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1.
Artigo em Inglês | MEDLINE | ID: mdl-33605405

RESUMO

OBJECTIVES: To evaluate the proportion of patients with ERA who have initiated or not GC, to analyse the baseline characteristics, and to assess the clinical benefit and side effects of GC during 5 years of follow-up. METHODS: We included patients with ERA from the UCLouvain Brussels cohort who met the ACR/EULAR 2010 classification criteria and were naïve to cDMARDs. We retrospectively collected patient characteristics prior to the introduction of cDMARDs with or without GC. Efficiency and serious adverse events were analysed at 6, 12, 36 and 60 months. RESULTS: Data from 474 eligible ERA patients were collected. 180 patients initiated GC compared with 294 who did not.At baseline, the increased CRP is the main factor that favors the initiation of GC followed by smoking, absence of ACPA, prescription of methotrexate as a monotherapy and age.5 years follow-up of DAS28-CRP, HAQ or VAS pain values did not differ between the two groups.We also analysed a subgroup of 139 patients who received >1 g of prednisolone during the 5 years period. We confirmed the same baseline differences and observed in addition more males and higher DAS-28CRP values. During the 5 years follow up, DAS-28CRP, VAS pain and HAQ remained significantly higher in this subgroup. More severe infections were also reported. CONCLUSION: In our ERA cohort, the initiation of GC treatment does not bring additional benefit for the short and long-term control of the disease. GC was more prescribed in seronegative RA patients with a higher level of inflammation. DISCLOSURE STATEMENT: the authors declare no conflicts of interest. ETHICS STATEMENT: authors declare that the study complies with the Declaration of Helsinki.

2.
Diagn Interv Imaging ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33583754

RESUMO

PURPOSE: To assess the agreement between readers using contrast-enhanced T1-weighted Dixon water- and fat-only images and OMERACT-recommended sequences for the scoring of osteitis and erosions according to the rheumatoid arthritis (RA) MRI scoring system (RAMRIS) in hands of patients with early RA. MATERIALS AND METHODS: Both hands of 24 patients (16 women, 8 men; mean age, 45.7±14.5 [SD] years; age range: 25-70 years) with early RA were prospectively imaged with fat-saturated T2-weighted sequences, non-Dixon T1-weighted imaging prior to contrast material injection and T1-weighted Dixon imaging after contrast material injection at 1.5T. There were Two radiologists separately quantified osteitis and erosions according to RAMRIS using contrast-enhanced T1-weighted Dixon water-only and fat-saturated T2-weighted images for osteitis and contrast-enhanced T1-weighted Dixon fat-only and T1-weighted images prior to contrast material injection for erosions. Intraclass correlation coefficients (ICC) were calculated to assess inter-technique, intra-observer and inter-observer agreement. RESULTS: Mean ICC for the agreement between Dixon and non-Dixon images ranged from 0.68 (95%CI: 0.20-0.90) to 0.99 (95%CI: 0.95-1.00) for the scoring of osteitis and from 0.77 (95%CI: 0.38-0.93) to 0.99 (95%CI: 0.95-1.00) for the scoring of erosions. Mean ICC for the agreement between first and second readings ranged from 0.94 (95%CI: 0.81-0.98) to 0.97 (95%CI: 0.91-0.99) for the scoring of osteitis using Dixon and 0.91 (95%CI: 0.72-0.97) to 0.98 (95%CI: 0.92-0.99) using non-Dixon images and from 0.80 (95%CI: 0.45-0.94) to 0.97 (95%CI: 0.91-0.99) for the scoring of erosions using Dixon and 0.72 (95%CI: 0.29-0.91) to 0.98 (95%CI: 0.92-0.99) using non-Dixon images. CONCLUSION: Contrast-enhanced T1-weighted Dixon water- and fat-only images can serve as an alternative to fat-saturated T2-weighted and T1-weighted MRI sequences for the assessment of osteitis and erosions according to the RAMRIS scoring system in hands of patients with early RA.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33590829

