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31058442 Evaluation of Response Criteria in Rheumatoid Arthritis Treated With Biologic Disease-Modi 2020 Jul OBJECTIVE: Biologic disease-modifying antirheumatic drugs (bDMARDs) used for rheumatoid arthritis (RA) treatment have several mechanisms of action. Interleukin-6 inhibitors (IL-6i) block the production of acute-phase reactants (APRs), which are some of the composite measures of disease activity. We undertook this study to examine the agreement between the European League Against Rheumatism (EULAR) response based on the erythrocyte sedimentation rate (ESR) or C-reactive protein level, the Simplified Disease Activity Index 50% response measure (SDAI50), and the Clinical Disease Activity Index 50% response measure (CDAI50) in patients treated with IL-6i and other bDMARDs. METHODS: We enrolled 306 patients with RA who started or switched bDMARDs. Treatment response at 6 months was analyzed. Kappa statistics were used to evaluate the agreement between different response measures. The contribution of APRs to improvement in disease activity scores was examined. The change of Health Assessment Questionnaire (HAQ) score was analyzed in IL-6i-treated patients. RESULTS: Good agreement was achieved between response measures, with κ >0.6 in patients treated with tumor necrosis factor inhibitors or cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin fusion protein. In IL-6i-treated patients, the agreement was low between the EULAR response (ESR) and the SDAI50 or the CDAI50 (κ = 0.43 and 0.37, respectively). Under IL-6i treatment, APR improvement accounted for 56.0% of total improvement of the Disease Activity Score in 28 joints (DAS28) using the ESR. When discordance was found between the CDAI50 and EULAR response in IL-6i-treated patients, all patients were classified as EULAR-only responders; there was no HAQ improvement in EULAR-only responders. CONCLUSION: EULAR response criteria overestimate the response under IL-6i treatment because the APR improvement largely contributes to the DAS28 improvement.
31369868 Factors influencing the choice of biologic therapy following Rituximab in patients with rh 2020 Jan OBJECTIVES: To assess factors influencing the choice and effectiveness of biological disease-modifying antirheumatic drugs (DMARDs) following failure of rituximab (RTX) in rheumatoid arthritis (RA), taking patient profile into account. METHODS: In a retrospective, multicenter study, data about RA patients starting a new biologic during the year after RTX discontinuation were collected at baseline (when the biologic was introduced after RTX), and during follow-up (3, 6, and 12 months). Characteristics of patients receiving tocilizumab (TCZ), abatacept (ABA), or a TNFα inhibitor (TNFi), EULAR response, and retention rate were compared using multidimensional factorial analysis for patient profiles and multivariate analysis including propensity score built on the patient profile. RESULTS: Among 152 patients analyzed (37.5% TCZ, 31.6% ABA, 30.9% TNFi), sex, disease characteristics and activity, concomitant DMARDs or glucocorticoids, and previous use of RTX and TNFi were similar at baseline. Patients receiving ABA were slightly older. Multimorbidity index was higher but not significantly different. Multidimensional factorial analysis showed a distinct profile of patients receiving ABA, characterized by older age, more men, more smokers, more comorbidities, and higher anti-cyclic citrullinated peptide antibody. At 1 year, drug retention was higher for ABA than TNFi after adjustment for disease duration, concomitant DMARDs, glucocorticoids, and propensity score (P=0.04). Tolerance and serious infections were similar among groups. CONCLUSIONS: The profile of patients receiving ABA following failure of RTX differed from TNFi and TCZ using multidimensional factorial analysis. After adjustment for propensity score, drug retention rate remained higher with ABA than TNFi.
