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1.
J Rheumatol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009390

RESUMO

Every year at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, new project ideas are presented and discussed with a view to obtaining feedback and support. Arising from previous work, a project proposal was presented at the 2023 meeting; the project aims to improve early diagnosis of psoriatic arthritis (PsA) by comparing a physician-based vs a patient questionnaire-based approach. This project has received the backing of the GRAPPA research committee, but additional funding will be required. A second project, approved by GRAPPA, was presented on delivering an epidemiology training module before the GRAPPA annual meeting in 2024, which will target both established GRAPPA clinicians and trainees. Attendance at such a module would enhance the quality of research in psoriatic disease.

2.
J Rheumatol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009394

RESUMO

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting was held on July 13 to 15, 2023, in Dublin, Ireland, and was attended by 285 rheumatologists, dermatologists, trainees, patient research partners (PRPs), representatives of patient organizations, and industry partners. The 20th anniversary of GRAPPA was celebrated with a special presentation and archival video. Ahead of the meeting, the PRP Network met, a workshop was held by the International Dermatology Outcome Measures (IDEOM) group, and there was a workshop in which researchers discussed advancing ultrasound use to improve the management of psoriatic disease (PsD). Young-GRAPPA also held a workshop and business meeting. Multiple presentations highlighted important topics currently influencing PsD, including ensuring that patients are included in advancing research, the role of depression in PsD, the use of magnetic resonance imaging for spinal lesions, and animal models of PsD, among others. Debates focused on whether biologics should be used for mild psoriasis, whether methotrexate should remain the first-line treatment for PsD, and whether PsD is really a primary enthesitis driving joint synovitis. Here we provide an overview of the features of the GRAPPA 2023 annual meeting and introduce the manuscripts published together in this supplement as a meeting report.

3.
J Rheumatol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009385

RESUMO

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Collaborative Research Network (CRN)/research committee met during the GRAPPA 2023 annual meeting. Updates were provided on GRAPPA research projects, including the Axial Involvement in Psoriatic Arthritis (AXIS), Axial Psoriatic Arthritis Molecular and Clinical Characterisation Study, Diagnostic Ultrasound Enthesitis Tool (DUET), and Sex- and Gender-Based Analysis of the Effectiveness of Advanced Therapies (SAGE) studies, as well as the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES) and Elucidating the Landscape of Immunoendotypes in Psoriatic Skin and Synovium (ELLIPSS) studies. The highlight of the meeting was a presentation and discussion on the use of digital tools to study psoriatic disease.

4.
J Rheumatol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009384

RESUMO

At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, members were updated on a number of ongoing activities during the key project update session. These activities included the Axial Involvement in Psoriatic Arthritis (AXIS) cohort, the Axial Psoriatic Arthritis Molecular and Clinical Characterization study, the Diagnostic Ultrasound Enthesitis Tool (DUET) study, the Sex- and Gender-Based Analysis of the Effectiveness of Advanced Therapies in Psoriatic Arthritis (SAGE-PsA) study, the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES), the GRAPPA slide library, and the GRAPPA treatment recommendations.

5.
J Rheumatol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009398

RESUMO

Research progress from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) pilot award program was presented and discussed at the GRAPPA 2023 annual meeting. Topics included identification of protein biomarkers associated with enthesitis in psoriatic arthritis (PsA), the role of HLA-B27 on gut microbial dysbiosis in PsA, single-cell profiling of synovial fluid vs psoriatic skin lesions in PsA, and the role of mechanotransduction in hyperactivation of transforming growth factor-ß via αVß6 integrin in psoriatic epidermis.