RESUMO

OBJECTIVE: To evaluate the impact of upadacitinib vs placebo and adalimumab treatment, on patient-reported outcomes (PROs) in SELECT-COMPARE in an active RA population with inadequate responses to methotrexate (MTX-IR). METHODS: PROs in patients receiving upadacitinib (15 mg QD), placebo, or adalimumab (40 mg EOW) while on background MTX were evaluated over 48 weeks. PROs included PtGA and pain by VAS, HAQ-DI, 36-Item Short Form Survey (SF-36), morning (AM) stiffness duration and severity, FACIT-F, and work instability. Least squares mean (LSM) changes and proportions of patients reporting improvements ≥ minimal clinically important differences (MCID) and scores ≥ normative values were evaluated. RESULTS: Upadacitinib and adalimumab resulted in greater LSM changes from baseline vs placebo across all PROs (p < 0.05) at week 12, and pain and AM stiffness severity (p < 0.05) at week 2. More upadacitinib- vs placebo-treated (p < 0.05) and similar percentages of upadacitinib- vs adalimumab-treated patients reported improvements ≥ MCID across all PROs at week 12. Upadacitinib vs adalimumab resulted in greater LSM changes from baseline in PtGA, pain, HAQ-DI, stiffness severity, FACIT-F, and SF-36 Physical Component Summary (PCS) (all p < 0.05) at week 12. More upadacitinib- vs adalimumab-treated patients reported scores ≥ normative values in HAQ-DI and SF-36 PCS (p < 0.05) at week 12. More upadacitinib- vs adalimumab-treated patients maintained clinically meaningful improvements in PtGA, pain, HAQ-DI, FACIT-F, and AM stiffness through 48 weeks. CONCLUSION: In MTX-IR patients with RA, treatment with upadacitinib resulted in statistically significant and clinically meaningful improvements in PROs equivalent to or greater than with adalimumab.

4.
Lancet ; 397(10271): 305-317, 2021 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-33485455

RESUMO

BACKGROUND: Although targeted biological treatments have transformed the outlook for patients with rheumatoid arthritis, 40% of patients show poor clinical response, which is mechanistically still unexplained. Because more than 50% of patients with rheumatoid arthritis have low or absent CD20 B cells-the target for rituximab-in the main disease tissue (joint synovium), we hypothesised that, in these patients, the IL-6 receptor inhibitor tocilizumab would be more effective. The aim of this trial was to compare the effect of tocilizumab with rituximab in patients with rheumatoid arthritis who had an inadequate response to anti-tumour necrosis factor (TNF) stratified for synovial B-cell status. METHODS: This study was a 48-week, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial (rituximab vs tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis; R4RA) done in 19 centres across five European countries (the UK, Belgium, Italy, Portugal, and Spain). Patients aged 18 years or older who fulfilled the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for rheumatoid arthritis and were eligible for treatment with rituximab therapy according to UK National Institute for Health and Care Excellence guidelines were eligible for inclusion in the trial. To inform balanced stratification, following a baseline synovial biopsy, patients were classified histologically as B-cell poor or rich. Patients were then randomly assigned (1:1) centrally in block sizes of six and four to receive two 1000 mg rituximab infusions at an interval of 2 weeks (rituximab group) or 8 mg/kg tocilizumab infusions at 4-week intervals (tocilizumab group). To enhance the accuracy of the stratification of B-cell poor and B-cell rich patients, baseline synovial biopsies from all participants were subjected to RNA sequencing and reclassified by B-cell molecular signature. The study was powered to test the superiority of tocilizumab over rituximab in the B-cell poor population at 16 weeks. The primary endpoint was defined as a 50% improvement in Clinical Disease Activity Index (CDAI50%) from baseline. The trial is registered on the ISRCTN database, ISRCTN97443826, and EudraCT, 2012-002535-28. FINDINGS: Between Feb 28, 2013, and Jan 17, 2019, 164 patients were classified histologically and were randomly assigned to the rituximab group (83 [51%]) or the tocilizumab group (81 [49%]). In patients histologically classified as B-cell poor, there was no statistically significant difference in CDAI50% between the rituximab group (17 [45%] of 38 patients) and the tocilizumab group (23 [56%] of 41 patients; difference 11% [95% CI -11 to 33], p=0·31). However, in the synovial biopsies classified as B-cell poor with RNA sequencing the tocilizumab group had a significantly higher response rate compared with the rituximab group for CDAI50% (rituximab group 12 [36%] of 33 patients vs tocilizumab group 20 [63%] of 32 patients; difference 26% [2 to 50], p=0·035). Occurrence of adverse events (rituximab group 76 [70%] of 108 patients vs tocilizumab group 94 [80%] of 117 patients; difference 10% [-1 to 21) and serious adverse events (rituximab group 8 [7%] of 108 vs tocilizumab group 12 [10%] of 117; difference 3% [-5 to 10]) were not significantly different between treatment groups. INTERPRETATION: The results suggest that RNA sequencing-based stratification of rheumatoid arthritis synovial tissue showed stronger associations with clinical responses compared with histopathological classification. Additionally, for patients with low or absent B-cell lineage expression signature in synovial tissue tocilizumab is more effective than rituximab. Replication of the results and validation of the RNA sequencing-based classification in independent cohorts is required before making treatment recommendations for clinical practice. FUNDING: Efficacy and Mechanism Evaluation programme from the UK National Institute for Health Research.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Rituximab/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Idoso , Artrite Reumatoide/patologia , Biópsia , Método Duplo-Cego , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Arthritis Res Ther ; 23(1): 3, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397481

