Treatment Of Early Rheumatoid Arthritis Research Articles

Obesity is a risk factor for poor response to treatment in early rheumatoid arthritis: a NORD-STAR study

ObjectiveThis report from the NORD-STAR (Nordic Rheumatic Diseases Strategy Trials and Registries) trial aimed to determine if obesity is associated with response to conventional and biological antirheumatic treatment in early...

Urinary prostanoids are elevated by anti-TNF and anti-IL6 receptor disease-modifying antirheumatic drugs but are not predictive of response to treatment in early rheumatoid arthritis

BackgroundDisease-modifying antirheumatic drugs (DMARDs) are widely used for treating rheumatoid arthritis (RA). However, there are no established biomarkers to predict a patient’s response to these therapies. Prostanoids, encompassing prostaglandins, prostacyclins, and thromboxanes, are potent lipid mediators implicated in RA progression. Nevertheless, the influence of DMARDs on prostanoid biosynthesis in RA patients remains poorly understood. This study aims to assess the impact of various DMARDs on urinary prostanoids levels and to explore whether urinary prostanoid profiles correlate with disease activity or response to therapy.MethodsThis study included 152 Swedish female patients with early RA, all rheumatoid factor (RF) positive, enrolled in the NORD-STAR trial (registration number: NCT01491815). Participants were randomized into four therapeutic regimes: methotrexate (MTX) combined with (i) prednisolone (arm ACT), (ii) TNF-α blocker certolizumab pegol (arm CZP), (iii) CTLA-4Ig abatacept (arm ABA), or (iv) IL-6R blocker tocilizumab (arm TCZ). Urine samples, collected before start of treatment and at 24 weeks post-treatment, were analyzed for tetranor-prostaglandin E metabolite (tPGEM), tetranor-prostaglandin D metabolite (tPGDM), 2,3-dinor thromboxane B2 (TXBM), 2,3-dinor-6-keto prostaglandin F1a (PGIM), leukotriene E4 (LTE4) and 12-hydroxyeicosatetraenoic acid (12-HETE) using liquid chromatography–mass spectrometry (LC–MS). Generalized estimating equation (GEE) models were used to analyze the change in urinary eicosanoids and their correlations to clinical outcomes.ResultsPatients receiving MTX combined with CZP or TCZ exhibited significant elevations in urinary tPGEM and TXBM levels after 24 weeks of treatment. Other eicosanoids did not show significant alterations in response to any treatment. Baseline urinary eicosanoid levels did not correlate with baseline clinical disease activity index (CDAI) levels, nor with changes in CDAI from baseline to week 24. Their levels were also similar between patients who achieved CDAI remission and those with active disease at week 24.ConclusionsTreatment with anti-TNF or anti-IL6R agents in early RA patients leads to an increased systemic production of proinflammatory and prothrombotic prostanoids. However, urinary eicosanoid levels do not appear to be predictive of the response to DMARDs therapy.

Genome-wide investigation of persistence with methotrexate treatment in early rheumatoid arthritis.

To investigate the influence of genetic factors on persistence with treatment of early RA with MTX monotherapy. We conducted a genome-wide association study (GWAS) in a sample of 3902 Swedish early-RA patients initiating MTX in DMARD monotherapy as their first-ever DMARD. The outcome, short- and long-term MTX treatment persistence, was defined as remaining on MTX at 1 and at 3 years, respectively, with no additional DMARDs added. As genetic predictors, we investigated individual SNPs, and then calculated a polygenic risk score (PRS) based on SNPs associated with RA risk. The SNP-based heritability of persistence was estimated overall and by RA serostatus. No individual SNP reached genome-wide significance (P < 5 × 10-8), either for persistence at 1 year or at 3 years. The RA PRS was not significantly associated with MTX treatment persistence at 1 year [relative risk (RR) = 0.98 (0.96-1.01)] or at 3 years [RR = 0.96 (0.93-1.00)]. The heritability of MTX treatment persistence was estimated to be 0.45 (0.15-0.75) at 1 year and 0.14 (0-0.40) at 3 years. The results in seropositive RA were comparable with those in the analysis of RA overall, while heritability estimates and PRS RRs were attenuated towards the null in seronegative RA. Despite being the largest GWAS on an MTX treatment outcome to date, no genome-wide significant associations were detected. The modest heritability observed, coupled with the broad spread of suggestively associated loci, indicate that genetic influence is of polygenic nature. Nevertheless, MTX monotherapy persistence was lower in patients with a greater genetic disposition, per the PRS, towards RA.

