Initiating tocilizumab, with or without methotrexate, compared with starting methotrexate with prednisone within step-up treatment strategies in early rheumatoid arthritis: an indirect comparison of effectiveness and safety of the U-Act-Early and CAMERA-II treat-to-target trials

2019 ◽  
Vol 78 (10) ◽  
pp. 1333-1338 ◽  
Author(s):  
Maxime MA Verhoeven ◽  
Marjolein JH de Hair ◽  
Janneke Tekstra ◽  
Johannes WJ Bijlsma ◽  
Jacob M van Laar ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Initial Treatment ◽  
Activity Index ◽  
Indirect Comparison ◽  
Specific Effect ◽  
Treat To Target ◽  
Early Ra ◽  
Outcome Score

ObjectivesMethotrexate (MTX), often combined with low moderately dosed prednisone, is still the cornerstone of initial treatment for early rheumatoid arthritis (RA). It is not known how this strategy compares with initial treatment with a biological. We therefore compared the effectiveness of tocilizumab (TCZ), or TCZ plus MTX (TCZ+MTX) with MTX plus 10 mg prednisone (MTX+pred), all initiated within a treat-to-target treatment strategy in early RA.MethodsUsing individual patient data of two trials, we indirectly compared tight-controlled treat-to-target strategies initiating TCZ (n=103), TCZ+MTX (n=106) or MTX+pred (n=117), using initiation of MTX (n=227) as reference. Primary outcome was Disease Activity Score assessing 28 joints (DAS28) over 24 months. To assess the influence of acute phase reactants (APRs), a disease activity composite outcome score without APR (ie, modification of the Clinical Disease Activity Index (m-CDAI)) was analysed. Secondary outcomes were remission (several definitions), physical function and radiographic progression. Multilevel models were used to account for clustering within trials and patients over time, correcting for relevant confounders.ResultsDAS28 over 24 months was lower for TCZ+MTX than for MTX+Pred (mean difference: −0.62 (95% CI −1.14 to −0.10)). Remission was more often achieved in TCZ+MTX and in TCZ versus MTX+pred (p=0.02/0.05, respectively). Excluding APRs from the disease activity outcome score, TCZ-based strategies showed a slightly higher m-CDAI compared with MTX+pred, but this was not statistically significant. Other outcomes were also not statistically significantly different between the strategies.ConclusionsIn patients with early RA, although TCZ-based strategies resulted in better DAS28 and remission rates compared with MTX+pred, at least part of these effects may be due to a specific effect of TCZ on APRs.

scholarly journals Long-term prognosis and quality of life in patients with early rheumatoid arthritis treated according to the 2015 ACR guideline (LELAND): protocol for a multicentre prospective observational study in Southern China

BMJ Open ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. e023798
Author(s):  
Jinjun Zhao ◽  
Taihe Zhan ◽  
Junqing Zhu ◽  
Meida Fan ◽  
Qin Huang ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Treat To Target ◽  
Early Ra ◽  
Long Term Prognosis

IntroductionRheumatoid arthritis (RA) is a chronic systemic disease and one of the most disabling diseases for patients. The American College of Rheumatology (ACR) issued a new guideline in 2015 for the treatment of RA based on the treat-to-target strategy to achieve better outcomes. This study will focus on the real-world rates of remission and low disease activity of patients with early RA in China, who will be treated according to the 2015 ACR guideline. Additionally, factors influencing treat-to-target outcomes will be analysed, and long-term prognosis and quality of life will be assessed.Method and analysisTwo-hundred patients with early RA will be enrolled, treated and followed up once every 3 months for 48 months. These patients should fulfil the 2010 RA classification criteria of the ACR/European League Against Rheumatism with a disease course of no more than 6 months and should also fulfil other eligibility criteria. The patients will be treated following the 2015 ACR guideline. Their disease activity will be assessed, and they will be instructed to complete several questionnaires once every 3 months. The primary outcomes are the Disease Activity Score on 28 joints and Health Assessment Questionnaire Disability Index. The secondary outcome variables are the Simplified Disease Activity Index, Clinical Disease Activity Index and Routine Assessment of Patient Index Data 3 results, imaging data and personal medical costs. The data will be analysed using appropriate statistical analyses.Ethics and disseminationThis research was approved by the Nanfang Hospital Ethics Committee (NFEC-2017–192). The results of the study will be published in international peer-reviewed journals.Trial registration numberNCT03508713; Pre-results.

