EULAR Response Research Articles

Anti-peptide antibodies, anti-SNRK and anti-HUWE1 antibodies, as potential predictors of good response to tofacitinib therapy in rheumatoid arthritis patients.

To maximize the cost-effectiveness of tofacitinib, one of Janus kinase inhibitors, there is an unmet need to identify predictors of therapeutic response. Utilizing phage immunoprecipitation sequencing (PhIP-Seq), we aim to identify peptide biomarkers for predicting good response to tofacitinib in rheumatoid arthritis (RA) patients. We enrolled 106 patients who had received 24-week tofacitinib therapy, including twelve patients undergoing PhIP-Seq analysis in the discovery stage and ninety-four patients validated with enzyme-linked immunosorbent assay (ELISA) in the replication stage. Disease activity was assessed using the 28-joint disease activity score-erythrocyte sedimentation rate, and therapeutic response was evaluated using EULAR response criteria. Plasma levels of caspase-1 and IL-18 were determined using ELISA. PhIP-Seq analysis identified antibodies to sucrose non-fermenting-related kinase (SNRK) and HUWE1 (ubiquitin E3 ligase) as peptide biomarkers for discriminating good responders from the non-good responders. Using ELISA for validation on another cohort, an optimal cut-off value of anti-SNRK antibody for predicting good response was 0.381, with AUC 0.823, specificity 80.6%, and sensitivity 78.1% (p = 3.01E-07), and anti-HUWE1 antibody at 0.362, with AUC 0.740, specificity 74.2%, and sensitivity 62.5% (p < 0.001). Plasma levels of anti-SNRK and anti-HUWE1 antibodies were positively correlated with levels of caspase-1 and IL-18 (both p < 0.05). Multivariate logistic regression analysis revealed anti-SNRK antibody as a significant predictor of good therapeutic response. After tofacitinib therapy, anti-SNRK antibody levels significantly declined in good responders, but not in non-good responders. We identify two peptide antibodies, anti-SNRK and anti-HUWE1 antibodies, as pretreatment predictors of good therapeutic response to tofacitinib in RA patients.

Association between body weight and tocilizumab effectiveness in rheumatoid arthritis: results from the BSRBR-RA.

Tocilizumab is an IL-6 receptor humanised monoclonal antibody for the treatment of rheumatoid arthritis (RA) with intravenous (IV) and subcutaneous (SC) preparations available. Only IV tocilizumab is dosed adjusting for weight. Therefore, we aimed to study the association between body weight and the effectiveness of tocilizumab by the route of administration. Patients with RA administered tocilizumab in the BSRBR-RA were included in the analysis and stratified by route of administration. Outcomes included the 6 month change in DAS28, the proportion of patients achieving DAS28 remission, 6-month EULAR response and persistence of the first route of tocilizumab administration. The exposure was every increase in 10 kg of body weight. Adjusted regression models appropriate to outcome were used to study the associations between body weight and outcomes. Multiple imputations accounted for missing data. 2612 patients were included. Body weight was associated with reduced response to SC tocilizumab measured by change in DAS28: adjusted regression coefficient (95% CI) all patients 0.01 (-0.04, 0.07); IV: -0.03, (-0.1, 0.5); SC: 0.1 (0.02, 0.2) but not odds in achieving DAS28 remission or EULAR response. There was no significant association between body weight and the persistence of IV or SC tocilizumab. Body weight was associated with the initial response to SC tocilizumab, although the difference in response was small, but not drug persistence. Physicians should monitor the body weight of patients and consider interventions to promote maintenance of a healthy weight.

Inclusion of fibrinoid necrosis increases the accuracy of synovial tissue assessment in predicting response to methotrexate: analysis of the UCLouvain Brussels ERA Cohort

ObjectiveRheumatoid Arthritis (RA) often exhibits suboptimal treatment response despite early diagnosis and treatment. This study aimed to analyze Early Rheumatoid Arthritis (ERA) synovial biopsies through histology and immunohistochemistry (IHC) to identify predictive factors for treatment response to Methotrexate (MTX).Methods140 ERA patients from the UCLouvain Arthritis Cohort underwent synovial biopsy and were monitored after initiating Disease-Modifying Antirheumatic Drug (DMARD) therapy. Histological features [Synovial Hyperplasia, Fibrinoid Necrosis (FN), Hypervascularization and Inflammatory Infiltrate] and IHC (CD3, CD20, CD138, CD68) were each semi-quantitatively assessed on a 0–3 scale with 7 levels.ResultsA strong association was observed between synovial CD68 and Fibrinoid Necrosis scores [r = 0.44 (0.27 − 0.56); p < 0.0001]. CD68 correlated with C-Reactive Protein (CRP), DAS28, SDAI and CDAI. Fibrinoid Necrosis score correlated with CRP and DAS28. Patients were then categorized as CD68NecrosisHIGH (CD68 + Necrosis ≥ 3) and CD68NecrosisLOW (CD68 + Necrosis < 3). CD68NecrosisHIGH exhibited higher pre-treatment disease activity [5.48 (1.6) versus 4.8 (1.7); p = 0.03] and a greater fall in DAS28 [1.99 (2.06) versus 1.1 (2.27), p = 0.03], SDAI [21.45 (IQR 23.3) versus 11.65 (IQR 17.5); p = 0.003] and CDAI [16 [14.9] versus 10.5 (20.1), p = 0.04]. CD68NecrosisHIGH patients had a higher EULAR Moderate/Good Response rate. CD68Necrosis score was incorporated into a probability matrix model together with clinical features (SJC44 and DAS28) to predict achieving a Moderate/Good EULAR Response Criteria at 3 months with a good performance (AUC 0.724).ConclusionFN and CD68 + in ERA synovial biopsies identify patients with higher disease activity and predict a better treatment response at three months. A model including synovial CD68 and fibrinoid necrosis with baseline clinical features predicts EULAR response at 3 months.