Estimation of the global prevalence, incidence, years lived with disability of rheumatoid arthritis in 2019 and forecasted incidence in 2040: results from the Global Burden of Disease Study 2019.

We aimed to provide a better understanding of the secular trends in rheumatoid arthritis (RA) burden at the regional and national levels, contributing to identifying the areas with high burden needs and finding the potential areas requiring additional attention, which will facilitate the development of strategies tailored to RA burden. Data were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 study. We presented the secular trends in the prevalence, incidence, and years lived with disability (YLDs) of RA needs by sex, age, sociodemographic index (SDI), region, country, and category between 1990 and 2019 using data from the GBD 2019 study. The age-standardized rates (ASR) and its estimated annual percentage changes (EAPCs) are employed to describe the secular trends in RA. Globally, there were an estimated 18.5 million [95% confidence interval (CI) 31.53 to 41.74)] prevalent cases of RA, with 1.07 million (95% CI 0.95 to 1.18) incident cases per year and almost 2.43 million YLDs (95% CI 1.68 to 3.28) in 2019. The age-standardized prevalence and incidence rates estimated for RA were 224.25 per 100,000 and 12.21 per 100,000 in 2019, with EAPCs of 0.37 (95% CI - 0.32, 0.42) and 0.30 (95% CI 0.25 to 0.34), respectively. The corresponding age-standardized YLDs estimated was 29.35 per 100,000 in 2019, with an EAPC of 0.38 (95% CI: 0.33, 0.43). During the study period, the ASR of RA was consistently higher in females than in males. Moreover, the age-standardized YLD rate of RA was associated with the sociodemographic index (SDI) in 2019 across all 204 countries and territories (R = 0.28). The projections indicate that the age-standardized incidence rates (ASIR) trend will continue to increase from 2019 to 2040, with a projected ASIR of 10.48 and 4.63/100,000 for females and males, respectively. RA is prevalent and remains a significant global public health challenge. Globally, the burden of RA has increased over the past 30years and will continue to increase. Prevention and early treatment of RA are pivotal to avoiding disease onset and alleviating the enormous burden. Key Points • The burden of rheumatoid arthritis is increasing globally. • Global estimates indicate that the number of RA incident cases will increase 1.4-fold globally, from approximately 1.07 million at the end of 2019 to approximately 1.5 million by 2040.

Do it fast! Early access to specialized care improved long-term outcomes in rheumatoid arthritis: data from the REAL multicenter observational study

BackgroundEarly rheumatoid arthritis (RA) offers an opportunity for better treatment outcomes. In real-life settings, grasping this opportunity might depend on access to specialized care. We evaluated the effects of early versus late assessment by the rheumatologist on the diagnosis, treatment initiation and long-term outcomes of RA under real-life conditions.MethodsAdults meeting the ACR/EULAR (2010) or ARA (1987) criteria for RA were included. Structured interviews were conducted. The specialized assessment was deemed “early” when the rheumatologist was the first or second physician consulted after symptoms onset, and “late” when performed afterwards. Delays in RA diagnosis and treatment were inquired. Disease activity (DAS28-CRP) and physical function (HAQ-DI) were evaluated. Student’s t, Mann-Whitney U, chi-squared and correlation tests, and multiple linear regression were performed. For sensitivity analysis, a propensity score-matched subsample of early- vs. late-assessed participants was derived based on logistic regression. The study received ethical approval; all participants signed informed consent.ResultsWe included 1057 participants (89.4% female, 56.5% white); mean (SD) age: 56.9 (11.5) years; disease duration: 173.1 (114.5) months. Median (IQR) delays from symptoms onset to both RA diagnosis and initial treatment coincided: 12 (6–36) months, with no significant delay between diagnosis and treatment. Most participants (64.6%) first sought a general practitioner. Notwithstanding, 80.7% had the diagnosis established only by the rheumatologist. Only a minority (28.7%) attained early RA treatment (≤ 6 months of symptoms). Diagnostic and treatment delays were strongly correlated (rho 0.816; p < 0.001). The chances of missing early treatment more than doubled when the assessment by the rheumatologist was belated (OR 2.77; 95% CI: 1.93, 3.97). After long disease duration, late-assessed participants still presented lower chances of remission/low disease activity (OR 0.74; 95% CI: 0.55, 0.99), while the early-assessed ones showed better DAS28-CRP and HAQ-DI scores (difference in means [95% CI]: -0.25 [-0.46, -0.04] and − 0.196 [-0.306, -0.087] respectively). The results in the propensity-score matched subsample confirmed those observed in the original (whole) sample.ConclusionsEarly diagnosis and treatment initiation in patients with RA was critically dependent on early access to the rheumatologist; late specialized assessment was associated with worse long-term clinical outcomes.

