scholarly journals POS0021 INTERMETATARSAL BURSITIS, A NOVEL FEATURE OF JUXTA-ARTICULAR INFLAMMATION IN EARLY RHEUMATOID ARTHRITIS: RESULTS FROM A LONGITUDINAL MRI-STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 212-213
Author(s):  
B. Van Dijk ◽  
Y. Dakkak ◽  
X. Matthijssen ◽  
E. Niemantsverdriet ◽  
M. Reijnierse ◽  
...  

Background:Rheumatoid arthritis (RA) is characterised by inflammation of the synovial lining. In addition to synovitis, the tendon sheaths of small hand and foot joints are also frequently inflamed. This results in tenosynovitis, which is often missed at clinical evaluation in early RA but visible on imaging, such as MRI. A third anatomical structure surrounded by a synovial lining is formed by the intermetatarsal bursae in the forefeet. Inflammation of these bursae (intermetatarsal bursitis; IMB) was recently identified at MRI-studies and shown to be specific for early RA.[1] This suggests that IMB is also a feature of early RA.Objectives:We hypothesised that if IMB is indeed an RA-feature, then (1) at diagnosis its presence associates with other measures of local inflammation (synovitis, tenosynovitis and osteitis) and (2) it responds to DMARD therapy similarly as these other local inflammatory measures. These hypotheses were tested in a comprehensive MRI-study.Methods:157 consecutive early RA patients underwent unilateral contrast-enhanced 1.5T MRI of the forefoot at diagnosis. MRIs were evaluated for presence of IMB and for synovitis, tenosynovitis and osteitis in line with the RA MRI scoring system (summed as RAMRIS-inflammation). MRIs at 4, 12 and 24 months were evaluated for presence and size of IMB-lesions in patients who had IMB at baseline and received early DMARD-therapy. Logistic regression was used for analyses at patient-level; generalised estimating equations were used for bursa-level analyses. Stratification for ACPA was performed.Results:69% of RA patients had ≥1 IMB. In multivariable analyses on bursa-level, presence of IMB was independently associated with local presence of synovitis and tenosynovitis (OR 1.69 (95%CI 1.12–2.57) and 2.83 (1.80–4.44), respectively), but not with osteitis. On patient-level, presence of IMB was most strongly associated with tenosynovitis (OR 2.92 (1.62–5.24)). During treatment with DMARDs, the average size of IMB-lesions decreased (Figure 1). This decrease was associated with decrease in RAMRIS-inflammation scores; most strongly with a decrease in synovitis but not in osteitis. Within ACPA-positive and ACPA-negative RA similar results were obtained.Conclusion:IMB particularly accompanies inflammation of the synovial lining of joints and tendon-sheaths, both regarding simultaneous occurrence at diagnosis and simultaneous treatment-response. These findings suggest that IMB represents juxta-articular synovial inflammation and indeed is a hallmark of early RA.References:[1]Dakkak YJ et al. Increased frequency of intermetatarsal and submetatarsal bursitis in early rheumatoid arthritis: a large case-controlled MRI study. Arthritis Res Ther 22, 277 (2020).Disclosure of Interests:None declared.

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Yousra J. Dakkak ◽  
Ellis Niemantsverdriet ◽  
Annette H. M. van der Helm-van Mil ◽  
Monique Reijnierse

