Choosing the right treatment for patients with psoriatic arthritis.
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ABSTRACT:
SUBMITTER: Noviani M
PROVIDER: S-EPMC7576918 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Choosing the right treatment for patients with psoriatic arthritis.
Noviani Maria M Feletar Marie M Nash Peter P Leung Ying Ying YY
Therapeutic advances in musculoskeletal disease 20201013
Psoriatic arthritis (PsA) is a chronic inflammatory condition with articular and extra-articular manifestations: peripheral arthritis, axial disease, enthesitis, dactylitis, psoriasis, inflammatory bowel disease and uveitis. Anti-tumour necrosis factors (anti-TNFs) have demonstrated clinical efficacies exceeding those of conventional disease-modifying antirheumatic drugs (DMARDs). New understanding in pathogenic pathways have led to novel therapeutic targets. The current treatment paradigms emph ...[more]
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Project description:Psoriatic arthritis (PsA) is a chronic, systemic inflammatory disease. Up to 40 % of patients with psoriasis will go on to develop PsA, usually within 5-10 years of cutaneous disease onset. Both conditions share common pathogenic mechanisms involving genetic and environmental factors. Because psoriasis is typically present for years before PsA-related joint symptoms emerge, dermatologists are in a unique position to detect PsA earlier in the disease process through regular, routine screening of psoriasis patients. Distinguishing clinical features of PsA include co-occurrence of psoriatic skin lesions and nail dystrophy, as well as dactylitis and enthesitis. Patients with PsA are usually seronegative for rheumatoid factor, and radiographs may reveal unique features such as juxta-articular new bone formation and pencil-in-cup deformity. Early treatment of PsA with disease-modifying anti-rheumatic drugs has the potential to slow disease progression and maintain patient quality of life. Optimally, a single therapeutic agent will control both the skin and joint psoriatic symptoms. A number of traditional treatments used to manage psoriasis, such as methotrexate and cyclosporine, are also effective for PsA, but these agents are often inadequately effective, temporary in benefit and associated with significant safety concerns. Biologic anti-tumour necrosis factor agents, such as etanercept, infliximab and adalimumab, are effective for treating patients who have both psoriasis and PsA. However, a substantial number of patients may lose efficacy, have adverse effects or find intravenous or subcutaneous administration inconvenient. Emerging oral treatments, including phosphodiesterase 4 inhibitors, such as apremilast, and new biologics targeting interleukin-17, such as secukinumab, brodalumab and ixekizumab, have shown encouraging clinical results in the treatment of psoriasis and/or PsA. Active and regular collaboration of dermatologists with rheumatologists in managing patients who have psoriasis and PsA is likely to yield more optimal control of psoriatic dermal and joint symptoms, and improve long-term patient outcomes.
| S-EPMC3958815 | biostudies-literature
Project description:Psoriatic arthritis (PsA) is a variable and complex inflammatory condition. Symptoms can compromise physical function, reduce quality of life, and accrue significant health costs. Commonly used patient-reported outcomes largely reflect the professionals' perspective, however it is not known whether they capture what is important to patients.The aim of our study was to identify treatment outcomes important to patients with PsA.Eight focus groups that were audio recorded, transcribed, anonymised and analysed using inductive thematic analysis were conducted at five hospital sites. The full data set was analysed by the lead researcher, and subsets analysed by three team members (including patient partners).Overall, 41 patients sampled for a range of phenotypes and domains of disease activity participated in the study: 20 males; mean age 58 years (range 28-75, standard deviation [SD] 11.4); mean disease duration 9 years (range 0.5-39, SD 8.3); and mean Health Assessment Questionnaire score of 1 (range 0.0-2.5, SD 0.7). Over 60 outcomes were identified and grouped into four themes: (i) symptom alleviation (e.g. pain, fatigue, itchy skin, swelling, and reducing variability); (ii) reduction of disease impact (e.g. tiredness and pain, mobility and dexterity, deteriorating physical fitness, negative emotional responses, and strained relationships and social interactions); (iii) improved prognosis (e.g. slowing down disease progression, maintaining independence, and enhancing quality of life); and (iv) minimisation of treatment harm and burden (e.g. nausea, long-term effects, and administration and monitoring of treatments).Outcomes from treatments that are important to patients, which relate to impacts from PsA and its treatment that range beyond those outcomes commonly measured, were identified. These patient perspectives need to be considered when evaluating treatments.