P014 Treatment response in psoriatic arthritis: a comparison between the disease activity scores psoriatic arthritis response criteria and disease activity score-28

Abstract Background/Aims Despite NICE guidelines recommending the use of the PsA response criteria (PsARC), to assess response to biologic therapies in patients with psoriatic arthritis (PsA), some clinicians use the Disease Activity Score (DAS-28) criteria, developed for rheumatoid arthritis. However, whether the two scores are interchangeable and/or capture similar information has not yet been explored. Here, we investigate the differences and overlap between these two disease activity scores, in identifying good/poor responders, in PsA. Methods Utilising treatment response data from the OUTPASS cohort; a UK based multi-centre observational study, PsA patients assessed with PsARC and DAS-28 scores were calculated at baseline (pre-treatment), 3-months and 6-months (3M),(6M), following treatment, where available. EULAR good/moderate response was combined and compared with PsARC responder status. Subgroup analysis of patients with both PsARC and DAS-28 scores at either 3M or 6M, were tested for agreement using the Cohen’s Kappa test. Statistical tests were also used, as appropriate, to investigate differences between the baseline subcomponents, in the observed concordant and discordant data. Results Response data from 418 patients was available. An average of 76% were classified as responders according to PsARC, and 80% according to the EULAR response criteria, for both 3M and 6M, with 12% discordance. A subgroup analysis of 218 patients assessed with both scores, (up to 6M), revealed 17.9% responder discordance between PSARC and DAS-28, and 82.1% concordance. The Cohen’s Kappa test defined the assessment of responder/non-responder outcome, as an ‘almost perfect agreement’ (0.82) between the two criteria. Further statistical analyses, of baseline subcomponents, of both response criteria, between these discordant/concordant subsets, showed no significant difference, except for PsARC Physician’s and Patient’s Global Assessments (PhGA), (PGA), (P = 0.01, P = 0.02, Table 1). Conclusion PsARC and EULAR response criteria show ‘almost perfect agreement’, strongly supporting clinical use for either score. PhGA, (not a subcomponent of DAS-28) and PsARC PGA were the only significantly different (P &amp;lt; 0.05) components between the discordant and concordant groups, highlighting the importance of considering psychosocial factors which may affect pain tolerance and treatment response. Comparative analyses with other widely used scores, such as DAPSA, would also be informative for future work. Disclosure K. Patel: Grants/research support; This project has received support from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 101007757 (HIPPOCRATES), the JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA, the results reflect only the author's view and the JU are not responsible for any use that may be made of the information it contains.. N. Nair: None. M. Jani: None. H. Chinoy: Consultancies; H.C. has received Consulting for PTC Therapeutics. Member of speakers’ bureau; H.C. has received fees as a speaker for GSK, UCB. Other; H.C. for Advisory Board member for Astra Zeneca, Pfizer, Argenx, Galapagos; Data and Science Monitoring Board chair for Horizon Therapeutics. J. Bluett: Grants/research support; J.B. has received a research grant award from Pfizer and travel/conference fees from UCB, Fresenius Kabi, Pfizer and Eli Lilly. (Pfizer: WI239449). A. Barton: Grants/research support; A.B. has received research grants from Bristol Myers Squibb and Pfizer and speaker fees from Galapagos.. P. Curry: None.

Evaluation of inflammatory biomarkers and the ratio of hemoglobin-red cell distribution width in patients with rheumatoid arthritis treated with tumor necrosis factor-alpha inhibitors.