31897960 The association between anxiety and disease activity and quality of life in rheumatoid art 2020 May OBJECTIVES: In people with rheumatoid arthritis (RA), mental health problems are common, but often not recognized or treated, contributing to increased morbidity and mortality. Most studies examining the impact of mental health problems in RA have focused on depression. We aimed to determine the association between anxiety, and disease activity and quality of life (QoL) in people with RA. METHODS: A systematic review and meta-analysis were performed. A protocol was registered with PROSPERO (CRD2-17062580). Databases (Web of Science, PsycINFO, CINAHL, Embase, Medline) were searched for studies examining the association between anxiety and disease activity and QoL, in adults with RA, from inception to February 2019. Primary outcome measures were DAS28 and SF-36. Eligibility screening and data extraction were completed by two reviewers. Disagreements were resolved by discussion or a third reviewer. Quality assessment was carried out using the Newcastle-Ottawa Scale. RESULTS: From 7712 unique citations, 60 articles were assessed for eligibility. The final review included 20 studies involving 7452 people with RA (14 cross-sectional, 6 cohort). Eleven examined disease activity, 6 reported QoL outcome measures and 3 included both. Anxiety was associated with increased disease activity and worse QoL. Meta-analysis showed anxiety to be correlated with increased DAS28 scores (r = 0.23, CI 0.14, 0.31) and reduced physical (r = - 0.39, CI - 0.57, - 0.20) and mental QoL (- 0.50, CI - 0.57, - 0.43). CONCLUSIONS: Anxiety in people with RA is associated with increased disease activity and worse QoL. Improved recognition and management of comorbid anxiety may help to improve outcomes for people with RA.Key Points• This is the first systematic review and meta-analysis to examine the relationship between anxiety and disease activity and QoL in people with RA.• Anxiety was associated with higher disease activity both cross-sectionally and at up to 12-month follow-up.• Anxiety may have a more significant impact on disease activity in early RA, highlighting the importance of early recognition and management of comorbid anxiety.• People with anxiety had poorer self-reported physical and mental QoL, although there was some heterogeneity in study findings, particularly for physical QoL (I(2) = 78.5%).
32851423 Nurse-led care for the management of rheumatoid arthritis: a review of the global literatu 2021 Mar Globally, increasing demand for rheumatology services has led to a greater reliance on non-physician healthcare professionals (HCPs), such as rheumatology nurse specialists, to deliver care as part of a multidisciplinary team. Across Africa and the Middle East (AfME), there remains a shortage of rheumatology HCPs, including rheumatology nurses, which presents a major challenge to the delivery of rheumatology services, and subsequently the treatment and management of conditions such as rheumatoid arthritis (RA). To further explore the importance of nurse-led care (NLC) for patients with RA and create a set of proposed strategies for the implementation of NLC in the AfME region, we used a modified Delphi technique. A review of the global literature was conducted using the PubMed search engine, with the most relevant publications selected. The findings were summarized and presented to the author group, which was composed of representatives from different countries and HCP disciplines. The authors also drew on their knowledge of the wider literature to provide context. Overall, results suggest that NLC is associated with improved patient perceptions of RA care, and equivalent or superior clinical and cost outcomes versus physician-led care in RA disease management. Expert commentary provided by the authors gives insights into the challenges of implementing nurse-led RA care. We further report practical proposed strategies for the development and implementation of NLC for patients with RA, specifically in the AfME region. These proposed strategies aim to act as a foundation for the introduction and development of NLC programs across the AfME region.
32798211 Innate immunity drives pathogenesis of rheumatoid arthritis. 2021 Apr Rheumatoid arthritis (RA) is an autoimmune disease affecting ∼1% of the general population. This disease is characterized by persistent articular inflammation and joint damage driven by the proliferating synovial tissue fibroblasts as well as neutrophil, monocyte and lymphocyte trafficking into the synovium. The factors leading to RA pathogenesis remain poorly elucidated although genetic and environmental factors have been proposed to be the main contributors to RA. The majority of the early studies focused on the role of lymphocytes and adaptive immune responses in RA. However, in the past two decades, emerging studies showed that the innate immune system plays a critical role in the onset and progression of RA pathogenesis. Various innate immune cells including monocytes, macrophages and dendritic cells are involved in inflammatory responses seen in RA patients as well as in driving the activation of the adaptive immune system, which plays a major role in the later stages of the disease. Here we focus the discussion on the role of different innate immune cells and components in initiation and progression of RA. New therapeutic approaches targeting different inflammatory pathways and innate immune cells will be highlighted here. Recent emergence and the significant roles of innate lymphoid cells and inflammasomes will be also discussed.