6.
BMC Emerg Med ; 24(1): 99, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862922

RESUMO

BACKGROUND: Timely dispatch of appropriate emergency medical services (EMS) resources to the scene of medical incidents, and/or provision of treatment at the scene by bystanders and medical emergency lay callers (referred to as 'callers' in this review) can improve patient outcomes. Currently, in dispatch systems worldwide, prioritisation of dispatch relies mostly on verbal telephone information from callers, but advances in mobile phone technology provide means for sharing video footage. This scoping review aimed to map and identify current uses, opportunities, and challenges for using video livestreaming from callers' smartphones to emergency medical dispatch centres. METHODS: A scoping review of relevant published literature between 2007 and 2023 in the English language, searched within MEDLINE; CINAHL and PsycINFO, was descriptively synthesised, adhering to the PRISMA extension for scoping reviews. RESULTS: Twenty-four articles remained from the initial search of 1,565 articles. Most studies were simulation-based and focused on emergency medical dispatchers' (referred to as 'dispatcher/s' in this review) assisted video cardiopulmonary resuscitation (CPR), predominantly concerned with measuring how video impacts CPR performance. Nine studies were based on real-life practice. Few studies specifically explored experiences of dispatchers or callers. Only three articles explored the impact that using video had on the dispatch of resources. Opportunities offered by video livestreaming included it being: perceived to be useful; easy to use; reassuring for both dispatchers and callers; and informing dispatcher decision-making. Challenges included the potential emotional impact for dispatchers and callers. There were also concerns about potential misuse of video, although there was no evidence that this was occurring. Evidence suggests a need for appropriate training of dispatchers and video-specific dispatch protocols. CONCLUSION: Research is sparse in the context of video livestreaming. Few studies have focussed on the use of video livestreaming outside CPR provision, such as for trauma incidents, which are by their nature time-critical where visual information may offer significant benefit. Further investigation into acceptability and experience of the use of video livestreaming is warranted, to understand the potential psychological impact on dispatchers and callers.


Assuntos
Smartphone , Humanos , Gravação em Vídeo , Operador de Emergência Médica , Sistemas de Comunicação entre Serviços de Emergência , Despacho de Emergência Médica , Serviços Médicos de Emergência , Reanimação Cardiopulmonar
7.
Rheumatology (Oxford) ; 62(9): 2989-2997, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36645243

RESUMO

OBJECTIVES: To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start (new) DMARD-therapy. METHODS: Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of two visits). The relation between T2T intensity and change in SvdH-score was modelled by generalized estimating equations. RESULTS: In total, 511 patients were included [mean (s.d.) age: 56 (13) years; 76% female]. Mean 2-year SvdH progression was 2.2 (4.1) units (median: 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval [parameter estimates (for yes vs no): +0.15 units (95% CI: -0.04, 0.33) for 2 vs 0 visits; and +0.08 units (-0.06; 0.22) for 1 vs 0 visits] nor did it reduce progression in the subsequent 6-month interval. CONCLUSIONS: In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude towards T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/induzido quimicamente , Antirreumáticos/uso terapêutico , Progressão da Doença , Índice de Gravidade de Doença , Indução de Remissão
8.
Clin Exp Rheumatol ; 41(3): 574-580, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35916294

RESUMO

OBJECTIVES: Around 30% of patients diagnosed with cutaneous psoriasis (PsC) will go on to develop psoriatic arthritis (PsA) which includes inflammation of the joints. Collagens are core proteins in all tissues, which are involved in the inflammatory process in both PsC and PsA. The aim of this study is to investigate collagen biomarkers and their potential use in separating the three patient groupings: PsC, PsA and healthy donors. METHODS: Healthy donors (n=41), patients with PsC (n=30) and patients with PsA (n=30) were recruited. Clinical disease parameters were recorded. Collagen remodelling was measured using ELISA immunoassays which detect the serological anabolic biomarkers quantifying formation of type I, III and IV collagen (PRO-C1, PRO-C3 and PRO-C4 respectively), and the catabolic biomarkers measuring degradation of type I, II, III, IV and X collagen (C1M, C2M, C3M, C4M and C10C respectively). RESULTS: Patients with PsC and PsA presented lower levels of PRO-C1 and C3M compared to healthy controls (p<0.05-p<0.0001), C1M was higher in PsA compared to healthy controls (p<0.0001) and C2M was all elevated in PsC and PsA compared to healthy controls (p=0.0002 and p=0.0004 respectively), reflecting alterations in the tissues. In addition, C1M was able to separate between PsC and PsA patients with an AUROC=0.664, indicating that this biomarker may be a biomarker of joint involvement. CONCLUSIONS: This work provides evidence that serum collagen biomarkers are dysregulated in PsC and PsA, as compared to healthy controls. C1M was able to differentiate patients with PsC from PsA and could be a potential biomarker of inflammatory systemic musculoskeletal involvement.