| S-EPMC5534194 | biostudies-other
Project description:TNF-blocking agents, non-biological disease-modifying anti-rheumatic drugs (nbDMARDs) and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed treatments in psoriatic arthritis. A large proportion of patients do not respond to these medications, although unfortunately clinically useful biomarkers that predict future response are currently lacking. Several candidate gene polymorphisms have been associated with responses to biologic therapies and nbDMARDs; however, replication and validation of these variants in large prospective psoriatic arthritis cohorts are required before translating these to clinical practice. In this review, we discuss the advances made in pharmacogenetics of treatment response in psoriatic arthritis to date, with focus on biologic therapies approved for use, nbDMARDs and NSAIDs, as well as outline emerging methodologies to obtain data that will help inform a future precision medicine approach in this condition.
| S-EPMC4435910 | biostudies-literature
Project description:IntroductionRisk of herpes zoster (HZ) is increased with Janus kinase inhibitor use. We evaluated clinical study data relating to HZ management in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) receiving tofacitinib.MethodsThis post hoc analysis included data from 21 RA and 3 PsA clinical studies; data were pooled for tofacitinib doses. Outcomes of HZ events (serious and non-serious) and tofacitinib treatment changes were evaluated in response to first and second HZ events. Median time to resolution was stratified by dermatomal involvement, history of HZ prior to tofacitinib, changes to tofacitinib treatment, anti-viral and corticosteroid use, and tofacitinib dose.ResultsSeven hundred eighty-three (11.1%, N = 7061) patients with RA experienced ≥ 1 HZ event, 63 (8.0%) of whom had ≥ 2 HZ events. In patients with PsA, 36 (4.6%, N = 783) experienced ≥ 1 HZ event, 1 (2.8%) of whom had ≥ 2 HZ events. For most HZ events, tofacitinib treatment was unchanged or temporarily discontinued. The majority of patients received anti-viral treatment, most within 3 days of onset. Post-herpetic neuralgia developed in 6.9% and 3.2% of patients with RA with first and second events, respectively, and in 2.8% of patients with PsA with a first event. Most first and second events resolved (RA: 97.6% and 96.8%, respectively; PsA: 94.4% and 100%, respectively). Median time to resolution was 22.0 days for first and 15.0 days for second events for RA and 20.5 days for first and 11.0 days for second events (n = 1) for PsA. Time to resolution of first events for RA and PsA was generally numerically shorter for patients with single dermatomal HZ, history of HZ, or anti-viral use versus those without.ConclusionAmong patients receiving tofacitinib, recurrent events were more common in patients with RA versus PsA; HZ duration was shorter for repeat events.Trial registrationNCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT02147587, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02187055, NCT00413699, NCT00661661, NCT01877668, NCT01882439, NCT01976364.
| S-EPMC8814083 | biostudies-literature
Project description:This is a pilot single cell mRNA sequencing experiment to study immune cells in psoriatic arthritis.