32248626 Efficacy of a Physical Activity Counseling Program With Use of a Wearable Tracker in Peopl 2020 Dec OBJECTIVE: To assess the efficacy of a multifaceted counseling intervention at improving physical activity participation and patient outcomes. METHODS: We recruited people with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). In weeks 1-8, the immediate group received education and counseling by a physical therapist, used a Fitbit and a web application to obtain feedback about their physical activity, and received 4 follow-up calls from the physical therapist. The delay group received the same intervention in weeks 10-17. Participants were assessed at baseline and at weeks 9, 18, and 27. The primary outcome was time spent in moderate/vigorous physical activity (MVPA; in bouts of ≥10 minutes) measured with a SenseWear device. Secondary outcomes included step count, time in sedentary behavior, pain, fatigue, mood, self-management capacity, and habitual behaviors. RESULTS: A total of 118 participants enrolled. The adjusted mean difference in MVPA was 9.4 minutes/day (95% confidence interval [95% CI] -0.5, 19.3, P = 0.06). A significant effect was found in pain (-2.45 [95% CI -4.78, -0.13], P = 0.04), and perceived walking habit (0.54 [95% CI 0.08, 0.99], P = 0.02). The remaining secondary outcomes improved, but were not statistically significant. Post hoc analysis revealed a significant effect in MVPA (14.3 minutes/day [95% CI 2.3, 26.3]) and pain (-4.05 [95% CI -6.73, -1.36]) in participants with RA, but not in those with SLE. CONCLUSION: Counseling by a physical therapist has the potential to improve physical activity in people with inflammatory arthritis, but further study is needed to understand the intervention effect on different diseases. We found a significant improvement in pain, suggesting that the intervention might have a positive effect on symptom management.
32326727 Effect of Yoga Therapy on Disease Activity, Inflammatory Markers, and Heart Rate Variabili 2020 Jun Background: Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease. Antirheumatoid treatment reduces disease activity and inflammation, but not all patients respond to treatment. Autonomic dysfunction is common in RA leading to frequent cardiovascular complications. Yoga therapy may be useful in these patients, but there are little data on the effect of yoga on disease activity, inflammatory markers, and heart rate variability (HRV). Objectives: This study assessed the effect of 12-week yoga therapy on disease activity, inflammatory markers, and HRV in patients with RA. Materials and Methods: This randomized control trial was conducted on newly diagnosed RA patients attending outpatient services at the Department of Clinical Immunology, JIPMER. One hundred and sixty-six participants were randomized into two groups: the control group (CG) (n = 83) and yoga group (YG) (n = 83). Yoga therapy was administered to participants in the YG for 12 weeks, along with standard medical treatment. The CG received only standard medical treatment. Primary outcomes were disease activity score 28, interleukin-1α (IL-1α), IL-6, tumor necrosis factor-α (TNF-α), cortisol, and HRV parameters. All parameters were measured at baseline and after 12 weeks. Results: Disease activity significantly decreased in both groups after 12 weeks, but it was reduced more in YG, which was statistically significant (p < 0.05). In both YG and CG, IL-1α, IL-6, TNF-α, and cortisol decreased after 12 weeks, but IL-1α and cortisol decreased more significantly in YG than in CG. Low-frequency component expressed as normalized unit (LFnu) and the low-frequency/high-frequency (LF-HF) ratio decreased significantly, and total power and HF component expressed as normalized unit (HFnu) increased significantly in the YG compared with CG. Conclusion: Twelve-week yoga therapy, if given along with standard medical treatment, significantly reduces disease activity and improves sympathovagal balance in RA patients.
32067722 Prevalence and clinical significance of extra-articular manifestations at diagnosis in the 2020 Jun OBJECTIVES: The aim of this study was to determine the prevalence and clinical significance of extra-articular manifestations (EAMs) at inclusion into a cohort of patients with recent-onset arthritis consistent with rheumatoid arthritis (RA). METHODS: The ESPOIR cohort included patients aged 18 to 70 years who had a definitive or probable diagnosis of RA. Symptoms consistent with EAMs were collected at baseline. We divided the patients into two groups, with vs. without baseline EAMs. We looked for associations linking the presence of EAMs at baseline to patient and disease characteristics at baseline and 5 years later, as well as to diagnostic certainty after 2 years. The analyses were adjusted for multiple comparisons using the Benjamini-Hochberg procedure to control the false discovery rate. RESULTS: Of 798 patients, 330 (41.4%) had at least one symptom consistent with EAM at baseline, with the most common being sicca syndrome (28.4%) and Raynaud's phenomenon (17.3%). The EAM+ group had a higher mean baseline DAS-28 value (5.3 ± 1.3 versus 5.0 ± 1.3; corrected p value = 0.005) compared to the EAM- group. The final diagnosis did not differ between the two groups. After 5 years, the EAM+ group had significantly higher values for the tender joint count (3.9 ± 6.4 versus 1.8 ± 3.3, corrected p value = 0.005) and swollen joint count (1.3 ± 2.8 versus 1.1 ± 2.3, corrected p value =0.0005) compared to the EAM- group. CONCLUSION: EAMs, particularly sicca syndrome and Raynaud's phenomenon, are very common in patients with early arthritis consistent with RA. In this population, several parameters reflecting disease activity were higher among patients with EAMs, at baseline and after 5 years.
