Change In DAS28-ESR Research Articles

A retrospective study of efficacy of tofacitinib combined with bDMARDs in the treatment of rheumatoid arthritis patients with inadequate response to bDMARDs.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation, joint swelling, and pain involving multiple joints. While biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are popular treatments for RA, there is limited research on their combined use. This study examined a cohort of RA patients who demonstrated inadequate response to bDMARDs and subsequently initiated combination therapy with tofacitinib and bDMARDs, assessing both the efficacy and safety profile of this therapeutic approach. In this study, we retrospectively collected the electronic medical records (EMR) of 62 adult patients with RA who were admitted to the Fourth Affiliated Hospital Zhejiang University School of Medicine between August 2018 and December 2022. All patients had received at least one bDMARD treatment for more than 3 months and still exhibited moderate-to-high disease activity. Tofacitinib 5 mg bid was added to their original biological treatment in 28 cases, and other 34 cases switched to another bDMARD or tsDMARD as control group. Treatment was continued for 24 weeks following the initiation of combination therapy. Changes in DAS28-ESR and ACR20, 50, 70 response rates at week 24 were collected and analyzed from baseline, while changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at weeks 4, 8, 12, 24 were also collected and analyzed. After 24 weeks of treatment, the DAS28-ESR score in combined treatment group decreased significantly from a baseline of 5.26 ± 0.90 (3.87-8.31) to 2.67 ± 0.86 (1.41-5.11), with remission achieved by 19 patients (67.9%) and low disease activity achieved by five patients (17.9%). The DAS28-ESR in the control group exhibited a decrease from 5.20 ± 0.77 (3.87-7.23) at baseline to 3.25 ± 1.29 (1.54-5.69). In all, 13 patients (38.2%) achieved remission, while another 11 patients (32.4%) achieved low disease activity. The ACR20, 50, 70 response rates were 85.71%, 75%, and 39.29% in the combined treatment group, whereas it were 75.0%, 53.57%, 21.43% in the control group. Additionally, both ESR and CRP levels decreased significantly during the course of treatment without any reported adverse events leading to discontinuation. Our findings offer some evidence, supporting the effectiveness and safety of combining bDMARD with JAKi tofacitinib in RA patients who have an inadequate response to bDMARD monotherapy. This combination effectively manages disease activity while maintaining a relatively low and manageable incidence of adverse events. Further prospective randomized controlled trials with large sample sizes are anticipated to provide evidence-based medical support.

Comparative effectiveness of biological disease-modifying antirheumatic drugs and Janus kinase inhibitor monotherapy in rheumatoid arthritis.

To examine the effectiveness and drug tolerability of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitor (JAKi) monotherapy in patients with rheumatoid arthritis (RA) in a multicentre cohort study. Patients with RA initiated with bDMARD/JAKi monotherapy without conventional synthetic DMARDs were included. Monotherapy regimens were categorised as interleukin-6 receptor inhibitors (IL-6Ri), cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4Ig), JAKi, or tumour necrosis factor inhibitors (TNFi). Multiple propensity score-based inverse probability weighting (IPW) was used to reduce selection bias. Linear mixed-effect models with IPW were used to examine changes in the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) at 24 weeks, and drug retention was compared among monotherapy using IPW Cox proportional hazards models. A total of 849 treatment courses from 635 patients were included (IL-6Ri, 218; CTLA4Ig, 183; JAKi, 92; TNFi, 356). The difference in change in DAS28-ESR at week 24 as the primary outcome was -0.93 (95% CI: -1.20 to -0.66) lower in the IL-6Ri group than TNFi, while that of CTLA4Ig and JAKi was similar with that of TNFi (-0.20 [-0.48 to 0.08], -0.25 [-0.67 to 0.16], respectively). IL-6Ri use was associated with significantly lower overall drug discontinuation than TNFi use (hazard ratio = 0.55 [0.39-0.78], P = 0.001). Similar retention rates were identified among CTLA4Ig and JAKi compared to TNFi. In the analysis with IPW to reduce selection bias, IL-6Ri monotherapy was superior to TNFi monotherapy in terms of effectiveness and drug retention. No significant differences were identified between CTLA4Ig, JAKi, and TNFi monotherapy.

