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      Poor prognostic factors in predicting abatacept response in a phase III randomized controlled trial in psoriatic arthritis

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          Abstract

          In ASTRAEA (NCT01860976), abatacept significantly increased American College of Rheumatology criteria 20% (ACR20) responses at Week 24 versus placebo in patients with psoriatic arthritis (PsA). This post hoc analysis explored relationships between prospectively identified baseline characteristics [poor prognostic factors (PPFs) ] and response to abatacept. Patients were randomized (1:1) to receive subcutaneous abatacept 125 mg weekly or placebo for 24 weeks; those without ≥ 20% improvement in joint counts at Week 16 switched to open-label abatacept. Potential predictors of ACR20 response were identified by treatment arm using multivariate analyses. Likelihood of ACR20 response to abatacept versus placebo was compared in univariate and multivariate analyses in subgroups stratified by the PPF, as defined by EULAR and/or GRAPPA treatment guidelines. Odds ratios (ORs) were generated using logistic regression to identify meaningful differences (OR cut-off: 1.2). 424 patients were randomized and treated (abatacept n = 213; placebo n = 211). In abatacept-treated patients, elevated C-reactive protein (CRP), high Disease Activity Score based on 28 joints (CRP), presence of dactylitis, and ≥ 3 joint erosions were identified as predictors of response (OR > 1.2). In placebo-treated patients, only dactylitis was a potential predictor of response. In the univariate analysis stratified by PPF, ACR20 response was more likely (OR > 1.2) with abatacept versus placebo in patients with baseline PPFs than in those without; multivariate analysis confirmed this finding. Response to abatacept versus placebo is more likely in patients with features indicative of high disease activity and progressive disease; these characteristics are recognized as PPFs in treatment guidelines for PsA.

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          Psoriatic arthritis: epidemiology, clinical features, course, and outcome.

          Psoriatic arthritis (PsA) has been defined as a unique inflammatory arthritis associated with psoriasis. Its exact prevalence is unknown, but estimates vary from 0.3% to 1% of the population. The clinical features described initially are recognised by most experienced clinicians, although they are most distinct in early disease. Initially, PsA typically presents as an oligoarticular and mild disease. However, with time PsA becomes polyarticular, and it is a severe disease in at least 20% of patients. Patients with PsA who present with polyarticular disease are at risk for disease progression. In addition to progression of clinical and radiological damage, health related quality of life is reduced among patients with PsA. It important to note that patients included in recent drug trials resemble patients followed prospectively in a clinic.
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            Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 Treatment Recommendations for Psoriatic Arthritis.

            To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA).
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              Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors

              Objectives: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. Methods: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (∼10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. Results: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. Conclusions: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile.
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                Author and article information

                Contributors
                pmease@philipmease.com
                Journal
                Rheumatol Int
                Rheumatol. Int
                Rheumatology International
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0172-8172
                1437-160X
                30 April 2020
                30 April 2020
                2020
                : 40
                : 7
                : 1021-1028
                Affiliations
                [1 ]Swedish Medical Center, University of Washington School of Medicine, Seattle, WA USA
                [2 ]GRID grid.8756.c, ISNI 0000 0001 2193 314X, Institute of Infection, Immunity and Inflammation, , University of Glasgow, ; Glasgow, UK
                [3 ]GRID grid.168010.e, ISNI 0000000419368956, Division of Immunology and Rheumatology, , Stanford University School of Medicine, ; Palo Alto, CA USA
                [4 ]St. Vincent’s University Hospital, The Conway Institute for Biomolecular Research, and University College Dublin, Dublin, Ireland
                [5 ]GRID grid.419971.3, Bristol-Myers Squibb, ; Princeton, NJ USA
                [6 ]Excelya, Boulogne-Billancourt, France
                [7 ]Seattle Rheumatology Associates, 601 Broadway, Suite 600, Seattle, WA 98122 USA
                Author information
                http://orcid.org/0000-0002-6620-0457
                Article
                4564
                10.1007/s00296-020-04564-x
                7256096
                32356115
                e995e38a-d5f9-4e0c-9127-90ec843eefd8
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 8 October 2019
                : 23 March 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100002491, Bristol-Myers Squibb;
                Categories
                Clinical Trials
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                Rheumatology
                psoriatic arthritis,prognosis,clinical trial,dmard,abatacept
                Rheumatology
                psoriatic arthritis, prognosis, clinical trial, dmard, abatacept

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