RESUMO

Baricitinib is an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 that has proved effective and well tolerated in the treatment of rheumatoid arthritis (RA) in an extensive programme of clinical studies of patients with moderate-to-severe disease. In a phase 2b dose-ranging study of baricitinib in combination with traditional disease-modifying antirheumatic drugs (DMARDs) in RA patients, magnetic resonance imaging showed that baricitinib 2 mg or 4 mg once daily provided dose-dependent suppression of synovitis, osteitis, erosion and cartilage loss at weeks 12 and 24 versus placebo. These findings correlated with clinical outcomes and were confirmed in three phase 3 studies (RA-BEGIN, RA-BEAM and RA-BUILD) using X-rays to assess structural joint damage. In patients naïve to DMARDs (RA-BEGIN study), baricitinib 4 mg once daily as monotherapy or combined with methotrexate produced smaller mean changes in structural joint damage than methotrexate monotherapy at week 24. Differences versus methotrexate were statistically significant for combined therapy. In patients responding inadequately to methotrexate (RA-BEAM study), baricitinib 4 mg plus background methotrexate significantly inhibited structural joint damage at week 24 versus placebo, and the results were comparable to those observed with adalimumab plus background methotrexate. In patients responding inadequately to conventional synthetic DMARDs (csDMARDs; RA-BUILD study), baricitinib 4 mg again significantly inhibited radiographic progression compared with placebo at week 24. Benefits were also observed with baricitinib 2 mg once daily, but the effects of baricitinib 4 mg were more robust. The positive effects of baricitinib 4 mg on radiographic progression continued over 1 and 2 years in the long-term extension study RA-BEYOND, with similar effects to adalimumab and significantly greater effects than placebo. Findings from the phase 3 studies of patients with RA were supported by preclinical studies, which showed that baricitinib has an osteoprotective effect, increasing mineralisation in bone-forming cells. In conclusion, baricitinib 4 mg once daily inhibits radiographic joint damage progression in patients with moderate-to-severe RA who are naïve to DMARDs or respond inadequately to csDMARDs, including methotrexate, and the beneficial effects are similar to those observed with adalimumab.

6.
BMJ Case Rep ; 14(1)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514619

RESUMO

We report the case of a 43-year-old man, suffering from ankylosing spondylitis and treated with Infliximab 5 mg/kg every 2 months, with an excellent disease control. During a follow-up consultation, an incipient renal insufficiency is detected. A urine analysis showed haematuria and proteinuria and a renal puncture-biopsy revealed an image of IgA nephropathy.Several cases of IgA nephropathy have been reported in the literature associated with ankylosing spondylitis. Some of them occur in patients treated with antitumour necrosis factor, but it is unclear whether this pathology is caused by the treatment or whether treatment failed to prevent its occurrence.Our clinical case highlights the importance of regular monitoring of renal function in patients with ankylosing spondylitis, as well as urinary spotting.The question of whether the disease itself, the treatment or other factors such as immune dysregulation could be held responsible for kidney disease will be addressed in the discussion.


Assuntos
Antirreumáticos/uso terapêutico , Glomerulonefrite por IGA/patologia , Infliximab/uso terapêutico , Espondilite Anquilosante/complicações , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Antirreumáticos/administração & dosagem , Biópsia , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/urina , Hematúria/diagnóstico , Humanos , Infliximab/administração & dosagem , Rim/patologia , Testes de Função Renal/normas , Masculino , Monitorização Fisiológica/normas , Proteinúria/diagnóstico , Remissão Espontânea , Espondilite Anquilosante/tratamento farmacológico
7.
Artigo em Inglês | MEDLINE | ID: mdl-33305638