scholarly journals Plasma interferon-alpha is associated with double-positivity for autoantibodies but is not a predictor of remission in early rheumatoid arthritis—a spin-off study of the NORD-STAR randomized clinical trial

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Marit Stockfelt ◽  
Anna-Carin Lundell ◽  
Merete Lund Hetland ◽  
Mikkel Østergaard ◽  
Till Uhlig ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trial ◽  
Disease Activity ◽  
Randomized Clinical Trial ◽  
Early Rheumatoid Arthritis ◽  
Treatment Initiation ◽  
Certolizumab Pegol ◽  
Type I ◽  
Protein Levels ◽  
Early Ra

Abstract Background The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. Methods Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFNα protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. Results IFNα protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFNα protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFNα protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. Conclusion IFNα protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFNα positivity did not predict remission in any of the treatment arms, suggesting that the IFNα system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, https://clinicaltrials.gov/ct2/show/NCT01491815.

scholarly journals SAT0033 USING CHROMOSOME CONFORMATION FOR INSIGHT INTO PATHOGENESIS OF EARLY RHEUMATOID ARTHRITIS ENDOTYPES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 946.2-947
Author(s):  
C. Duncan ◽  
E. Hunter ◽  
C. Koutsothanasi ◽  
M. Salter ◽  
A. Akoulitchev ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Inadequate Response ◽  
Loss Of Function ◽  
Inception Cohort ◽  
Chromosome Conformation ◽  
Patient Response ◽  
Early Ra ◽  
Longitudinal Response

Background:Rheumatoid arthritis (RA) is a chronic autoimmune disease with substantial immunopathogenic heterogeneity. It is well established that early diagnosis and initiation of effective therapy is crucial to prevent loss of function. Previously, various RA treatment trajectories have been identified, however there are currently no clinically validated biomarkers that can identify these trajectories at the start of treatment. Evaluation of the structural epigenome has revealed that chromosome conformation signatures (CCS) offer great potential as binary, informative biomarkers, and have been previously shown to predict early RA patient response to Methotrexate with 90% sensitivity (1). These signatures can also reveal highly regulated areas of the genome, which may be underpinning disease endotypes.Objectives:The objective of this study was to evaluate the structural epigenome in early RA over longitudinal samples to determine whether it is associated with treatment trajectories.Methods:Patient data and samples were from the Scottish Early Rheumatoid Arthritis (SERA) cohort; a pan-Scotland inception cohort. CDAI, DAS28 ESR and DAS28 CRP measurements were calculated at baseline, 6 months and 12 months to determine longitudinal treatment response. From 3 principal longitudinal response trajectories, 18 patients (who had equivalent disease activity at baseline) were chosen to investigate the structural epigenome. These 18 comprised of responders (R), non-responders (NR) and initial responders (IR; low disease activity/remission at 6 months but moderate/high disease activity at 12 months) with 6 patients per group at each time point. 20 pooled healthy samples were used as a comparator population. EpiSwitch libraries were probed on 180K Agilent SureSelect custom arrays that were designed using EpiSwitch propriety information and publicly available data from Walshet al(2). Microarray data was analysed using the Limma package within R studio.Results:EpiSwitch array analysis showed that there were >10,000 statistically significant differential chromosomal loops between R, NR and IR. Evaluation of the 3 trajectory groups (R, NR and IR), taking into account the healthy chromosomal conformation, revealed an RA-associated structural epigenome that comprised of 10,445 chromosomal loops that were stable, over the three time points. Subsequent analysis of the distinct treatment trajectories demonstrated that 3683 of the stable, disease-associated chromosomal loops were shared by all 3. However, 4496 were associated with distinct response trajectories, with 1221, 2574 and 701 loops unique to R, NR and IR respectively.Conclusion:The stable chromosomal architecture unique to each treatment trajectory suggests that various underlying molecular endotypes may exist. Moreover, the stable loops common to all groups allude to a baseline level of dysregulation in RA and offers the potential to discover novel drivers of disease. This work provides the foundation to further our understanding of RA pathogenesis and the potential of finding a biomarker that would be of significant value in a clinical setting.References:[1] Carini, C., Hunter, E., Scottish Early Rheumatoid Arthritis Inception cohort Investigators, Ramadass, A. S., Green, J., Akoulitchev, A., et al. (2018). Chromosome conformation signatures define predictive markers of inadequate response to methotrexate in early rheumatoid arthritis.Journal of Translational Medicine,16(1), 18–11[2] Walsh, A. M., Whitaker, J. W., Huang, C. C., Cherkas, Y., Lamberth, S. L., Brodmerkel, C., et al. (2016). Integrative genomic deconvolution of rheumatoid arthritis GWAS loci into gene and cell type associations.Genome Biology,17(1), 2205Disclosure of Interests:Caitlin Duncan: None declared, Ewan Hunter: None declared, Christina Koutsothanasi: None declared, Matthew Salter: None declared, Alexandre Akoulitchev: None declared, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Carl Goodyear: None declared