The aim of this study was to examine pre-treatment and post-treatment hemogram-derived inflammatory biomarkers in patients with rheumatoid arthritis (RA) who received anti-tumor necrosis factor (TNF)-α treatment. The data of 1182 patients with RA were screened. Among them, 207 patients who met the eligibility criteria were included in the retrospective study. Demographic parameters, disease activity, and blood cell-derived indexes were evaluated. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and hemoglobin-red cell distribution width (Hb/RDW) rates were evaluated before treatment and at the third month of treatment in patients with RA who received anti-TNF-α treatment. According to the EULAR response criteria, 12.6% of the 207 patients responded to anti-TNF-α treatment as none, 21.3% as good, and 66.2% as moderate, respectively. Post-treatment NLR and PLR values were significantly lower than pre-treatment values (p < 0.001), whereas post-treatment LMR and Hb/RDW values were significantly higher than pre-treatment values (respectively, p = 0.001 and p = 0.012). The difference between pre-treatment and post-treatment values of LMR and Hb/RDW was significantly higher when compared to the moderate + good response groups than the none-response group (p = 0.002 and p = 0.014, respectively). However, in the receiver operating characteristic curve analysis, these parameters were not found to be significant in predicting treatment response. Significant changes were detected in hemogram-derived inflammatory markers of the groups responding to anti-TNF-α treatment. They can be used as a guide during treatment follow-up. Yet, they do not predict treatment response. Key Points • RA may manifest with periods of remission and activation, and regular follow-up is essential. • There is a demand for readily available, reproducible, and cost-effective parameters to assess treatment response. • Hemogram-derived inflammatory markers differ in relation to anti-TNF-α treatment response in RA. • None of those markers demonstrate an acceptable predictive performance in distinguishing patients based on their response to TNF-α inhibitors.

Association of HLA-DRB1 locus with treatment response to abatacept or TNF inhibitors in patients with seropositive rheumatoid arthritis

The strongest genetic risk factor for rheumatoid arthritis (RA) has been known as HLA-DRB1 based on amino acid positions 11, 71, and 74. This study analyzed the association between specific HLA-DRB1 locus and treatment response to abatacept or TNF inhibitors (TNFi) in patients with seropositive RA. A total of 374 Korean RA patients were treated with abatacept (n = 110) or TNFi (n = 264). Associations between HLA-DRB1 and treatment response after 6 months were analyzed using multivariable logistic regression. Seropositive RA patients with HLA-DRB1 shared epitope (SE) had a favorable response to abatacept (OR = 3.67, P = 0.067) and an inversely associated response to TNFi (OR 0.57, P = 0.058) based on EULAR response criteria, but the difference was not statistically significant in comparison to those without SE. In analyses using amino acid positions of HLA-DRB1, a significant association was found between valine at amino acid position 11 of SE and good response to abatacept (OR = 6.46, P = 5.4 × 10–3). The VRA haplotype also showed a good response to abatacept (OR = 4.56, P = 0.013), but not to TNFi. Our results suggest that treatment response to abatacept or TNFi may differ depending on HLA-DRB1 locus in seropositive RA, providing valuable insights for selecting optimal therapy.

Baseline ANA and Anti‐Ro60/SSA Antibody as Potential Predictors for Immunogenicity and Poor EULAR Response in Adalimumab‐Treated RA Patients

What Is Known and Objective. Given that autoantibodies are relatively abundant and easily measured, the detection of antibody biomarkers would be ideal for predicting therapeutic responses. Although anti‐Ro60/SSA (anti‐TROVE2) antibody has been identified as a useful predictor for the development of immunogenicity and therapeutic failure to adalimumab in RA patients, autoantibodies with similar predictive potentials are not yet sufficiently validated. Methods. We aimed to investigate the baseline autoantibodies, including rheumatoid factor (RF)‐IgM, anti‐citrullinated peptide antibodies (ACPA), antinuclear antibody (ANA), anti‐Ro60/SSA antibody, and anti‐La/SSB antibody, for their relationships with drug immunogenicity and therapeutic responses in RA patients assessed at week 48 of adalimumab therapy. We also compared adalimumab drug survival between participants with or without these autoantibodies. Results and Discussion. Our results showed that poor EULAR responders had significantly higher positive rates of baseline ANA, anti‐Ro60/SSA antibody, and anti‐La/SSB antibody than moderate or good responders. However, no significant differences in circulating levels of RF‐IgM or ACPA were observed among groups with different responses. The multivariate logistic regression analysis revealed that ANA and anti‐Ro60/SSA antibodies were significant predictors of developing immunogenicity to adalimumab (both p &lt; 0.001). The presence of ANA, anti‐Ro60/SSA, and anti‐SSB antibodies could significantly predict poor EULAR response in adalimumab‐treated RA patients (odds ratio, 4.98, 5.60, and 8.08, respectively, all p &lt; 0.01). In Kaplan–Meier analysis, the adalimumab drug survival rate was significantly lower in RA patients with positivity for ANA, anti‐Ro60/SSA, anti‐SSB, and anti‐drug antibodies than in the seronegative group. What Is New and Conclusion. Our results suggest that baseline ANA and anti‐Ro60/SSA antibodies are potential predictive markers of drug immunogenicity and poor EULAR response in adalimumab‐treated RA patients.