Dasatinib, a selective tyrosine kinase inhibitor, prevents joint destruction in rheumatoid arthritis animal model.

We aimed to evaluate the preventive role of the tyrosine kinase inhibitor dasatinib in an animal model of rheumatoid arthritis (RA). DBA/1J mice were injected with bovine type II collagen to induce arthritis (collagen-induced arthritis [CIA]). There were four experimental groups of mice, namely negative control (non-CIA), vehicle-treated CIA, dasatinib-pretreated CIA, and dasatinib-treated CIA. After collagen immunization, arthritis progression in the mice was clinically scored twice weekly for 5 weeks. Flow cytometry was used to evaluate in vitro CD4+ T-cell differentiation and ex vivo mast cell/CD4+ T-cell differentiation. Osteoclast formation was evaluated using tartrate-resistant acid phosphatase (TRAP) staining and by estimating the resorption pit area. We found that the clinical arthritis histological scores were lower in the dasatinib pretreatment group than in the vehicle and dasatinib post-treatment groups. Flow cytometry showed that FcεR1+ cells were downregulated and regulatory T cells were upregulated in splenocytes of the dasatinib pretreatment group compared with those in the vehicle group. Additionally, there was a decline in IL-17+ CD4+ T-cell differentiation and an increase in CD4+ CD24high Foxp3+ T-cell differentiation with in vitro dasatinib treatment of human CD4+ T cells. The number of TRAP+ osteoclasts and the area of the resorption were decreased in the bone marrow cells derived from dasatinib-pretreated mice compared with those derived from vehicle group. Dasatinib protected against arthritis in an animal model of RA by regulating the differentiation of regulatory T cells and IL-17+ CD4+ T cells and inhibiting osteoclastogenesis, indicating the therapeutic potential of dasatinib in the treatment of early RA.

Bifidobacterium pseudocatenulatum-Mediated Bile Acid Metabolism to Prevent Rheumatoid Arthritis via the Gut–Joint Axis

Early intervention in rheumatoid arthritis (RA) is critical for optimal treatment, but initiation of pharmacotherapy to prevent damage remains unsatisfactory currently. Manipulation of the gut microbiome and microbial metabolites can be effective in protecting against RA. Thus, probiotics can be utilized to explore new strategies for preventing joint damage. The aim of this study was to explore the metabolites and mechanisms by which Bifidobacterium pseudocatenulatum affects RA. Based on 16S rRNA sequencing and UPLC-MS/MS assays, we focused on bile acid (BA) metabolism. In a collagen-induced arthritis (CIA) mouse model, B. pseudocatenulatum prevented joint damage by protecting the intestinal barrier and reshaped gut microbial composition, thereby elevating bile salt hydrolase (BSH) enzyme activity and increasing the levels of unconjugated secondary BAs to suppress aberrant T-helper 1/17-type immune responses; however, these benefits were eliminated by the Takeda G protein-coupled receptor 5 (TGR5) antagonist SBI-115. The results suggested that a single bacterium, B. pseudocatenulatum, can prevent RA, indicating that prophylactic administration of probiotics may be an effective therapy.

Towards a simplified fluid-sensitive MRI protocol in small joints of the hand in early arthritis patients: reliability between modified Dixon and regular Gadolinium enhanced TSE fat saturated MRI-sequences.

