P. Studenic

Discrepancies between patients and physicians in their perceptions of rheumatoid arthritis disease activity

OBJECTIVE Patients and physicians often differ in their perceptions of rheumatoid arthritis (RA) disease activity, as quantified by the patients global assessment (PGA) and by the evaluators global assessment (EGA). The purpose of this study was to explore the extent and reasons for this discordance. METHODS We identified variance components for the PGA and EGA in RA patients who were starting therapy with methotrexate in an academic outpatient setting. We analyzed predictors of the observed discrepancy in these measures (calculated as the PGA minus the EGA) and in their changes (calculated as the PGA(change) minus the EGA(change) ). RESULTS We identified 646 RA patients, and among them, 77.4% of the variability in the PGA and 66.7% of the variability in the EGA were explainable. The main determinants for the PGA were pain (75.6%), function (1.3%, by Health Assessment Questionnaire), and number of swollen joints (0.5%); those for the EGA were the number of swollen joints (60.9%), pain (4.5%), function (0.6%), C-reactive protein (0.4%), and the number of tender joints (0.3%). Increased pain led to a discrepancy toward worse patient perception, while increased numbers of swollen joints led to a discrepancy toward worse evaluator perception, both explaining 65% of the discordance between the PGA and the EGA. Likewise, changes in pain scores and numbers of swollen joints proved to be the main determinants for discrepant perceptions of changes in RA disease activity, explaining 34.6% and 12.5% of the discordance, respectively. CONCLUSION The most significant determinants for the cross-sectional and longitudinal discrepancy between the PGA and the EGA are pain and joint swelling, respectively. Understanding the reasons for a discordant view of disease activity will help to facilitate the sharing of decision-making in the management of RA.

Near misses of ACR/EULAR criteria for remission: effects of patient global assessment in Boolean and index-based definitions

Background The American College of Rheumatology/European League Against Rheumatism remission criteria for rheumatoid arthritis (RA) have been published recently. Objective To quantify the proportions of patients fulfilling only three of the four Boolean criteria and the relevance of patient global assessment (PGA) in context of remission. Methods From an observational prospective RA database the first visit of patients, fulfilling just three of the four Boolean criteria was identified. Logistic regression and descriptive analyses were processed, also defining remission by index-based (Simplified Disease Activity Index (SDAI)) definition and comparing outcomes with the evaluator global assessment (EGA). Results 52% had at least one visit, fulfilling just three criteria (not fulfilled were: PGA 61%; swollen joints 20%; tender joints 13%; C-reactive-protein 7%). 67% of patients not fulfilling the PGA criterion had an EGA≤1 cm, 25% of those fulfilled the SDAI definition. Increased pain (OR=1.28), EGA (OR=1.10) and discrepancy towards higher PGA than EGA (OR=1.28) could explain PGA failure to reach remission. Conclusions PGA is often the limiting factor for reaching remission; index-based remission showed balancing effects by adjusting for elevated variables in the summative score.

Relationship between radiographic joint space narrowing, sonographic cartilage thickness and anatomy in rheumatoid arthritis and control joints.

Objective To validate ultrasound (US) for measuring metacarpal cartilage thickness (MCT), by comparing it with anatomical measurement using cadaver specimens. To correlate US MCT with radiographic joint space narrowing (JSN) or width (JSW) in patients with rheumatoid arthritis (RA). Methods Bilateral metacarpophalangeal (MCP) joints of 35 consecutive outpatients, with recent hand X-rays, were included in the analysis. Metacarpal and phalangeal cartilage of MCP 2–5 was assessed bilaterally by US. JSW and JSN were evaluated on X-rays by the van der Heijde modified Sharp method (vdHS). In addition, cadaver specimens of MCP 2–5 joints (n=19) were evaluated by anatomical measurement and US. Results The agreement (intraclass correlation coefficient) between sonographic and anatomical MCT on cadaver specimens of MCP joints was 0.61. MCT of individual MCP joints correlated with individual MCP JSN (r=−0.32, p<0.001) and individual MCP JSW (r=0.72, p<0.001). No correlation was found between phalangeal cartilage thickness and JSN in individual MCP joints. The US MCT summary score for MCP joints 2–5 correlated with summary scores for JSW (r=0.78, p<0.001), JSN (r=−0.5, p<0.001), erosion score of the vdHS (r=−0.39, p<0.001) and total vdHS (r=−0.47, p<0.001). Conclusions Sonographic cartilage assessment in MCPs is closely related to anatomical cartilage thickness. Both JSW and JSN by radiography represent cartilage thickness in the MCP joints of patients with RA quite well. Thus, US is a valid tool for measuring MCT if radiographs are not available or in case of joint malalignment.

