Clinical Diagnosis Of Rheumatoid Arthritis Research Articles

Virtual Reality Meditation for Fatigue in Persons With Rheumatoid Arthritis: Mixed Methods Pilot Study.

Effective symptom management is crucial to enhancing the quality of life for individuals with chronic diseases. Health care has changed markedly over the past decade as immersive, stand-alone, and wearable technologies including virtual reality have become available. One chronic pain population that could benefit from such an intervention is individuals with rheumatoid arthritis (RA). Recent pharmacologic advances in the management of RA have led to a decrease in inflammatory symptoms (eg, chronic pain) or even disease remission, yet up to 70% of patients with RA still suffer from fatigue. While VR-delivered behavior, meditation, and biofeedback programs show promise for pain and anxiety management, there is little information on the use of virtual reality meditation (VRM) for fatigue management among individuals with RA. This study aims to (1) examine the feasibility of implementing a study protocol that uses VRM, (2) determine the acceptability of using VRM for fatigue management in an outpatient population, and (3) identify barriers and contextual factors that might impact VRM use for fatigue management in outpatients with RA. We used a convergent, mixed methods design and enrolled adults aged 18 years or older with a clinical diagnosis of RA. Patient-Reported Outcome Measure Information System (PROMIS) measures of fatigue, depression, anxiety, pain behavior, and physical function were assessed alongside the brief mood introspection scale at baseline and weekly for 4 weeks. VRM use across the 4-week study period was automatically stored on headsets and later extracted for analysis. Semistructured interview questions focused on feedback regarding the participant's experience with RA, previous experience of fatigue, strategies participants use for fatigue management, and the participant's experience using VRM and recommendations for future use. A total of 13 participants completed this study. Most participants completed all study surveys and measures (11/13, 84% and 13/13, 100%, respectively) and were active participants in interviews at the beginning and end of the program. Participants used VRM an average of 8.9 (SD 8.5) times over the course of the 4-week program. Most participants enjoyed VRM, found it relaxing, or recommended its use (12/13, 92%), but 8 (62%) noted barriers and conceptual factors that impacted VRM use. On average, participants saw decreases in PROMIS fatigue (-6.4, SD 5.1), depression (-5.6, SD 5.7), anxiety (-4.5, SD 6), and pain behavior (-3.9, SD 5.3), and improvements in PROMIS physical function (1.5, SD 2.7) and Brief Mood Introspection Scale mood (5.3, SD 6.7) over the course of this 4-week study. While this study's implementation was feasible, VRM's acceptability as an adjunctive modality for symptom management in RA is contingent on effectively overcoming barriers to use and thoughtfully addressing the contextual factors of those with RA to ensure successful intervention deployment. ClinicalTrials.gov NCT04804462; https://classic.clinicaltrials.gov/ct2/show/NCT04804462.

Recent advances in nano-targeting drug delivery systems for rheumatoid arthritis treatment

Rheumatoid arthritis is a systemic inflammatory disease that can lead to articular cartilage destruction and periarticular bone erosion, thus ultimately compromising joint integrity and function. Anti-inflammatory drugs and biological agents are commonly used to treat rheumatoid arthritis, but they cannot selectively target inflamed joints, because of their systemic mechanisms, short half-lives and low bioavailability. Consequently, these agents must be used at high doses and delivered frequently, thereby increasing costs and the risk of adverse effects. Drug delivery systems, such as nanoparticles, liposomes and micelles, can significantly prolong drug half-life in the body and enable targeted delivery into the joints. In this review, we comprehensively describe the pathogenesis and clinical diagnosis of rheumatoid arthritis, and summarize recent advances in targeted therapeutic strategies, particularly nano-targeting systems for rheumatoid arthritis.

Оценка фармакотерапии ревматоидного артрита у пожилых в реальной клинической практике на юге Кыргызстана

Research relevance: actual practice of pharmacotherapy in elderly patients does not always meet standards of treatment and recommendations, and currently there are no publicly available works on the age-related characteristics of the rheumatoid arthritis pharmacotherapy which complicates analysis and interpretation of the obtained results. Research objectives: to conduct a pharmacoepidemiological analysis in order to assess the actual use of drugs in elderly patients with rheumatoid arthritis and to identify their irrational use and increase the effectiveness of pharmacotherapy. Research methods and materials: case histories of 119 elderly patients treated from 2015 to 2018 with a clinical diagnosis of rheumatoid arthritis in the Department of Rheumatology of the Osh Interregional Clinical Hospital of Kyrgyzstan were analyzed. Research results: the individual characteristics of elderly patients, comorbidities should determine the choice of a specific treatment regimen. Conclusion: when analyzing the pharmacotherapy of rheumatoid arthritis in elderly people, insufficient use of basic anti-inflammatory drugs with proven efficacy was revealed.

