EULAR Response Research Articles

Non-Trough Adalimumab and Certolizumab Pegol Serum Drug Levels in Rheumatoid Arthritis Associated with a Therapeutic EULAR Response: Results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGS) Cohort

Non-Trough Adalimumab and Certolizumab Pegol Serum Drug Levels in Rheumatoid Arthritis Associated with a Therapeutic EULAR Response: Results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGS) Cohort

Real-life experience of tofacitinib in patients with treatment-resistant rheumatoid arthritis: A 5-year follow-up: Monocentric experience.

OBJECTIVEThe present study aims to assess the short- and long-term effects of tofacitinib (TOFA) therapy on efficacy, safety, and drug retention rate patients with rheumatoid arthritis (RA) refractory to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and/or biological disease-modifying anti-rheumatic drugs (bDMARDs).METHODSThirty-five patients with RA who received TOFA therapy for at least 3 months in rheumatology outpatient clinic between December 2015 and December 2020 were included in the study. The prospectively follow-up results of the patients obtained on the 6th month and 5th year are presented. Demographic characteristics of the patients, the disease activity score-28 for RA with erythrocyte sedimentation rate (DAS 28-4 [ESR]), change in DAS-28, health assessment questionnaire score, patient visual analog scale score, and laboratory parameters were recorded. The data at 6 months and 5 years of treatment were compared with baseline data. All side effects were recorded at each follow-up visit. Wilcoxon signed-rank tests were used for analysis.RESULTSOf the 35 patients, 23 received TOFA treatment after receiving ≥1 bDMARDs, while the remaining 12 patients received TOFA therapy were biologic naive. On the 6-month follow-up, DAS 28-4 (ESR) score and DAS28 improvement significantly decreased at the 6th months from baseline (p<0.001 and p<0.001, respectively), and moderate disease activity was achieved in 13 patients. High disease activity persisted in four patients. DAS28 improvement according to the EULAR response criteria was good response in 86% of the patients. DAS 28-4 (ESR) score and DAS28 improvement significantly decreased at 5 years from baseline (p<0.01 and p<0.001, respectively), and the moderate disease activity was achieved in 10 patients. High disease activity persisted in two patients. Drug retention rate at 5-year follow-up was 54% and the daily glucocorticoid therapy could be discontinued in 9 patients (47%). Three patients (15%) were tested positive for COVID-19. None of them required hospitalization and no deaths were occurred due to COVID-19.CONCLUSIONTOFA is effective and well-tolerated treatment options that reduce the need for steroids in patients with RA.

Intravenous pegylated liposomal prednisolone outperforms intramuscular methylprednisolone in treating rheumatoid arthritis flares: A randomized controlled clinical trial

Glucocorticoids (GCs) are potent anti-inflammatory drugs but their use is limited by systemic exposure leading to toxicity. Targeted GC delivery to sites of inflammation via encapsulation in long-circulating liposomes may improve the therapeutic index. We performed a randomized, double-blind, active-controlled, multi-center study in which intravenously (i.v.) administered pegylated liposomal prednisolone sodium phosphate (Nanocort) was compared to equipotent intramuscular (i.m.) methylprednisolone acetate (Depo-Medrol®; i.e. a current standards-of-care for treating flares in rheumatoid arthritis patients). We enrolled 172 patients with active arthritis who met all eligibility criteria, eventually resulting in 150 patients randomized in three groups: (1) Nanocort 75 mg i.v. infusion plus i.m. saline injection; (2) Nanocort 150 mg i.v. infusion plus i.m. saline injection; and (3) Depo-Medrol® 120 mg i.m. injection plus i.v. saline infusion. Dosing in each group occurred at baseline and on day 15 (week 2). Study visits occurred at week 1, 2, 3, 4, 6, 8 and 12, to assess both efficacy and safety. The primary endpoint was the “European League Against Rheumatism” (EULAR) responder rate at week 1. Safety was determined by the occurrence of adverse events during treatment and 12 weeks of follow-up. Treatment with Nanocort was found to be superior to Depo-Medrol® in terms of EULAR response at week 1, with p-values of 0.007 (good response) and 0.018 (moderate response). Treatments were well tolerated with a comparable pattern of adverse events in the three treatment groups. However, the Nanocort groups had a higher incidence of hypersensitivity reactions during liposome infusion. Our results show that liposomal Nanocort is more effective than Depo-Medrol® in treating patients with rheumatoid arthritis flares and has similar safety. This is the first clinical study in a large patient population showing that i.v. administered targeted drug delivery with a nanomedicine formulation improves the therapeutic index of glucocorticoids.