Assuntos
Artrite Psoriásica , Psoríase , Humanos , Artrite Psoriásica/diagnóstico , Psoríase/diagnóstico , Colágeno , Biomarcadores
9.
BMC Musculoskelet Disord ; 22(1): 817, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556105

RESUMO

INTRODUCTION: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with osteoporosis. There have not been many peripheral quantitative computed tomography (QCT) studies in patients receiving biologics. We assessed volumetric and areal bone mineral density (BMD) by forearm QCT and dual-energy X-ray absorptiometry (DXA), respectively in addition to laboratory biomarkers in these arthritides. METHODS: Forty RA and AS patients treated with either etanercept (ETN) or certolizumab pegol (CZP) were undergoing follow-ups for one year. Volumetric and areal BMD, as well as parathyroid hormone (PTH), osteocalcin, RANKL, 25-hydroxyvitamin D (VITD), P1NP, CTX, sclerostin (SOST), Dickkopf 1 (DKK-1) and cathepsin K (CATHK) were determined. RESULTS: We did not observe any further bone loss during the 12-month treatment period. Volumetric and areal BMD showed significant correlations with each other (p<0.017 after Bonferroni's correction). Trabecular QCT BMD at baseline (p=0.015) and cortical QCT BMD after 12 months (p=0.005) were inversely determined by disease activity at baseline in the full cohort. Trabecular QCT BMD at baseline also correlated with CTX (p=0.011). In RA, CRP negatively (p=0.014), while SOST positively (p=0.013) correlated with different QCT parameters. In AS, RANKL at baseline (p=0.014) and after 12 months (p=0.007) correlated with cortical QCT BMD. In the full cohort, 12-month change in QTRABBMD was related to TNF inhibition together with elevated VITD-0 levels (p=0.031). Treatment and lower CATHK correlated with QCORTBMD changes (p=0.006). In RA, TNF inhibition together with VITD-0 (p<0.01) or CATHK-0 (p=0.002), while in AS, treatment and RANKL-0 (p<0.05) determined one-year changes in QCT BMD. CONCLUSIONS: BMD as determined by QCT did not change over one year of anti-TNF treatment. Disease activity, CATHK, RANKL and VITD may be associated with the effects of anti-TNF treatment on QCT BMD changes. RA and AS may differ in this respect.


Assuntos
Artrite Reumatoide , Espondilite Anquilosante , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Densidade Óssea , Humanos , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/tratamento farmacológico , Tomografia Computadorizada por Raios X , Inibidores do Fator de Necrose Tumoral
10.
J Rheumatol Suppl ; 97: 39-44, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34074665