AB0341 EFFICACY AND DRUG SURVIVAL AFTER MULTIPLE-SWITCHING FROM ADALIMUMAB ORIGINATOR TO THE BIOSIMILARS ABP501 AND SB5: A REAL-LIFE STUDY

BackgroundAntiTNF-α biosimilars are broadly available for the treatment of inflammatory arthritis. There are a lot of data concerning the maintenance of clinical efficacy after switching from originators to biosimilars. However, there is lack of data on the switch between biosimilars. The current evidence on the safety, efficacy, and immunogenicity of switching multiple times from a biosimilar to another biosimilar comes from a limited number of randomized-controlled trials and real world evidence studies.ObjectivesThe aim of our work was to evaluate the disease activity trend after multiple switching from ADA originator-Humira (oADA) to its biosimilars (bsADA; ABP 501 and SB5 subsequently) in a cohort of inflammatory arthritis patients.MethodsIn this real-life study, we selected patients with clinical diagnosis of rheumatoid Arthritis (RA), psoriatic Arthritis (PsA) and ankylosing spondylitis (AS). Patients had been previously treated with oADA and switched to the bsADA (first ABP 501 and then SB5). At each outpatient visit, we recorded demographic features (age, sex, and time since diagnosis) and the following disease activity measures: DAS28, DAPSA, BASDAI and the HAQ. Rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), C-reactive protein (CRP) and HLAB27 were also measured over the observational period (visits 0, 12, 24 and 36 months). The disease activity was evaluated during the year before the introduction of the bsADA, and then evaluated in the following 36 months during the first and the second bsADA treatment. We also examined whether some baseline characteristics, such as the duration of ADA treatment, concomitant therapy, comorbid disease and baseline disease activity, could influence the bsADA discontinuation.ResultsWe evaluated the 3-year drug survival and efficacy of the multiple switch of bsADA in RA, PsA and AS patients, previously treated with oADA in 127 patients (Table 1). All the patients enrolled underwent a first switch lasting one year and then a second switch with a follow up of one year too. The 1-year retention rate for ABP501 was 84.4%, 78% and 76% in AS, RA and PsA patients, respectively. The 1-year retention rate for SB5 was 82.1%, 78,7% and 77,5% in AS, RA and PsA patients, respectively. Disease activity, as measured by DAS28, DAPSA and BASDAI remained stable over the 3 years (Figure 1). Comorbid disease (HR: 3.04, p < 0.001) and HAQ at baseline (HR: 2.12, p = 0.001) significantly increased the risk of ADA discontinuation, while previous ADA duration was positively associated with bsADA retention rate (HR: 0.83, p = 0.0024). 27.4% patients left the study due to the interruption of the bsADA, 76.5% discontinued due to inefficacy and 23.5% due to adverse events.Table 1.Baseline characteristics of RA, PsA and AS patientsCharacteristicsTotal cohort N=127RA N=41PsA N=52AS N=34Female gender (%)75 (60)35 (85)31 (59)9 (26)Age (years)61.7±12.7860.5±12.6461.55±11.656.3±10.71Disease duration (years)15.86±9.4917.23±10.6413.75±6.5714.92±9.50Comorbidities, (%)17,8 (14)5,7 (14)9,8 (19)2 (6)ACPA+, n (%)-25 (63.3)--RF+, n (%)24 (62.5)HLAB27+, n (%)--8 (15)17 (50)CRP (mg/L)1.65±2.272.31±1.900.42±0.271.36±1.91DAS 28-2.65±0.75DAPSA-8.25±3.69BASDAI-3.23±1.58HAQ0.73±0.570.72±0.550.73±0.520.76±0.69Prednisone, n (%)46 (36)23 (55)20 (44)3 (13)Combo Therapy65 (51)29 (68)25 (48)11 (32)oADA duration (months)49.74±40.7556.43±41.2725.00±13.6740.08±37.78ABP501 duration (months)12.42±2.4112.77±2.3412.82±1.4912.49±2.95SB501 duration (months)11.92±1.4112.47±1.7412.72±1.4912.41±1.95ABP501 (Adalimumab biosimilar, Amgevita), SB501 (Adalimumab biosimilar, Imraldi)ConclusionNo difference was found between oADA and bsADA in terms of efficacy. This real-life study confirms the similar efficacy profile of multiple switch bsADA with long-term retention and a good safety profile in inflammatory arthritis patients.