Predictors of response to TNF inhibitors in rheumatoid arthritis: an individual patient data pooled analysis of randomised controlled trials

ObjectiveTo identify patient characteristics associated with responsiveness to tumour necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA).Materials and methodsIndividual patient data from 29 randomised controlled trials (RCTs) evaluating the efficacy...

Metabolomics profiling predicts outcome of tocilizumab in rheumatoid arthritis: an exploratory study

To study metabolic signatures can be used to identify predictive biomarkers for a patient's therapeutic response. We hypothesized that the characterization of a patients' metabolic profile, utilizing one-dimensional nuclear magnetic resonance (1H-NMR), may predict a response to tocilizumab in patients with rheumatoid arthritis (RA). 40 active RA patients meeting the 2010 ACR/EULAR classification criteria initiating treatment with tocilizumab were recruited. Clinical outcomes were determined at baseline, and after six and twelve months of treatment. EULAR response criteria at 6 and 12months to categorize patients as responders and non-responders. Blood was collected at baseline and after six months of tocilizumab therapy. 1H-NMR was used to acquire a spectra of plasma samples. Chenomx NMR suite 8.5 was used for metabolite identification and quantification. SPSS v.27 and MetaboAnalyst 4.0 were used for statistical and pathway analysis. Isobutyrate, 3-hydroxybutyrate, lysine, phenylalanine, sn-glycero-3-phosphocholine, tryptophan and tyrosine were significantly elevated in responders at the baseline. OPLS-DA at baseline partially discriminated between RA responders and non-responders. A multivariate diagnostic model showed that concentrations of 3-hydroxybutyrate and phenylalanine improved the ability to specifically predict responders classifying 77.1% of the patients correctly. At 6months, levels of methylamine, sn-glycero-3-phosphocholine and tryptophan tended to still be low in non-responders. The relationship between plasma metabolic profiles and the clinical response to tocilizumab suggests that 1H-NMR may be a promising tool for RA therapy optimization. More studies are needed to determine if metabolic profiling can predict the response to biological therapies in RA patients.

The efficacy of low dose short-term prednisone therapy for remission induction in newly diagnosed rheumatoid arthritis patients

BackgroundThe ACR/EULAR recommendations endorse the use of glucocorticoids (GCs) for rheumatoid arthritis (RA) patients’ flares and as a bridge to a DMARD. However, the recommendation of low dose short-term monotherapy with (GCs) remains open to the discretion of the clinician. The aim of this study was to assess whether a short-term use of low dose prednisone monotherapy was effective in inducing remission in newly diagnosed RA patients.MethodsA retrospective analysis of patients newly diagnosed with RA at a Community Health Center in North Dakota was performed based on the ACR/EULAR RA classification criteria. Demographic and clinical data were abstracted from patients’ medical charts. Patients treated with (< 10 mg/day) of prednisone up to 6 months were included. Response to prednisone was analyzed according to pre- and post-treatment DAS28-ESR score and EULAR response criteria.ResultsData on 201 patients were analyzed. The mean prednisone dose was 8 mg/day (range: 5–10; SD = 1.2) and the mean treatment duration was 42.2 days (12–177; 16.9). Disease severity significantly improved from baseline to follow-up for: tender joint count (8.6 ± 4.8 vs. 1.5 ± 3.3; P < 0.001), swollen joint count (6.2 ± 5.0 vs. 1.4 ± 3.0; P < 0.001), and visual analog pain score (4.8 ± 2.6 vs. 2.1 ± 2.5; P < 0.001). DAS28-ESR disease severity significantly improved from baseline to follow-up: (5.1 ± 1.2 vs. 2.7 ± 1.3; P < 0.001). Per EULAR response criteria, 69.7% of patients showed good response to treatment and 20.4% showed moderate response. 54.2% of patients reached remission.ConclusionShort-term use of low dose prednisone monotherapy induced disease remission and improved clinical severity of RA in the majority of newly diagnosed patients.