RESUMO

OBJECTIVE: To test the addition of pain and fatigue to the Composite Psoriatic Arthritis Disease Activity (CPDAI) and the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) Composite Exercise (GRACE) composite measures of psoriatic arthritis (PsA). METHODS: Clinical and patient-reported outcome measures were assessed in patients with PsA at 3 consecutive follow-up visits over 6 months in a UK multicenter observational study. A pain visual analog scale and Functional Assessment of Chronic Illness Therapy Fatigue scale were added as modifications to the CPDAI and GRACE composite measures. Original and modified versions were tested against the PsA Disease Activity Score (PASDAS) and the Disease Activity Index for PsA (DAPSA). Discrimination between disease states and responsiveness were tested with t-scores, standardized response means (SRMs), and effect sizes. Data were presented to members at the 2020 annual meeting who then voted on the GRAPPA-recommended composite and treatment targets for clinical trials. RESULTS: One hundred forty-one patients were recruited with a mean PsA disease duration of 6.1 years (range 0-41 yrs). The SRMs for the GRACE and modified GRACE (mGRACE) were 0.67 and 0.64, respectively, and 0.54 and 0.46, respectively, for the CPDAI and modified CPDAI (mCPDAI). The t-scores for the GRACE and mGRACE were unchanged at 7.8 for both, and 6.8 and 7.0 for the CPDAI and mCPDAI, respectively. The PASDAS demonstrated the best responsiveness (SRM 0.84) and discrimination (t-scores 8.3). Most members (82%) agreed the composites should not be modified and 77% voted for the PASDAS as the GRAPPA-recommended composite for clinical trials, with 90% minimal disease activity (MDA) as the target. CONCLUSION: Modifying the CPDAI and GRACE with the addition of pain and fatigue does not enhance responsiveness nor the measures' ability to detect disease status in terms of requiring treatment escalation. GRAPPA members voted for the PASDAS as the composite measure in clinical trials and MDA as the target.


Assuntos
Artrite Psoriásica , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/terapia , Fadiga/diagnóstico , Fadiga/etiologia , Humanos , Dor , Índice de Gravidade de Doença , Reino Unido
11.
J Rheumatol Suppl ; 97: 45-49, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34074666

RESUMO

OBJECTIVE: To test shortened versions of the psoriatic arthritis (PsA) composite measures for use in routine clinical practice. METHODS: Clinical and patient-reported outcome measures (PROMs) were assessed in patients with PsA at 3 consecutive follow-up visits in a UK multicenter observational study. Shortened versions of the Composite Psoriatic Arthritis Disease Activity Index (CPDAI) and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Composite Exercise (GRACE) measures were developed using PROMs and tested against the Disease Activity Score in 28 joints (DAS28), composite Disease Activity in Psoriatic Arthritis, and Routine Assessment of Patient Index Data (RAPID3). Discrimination between disease states and responsiveness were tested with the t-score, standardized response mean (SRM), and effect size (ES). Data were presented to members at the GRAPPA 2020 annual meeting and members voted on the recommended composite routine practice. RESULTS: The SRM for the GRACE, 3 visual analog scale (VAS), and 4VAS were 0.67, 0.77, and 0.63, respectively, and for CPDAI and shortened CPDAI (sCPDAI) were 0.54 and 0.55, respectively. Shortened versions of the GRACE increased the t-score from 7.8 to 8.7 (3VAS) and 9.0 (4VAS), but reduced the t-score in the CPDAI/sCPDAI from 6.8 and 6.1. The 3VAS and 4VAS had superior performance characteristics to the sCPDAI, DAS28, Disease Activity in Psoriatic Arthritis, and RAPID3 in all tests. Of the members, 60% agreed that the VAS scales contained enough information to assess disease and response to treatment, 53% recommended the 4VAS for use in routine care, and 26% the 3VAS, while leaving 21% undecided. Conclusion. Shortening the GRACE to VAS scores alone enhances the ability to detect status and responsiveness and has the best performance characteristics of the tested composite measures. GRAPPA members recommend further testing of the 3VAS and 4VAS in observational and trial datasets.