Comparison of 99mTc-methyl diphosphonate bone scintigraphy and 68Ga-DOTANOC PET/computed tomography in articular manifestation of rheumatoid arthritis.

Tc-99m methyl diphosphonate (MDP) bone scintigraphy is used to assess disease activity in rheumatoid arthritis (RA). Somatostatin receptor (SSTR) expression in RA has been reported previously. SSTR-based PET/computed tomography (CT) may be superior to bone scintigraphy to know disease extent and in locating inflammatory joints that can be further targeted with peptide receptor radionuclide therapy thereby opening up new theranostic avenues. Based on these facts, the present study was designed to compare Tc-99m MDP bone scintigraphy and Ga-68 DOTANOC PET/CT in patients with RA. Patients with a clinical diagnosis of RA were injected with 111-185 MBq of Ga-68 DOTANOC and 740 MBq of Tc-99m MDP intravenously. Images were acquired 30-45 min postinjection for Ga-68 DOTANOC on dedicated PET/CT scanners. Triple-phase bone scans were acquired on a dual-head gamma camera. PET/CT and MDP scan images were visually assessed by two experienced nuclear medicine physicians. Nineteen patients (16 women and 3 men) with a clinical diagnosis of RA were included in the study. Clinically, 196 joints in these 19 patients were diagnosed positive for RA. Of these 196 joints, Tc-99m MDP uptake was seen in 157 joints (80%). On Ga-68 DOTANOC scan, tracer uptake was seen in 151 of 196 joints (77%) with a lesion to background ratio of at least 2 in most of the joints. Ga-68 DOTANOC is equally good as an MDP scan for detection of RA with the added advantage of being used as a theranostic modality. However, further evaluation with a larger sample size and joint-to-joint comparison is warranted.

Validation of the Simplified Disease Activity Index (SDAI) with a quick quantitative C-reactive protein assay (SDAI-Q) in patients with rheumatoid arthritis: a prospective multicenter cross-sectional study

Objectives:The Simplified Disease Activity Index (SDAI) is a recommended composite score for assessing the remission status in patients with rheumatoid arthritis (RA). However, determination of C-reactive protein (CRP) levels takes several hours and sometimes days and limits the use of the SDAI in the clinical setting. The aim of this study was to validate the SDAI using a quick quantitative C-reactive protein (qCRP) assay (as SDAI-Q) in RA patients.Design:This is a multicenter, prospective, cross-sectional pilot study in RA patients.Methods:Adult patients (⩾18 years) with a clinical diagnosis of RA were recruited between January 2020 and September 2020 from five rheumatologic centers located in Berlin, Germany. SDAI, SDAI-Q, Clinical Disease Activity Index (CDAI), and DAS28 scores comprising CRP, qCRP, or erythrocyte sedimentation rate (ESR) were calculated. The agreement of disease activity categories was analyzed using cross tabulations and weighted Cohen’s kappa. The agreement of numerical values was analyzed with Bland–Altman plots and intraclass correlation coefficients (ICCs).Results:Overall, 100 RA patients were included in the statistical analysis. The mean value of qCRP (7.89 ± 16.98 mg/l) was slightly higher than that of routine laboratory CRP (6.97 ± 15.02 mg/l). Comparing SDAI and SDAI-Q, all patients were assigned to identical disease activity categories. Agreement of disease activity categories by CDAI and SDAI/SDAI-Q was observed in 93% with a weighted Cohen’s kappa of 0.929 (95% confidence interval (CI) = 0.878; 0.981).Conclusion:The SDAI-Q showed an absolute agreement regarding the assignment of disease activity categories in comparison with the conventional SDAI. Therefore, the SDAI-Q may facilitate the application of a treat-to-target concept in clinical trials and clinical routine as a quickly available disease activity score incorporating CRP as an objective parameter.

SARS-CoV-2 outbreak in immune-mediated inflammatory diseases: the Euro-COVIMID multicentre cross-sectional study.