MRI of small joints plays an important role in the early detection and early treatment of rheumatoid arthritis. Despite its sensitivity to demonstrate inflammation, clinical use is hampered by accessibility, long scan time, intravenous contrast, and consequent high costs. To improve the feasibility of MRI implementation in clinical practice, we introduce a modified Dixon sequence, which does not require contrast and reduces total acquisition time to 6min. Because the reliability in relation to conventional MRI sequences is unknown, we determined this. In 29 consecutive early arthritis patients, coronal and axial T2-weighted modified Dixon acquisitions on 3.0T MRI scanner were acquired from metacarpophalangeal 2-5 to the wrist, followed by the standard contrast-enhanced protocol on 1.5T extremity MRI. Two readers scored osteitis, synovitis and tenosynovitis (summed as total MRI-inflammation), and erosions (all summed as total Rheumatoid Arthritis MRI Score (RAMRIS)). Intraclass correlation coefficients (ICCs) between readers, and comparing the two sequences, were studied. Spearman correlations were determined. Performance between readers was good/excellent. Comparing modified Dixon and conventional sequences revealed good/excellent reliability: ICC for total MRI-inflammation score was 0.84 (95% CI:0.70-0.92), for erosions 0.90 (95% CI:0.79-0.96), and for the total RAMRIS score 0.88 (95% CI:0.77-0.94). The scores of total MRI-inflammation, total erosions, and total RAMRIS were highly correlated (ρ = 0.80, ρ = 0.81, ρ = 0.82, respectively). The modified Dixon protocol is reliable compared to the conventional MRI protocol, suggesting it is accurate to detect MRI inflammation. The good correlation may be the first step towards a patient-friendly, short and affordable MRI protocol, which can facilitate the implementation of MRI for early detection of inflammation in rheumatology practice.

Comparison of High-Resolution Ultrasonography With Magnetic Resonance Imaging in Rheumatoid Arthritis

Objective: The aim of this study was to examine whether high-resolution ultrasonography (HRUS) can provide information, on signs of inflammation and destruction, due to rheumatoid arthritis (RA). The focus was on the wrist joint, during early and late disease and compared the findings to those with magnetic resonance imaging (MRI). Materials and Methods: The study was based on 31 RA patients, with joint involvements, who were selected from those attending the outpatient rheumatology clinic. The patients completed both HRUS and MRI examinations, and their results were compared. Results: The HRUS and MRI images had near-perfect agreement, for detecting joint anomalies, in those RA patients. While comparing the overall performance of the HRUS and MRI studies, it was observed that HRUS was equal or nearly equal, demonstrating 90.83%, 100.0% and 94.93%, diagnostic sensitivity, specificity, and accuracy, respectively, for diagnosing RA pathologies. Conclusion: The early diagnosis of RA with HRUS and MRI examinations is very important, in the early treatment of RA. The HRUS examinations demonstrated a sensitive and reliable diagnostic method for assessing inflammatory activity and destructive changes in the joints of these RA patients, with HRUS findings comparable to those of MRI.

Application of Dynamic Contrast-Enhanced MRI in the Diagnosis of Rheumatoid Arthritis.

In order to solve the application problem of dynamic contrast-enhanced MRI in the diagnosis of rheumatoid arthritis, this paper proposes application research based on dynamic contrast-enhanced MRI in the staging diagnosis of rheumatoid arthritis. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has a high value in evaluating the activity of patients with early rheumatoid arthritis (RA). This paper discusses the correlation between hemodynamic parameters and omeractramris score, clinical laboratory indexes, and activity score (DAS28), analyzes its feasibility in evaluating the prognosis of RA, and provides a reliable basis for the rational formulation of an early RA treatment plan. After reviewing the previous cases, 33 patients with subclinical synovitis of RA were selected for wrist joint contrast-enhanced ultrasonography. The data were analyzed by contrast-enhanced software, and the quantitative parameters of contrast-enhanced were obtained: start development time (AT), peak time (TTP), peak intensity (PI), grad gradient, and area under the curve (AUC). The synovial blood supply was classified by CEUS, and the CEUS blood supply classification and power Doppler (PDUS) blood supply classification were compared. The results of regression analysis showed that AUC (or = 1.026, 95% CI: 1.001–1.052) and PI (or = 1.561, 95% CI: 1.019–2.393) were independent risk factors for predicting the aggravation of the disease. The diagnostic efficacy of AUC and PI in predicting the aggravation of the disease was analyzed. The areas under the ROC curve of AUC and PI were 0.935 and 0.927, respectively, and the difference between them was not statistically significant.