Identification of gene expression biomarkers to predict clinical response to methotrexate in patients with rheumatoid arthritis

ObjectivesTo identify biomarkers at the gene expression level to predict response to methotrexate (MTX) in patients with rheumatoid arthritis (RA).MethodsMTX-naïve patients with RA were started on MTX and followed up over three months. The disease activity score 28 (DAS28) was used to classify patients into responders and non-responders. Genome-wide gene expression analysis was performed in CD4 + and CD14 + mononuclear cells sampled from whole blood at baseline to identify differentially expressed genes in responders versus non-responders. Gene selection methods and prediction modelling obtained the most relevant differentially expressed genes. A logistic regression prediction model was subsequently constructed and validated via bootstrapping. The area under the receiver operating characteristic (AUC) curve was calculated to judge model quality.ResultsSeventy-nine patients with RA (53.4 ± 13.9 years, 74.7% females) were enrolled, and 70 finished the study with a documented treatment EULAR response (77.1% responders). Forty-six differentially expressed genes were found. The most promising genes were KRTAP4-11, LOC101927584, and PECAM1 in CD4 + cells and PSMD5 and ID1 in CD14 + cells. The final prediction model using these genes reached an AUC of 90%; the validation set’s AUC was 82%.ConclusionsOur prediction model constructed via genome-wide gene expression analysis in CD4 + and CD14 + mononuclear cells yielded excellent predictions. Our findings necessitate confirmation in other cohorts of MTX-naïve RA patients. Especially if used in conjunction with previously identified clinical and laboratory (bio)markers, our results could help predict response to MTX in RA to guide treatment decisions.Key Points• Patients with rheumatoid arthritis may or may not respond to treatment with methotrexate, which is the recommended first-line drug in guidelines around the world.• In non-responders, valuable time is lost until second-line treatments are started.• This study aimed at predicting response to methotrexate by identifying differentially expressed genes from peripheral blood samples.• The final prediction model yielded excellent prognostic values, but validation in other cohorts is necessary to corroborate these findings.

What is the association of depression with clinical response to therapy in patients with psoriatic arthritis treated with biologic disease-modifying antirheumatic drugs?

Psoriatic arthritis (PsA) is a chronic, progressive inflammatory joint disease that is associated with higher prevalence of depression. There is limited literature about the impact of depression, particularly regarding the response to therapy. A retrospective cohort study with PsA patients that started their first biologic disease-modifying antirheumatic drugs (bDMARD) was conducted. In the majority of cases, a cutoff score of ≥ 8 in Hospital Anxiety and Depression Scale (HADS) was used to define cases of depression. In cases where patients did not complete the questionnaire, a previous diagnosis made by a psychiatrist was used to establish the presence of depression. Response to therapy 12 months after the start of bDMARD was evaluated and the switch rate to another bDMARD due to inefficacy was assessed at month 12. A total of 129 patients (66 females, 51.2%; mean age of 47.7 ± 11.0 years and mean disease duration of 10.0 ± 7.7 years) with PsA were included. Thirty-two (24.8%) patients had depression. Patients with depression and peripheral involvement had a significantly lower ACR20/50/70 responses (p = 0.001, p = 0.002, and p = 0.001 respectively) after 12 months of therapy and a significantly worse EULAR response (p = 0.002). Furthermore, patients with depression and axial involvement had a significantly worse response based on ASDAS response criteria (p = 0.031). Switch due to ineffectiveness in the first 12 months was significantly higher in patients with depression (p = 0.002). Depression in PsA is a frequent yet often understudied comorbidity. The causal relationship between depression and PsA is difficult to decrypt and further research is needed. Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity. Key Points • Depression in PsA is a frequent yet often understudied comorbidity. In our study, the prevalence of depression was 24.8%. • Depression in PsA seems to be associated to lower response to therapy and higher discontinuation rates of bDMARD. • Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity.

Value of Magnetic Resonance T1 Mapping in Evaluating the Early Response to Treatment for Rheumatoid Arthritis.

Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) is usually used for the semi-quantitative evaluation of joint changes in Rheumatoid Arthritis (RA). However, this method cannot evaluate early changes in bone marrow edema (BME). To determine whether T1 mapping of wrist BME predicts early treatment response in RA. This study prospectively enrolled 48 RA patients administered oral anti-rheumatic drugs. MRI of the most severely affected wrist was performed before and after 4 (48 patients) and 8 weeks of treatment (38 patients). Mean T1 values of BME in the lunate, triangular, and capitate bones; RAMRIS for each wrist; Erythrocyte-Sedimentation Rate (ESR); and 28-joint Disease Activity Score (DAS28)-ESR score were analyzed. Patients were divided into responders (4 weeks, 30 patients; 8 weeks, 32 patients) and non-responders (4 weeks, 18 patients; 8 weeks, 6 patients), according to EULAR response criteria. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of T1 values. ESR and DAS28-ESR were not correlated with T1 value and RAMRIS at each examination (P > 0.05). Changes in T1 value and DAS28-ESR relative to the baseline were moderately positively correlated with each other at 4 and 8 weeks (r = 0.555 and 0.527, respectively; P < 0.05). At 4 weeks, the change and rate of change in T1 value significantly differed between responders and non-responders (-85.63 vs. -19.92 ms; -12.89% vs. -2.81%; P < 0.05). The optimal threshold of the rate of change in T1 value at 4 weeks for predicting treatment response was -5.32% (area under the ROC curve, 0.833; sensitivity, 0.900; specificity, 0.667). T1 mapping provides a new imaging method for monitoring RA lesions; changes in wrist BME T1 values reflect early treatment response.