scholarly journals AB0179 INFLUENCE OF AINFLUENCE OF ANTI-CITRULLINATED PROTEIN/PEPTIDE ANTIBODIES (ACPAS)ON ARTICULAR MANIFESTATIONS, DISEASE ACTIVITY AND STRUCTURAL SEVERITY IN ALGERIAN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1115.1-1115
Author(s):  
F. Rahal ◽  
N. Brahumi ◽  
A. Ladjouze-Rezig ◽  
S. Lefkir
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Disease Activity Score ◽  
Activity Score ◽  
Symptom Duration ◽  
Early Ra ◽  
The Mean ◽  
Citrullinated Protein ◽  
Peptide Antibodies

Background:Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific and sensitive markers for rheumatoid arthritis (RA). There are also suggested to have a more severe rheumatoid arthritis.Objectives:The aim of this study was to assess the influence of ACPA on disease activity, radiological severity, and functional disability in Algerian patient with early rheumatoid arthritis (RA).Methods:Consecutive early RA patients (symptom duration ≤24 months) recruited were included in the descriptive, longitudinal, prospective study. Demographic, biological, immunological and radiographic data were collected at the time of inclusion in the study. Disease activity as determined by the Disease Activity Score 28-CPR (DAS28- CPR: 4 variables), functional handicap as calculated by Heath Assessment Score (HAQ), and bone and joint damage as evaluated by Sharp-Van der Heijde (SVDH) erosion and narrowing score.Results:One hundred and sixty-one patients with RA were recruited. Patients mean age 43.71±14 years and mean symptom duration at inclusion was 10.48±7 months. Small and larges were affected in 64,3%. The mean ESR was 23,53±15,2 mm/1st hour, and the mean CRP level was 19,42±39.8 mg/l. Rheumatoid Factors (RFs) and Anti-Citrullinated Protein Antibodies (ACPAs) were present in 74% and 88% of patients, respectively. The presence of ACPAs was significantly associated with DAS28 (p=0,004) and HAQ (p=0,002). There was no significant difference in inflammatory markers and radiographic SVDH score between patients with and without ACPAs. Stepwise regression analysis showed that the presence of ACPAs was independently associated with localization when RA affected smalls and larges joint in the same time (OR=5,24; IC 95% 1,224-22,483; p=0,026).Conclusion:These data show that in patients with early RA, ACPAs positivity was significantly associated with articular manifestations, activity disease and functional handicap, but not with structural damage.References:[1]Nikiphorou E, Norton S, Young A, et al. Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery: combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds. Ann Rheum Dis. 2016;75(12):2080-2086. doi:10.1136/annrheumdis-2015-208669.[2]Karimifar M, Salesi M, Farajzadegan Z. The association of anti-CCP1 antibodies with disease activity score 28 (DAS-28) in rheumatoid arthritis. Adv Biomed Res. 2012;1:30. doi:10.4103/2277-9175.98156.[3]Boman A, Brink M, Lundquist A, et al. Antibodies against citrullinated peptides are associated with clinical and radiological outcomes in patients with early rheumatoid arthritis: a prospective longitudinal inception cohort study. RMD Open. 2019;5(2):e000946. Published 2019 Sep 3. doi:10.1136/rmdopen-2019-000946.Disclosure of Interests:None declared

scholarly journals FRI0020 CLINICAL TREATMENT RESPONSE STILL DOES NOT MATCH PATIENT REPORTED IMPROVEMENT, EVEN IN EARLY RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 582.1-582
Author(s):  
S. Pazmino ◽  
A. Lovik ◽  
A. Boonen ◽  
D. De Cock ◽  
V. Stouten ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Health Assessment ◽  
Sustained Remission ◽  
Research Support ◽  
Early Ra ◽  
Severity Scores ◽  
Patient Reported ◽  
Over Time