BackgroundThe COVID-19 pandemic has raised numerous questions among patients with immune-mediated inflammatory diseases regarding potential reciprocal effects of COVID-19 and their underlying disease, and potential effects of immunomodulatory therapy on outcomes related to COVID-19. The seroprevalence of SARS-CoV-2 and factors associated with symptomatic COVID-19 in patients with immune-mediated inflammatory diseases are still unclear. The Euro-COVIMID study aimed to determine the serological and clinical prevalence of COVID-19 among patients with immune-mediated inflammatory diseases, as well as factors associated with COVID-19 occurrence and the impact of the pandemic in its management.MethodsIn this multicentre cross-sectional study, patients aged 18 years or older with a clinical diagnosis of rheumatoid arthritis, axial spondyloarthritis, systemic lupus erythematosus, Sjögren's syndrome, or giant cell arteritis were recruited from six tertiary referral centres in France, Germany, Italy, Portugal, Spain, and the UK. Demographics, comorbidities, treatments, and recent disease flares, as well as information on COVID-19 symptoms, were collected through a questionnaire completed by participants. SARS-CoV-2 serology was systematically tested. The main outcome was the serological and clinical prevalence of COVID-19. Factors associated with symptomatic COVID-19 were assessed by multivariable logistic regression, and incidence of recent disease flares, changes in treatments for underlying disease, and the reasons for treatment changes were also assessed. This study is registered with ClinicalTrials.gov, NCT04397237.FindingsBetween June 7 and Dec 8, 2020, 3136 patients with an immune-mediated inflammatory disease answered the questionnaire. 3028 patients (median age 58 years [IQR 46–67]; 2239 [73·9%] women and 789 [26·1%] men) with symptomatic COVID-19, serological data, or both were included in analyses. SARS-CoV-2 antibodies were detected in 166 (5·5% [95% CI 4·7–6·4]) of 3018 patients who had serology tests. Symptomatic COVID-19 occurred in 122 (4·0% [95% CI 3·4–4·8]) of 3028 patients, of whom 24 (19·7%) were admitted to hospital and four (3·3%) died. Factors associated with symptomatic COVID-19 were higher concentrations of C-reactive protein (odds ratio 1·18, 95% CI 1·05–1·33; p=0·0063), and higher numbers of recent disease flares (1·27, 1·02–1·58; p=0·030), whereas use of biological therapy was associated with reduced risk (0·51, 0·32–0·82; p=0·0057). At least one disease flare occurred in 654 (21·6%) of 3028 patients. Over the study period, 519 (20·6%) of 2514 patients had treatment changes, of which 125 (24·1%) were due to the pandemic.InterpretationThis study provides key insights into the epidemiology and risk factors of COVID-19 among patients with immune-mediated inflammatory diseases. Overall, immunosuppressants do not seem to be deleterious in this scenario, and the control of inflammatory activity seems to be key when facing the pandemic.FundingPfizer, Sanofi, Amgen, Galapagos, and Lilly.

Orofacial manifestations of rheumatoid arthritis and systemic lupus erythematosus: a narrative review.

Both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are classified as autoimmune diseases, where the body's own immune response causes it to attack the host tissues, as if the latter were antigens. RA is the most common autoimmune disease that affects joints. The clinical diagnosis of RA is based on the history and examination, integrated with laboratory tests including blood tests on inflammatory markers, serology, and imaging. There are no diagnostic criteria, but there are classification criteria. SLE affects most major organ systems in the body. The diagnosis of SLE relies on the constellation of characteristic symptoms, signs, and laboratory findings in the appropriate clinical context and after excluding other reasonable diagnoses. Epidemiologically, both conditions show a definitive female predilection. The focus of this review article is epidemiology, and the major clinical features with an emphasis on the orofacial manifestations. The relevant clinical points for the dental practitioner area summarized.

Computer-aided diagnosis based on hand thermal, RGB images, and grip force using artificial intelligence as screening tool for rheumatoid arthritis in women.

