Remission In Rheumatoid Arthritis Research Articles

Wangbi granule as a combination therapy to achieve clinical deep remission in rheumatoid arthritis: protocol for a multicenter, triple-blind, randomised, placebo-controlled trial

IntroductionRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that may lead to bone erosion and disability. Although there are many biological therapies in RA treatment nowadays, such as etanercept and tofacitinib, there are still a considerable number of patients who cannot achieve clinical deep remission, which makes patients feel pain and stiffness of joints. As a traditional Chinese medicine preparation, Wangbi granule showed a synergistic role with methotrexate in the treatment of RA patients with “kidney deficiency and dampness” or “stasis blocking channels”. Therefore, it is a promising therapeutic strategy for the clinical deep remission of RA. In this study, Wangbi granule will be used as the test drug. The investigators conduct this study to evaluate the efficacy and safety of Wangbi granule in the treatment of patients who have not achieved deep remission despite the use of methotrexate and tofacitinib.Methods and analysisTwo parallel randomized, triple-blind, placebo-controlled trials will be conducted. In six study centers, 340 eligible RA patients will be recruited and randomly allocated to either the intervention group or the control group (in a 1:1 ratio). They will receive Wangbi granule or Wangbi placebo 12.0 g each time, three times a day for 12 weeks. The primary outcome is the disease activity score derivative for 28 joints (DAS28). Secondary outcomes are patient-reported outcomes, American College of Rheumatology 50% response criteria (ACR50), fatigue scale-14 (FS-14), visual analogue scale for pain (VAS), health assessment questionnaire disability index (HAQ-DI) and biomarkers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).Expected outcomesThe success of this study will provide strong evidence to confirm the efficacy and safety of Wangbi granule in the treatment of RA.Trial registration The trial has been registered in the ClinicalTrials Registry (NCT05540938, Date: 09/15/2022, https://clinicaltrials.gov/ct2/show/NCT05540938)

Prevalence and predictors of long-term remission in rheumatoid arthritis in real-world practice: a longitudinal study.

The aim of the present study was to provide real-world evidence for factors predicting long-term remission in a longitudinal study of rheumatoid arthritis (RA) patients. Long-term remission was defined by meeting American Rheumatism Association (ARA) criteria for remission and prednisolone dose ≤ 5mg/d for at least 5years. Patients in this cohort were treated by tight control strategy using step-up combination therapy with conventional synthetic DMARDs (csDMARDs), biologic DMARDs. The parameters associated with long-term remission were subjected to univariate analysis, and parameters with P-values of < 0.1 in univariate analysis were included in a multivariate regression analysis. One thousand two hundred and eighty-six RA subjects were considered for eligibility, and finally, 499 patients were included in the study. Median duration of follow-up was 108months. Long-term remission occurred in 157 (31.5%) patients. Median time to long-term remission was 8 (5, 41) months. Predictors of long-term remission were absence of flare during the course of disease, occurrence of sustained remission during 6months after starting therapy, age at the disease onset > 60, being anti-citrullinated protein antibodies (ACPA) negative, and Disease Activity Score-28 (DAS28) at cohort entry ≤ 5.1. In real-world practice, long-term remission occurs in 31.5% of patients treated with a tight control strategy. Absence of flare during the course of disease, occurrence of sustained remission during 6months after starting therapy, age at the disease onset > 60, being ACPA negative, and DAS28 at baseline ≤ 5.1 are independent predictors of long-term remission. Key Points • In real-world practice, long-term remission occurs in 31.5% of patients treated with a tight control strategy. • Median time to long-term remission was 8months. • Absence of flare during the course of disease, occurrence of sustained remission during 6months after starting therapy, age at the disease onset >60, being ACPA negative, and DAS28 at baseline ≤ 5.1 are independent predictors of long-term remission.

Suppression of Macrophage Activation by Sodium Danshensu via HIF-1α/STAT3/NLRP3 Pathway Ameliorated Collagen-Induced Arthritis in Mice.