Influence of the FCGR2A rs1801274 and FCGR3A rs396991 Polymorphisms on Response to Abatacept in Patients with Rheumatoid Arthritis.

Abatacept (ABA) is an immunosuppressant indicated for treatment of rheumatoid arthritis (RA). Effectiveness might be influenced by clinical RA variants and single-nucleotide polymorphisms (SNPs) in genes encoding protein FCGR2A (His131Arg) and FCGR3A (Phe158Val) involved in pharmacokinetics of ABA. An observational cohort study was conducted in 120 RA Caucasian patients treated with ABA for 6 and 12 months. Patients with the FCGR2A rs1801274-AA genotype (FCGR2A-p.131His) showed a better EULAR response (OR = 2.43; 95% CI = 1.01–5.92) at 12 months and low disease activity (LDA) at 6 months (OR = 3.16; 95% CI = 1.19–8.66) and 12 months (OR = 6.62; 95% CI = 1.25–46.89) of treatment with ABA. A tendency was observed towards an association between the FCGR3A rs396991-A allele (FCGR3A-p.158Phe) and better therapeutic response to ABA after 12 months of treatment (p = 0.078). Moreover, we found a significant association between the low-affinity FCGR2A/FCGR3A haplotypes variable and LDA after 12 months of ABA treatment (OR = 1.59; 95% CI = 1.01–2.58). The clinical variables associated with better response to ABA were lower age at starting ABA (OR = 1.06; 95% CI = 1.02–1.11) and greater duration of ABA treatment (OR = 1.02; 95% CI = 1.01–1.04), lower duration of previous biological therapies (OR = 0.99; 95% CI = 0.98–0.99), non-administration of concomitant disease-modifying antirheumatic drugs (DMARDs) (OR = 24.53; 95% CI = 3.46–523.80), non-use of concomitant glucocorticoids (OR = 0.12; 95% CI = 0.02–0.47), monotherapy (OR = 19.22; 95% CI = 2.05–343.00), lower initial patient’s visual analogue scale (PVAS) value (OR = 0.95; 95% CI = 0.92–0.97), and lower baseline ESR (OR = 0.92; 95% CI = 0.87–0.97). This study showed that high-affinity FCGR2A-p.131His variant, low-affinity FCGR3A-p.158Phe variant, and combined use of FCGR2A/FCGR3A genetic variations could affect ABA effectiveness. Further studies will be required to confirm these results.

Comparison of two dose escalation strategies of methotrexate in active rheumatoid arthritis: a multicentre, parallel group, randomised controlled trial

ObjectivesThere are no head-to-head trials of different dose escalation strategies of methotrexate (MTX) in RA. We compared the efficacy, safety and tolerability of ‘usual’ (5 mg every 4 weeks) versus...