Longitudinal associations between body mass index and changes in disease activity and radiographic progression in rheumatoid arthritis patients treated with infliximab

ObjectivesTreatment response is worse in obese patients with rheumatoid arthritis (RA), including patients on weight-adjusted therapies like infliximab. We aimed to assess the association between body mass index (BMI) and...

Predicting the clinical efficacy of JAK inhibitor treatment for patients with rheumatoid arthritis based on Fas+ T cell subsets.

Rheumatoid arthritis (RA) is a common autoimmune disease. Janus kinase inhibitors (JAKi) have been approved for the treatment of RA; however, the impact of JAKi on immune cells remains inconclusive. This study investigated the response of immune cells to JAKi treatment to identify biomarkers by which to evaluate and predict clinical outcomes. Blood samples were collected from RA patients before and after JAKi treatment for the analysis of immunophenotypes. Our results revealed that JAKi mainly inhibited Fas+ T cell subsets. The percentage changes of Th Fas+ and Naive Th Fas+ cells were positively correlated with the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) values. Following treatment, moderate response (MR) RA patients presented a decrease in the number of Naive Th Fas+ cells (p = 0.0001). Initial percentages of 14 T cell and 20 B cell subsets were correlated with percentage changes in DAS28-ESR. Overall, 16 cell subsets presented significant differences between the non-response (NR) and MR groups. Excluding the multicollinearity of the immune cells, we constructed a JAKi treatment response prediction index (JRPI) using 5 subsets of T/B cells, the results of which were strongly correlated with percentage changes in DAS28-ESR (receiver operating characteristic curve of 1). Note that the NR group was clearly distinguished from the MR group (p = 0.0167). In conclusion, the efficacy of JAKi can be attributed mainly to the suppression of Fas+ T cell subsets. A positive correlation was shown between the therapeutic efficacy of JAKi and the percentage changes in both Th Fas+ cells and Naive Th Fas+ cells. Furthermore, the proposed JRPI could potentially be used as an indicator to predict the efficacy of JAKi prior to treatment in RA patients. These findings may contribute to the development of personalized treatment strategies for RA patients using JAKi.

IFABP2 as a new prognostic biomarker for secondary non-response in rheumatoid arthritis

Increased intestinal permeability promotes the translocation of bacterial products from the local microbiome to the circulation, inducing inflammation and increasing clinical activity in rheumatoid arthritis (RA). This study evaluates whether intestinal fatty acid binding protein 2 (IFABP2) serum levels are prognostic biomarkers of non-response to conventional synthetic disease-modifying antirheumatic drug therapy (csDMARDs) in RA. The therapeutic schemes administered to 60 women with RA for at least 18months were assessed retrospectively, and the treatment response was classified according to the change in DAS28-ESR over time. Serum levels of IFABP2 and TNF-α were determined by ELISA. Receiver operating characteristics (ROC) curve analysis and logistic regression models were used to assess the predictive value and the association of IFABP2 with the non-responder phenotype in RA patients. Eleven women had a responder phenotype, 23 had a primary non-responder phenotype, and 26 had a secondary non-responder phenotype. Secondary non-responders showed higher DAS28-ESR (P=0.009) and higher IFABP2 serum levels compared to the responder group (P=0.023) and the primary non-responder group (P=0.018). IFABP2 serum levels were positively correlated with chloroquine dose (r=0.581, P=0.007) and negatively correlated with total cholesterol (r=-0.456, P=0.019) in secondary non-responders. The area under the curve (AUC) value of IFABP2 for predicting secondary non-response was 0.736, and IFABP2 serum levels>9.311ng/mL were associated with secondary non-response to csDMARDs (OR=6.00, P=0.003). IFABP2 serum levels are potentially a new biomarker predictive of secondary non-response to csDMARDs in RA, although our findings should be validated externally and in a larger cohort.