Abstract Background The forefoot is a preferential location for joint and tendon sheath inflammation in rheumatoid arthritis (RA). It also contains bursae, of which the intermetatarsal bursae have a synovial lining. Some small imaging studies suggested that intermetatarsal bursitis (IMB) and submetatarsal bursitis (SMB) are involved in RA, but their association has not been thoroughly explored. Healthy control studies suggested that lesion size might be relevant. We studied the relation between IMB and SMB in early RA, compared to other arthritides and healthy controls, and the relevance of lesion sizes. Methods Six hundred and thirty-four participants were studied: 157 consecutive patients presenting with early RA, 284 other arthritides, and 193 healthy controls. All underwent unilateral contrast-enhanced MRI of the forefoot at presentation. Two readers independently scored IMB and SMB and measured transverse and dorsoplantar diameters, blinded to clinical data. Subsequently, consensus was reached. Intra-reader ICC was 0.89. Logistic regression models were used, and test characteristics were calculated. Results IMB and SMB associated with RA independent of each other (P < 0.001) and independent of age, gender, BMI, RA-MRI inflammation, and anti-CCP-antibodies (P = 0.041). Sensitivity for RA of IMB was 69%, and for SMB 25%. Specificity for IMB was 70% compared to other arthritides, and 84% compared to healthy controls. For SMB, this was 94% and 97% respectively. Regarding lesion size, the groups had considerable overlap: no cut-off size for RA could be distinguished with high sensitivity and specificity. Conclusion Intermetatarsal and submetatarsal bursitis associated with early rheumatoid arthritis, contributing to the emerging evidence that inflammation of juxta-articular soft tissues is an early feature of RA.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Marit Stockfelt ◽  
Anna-Carin Lundell ◽  
Merete Lund Hetland ◽  
Mikkel Østergaard ◽  
Till Uhlig ◽  
...  

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.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 422.2-423
Author(s):  
B. van Dijk ◽  
F. Wouters ◽  
E. van Mulligen ◽  
M. Reijnierse ◽  
A. van der Helm - van Mil

Background:Inflammation of the synovial lining is a hallmark of rheumatoid arthritis (RA). A synovial lining is not only present at synovial joints and tendon sheaths but also at bursae. Inflammation of the synovium-lined intermetatarsal bursae in the forefoot, intermetatarsal bursitis (IMB), was recently identified with MRI. It is specific for early RA and present in the majority of RA patients at diagnosis. During development of RA, MRI-detectable subclinical synovitis and tenosynovitis often occur before clinical arthritis presents. Whether IMB is also present in a pre-arthritis stage is unknown.Objectives:To assess the occurrence of IMB in patients with clinically suspect arthralgia (CSA) and its association with progression to clinical arthritis in a large MRI-study.Methods:We studied 524 consecutive patients presenting with CSA. CSA was defined as recent-onset arthralgia of small joints that is likely to progress to RA based on the clinical expertise of the rheumatologist. Participants underwent unilateral contrast-enhanced 1.5T MRI of the forefoot, metacarpophalangeal (MCP) joints and wrist at baseline. Thereafter patients were followed for detection of clinical arthritis, as identified at physical joint examination by the rheumatologist. Baseline MRIs were evaluated for IMB at all 4 intermetatarsal spaces. Also synovitis, tenosynovitis and osteitis were assessed in line with the RA MRI scoring system (summed as RAMRIS-inflammation). Both IMB and RAMRIS-inflammation were dichotomised into positive/negative using data from age-matched symptom-free controls as a reference. Cox regression analysed the association of IMB with progression to clinical arthritis; multivariable analyses were used to adjust for RAMRIS-inflammation which is known to associate with progression to clinical arthritis. Analyses were repeated stratified for ACPA-status, since ACPA-positive and ACPA-negative RA are considered separate entities with differences in pathophysiology.Results:The baseline MRIs showed ≥1 IMB in 35% of CSA-patients. Patients with IMB were more likely to also have synovitis (OR 2.5 (95%CI 1.2–4.9)) and tenosynovitis (8.9 (3.4–22.9)) on forefoot MRI, but not osteitis (0.9 (0.5–1.8)). Patients were followed for median 25 months (IQR 19–27). IMB-positive patients developed clinical arthritis more often than IMB-negative patients (HR 3.0 (1.9-4.8)). This association was independent of RAMRIS-inflammation (adjusted HR 2.2 (1.4–3.6)). In stratified analyses, IMB was more frequent in ACPA-positive than in ACPA-negative CSA (68% vs. 30%, p<0.001). Moreover IMB predicted clinical arthritis development in ACPA-positive CSA (HR 2.5 (1.1–5.7)) but not in ACPA-negative CSA patients (1.0 (0.5–2.2)).Conclusion:One-third of CSA patients have IMB. IMB is frequently present in conjunction with subclinical synovitis and tenosynovitis. It precedes the development of clinical arthritis, and in particular the development of ACPA-positive RA. These results reinforce the notion that not only intra- but also juxta-articular synovial inflammation is involved in the development of RA.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 946.2-947
Author(s):  
C. Duncan ◽  
E. Hunter ◽  
C. Koutsothanasi ◽  
M. Salter ◽  
A. Akoulitchev ◽  
...  