31242798 14-3-3η Protein in serum and synovial fluid correlates with radiographic damage and progr 2020 Jul Objectives: The aim of the study is to examine the association between 14-3-3η protein levels in both serum and synovial fluid (SF) with various parameters in a longitudinal cohort of patients with established rheumatoid arthritis (RA).Methods: Serum and SF samples were obtained from RA patients and 14-3-3η levels were measured. Radiological damage and progression were evaluated using Sharp/van der Heijde score (SHS) at study entry and at 2-years follow-up.Results: A total of 39 RA patients were included with a mean disease duration of 9.6 ± 8 years. Levels of 14-3-3η were two-fold higher in SF than in serum (mean of 3.7 versus 1.7 ng/mL, respectively). While no significant association was found between 14-3-3η levels with disease activity or other laboratory assessments, both serum and SF 14-3-3η levels positively correlated with radiographic damage at baseline (SHS; p < .001). SF, but not serum, 14-3-3η levels correlated with absolute progression (p < .03).Conclusion: 14-3-3η levels are significantly higher in RA SF than in serum in an established RA cohort. Serum and SF 14-3-3η levels correlate with radiographic damage at baseline and at 2-years follow-up. This study further substantiates the utility of 14-3-3η as a biomarker for mechanistic joint damage in established RA.
33212462 Influence of Biological Therapeutics on Patient-Reported Quality-Of-Life Outcomes (Whoqol- 2020 Nov BACKGROUND: Rheumatoid arthritis (RA) is a chronic and disabling disease with a great impact on the quality of life (QOL). The aim of this study was to assess QOL and health in RA patients treated with biological disease-modifying drugs (bDMARDs) as opposed to those treated with conventional synthetic DMARDs (csDMARDs). We analysed four domains of QOL: physical health (D1), mental health (D2), social relationships (D3) and one's surroundings (D4); as well as general quality of life (W1), general state of health (W2), and disease activity and physical disability. SUBJECTS AND METHODS: Seventy-seven RA patients (group A=29 on bDMARDs, group B=48 on csDMARDs) were enrolled in the study. QOL was evaluated using WHO questionnaire (WHOQOL-BREF), disease activity using Disease Activity Score 28C-reactive protein (DAS28CRP) and functional status using Health Assessment Questionnaire (HAQ). RESULTS: There was no statistically significant difference of mean values in the four domains of QOL, nor in the general QOL, between groups A and B. There was also no statistically significant difference regarding RA activity (3.51 vrs 3.54, p=0.56). However, we have found that the variable of the general state of health domain was statistically significantly higher in group B (2.66 vrs 2.89, p=0.001), while HAQ was statistically significantly higher in group A (1.19 vrs 1.07, p=0.018), as well as the duration of RA (6.25vrs 3.75 years, p=0.0006). Statistically significant correlation was found between HAQ and W2, disease duration and D3 in group A and DAS28CRP and D1, D2, W2 and HAQ and D1 and D2 in group B. CONCLUSION: These findings suggest that the inclusion of bDMARDs in the treatment regimen was overdue, with RA already advancing with developed functional disability, which prevented the achievement of the primary goals of treatment: low disease activity or remission and the improvement of patient's QOL.