It is still a clinical challenge to sustain the remission of rheumatoid arthritis (RA); thus, identifying more effective and safer agents for RA treatment remains an urgent demand. We investigated the anti-arthritic activity and potential mechanism of action of sodium Danshensu (SDSS), a structurally representative water-soluble derivative of Danshen, on collagen-induced arthritis (CIA) mice. Our results showed that paw edema, synovium hyperplasia, bone destruction, and the serum levels of both IL-1β and IL-6 were ameliorated by SDSS (40 mg/kg·d) in CIA mice. In addition, there was no difference between SDSS and methotrexate (MTX, 2 mg/kg·3d) treatment in the above indicators. Further mechanism studies illustrated that SDSS inhibited IL-1β secretion by downregulating the HIF-1α/STAT3/NLRP3 pathway in macrophages. On the other hand, HIF-1α accumulation and HIF-1α/STAT3/NLRP3 pathway activation by IOX4 stimulation reduced the therapeutic effect of SDSS. These findings demonstrate that SDSS displays anti-arthritic activity in CIA mice and prevents proinflammatory cytokines secretion in macrophages by suppressing the HIF-1α/STAT3/NLRP3 pathway.

Continuation, reduction, or withdrawal of tofacitinib in patients with rheumatoid arthritis achieving sustained disease control: a multicenter, open-label, randomized controlled trial.

Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. Chictr.org, ChiCTR2000039799.

Tight control in patients with rheumatoid arthritis treated with targeted therapies across the COVID-19 pandemic era.

To analyze the impact of different patterns of healthcare delivery on remission of rheumatoid arthritis (RA) patients treated with targeted therapies during the first wave (2020) and second/third waves (2021) of the pandemic compared to the pre-pandemic period (2019). In this observational real-life study, data from RA patients treated with biologic or targeted synthetic drugs were extracted from a longitudinal registry. Clinical Disease Activity Index (CDAI) was analyzed in the same period from the 22nd of February to the 18th of May for three consecutive years. These three periods were characterized by different patterns of healthcare delivery: (1) before the pandemic (2019) only in-person visits, (2) during the first wave (2020) both in-person visits and telehealth, and (3) during the second/third waves (2021) only in-person visits. A generalized linear model with the binomial error was fitted to evaluate the difference in the proportion of patients in CDAI remission. Quantile regression was used to compare the median of CDAI in difficult-to-treat (D2T) patients. In the three periods, we included 407, 450, and 540 RA patients respectively. The percentages of patients in CDAI remission were similar in the three periods (prevalence ratio 1.07, p value 0.423 between 2020 and 2019, and 1.01, p-value 0.934 between 2021 and 2019). The CDAI remission rate was 40.55% (N = 163), 43.18% (N = 155) and 40.82% (N = 220) in 2019, 2020 and 2021, respectively. Among our cohort of D2T patients, CDAI remission was similar across the three periods (N = 30, 22.22%; N = 27, 23.68%; and N = 34, 21.52% respectively). Although the pandemic has imposed changes in our healthcare delivery, these different strategies seem to be effective in ensuring satisfactory management of RA treated with targeted therapies. The approaches modulated in the context of the different periods have been a feasible compensation for ensuring disease control even in D2T patients.

Transcranial Direct Current Stimulation Combined with Peripheral Neuromuscular Stimulation Improves Quality of Life, Fatigue, and Pain in a Patient with Rheumatoid Arthritis and Refractory Radicular Pain Related to Spinal Stenosis

Background: Transcranial direct current stimulation (tDCS) has emerged as an adjuvant noninvasive neuromodulation tool to control fatigue and pain. To date, no studies have assessed the safety and efficiency of tDCS in patients with rheumatoid arthritis and with fatigue, poor quality of life, and refractory radicular pain associated with spinal stenosis. Case Presentation: An 85-year-old woman patient presented with rheumatoid arthritis in remission, refractory radicular pain-associated spinal stenosis, fatigue, and impaired quality of life. The patient underwent 16 daily sessions of tDCS intervention (2 mA, 20 min, positively and negatively charged electrodes were positioned at C1 and Fp2, respectively), in addition to simultaneous peripheral neuromuscular electrical stimulation (frequency of 100 Hz and amplitude of 500 μs). After the intervention, neither disease relapse nor clinical intercurrence occurred. Moreover, there was a significant and sustained improvement in her health-related quality of life, with a reduction in the level of pain and chronic fatigue. Conclusion: The present case report shows that tDCS is safe and may be an adjuvant tool for the treatment of pain and fatigue in patients with systemic autoimmune disease, as well as for improving quality of life. Further studies are required to corroborate this case report.