Background:Commonly used disease activity scores in rheumatoid arthritis (RA) include one patient reported outcome (PRO) -the patient’s global health assessment (PGA). Exploratory factor analysis (EFA) was performed on data from the 2 year Care in early Rheumatoid Arthritis (CareRA) trial to explain the evolution of disease burden extracting 3 factors.1Objectives:To assess the evolution and relative responsiveness over time of clinical, laboratory and patient assessments included in composite scores, together with other PROs like pain, fatigue and functionality in patients with early RA (≤1 year) treated to target (T2T) within the CareRA trial.Methods:DMARD naïve patients with early RA (n=379) were included, randomized to remission induction with COBRA-like treatment schemes (n=332) or MTX monotherapy (n=47) and T2T.Components of disease activity scores (swollen/tender joint count (S/TJC), C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), and physician (PhGH) or patient (PGA) global health assessment), pain and fatigue (both on 0-100 scale) and HAQ were recorded at every visit.Missing data was handled with multiple imputation (n=15). Clustering was removed with multiple outputation (n=1000), then each of the 15 000 datasets was analyzed by EFA with principal component extraction and oblimin rotation. The analyses were combined after re-ordering the factors by maximizing factor congruence. The 3 extracted factors and their individual components (with their loadings) were: 1. Patient containing PGA (0.87), pain (0.86), fatigue (0.90) and HAQ (0.5) 2.Clinical with SJC (0.92), TJC (0.89) and PhGH (0.76) and 3.Laboratory with CRP(0.87) and ESR (0.78).1(Pazmino, ACR 2019 abstract, Table 3)Afterwards, variables were first normalized to a 0-1 scale, then multiplied -weighted- by the factor loadings previously obtained.1For each Patient, Clinical and Laboratory severity score, the weighted variables belonging to each score were summed together and then re-scaled to 0-1 (higher values suggest more burden).The percentage (%) improvement from baseline to week 104 and the area under the curve (AUC) across time points were calculated per factor.Differences in % improvement and AUC were compared between patients not achieving and achieving early and sustained (week 16 to 104) disease activity score remission (DAS28CRP <2.6) with ANOVA. Bonferroni correction was used for multiple testing.Results:Severity scores of Patient, Clinical and Laboratory factors improved rapidly over time (Figure 1). In patients achieving sustained remission (n=122), Patient, Clinical and Laboratory scores improved 56%, 90% and 27% respectively. In patients not achieving sustained remission (n=257) the improvement was 32%, 78% and 9% respectively (p<0.001 only for clinical improvement).Patients in CareRA who achieved sustained remission had an AUC of 15.1, 3.4 and 4.7 in Patient, Clinical and Laboratory scores respectively, compared to 32.3, 10.0, and 7.2 in participants not achieving sustained remission (p<0.001 for all comparisons).Conclusion:Patient, Clinical and Laboratory severity scores improved rapidly over time in patients achieving rapid and sustained disease control. However, overall, Patient burden seemed not to improve to the same extent as Clinical burden. Patient’s unmet needs in terms of pain, fatigue, functionality and overall well-being should thus be given more attention, even in patients in sustained remission.References:[1]Pazmino S,et al.Including Pain, Fatigue and Functionality Regularly in the Assessment of Patients with Early Rheumatoid Arthritis Separately Adds to the Evaluation of Disease Status [abstract]. ACR. 2019.Disclosure of Interests:Sofia Pazmino: None declared, Anikó Lovik: None declared, Annelies Boonen Grant/research support from: AbbVie, Consultant of: Galapagos, Lilly (all paid to the department), Diederik De Cock: None declared, Veerle Stouten: None declared, Johan Joly: None declared, Delphine Bertrand: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies

scholarly journals Do Poor Prognostic Factors in Rheumatoid Arthritis Affect Treatment Choices and Outcomes? Analysis of a US Rheumatoid Arthritis Registry