Disease activity at baseline is an independent predictor of frailty at one year in pre-frail patients with rheumatoid arthritis; a multicenter retrospective observational study

ObjectivesTo investigate factors predicting frailty for one year in pre-frail patients with rheumatoid arthritis (RA). MethodA total of 298 RA patients who were pre-frail in 2020 were evaluated in this structured, retrospective observational study. Of the 298 patients, 42 who were frail and 256 who were not in 2021 were assigned to the frailty and non-frailty groups, respectively. After comparing characteristics of both groups using univariate analysis, predictive factors of frailty were assessed by logistic regression analysis. The proportion of frail patients in 2021 by DAS28-ESR level in 2020 was examined by the Cochran-Armitage trend test and chi-squared test. After dividing pre-frail patients into those with DAS28-ESR ≥3.2 and DAS28-ESR <3.2 in 2020, one-year change in DAS28-ESR in the frailty and non-frailty groups for both subgroups were compared by the paired t-test. ResultsThe frailty group was older (mean: 71.0 vs. 65.4 years) and had a higher DAS28-ESR (mean: 3.22 vs. 2.70) than the non-frailty group. DAS28-ESR was identified as a predictive factor for frailty (OR: 1.49). Among patients with DAS28-ESR ≥3.2 in 2020, DAS28-ESR improved in the non-frailty group in 2021 (mean: 3.97 in 2020 vs. 3.13 in 2021) but did not in the frailty group (3.97 in 2020 vs. 3.81 in 2021). Among those with DAS28-ESR <3.2 in 2020, DAS28-ESR was unchanged in the non-frailty group in 2021 (2.15 in 2020 vs. 2.23 in 2021) but increased in the frailty group (2.53 in 2020 vs. 3.23 in 2021). ConclusionsDisease activity at baseline is an independent predictor of frailty one year later in pre-frail patients with RA.

Associations Between microRNA-related Genetic Polymorphisms and Clinical Response to Methotrexate in Chinese Rheumatoid Arthritis Patients.

Emerging evidence indicates that microRNA (miRNA)-related genetic polymorphisms are strongly involved in the post-transcriptional regulation of the expression of pharmacokinetics and pharmacodynamics- related genes, therefore contributing to the genetic variability of drug response. To investigate the associations of miRNA-related genetic polymorphisms, including miRNA-5189 rs562929801, miRNA-595 rs4909237, SLCO1A2 rs4149009 and MTHFR rs3737966, and clinical response to methotrexate in Chinese rheumatoid arthritis patients. One hundred patients treated with MTX for approximately 3 months were prospectively followed up to evaluate the clinical response according to European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts - erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA) and remission (REM), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR > 0.6. Genetic polymorphisms were genotyped utilizing the HI-SNP technology. Of the 100 patients with a mean age of 52.23 ± 12.71 years, 81 patients were female (81.00%). After adjusting potential confounders, the major allele of miRNA-5189 rs562929801 was found to be significantly associated with EULAR response (A/A + A/G versus G/G, RR = 0.81, 95% CI = 0.67-0.99, P = 0.04) and ΔDAS28-ESR > 0.6 under dominant model (A/A + A/G versus G/G, RR = 0.83, 95% CI = 0.71-0.98, P = 0.03). However, nonsignificant evidence was detected for the remaining three miRNA-related genetic polymorphisms in neither univariable analysis nor multivariable analysis. Our results indicated that miRNA-5189 rs562929801 was significantly associated with clinical response to MTX, and this association warrants further replication studies with larger sample sizes.

Plasma metabolomic profiling as a tool to identify predictive biomarkers of methotrexate efficacy in rheumatoid arthritis

ObjectiveMethotrexate (MTX) remains the first-choice disease-modifying therapy in rheumatoid arthritis (RA). However, clinical response is variable, and no reliable predictive biomarkers of efficacy currently exist. In this study, plasma metabolomic profiling is evaluated as a tool to identify pretreatment biomarkers of MTX response in RA. MethodsPlasma collected from RA patients initiating MTX therapy (n = 20) were analyzed by metabolomic profiling totaling 648 identified metabolites. Pretreatment metabolomic profiles were compared based on clinical response after 16-weeks of MTX therapy. Clinical response to MTX was defined by a clinically meaningful reduction in disease activity score in 28 joints (DAS28-ESR) of greater than 1.2. ResultsPretreatment plasma levels of 19 metabolites were found to differ (p < 0.05) between RA patients based on response to MTX at 16-weeks. Spearman's correlation of pretreatment plasma metabolite levels with change in DAS28-ESR over the treatment period further supported three of the identified metabolites as associated with MTX response (p < 0.05). The identified metabolite levels were all found to be lower in RA patients responsive to MTX but were not found to be intercorrelated. Receiver operating characteristic analysis of each of the identified metabolites, alone or in combination, demonstrated an excellent discrimination between responders and non-responders based on pretreatment plasma levels of nornicotine (AUC = 0.84), N-methylisoleucine (AUC = 0.82), 2,3-dihydroxybutanoic acid (AUC = 0.82), and a combination biomarker panel score (AUC = 0.98). ConclusionPretreatment plasma metabolomic profiling identified multiple metabolites associated with early response to MTX therapy in RA and represents a promising approach for the identification of clinical biomarkers of MTX response in RA.