A systematic comparison of different composite measures (DAS 28, CDAI, SDAI, and Boolean approach) for determining treatment effects on low disease activity and remission in rheumatoid arthritis.

Some composite measures for determining the treatment effects of disease-modifying antirheumatic drugs on remission and low disease activity (LDA) in rheumatoid arthritis (RA) may produce misleading results if they include an acute phase reactant (APR). To inform the choice of appropriate measure, we performed a systematic comparison of treatment effects using different composite measures. We used data generated for a systematic review of biologics in RA conducted by the Institute for Quality and Efficiency in Health Care and data from systematic reviews of newer biologics and Janus kinase (JAK) inhibitors provided by sponsors. The studies included had been conducted up to 2020 and investigated comparisons of biologics with placebo and head-to-head comparisons of biologics. Treatment effects on LDA and remission in studies investigating biologics or JAK inhibitors in RA were compared among 4 composite measures: the disease activity score 28 (DAS 28), the simplified disease activity index (SDAI), the Boolean approach (remission only), and the clinical disease activity index (CDAI)-only the latter does not include an APR. 49 placebo-controlled studies included 9 different biologics; 48 studies (16,233 patients) investigated LDA and 49 (16,338 patients) investigated remission. 11 active-controlled studies (5996 patients) investigated both LDA and remission and included 5 different head-to-head comparisons of biologics and 5 different comparisons (6 studies) of biologics with JAK inhibitors. Statistically significantly larger treatment effects were found for biologics or JAK inhibitors versus placebo or active control in 16% of pairwise comparisons of composite measures (27 of 168). Most of these larger effects were observed for composite measures with an APR, i.e. the DAS28 (19 comparisons) followed by the SDAI (n = 7). Larger effects were most frequently detected in favour of interleukin (IL)-6 inhibitors and to a lesser extent for JAK inhibitors versus treatments with different modes of action. The use of the DAS 28 and SDAI in clinical studies may generate results favouring certain treatments based on their mode of action (e.g. IL-6 inhibitors versus other biologics). To enable unbiased comparative effectiveness research, a composite measure without an APR (i.e. the CDAI) should thus be the measure of choice.

Psychosocial Burden Predicts Sustained Remission in Early Rheumatoid Arthritis: Unraveling the Complex Interplay of Well-Being and Disease Activity.

This study investigated how psychosocial aspects of disease affect the probability of achieving sustained remission in early rheumatoid arthritis (RA) and explored the directionality of this relationship. Data were analyzed from the randomized controlled Care in Early RA trial. Sustained remission was defined as a continued Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) of <2.6 from weeks 16 to 104. Patients completed the Short Form 36 (SF-36) health survey, Revised Illness Perception Questionnaire (IPQ-R), and the Utrecht Coping List. These psychosocial variables were studied at baseline and at week 16 as predictors of sustained remission with logistic regression. Next, subgroups of patients in remission at week 16 were identified by Latent Profile Analysis based on these psychosocial indicators. Time to first loss of remission was then compared between groups by Cox proportional hazards regression. Finally, directionality of associations between psychosocial indicators and DAS28-CRP was explored with cross-lagged panel models (CLPMs). Sustained DAS28-CRP remission was associated with higher SF-36 scores and less passive coping at baseline and with higher SF-36 scores and more positive IPQ-R outcomes at week 16. Among patients in DAS28-CRP remission at week 16 (n=287), 2 subgroups were identified: a low psychosocial burden group (n=231 of 287) and a high psychosocial burden group (n=56 of 287). The low psychosocial burden group retained remission longer (hazard ratio 0.51 [0.35-0.73]). In the CLPM, temporal relationships between psychosocial well-being and DAS28-CRP were complex, bidirectional, and disease-phase dependent. Suboptimal psychosocial well-being and negative illness perceptions predicted lower probability of sustained remission in an early RA cohort. Illness perceptions appeared to become more clinically relevant with time. Finally, 1 in 5 patients showed worse psychosocial outcomes despite early remission, and these patients tended to lose remission earlier.