RESUMO

OBJECTIVES: There are few comparative data for tumor necrosis factor inhibitors in patients with rheumatoid arthritis (RA). METHODS: Historical data for reference product/biosimilar intravenous infliximab, or adalimumab and etanercept, were pooled and compared with phase 3 study results for a subcutaneous (SC) formulation of the infliximab biosimilar CT-P13, in a systematic review and meta-analysis (PROSPERO: CRD42019149621). RESULTS: The authors identified 13 eligible controlled trials that randomized over 5400 participants to prespecified treatments of interest. Comparison with pooled historical data suggested a numerical advantage for CT-P13 SC over intravenous infliximab for almost every prespecified efficacy outcome evaluated, including Disease Activity Score in 28 joints (C-reactive protein/erythrocyte sedimentation rate), Clinical/Simplified Disease Activity Index scores, American College of Rheumatology responses, and multiple measures of disease remission and low disease activity; for the majority of outcomes, there was no overlap in 95% confidence intervals between groups. A numerical advantage for CT-P13 SC was also observed for safety outcomes (adverse events, infections and discontinuations). Similar, but less marked, trends were observed for comparison with historical efficacy and safety data for adalimumab/etanercept. CONCLUSION: CT-P13 SC offers an improved or similar benefit-to-harm ratio compared with infliximab (intravenous) and adalimumab/etanercept, for the treatment of moderate-to-severe RA.

8.
Front Immunol ; 11: 593083, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329580

RESUMO

Objectives: We explored histological and transcriptomic profiles of paired synovial biopsies from rheumatoid arthritis (RA) patients, in order to assess homogeneity in synovial tissue at the individual level. Methods: Synovial biopsies were performed simultaneously in one small and one large joint per patient using needle-arthroscopy for the knee and ultrasound-guided biopsy for the hand or wrist. Synovium from individuals with osteoarthritis was used as controls. Paraffin-embedded samples were stained for CD3, CD20, and CD68. Total RNA was hybridized on high-density microarrays. TCRB variable sequences were obtained from synovial and blood RNA samples. Results: Twenty paired biopsies from 10 RA patients with active disease were analyzed. Semi-quantification of histological markers showed a positive correlation for synovial hyperplasia, inflammatory infiltrates and CD3-positive T cells between pairs. Pairwise comparison of transcriptomic profiles showed similar expression of RA-related molecular pathways (TCR signaling, T cell costimulation and response to TNFα). T cells clonotypes were enriched in all but one joints compared to blood, regardless of the magnitude of T cell infiltration. Enriched clonotypes were shared between pairs (23-100%), but this was less the case in pairs of joints displaying weaker T cell signatures and more pronounced germinal center-like transcriptomic profiles. Conclusion: Cellular and molecular alterations in RA synovitis are similar between small and large joints from the same patient. Interindividual differences in magnitude of T cell infiltrates and distribution of enriched T cell clonotypes support the concept of distinct synovial pathotypes in RA that are associated with systemic versus local antigen-driven activation of T cells.

9.
Clin Exp Rheumatol ; 38(6): 1056-1067, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33253107

RESUMO

OBJECTIVES: Despite availability of efficacious treatments, unmet needs still exist, preventing optimal and comprehensive management of rheumatoid arthritis (RA). Evolving the management of RA (eRA) is a European-wide educational initiative aiming to support improved patient care through practical and educational tools addressing specific unmet needs. METHODS: A multidisciplinary Steering Committee (17 members, 12 countries) identified unmet needs within the management of RA and prioritised those with the greatest impact on patient outcomes. Practical educational tools addressing priority needs were then developed for dissemination and implementation by the rheumatology community across Europe. RESULTS: Five areas of priority need were identified: increasing early recognition of RA and treatment initiation; treating RA to target; optimal, holistic approach to selection of treatment strategy, including shared decision-making; improving identification and management of comorbidities; and non-pharmacological patient management. A suite of 14 eRA tools included educational slides, best-practice guidance, self­assessment questionnaires, clinical checklists, a multidisciplinary team training exercise, an interactive patient infographic, and case scenarios. By April 2020, rheumatology professionals in 17 countries had been actively engaged in the eRA programme; in 11 countries, eRA tools were selected by national leaders in rheumatology and translated for local dissemination. A web platform, with country-specific pages, was developed to support access to the translated tools (https://www.evolvingthemanagementofra.com/). CONCLUSIONS: The eRA programme supports comprehensive management of RA across Europe through development and dissemination of practical educational tools. The eRA tools address priority needs and are available free of charge to the rheumatology community.