32338754 Assessment of Expected Out-of-Pocket Spending for Rheumatoid Arthritis Biologics Among Pat 2020 Apr 1 IMPORTANCE: The closure of the Medicare Part D coverage gap from 2010 to 2019 was intended to help decrease out-of-pocket costs for beneficiaries, especially those taking high-cost drugs. However, yearly increases in list prices and the introduction of newer and more expensive drugs may have limited savings for beneficiaries. OBJECTIVE: To assess the association of closure in the Medicare Part D coverage gap with projected annual out-of-pocket costs from 2010 through 2019 for rheumatoid arthritis (RA) biologics. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis used data from the Medicare Formulary and Pricing Files for the first quarter (January 1 to March 31) in each calendar year from 2010 to 2019 for 17 RA biologic drug and strength combinations. EXPOSURES: Medicare Part D plan design and drug price by year. MAIN OUTCOMES AND MEASURES: Expected annual out-of-pocket costs for 1 year of treatment. RESULTS: Among the 17 drug and strength combinations assessed, list prices increased each year for every product, with a mean increase of 160% for the 6 drugs available during the entire study period. For the 6 products available during the entire study period, projected mean (SD) annual out-of-pocket costs were 34% (2%) lower in 2011 than in 2010 ($6108 in 2010 to $4026 in 2011) but only 21% (8%) lower in 2019 ($4801) because of yearly increases in list price. All 4 products with higher out-of-pocket costs in 2019 than in the first year available entered the market between 2011 and 2015. For all products studied, the percentage of money spent in the catastrophic phase increased each year and was a mean (SD) of 22% (14%) higher in 2019 than in 2010 or the year first available. CONCLUSIONS AND RELEVANCE: Although beneficiaries experienced large reductions in out-of-pocket spending from 2010 to 2011, more than half of those savings were lost by 2019 because of annual increases in list prices, even as the coverage gap continued to close in subsequent years.
32478474 Tofacitinib in the treatment of Indian patients with rheumatoid arthritis: A post hoc anal 2020 Jul OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized tofacitinib efficacy/safety in Indian vs rest of the world (ROW; excluding India) RA patients. METHODS: Efficacy data were pooled for disease-modified antirheumatic drug (DMARD) inadequate responders from Phase (P)3 studies. For Indian patients, ORAL Solo and ORAL Scan; ROW (excluding India), these studies plus ORAL Step, ORAL Sync, and ORAL Standard. Safety data also included ORAL Start (P3; methotrexate-naïve) and ORAL Sequel (long-term extension [LTE] study; data cut-off March 2017) for Indian patients, and these studies plus A3921041 (LTE study; Japanese study) for ROW. Efficacy outcomes at months 3/6: American College of Rheumatology (ACR)20/50/70; Disease Activity Score in 28 joints, erythrocyte sedimentation rate remission/low disease activity; change from baseline in Health Assessment Questionnaire-Disability Index. Incidence rates (IRs; patients with events/100 patient-years) for adverse events of special interest (AESIs) were assessed throughout. Descriptive data underwent no formal comparison. RESULTS: One-hundred-and-ninety-seven Indian and 3879 ROW patients were included. Compared with ROW patients, Indian patients were younger, had lower body mass index, shorter RA duration, and higher baseline disease activity; most Indian patients were non-smokers and all were biologic DMARD (bDMARD)-naïve. Month 3 ACR20 rates with tofacitinib 5 mg twice daily/10 mg twice daily/placebo were 67.4%/82.1%/40.9% (India) and 59.0%/66.1%/28.2% (ROW), and month 6 rates were 76.2%/92.1%/88.9% (India) and 69.0%/74.2%/66.5% (ROW). Month 3/6 improvements in other outcomes were generally numerically greater with tofacitinib vs placebo, and similar in both populations. Compared with ROW, Indian patients had numerically fewer AEs/serious AEs, and similar IRs for discontinuations due to AEs and AESIs, except that tuberculosis (TB) IR was higher in Indian (IR = 1.21; 95% CI 0.49, 2.49) vs ROW patients (IR = 0.17; 95% CI 0.11, 0.25). CONCLUSIONS: Tofacitinib efficacy/safety were similar in both populations, except TB IR, which was higher in Indian patients but in line with those in bDMARD-treated RA patients from high-risk countries (IR = 0.00-2.56; TB IR >0.05 [World Health Organization]). Limitations included the small Indian population and baseline differences between populations.