2018 ◽  
Vol 45 (10) ◽  
pp. 1353-1360 ◽  
Author(s):  
Evo Alemao ◽  
Heather J. Litman ◽  
Sean E. Connolly ◽  
Sheila Kelly ◽  
Winnie Hua ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Prognostic Factors ◽  
Disease Activity ◽  
Clinical Outcomes ◽  
Activity Index ◽  
Functional Limitation ◽  
Disease Activity Index ◽  
Treat To Target ◽  
Work Status ◽  
Logistic Regression Models

Objective.To characterize patients with rheumatoid arthritis (RA) by number of poor prognostic factors (PPF: functional limitation, extraarticular disease, seropositivity, erosions) and evaluate treatment acceleration, clinical outcomes, and work status over 12 months by number of PPF.Methods.Using the Corrona RA registry (January 2005–December 2015), biologic-naive patients with diagnosed RA having 12-month (± 3 mos) followup were identified and categorized by PPF (0–1, 2, ≥ 3). Changes in medication, Clinical Disease Activity Index (CDAI), and work status (baseline–12 mos) were evaluated using linear and logistic regression models.Results.There were 3458 patients who met the selection criteria: 1489 (43.1%), 1214 (35.1%), and 755 (21.8%) had 0–1, 2, or ≥ 3 PPF, respectively. At baseline, patients with ≥ 3 PPF were older, and had longer RA duration and higher CDAI versus those with 0–1 PPF. In 0–1, 2, and ≥ 3 PPF groups, respectively, 20.9%, 23.2%, and 26.5% of patients received ≥ 1 biologic (p = 0.011). Biologic/targeted synthetic disease-modifying antirheumatic drug (tsDMARD) use was similar in patients with/without PPF (p = 0.57). After adjusting for baseline CDAI, mean (standard error) change in CDAI was −4.95 (0.24), −4.53 (0.27), and −2.52 (0.34) for 0–1, 2, and ≥ 3 PPF groups, respectively. More patients were working at baseline but not at 12-month followup in 2 (13.9%) and ≥ 3 (12.5%) versus 0–1 (7.3%) PPF group.Conclusion.Despite high disease activity and worse clinical outcomes, number of PPF did not significantly predict biologic/tsDMARD use. This may warrant reconsideration of the importance of PPF in treat-to-target approaches.

scholarly journals Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis

2020 ◽  
pp. annrheumdis-2020-218412
Author(s):  
Roy M Fleischmann ◽  
Ricardo Blanco ◽  
Stephen Hall ◽  
Glen T D Thomson ◽  
Filip E Van den Bosch ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Kinase Inhibitor ◽  
Activity Index ◽  
Disease Activity Index ◽  
Initial Therapy ◽  
Janus Kinase ◽  
Treat To Target ◽  
Efficacy And Safety ◽  
Insufficient Response

ObjectivesTo evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy.MethodsSELECT-COMPARE randomised patients to upadacitinib 15 mg once daily (n=651), placebo (n=651) or adalimumab 40 mg every other week (n=327). A treat-to-target study design was implemented, with blinded rescue occurring prior to week 26 for patients who did not achieve at least 20% improvement in both tender and swollen joint counts (‘non-responders’) and at week 26 based on Clinical Disease Activity Index (CDAI) >10 (‘incomplete-responders’) without washout.ResultsA total of 39% (252/651) and 49% (159/327) of patients originally randomised to upadacitinib and adalimumab were rescued to the alternate therapy. In both switch groups (adalimumab to upadacitinib and vice versa) and in non-responders and incomplete-responders, improvements in disease activity were observed at 3 and 6 months following rescue. CDAI low disease activity was achieved by 36% and 47% of non-responders and 45% and 58% of incomplete-responders switched to adalimumab and upadacitinib, respectively, 6 months following switch. Overall, approximately 5% of rescued patients experienced worsening in disease activity at 6 months postswitch. The frequency of adverse events was similar between switch groups.ConclusionsThese observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes. No new safety findings were observed despite immediate switch without washout.

scholarly journals Clinical and ultrasound remission after 6 months of treat-to-target therapy in early rheumatoid arthritis: associations to future good radiographic and physical outcomes