Assuntos
Artrite Psoriásica , Psoríase , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/terapia , Humanos , Medição da Dor , Índice de Gravidade de Doença , Reino Unido
12.
J Rheumatol Suppl ; 97: 4-9, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34074658

RESUMO

At the 2020 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Collaborative Research Network (CRN) annual meeting, the GRAPPA-CRN group presented a pilot investigator-initiated study protocol to test electronic case report forms (eCRFs) and proposed Standardized Operating Procedures (SOPs) to evaluate biomarkers of psoriatic arthritis (PsA) associated with axial disease. The progress on 3 studies was also presented: BioDAM PsA (Biomarkers as Predictors of structural DAMage in PsA; to validate soluble biomarkers as predictors of structural damage in PsA), PreventPsA (examining the development of PsA and risk factors among patients with psoriasis and no arthritis), and PredictORPsA (Predicting Treatment respOnse in patients with eaRly PsA; in collaboration with Pfizer using samples from the Oral Psoriatic Arthritis TriaL [OPAL], to identify biomarkers of treatment response). GRAPPA-CRN funding partnerships and applications are also underway with both the Innovative Medicines Initiative (IMI) in Europe and Accelerating Medicines Partnerships (AMP) 2.0 in the USA, and the progress of these applications and associated objectives were presented.


Assuntos
Artrite Psoriásica , Psoríase , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Biomarcadores , Europa (Continente) , Humanos , Pesquisadores
13.
J Rheumatol Suppl ; 97: 60-63, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34074670

RESUMO

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Working Group provided updates at the 2020 GRAPPA annual meeting on its work toward developing a core outcome set for PsA. Working groups were set up for the 4 prioritized domains: enthesitis, fatigue, structural damage, and physical function. Two instruments for measurement of physical function were provisionally endorsed: (1) the Health Assessment Questionnaire-Disability Index and (2) the physical functioning domain in the Medical Outcomes Study 36-item Short Form survey.


Assuntos
Artrite Psoriásica , Entesopatia , Psoríase , Reumatologia , Artrite Psoriásica/diagnóstico , Humanos , Avaliação de Resultados em Cuidados de Saúde
14.
Curr Opin Rheumatol ; 32(4): 330-336, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32412996

RESUMO

PURPOSE OF REVIEW: To provide an overview of the heterogeneous human leucocyte antigen (HLA) associations of psoriatic arthritis, their relationship to particular clinical features of the disease, and how a hypothesis of binding specific peptides could provide a unifying basis for this heterogeneity. RECENT FINDINGS: There have been substantive advances in understanding the role of HLA molecules in binding self-peptides that select our repertoire of T cells, the specific peptide-binding properties of these HLA allotypes, and their crystallographic structure. These advances provide a means to envision the significance of the heterogeneous psoriatic arthritis HLA associations. The clinical relevance of these allotypes if heightened by emerging knowledge of their relationship to particular clinical features of the disease that serve as subphenotypes. SUMMARY: We propose a peptide binding hypothesis of psoriatic arthritis based on a shared pattern of negative charge in the 'B' pocket of the HLA-B and HLA-C molecules encoded by the susceptibility allotypes. This hypothesis suggests that peptides characterized by the presence of arginine at position 2 or 3 are bound to the susceptibility allotypes and drive the T-cell clones selected on them to attack molecules containing these peptides located in sites of psoriatic arthritis inflammation.


Assuntos
Artrite Psoriásica/genética , Artrite Psoriásica/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Ligação Proteica , Predisposição Genética para Doença , Antígenos HLA/genética , Antígenos HLA/imunologia , Antígeno HLA-B27/genética , Antígeno HLA-B27/imunologia , Humanos , Peptídeos/imunologia , Ligação Proteica/genética , Ligação Proteica/imunologia
15.
N Engl J Med ; 377(16): 1537-1550, 2017 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-29045212