31907694 Ultrasonography supplements clinical exam to improve early rheumatoid arthritis disease ac 2020 May INTRODUCTION: Compared with clinical examination (CE), ultrasonography (US) provides additional and more accurate assessment of inflammation and visualization of structural damage. To better understand the effectiveness of US in metatarsophalangeal joints (MTPJs), we compared disease activity in MTPJs 2-5 assessed by CE and US, with magnetic resonance imaging (MRI) as reference standard. METHOD: Treatment-naïve adult patients with early RA (ACR criteria, disease duration < 2 years) were consecutively recruited. MTPJs 2-5 were assessed for swelling and tenderness, and imaged by US (Esaote MyLab70). The most symptomatic foot was imaged by peripheral MRI (1.0 Tesla). US was semiquantitatively graded for synovial thickening (ST) and power Doppler (PD) (0-3), and erosions (yes/no). MRI was semiquantitatively graded for bone marrow edema (BME), synovitis, and erosions (OMERACT). Kappa agreement, sensitivity, specificity, and predictive values were analyzed using cut-offs at ST ≥ 2, PD ≥ 1, and MRI synovitis and BME at both ≥ 1 and ≥ 2. RESULTS: This study included 39 patients (85% female, mean (SD) age = 51.6 (10.3)). Using MRI synovitis and BME grade ≥ 2 as the reference, PD had superior sensitivity (82%) and kappa agreement (k = 0.43) than swollen joint count (55%, k = 0.20), but similar high specificity (88%, 83%). ST and PD were often observed in clinically asymptomatic MTPJs. US detected very few MRI erosions, but several observed erosions corresponded to grade ≥ 2 MRI erosions. CONCLUSION: Clinical swelling and PD are highly specific for active inflammation in the MTPJs. US supplemented CE by allowing observation of subclinical inflammation and structural damage. Key Points • Ultrasonography detected many subclinical synovial inflammations in metatarsophalangeal joints (MTPJs), many confirmed by MRI • Ultrasonography may best be used clinically to supplement clinical examination by assessing non-swollen joints • Ultrasonography provided quick method of visualizing bone erosions that were grade ≥ 2 on MRI.
33322978 Serum progranulin level is associated with disease activity following orthopedic surgery i 2020 Dec BACKGROUND: Few studies have focused on the ability of progranulin to predict postoperative disease activity in rheumatoid arthritis (RA) patients who have undergone surgery. This study evaluated serum progranulin levels in active RA patients and analyzed its relationship with postoperative disease activity. METHODS: One hundred thirty-two patients with active RA and 72 healthy subjects were included in this study. Serum progranulin was measured, and clinical data were collected. The postoperative 1-year Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) scores was evaluated as an indicator of disease activity. The predictive value of progranulin in postoperative 1-year disease activity in RA patients was also analyzed. RESULTS: Serum progranulin was significantly associated with the postoperative 1-year RA disease activity. The mean serum progranulin level in patients with a high disease activity was significantly higher than that of RA patients with low-to-moderate disease activity (54.2 ± 10.6 ng/mL vs. 46.7 ± 8.8 ng/mL). Serum progranulin was also evaluated as an independent predictive factor for postoperative 1-year RA disease activity in multivariate analysis (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.02-8.85). CONCLUSIONS: Serum progranulin levels may be a promising indicator of postoperative disease activity in RA patients who underwent orthopedic surgery.
33384392 Risk of infections and cardiovascular and venous thromboembolic events associated with JAK 2020 Dec 31 INTRODUCTION: Janus kinases (JAK) inhibitors demonstrated to be effective in the treatment of adult patients with moderate-to-severe active rheumatoid arthritis (RA) but have been associated with serious cardiovascular and serious events. Two systematic reviews and network meta-analyses will be carried aiming to compare the relative safety of the different JAK inhibitors with regard to the risk of (1) cardiovascular and thromboembolic events and (2) serious infections in patients with RA. METHODS AND ANALYSIS: PUBMED, Embase, Cochrane Controlled Register of Trials and ClinicalTrials.gov will be searched in order to identify randomised controlled trials evaluating the efficacy and safety of JAK inhibitors in patients with RA. The following events will be assessed: (1) any cardiovascular event; major adverse cardiovascular events and venous thromboembolism and (2) any infection; serious infections; herpes zoster infection and tuberculosis. Search terms will comprise RA and drugs names, including the thesaurus terms and the International Nonproprietary Names. The assessment of the methodological quality of the included studies will be performed through the RoB 2 tool: a revised Cochrane risk of bias tool for randomised trials. Network meta-analyses will be performed using STATA V.13.0. For each outcome, treatments will be ranked according to the probability of being the safest (best) alternative using the surface under the cumulative ranking curve. ETHICS AND DISSEMINATION: Ethical approval is not required as no primary data are collected. This systematic review will be disseminated through peer-reviewed publications and at conference meetings.