Different Rating of Global Rheumatoid Arthritis Disease Activity in Rheumatoid Arthritis Patients With Multiple Morbidities

To quantify differences and determine the factors contributing to the difference in patient global assessment of rheumatoid arthritis (RA) disease activity (PtGA) between RA patients with multiple morbidities (RA‐MM) and those with RA only.

Reliability of patient-reported outcomes in rheumatoid arthritis patients: an observational prospective study

OBJECTIVE Patient-reported outcomes (PROs) such as pain, patient global assessment (PGA) and fatigue are regularly assessed in RA patients. In the present study, we aimed to explore the reliability and smallest detectable differences (SDDs) of these PROs, and whether the time between assessments has an impact on reliability. METHODS Forty RA patients on stable treatment reported the three PROs daily over two subsequent months. We assessed the reliability of these measures by calculating intraclass correlation coefficients (ICCs) and the SDDs for 1-, 7-, 14- and 28-day test-retest intervals. RESULTS Overall, SDD and ICC were 25 mm and 0.67 for pain, 25 mm and 0.71 for PGA and 30 mm and 0.66 for fatigue, respectively. SDD was higher with longer time period between assessments, ranging from 19 mm (1-day intervals) to 30 mm (28-day intervals) for pain, 19 to 33 mm for PGA, and 26 to 34 mm for fatigue; correspondingly, ICC was smaller with longer intervals, and ranged between the 1- and the 28-day interval from 0.80 to 0.50 for pain, 0.83 to 0.57 for PGA and 0.76 to 0.58 for fatigue. The baseline simplified disease activity index did not have any influence on reliability. Lower baseline PRO scores led to smaller SDDs. CONCLUSION Reliability of pain, PGA and fatigue measurements is dependent on the tested time interval and the baseline levels. The relatively high SDDs, even for patients in the lowest tertiles of their PROs, indicate potential issues for assessment of the presence of remission.

Different Rating of Global Rheumatoid Arthritis (RA) Disease Activity in Multimorbid Patients with RA

To quantify differences and determine the factors contributing to the difference in patient global assessment of rheumatoid arthritis (RA) disease activity (PtGA) between RA patients with multiple morbidities (RA‐MM) and those with RA only.

Missing pebble in the mosaic of rheumatic diseases and mental health: younger does not always mean happier

We have read with great interest the article by Redeker et al 1 investigating the determinants of psychological well-being in axial spondyloarthritis (SpA). The authors observed that among 1736 patients aged 18–79 years, 68% of subjects displayed depressive symptoms, ranging from mild to severe according to the five-item WHO Well-Being Index. This article clearly points out the burden of depressive symptoms in patients with SpA and its correlation with disease activity, functional impairment and other parameters including younger age. The authors emphasise that a potential explanation for the negative association between depressive symptoms and age might be a better capability to cope with the disease of adult compared with young patients. This aspect prompted our reflections, as the psychological impact of rheumatic and musculoskeletal diseases (RMDs) in young people is a major unmet need. We previously reported that over 90% of young patients with RMDs outline an impact of their condition on mental health which, …

SAT0081 The Diagnostic and Predictive Value of Anti-Acetylated Peptide Antibodies (AAPA) in Rheumatoid Arthritis Patients Starting Their First Dmard Treatment on Methotrexate: Table 1.