Glucocorticoid trajectories over 2 years in patients with rheumatoid arthritis in a real-life setting

ObjectivesTo analyse glucocorticoid (GC) use and trajectories in a real-life cohort of rheumatoid arthritis (RA).MethodsPatients with RA included in the longitudinal RCVRIC cohort for initiating or changing biological disease-modifying antirheumatic...

Can efficacy and safety data from clinical trials of rituximab in RA be extrapolated? Insights from 1984 patients from the AIR-PR Registry.

To investigate whether the efficacy and safety data from drug-registration trials can be extrapolated to real-life RA patients receiving RTX. The 'AutoImmunity and Rituximab' (AIR-PR) registry is a French multicentre, prospective cohort of RA patients treated with RTX in a real-life setting. We compared treatment responses at 12 months and serious adverse events (AEs) between eligible and non-eligible patients, by retrieving the eligibility criteria of the three rituximab-registration trials. We determined critical eligibility criteria and modelled the benefit-risk ratio according to the number of fulfilled critical eligibility criteria. Among 1984 RA patients, only 9-12% fulfilled all eligibility criteria. Non-eligible patients had fewer EULAR responses at 12 months (40.3% vs 46.9%, P = 0.044). Critical inclusion criteria included swollen joints count ≥4, tender joints count ≥4, CRP ≥15 mg/l and RF positivity. Critical exclusion criteria were age >80 years, RA-associated systemic diseases, ACR functional class IV, DMARD other than MTX and prednisone >10 mg/day. Only 20.8% fulfilled those critical eligibility criteria. During the first year, serious AEs occurred for 182 (9.2%) patients (70.3% serious infections) and patients with ≥1 critical exclusion criterion were at higher risk (hazard ratio 3.03; 95% CI 2.25-4.06; for ≥3 criteria vs 0). The incremental risk-benefit ratio decreased with the number of unmet critical inclusion criteria and of fulfilled exclusion criteria. Few real-life RA patients were eligible for the drug-registration trials. Non-eligible patients had lower chance of response, and higher risk of serious AEs. Efficacy and safety data obtained from those trials may not be generalizable to RA patients receiving RTX in real-world clinical practice.

Improvement in Disease Activity in Refractory Juvenile Dermatomyositis Following Abatacept Therapy.

This open-label, 24-week study was conducted to evaluate the safety and efficacy of abatacept in patients with refractory juvenile dermatomyositis (DM). Ten patients ≥7 years of age with moderate disease activity were enrolled in a 24-week study to examine the safety of subcutaneous abatacept and patient responses to the treatment. The primary endpoint was the International Myositis Assessment and Clinical Studies (IMACS) group Definition Of Improvement (DOI). Secondary endpoints included safety, changes in the core set activity measures (CSMs) of the IMACS group and the Pediatric Rheumatology International Trials Organization, and improvements in disease activity based on the American College of Rheumatology (ACR)/EULAR response criteria for juvenile DM. Radiologists blinded with regard to participant data assessed magnetic resonance images (MRIs) of patient thigh muscles. Interferon (IFN)-regulated gene score was performed on whole-blood RNA samples using a NanoString assay, and cytokines were assessed using a Luminex assay. Five patients achieved DOI at week 12, and 9 patients achieved DOI at week 24, including 2 patients with minimal, 4 patients with moderate, and 3 patients with major improvement by the 2016 ACR/EULAR response criteria for juvenile DM when patients were assessed using the CSMs of the IMACS Group. Improvements from baseline were seen in all CSMs at weeks 12 and 24, except in muscle enzymes. Daily glucocorticoid doses decreased from a mean of 16.7 mg at baseline to 10.2 mg at week 24 (P=0.002). Average MRI muscle edema scores decreased from a mean baseline score of 5.3 to 2.3 at week 24 (P=0.01). Six patients had down-trending IFN-regulated gene scores and galectin-9 expression at week 24. Decreases in IFN-regulated gene scores and in levels of interferon-γ-inducible protein 10kDa, galectin-9, and interleukin-2 correlated with improvements in disease activity and in muscle edema shown on MRI. Eleven grade 2 or 3 treatment-emergent adverse events were observed. This open-label study demonstrated that abatacept may be beneficial for patients with treatment-refractory juvenile DM.

Anti-citrullinated protein antibody profiles predict changes in disease activity in patients with rheumatoid arthritis initiating biologics.