10.
Eur J Radiol ; 134: 109412, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33221617

RESUMO

PURPOSE: To compare fat suppression effectiveness, image quality and disease activity scores between MRI protocols based on the Dixon method and the Chemical Shift Selective (CHESS) technique in hands of patients with suspicion of early rheumatoid arthritis (RA). METHOD: Both hands of 28 patients (19 women; mean age 45.2 years old) with suspicion of early RA were prospectively imaged with Dixon- and CHESS-based OMERACT recommended protocols at 1.5 T including fat-suppressed T2-weighted and contrast-enhanced T1-weighted imaging. Two radiologists (R1/R2) separately assessed effectiveness of fat suppression and determined RAMRIS scores woth the Dixon- and CHESS-based protocols. R1 repeated the RAMRIS scoring and measured contrast-to-noise ratios (CNRs) on Dixon and CHESS images. Statistics included 2-way ANOVA test for the comparison of CNRs and Bland-Altman methodology for inter-technique and intra-observer agreement (p < 0.05). RESULTS: Fat suppression failure occurred in up to 1 patient with the Dixon- and 25 patients with the CHESS-based protocols. CNRs were significantly higher on T1-weighted and lower on T2-weighted Dixon images than on the corresponding CHESS images (p ≤ 0.042). Median bias of the difference between Dixon- and CHESS-based RAMRIS scores was not significantly different from 0 (-0.8 to +1.0 and -1.1 to +1.4 for R1/R2). Median bias of the difference between RAMRIS scores at first and second readings was significantly different from 0 with the CHESS-based protocols (-0.8 to +1.7) but not with the Dixon-based protocols (+0.0 to +1.0). CONCLUSIONS: Dixon sequences yield more effective fat suppression and more reproducible RAMRIS scoring than CHESS sequences in hands with suspicion of early RA.

11.
Acta Clin Belg ; : 1-8, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32936748

RESUMO

A better understanding of disease pathology, improvements in relevant disease outcomes, better treatment strategies and the development of novel therapies all contribute to improving healthcare and treatment options. However, the global drug development model today is under increasing pressure, with very high drug development costs. Collaborative research is critical for bringing together different capabilities and expertise to increase the success of drug development, and large-scale collaborations with multiple partners are becoming increasingly common. Research clusters supported by local governments play an important role in bringing together academic centres, hospitals, scientists, and pharmaceutical and biotechnology industries. The 'triple helix' model, with academia, industry and governments working together, has been an important factor in the successful development of novel therapies. During the past 20 years, Galapagos has worked closely with academic centres, hospitals, governments and pharmaceutical companies to conduct innovative research and to develop a novel therapy for rheumatoid arthritis. These collaborations have brought unique knowledge, expertise and skills together, as well as crucial funding at various stages. Local governments in the Benelux have operated in this triple helix model to provide the necessary environment and to stimulate companies to achieve innovation through collaboration. Although the triple helix has already proved successful, evolution to a quadruple helix that includes patients and patient representatives could be the next step to ensure innovation remains transformational.

12.
Biochem Med (Zagreb) ; 30(3): 030801, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32774126

RESUMO

Laboratory investigations of hypercalcemia involve testing of various biochemical parameters such as parathyroid hormone (PTH), 25-(OH) Vitamin D (25-(OH) VitD), 1,25-(OH)2 Vitamin D3 (calcitriol) and PTH related peptide (PTHrp). We herein present an atypical case of severe hypercalcemia in a patient with rheumatoid arthritis who has been treated for years by various biological disease-modifying antirheumatic drugs (DMARDs) and suddenly presented with general state alteration, oedema and ulceration of her right ankle. We illustrate how tuberculosis (TB) can cause high calcitriol concentration and subsequently lead to potentially severe hypercalcemia. Moreover, we highlight the importance of TB testing and follow-up in patients treated with biological DMARDs.

13.
RMD Open ; 6(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32683326

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with a global prevalence of approximately 0.5-1%. Patients with RA are at an increased risk of developing comorbidities (eg, cardiovascular disease, pulmonary disease, diabetes and depression). Despite this, there are limited recommendations for the management and implementation of associated comorbidities. This study aimed to identify good practice interventions in the care of RA and associated comorbidities. METHODS: A combination of primary research (180+ interviews with specialists across 12 European rheumatology centres) and secondary research (literature review of existing publications and guidelines/recommendations) were used to identify challenges in management and corresponding good practice interventions. Findings were prioritised and reviewed by a group of 18 rheumatology experts including rheumatologists, comorbidity experts, a patient representative and a highly specialised nurse. RESULTS: Challenges throughout the patient pathway (including delays in diagnosis and referral, shortage of rheumatologists, limited awareness of primary care professionals) and 18 good practice interventions were identified in the study. The expert group segmented and prioritised interventions according to three distinct stages of the disease: (1) suspected RA, (2) recent diagnosis of RA and (3) established RA. Examples of good practice interventions included enabling self-management (self-monitoring and disease management support, for example, lifestyle adaptations); early arthritis clinic; rapid access to care (online referral, triage, ultrasound-guided diagnosis); dedicated comorbidity specialists; enhanced communication with primary care (hotline, education sessions); and integrating patient registries into daily clinical practice. CONCLUSION: Learning from implementation of good practice interventions in centres across Europe provides an opportunity to more widely improved care for patients with RA and associated comorbidities.