Rheumatoid arthritis (RA) is an autoimmune disorder that typically affects people between 23 and 60years old causing chronic synovial inflammation, symmetrical polyarthritis, destruction of large and small joints, and chronic disability. Clinical diagnosis of RA is stablished by current ACR-EULAR criteria, and it is crucial for starting conventional therapy in order to minimize damage progression. The 2010 ACR-EULAR criteria include the presence of swollen joints, elevated levels of rheumatoid factor or anti-citrullinated protein antibodies (ACPA), elevated acute phase reactant, and duration of symptoms. In this paper, a computer-aided system for helping in the RA diagnosis, based on quantitative and easy-to-acquire variables, is presented. The participants in this study were all female, grouped into two classes: class I, patients diagnosed with RA (n = 100), and class II corresponding to controls without RA (n = 100). The novel approach is constituted by the acquisition of thermal and RGB images, recording their hand grip strength or gripping force. The weight, height, and age were also obtained from all participants. The color layout descriptors (CLD) were obtained from each image for having a compact representation. After, a wrapper forward selection method in a range of classification algorithms included in WEKA was performed. In the feature selection process, variables such as hand images, grip force, and age were found relevant, whereas weight and height did not provide important information to the classification. Our system obtains an AUC ROC curve greater than 0.94 for both thermal and RGB images using the RandomForest classifier. Thirty-eight subjects were considered for an external test in order to evaluate and validate the model implementation. In this test, an accuracy of 94.7% was obtained using RGB images; the confusion matrix revealed our system provides a correct diagnosis for all participants and failed in only two of them (5.3%). Graphical abstract.

Severely destructive unilateral wrist arthritis as a rare variant of rheumatoid arthritis: analysis of clinical and imaging features

Rheumatoid arthritis (RA) is a common autoimmune disease typically affecting joints symmetrically. A small number of patients develop unilateral and severely destructive wrist arthritis (DWA). The objective of our study was to characterise patients with this type of affection. This was a retrospective cohort study of RA patients with positive RF/anti-CCP antibodies. Clinical characteristics, including, age, gender, disease duration, dexterity, occupational history, smoking status, and the number of prescribed DMARDs were recorded. Conventional radiographs were evaluated using the modified Sharp/van der Heijde scoring (mSS) method. We analysed our laboratory database of 1247 patients and identified 559 patients with a clinical diagnosis of RA. For 395 of the patients, radiographs of the hands were available for evaluation. 25 patients had extensive unilateral DWA, corresponding to a prevalence of 6.3% (25 of 395 patients). 11 patients were excluded due to incomplete data. Of the remaining 14 patients, 13 were female with a median age of 61 (33-83) years, and median disease duration of 18 (1-33) years. 8 of 11 (72.7%) patients were smokers; in three, smoking status was not known. 80% with known dexterity developed unilateral DWA in the dominant hand. Total mSS was significantly higher on the affected side (39, interquartile range 35.25-46.25) versus non-affected (13, IQR 3-23). MSS were not different if the carpal bones were excluded from scoring. Side of involvement (left vs. right), or dominant versus non-dominant hand, did not result in a different mSS. Unilateral DWA is a rare variant of RA which predominantly affects women who smoke.

Comparative Evaluation of 68Ga-Citrate PET/CT and 18F-FDG PET/CT in the Diagnosis of Type II Collagen-Induced Arthritis in Rats.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic, symmetrical, and erosive synovitis. RA is one of the most common disabling diseases in the clinic. The main clinical intervention strategies are early diagnosis and early treatment. This study aims to predict the diagnostic value of 68Ga-citrate and 18F-FDG PET/CT in RA by comparing and analyzing the value of 68Ga-citrate and 18F-FDG PET/CT for diagnosing type II collagen-induced arthritis (CIA) in rats. Some CIA models were established. Normal rats were selected as the control group, and 23 days and 40 days were selected as the early and late time points of arthritis, respectively. The semiquantitative analysis of CIA rats was carried out with 68Ga-citrate PET/CT and 18F-FDG PET/CT, and the ratio of the maximum standardized uptake (SUVmax) values in the regions of interest (ROIs) of the hind foot ankle joint and thigh muscle was calculated and statistically analyzed. The distribution of CIA rats in vivo at the 68Ga-citrate 90 min time point was studied, and the ankle tissues were evaluated with hematoxylin and eosin (HE) staining. 68Ga-citrate PET/CT is obviously superior to 18F-FDG PET/CT for CIA imaging, and the statistical results show that the difference between the two examination methods is statistically significant (P < 0.001). The uptake of these two radiopharmaceuticals showed the same trend in arthritis rats with different scores. The distribution of 68Ga-citrate at 90 min is consistent with the trend shown by 68Ga-citrate PET/CT. 68Ga-citrate PET/CT can reflect the inflammatory activity of affected joints in CIA rats earlier and more sensitively than 18F-FDG PET/CT, and this imaging advantage continues until the later stage of inflammation. Therefore, 68Ga-citrate PET/CT is worthy of further promotion and application in the clinical diagnosis of RA.