The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis

BackgroundDysbiotic intestinal and oral microbiota have been implicated in the pathogenesis of rheumatoid arthritis (RA), but the mechanisms how microbiota could impact disease activity have remained elusive. The aim of this study was to assess the association of the biological activity of serum lipopolysaccharides (LPS) with disease activity and likelihood of achieving remission in RA patients.MethodsWe measured Toll-like receptor (TLR) 4-stimulating activity of sera of 58 RA patients with a reporter cell line engineered to produce secreted alkaline phosphatase in response to TLR4 stimulation. Levels of LPS-binding protein, CD14, and CD163 were determined by ELISA assays.ResultsThe patient serum-induced TLR4 activation (biological activity of LPS) was significantly associated with inflammatory parameters and body mass index at baseline and at 12 months and with disease activity (DAS28-CRP, p<0.001) at 12 months. Importantly, baseline LPS bioactivity correlated with disease activity (p=0.031) and, in 28 early RA patients, the likelihood of achieving remission at 12 months (p=0.009). The level of LPS bioactivity was similar at baseline and 12-month visits, suggesting that LPS bioactivity is an independent patient-related factor. Neutralization of LPS in serum by polymyxin B abrogated the TLR4 signaling, suggesting that LPS was the major contributor to TLR4 activation.ConclusionWe describe a novel approach to study the biological activity of serum LPS and their impact in diseases. The results suggest that LPS contribute to the inflammatory burden and disease activity on patients with RA and that serum-induced TLR4 activation assays can serve as an independent prognostic factor.Graphical A graphical summary of the conclusions of the study.

Case of successful use of sarilumab in secondary renal amyloidosis in a patient with rheumatoid arthritis

Clinical observation of the successful use of the interleukin 6 (IL6) inhibitor sarilumab in secondary renal amyloidosis in a patient with active seropositive rheumatoid arthritis, is presented. This complication was confirmed by biopsy of rectum. The presented clinical example demonstrates a fairly rapid, within five years from the onset of the disease, the development of secondary renal amyolidosis with the formation of a persistent nephrotic syndrome that is resistant to therapy with cyclophosphamide and rituximab. Prescription of the IL6 inhibitor tocilizumab contributed to a decrease in the clinical and laboratory activity of the underlying disease, a decrease in the severity of daily proteinuria, but did not allow to achieve the full effect. The use of another IL6 inhibitor – sarilumab, led to a complete regression of nephrotic syndrome with normalization of general urine analysis, biochemical blood tests – total protein, albumin, total cholesterol, against the background of stable clinical and laboratory remission of rheumatoid arthritis.

Validity of Remission Criteria in Rheumatoid Arthritis Compared to Ultrasound-Defined Remission.

Remission is the ultimate purpose of treatment in rheumatoid arthritis (RA). However, even when the most stringent composite scores are used, structural damages can occur; hence, ultrasonography (US) appears to be the best way to assess real remission. This study aimed to investigate the validity of different RA remission scores using US as a reference. An analytic diagnostic study, of 30 RA patients in remission (according to the Disease Activity Score in 28 Joints [DAS28]) and a control group with active RA, was conducted between January and October 2018 at Mongi Slim Hospital in Tunis, Tunisia. Among them, patients in remission were identified according to their Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and the Boolean American College of Rheumatology/European League against Rheumatism activity index (ACR/EULAR) remission scores. The validity of each activity score for remission was calculated by considering the absence of power Doppler (PD) signals as a gold standard. All patients were in remission according to the DAS28, with an average score of 2.03 (1.1-2.6). US examination showed PD signals in 57% of patients. A total of 26 patients were in remission according to the CDAI; a Doppler signal was detected in 58% of those cases. SDAI remission was accomplished in 19 patients, with PD activity in 53% of cases. Of the 14 patients in remission according to the Boolean ACR/EULAR criteria, synovial hyper-vascularisation was found in 64%. Considering true remission as the absence of PD signals, the most sensitive and specific score was the DAS28 (93% and 68%, respectively). Considering remission in RA as the absence of vascularised synovitis, the DAS28 is the most sensitive and most specific score.