Associations Between Genetic Polymorphisms Within Transporter Genes and Clinical Response to Methotrexate in Chinese Rheumatoid Arthritis Patients: A Pilot Study.

PurposeTo investigate the associations between genetic polymorphisms within transporter genes and clinical response to methotrexate (MTX) in Chinese rheumatoid arthritis (RA) patients.Patients and MethodsA total of 100 RA patients receiving MTX were prospectively followed up for approximately 3 months to determine the clinical response based on several criteria, including European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts – erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR >0.6. Fifty-four single nucleotide polymorphisms (SNPs) within seven transporter genes, including SLC19A1, ABCB1, ABCC1~4 and ABCG2, were genotyped.ResultsMultivariable analysis revealed that SLC19A1 rs12659 and rs3788200, ABCC2 rs3740066, rs4148396 and rs717620 were significantly associated with EULAR good and moderate response, and ABCC2 rs3740066 and rs717620 were significantly associated with DAS28-ESR LDA, and ABCB1 rs1128503, rs4148737 and ABCC3 rs2277624, rs4148416 were significantly associated with ΔDAS28-ESR. Moreover, 12 genetic polymorphisms were found to be significantly associated with ΔDAS28-ESR >0.6. With adjustment for corresponding confounders, SLC19A1 TGAA haplotype consisting of rs1051266, rs1131596, rs12659 and rs3788200 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR >0.6 compared with the most common haplotype CAGG. The ABCC2 haplotype TTT composed of rs717620, rs4148396 and rs3740066 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR >0.6 compared with the most common haplotype CCC.ConclusionOur results highlight the potential of genetic polymorphisms within transporter genes, particularly SLC19A1 and ABCC2, as predictors of clinical response to MTX in Chinese RA patients.

Low-dose rituximab protocol in rheumatoid arthritis-outcome and economic impact.

ObjectivesA significant proportion of RA patients, particularly those associated with poor prognostic factors, fail on conventional DMARDs (cDMARDs). Although rituximab (RTX) has been effective in these patients, the cost of therapy makes it unaffordable, particularly in poor and developing countries. Numerous, albeit small, studies using lower doses have shown contradictory results. We aimed to analyse the effectiveness of a low-dose RTX protocol based on clinical outcomes in RA patients.MethodsSeropositive RA patients with moderate to high disease activity (DAS28-ESR > 3.2) despite combination cDMARDs, treated with RTX, were included in retrospective analysis. All patients were treated according to a predefined protocol, using 500 mg RTX with ongoing cDMARDs at baseline and repeat dosing at 6 weeks or beyond, on lack of moderate to good EULAR response. The B cell count was assessed at baseline, 2 and 24 weeks.ResultsAt 12 weeks, 93% of 166 patients [mean (s.d.) age, 51.5 (11.96) years, 25 men and 141 women, with a disease duration of 10.4 (6.29) years] achieved moderate to good EULAR response. At 24 weeks, 90.8% of patients achieved moderate to good EULAR response, 19.8% achieved low disease activity and 29.5% achieved remission, with a mean change in DAS28-ESR from baseline of 2.9 (1.3). RTX failure and relapse were seen in 5.4% and 3.6%, respectively. The response was maintained for 12.3 (7.2) months with a mean RTX dose 521.1 (100.8) mg. Adverse events were seen in 9.6%. When compared with the standard dosing regimen with the originator molecule, a cost reduction of 90% was achieved.ConclusionA low-dose RTX regimen achieved reasonably good clinical outcomes at the end of 6 months, with a significantly lower cost.