Stress management as a patient-prioritised treatment target for rheumatoid arthritis in a New Zealand population

To investigate the lived experience of rheumatoid arthritis (RA), and identify patient-prioritised treatment targets in a New Zealand population. Eighteen participants (12 female, 6 male) with a clinical diagnosis of RA were recruited from a regional hospital, and consecutively allocated to one of

Rheumatoid arthritis reprograms circadian output pathways

ObjectiveWe applied systems biology approaches to investigate circadian rhythmicity in rheumatoid arthritis (RA).MethodsWe recruited adults (age 16–80 years old) with a clinical diagnosis of RA (active disease [DAS28 > 3.2]). Sleep profiles were determined before inpatient measurements of saliva, serum, and peripheral blood mononuclear leukocytes (PBML). Transcriptome and proteome analyses were carried out by RNA-SEQ and LC-MS/MS. Serum samples were analysed by targeted lipidomics, along with serum from mouse collagen induced-arthritis (CIA). Bioinformatic analysis identified RA-specific gene networks and rhythmic processes differing between healthy and RA.ResultsRA caused greater time-of-day variation in PBML gene expression, and ex vivo stimulation identified a time-of-day-specific RA transcriptome. We found increased phospho-STAT3 in RA patients, and some targets, including phospho-ATF2, acquired time-of-day variation in RA. Serum ceramides also gained circadian rhythmicity in RA, which was also seen in mouse experimental arthritis, resulting from gain in circadian rhythmicity of hepatic ceramide synthases.ConclusionRA drives a gain in circadian rhythmicity, both in immune cells, and systemically. The coupling of distant timing information to ceramide synthesis and joint inflammation points to a systemic re-wiring of the circadian repertoire. Circadian reprogramming in response to chronic inflammation has implications for inflammatory co-morbidities and time-of-day therapeutics.

Association of serum lipids with autoantibodies and inflammatory markers in rheumatoid arthritis patients

BackgroundWe studied the relationship between serum lipids and autoantibodies and inflammatory markers in rheumatoid arthritis (RA) patients to explore the effect of serum lipids on the diagnosis and judgment of disease activity in RA patients. MethodsSerum lipids including TCHO, TG, HDLC and LDLC and anti-CCP, RF, CRP, ESR of RA patients from May 2013 to August 2017 were retrospectively analyzed in the First Affiliated Hospital of Fujian Medical University. ResultsWith the dilution factor increased, the concentrations of serum lipids and anti-CCP, CRP and RF showed the same downward trend, indicating that the detection methods of the above indicators were reasonable and would not be affected by hyperlipidemia. CRP and ESR levels were negatively correlated with HDLC concentration in male and female RA patients. However, the concentration of anti-CCP and RF were closely related to TG. In all the RA patients and female RA patients, the RF level was negatively correlated with the TG concentration. Moreover, with the TG concentration increased, the proportion of patients with high concentrations of anti-CCP levels decreased. In addition, in male RA patients, anti-CCP and ESR concentration increased with the increase of LDLC. ConclusionThe concentrations of HDLC, TG and LDLC were associated with the concentration of anti-CCP, RF, CRP and ESR in RA patients. Therefore, clinical diagnosis of RA and determination of disease activity should consider the impact of the concentration of serum lipids in order to make a reasonable judgment on the diagnosis of the disease.

Treat to target strategy in early rheumatoid arthritis versus routine care – A comparative clinical practice study

ObjectiveTo assess the 2-year effect on disease activity and health-related quality of life (HRQoL) of implementing a clinical practice treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA). MethodsPatients in the Norwegian Very Early Arthritis Cohort 2.0 (NOR-VEAC 2.0), included 2010–2015, were treated according to T2T principles with visits at baseline, 3, 6, 9, 12 months, then every 6 months plus monthly visits until DAS28 <2.6. These patients were compared to a pre-T2T cohort of patients included in the Norwegian Disease Modifying Anti-Rheumatic Drug (NOR-DMARD) register 2006–2009. Both groups had a clinical diagnosis of RA (≤1 year) and were DMARD naïve. Disease activity and HRQoL outcomes were analysed, and the primary outcome was SDAI remission (≤3.3) at 2years. ResultsThe T2T cohort included 293 patients (mean (SD) age 54 (13) years, 66% females, disease duration median (25,75 perc) 98 (57,164) days) and the routine care cohort 392 patients (age 54 (13) years, 68% females, 4 (0,30) days since diagnosis). At 2years, the proportion of patients achieving SDAI remission was 46% in the T2T cohort compared to 31% in the routine care cohort. EQ-5D was similar at baseline, but differed significantly between groups at 2years (median (25,75 perc) 0.77 (0.69, 0.85) vs 0.73 (0.59, 0.80), p < 0.001). Methotrexate monotherapy was the dominant DMARD regimen used to achieve SDAI remission in both cohorts. ConclusionHigher remission rates and better HRQoL were achieved in patients following a T2T strategy in clinical practice compared to routine care.