RESUMO

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who previously had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs). METHODS: In this 12-month, double-blind, active-controlled and placebo-controlled, phase 3 trial, we randomly assigned patients in a 2:2:2:1:1 ratio to receive one of the following regimens: tofacitinib at a 5-mg dose taken orally twice daily (107 patients), tofacitinib at a 10-mg dose taken orally twice daily (104), adalimumab at a 40-mg dose administered subcutaneously once every 2 weeks (106), placebo with a blinded switch to the 5-mg tofacitinib dose at 3 months (52), or placebo with a blinded switch to the 10-mg tofacitinib dose at 3 months (53). Placebo groups were pooled for analyses up to month 3. Primary end points were the proportion of patients who had an American College of Rheumatology 20 (ACR20) response (≥20% improvement from baseline in the number of tender and swollen joints and at least three of five other important domains) at month 3 and the change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score (scores range from 0 to 3, with higher scores indicating greater disability) at month 3. RESULTS: ACR20 response rates at month 3 were 50% in the 5-mg tofacitinib group and 61% in the 10-mg tofacitinib group, as compared with 33% in the placebo group (P=0.01 for the comparison of the 5-mg dose with placebo; P<0.001 for the comparison of the 10-mg dose with placebo); the rate was 52% in the adalimumab group. The mean change in the HAQ-DI score was -0.35 in the 5-mg tofacitinib group and -0.40 in the 10-mg tofacitinib group, as compared with -0.18 in the placebo group (P=0.006 for the comparison of the 5-mg dose with placebo; P<0.001 for the comparison of the 10-mg dose with placebo); the score change was -0.38 in the adalimumab group. The rate of adverse events through month 12 was 66% in the 5-mg tofacitinib group, 71% in the 10-mg tofacitinib group, 72% in the adalimumab group, 69% in the placebo group that switched to the 5-mg tofacitinib dose, and 64% in the placebo group that switched to the 10-mg tofacitinib dose. There were four cases of cancer, three serious infections, and four cases of herpes zoster in patients who received tofacitinib during the trial. CONCLUSIONS: The efficacy of tofacitinib was superior to that of placebo at month 3 in patients with psoriatic arthritis who had previously had an inadequate response to conventional synthetic DMARDs. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Broaden ClinicalTrials.gov number, NCT01877668 .).


Assuntos
Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Janus Quinases/antagonistas & inibidores , Piperidinas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Pirróis/administração & dosagem , Adalimumab/efeitos adversos , Administração Oral , Adulto , Antirreumáticos/efeitos adversos , Avaliação da Deficiência , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos
16.
Ann Rheum Dis ; 79(4): 453-459, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32094157

RESUMO

OBJECTIVES: To investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target. METHODS: RA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44 <1.6) as the target. Sustained T2T was defined as T2T followed in ≥2 consecutive visits. The main outcome was the achievement of DAS44 remission at the subsequent 3-month visit. Other outcomes were remission according to 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definitions. The association between T2T and remission was tested in generalised estimating equations models. RESULTS: In total 4356 visits of 571 patients (mean (SD) age: 56 (13) years, 78% female) were included. Appropriate application of T2T was found in 59% of the visits. T2T (vs no T2T) did not yield a higher likelihood of DAS44 remission 3 months later (OR (95% CI): 1.03 (0.92 to 1.16)), but sustained T2T resulted in an increased likelihood of achieving DAS44 remission (OR: 1.19 (1.03 to 1.39)). Similar results were seen with DAS28-ESR remission. For more stringent definitions (CDAI, SDAI and ACR/EULAR Boolean remission), T2T was consistently positively associated with remission (OR range: 1.16 to 1.29), and sustained T2T had a more pronounced effect on remission (OR range: 1.49 to 1.52). CONCLUSION: In daily clinical practice, the correct application of a T2T-strategy (especially sustained T2T) in patients with RA leads to higher rates of remission.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Planejamento de Assistência ao Paciente , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Idoso , Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Sedimentação Sanguínea , Proteína C-Reativa/imunologia , Tomada de Decisão Clínica , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Fator Reumatoide/imunologia
17.
Rheumatology (Oxford) ; 59(Suppl 1): i4-i9, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32159794