2018 ◽  
Vol 77 (10) ◽  
pp. 1421-1425 ◽  
Author(s):  
Nina Paulshus Sundlisæter ◽  
Anna-Birgitte Aga ◽  
Inge Christoffer Olsen ◽  
Hilde Berner Hammer ◽  
Till Uhlig ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Radiographic Progression ◽  
Activity Index ◽  
Power Doppler ◽  
Disease Activity Index ◽  
Treat To Target ◽  
Good Outcome ◽  
Grey Scale

ObjectiveTo explore associations between remission, based on clinical and ultrasound definitions, and future good radiographic and physical outcome in early rheumatoid arthritis (RA).MethodsNewly diagnosed patients with RA followed a treat-to-target strategy incorporating ultrasound information in the Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen (ARCTIC) trial. We defined 6-month remission according to Disease Activity Score, Disease Activity Score in 28 joints-erythrocyte sedimentation rate, American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean criteria, Simplified Disease Activity Index, Clinical Disease Activity Index and two ultrasound definitions (no power Doppler signal, grey scale score ≤2). Two outcomes were defined: no radiographic progression and good outcome (no radiographic progression+physical function≥general population median), both sustained 12–24 months. We calculated the ORs of these outcomes for the remission definitions.ResultsOf 103 patients, 42%–82% reached remission at 6 months, dependent on definition. Seventy-one per cent of patients had no radiographic progression and 37% had good outcome. An association between 6-month remission and no radiographic progression was observed for ACR/EULAR Boolean remission (44 joints, OR 3.2, 95% CI 1.2 to 8.4), ultrasound power Doppler (OR 3.6, 95% CI 1.3 to 10.0) and grey scale remission (OR 3.2, 95% CI 1.2 to 8.0). All clinical, but not ultrasound remission criteria were associated with achievement of a good outcome.ConclusionsOur data support ACR/EULAR Boolean remission based on 44 joints as the preferred treatment target in early RA. Absence of ultrasound inflammation was associated with no radiographic progression.Trial registration numberNCT01205854; Post-results.

scholarly journals Potential applicability of cytokines as biomarkers of disease activity in rheumatoid arthritis: Enzyme-linked immunosorbent spot assay-based evaluation of TNF-α, IL-1β, IL-10 and IL-17A

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0246111
Author(s):  
Keerthie Dissanayake ◽  
Chandrika Jayasinghe ◽  
Priyani Wanigasekara ◽  
Ajith Sominanda
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Elispot Assay ◽  
Disease Activity Score ◽  
Activity Index ◽  
Pivotal Role ◽  
Activity Score ◽  
Early Ra ◽  
Tnf Α ◽  
Potential Applicability

Biomarkers play a pivotal role in the management of rheumatoid arthritis (RA) by facilitating early diagnosis and ‘treat to the target.’ However, no gold standard biomarker has been identified for monitoring the disease activity in RA. Cytokines, a diverse group of small protein molecules secreted by peripheral blood mononuclear cells (PBMCs), play a pivotal role in pathogenesis and disease progression in RA. Research is currently underway to find out the applicability of cytokines as biomarkers in RA. This study aimed to quantify the PBMCs that secrete four types of cytokines; TNF-α, IL-1β, IL-10 and IL-17A in two cohorts of active RA patients (early RA patients and established RA patients), compared to healthy controls (HC), using the enzyme-linked immunosorbent spot (ELISPOT) assay, and to assess their association with measures of disease activity of RA. Patients were recruited from outpatient rheumatology clinics, and the disease activity was assessed using single and composite measures of disease activity. The cytokine expression was evaluated using freshly separated PBMCs from whole blood of RA patients using the ELISPOT assay. The number of PBMCs (counted as spot-forming cells (SFCs) per 105 PBMCs) that secreted the cytokine of interest were statistically significantly higher in early RA patients, compared to HC, for IL-17A (P<0.05). Such an increased number of SFCs was not observed in the established RA group, compared to controls, for any of the cytokines tested. The correlation analysis showed that IL-17A is having a moderate correlation (Spearman`s ρ, p <0.05) with five clinical measures of disease activity, including disease activity score 28 (DAS28). According to the multivariable linear regression models, IL17A was a good predictor of both the disease activity score 28 (DAS28) and clinical disease activity index (CDAI). In conclusion, IL-17A has potential applicability as a biomarker of disease activity of RA.

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