Predictive ability, validity, and responsiveness of the multi-biomarker disease activity score in patients with rheumatoid arthritis initiating methotrexate

Background/ObjectiveWe assessed the predictive value, validity, and responsiveness of the multi-biomarker disease activity (MBDA) score in rheumatoid arthritis (RA) patients initiating methotrexate. MethodsWe examined data from a 16-week, open-label study of methotrexate in RA. Disease activity was assessed and the MBDA score was calculated using serum that was collected and banked from baseline and week 16. Multivariable logistic regression models assessed whether MBDA scores predicted treatment response. Pearson correlations assessed the convergent validity and external responsiveness of the MBDA score with other measures of RA disease activity. Internal responsiveness was assessed by calculating standardized response means (SRMs). ResultsA total of 130 patients initiated the study, with follow-up MBDA scores available on 95 patients. Baseline MBDA scores did not predict ACR response or achieving low disease activity. Higher baseline DAS28-ESR scores were significantly associated with an ACR20 response (odds ratio 1.89 per unit, 95% CI 1.20–2.96) but not ACR50, ACR70, or low disease activity. The MBDA score moderate-to-weakly correlated with the DAS28-ESR and ESR at baseline and week 16, with weak-to-very weak correlations with patient global and function. Change in MBDA scores moderately correlated with changes in DAS28-ESR and ESR, while weakly correlating with changes in patient global and function. The DAS28-ESR (SRM 1.31) demonstrated greater responsiveness following methotrexate treatment than the MBDA score (SRM 0.71). ConclusionsMBDA scores did not predict treatment response to methotrexate. The MBDA score weak-to-moderately correlated with baseline and post-treatment disease activity measures and was less responsive to methotrexate-related improvement than the DAS28-ESR.

AB0295 CHANGE IN DISEASE ACTIVITY AND TREATMENT RESPONSE AFTER ABATACEPT TREATMENT FOR RHEUMATOID ARTHRITIS: REAL-WORLD EVIDENCE FROM THE UK

Background:Patients with moderate to severe active rheumatoid arthritis (RA) may be treated with biological disease-modifying antirheumatic drugs (bDMARDs), such as abatacept, after treatment failure with conventional synthetic DMARDs (csDMARDs). Abatacept has shown equivalent efficiency with other targeted therapies for RA in clinical trials and network meta-analyses. However, there is limited real-world evidence on patient outcomes associated with abatacept treatment in UK routine clinical practice.Objectives:To describe the clinical outcomes of RA patients treated with abatacept in UK real-world clinical practice.Methods:A multi-centre, retrospective observational study was undertaken in RA patients treated with abatacept at any line of therapy (LOT). Data were extracted from medical records at four UK hospitals. Patients aged 18 years or older who received abatacept between 1 January 2013 and 31 December 2017 were included. The index date was the date of first bDMARD initiation, with follow-up from index date to latest RA clinic visit, death or 31 December 2017, whichever occurred first.Clinical outcomes (disease activity and response to treatment) were measured using the 28-joint Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) and European League Against Rheumatism (EULAR) response criteria1-3.Results:The study included 213 patients (mean age 55.2 years, 71.4% female, 7.0 years mean duration of RA at index date). Where ACPA and RF status were recorded, 66.1% of patients were anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) positive at index. Mean DAS28-ESR at index was 6.2 (SD 1.0) and 80.9% of patients were categorised with high disease activity.Irrespective of LOT, changes in DAS28-ESR (where recorded) from LOT initiation among patients treated with abatacept versus other bDMARDs were -1.59 vs -1.56 (LS mean (SE): -0.04; 95% CI: -0.45,0.38; p=0.86) at 6 months and -1.98 vs -1.42 (LS mean (SE): -0.56; 95% CI: -1.04,-0.07; p=0.03) at 12 months, respectively. Table 1 shows that compared with other bDMARDs, patients treated with abatacept at any LOT experienced good response to treatment at 6 months (22.8%, n= 21/92 vs 15.9%, n= 24/151) and 12 months (27.9%, n= 17/61 vs 20.5%, n= 24/117) according to EULAR criteria.Table1.Treatment response at 6 and 12 months after initiation of any LOT*EULAR response6 months12 monthsAbatacept,n = 92Other bDMARDs,n = 151Abatacept,n = 61Other bDMARDs,n = 117Good21 (22.8%)24 (15.9%)17 (27.9%)24 (20.5%)Moderate38 (41.3%)60 (39.7%)22 (36.1%)40 (34.2%)None33 (35.9%)67 (44.4%)22 (36.1%)53 (45.3%)n = number of unique LOTs in which a patient has both a DAS28-ESR collected at initiation and 6 and/or 12 months (a patient may be included in this analysis multiple times)Patients who received abatacept remained on treatment for significantly longer than patients who received other bDMARDs at LOT1 (median 53.4 vs 17.4 months; p&lt;0.01) (Figure 1) and at LOT2 (median 40.1 vs 17.1 months; p&lt;0.01).Figure 1.Time on treatment from first LOT initiation, abatacept versus other bDMARDsConclusion:RA patients who received bDMARDs, including abatacept, experienced reduced disease activity. These findings are comparable with those from a European, multicentre, observational study on patients receiving abatacept4. The mechanisms associated with such clinical benefit should be elucidated in future research.