14.
Arthritis Res Ther ; 22(1): 96, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345367

RESUMO

BACKGROUND/PURPOSE: Studies have demonstrated that rheumatoid arthritis (RA) patients who achieve low disease activity or remission are able to taper biological disease-modifying antirheumatic drugs (bDMARDs). The aim of this study was to evaluate the proportion of patients in whom bDMARDs can be tapered in daily practice and to analyse the characteristics of these patients. Other objectives were to analyse which bDMARDs are more suitable for dose reduction and the cost savings. RESULTS: Data from 332 eligible RA patients from our Brussels UCLouvain cohort were retrospectively analysed; 140 patients (42.1%) received a tapered regimen, and 192 received stable doses of bDMARDs. The age at diagnosis (43.1 vs 38.7 years, p = 0.04), health assessment questionnaire (HAQ) score (1.3 vs 1.5, p = 0.048), RF positivity rate (83.3 vs 72.9%, p = 0.04) and disease duration at the time of bDMARD introduction (9.7 vs 12.1 years, p = 0.034) were significantly different between the reduced-dose and stable-dose groups. Interestingly, relatively more patients receiving a tapered dose were treated with a combination of bDMARDs and methotrexate (MTX) (86.7% vs 73.8%, p = 0.005). In our cohort, anti-TNF agents were the most commonly prescribed medications (68%). Only 15 patients experienced a flare during follow-up. Adalimumab, etanercept and rituximab were the most common bDMARDs in the reduced-dose group and were associated with the most important reductions in annual cost. CONCLUSION: In daily practice, tapering bDMARDs in RA patients who have achieved low disease activity or remission is an achievable goal in a large proportion of patients, thereby reducing potential side effects and annual drug-associated costs. The combination of bDMARDs with MTX could improve the success of dose reduction attempts. TRIAL REGISTRATION: This retrospective non-interventional study was retrospectively registered with local ethics approval.

15.
J Transl Med ; 18(1): 8, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907043

RESUMO

BACKGROUND: Serum protein glycosylation is an area of investigation in inflammatory arthritic disorders such as rheumatoid arthritis (RA). Indeed, some studies highlighted abnormalities of protein glycosylation in RA. Considering the numerous types of enzymes, monosaccharides and glycosidic linkages, glycosylation is one of the most complex post translational modifications. By this work, we started with a preliminary screening of glycoproteins in serum from RA patients and controls. METHODS: In order to isolate glycoproteins from serum, lectin wheat germ agglutinin was used and quantitative differences between patients and controls were investigated by LC-MS/MS. Consequently, we focused our attention on two glycoproteins found in this explorative phase: corticosteroid-binding globulin (CBG) and lipopolysaccharide-binding protein (LBP). The subsequent validation with immunoassays was widened to a larger number of early RA (ERA) patients (n = 90) and well-matched healthy controls (n = 90). RESULTS: We observed a significant reduction of CBG and LBP glycosylation in ERA patients compared with healthy controls. Further, after 12 months of treatment, glycosylated CBG and LBP levels increased both to values comparable to those of controls. In addition, these changes were correlated with clinical parameters. CONCLUSIONS: This study enables to observe that glycosylation changes of CBG and LBP are related to RA disease activity and its response to treatment.

16.
Arthritis Care Res (Hoboken) ; 72(7): 959-964, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31549793

RESUMO

OBJECTIVE: High magnetic resonance imaging (MRI)-detected inflammation is associated with greater progression and poorer outcomes in rheumatoid arthritis (RA). This analysis aimed to determine if baseline MRI inflammation was related to clinical response and remission in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) study. METHODS: AVERT was a phase IIIb, randomized, controlled trial with a 12-month, double-blind treatment period enrolling patients with early (≤2 years' duration), anti-citrullinated peptide-positive methotrexate (MTX)-naive RA. In this post hoc analysis, patients in the abatacept plus MTX (n = 114) and MTX (n = 111) arms with available MRI results were stratified into low and high baseline MRI inflammation groups based on previously developed cutoffs of synovitis and osteitis on unilateral hand-wrist contrast-enhanced MRI. Simplified Disease Activity Index (SDAI) remission (≤3.3), Clinical Disease Activity Index (CDAI) remission (≤2.8), Boolean remission, and Disease Activity Score in 28 joints using the C-reactive protein level (<2.6) were assessed. RESULTS: Overall, 100 of 225 patients (44.4%) had high baseline MRI inflammation. In patients with high baseline MRI inflammation, a significantly greater proportion achieved remission at 12 months with abatacept plus MTX versus MTX across SDAI (45.1% versus 16.3%; P = 0.0022), CDAI (47.1% versus 20.4%; P = 0.0065), and Boolean indices (39.2% versus 16.3%; P = 0.0156). In patients with low baseline MRI inflammation, remission rates were not significantly different with abatacept plus MTX versus MTX (SDAI: 39.7% versus 32.3%; P = 0.4961). CONCLUSION: In seropositive, MTX-naive patients with early RA and presence of objectively measured high inflammation by MRI, indicating poor prognosis, remission rates were higher with abatacept plus MTX treatment versus MTX.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Inflamação/diagnóstico por imagem , Abatacepte/uso terapêutico , Adulto , Artrite Reumatoide/patologia , Método Duplo-Cego , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Imagem por Ressonância Magnética , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento
17.
Ann Rheum Dis ; 78(11): 1454-1462, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31362993