Inflammation mediates approximately one quarter of excess relative all-cause mortality in persons with rheumatoid arthritis: the Trøndelag Health Study

Inflammation may contribute to excess mortality in rheumatoid arthritis (RA) patients. We investigated associations to all-cause mortality of the inflammation markers high-sensitivity C-reactive protein (CRP), lactoferrin (neutrophil activation marker), and neopterin (monocyte activation marker). From the population-based Trøndelag Health Study (3rd wave 2006–2008), 316 RA patients and 43,579 controls were included. Lactoferrin and neopterin were quantified in a nested cohort (n = 283 RA patients, n = 3698 controls). Follow-up was until death found by linkage to the Norwegian Cause of Death Registry or 31.12.2018. All-cause mortality was analyzed using Cox regression and Cox regression-based mediation analysis. Having RA (hazard ratio (HR): 1.25, 95%CI: 1.00, 1.56, p = 0.048), and CRP ≥ 3 mg/L (HR: 1.50, 95%CI: 1.41, 1.60, p < 0.001) were associated with all-cause mortality. The overall excess relative mortality risk of having RA was 38%. CRP ≥ 3 mg/L mediated approximately 1/4 of this risk (p < 0.001). In the nested cohort, CRP ≥ 3 mg/L (HR: 1.51, 95%CI: 1.26, 1.80, p < 0.001) and neopterin (HR: 1.17, 95%CI: 1.01, 1.36, p = 0.031) were associated with all-cause mortality. In conclusion, CRP levels ≥ 3 mg/L mediated approximately a quarter of the 38% excess relative all-cause mortality risk associated with RA. Using definitions of RA remission with emphasis both on joint status and the level of general inflammation may help guide the most efficient treatment regimens.

American College of Rheumatology/EULAR Remission Criteria for Rheumatoid Arthritis: 2022 Revision.

In 2011, the American College of Rheumatology (ACR) and EULAR endorsed provisional criteria for remission in rheumatoid arthritis (RA), both Boolean- and index-based. Based on recent studies indicating that a higher threshold for the patient global assessment (PtGA) may improve agreement between the 2 sets of criteria, our goals were to externally validate a revision of the Boolean remission criteria using a higher PtGA threshold and to validate the provisionally endorsed index-based criteria. We used data from 4 randomized trials comparing biologic disease-modifying antirheumatic drugs to methotrexate or placebo. We tested the higher proposed PtGA threshold of 2 cm (Boolean2.0) (range 0-10 cm) compared to the original threshold of 1 cm (Boolean1.0). We analyzed agreement between the Boolean- and index-based criteria (Simplified Disease Activity Index [SDAI] and Clinical Disease Activity Index [CDAI]) for remission and examined how well each remission definition predicted later good physical function (Health Assessment Questionnaire [HAQ] score ≤0.5) and radiographic nonprogression. Data from 2,048 trial participants, 1,101 with early RA and 947 with established RA, were included. The proportion of patients with disease in remission at 6 months after treatment initiation increased when using Boolean2.0 compared to Boolean1.0, from 14.8% to 20.6% in early RA and 4.2% to 6.0% in established RA. Agreement between Boolean2.0 and the SDAI or CDAI remission criteria was better than for Boolean1.0, particularly in early disease. Boolean2.0, SDAI, and CDAI remission criteria had similar positive likelihood ratios (LRs) to predict radiographic nonprogression and a HAQ score of ≤0.5 (positive LR 3.8-4.3). The omission of PtGA (BooleanX) worsened the prediction of good functional outcomes. Using the Boolean 2.0 criteria classifies more patients as achieving remission and increases the agreement with index-based remission criteria without jeopardizing predictive value for radiographic or functional outcomes. This revised Boolean definition and the previously provisionally endorsed index-based criteria were endorsed by ACR and EULAR.