AB0229 A NATIONAL, MULTICENTER, SECONDARY DATA USE STUDY EVALUATING EFFICACY AND RETENTION OF FIRST-LINE BIOLOGIC TREATMENT WITH TOCILIZUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS IN REAL-LIFE SETTING FROM TURKBIO REGISTRY

Background:Tocilizumab (TCZ) is a human anti-interleukin (IL)-6 receptor antibody approved in Turkey for the treatment of rheumatoid arthritis (RA).Objectives:In this study our purpose was to describe the disease activity, quality of life (QoL), and retention rate in RA patients who were prescribed TCZ as first-line biologic treatment in a real-world setting.Methods:Anonymized patient registry of TURKBIO was used based in a national, multicenter, and retrospective context. We conducted a search in the registry between years 2013 and 2020 and included adult RA patients who were prescribed with TCZ as their first-line biologic treatment with a post-TCZ follow-up of at least 6 months. CDAI, DAS28-(ESR), and HAQ-DI scores in 6, 12, and 24 months were obtained. Pairwise comparison was carried out for survey scores across baseline and timepoints. Subgroup analysis for route of TCZ administration was performed. EULAR response criteria were used for response evaluation. Retention of TCZ was evaluated by Kaplan-Meier analysis.Results:Overall,130 patients with a mean RA duration of14 years were included in the study. 87.7% of the patients were female and mean age was53 (SD; 15.0). Median duration of follow-up was 18.5 months. Majority (90.8%) of patients were given tocilizumab via intravenous route at baseline. Number of patients with ongoing TCZ treatment and follow-up at 6, 12, and 24 months were 121 (93%), 85 (65%), and 46 (35%), respectively. Remission rates at 6, 12, and 24 months per CDAI (&lt;2.8) and DAS28-(ESR) (&lt;2.6) scores were 61.5%, 44.6%, 30%, and 54.6%, 40.8%, 27.7%, respectively. CDAI, DAS28-(ESR) and HAQ-DI survey scores significantly improved at 6, 12 and 26 months, respectively (p&lt;0.001) (Table 1) in both IV and SC TCZ subgroups. At 6, 12 and 24months 74.8%, 82.5% and 86.4% of patients achieved a EULAR good response respectively. Twenty-three patients (17.6%) discontinued TCZ at 24 months. Of these, 19 patients discontinued due to unsatisfactory response. Retention rates of TCZ at 6, 12, and 24 months were 93%, 84.3%, and 72.2%, respectively (Figure 1).Conclusion:TCZ as a first-line biologic treatment was found to be clinically effective in this real-world study with a high retention rate. These results are in line with the results gathered from previous TCZ controlled and real-life studies in which TCZ was found clinically safe and effective.

AB0155 COMPARATIVE ANALYSES OF SEROLOGICAL BIOMARKERS AND DISEASE CHARACTERISTICS BETWEEN ELDERLY ONSET RHEUMATOID ARTHRITIS (EORA) AND YOUNGER ONSET RHEUMATOID ARTHRITIS (YORA)

Background:Several studies have reported differences in disease characteristics between elderly onset RA (EORA: age of onset &gt; 60 years) and younger-onset RA (YORA). However, the findings across the studies have been rather inconsistent owing partially to the genetic variation across the populations studied. While a few studies have looked into the clinical aspects of EORA, there is a profound lack of comparative data on serological findings between EORA and YORA. Seropositive RA is known to be associated with more aggressive disease and the titres of the autoantibodies may predict the disease activity and the severity of radiographic progression.Objectives:The main aim of this study was to compare the levels of the autoantibodies namely anti–CCP (cyclic citrulinated peptide), IgA, IgM, IgG rheumatoid factors(RF) and disease characteristics between the EORA and YORA groups.Methods:We consecutively recruited a total of 151 female RA patients who were tested for IgA RF, IgG RF, IgM RF and anti CCP antibodies. Participants were aged above 18 years and met the 2010 ACR/EULAR RA criteria. Data on the disease characteristics (age at onset, disease activity at onset, disease duration and medications)were obtained by reviewing the medical records of the subjects. Subjects were divided into 2 groups i.e EORA and YORA based on age at onset of RA. All subjects were assessed for the severity of radiographic joint damage and functional disability based on Modified Sharp Score (MSS) and Health-assessment questionnaire-disability index (HAQ- DI), respectively. The EULAR response criteria was used to determine the subjects’ response to disease-modifying anti-rheumatic drugs.Results:The EORA group had 69 patients whereas the YORA group had 82 patients. The mean anti-CCP and IgA RF levels were significantly higher in the YORA group with p values of 0.002 and 0.035, respectively. The YORA group had significantly more severe disease at onset (p value for DAS 28 at onset was 0.009) with worse radiographic joint damage (p value for MSS was 0.006). In parallel with these findings, the YORA group had significantly higher ESR and CRP at onset with higher frequency of subjects requiring advanced therapies. The differences in frequency of RF positivity, disease duration, number of DMARDs, prednisolone dose and HAQ-Di scores between the groups did not reach statistical significance.Conclusion:EORA is characterized by lower levels of anti-CCP and IgA autoantibodies with less aggressive disease as compared to YORA.