RESUMO

In this review, we propose a model of PsA as a complex genetically determined autoimmune-mediated disease having a heterogeneous variety of subphenotypes, with each subphenotype under the control of a different susceptibility-associated HLA allele. Since the specific HLA molecules encoded by each susceptibility allele dominantly select a T cell repertoire with the property of recognizing different peptides, we hypothesize each subphenotype reflects a distinct adaptive autoimmune response directed to different target molecules that is mediated by T cells within each selected repertoire. The interaction among the patients' susceptibility alleles in the selection of their T cell repertoires determines a spectrum of overall clinical disease severity, varying from mild to severe. We further speculate that these different immune responses may result in activation of different immune effector pathways, which might therefore respond differently to various specific biologic agents.


Assuntos
Artrite Psoriásica/genética , Antígenos HLA/imunologia , Linfócitos T/imunologia , Alelos , Artrite Psoriásica/imunologia , Artrite Psoriásica/patologia , Autoimunidade , Determinismo Genético , Predisposição Genética para Doença , Genótipo , Humanos , Índice de Gravidade de Doença , Linfócitos T/metabolismo
18.
Curr Rheumatol Rep ; 22(11): 78, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32959152

RESUMO

PURPOSE OF REVIEW: To provide a general overview of the organizations dedicated to advance clinical and translational research in the field of psoriatic disease and to describe the current and future opportunities for team science approaches to overcome unmet needs in the field. Descriptions of initiatives from the NPF, PPACMAN, and GRAPPA are summarized. RECENT FINDINGS: Program projects have recently identified areas of knowledge gaps in diagnosis, treatment, and prevention of psoriasis and psoriatic arthritis (PsA). NPF's Psoriasis Prevention Initiative aims to identify interventions that can prevent the onset and relapse of psoriatic disease or related comorbidities. The Psorcast Study is a joint venture between PPACMAN and Sage Bionetworks based on patient-generated smartphone measurements of psoriatic disease. Similarly, GRAPPA is involved in a number of projects related to axial PsA, enthesitis prevalence, and biomarker discoveries. As important initiatives bring new targets for diagnosis and therapeutics in psoriatic disease, supra-endeavors such as the NIH-Accelerating Medicines Partnership (AMP) and the European Innovative Medicines Initiative (IMI) are promising public-private partnerships that can significantly catapult the field forward.


Assuntos
Artrite Psoriásica , Psoríase , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/prevenção & controle , Pesquisa Biomédica , Comorbidade , Entesopatia , Humanos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/prevenção & controle
19.
Rheumatol Int ; 40(7): 1021-1028, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32356115

RESUMO

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.


Assuntos
Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Adulto , Artrite Psoriásica/metabolismo , Artrite Psoriásica/fisiopatologia , Proteína C-Reativa/metabolismo , Feminino , Articulações dos Dedos/fisiopatologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Índice de Gravidade de Doença , Articulação do Dedo do Pé/fisiopatologia
20.
J Rheumatol Suppl ; 96: 19-24, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32482763

RESUMO

Current management approaches for the treatment of psoriasis and psoriatic arthritis (PsA) are imprecise and depend largely on clinical assessment. A more precise approach, which takes into account an individual patient's variations in genes, proteins, environment, and lifestyle, is beginning to receive attention with the most advanced progress seen in the treatment of cancer. Herein, the methodological approaches required for this precision medicine approach to be adopted in psoriatic disease, as well as their advantages, are reviewed. In addition, advances that are being made to address areas of unmet need in PsA, notably the use of proteomic approaches, are presented with suggestions that combine genetic and protein data (proteogenomics). Finally, progress that is being made in 2 large-scale, multipartner studies focused on the development of a precision medicine approach to the treatment of skin psoriasis is presented and discussed.


Assuntos
Artrite Psoriásica , Medicina de Precisão , Proteômica , Artrite Psoriásica/terapia , Humanos , Proteogenômica , Psoríase/terapia
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