Does remission in rheumatoid arthritis bring kinesiophobia, quality of life, fatigue, and physical activity closer to normal?

This study aimed to compare kinesiophobia, fatigue, physical activity, and quality of life (QoL) between the patients with rheumatoid arthritis (RA) in remission and a healthy population. The prospective controlled study included 45 female patients (mean age: 54.22±8.2 year; range, 37 to 67 year) with a diagnosis of RA determined to be in remission according to the Disease Activity Score in 28 Joints (DAS28) being ≤2.6 between January 2022 and February 2022. As a control group, 45 female healthy volunteers (mean age: 52.2±8.2 year; range, 34 to 70 year) of similar age were evaluated. The QoL, disease activity, pain, kinesiophobia, fatigue severity, and physical activity were assessed using the Health Assessment Questionnaire, DAS28, Visual Analog Scale, Tampa Scale of Kinesiophobia, Fatigue Severity Scale, and International Physical Activity Questionnaire, respectively. There was no significant difference between the groups in demographic data. A statistically significant difference was found between the groups in terms of pain, C-reactive protein level, fatigue, kinesiophobia, QoL, and total, high, and moderate physical activity scores (p<0.001). Among the RA patients in remission, there was a significant correlation between kinesiophobia and moderate physical activity and QoL, as well as between fatigue and high physical activity (p<0.05). Patient education and multidisciplinary approach strategies should be developed to increase the QoL and physical activity and reduce kinesiophobia in RA patients in remission since there may be a decrease in physical activity due to kinesiophobia, fatigue, and fear of movement in this patient group compared to the healthy population, impairing their QoL.

Association of adiponectin levels with disease activity score, RA factor and ESR in rheumatoid arthritis patients

Introduction: Rheumatoid arthritis is a chronic inflammatory polyarthritis of relatively common occurrence affecting about 1-2% of adult population world-wide and 0.75% of Indian adults. The disease occurs at all ages and affects all ethnic groups. For early diagnosis and progression of rheumatoid arthritis might be useful for to better treatment of the patients. Present study aimed to assessment of adiponectin in newly diagnosed and remission rheumatoid arthritis patients. Materials and Methods: 100 Rheumatoid arthritis patients and 50 healthy volunteers with matching age, gender, and BMI were included in the study. All the subjects' biochemical, disease activity score, RA factor,ESR Rheumatoid Arthritis Patients and serum adiponectin levels were assessed. SPSS and Microsoft Excel Spreadsheets were used to conduct the necessary statistical analysis. Results: The patients with rheumatoid arthritis shown significantly higher levels of fasting blood sugar, postprandial blood sugars ,triglycerides , RA factor, ESR when compared to healthy controls (P=0.001**). Additionally we also discovered to be considerably significantly elevated levels of serum adiponectin (P= 0.001**). Furthermore there was very high significant positive correlation between serum adiponectin and disease activity score, RA factor, ESR.

Association between patient-reported outcomes and impairments in work and activity in patients with rheumatoid arthritis in clinical remission: A retrospective analysis using the IORRA database.

