Psychosocial burden predicts sustained remission in early rheumatoid arthritis: unraveling the complex interplay of wellbeing and disease activity

2021 ◽  
Author(s):  
Michaël Doumen ◽  
Diederik De Cock ◽  
Sofia Pazmino ◽  
Delphine Bertrand ◽  
Johan Joly ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Sustained Remission ◽  
Complex Interplay ◽  
Psychosocial Burden

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 Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period

2014 ◽  
Vol 74 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Paul Emery ◽  
Gerd R Burmester ◽  
Vivian P Bykerk ◽  
Bernard G Combe ◽  
Daniel E Furst ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Safety Profile ◽  
Treatment Withdrawal ◽  
Sustained Remission ◽  
Double Blind ◽  
Antibody Positivity ◽  
Registration Number ◽  
Maintenance Of Remission

ObjectivesTo evaluate clinical remission with subcutaneous abatacept plus methotrexate (MTX) and abatacept monotherapy at 12 months in patients with early rheumatoid arthritis (RA), and maintenance of remission following the rapid withdrawal of all RA treatment.MethodsIn the Assessing Very Early Rheumatoid arthritis Treatment phase 3b trial, patients with early active RA were randomised to double-blind, weekly, subcutaneous abatacept 125 mg plus MTX, abatacept 125 mg monotherapy, or MTX for 12 months. Patients with low disease activity (Disease Activity Score (DAS)28 (C reactive protein (CRP)) <3.2) at month 12 entered a 12-month period of withdrawal of all RA therapy. The coprimary endpoints were the proportion of patients with DAS28 (CRP) <2.6 at month 12 and both months 12 and 18, for abatacept plus MTX versus MTX.ResultsPatients had <2 years of RA symptoms, DAS28 (CRP) ≥3.2, anticitrullinated peptide-2 antibody positivity and 95.2% were rheumatoid factor positive. For abatacept plus MTX versus MTX, DAS28 (CRP) <2.6 was achieved in 60.9% versus 45.2% (p=0.010) at 12 months, and following treatment withdrawal, in 14.8% versus 7.8% (p=0.045) at both 12 and 18 months. DAS28 (CRP) <2.6 was achieved for abatacept monotherapy in 42.5% (month 12) and 12.4% (both months 12 and 18). Both abatacept arms had a safety profile comparable with MTX alone.ConclusionsAbatacept plus MTX demonstrated robust efficacy compared with MTX alone in early RA, with a good safety profile. The achievement of sustained remission following withdrawal of all RA therapy suggests an effect of abatacept's mechanism on autoimmune processes.Trial registration numberNCT01142726.

FRI0076 Low Disease Activity or DAS-Remission as Treatment Target in Early Rheumatoid Arthritis Patients

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 454.1-454
Author(s):  
G. Akdemir ◽  
I.M. Markusse ◽  
A.A. Schouffoer ◽  
P.B. de Sonnaville ◽  
B.A. Grillet ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Treatment Target ◽  
Low Disease Activity

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 POS0647 EFFICACY, SAFETY AND CHARACTERISTICS OF IGURATIMOD-BASED THERAPY IN THE TREATMENT OF UA, ERA AND RA PATIENTS FOR 24 WEEKS: A PROSPECTIVE COHORT STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 561.2-562
Author(s):  
X. Liu ◽  
Z. Sun ◽  
W. Guo ◽  
F. Wang ◽  
L. Song ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Adverse Events ◽  
Disease Activity ◽  
Prospective Cohort Study ◽  
Early Rheumatoid Arthritis ◽  
Prospective Cohort ◽  
Combined Treatment ◽  
Serious Adverse Events