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


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1115.1-1115
Author(s):  
F. Rahal ◽  
N. Brahumi ◽  
A. Ladjouze-Rezig ◽  
S. Lefkir

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


2015 ◽  
Vol 42 (7) ◽  
pp. 1112-1118 ◽  
Author(s):  
Michaela Krohn ◽  
Sarah Ohrndorf ◽  
Stephanie G. Werner ◽  
Bernd Schicke ◽  
Gerd-Rüdiger Burmester ◽  
...  

Objective.Near-infrared fluorescence optical imaging (FOI) is a novel imaging technology in the detection and evaluation of different arthritides. FOI was validated in comparison to magnetic resonance imaging (MRI), greyscale ultrasonography (GSUS), and power Doppler ultrasonography (PDUS) in patients with early rheumatoid arthritis (RA).Methods.Hands of 31 patients with early RA were examined by FOI, MRI, and US. In each modality, synovitis of the wrist, metacarpophalangeal joints (MCP) 2–5, and proximal interphalangeal joints (PIP) 2–5 were scored on a 4-point scale (0–3). Sensitivity and specificity of FOI were analyzed in comparison to MRI and US as reference methods, differentiating between 3 phases of FOI enhancement (P1–3). Intraclass correlation coefficients (ICC) were calculated to evaluate the agreement of FOI with MRI and US.Results.A total of 279 joints (31 wrists, 124 MCP and 124 PIP joints) were evaluated. With MRI as the reference method, overall sensitivity/specificity of FOI was 0.81/0.00, 0.49/0.84, and 0.86/0.38 for wrist, MCP, and PIP joints, respectively. Under application of PDUS as reference, sensitivity was even higher, while specificity turned out to be low, except for MCP joints (0.88/0.15, 0.81/0.76, and 1.00/0.27, respectively). P2 appears to be the most sensitive FOI phase, while P1 showed the highest specificity. The best agreement of FOI was shown for PDUS, especially with regard to MCP and PIP joints (ICC of 0.57 and 0.53, respectively), while correlation with MRI was slightly lower.Conclusion.FOI remains an interesting diagnostic tool for patients with early RA, although this study revealed limitations concerning the detection of synovitis. Further research is needed to evaluate its full diagnostic potential in rheumatic diseases.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 582.1-582
Author(s):  
S. Pazmino ◽  
A. Lovik ◽  
A. Boonen ◽  
D. De Cock ◽  
V. Stouten ◽  
...  

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


2020 ◽  
Author(s):  
MARIA RYDHOLM ◽  
INGEGERD WIKSTROM ◽  
SOFIA HAGEL ◽  
LENNART T.H. JACOBSSON ◽  
CARL TURESSON

Abstract Background: The objective of this study was to investigate the course of disability related to the upper extremities (UE) in early rheumatoid arthritis (RA), and to assess correlations between such disability and clinical parameters, including grip force. Methods: In an inception cohort of patients with early RA (N=222), disability of the UE was assessed using a subscore of the Health assessment questionnaire disability index (HAQ-DI), and average grip force of the dominant hand was measured. Changes between consecutive follow-up visits in the HAQ-DI-UE subscore were assessed using the paired samples t-test, and correlations with key disease parameters using Spearman’s rank test. The relation between joint involvement and HAQ-DI-UE was examined using multivariate linear regression analysis. Results: The HAQ-DI-UE decreased significantly from inclusion to the 6-month follow-up (mean change -0.26; 95% CI -0.18 to -0.34), and increased significantly after 2 years. There were fairly strong correlations for HAQ-DI-UE with grip force (r: -0.50 to -0.62), patient’s global assessment (r:0.58 to 0.64) and patient’s assessment of pain (r:0.54 to 0.60) at all time points up to 5 years, but only moderate to weak correlations with swollen joints, CRP and ESR. At inclusion wrist synovitis and tender PIP joints had both an independent impact on HAQ-DI-UE, whereas tenderness of the shoulder and the wrist had a greater importance at 6 months. Conclusions: Disability related to the upper extremities decreased significantly during the first 6 months, and increased again after 2 years. The correlations with clinical parameters underline the major impact of pain and impaired hand function in early RA.