RESUMO

BACKGROUND: In SELECT-COMPARE, a randomised double-blind study, upadacitinib 15 mg once daily was superior to placebo or adalimumab on background methotrexate (MTX) for treating rheumatoid arthritis signs and symptoms and inhibited radiographical progression versus placebo at 26 weeks. Here we report 48-week safety and efficacy in patients who continued their original medication or were rescued to the alternative medication for insufficient response. METHODS: Patients on MTX received upadacitinib 15 mg, placebo or adalimumab for 48 weeks. Rescue without washout, from placebo or adalimumab to upadacitinib or upadacitinib to adalimumab occurred if patients had <20% improvement in tender joint count (TJC) or swollen joint count (SJC) (weeks 14/18/22) or Clinical Disease Activity Index (CDAI) >10 (week 26); remaining placebo patients were switched to upadacitinib at week 26. Efficacy was analysed by randomised group (non-responder imputation), as well as separately for rescued patients (as observed). Treatment-emergent adverse events per 100 patient-years were summarised. RESULTS: Consistent with responses through week 26, from weeks 26 to 48, responses by randomised group including low disease activity, clinical remission and improvements in pain and function remained superior for upadacitinib versus adalimumab; radiographical progression remained lower for upadacitinib versus placebo (linear extrapolation). Although both switch groups responded, a higher proportion of patients rescued to upadacitinib from adalimumab achieved CDAI ≤10 at 6 months postswitch versus patients rescued from upadacitinib to adalimumab. Safety at week 48 was comparable to week 26. CONCLUSION: Upadacitinib+MTX demonstrated superior clinical and functional responses versus adalimumab+MTX and maintained inhibition of structural damage versus placebo+MTX through week 48. Patients with an insufficient response to adalimumab or upadacitinib safely achieved clinically meaningful responses after switching to the alternative medication without washout.


Assuntos
Adalimumab/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Metotrexato/administração & dosagem , Adulto , Artrite Reumatoide/diagnóstico por imagem , Progressão da Doença , Método Duplo-Cego , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Resultado do Tratamento
18.
Arthritis Rheumatol ; 71(11): 1788-1800, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31287230

RESUMO

OBJECTIVE: To evaluate the efficacy, including capacity for inhibition of radiographic progression, and safety of upadacitinib, a JAK1-selective inhibitor, as compared to placebo or adalimumab in patients with rheumatoid arthritis (RA) who have experienced an inadequate response to methotrexate (MTX). METHODS: In total, 1,629 RA patients with an inadequate response to MTX were randomized (2:2:1) to receive upadacitinib (15 mg once daily), placebo, or adalimumab (40 mg every other week) while continuing to take a stable background dose of MTX. The primary end points were achievement of an American College of Rheumatology 20% (ACR20) improvement response and a Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) of <2.6 in the upadacitinib group compared to the placebo group at week 12; inhibition of radiographic progression was evaluated at week 26. The study was also designed and powered to test for the noninferiority and superiority of upadacitinib compared to adalimumab, as measured both clinically and functionally. RESULTS: At week 12, both primary end points were met in patients receiving upadacitinib compared to those receiving placebo (P ≤ 0.001). An ACR20 improvement response was achieved by 71% of patients in the upadacitinib group compared to 36% in the placebo group, and a DAS28-CRP score of <2.6 was observed in 29% of patients receiving upadacitinib compared to 6% of patients receiving placebo. Upadacitinib was superior to adalimumab based on the ACR50 response rate, achievement of a DAS28-CRP score of ≤3.2, change in pain severity score, and change in the Health Assessment Questionnaire disability index. At week 26, more patients receiving upadacitinib than those receiving placebo or adalimumab achieved low disease activity or remission (P ≤ 0.001). Radiographic progression was significantly inhibited in patients receiving upadacitinib and was observed in fewer upadacitinib-treated patients than placebo-treated patients (P ≤ 0.001). Up to week 26, adverse events (AEs), including serious infections, were comparable between the upadacitinib and adalimumab groups. The proportions of patients with serious AEs and AEs leading to discontinuation were highest in the adalimumab group; the proportions of patients with herpes zoster and those with creatine phosphokinase (CPK) elevations were highest in the upadacitinib group. Three malignancies, 5 major adverse cardiovascular events, and 4 deaths were reported among the groups, but none occurred in patients receiving upadacitinib. Six venous thromboembolic events were reported (1 in the placebo group, 2 in the upadacitinib group, and 3 in the adalimumab group). CONCLUSION: Upadacitinib was superior to placebo and adalimumab for improving signs, symptoms, and physical function in RA patients who were receiving background MTX. In addition, radiographic progression was significantly inhibited by upadacitinib as compared to placebo. The overall safety profile of upadacitinib was generally similar to that of adalimumab, except for higher rates of herpes zoster and CPK elevations in patients receiving upadacitinib.