Levels of CXCL13 and sICAM-1 correlate with disease activity score in patients with rheumatoid arthritis treated with tocilizumab

BackgroundTocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 receptor, has been proven to be a safe and effective treatment for rheumatoid arthritis (RA). Because RA is a heterogenous disease and patient response to treatments can vary, identifying characteristics that predict which patients are more likely to respond to TCZ is important for optimal patient care. Serum levels of C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) have been associated with response to TCZ in patients with RA.ObjectivesTo evaluate the association of CXCL13 and sICAM-1 with disease activity and response to TCZ in patients with early RA and those with inadequate response to disease-modifying antirheumatic drugs (DMARD-IR).MethodsBaseline and week 24 serum CXCL13 and sICAM-1 levels were measured using available patient samples from the FUNCTION (early RA) and LITHE (DMARD-IR) trials. Correlations between CXCL13 and sICAM-1 levels and Disease Activity Score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR) at baseline and between change in CXCL13 and sICAM-1 and change in DAS28-ESR at week 24 were estimated. CXCL13 and sICAM-1 changes from baseline to week 24 were compared between treatment arms. The effects of TCZ treatment and baseline DAS28-ESR, CXCL13 and sICAM-1 levels on DAS28-ESR remission and 50% improvement per the American College of Rheumatology (ACR50) response at week 24 were determined.ResultsOverall, 458 patients from FUNCTION and 287 patients from LITHE were included. Correlation of baseline serum CXCL13 and sICAM-1 levels with DAS28-ESR was weak to moderate. CXCL13 and sICAM-1 levels decreased significantly at week 24 in TCZ-treated patients in both the early-RA and DMARD-IR populations. CXCL13 and sICAM-1 changes correlated moderately to weakly with DAS28-ESR changes at week 24 in both populations. The treatment regimen, but not baseline CXCL13 and sICAM-1 levels, had a significant effect on the likelihood of DAS28-ESR remission and ACR50 response.ConclusionsAlthough CXCL13 and sICAM-1 are modestly associated with RA disease activity, they do not predict response to TCZ in all RA populations.

Effect of medication adherence on disease activity among Japanese patients with rheumatoid arthritis.

For the optimum efficacy of disease-modifying anti-rheumatic drugs (DMARDs), patients need to be adherent to their medication regimen. To clarify the effects of medication adherence on disease activity in Japanese patients with rheumatoid arthritis (RA), we conducted a cohort study in patients with various stages of RA. Patients were enrolled from the Kyoto University RA Management Alliance cohort, and followed up prospectively for 12 months. In this study, a total of 475 patients were analyzed and divided into 9 groups according to their medication adherence and the RA disease duration. The primary outcomes were based on the rate of a disease flare. The secondary outcomes were the changes in disease activity score using 28 joints (DAS28-ESR), simplified disease activity index (SDAI) and physical disability by health assessment questionnaire-disability index (HAQ). The changes in DAS28-ESR, HAQ, and the risk of disease flare in the highly adherent patients were significantly lower than those of the less adherent patients among the groups with RA ≤ 4.6 years but not those among the other groups. Taken together, this study identified a significant association between medication adherence and the disease flare during early-stage RA or short disease duration. These results emphasize the need to pay more attention to medication adherence in preventing the disease progression of RA.