| EGAS00001002104 | EGA
Project description:INTRODUCTION:We compared treatment switch patterns and healthcare costs among biologic-naive patients with psoriatic arthritis (PsA) who initiated apremilast or biologics. METHODS:A 1:2 propensity score match was used to adjust administrative claims data for adults initiating apremilast or biologics from January 1, 2014, to September 30, 2016, for possible selection bias. Patients had at least 12 months of pre- and post-index continuous enrollment in the Optum Clinformatics™ Data Mart database. Outcomes included switch frequency, days to switch, adherence on index treatment, and healthcare costs (total and per patient per month). Switch rate was defined as the proportion of patients who switched to a new treatment after initiation of the index treatment, and days to switch was calculated as the days between initiation of the index treatment and initiation of the new treatment. Adherence was calculated using the proportion of days covered and the medication possession ratio. The t test and chi-square, Kaplan-Meier, and Wilcoxon rank-sum tests were used to evaluate differences between the cohorts. RESULTS:Patient characteristics and switch rates were similar between the matched apremilast (n?=?170) and biologic (n?=?327) cohorts. After matching, patient characteristics were similar between the matched cohorts. The 12-month switch rates were similar for patients initiating apremilast versus those on biologics (17.7% vs. 25.1%, P?=?0.06). This trend was similar at 6 months (7.7% vs. 13.2%, P?=?0.07) and 18 months (24.4% vs. 29.3%, P?=?0.33). Regardless of treatment switching, 12-month total healthcare costs were lower with apremilast versus biologics (all: $28,423 vs. $41,178, P?<?0.0001; switched: $39,803 vs. $51,517, P?=?0.0040; did not switch: $25,984 vs. $37,717, P?<?0.0001). CONCLUSIONS:Biologic-naive patients with PsA who initiated apremilast had switch rates similar to biologic users and significantly lower healthcare costs, regardless of treatment switching.
| S-EPMC7467475 | biostudies-literature
Project description:IntroductionPsoriatic arthritis (PsA) is an immune-mediated chronic inflammatory arthropathy associated with impaired physical function and reduced quality of life. Biologic therapies that target tumor necrosis factor (anti-TNF) have significantly improved clinical outcomes. Partial, non- and transient responses remain common comprising significant unmet clinical need. New therapies with novel modes of action are urgently required.ObjectivesThe interleukin (IL)-17 pathway has recently been attributed a critical role in the pathogenesis of spondyloarthritides. Herein, we review data from clinical studies with secukinumab, a novel fully human IgG1κ anti-IL-17A monoclonal antibody (mAb), in patients with active PsA.ResultsAcross two pivotal phase 3 studies, secukinumab provided significant and sustained reductions in the signs and symptoms of PsA, inhibition of radiographic progression, and improved patient-reported outcomes and measures of quality of life. The primary efficacy endpoint, a ≥20% improvement from baseline according to the American College of Rheumatology 20 (ACR20) response at Week 24, was significantly higher in patients treated with secukinumab compared with placebo, with improvements sustained through at least 52 weeks. Clinical benefits were seen with secukinumab regardless of concomitant methotrexate treatment and in patients who were either anti-TNF-naïve or who were inadequate responders to anti-TNF therapy. Secukinumab was well-tolerated, with a safety profile consistent with that previously reported in psoriasis trials. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and headache.ConclusionSecukinumab offers an effective new addition to the available treatment options for PsA. Regulatory submissions have been filed worldwide, with the first approvals recently obtained in Japan and Europe. Future studies are required to define the optimal timing and strategic use of this novel treatment modality.FundingNovartis Pharma.
| S-EPMC4999581 | biostudies-literature
Project description:Since the second version of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations were published in 2015, therapeutic options for psoriatic arthritis (PsA) have advanced considerably. This work reviews the literature since the previous recommendations (data published 2013-2020, including conference presentations between 2017 and 2020) and reports high-quality, evidence-based, domain-focused recommendations for medication selection in PsA developed by GRAPPA clinicians and patient research partners. The overarching principles for the management of adults with PsA were updated by consensus. Principles considering biosimilars and tapering of therapy were added, and the research agenda was revised. Literature searches covered treatments for the key domains of PsA: peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis; additional searches were performed for PsA-related conditions (uveitis and inflammatory bowel disease) and comorbidities. Individual subcommittees used a GRADE-informed approach, taking into account the quality of evidence for therapies, to generate recommendations for each of these domains, which were incorporated into an overall schema. Choice of therapy for an individual should ideally address all disease domains active in that patient, supporting shared decision-making. As safety issues often affect potential therapeutic choices, additional consideration was given to relevant comorbidities. These GRAPPA treatment recommendations provide up-to-date, evidence-based guidance on PsA management for clinicians and people with PsA.