To explore the patient-reported outcomes (PROs) associated with work productivity and activity impairment (WPAI) in patients with rheumatoid arthritis (RA) in clinical remission. We enrolled patients with RA ≥18 years and with a simplified disease activity index ≤3.3 from the Institute of Rheumatology, Rheumatoid Arthritis data set collected in October 2017. The pain-visual analogue scale, patients' global assessment visual analogue scale (VAS), Japanese version of the Healthcare Assessment Questionnaire (J-HAQ) Disability Index, and duration of morning joint stiffness were selected as the PROs. To evaluate work productivity and activity, the WPAI for RA instrument (WPAI-RA) was used. To assess the contribution of each PRO to the WPAI-RA score, an analysis of variance model was constructed. The mean age of the 2614 patients was 62.4 years; 85.1% were female. Median values of the WPAI-RA score were 1.1% for absenteeism, 6.5% for presenteeism, 7.4% for work impairment, and 10.2% for activity impairment. Morning joint stiffness contributed the most to absenteeism (18.0%), while pain-VAS contributed the most to presenteeism (57.4%), work productivity loss (51.1%), and daily activity impairment (53.7%). J-HAQ was the second most contributing factor to presenteeism (17.4%), work productivity loss (16.3%), and daily activity impairment (26.0%). The pain-VAS and J-HAQ highly contributed to WPAI in patients with RA in clinical remission.

Disease activity trajectories for early and established rheumatoid arthritis: Real-world data from a rheumatoid arthritis cohort.

Disease activity status described at fixed time points does not accurately reflect disease course in chronic and relapsing diseases such as rheumatoid arthritis (RA). We described longitudinal disease activity trajectories in early and established RA. Patients with available 28-Joint Disease Activity Score-erythrocyte sedimentation rate (DAS28-ESR) and Clinical Disease Activity Index (CDAI) over two years were included. Using latent growth curve modelling (LCGM), subgroups of patients following distinct patterns were identified. 1920 patients were included with 34.4% in early RA (< 2 years' disease duration). Three subgroups were identified using DAS28-ESR in early RA: 1) low disease activity to remission (LDA-REM: 19.1%); 2) moderate disease to remission (MD-REM: 54%); 3) high to moderate disease (HD-MD: 26.9%). The HD-MD group had a significantly higher number of comorbidities, biologic and steroid use and lower post-secondary education. Using CDAI, we identified seven subgroups with only 1.9% remission in early RA. In established RA, seven subgroups were identified using either DAS28-ESR or CDAI. Using DAS28-ESR 27.8% with HD showed improvement in disease status (14.2% HD-REM, 10.3% HD-LDA and 3.3% HD-MD) while using CDAI 17.9% showed improvement. Disease course was different in early and established RA. Only 14.2% of established RA reached DAS28-ESR remission compared to 73.1% of early RA. Using CDAI only 1.9% of early RA and none of the established RA achieved remission, likely reflecting the impact of the patient global assessment on this score. Findings also illustrate the impact of sociodemographic characteristics and early treatment on disease course.

Correlation between anti-mutated citrullinated vimentin and bone turnover markers (CTX-1 and P1NP) in patients with rheumatoid arthritis in remission and low-disease activity

IntroductionRheumatoid arthritis is associated with bone loss and the risk of osteoporotic fracture. Bone loss in this disease is mediated by inflammation and autoimmunity. Many studies have shown that anti-citrullinated protein antibody is capable of inducing bone loss through several mechanisms.This study aimed to determine the relationship between autoimmunity, represented by anti-mutated citrullinated vimentin (anti-MCV) in this study, and bone loss, represented by C-terminal cross-linking telopeptide of type I collagen (CTX-1), and N-terminal pro-peptide of type 1 procollagen (P1NP) in this study, in patients with rheumatoid arthritis in remission and low disease activity.Material and methodsThis study enrolled 38 rheumatoid arthritis patients with disease remission and low disease activity in Cipto Mangunkusumo Hospital between August and September 2019. We collected the patients’ demographic data, Disease Activity Score 28 (DAS28), and treatment history. All participants underwent blood work for anti-MCV, CTX-1, and P1NP.ResultsThirty-four of the subjects were women (89.5%), with the mean age of 40 ±7.6 years and the median disease duration of 36 months. Among the subjects, 26 patients (68.4%) were anti-MCV positive. There was no correlation between anti-MCV and CTX-1 levels (r = 0.101, p = 0.274). There was a moderate negative correlation between anti-MCV and P1NP (r = –0.449, p = 0.001). The mean difference of P1NP according to anti-MCV level also showed a significant difference (p = 0.019)ConclusionsThe anti-MCV levels are not directly correlated with CTX-1 levels, indicating heterogeneity in the disease course even after inflammation has ceased. The anti-MCV and P1NP levels are moderately correlated, indicating that bone formation is resumed during the suppression of autoimmunity.