OA26 Erythrocyte mean corpuscular volume as a surrogate marker for methotrexate polyglutamation during early treatment in rheumatoid arthritis

Abstract Background/Aims The long-term outcomes for patients with rheumatoid arthritis (RA) depend on early and effective disease control. Methotrexate remains the key first-line disease-modifying therapy for the majority of patients. The gradual onset of action of methotrexate has been proposed to be linked to the build-up of intracellular stores of the drug, achieved through the process of polyglutamation. This is a complex and expensive assay. Recent work has shown an association between the increase in mean corpuscular volume (MCV) of erythrocytes and improvements in disease activity. This study seeks to relate intracellular methotrexate and 5-methyl-tetrahydrofolate polyglutamate concentrations with changes in MCV and their association with early ‘steroid free’ remission in RA patients. Methods 68 drug-naïve, newly diagnosed RA patients were recruited form the Newcastle Early Arthritis Clinic (NEAC). These patients were followed up for 6 months with serial blood sampling and quantification of the erythrocyte methotrexate and 5-methyl-tetrahydrofolate polyglutamate levels by liquid chromatography-mass spectrometry (LC-MS). This was then related to the contemporaneous erythrocyte MCV values from the clinical monitoring bloods on those occasions and the treatment outcome at 6 months. The outcome measure used was 4 component DAS28CRP remission (&amp;lt;2.4) with only the baseline intramuscular steroid permitted for the definition of remission. Results The majority of patients displayed a gradual increase in MCV over the first 6 months of treatment (MCV change from patient baseline used to normalise the data). When grouped by the ‘steroid free’ remission outcome, there was a divergence in MCV change with greater MCV increases observed in those achieving remission from 4 months of treatment onward (p &amp;lt; 0.05). In the same patient group, the accumulation of longer chain methotrexate polyglutamates (chain length 3 to 5) was observed to follow a similar trend to MCV with higher polyglutamate concentrations in those achieving the remission outcome from 2 months of treatment (P &amp;lt; 0.05). When the contemporaneous MCV and MTX polyglutamate samples were compared, an association was observed between the longer chain MTX polyglutamates and the change in MCV values (R2 = 0.39, p &amp;lt; 0.001), but not between intracellular 5-methyl-tetrahydrofolate and MCV (R2 = 0.01, p = NS). Conclusion Change in MCV shows an association with early remission induction with MTX therapy in treatment-naïve RA patients. This change in MCV appears to be associated with the accumulation of intracellular MTX metabolites, rather than via depletion of intracellular folates. MCV may therefore represent a tractable proxy measure of methotrexate polyglutamation for application in larger studies or for the purpose of drug monitoring. Disclosure P.M. Brown: None. A.G. Pratt: None. A.E. Anderson: None. A.W. Morgan: None. J.D. Isaacs: None.

Does persistence to methotrexate treatment in early rheumatoid arthritis have a familial component?

ObjectivesTo assess whether persistence to treatment with methotrexate (MTX) in early rheumatoid arthritis (RA) is shared among first-degree relatives with RA and to estimate any underlying heritability.MethodsFirst-degree relative pairs diagnosed with RA 1999–2018 and starting MTX (in monotherapy) as their first disease-modifying anti-rheumatic drug (DMARD) treatment were identified by linking the Swedish Rheumatology Quality Register to national registers. Short- and long-term persistence to MTX was defined as remaining on treatment at 1 and 3 years, respectively, with no additional DMARDs added. We assessed familial aggregation through relative risks (RR) using log-binomial regression with robust standard errors and estimated heritability using tetrachoric correlations. We also explored the familial aggregation of EULAR treatment response after 3 and 6 months. To mimic the clinical setting, we also tested the association between having a family history of MTX persistence and persistence within the index patient.ResultsFamilial persistence was not associated with persistence at 1 (RR=1.02, 95% CI 0.87–1.20), only at 3 (RR=1.41, 95% CI 1.14–1.74) years. Heritability at 1 and 3 years was estimated to be 0.08 (95% CI 0–0.43) and 0.58 (95% CI 0.27–0.89), respectively. No significant associations were found between family history and EULAR response at 3 and 6 months, neither overall nor in the clinical setting analysis.ConclusionsOur findings imply a familial component, including a possible genetic element, within the long-term persistence to MTX following RA diagnosis. Whether this component is reflective of characteristics of the underlying RA disease or determinants for sustained response to MTX in itself will require further investigation.