The association between increased body mass index and response to conventional synthetic disease-modifying anti-rheumatic drug treatment in rheumatoid arthritis: results from the METEOR database.

Few data exist on the association between increased BMI and response to conventional synthetic DMARDs (csDMARDs) in RA. We aimed to explore the association between increased (overweight or obese) BMI on csDMARD prescribing, MTX dose and disease activity over 12 months. Participants in an international RA database were stratified into early (<1 year post-diagnosis) and established RA. EULAR response, 28-joint DAS (DAS28) remission and treatments were recorded at baseline, 6 months and 12 months. Increased BMI was explored in early and established RA as predictors of good EULAR response, DAS28 remission, number of csDMARDs and MTX dose, using logistic and linear regression. Data from 1313 patients, 44.3% with early RA, were examined. In early RA, increased BMI was not significantly associated with remission. In established RA, obese patients on monotherapy were significantly less likely to achieve good EULAR response or DAS28 remission at 6 months and more likely to be treated with combination csDMARDs compared with normal BMI. In patients taking MTX, overweight and obese patients with early and established RA were exposed to higher MTX doses (mono- and combination therapy), with a mean dose of 20 mg/week, compared with 15 mg/week in those of normal BMI. We observed that compared with patients with normal BMI, overweight and obese individuals experienced more intensive csDMARD exposures. Similar response rates were observed in early RA but increased BMI was associated with reduced response in established RA. Optimization of targeted RA treatment remains important, particularly in those with increased BMI where response in established disease may be attenuated.

Prediction of response of methotrexate in patients with rheumatoid arthritis using serum lipidomics

Methotrexate (MTX) is a common first-line treatment for new-onset rheumatoid arthritis (RA). However, MTX is ineffective for 30–40% of patients and there is no way to know which patients might benefit. Here, we built statistical models based on serum lipid levels measured at two time-points (pre-treatment and following 4 weeks on-drug) to investigate if MTX response (by 6 months) could be predicted. Patients about to commence MTX treatment for the first time were selected from the Rheumatoid Arthritis Medication Study (RAMS). Patients were categorised as good or non-responders following 6 months on-drug using EULAR response criteria. Serum lipids were measured using ultra‐performance liquid chromatography–mass spectrometry and supervised machine learning methods (including regularized regression, support vector machine and random forest) were used to predict EULAR response. Models including lipid levels were compared to models including clinical covariates alone. The best performing classifier including lipid levels (assessed at 4 weeks) was constructed using regularized regression (ROC AUC 0.61 ± 0.02). However, the clinical covariate based model outperformed the classifier including lipid levels when either pre- or on-treatment time-points were investigated (ROC AUC 0.68 ± 0.02). Pre- or early-treatment serum lipid profiles are unlikely to inform classification of MTX response by 6 months with performance adequate for use in RA clinical management.

Anti-TROVE2 Antibody Determined by Immune-Related Array May Serve as a Predictive Marker for Adalimumab Immunogenicity and Effectiveness in RA.