| S-EPMC9244095 | biostudies-literature
Project description:BACKGROUND: Psoriasis and psoriatic arthritis (PsA) impair quality of life, including reduction in employment or job duties. The PRESTA (Psoriasis Randomized Etanercept STudy in Patients with Psoriatic Arthritis) study, a randomized, double-blind, two-dose trial, examined the efficacy of etanercept treatment in patients with moderate-to-severe plaque psoriasis and PsA and the main results have been presented previously. This analysis examined employment status, job duties and sick days, pre-defined endpoints in PRESTA, among this patient population. METHODS: Participants (N=752) were randomized to receive etanercept 50 mg twice weekly (BIW; n=379) or 50 mg once weekly (QW; n=373) for 12 weeks by subcutaneous injection. All participants then received open-label etanercept 50 mg QW for 12 additional weeks, while remaining blinded to the randomization. A pharmacoeconomic questionnaire was administered at baseline, week 12 and week 24 of treatment. The questionnaire included employment status and changing job responsibilities and sick time taken due to psoriasis or PsA. The statistical methods included analysis of covariance, t-test, Fisher's exact test and McNemar's test. Last-observation-carried-forward imputation was used for missing data. RESULTS: Employment was at least maintained from baseline to week 24 in both dose groups (56% [BIW/QW] and 60% [QW/QW] at baseline, 61% and 60%, respectively, at week 24). Among employed participants, the proportion of patients whose job responsibilities changed due to PsA decreased significantly from baseline to week 24 (17-23% to 5-8%; p<0.01). Similar results were seen with job responsibility changes due to psoriasis (11-14% to 4%; p<0.01). The number of monthly sick days also decreased from baseline to week 24 (2.4 days for both treatment groups to 0.7 (BIW/QW) and 1.1 (QW/QW); p?0.03 for each). No significant differences between the treatment groups were observed for any economic endpoint at any time point. CONCLUSIONS: For patients with moderate-to-severe plaque psoriasis and PsA, etanercept treatment resulted in reducing job responsibility changes due to disease and in reducing sick time. Effective treatment of psoriasis and PsA may reduce missed work days.
| S-EPMC4147874 | biostudies-other
Project description:INTRODUCTION:Psoriatic arthritis (PsA) occurs in 10%-15% of people with psoriasis and accounts for 10%-20% of early arthritis clinics referral. Only a few prognostic factors of therapeutic response in patients with PsA have been identified. In the last years, the role of imaging has grown up and the European League Against Rheumatism recognised that ultrasound (US) has higher sensitivity than clinical examination to detect inflammatory disease activity. The aims of the Ultrasound in PSoriatic arthritis TREAtMent (UPSTREAM) study are to integrate clinic and US in order to inform whether US has provide an added prognostic value in PsA. METHODS AND ANALYSIS:UPSTREAM is an observational prospective cohort study enrolling patients with PsA having clinically active joint disease and starting a new course of therapy. The primary objective is to evaluate the additional value of US over clinical examination in detecting patients achieving minimal disease activity after 6 months. Data will be obtained at baseline and at standard clinical follow-up visits. Patient's clinical assessment will be performed according to the core set proposed by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis-Outcome Measures in Rheumatology. Sonographic evaluations will be performed by expert sonographers in 42 joints, 36 tendons, 12 entheses and 2 bursae, according to a score that will be purposely developed for PsA by the US Study Group of the Italian Society for Rheumatology. The UPSTREAM study will identify clinical and US predictors of response to treatment in patients with PsA and active peripheral arthritis starting a new course of therapy. ETHICS AND DISSEMINATION:Ethic approval for this study has been obtained from the institutional review board (IRB)/independent ethics committee (IEC) Comitato Etico Lazio 1 (Prot. N 198 02-02-2017) and then locally from the IRB/IEC of each participating centre. Results will be published in relevant scientific journals and be disseminated in international conferences. Fully anonymised data will be accessible from authors upon request. TRIAL REGISTRATION NUMBER:NCT03330769; Pre-results.
| S-EPMC6082450 | biostudies-literature