Effectiveness of biologics and targeted synthetic disease‐modifying anti‐rheumatic drugs in conjunction with methotrexate for the treatment of early rheumatoid arthritis: A systematic review of randomized controlled trials

AbstractObjectivesThe treatment goal for rheumatoid arthritis has undergone a dramatic change over recent years with the advent of biologic and targeted synthetic disease‐modifying antirheumatic drugs (b/tsDMARDs). This systematic review aims to discuss the comparative efficiency of new drugs versus the standard of care methotrexate.MethodsPubmed, Google Scholar, and Science Direct were searched, and 7072 records were retrieved. Randomized controlled trials published in the last five years with full‐text papers, blinded studies, and studies with an open‐label extension were included. Studies with a high risk of bias as calculated by the Cochrane risk of bias (RoB2) tool were excluded. The last database search was conducted on 21 August 2021.ResultsFifteen studies were identified and analyzed by categorizing drugs into Janus kinase (JAK) inhibitors, tumour necrosis factor (TNF) inhibitors, and monoclonal antibodies with other targets (anti‐GM‐CSF receptor, anti‐IL6 receptor, anti‐IL‐17 monoclonal antibodies), with a total of 7963 participants. Data were synthesized with tables and the PRISMA flow diagram. Our analysis included baricitinib, filgotinib, peficitinib, infliximab, certolizumab, sarilumab, tocilizumab namilumab, mavrilimumab, golimumab, and CNT06785.ConclusionsThese studies showed that except for CNT 06785 (anti‐Interleukin 17A monoclonal antibody), biologic and targeted synthetic disease‐modifying drugs combined with methotrexate or as monotherapy yield better clinical and radiographical outcomes. This systematic review does not discuss biosimilars and the adverse effects of biologic drugs in detail. Infections remain a significant adverse drug reaction of monoclonal antibodies. However, these drugs play a crucial role in adequately managing this disease for patients with severe arthritis.

Association Between Subjects with Newly Diagnosed Rheumatoid Arthritis and Dental Caries

Alterations in saliva, temporomandibular joint disorders, dysphagia, Sjogren's syndrome, dental caries, periodontal disease, and tooth loss have been identified in patients with Rheumatoid Arthritis. The aims of this research were 1) to study the association between newly diagnosed rheumatoid arthritis and dental caries and 2) to identify most frequent teeth with caries in study groups. A descriptive pilot study was performed. A total of 620 participants were evaluated, 29 met the selection criteria. The subjects were divided into 2 groups: 13 subjects with newly diagnosed rheumatoid arthritis and 16 subjects without rheumatoid arthritis. Salivary parameters, DMFT index, care index, FS-T index and Treatment Needs Index were evaluated in all participants. The Fisher’s Exact test and Mann-Whitney U test we used to establish the differences between groups. Low mean in all salivary parameters and a high caries frequency were observed in subjects with newly diagnosed rheumatoid arthritis compared to a control group (p&lt;0.01). The right maxillary second premolar (n=6, 46%, p=0.0100); right mandibular second premolar (n=7,54%, p=0.0462) and left mandibular second molar (n=10,77%, p=0.0001) were the most frequent teeth with caries. Early diagnosis and early treatment of rheumatoid arthritis can improve the prognosis in most of patients. The development of new public health policies and care based on the prevention are necessary to improve the quality of patient's lives.

Observation of the curative effect of Guizhi-Shaoyao-Zhimu decoction combined with methotrexate in the treatment of early rheumatoid arthritis based on ultrasonic evaluation: study protocol of a randomized, double-blind, controlled clinical trial

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with the primary clinical symptoms of joint swelling and pain. Early detection of erosion and synovial inflammation at an active stage resulting from RA can prevent damage to the joints and activity restriction. However, there are still many patients who do not respond to these treatments; the development of newer, safer drugs is urgently needed. Compared to Western medicine, Guizhi-Shaoyao-Zhimu decoction has equal or higher efficacy and safety for RA patients. With the widespread use of musculoskeletal ultrasound (MSUS), this technology holds great value for the degree of joint damage in RA patients, guiding the clinical selection of treatments, and assessing of prognosis. Therefore, we designed a double-blinded randomized controlled clinical trial to measure the safety and efficacy of Guizhi-Shaoyao-Zhimu decoction in treating early-stage RA using MSUS.MethodsThis study is a randomized, double-blinded, parallel group, placebo-controlled trial. A total of 152 adult participants with early RA will be enrolled, with balanced treatment allocation (1:1). The experimental intervention will be Guizhi-Shaoyao-Zhimu decoction plus the conventional medicine methotrexate and the control intervention will be placebo plus the conventional drug methotrexate for 3 months. In addition, both groups will receive folic acid during treatment to prevent side effects from methotrexate. The primary outcomes are the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hepatic and renal function, visual analog scale, disease activity score in 28 joints, measurement scale for TCM symptoms, and 7-joint ultrasound score.DiscussionWe designed this double-blinded randomized controlled clinical trial to evaluate the efficacy and safety of Guizhi-Shaoyao-Zhimu decoction in RA patients using MSUS. The results of this trial may provide insights into how to improve the clinical symptoms of RA patients and delay further joint destruction. We hope that this trial may provide preliminary evidence of the efficacy of Guizhi-Shaoyao-Zhimu decoction in treating RA patients and that these results aid researchers, practitioners, and patients alike.AimThe main aim of the study is to clarify the efficacy and safety of Guizhi-Shaoyao-Zhimu decoction in patients with early RA.Trial registrationChinese Clinical Trials Register ChiCTR2000036141. Registered on 21 August 2020 (retroactively registered)