Anti-drug antibody (ADAb) development is associated with secondary therapeutic failure in biologic-treated rheumatoid arthritis (RA) patients. With a treat-to-target goal, we aimed to identify biomarkers for predicting ADAb development and therapeutic response in adalimumab-treated patients. Three independent cohorts were enrolled. In Cohort-1, 24 plasma samples (6 ADAb-positive and 6 ADAb-negative patients at baseline and week 24 of adalimumab therapy, respectively) were assayed with immune-related microarray containing 1,636 correctly folded functional proteins. Next, we executed statistically powered autoantibody profiling analysis of 50 samples in Cohort-2 (24 ADAb-positive and 26 ADAb-negative patients). Subsequently, immunofluorescence assay was performed on 48 samples in Cohort-3 to correlate with ADAb titers and drug levels. The biomarkers were identified for predicting ADAb development and therapeutic response using the immune-related microarray and machine learning approach. ADAb-positive patients had lower drug levels at week 24 (median = 0.024 μg/ml) compared with ADAb-negative patients (median = 6.38 μg/ml, p < 0.001). ROC analysis based on the ADAb status revealed the top 20 autoantibodies with AUC ≥ 0.7 in differentiating both groups in Cohort-1. Analysis of Cohort-2 dataset identified a panel of 8 biomarkers (TROVE2, SSB, NDE1, ZHX2, SH3GL1, CARD9, PTPN20, and KLHL12) with 80.6% specificity, 77.4% sensitivity, and 79.0% accuracy in discriminating poor from EULAR responders. Immunofluorescence assay validated that anti-TROVE2 antibody could highly predict ADAb development and poor EULAR response (AUC 0.79 and 0.89, respectively). Multivariate regression analysis proved anti-TROVE2 antibody to be an independent predictor for developing ADAb. Immune-related protein microarray and replication analysis identified anti-TROVE2 antibody as a useful biomarker for predicting ADAb development and therapeutic response in adalimumab-treated patients.

Is improvement of fatigue in rheumatoid arthritis a proper effect of biologics?

Background. The objective of our present study is to assess the relation between persistent fatigue and rheumatoid arthritis (RA) disease activity and its functional impact and to determine if the positive effect of biologics on fatigue is due to good disease response or to a different pathway.Methods. A study cohort of patients with established RA was conducted. We included patients who had been prescried a biologic after at least failure of one conventional synthetic Disease Modifying Anti-Rheumatic Drug synthetic (csDMARDs). At baseline, patients had a moderately to highly active disease. Demographic characteristics, disease activity and functional impact were assessed by disease activity score (DAS28CRP) and health assessment questionnaire (HAQ) scores. Fatigue was evaluated by the Functional Assessment of Chronic Illness Therapy-Fatigue scale questionnaire (FACIT-F). Patients were examined before initiating biotherapy, then after three months and six months.Results. Thirty women with RA, with a mean age of 52.5 years, were included. At baseline, 57% received anti-TNFα: Etanercept (n = 9), Adalimumab (n = 6), Infliximab (n = 2) and 43% received Rituximab. Good Eular response was obtained in 80% of patients at the third month and 97% of patients at the sixth month. In the analytic study, a significant amelioration after 3 months of biotherapy was found in both disease response (DAS28CRP) and fatigue (FACIT-F), respectively (p = 0.01, p<0.001 and p<0.001). The disease activity decreased significantly also after sixth month (p = 0.01, p<0.001 and p = 0.012). In the linear multivariate analysis, the regression of visual analogic pain (VAS pain) was the only predictors of the improvement of fatigue.Conclusion. Biologics contribute to improve fatigue in patients with established RA and this effect seems to be independent from the clinical efficacy of this treatment.