Assuntos
Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Adulto , Idoso , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/fisiopatologia , Creatina Quinase/metabolismo , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Herpes Zoster/epidemiologia , Humanos , Infecções/epidemiologia , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Tromboembolia Venosa/epidemiologia
19.
Joint Bone Spine ; 86(5): 594-599, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30928534

RESUMO

OBJECTIVES: The primary objective was to evaluate the correlation between 5-year radiographic structural disease progression and early clinical remission in recent-onset rheumatoid arthritis (RA). The secondary objective was to assess the correlation between erosion development in joints free of damage at baseline and early clinical remission. METHODS: A single-center retrospective study was performed in 133 patients meeting ACR criteria for RA of recent onset. Two radiologists independently quantified radiographic structural lesions at the hands and forefeet using the Sharp van der Heijde (SVdH) Score at the diagnosis then 5 years later. The patients were divided into two groups based on whether the lesions were stable (SVdH Score increase ≤ 10 points, Xray-STAB group) or had worsened (SVdH Score increase > 10 points, Xray-PROG group). The clinical response was assessed after 3, 6, and 12 months. Clinical remission was defined based on the DAS28-CRP, SDAI, CDAI, and ACR/EULAR Boolean remission criteria. RESULTS: Of the 133 patients, 90 were in the Xray-STAB group (mean SVdH score increase, 2.4 ± 2.9) and 43 in the Xray-PROG group (22.9 ± 13.4). The 6-month disease activity indices were higher in the Xray-PROG group (P < 0.05). Achieving a 6-month clinical remission had 58.6%, 39.1%, 40.0%, and 32.2% sensitivity for predicting 5-year radiographic stability when the DAS28-CRP, SDAI, CDAI, and Boolean definition were used, respectively; corresponding values for specificity were 73.8%, 85.7%, 83.7%, and 90.5%. CONCLUSION: Achieving a clinical remission within 6 months is key to preventing radiographic structural progression in patients with recent-onset RA.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Radiografia/métodos , Indução de Remissão/métodos , Artrite Reumatoide/tratamento farmacológico , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo
20.
Arthritis Res Ther ; 20(1): 265, 2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30509322

RESUMO

BACKGROUND: The aim of this global collaboration was to develop a consensual set of items for the analysis of synovial biopsies in clinical practice and translational research through the EULAR Synovitis Study Group (ESSG) and OMERACT Synovial Tissue Biopsy Group. METHODS: Participants were consulted through a modified Delphi method. Three sequential rounds occurred over 12 months. Members were sent a written questionnaire containing items divided into two parts. Items were identified and formulated based on a scoping review. The first part of the questionnaire referred to synovial biopsies in clinical practice including five subsections, and the second part to translational research with six subsections. Every participant was asked to score each item on a 5-point Likert scale. Items with a median score above 3.5 and a ≥ 70% agreement were selected for the next round. The last round was conducted orally at EULAR in June 2017. RESULTS: Twenty-seven participants from 19 centers were contacted by email. Twenty participants from 17 centers answered. Response rates for next rounds were 100%. For the first part relating to clinical practice, 20/44 items (45.5%) were selected. For the second part relating to translational research, 18/43 items (41.9%) were selected for the final set. CONCLUSIONS: We herein propose a consensual set of analysis items to be used for synovial biopsies conducted in clinical practice and translational research.


Assuntos
Biópsia/métodos , Doenças Reumáticas/diagnóstico , Membrana Sinovial/patologia , Sinovite/patologia , Biópsia/normas , Consenso , Técnica Delfos , Humanos , Padrões de Referência , Inquéritos e Questionários , Pesquisa Médica Translacional/métodos
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