To determine whether an expanded antigen-specific ACPA profile predicts changes in disease activity in patients with RA initiating biologics. The study included participants from a prospective, non-randomized, observational RA cohort. For this sub-study, treatment groups of interest included biologic-naïve initiating anti-TNF, biologic-exposed initiating non-TNF, and biologic-naïve initiating abatacept. ACPAs to 25 citrullinated peptides were measured using banked enrolment serum. Principal component analysis (PCA) was performed and associations of resulting principal component (PC) scores (in quartiles) and anti-CCP3 antibody (≤15, 16-250 or >250 U/ml) with EULAR (good/moderate/none) treatment response at 6 months were examined using adjusted ordinal regression models. Participants (n = 1092) had a mean age of 57 (13) years and 79% were women. At 6 months, 68.5% achieved a moderate/good EULAR response. There were three PCs that cumulatively explained 70% of variation in ACPA values. In models including the three components and anti-CCP3 antibody category, only PC1 and PC2 were associated with treatment response. The highest quartile for PC1 (odds ratio [OR] 1.76; 95% CI: 1.22, 2.53) and for PC2 (OR 1.74; 95% CI: 1.23, 2.46) were associated with treatment response after multivariable adjustment. There was no evidence of interaction between PCs and treatment group in EULAR responses (P-value for interaction >0.1). An expanded ACPA profile appears to be more strongly associated with biologic treatment response in RA than commercially available anti-CCP3 antibody levels. However, further enhancements to PCA will be needed to effectively prioritize between different biologics available for the treatment of RA.

Potential efficacy of T and B lymphocyte-targeted therapies on articular involvement of patients with rheumatoid arthritis and systemic sclerosis overlap syndrome. Results from a 2-centre series of 19 cases.

To analyse in routine practice the efficacy of targeted therapies on joint involvement of patients with rheumatoid arthritis/systemic sclerosis (RA/SSc) overlap syndrome. This was a retrospective analysis of medical records of two academic centres over a 10-year period. Joint response to targeted therapies was measured according to EULAR criteria based on Disease Activity Score (DAS)-28. In addition, changes in CRP level and glucocorticoid consumption were recorded. Nineteen patients were included. Methotrexate (n=11) and hydroxychloroquine (n=4) were the most used first-line treatments. Targeted therapies were frequently used (n=14). Tocilizumab was the most selected therapy (n=8), then rituximab (n=5), abatacept and anti-tumour necrosis factor (n=4). Twenty-one treatment sequences were assessed, including 18 with EULAR response criteria. Responses were "good" or "moderate" in 100% (4/4) of patients treated with abatacept, 80% (4/5) with rituximab, 40% (2/5) with tocilizumab, and 25% (1/4) with anti-TNF. T and B lymphocyte-targeted therapies (abatacept, rituximab) resulted more frequently in a "good" or "moderate" response compared to cytokine inhibitors (tocilizumab, etanercept, infliximab) with a significant decrease in DAS-28 at 6 months (-1.75; p=0.016) and a trend to a lower consumption of glucocorticoids. In patients with RA/SSc overlap syndrome refractory to conventional synthetic-DMARDs, T and B lymphocyte-targeted therapies seem to be a promising therapeutic option to control joint activity.

Identification of Cell-Specific Differential DNA Methylation Associated With Methotrexate Treatment Response in Rheumatoid Arthritis.

We undertook this study to estimate changes in cell-specific DNA methylation (DNAm) associated with methotrexate (MTX) response using whole blood samples collected from rheumatoid arthritis (RA) patients before and after initiation of MTX treatment. Patients included in this study were from the Rheumatoid Arthritis Medication Study (n=66) and the University of California San Francisco Rheumatoid Arthritis study (n=11). All patients met the American College of Rheumatology RA classification criteria. Blood samples were collected at baseline and following treatment. Disease Activity Scores in 28 joints using the C-reactive protein level were collected at baseline and after 3-6 months of treatment with MTX. Methylation profiles were generated using the Illumina Infinium HumanMethylation450 and MethylationEPIC v1.0 BeadChip arrays using DNA from whole blood. MTX response was defined using the EULAR response criteria (responders showed good/moderate response; nonresponders showed no response). Differentially methylated positions were identified using the Limma software package and Tensor Composition Analysis, which is a method for identifying cell-specific differential DNAm at the CpG level from tissue-level ("bulk") data. Differentially methylated regions were identified using Comb-p software. We found evidence of differential global methylation between treatment response groups. Further, we found patterns of cell-specific differential global methylation associated with MTX response. After correction for multiple testing, 1 differentially methylated position was associated with differential DNAm between responders and nonresponders at baseline in CD4+ T cells, CD8+ T cells, and natural killer cells. Thirty-nine cell-specific differentially methylated regions associated with MTX treatment response were identified. There were no significant findings in analyses of whole blood samples. We identified cell-specific changes in DNAm that were associated with MTX treatment response in RA patients. Future studies of DNAm and MTX treatment response should include measurements of DNAm from sorted cells.