Outcomes in rheumatoid arthritis patients treated with abatacept: a UK multi-centre observational study

BackgroundRheumatoid arthritis (RA) is an inflammatory autoimmune disease that causes chronic synovitis, resulting in progressive joint destruction and functional disability and affects approximately 400,000 people in the UK. This real-world study aimed to describe the characteristics, treatment patterns and clinical outcomes of patients who received abatacept in UK clinical practice.MethodsThis was a multi-centre, retrospective, observational study of patients with RA treated with abatacept at four UK centres between 01 January 2013 and 31 December 2017. Data were collected from medical records of each patient from the index date (date of first bDMARD initiation) until the most recent visit, death or end of study (31 December 2017).ResultsIn total, 213 patients were included in the study. Patients received up to eight lines of therapy (LOTs). Treatment with abatacept, or any other bDMARD, was associated with reductions in DAS28-ESR and DAS28-CRP scores at 6 and 12 months. The distribution of EULAR responses (good/moderate/no response) tended to be more favourable for patients when receiving abatacept than when receiving other bDMARDs (22.8%/41.3%/35.9% versus 16.6%/41.4%/42.1% at 6 months, and 27.9%/36.1%/36.1% versus 21.2%/34.5%/44.2% at 12 months). Patients receiving abatacept at LOT1 (n = 68) spent significantly longer on treatment compared with patients receiving other bDMARDs (53.4 vs. 17.4 months; p< 0.01); a similar trend was observed for LOT2. Among patients who discontinued after 6 months, a greater proportion experienced infection requiring antibiotics when receiving other bDMARDs compared to those receiving abatacept.ConclusionsRA patients who received bDMARDs, including abatacept, experienced reduced disease activity. When receiving abatacept as first or second line of therapy, patients persisted with treatment significantly longer than those receiving other bDMARDs.

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.

Comparison of long-term efficacy between biological agents following tumor necrosis factor inhibitor failure in patients with rheumatoid arthritis: a prospective cohort study.

Background:Currently, there is contradictory evidence regarding the best strategy to follow after discontinuation of a first biological agent in patients with rheumatoid arthritis (RA). We aimed to compare the long-term efficacy of switching to a second tumor necrosis factor inhibitor (TNFi) versus biopharmaceuticals with other mechanisms of action (non-TNFi) in patients with RA who previously failed a first TNFi.Methods:This prospective cohort study analyzed data from 127 patients who discontinued a previous TNFi between 1999 and 2016. Disease activity was assessed at baseline and at 6, 12, and 24 months (m-6, m-12, m-24) after switching. Primary outcome was the proportion of patients achieving good/moderate EULAR response (E-resp). Factors associated with clinical outcomes were assessed using univariate and multivariate logistic regression models.Results:Seventy-seven (61%) patients received a second TNFi and 50 (39%) switched to a non-TNFi. At m-6 and m-12, no differences were observed between groups; nevertheless, at m-24, the proportion of patients with E-resp was higher in the non-TNFi group (49% TNFi group versus 77% non-TNFi group; p = 0.002). In regression models, switching to a non-TNFi was significantly associated with E-resp at m-24 (odds ratio = 3.21; p = 0.01). When assessing the response to the second biological agent based on the reason for discontinuation of the first TNFi, similar results were obtained; at m-24, patients who discontinued the first TNFi due to inefficacy (either primary or secondary) experienced a better E-resp if they had switched to a non-TNFi (primary inefficacy: 52% TNFi group versus 79% non-TNFi group, p = 0.09; secondary inefficacy: 50% versus 76%, p = 0.03).Conclusion:In our cohort of RA patients who discontinued a first TNFi, those who switched to a non-TNFi were three times more likely to attain a sustained clinical response, regardless of whether they had discontinued the first biologic due to a primary or secondary inefficacy.

Baricitinib in the treatment of rheumatoid arthritis: clinical and ultrasound evaluation of a real-life single-centre experience.

