutaneously were pooled from the Adalimumab Trial Evaluating Long-Term Efficacy and Safety for Ankylosing Spondylitis (ATLAS) study and a Canadian AS study (M03-606). Radiographic progression from baseline to 2 years in the spine of adalimumab-treated patients from these two studies (adalimumab cohort, n = 307) was compared with an historic anti-TNF-naĂŻve cohort (Outcome in AS International Study [OASIS], n = 169) using the modified Stoke AS Spine Score (mSASSS) method. mSASSS results were not significantly different between the adalimumab cohort and the OASIS cohort, based on baseline and 2-year radiographs. Mean changes in mSASSS from baseline to 2 years were 0.9 for the OASIS cohort and 0.8 for the adalimumab cohort (P = 0.771), indicating similar radiographic progression in both groups. When results for patients in the OASIS cohort who met the baseline disease activity criteria for the ATLAS and Canadian studies (OASIS-Eligible cohort) were analyzed, there was no significant difference in mean change in mSASSS from baseline to 2 years between OASIS-Eligible patients and adalimumab-treated patients; the mean changes in mSASSS were 0.9 for the OASIS-Eligible cohort and 0.8 for the adalimumab cohort (P = 0.744). Two years of treatment with adalimumab did not slow radiographic progression in patients with AS, as assessed by the mSASSS scoring system, when compared with radiographic data from patients naĂŻve to TNF antagonist therap
Assessing Disease Activity in Psoriatic Arthritis: A Literature Review
Psoriatic arthritis (PsA) is a multifaceted disease, with a high impact on patientsâ psychological and physical well-being. There is increasing recognition that assessment of both clinical aspects of disease and patient identified concerns, such as fatigue, work disability, and treatment satisfaction need to be addressed. Only then can we fully understand disease burden and make well-informed treatment decisions aimed at improving patientsâ lives. In recent years, there has been much progress in the development of unidimensional and composite measures of disease activity, as well as questionnaires capturing the patientâs perspective in psoriatic disease. Despite these advances, there remains disagreement amongst clinicians as to which instruments should be used. As a consequence, they are yet to receive widespread implementation in routine clinical practice. This review aims to summarize currently available clinical and patient-derived assessment tools, which will provide clinicians with a practical and informative resource
A Genome-Wide Association Study of Psoriasis and Psoriatic Arthritis Identifies New Disease Loci
A genome-wide association study was performed to identify genetic factors involved in susceptibility to psoriasis (PS) and psoriatic arthritis (PSA), inflammatory diseases of the skin and joints in humans. 223 PS cases (including 91 with PSA) were genotyped with 311,398 single nucleotide polymorphisms (SNPs), and results were compared with those from 519 Northern European controls. Replications were performed with an independent cohort of 577 PS cases and 737 controls from the U.S., and 576 PSA patients and 480 controls from the U.K.. Strongest associations were with the class I region of the major histocompatibility complex (MHC). The most highly associated SNP was rs10484554, which lies 34.7 kb upstream from HLA-C (Pâ=â7.8Ă10â11, GWA scan; Pâ=â1.8Ă10â30, replication; Pâ=â1.8Ă10â39, combined; U.K. PSA: Pâ=â6.9Ă10â11). However, rs2395029 encoding the G2V polymorphism within the class I gene HCP5 (combined Pâ=â2.13Ă10â26 in U.S. cases) yielded the highest ORs with both PS and PSA (4.1 and 3.2 respectively). This variant is associated with low viral set point following HIV infection and its effect is independent of rs10484554. We replicated the previously reported association with interleukin 23 receptor and interleukin 12B (IL12B) polymorphisms in PS and PSA cohorts (IL23R: rs11209026, U.S. PS, Pâ=â1.4Ă10â4; U.K. PSA: Pâ=â8.0Ă10â4; IL12B:rs6887695, U.S. PS, Pâ=â5Ă10â5 and U.K. PSA, Pâ=â1.3Ă10â3) and detected an independent association in the IL23R region with a SNP 4 kb upstream from IL12RB2 (Pâ=â0.001). Novel associations replicated in the U.S. PS cohort included the region harboring lipoma HMGIC fusion partner (LHFP) and conserved oligomeric golgi complex component 6 (COG6) genes on chromosome 13q13 (combined Pâ=â2Ă10â6 for rs7993214; ORâ=â0.71), the late cornified envelope gene cluster (LCE) from the Epidermal Differentiation Complex (PSORS4) (combined Pâ=â6.2Ă10â5 for rs6701216; OR 1.45) and a region of LD at 15q21 (combined Pâ=â2.9Ă10â5 for rs3803369; ORâ=â1.43). This region is of interest because it harbors ubiquitin-specific protease-8 whose processed pseudogene lies upstream from HLA-C. This region of 15q21 also harbors the gene for SPPL2A (signal peptide peptidase like 2a) which activates tumor necrosis factor alpha by cleavage, triggering the expression of IL12 in human dendritic cells. We also identified a novel PSA (and potentially PS) locus on chromosome 4q27. This region harbors the interleukin 2 (IL2) and interleukin 21 (IL21) genes and was recently shown to be associated with four autoimmune diseases (Celiac disease, Type 1 diabetes, Grave's disease and Rheumatoid Arthritis)
Systematic review, network meta-analysis and economic evaluation of biological therapy for the management of active psoriatic arthritis
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