Adaptation of a Shared Decision-Making Tool for Early Rheumatoid Arthritis Treatment Decisions with Indigenous Patients.

BackgroundPatient decision aids (PtDAs) enable shared decision-making between patients and healthcare providers. Adaptations to PtDAs for use with populations facing inequities in healthcare can improve the relevancy of information presented, incorporate appropriate cultural context, and address health literacy concerns. Our objective was to adapt the Early RA (rheumatoid arthritis) PtDA for use with Canadian Indigenous patients.MethodsThe Early RA PtDA was modified through an iterative process using data obtained from semi-structured interviews of two sequential cohorts of Indigenous patients with RA. Interview data were analyzed using thematic analysis.ResultsSeven participants provided initial feedback on the existing PtDA. The modifications they suggested were made and shared with another nine participants to confirm acceptability and provide further feedback. The first cohort suggested revisions to clarify medical and cost coverage information, include Indigenous traditional healing practice options, simplify text, and include Indigenous images and colors aligned with Canadian Indigenous community representation. Additional revisions were suggested by the second cohort to increase the legibility of the text, insert more Indigenous imagery, address formulary coverage for non-status First Nations patients, and include information about lifestyle factors in managing RA.ConclusionIncorporating Indigenous-specific adaptations in the design of PtDAs may increase use and relevancy to support engagement in treatment decisions, thereby supporting health-equity oriented health service interventions. Indigenous patient-specific evidence and translation of key words into the end-users’ Indigenous languages should be included for implementation of the PtDA.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40271-021-00546-8.

Blood PD-1+TFh and CTLA-4+CD4+ T cells predict remission after CTLA-4Ig treatment in early rheumatoid arthritis.

ObjectiveTreatment with CTLA-4Ig blocks T-cell activation and is clinically effective in RA. However, it is unknown if specific CD4+ T-cell subsets in blood at baseline predict remission after CTLA-4Ig, or other biological treatments with different modes of action, and how treatment affects CD4+ T cells in patients with untreated early RA (eRA). MethodsThis study included 60 patients with untreated eRA from a larger randomized trial. They were treated with methotrexate combined with CTLA-4Ig (abatacept, n = 17), anti-IL6 receptor (tocilizumab, n = 21) or anti-TNF (certolizumab-pegol, n = 22). Disease activity was assessed by clinical disease activity index (CDAI), DAS28, swollen joint counts, tender joint counts, CRP and ESR. The primary outcome was CDAI remission (CDAI ≤ 2.8) at week 24. Proportions of 12 CD4+ T-cell subsets were measured by flow cytometry at baseline and after 4, 12 and 24 weeks of treatment.ResultsIn patients treated with CTLA-4Ig, the proportions of PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline predicted CDAI remission at week 24. CD4+ T-cell subset proportions could not predict remission after treatment with anti-IL6R or anti-TNF. The percentage of regulatory T cells (Tregs) expressing CTLA-4 decreased in all treatment arms by 24 weeks, but only CTLA-4Ig treatment significantly reduced the proportions of Tregs and PD-1+T follicular helper (TFh) cells.ConclusionThese findings indicate that circulating proportions PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline may serve as predictive biomarkers for remission in early RA after CTLA-4Ig treatment.

Repurposed drugs could target PIM kinases in early RA.

Preclinical research suggests that inhibitors of PIM kinases currently in development in oncology could be repurposed for the treatment of early rheumatoid arthritis.

Comment on: what is the best treatment for early rheumatoid arthritis?

Comment on: what is the best treatment for early rheumatoid arthritis?

Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial

ObjectiveTo evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis.DesignInvestigator initiated, randomised, open label,...