31787604 Pain and Self-reported Swollen Joints Are Main Drivers of Patient-reported Flares in Rheum 2020 Sep 1 OBJECTIVE: To examine prospectively self-reported flare characteristics and their longitudinal association with disease activity and patient-reported outcomes (PRO) in patients with rheumatoid arthritis (RA). METHODS: Consecutive RA patients with 28-joint count Disease Activity Score based on C-reactive protein (DAS28-CRP) < 3.2 and no swollen joints were examined at baseline, Month 6, and Month 12. Assessments included joint counts, DAS28-CRP, visual analog scale-evaluator's global assessment (EGA), and PRO. Every third month, patients completed the Flare Assessment in Rheumatoid Arthritis and RA Flare Questionnaire, and disclosed self-management strategies. Flaring and non-flaring patients were compared and longitudinal associations between self-reported flare status (yes/no) and disease activity, PRO, and treatment escalation were explored. RESULTS: Among 80 patients with RA [74% females, mean (SD) age 63 (10) yrs, disease duration 11 (7) yrs, and baseline DAS28-CRP 1.9 (0.6)], 64 (80%) reported flare at least once during 12 months. Fifty-five percent of flares lasted less than 1 week. Common self-management strategies were analgesics (50%) and restricted activities (38%). Patients who reported being in flare had consistently higher disease activity measures and PRO compared to patients without flare. In a partly adjusted model, all flare domains, patient-reported swollen and tender joint counts and disease activity measures were associated with flares. In fully adjusted analyses, present flare was independently associated with pain (OR 1.85, 95% CI 1.34-2.60), patient-reported swollen joints (OR 1.18, 95% CI 1.03-1.36), and higher EGA (OR 1.15, 95% CI 1.04-1.28). Treatment escalation was associated with present flare (p ≤ 0.001). CONCLUSION: In RA, self-reported flares were frequent, mainly managed by analgesics, substantiated by higher disease activity measures, independently associated with pain and patient-reported swollen joints, and related to treatment escalation.
32340503 Prevalence of anti-cyclic citrullinated peptide antibodies in patients with spondyloarthri 2021 Mar OBJECTIVES: Anti-cyclic citrullinated peptide (CCP) antibodies are frequently detected in the sera of patients with rheumatoid arthritis (RA). However, recent studies have revealed a potentially high prevalence rate of these antibodies in patients with other rheumatic disorders, causing confusion while diagnosing RA. Therefore, this study aimed to evaluate the positive rate of anti-CCP antibodies in other chronic arthritis diseases focusing on patients with spondyloarthritis (SpA). METHODS: A total of 109 patients who were diagnosed with SpA at Yukioka Hospital from 1993 to 2018 were included in this retrospective analysis, including patients with ankylosing spondylitis (AS); psoriatic arthritis (PsA); synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome (SAPHO); undifferentiated spondyloarthritis (uSpA); reactive arthritis (ReA); and inflammatory bowel disease-associated SpA (IBD). RESULTS: Overall, 15.3% (16/109) of patients with SpA were positive for anti-CCP antibodies, including 2.3% (1/43) in AS, 23.1% (3/13) in SAPHO, 35.0% (7/20) in PsA, 14.8% (4/27) in uSpA, 0% (0/3) in ReA, and 33.3% (1/3) in IBD. CONCLUSION: PsA patients have a significantly higher prevalence rate of positive anti-CCP antibodies among SpA patients, and the positive rates in SAPHO and uSpA were also high. These findings provide insight into the heterogeneity of SpA with relevance for RA differential diagnosis.