RMD Open ◽  
2020 ◽  
Vol 6 (2) ◽  
pp. e001339
Author(s):  
Kristien Van der Elst ◽  
Elke G E Mathijssen ◽  
Ellen Landgren ◽  
Ann Bremander ◽  
An De Groef ◽  
...  

ObjectivesTo explore treatment outcomes preferred by patients with early rheumatoid arthritis (RA) and how these change throughout the early disease stage across three European countries.MethodsA longitudinal, qualitative, multicentre study was conducted in Belgium, the Netherlands and Sweden. 80 patients with early RA were individually interviewed 3–9 months after treatment initiation and 51 of them participated again in either a focus group or an individual interview 12–21 months after treatment initiation. Data were first analysed by country, following the Qualitative Analysis Guide of Leuven (QUAGOL). Thereafter, a meta-synthesis, inspired by the principles of meta-ethnography and the QUAGOL, was performed, involving the local research teams.ResultsThe meta-synthesis revealed 11 subthemes from which four main themes were identified: disease control, physical performance, self-accomplishment and well-being. ‘A normal life despite RA’ was an overarching patient-preferred outcome across countries. Belgian, Dutch and Swedish patients showed many similarities in terms of which outcomes they preferred throughout the early stage of RA. Some outcome preferences (eg, relief of fatigue and no side effects) developed differently over time across countries.ConclusionsThis study on patient-preferred outcomes in early RA revealed that patients essentially want to live a normal life despite RA. Our findings help to understand what really matters to patients and provide specific insights into the early stage of RA, which should be addressed by clinicians of different disciplines from the start of treatment onwards.


2020 ◽  
Vol 47 (12) ◽  
pp. 1746-1751
Author(s):  
Andrew D. Foers ◽  
Alexandra L. Garnham ◽  
Gordon K. Smyth ◽  
Susanna M. Proudman ◽  
Lesley Cheng ◽  
...  

ObjectiveTo identify small noncoding RNA (sncRNA) serum biomarkers that predict response to triple disease-modifying antirheumatic drug (DMARD) therapy in patients with early rheumatoid arthritis (RA).MethodsEarly RA patients entered into a treat-to-target management algorithm, with triple DMARD therapy (methotrexate, sulfasalazine, hydroxychloroquine). Patients were assessed following 6 months of therapy and classified as European League Against Rheumatism responders or nonresponders. RNA was isolated from 42 archived serum samples, collected prior to commencement of triple DMARD therapy. Small RNA sequencing was performed and the reads mapped to annotations in a database of human sncRNA. Differential expression analysis was performed, comparing responders (n = 24) and nonresponders (n = 18).ResultsPretreatment levels of 4 sncRNA were significantly increased in nonresponders: chr1. tRNA131-GlyCCC (4.1-fold, adjusted P = 0.01), chr2.tRNA13-AlaCGC (2.2-fold, adjusted P = 0.02), U2-L166 (6.6-fold, adjusted P = 0.02), and piR-35982 (2.4-fold, adjusted P = 0.03). 5S-L612 was the only sncRNA significantly increased in responders (3.3-fold; adjusted P = 0.01). Reads for chr1. tRNA131-GlyCCC and chr2.tRNA13-AlaCGC mapped to the 5′ end of each tRNA gene and were truncated at the anticodon loop, consistent with these sncRNA having roles as 5′ translation interfering tRNA halves (tiRNA).ConclusionPretreatment levels of specific serum sncRNA might facilitate identification of patients more likely to respond to triple DMARD therapy.


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