Background Anti-acetylated-peptide antibodies (AAPA) have recently been described in rheumatoid arthritis (RA) patients and may be used as a further diagnostic marker in patients with undifferentiated arthritis (1). Objectives To determine the prevalence of AAPA in a cohort of RA patients starting their first conventional synthetic DMARD treatment (csDMARD). In addition, we aimed to evaluate the usefulness of AAPA as potential predictors of clinical response to methotrexate (MTX) therapy. Methods We measured IgG and IgA AAPA by ELISA using two acetylated peptides derived from vimentin. We tested by regression, parametric and non-parametric analyses of disease activity measures if AAPA show potency for predicting response to MTX. Results Among 110 patients starting treatment on MTX, 74.5% were positive for IgG and/or IgA AAPA: 49% were positive for either IgA or IgG antibodies and 25.5% were IgA/IgG double positive. In comparison, 63.6% of the patients were positive for either RF or ACPA (measured by the CCP assay). In the AAPA positive patients; in total, 26.4% of the patients showed IgA antibodies and 73.6% were positive for IgG AAPA. Importantly, of the 36.4% of patients negative for both RF and ACPA (double negative), 55% were positive for IgG and/or IgA AAPA, and the remaining 45% (i.e. 16% of the total cohort) were completely seronegative (triple-negative; see table). When comparing triple negative patients with the AAPA positive double-negative ones, no significant difference in baseline characteristics was found but a trend that patients with more seroreactivities showed higher composite disease activity scores. Analyzing the clinical response to MTX, AAPA positive double-negative patients showed a significantly greater relative SDAI change after 6 months compared to triple-negative patients (p=0.028; median (IQR): -44.6% (-58.5 - -28.90) vs. 5.26% (-23.9 - 55.5%). In addition, there was a significantly greater relative change in CRP and erythrocyte sedimentation rate in AAPA positive double-negative patients. In a backward regression model only RF could significantly be associated with the SDAI response, leading to + 30% relative change in SDAI (p=0.024). Status of ACPA and AAPA as potential predictors had to be excluded. Furthermore, RF positive patients showed larger relative changes in CRP, ESR, SDAI, CDAI and DAS after 6 months of MTX treatmentTable 1. Crosstable of status of RF, ACPA and anti-acetylated peptide antibodies (AAPA) Anti-acetylated peptide antibodies Total Negative IgA or IgG positive IgA and IgG positive Negative 16.4% 16.4% 3.6% 36.4% RF 3.6% 3.6% 2.7% 10% ACPA .9% 1.8% 0.9% 3.6% RF+ACPA 4.5% 27.3% 18.2% 50% Total 25.5 49.1 25.4 100% Conclusions AAPA commonly occur in RA patients and were, in fact, the most prevalent autoantibodies in our cohort. Measuring AAPA in addition to RF and ACPA reduced the prevalence of seronegative patients by more than 50%. These AAPA positive but RF and ACPA negative patients responded significantly better to MTX. Therefore, AAPA positivity in RF and ACPA negative patients identifies a subgroup of patients with a more favourable response to MTX. References Juarez M, Bang H, Hammar f et al. Ann Rheum Dis 2015 Jul 9; Epub ahead of print. Disclosure of Interest P. Studenic: None declared, S. Blüml: None declared, H. Bang Employee of: has developed the assay, M. Unger: None declared, K. Raza: None declared, D. Aletaha: None declared, J. Smolen: None declared, G. Steiner: None declared

AB0303 When it's the First, Stay on the First and Fight Anemia! Analyses of Treatment Retention in an Observational Rheumatoid Arthritis Cohort