Background:Ultrasound (US) is useful in monitoring RA patients, with the US7 score allowing grey-scale and power-Doppler (PD) semi-quantitative evaluation of synovitis and teno-synovitis. We evaluated real-life efficacy and safety of Baricitinib, an oral selective JAK1-2 inhibitor, in RA patients using clinical, clinimetric, and US assessments.Methods:Disease activity score in 28 joints calculated with C-reactive protein (DAS28-CRP), disease activity score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), simplified disease activity index (SDAI), visual analogue scale (VAS)-pain, health assessment questionnaire (HAQ), COCHIN scale, adverse events (AE), concomitant medications, laboratory parameters, and US7 were performed/recorded at baseline, 1, 3, and 6 months in RA patients starting Baricitinib. Responder/non-responder status was determined according to the EULAR Response Criteria at 3 months. SDAI clinical remission or low disease activity (LDA) were calculated at 3 and 6 months.Results:In 43 enrolled patients, a significant improvement in disease activity and US7 components (except tendon PD) and a reduction of steroid dosage were observed. Responders at 3 months showed a significantly higher reduction of CDAI, SDAI, COCHIN scale, VAS-pain, and US7 synovialPD, compared with non-responders. At 3 and 6 months, remission/LDA was achieved by 12.8/53.8% and 21.6/51.3% patients, respectively. The csDMARD co-treatment was independently associated with remission/LDA at 3 months. Safety-related drop-outs were in line with literature data. The steroid dosage was associated with AE development at 6 months.Conclusion:The real-life data, also obtained with US evaluation, confirmed the Baricitinib efficacy in RA disease control, as well as the utility of assessment during the follow up of disease activity.

Identification of Metabolic Biomarkers in Relation to Methotrexate Response in Early Rheumatoid Arthritis.

This study aimed to identify baseline metabolic biomarkers for response to methotrexate (MTX) therapy in rheumatoid arthritis (RA) using an untargeted method. In total, 82 baseline plasma samples (41 insufficient responders and 41 sufficient responders to MTX) were selected from the Treatment in the Rotterdam Early Arthritis Cohort (tREACH, trial number: ISRCTN26791028) based on patients’ EULAR response at 3 months. Metabolites were assessed using high-performance liquid chromatography-quadrupole time of flight mass spectrometry. Differences in metabolite concentrations between insufficient and sufficient responders were assessed using partial least square regression discriminant analysis (PLS-DA) and Welch’s t-test. The predictive performance of the most significant findings was assessed in a receiver operating characteristic plot with area under the curve (AUC), sensitivity and specificity. Finally, overrepresentation analysis was performed to assess if the best discriminating metabolites were enriched in specific metabolic events. Baseline concentrations of homocystine, taurine, adenosine triphosphate, guanosine diphosphate and uric acid were significantly lower in plasma of insufficient responders versus sufficient responders, while glycolytic intermediates 1,3-/2,3-diphosphoglyceric acid, glycerol-3-phosphate and phosphoenolpyruvate were significantly higher in insufficient responders. Homocystine, glycerol-3-phosphate and 1,3-/2,3-diphosphoglyceric acid were independent predictors and together showed a high AUC of 0.81 (95% CI: 0.72–0.91) for the prediction of insufficient response, with corresponding sensitivity of 0.78 and specificity of 0.76. The Warburg effect, glycolysis and amino acid metabolism were identified as underlying metabolic events playing a role in clinical response to MTX in early RA. New metabolites and potential underlying metabolic events correlating with MTX response in early RA were identified, which warrant validation in external cohorts.

Combination of human umbilical cord mesenchymal stem (stromal) cell transplantation with IFN-γ treatment synergistically improves the clinical outcomes of patients with rheumatoid arthritis

ObjectivesTo clarify the key role of circulating interferon-γ (IFN-γ) and to improve the clinical efficacy of mesenchymal stem cell (MSC) transplantation (MSCT) in patients with rheumatoid arthritis (RA).MethodsStudy of wild-type...