Correlation of serum citrullinated histone H3 levels with disease activity in patients with rheumatoid arthritis.

Serum citrullinated histone H3 (CitH3) levels in humans with rheumatoid arthritis (RA) were examined and the associations between CitH3 levels and disease variables were investigated. Serum CitH3 levels were measured using an enzyme-linked immunosorbent assay in 151 RA patients (69 with highly, 32 with moderately, and 20 with mildly active RA and 30 with RA in remission) and 56 healthy controls. Receiver operating characteristic curve analysis was performed to evaluate the discriminant capacity of CitH3 between highly/moderately active RA and RA in remission/mild activity. Furthermore, machine-learning methods were applied to construct a predictive model. CitH3 concentration was more upregulated in patients with highly and moderately active RA than in those with mild activity and remission. The area under the curve for CitH3 was 0.825 for discriminating between highly and mildly active RA, 0.840 for discriminating between highly active RA and RA in remission, 0.789 for discriminating between moderately and mildly active RA, and 0.829 for discriminating between moderately active RA and RA in remission. The correlation analysis revealed that serum CitH3 levels were positively associated with Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR), ESR, C-reactive protein, rheumatoid factor, and some routine blood parameters (WBC, RDW, PLT, N, and N%), while negatively associated with haemoglobin, lymphocyte percentage, and thyroid-stimulating hormone. Through machine learning, the optimal predictive model was selected and had high performance. CitH3 is significantly associated with disease activity and could serve as a useful candidate biomarker to assess disease activity in patients with RA.

Validation and predictive capacity of a Dutch version of the FLARE-RA questionnaire within the context of a TNFi-tapering trial.

Flare Assessment in Rheumatoid Arthritis (FLARE-RA) is a self-administered tool aiming to capture current or recent flares in rheumatoid arthritis (RA). We aimed to externally validate the FLARE-RA instrument and its existing cutoffs for flare detection within a bDMARD-tapering context in established RA. Data were analyzed from the Tapering Etanercept in Rheumatoid Arthritis (TapERA) trial, which studied the feasibility of tapering etanercept in patients with established RA in sustained remission. The English FLARE-RA was translated and cross-culturally adapted into Dutch, and internal consistency and test-retest reliability were evaluated with Crohnbach's alpha and intraclass correlation coefficient (ICC). Participants completed the FLARE-RA 3-monthly for 12months. Accuracy and optimal cutoffs of FLARE-RA to detect DAS28-defined flares were assessed using area under the receiver operating characteristic curves (AUC). Association of FLARE-RA scores with current and future flares was studied using logistic generalized estimating equations (GEE). The Dutch FLARE-RA showed excellent internal consistency and test-retest reliability (Cronbach's alpha 0.96; ICC 0.96 [95% CI 0.70-1.00]). Discriminatory capacity of FLARE-RA to detect flares was acceptable (AUC 0.77, 0.80, and 0.72 for global, arthritis, and general symptoms subscales, respectively), with an optimal global score cutoff of 4/10. In GEE-models, higher FLARE-RA scores were associated with increased odds of both current and future flares. We successfully translated and cross-culturally adapted the FLARE-RA into a Dutch version and validated its capacity to detect flares in a bDMARD-tapering context in established RA. Finally, higher FLARE-RA scores might indicate an increased risk of future flares.Trial registration: EU Clinical Trials Register, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-004631-22/BE , EudraCT number 2012-004,631-22. Key Points • Translation and cross-cultural adaptation of the FLARE-RA resulted in a Dutch version with excellent internal consistency and test-retest reliability. • The FLARE-RA is a valid instrument to detect current OMERACT-defined flares within a bDMARD tapering setting, with an optimal global score cutoff of 4/10. • Higher scores on the FLARE-RA are associated with increased risk of future flares, which could be particularly relevant when considering DMARD tapering.