Background The last decade brought major advances in treatment choices for rheumatoid arthritis (RA) patients. The first choice in the treatment of RA patients is methotrexate (MTX) with a rapid step up to alternative conventional disease modifying antirheumatic drugs (DMARDs) or biologicals according to established treatment algorithms. Following these strategies, treatment retention can be seen as a surrogate marker for treatment response in clinical practice. Objectives We aimed to identify patient or treatment characteristics or comorbidities that are associated with treatment retention in an observational cohort of RA patients. Methods We identified patients starting DMARD treatment for RA patients from a longitudinal observational database. We considered the first 6 sequential treatments in our analysis, because the number of patients with >6 treatment was small. We used a two step forward conditional Cox regression model. In the first step we tested clinical variables and the impact of the sequence of the treatment as well as DMARD category (eg. csDMARD monotreatment, Non-TNFi biological DMARD, etc); and in the second step we tested the effects of comorbidities using hemoglobin levels, leukocyte counts, serum creatinine and glomerular filtration rate (GFR), alanin-aminotransferase (ALT) and gamma-glutamyl-transferase (GGT) as additional predictors. We finally repeated the analyses using only patients of an inception cohort. Results 695 patients were identified in our longitudinal observational database for analyses: 78% female; mean ± SD disease duration: 4.7±7.9 years; CDAI: 17.6±11.1; age: 54.3±12.9; 61% rheumatoid factor positive). The inception cohort comprised 260 patients starting their first DMARD: 74% female; disease duration: 0.09±0.46 years; CDAI: 17.6±10.9; age: 54.3±13.5; 56% rheumatoid factor positive. In analyses of the inception group we found that CDAI, age and treatment segment function as clinical predictors for treatment retention. Function, rheumatoid factor status, anti-citrullinated antibody or disease duration did not contribute significantly in explaining the outcome. The more previous treatments the patient had received, the higher the disease activity, and the younger the patient, the higher the risk for discontinuation of therapy. Considering comorbidities in step 2, only ALT could add significantly in step 2 of the analysis, with higher ALT levels being associated with lower risk of treatment discontinuation (Table 1). Whether the high baseline ALT is a consequence of chronic use of pain killers needs to be explored. In this case, the subjective benefit of DMARDs may also contribute to longer retention. When using the complete cohort the same clinical variables were found significant. Concerning laboratory surrogates of comorbidities, only higher hemoglobin levels were associated with a lower risk of treatment discontinuation (Table 1). ALT did not associate with treatment retention in the complete cohort. Conclusions Patients on their first DMARD treatment show higher retention rates than on subsequent treatments, independent of DMARD category. Anemia is an important independent risk factor of DMARD discontinuation. Disclosure of Interest None declared

Targeted inhibition of Janus kinases abates interfon gamma-induced invasive behaviour of fibroblast-like synoviocytes

Objectives The aim was to explore the function of the T-cell cytokine IFNγ for mesenchymal tissue remodelling in RA and to determine whether IFNγ signalling controls the invasive potential of fibroblast-like synoviocytes (FLS). Methods To assess architectural responses, FLS were cultured in three-dimensional micromasses. FLS motility was analysed in migration and invasion assays. Signalling events relevant to cellular motility were defined by western blots. Baricitinib and small interfering RNA pools were used to suppress Janus kinase (JAK) functions. Results Histological analyses of micromasses revealed unique effects of IFNγ on FLS shape and tissue organization. This was consistent with accelerated migration upon IFNγ stimulation. Given that cell shape and cell motility are under the control of the focal adhesion kinase (FAK), we next analysed its activity. Indeed, IFNγ stimulation induced the phosphorylation of FAK-Y925, a phosphosite implicated in FAK-mediated cell migration. Small interfering RNA knockdown of JAK2, but not JAK1, substantially abrogated FAK activation by IFNγ. Correspondingly, IFNγ-induced FAK activation and invasion of FLS was abrogated by the JAK inhibitor, baricitinib. Conclusion Our study contributes insight into the synovial response to IFNγ and reveals JAK2 as a potential therapeutic target for FLS-mediated joint destruction in arthritis, especially in RA.