33348817 Antibodies Isolated from Rheumatoid Arthritis Patients against Lysine-Containing Proteus m 2020 Dec 17 Most rheumatic diseases, including rheumatoid arthritis (RA), are characterized by immune disorders that affect antibody activity. In the present study, using Dot blot and ELISA assay, we showed that patients with rheumatic disease produced significantly more antibodies against lipopolysaccharide (LPS) P. mirabilis O3 compared to healthy donors (p < 0.05), and affinity purified antibodies against LPS O3 may cross-react with collagen type I. It was demonstrated that purified of antibodies isolated from RA patients sera, reacted stronger with the collagen than healthy donors (p = 0.015), and cross-reaction was correlated with level of anti-citrullinated peptide antibodies (r = 0.7, p = 0.003). Moreover, using six different lipopolysaccharides were demonstrated the significant correlations in sera reactivity among lysine-containing lipopolysaccharides observed in patients' sera (p < 0.05). Using Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR) it was shown that unique wavenumbers of sera spectra correlate with reactivity with lipopolysaccharides allowing distinguish patients from healthy blood donors. Antibodies adsorption by synthetic antigens shows that in patients' group anti-LPS O3 antibodies can be adsorbed by both amides of galacturonic acid and lysine or threonine, which suggests less specificity of antibodies binding with non-carbohydrate LPS component. The observed correlations suggest that non-carbohydrate components of LPS may be an important epitope for less specific anti-LPS antibodies, which might lead to cross-reactions and affect disease development.
31995963 Subcalcaneal bursitis as the initial manifestation of rheumatoid arthritis: ultrasonograph 2020 Jan 28 In early rheumatoid arthritis (RA), proliferative synovitis sometimes occurs earlier in the tenosynovium or bursal synovium than in the articular synovium. Here we report two patients who presented with subcalcaneal bursitis while progressing from undifferentiated arthritis with high-titer anti-CCP antibodies (ACPA) to a diagnosis of RA. They had initially presented with palindromic transient pain in the hands and the feet. They were strongly positive for ACPA and negative for rheumatoid factor (RF) at the onset of symptoms. A few years later, they developed persistent plantar heel pain and underwent musculoskeletal ultrasonography (MSUS). MSUS revealed subcalcaneal bursitis with synovial proliferation. At that time, they became positive for RF and they were clinically diagnosed and began receiving treatment for RA. They developed overt synovitis in their wrists and fingers several months later. To the best of our knowledge, this is the first report on MSUS-detection of subcalcaneal bursitis with synovial proliferation in patients in the very early phase of RA, although there have been many reports of forefoot bursitis. These cases suggest that MSUS scanning of the plantar surface of the heel may be useful for patients with plantar heel pain who are suspected of having a very early phase of RA, because proliferative synovitis can be detected as subcalcaneal bursitis.
32083543 Improvement in matrix metalloproteinase-3 independently predicts low disease activity at 5 2020 Sep OBJECTIVES: To explore predictive factors including MMP-3 for achievement of low disease activity (LDA) at 52 weeks in bio-switch rheumatoid arthritis (RA) patients treated with abatacept, for whom obtaining a good clinical response can be difficult. METHODS: Participants were 423 consecutive patients with RA treated with abatacept who were observed for longer than 52 weeks and registered in the TBCR, a Japanese multicentre registry system. Multivariate logistic regression analysis was used to study factors that predict the achievement of LDA at 52 weeks in bio-naïve (n=234) and bio-switch (n=189) groups. RESULTS: ROC analysis revealed that MMP-3 improvement rates at 12 weeks in bio-switch patients had the highest AUC with a cut-off value of 20.0% for predicting LDA achievement at 52 weeks. Multivariate logistic regression analysis revealed that, in addition to DAS28-CRP at baseline, achieving 20% improvement in MMP-3 levels at 12 weeks was an independent predictive factor (adjusted OR: 4.277, p=0.003) in the bio-switch group, whereas DAS28 was the only predictor in the bio-naïve group. Patients who achieved 20% improvement in MMP-3 levels at 12 weeks had significantly higher achievement rates of LDA at 52 weeks compared to those who did not achieve 20% improvement in the bio-switch group (60.0 vs. 33.3%, p=0.001). CONCLUSIONS: Our findings suggest that improvement in MMP-3 levels is key to predicting the clinical efficacy of abatacept. Closer attention paid not only to major clinical indices, but also changes in MMP-3 levels, could improve our ability to optimise clinical results when treating bio-switch patients.