Pivotal factors for successful withdrawal of nonsteroidal anti-inflammatory drugs in rheumatoid arthritis patients in remission or with low-disease activity.

The purpose of this study is to examine the patient-reported outcomes (PRO) after discontinuing nonsteroidal anti-inflammatory drugs (NSAIDs) and clinical factors associated with a favorable outcome in patients with rheumatoid arthritis (RA) in remission or with low-disease activity (LDA). A 16-week prospective open-label trial was conducted at eight rheumatology clinics in Korea. RA patients with 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) <3.2 who were on NSAIDs for more than a month were enrolled, and NSAIDs were discontinued. Acetaminophen (AAP) was used as the rescue medication, and NSAIDs were restarted when joint pain was intolerable with AAP. The endpoint was to analyze the group of patients who continued to withdraw NSAIDs. Among 109 enrolled patients, 105 completed the 16-week follow-up. Eighty-nine (84.8%) patients remained without restarting NSAIDs. In these patients, there was a slight increase in their pain levels compared with baseline (median 14.0 versus 19.0 using the pain-visual analog scale, p=0.010). However, changes in DAS28-ESR (p=0.638) and routine assessment of patient index data 3 (RAPID-3) (p=0.128) were insignificant. Moreover, 66 (62.9%) patients showed sustained effectiveness on PRO without restarting NSAIDs. In the multivariate regression models, joint swelling was the detrimental factor in NSAID withdrawal (odds ratio [OR] 0.149, 95% confidence interval [CI] 0.033-0.680, p=0.014) and sustained effectiveness (OR 0.284, 95% CI 0.091-0.883, p=0.030). Joint pain in RA patients in remission or with LDA can be well managed without NSAIDs, especially in those without swollen joints at the time of cessation.

Association of baseline cytokine levels with anti-tumour necrosis factor treatment response in rheumatoid arthritis

Abstract Background Clinical trials of anti-tumour necrosis factor alpha (TNF) have shown efficacy in 60–70% of rheumatoid arthritis patients (RA). Predicting response to anti-TNF drugs at baseline remains an elusive goal in RA management. The purpose of this study was to determine if baseline levels of circulating cytokines, soluble receptors, adhesion molecules and metabolic factors differentiate future responders. Methods RA patients (n=29) with active disease were recruited, who had failed on disease modifying drugs and were recommended for anti-TNF treatment. Peripheral blood samples were collected at baseline. Responders were identified by a ≥1.2 reduction in disease activity score (DAS28-ESR) at 6 months. Five protein arrays quantified 33 proteins in pre-treatment plasma (Cytokine I, III and IV; Metabolic I; Adhesion molecule; Randox Laboratories Ltd., UK). Data was analysed by Pearson ranked correlation and logistic regression to clinical measures of disease activity at baseline and six months anti-TNF treatment. Results Elevated levels of interleukin 8 (p=0.043), monocyte chemoattractant protein (p=0.027), granulocyte-macrophage colony-stimulating factor (p=0.020) and soluble interleukin 2α receptor (p=0.01) were associated with high TJC at baseline. No significant relationship with the protein array panels was recorded relative to baseline DAS28-ESR. Significant inverse correlations were observed between absolute change in DAS28-ESR after 6 months of anti-TNF therapy and baseline levels of interleukin 6 (p=0.026) and resistin (p=0.044). Conclusions These findings suggest that baseline levels of specific circulating proteins may help to differentiate RA patient responders to anti-TNF therapies.

Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis who require biological treatment (ORBIT): an open-label, randomised controlled, non-inferiority, trial