Background:Experts emphasize early diagnosis and treatment in RA, but the widely used diagnostic criterias fail to meet the accurate judgment of early rheumatoid arthritis. In 2012, Professor Zhanguo Li took the lead in establishing ERA “Chinese standard”, and its sensitivity and accuracy have been recognized by peers. However, the optimal first-line treatment of patients (pts) with undifferentiated arthritis (UA), early rheumatoid arthritis (ERA), and rheumatoid arthritis (RA) are yet to be established.Objectives:To evaluate the efficacy and safety of Iguratimod-based (IGU-based) Strategy in the above three types of pts, and to explore the characteristics of the effects of IGU monotherapy and combined treatment.Methods:This prospective cohort study (ClinicalTrials.gov Identifier NCT01548001) was conducted in China. In this phase 4 study pts with RA (ACR 1987 criteria[1]), ERA (not match ACR 1987 criteria[1] but match ACR/EULAR 2010 criteria[2] or 2014 ERA criteria[3]), UA (not match classification criteria for ERA and RA but imaging suggests synovitis) were recruited. We applied different treatments according to the patient’s disease activity at baseline, including IGU monotherapy and combination therapies with methotrexate, hydroxychloroquine, and prednisone. Specifically, pts with LDA and fewer poor prognostic factors were entered the IGU monotherapy group (25 mg bid), and pts with high disease activity were assigned to combination groups. A Chi-square test was applied for comparison. The primary outcomes were the proportion of pts in remission (REM)or low disease activity (LDA) that is DAS28-ESR<2.6 or 3.2 at 24 weeks, as well as the proportion of pts, achieved ACR20, Boolean remission, and good or moderate EULAR response (G+M).Results:A total of 313 pts (26 pts with UA, 59 pts with ERA, and 228 pts with RA) were included in this study. Of these, 227/313 (72.5%) pts completed the 24-week follow-up. The results showed that 115/227 (50.7%), 174/227 (76.7%), 77/227 (33.9%), 179/227 (78.9%) pts achieved DAS28-ESR defined REM and LDA, ACR20, Boolean remission, G+M response, respectively. All parameters continued to decrease in all pts after treatment (Fig 1).Compared with baseline, the three highest decline indexes of disease activity at week 24 were SW28, CDAI, and T28, with an average decline rate of 73.8%, 61.4%, 58.7%, respectively. Results were similar in three cohorts.We performed a stratified analysis of which IGU treatment should be used in different cohorts. The study found that the proportion of pts with UA and ERA who used IGU monotherapy were significantly higher than those in the RA cohort. While the proportion of triple and quadruple combined use of IGU in RA pts was significantly higher than that of ERA and UA at baseline and whole-course (Fig 2).A total of 81/313 (25.8%) pts in this study had adverse events (AE) with no serious adverse events. The main adverse events were infection(25/313, 7.99%), gastrointestinal disorders(13/313, 4.15%), liver dysfunction(12/313, 3.83%) which were lower than 259/2666 (9.71%) in the previous Japanese phase IV study[4].The most common reasons of lost follow-up were: 1) discontinued after remission 25/86 (29.1%); 2) lost 22/86 (25.6%); 3) drug ineffective 19/86 (22.1%).Conclusion:Both IGU-based monotherapy and combined therapies are tolerant and effective for treating UA, ERA, and RA, while the decline in joint symptoms was most significant. Overall, IGU combination treatments were most used in RA pts, while monotherapy was predominant in ERA and UA pts.References:[1]Levin RW, et al. Scand J Rheumatol 1996, 25(5):277-281.[2]Kay J, et al. Rheumatology 2012, 51(Suppl 6):vi5-9.[3]Zhao J, et al. Clin Exp Rheumatol 2014, 32(5):667-673.[4]Mimori T, et al. Mod Rheumatol 2019, 29(2):314-323.Disclosure of Interests:None declared

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 Sex-based differences in association between circulating T cell subsets and disease activity in untreated early rheumatoid arthritis patients

2018 ◽  
Vol 20 (1) ◽  
Author(s):  
Jonathan Aldridge ◽  
Jayesh M. Pandya ◽  
Linda Meurs ◽  
Kerstin Andersson ◽  
Inger Nordström ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
T Cell Subsets

scholarly journals Effective Treatment for Rapid Improvement of Both Disease Activity and Self-Reported Physical Activity in Early Rheumatoid Arthritis

2016 ◽  
Vol 68 (2) ◽  
pp. 280-284 ◽  
Author(s):  
Nicole P. C. Konijn ◽  
Lilian H. D. van Tuyl ◽  
Maarten Boers ◽  
Debby den Uyl ◽  
Marieke M. ter Wee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Physical Activity ◽  
Disease Activity ◽  
Effective Treatment ◽  
Early Rheumatoid Arthritis ◽  
Rapid Improvement
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