E039 Association between ethnicity and initial response to TNF inhibitors in people with rheumatoid arthritis: Results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

Abstract Background/Aims Little is known about the association between ethnicity and response to TNF inhibitors (TNFi) in people with rheumatoid arthritis (RA). This study examines the association between self-reported ethnicity and DAS28 response after 6 months of treatment in patients starting their first TNFi using data from the British Society for Rheumatology Biologics Register for RA. Methods 14133 RA patients with self-reported ethnicity starting their first TNFi were included. Due to a very low proportion of non-white patients, ethnicity was divided into white or non-white for analysis. Outcomes included the change in disease activity using DAS28, the proportion of patients who achieved DAS28 remission and EULAR response at month 6. Adjusted regression models appropriate to outcome were used to compare between the two groups. Multiple imputation was used to account for missing data. Results Of 14133 patients starting TNFi with recorded ethnicity, only 607 (4.3%) recorded themselves as non-white (389 Asian, 134 Black, 57 Mixed ethnicity and 27 other) (Table). At start of TNFi, non-white patients were younger (non-white vs. white: mean 51 vs. 57 years; p &amp;lt; 0.001), with shorter disease duration (median 8 vs. 10 years; p &amp;lt; 0.001), higher proportion of females (86% vs. 76%; p &amp;lt; 0.001) and fewer current cigarette smokers (9% vs. 20%; p &amp;lt; 0.001). Non-white patients had lesser improvement in DAS28 at month 6 (adjusted regression coefficient (95% confidence interval (95%CI)): 0.3 (0.04-0.5)). However, using the white patients as a reference, non-white patients were not associated with the achievement of DAS28 remission (adjusted odds ratio (95%CI): 0.7 (0.5-1.1)) or EULAR response (aOR (95%CI): 0.8 (0.7-1.0)) at month 6. Conclusion Recruitment to the BSRBR-RA of non-white patients was exceptionally low compared to expected population distribution - the reasons for this are not immediately evident. Among those recruited, there were no significant differences observed in initial treatment response although non-white patients were younger, more likely to be female, had shorter disease duration and less likely to be smokers. Further evaluation into ways to both increase representativeness in our national RA treatment register and influence of ethnic differences on longer term outcomes with biologic therapies is warranted. Disclosure M. Tsoi: None. R.S. Andev: Other; R.S.A. reports speaker fees from Novartis. L. Kearsley-Fleet: None. K. Watson: None. S. Dubey: Honoraria; S.D. reports honoraria from Boehringer Ingelheim. Other; S.D. reports speaker fees from Janssen. K. Kumar: None. A. Moorthy: Honoraria; A.M. reports honoraria from Eli-Lilly and UCB. Other; A.M. reports speaker fees from Novartis and Galapagos. M. Gupta: None. A.O. Adebajo: None. K.L. Hyrich: Honoraria; K.L.H. reports honoraria from Abbvie. Grants/research support; K.L.M reports grant income from Pfizer and BMS.

P144 Socioeconomic deprivation is associated with reduced response and lower treatment persistence with anti-TNF therapies in people with rheumatoid arthritis

Abstract Background/Aims Recent global health crises have highlighted the importance of socioeconomic (SE) inequalities and its influence on health provision and outcomes. The impact of SE deprivation on treatment of rheumatoid arthritis (RA) is understudied in contemporary biologic-treated populations. The aim of this study was to investigate the association between SE deprivation and outcomes of TNF inhibitor (TNFi) treatment. Methods Individuals commencing their first TNFi in the BSR Biologics Register for RA from 2001 to 2020 were included. SE deprivation was proxied using the Index of Multiple Deprivation (IMD), which measures relative deprivation of geographic areas. Using the participants' residential postcode, each individual was assigned a relative rank score and categorised into the 20% most deprived, middle 40%, and 40% least deprived; thresholds were chosen because IMD gives greater distinction within the most deprived areas. DAS28, low disease activity (LDA) and EULAR response at 6 months were compared using linear, logistic and ordinal logistic regression models with the 40% least deprived as referent. Risk of drug discontinuation was compared using Cox models. Models were first unadjusted, then adjusted for potential confounders and/or mediators, namely age, gender, baseline DAS28, BMI, HAQ, number of comorbidities, age at diagnosis, ever smoking status and rheumatoid factor status. Multiple imputation was used for missing data. Results 17,117 individuals were included (mean±SD age 56±12 years, 76% female), of whom 3002 (18%) were in the 20% most, 6999 (41%) in the middle 40%, and 7116 (41%) in the 40% least deprived groups (Table 1). The 20% most deprived group had higher DAS28 at 6 months (beta=0.30, 95%CI 0.22-0.37) and were less likely to achieve LDA (OR 0.76; 0.68-0.84) and EULAR response (OR 0.73; 0.67-0.80) in unadjusted models. They were also more likely to discontinue treatment (HR 1.19; 1.13-1.25). Adjusted estimates were broadly similar (Table 1). Conclusion SE deprivation is associated with reduced response to TNFi and increased risk of treatment discontinuation. Estimates were largely unchanged despite adjusting for potential mediators. SE inequality embodies a multitude of factors that can be intervened upon, including behaviours and biases of clinicians or institutes, which should be a focus of future research. Disclosure S. Zhao: None. L. Kearsley-Fleet: None. K. Rogers: None. K. Watson: None. A. Bosworth: None. J. Galloway: None. S.M. Verstappen: None. J.H. Humphreys: None. A. Barton: None. K.L. Hyrich: None.