Tumour necrosis factor (TNF) inhibition and B-cell depletion are highly effective treatments for active rheumatoid arthritis, but so far no randomised controlled trials have directly compared their safety, efficacy, and cost-effectiveness. This study was done to test the hypothesis that using rituximab would be clinically non-inferior and cheaper compared with TNF inhibitor treatment in biological-treatment naive patients with rheumatoid arthritis. This open-label, randomised controlled, non-inferiority trial enrolled patients with active, seropositive rheumatoid arthritis and an inadequate response to synthetic disease modifying anti-rheumatic drugs (DMARDs) from 35 rheumatology departments in the UK. Patients were randomly assigned 1:1 to the rituximab or TNF inhibitor groups with minimisation to account for methotrexate intolerance using a web-based randomisation system. Patients were given intravenous rituximab 1 g on days 1 and 15, and after 26 weeks if they responded to treatment but had persistent disease activity (28 joint count disease activity score [DAS28-ESR] >3.2; rituximab group) or a TNF inhibitor-adalimumab (40 mg subcutaneously every other week) or etanercept (50 mg per week subcutaneously) according to the patient's and rheumatologist's choice (TNF inhibitor group). Patients could switch treatment in the case of drug-related toxic effects or absence or loss of response. The primary outcome measure was the change in DAS28-ESR between 0 and 12 months in the per-protocol population of patients who were assigned to treatment and remained in follow-up to 1 year. We assessed safety in all patients who received at least one dose of study drug. We also assessed the cost-effectiveness of each strategy. The non-inferiority margin was specified as 0.6 DAS28-ESR units. This study is registered with ClinicalTrials.gov, number NCT01021735. Between April 6, 2009, and Nov 11, 2013, 295 patients were randomly assigned and given either rituximab (n=144) or TNF inhibitor (n=151) treatment. After 12 months, the change in DAS28-ESR for patients assigned to rituximab was -2.6 (SD 1.4) and TNF inhibitor was -2.4 (SD 1.5), with a difference within the prespecified non-inferiority margin of -0.19 (95% CI -0.51 to 0.13; p=0.24). The health-related costs associated with the rituximab strategy were lower than the TNF inhibitor strategy (£9,405 vs £11,523 per patient, p<0.0001). 137 (95%) of 144 patients in the rituximab group and 143 (95%) of 151 patients in the TNF inhibitor group had adverse events. 37 serious adverse events occurred in patients receiving rituximab compared with 26 in patients receiving TNF inhibitors, of which 27 were deemed to be possibly, probably, or definitely related to the treatment (15 vs 12, p=0.5462). One patient in each group died during the study. Initial treatment with rituximab is non-inferior to initial TNF inhibitor treatment in patients seropositive for rheumatoid arthritis and naive to treatment with biologicals, and is cost saving over 12 months. Arthritis Research UK, Roche.

AB0468 The Unique Subset of Monocytes Expressing CD14bright and CD16 is Increased with Disease Activity and Changed with Treatment Response in Patients with Rheumatoid Arthritis

BackgroundWe reported that the expression of CD16 on peripheral monocytes was significantly increased in patients with rheumatoid arthritis (RA) compared with healthy controls (HCs). Recently, it has been shown that...

THU0159 Disease Activity Assessment Using the DAS28, CDAI and SDAI and Effect of Anti-Drug Antibody on Clinical Response in a Randomized, Double-Blind, Comparative Trial of CT-P13 and Innovator Infliximab: Planetra Study

BackgroundCT-P13 is a biosimilar to innovator infliximab (INX) approved by the European Medicines Agency. From the PLANETRA, which is randomized, double-blind, active-controlled trial to assess efficacy and safety of CT-P13...

Association of a complement receptor 1 gene variant with baseline erythrocyte sedimentation rate levels in patients starting anti-TNF therapy in a UK rheumatoid arthritis cohort: results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort

Eligibility for anti-tumour necrosis factor (TNF) therapy in most European countries is restricted to severe, active rheumatoid arthritis (RA). The DAS28 score is a marker of disease severity and incorporates one of two inflammatory markers, erythrocyte sedimentation rate (ESR) or C-reactive protein. We aimed to determine the relation between genetic variants known to affect ESR and levels of ESR in patients with active RA. DNA samples were genotyped for four single-nucleotide polymorphisms (SNPs) rs7527798 (CR1L), rs6691117 (CR1), rs10903129 (TMEM57) and rs1043879 (C1orf63). The association between SNPs and baseline ESR, baseline DAS28-ESR, and change in DAS28-ESR was evaluated. Baseline ESR was significantly associated with CR1 rs6691117 genotype (P=0.01). No correlation was identified between baseline DAS28-ESR or change in DAS28-ESR. In conclusion, genetic variation in the gene encoding CR1 may alter ESR levels but not DAS28-ESR, indicating no adjustment for CR1 genotype is required in the assessment of patients with severe active RA.