P183 Disease activity, comorbidities and functional status predict treatment response to biologic and targeted synthetic disease-modifying anti-rheumatic drugs in psoriatic arthritis

Abstract Background/Aims Much discussion surrounds the optimal therapeutic treatment plan for biologic and targeted synthetic disease modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) when treating psoriatic arthritis (PsA). The current study aims to identify predictors of treatment response among PsA patients initiating bDMARD/tsDMARD treatment, focusing on disease activity, functional status (Health Assessment Questionnaire, HAQ), and comorbidities. Methods The systematic review of clinical trials and observational studies used Medline, Embase and Cochrane databases. Eligible studies included full text papers with quantitative estimates of effect (or data to allow these to be computed). Papers also required a validated assessment of treatment response i.e., Minimal Disease Activity (MDA), or some other marker of treatment response such as treatment continuation. Case reports and conference abstracts were excluded. Results From 2824 articles identified, 27 were included. Across these, &amp;gt;15 different outcomes were used, and measured at &amp;gt; 10 different timepoints. There was consistent evidence to suggest that higher baseline disease activity was associated with a reduction in the likelihood of treatment response, see Table 1. Some studies reported up to 20% reduction in odds of LDA at 6 months associated with each 1 unit increase in DAPSA. Others demonstrated that patients with a high DAS28 (&amp;gt;3.2) experienced over a 90% reduction in the odds of MDA at 12 weeks. Eleven studies (from 15) demonstrated a significant association between baseline function and odds of treatment response. Each 1 unit increase in HAQ-DI decreased the odds of a good EULAR response at 3 months by up to 66%. The presence of comorbidities was also consistently associated with a decrease in treatment response. Studies showed that the presence of comorbidities at baseline lessened the odds of MDA at 6 months by up to 80%. Others reported that comorbidities were associated with a reduction in the odds of 5 year treatment persistence by up to 40%. Conclusion This review shows clear evidence of reduced bDMARD/tsDMARD response in PsA among patients with disease activity, poor function, and comorbidities. Clinicians should be aware of the reduced chances of treatment success and should consider early review of therapy, to consider whether treatment escalation or switching is required. Disclosure C. Addae-Kyereme: None. S. Lembke: None. G.J. Macfarlane: None. G.T. Jones: None.

P136 T-cell-Specific Biomarkers of Early Treatment Response in Patients with Rheumatoid Arthritis Treated with a Tumour Necrosis Factor Inhibitor

Abstract Background/Aims The use of tumour necrosis factor inhibitors (TNFi) has advanced the clinical management of rheumatoid arthritis (RA). However, only 30-40% of patients who receive initial treatment with a TNFi experience a beneficial response. The discovery of reliable biomarkers of TNFi response is, therefore, a priority. Whilst T-cell dysfunction is documented in RA pathophysiology, T-cell involvement in TNFi treatment response is unclear. We aimed to phenotype peripheral blood-derived T-cells in RA patients over a number of time-points through the first 12-weeks of TNFi treatment; and to apply a cluster-free association testing method developed on single-cell CITE-seq data—co-varying neighbourhood analysis (CNA)—to high-dimensional single-cell CyTOF data. Methods 16 TNFi-naïve RA patients commenced treatment with a TNFi (10 on Adalimumab, 6 on Etanercept) and peripheral blood samples were collected at 6-7 time-points between pre-treatment and 12-weeks. Peripheral blood mononuclear cells were extracted, and stained with a 35-marker CyTOF panel. Treatment response was classified using the EULAR response criteria, and patients were characterised as good, moderate or non-responders. Data were cleaned in FlowJo and analysed using both i) a cluster-based approach, where data were clustered into 12 populations, and linear mixed models were fitted per cluster to test for significant differences in population abundance and ii) a cluster-free approach called CNA where association testing is purely data-driven. Both analyses controlled for age, sex, type of TNFi and TNFi concentration. Results Cluster-based analysis showed at 12-weeks, 1 of the 12 clusters (CD4+CD39+HLA-DR+) significantly increased in abundance in the non-responder cohort compared to the good and moderate responders (adjusted p = 0.037). Interestingly, HLA-DR and CD39 genetic effects have previously been associated with TNFi response. No significant differences were observed with CNA. Conclusion These results demonstrate that significant differences in T-cell abundance can be seen as early as 12-weeks after commencing treatment with a TNFi. Validation of these findings is required before the predictive value of this T-cell population can be tested. Disclosure M.A. Sutcliffe: None. S. Ling: None. A. Banyard: None. L. Rumker: None. S. Viatte: None. A. Morris: None. A. Barton: None. S. Raychaudhuri: None. D. Plant: None.