Combination of anti-citrullinated protein antibodies and rheumatoid factor is associated with increased systemic inflammatory mediators and more rapid progression from preclinical to clinical rheumatoid arthritis

The development of rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPAs) can be observed years prior to clinical diagnosis of rheumatoid arthritis (RA). Nevertheless, the interaction between these two autoantibodies and their combined effect on development of RA is unclear. We measured RF, cytokines, and ACPA subtypes in serial pre-clinical serum samples collected from 83 US veterans who all developed RA. Levels of cytokines and ACPAs were compared between the following groups: anti-cyclic citrullinated peptide (anti-CCP)-/RF- (double negative), anti-CCP+/RF-, anti-CCP-/RF+, or anti-CCP+/RF+ (double-positive). The double-positive subgroup had significantly higher levels of 20 inflammatory cytokines and 29 ACPA reactivities, and the shortest interval, 1.3 years, between the preclinical sample timepoint and diagnosis of RA. Thus, the combined presence of ACPAs and RF is associated with a more rapid progression to RA, suggesting that anti-CCP+/RF+ individuals have a more advanced preclinical disease state and that the onset of RA may be imminent.

Long-term disease and patient-reported outcomes of a continuous treat-to-target approach in patients with early rheumatoid arthritis in daily clinical practice

Patients in real life may differ from those in clinical trials. The aim of this study is to report 5-year outcomes of a continuous treat-to-target (T2T) approach in patients with rheumatoid arthritis (RA) in daily clinical practice. In the Dutch RhEumatoid Arthritis Monitoring cohort, all patients with a clinical diagnosis of RA were treated according to a protocolled T2T strategy, aimed at 28-joint Disease Activity Score (DAS28) < 2.6. Outcomes were percentages of patients in distinct levels of disease activity, mean course of DAS28 and prevalence of sustained (drug-free) remission. Also, data on functional disability (Health Assessment Questionnaire) and health-related quality of life (Short-Form 36) were examined. Mean DAS28 improved from 4.93 (95% CI 4.81–5.05) at baseline to 2.49 (95% CI 2.35–2.63) after 12 months and remained stable thereafter. Percentages of patients at 12 months with DAS28 < 2.6 (remission), DAS28 ≥ 2.6 and ≤ 3.2 (low disease activity), DAS28 > 3.2 and ≤ 5.1 (moderate disease activity) and DAS28 > 5.1 (high disease activity) were 63, 16, 18 and 3%, respectively. Sustained remission (DAS28 < 2.6 during ≥ 6 months) was observed at least once in 84% of the patients and drug-free remission (DAS28 < 2.6 during ≥ 6 months after withdrawal of all disease-modifying anti-rheumatic drugs) in 36% of the patients. Functional disability and health-related quality of life significantly improved during the first 24 weeks. Continuous application of T2T in real-life RA patients leads to favourable disease- and patient-related outcomes.

Clinical value for detection of anti-carbamylated antibody in diagnosis and treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a common chronic autoimmune disease. A variety of autoantibodies appears in RA patients and the detection of autoantibodies could be used for the diagnosis and treatment for RA. Anti-citrullinated protein antibodies and rheumatoid factor has been currently used in clinical diagnosis of RA. Recently, a new widely concerned autoantibody, anti-carbamylated protein antibody, is expected to become one of the markers for early diagnosis and evaluation of disease activity and bone destruction.(Chin J Lab Med, 2018, 41: 77-80) Key words: Rheumatoid arthritis; Anti-carbamylated protein antibody; Anti-citrullinated antibody; Arthralgia

Role of erosions typical of rheumatoid arthritis in the 2010 ACR/EULAR rheumatoid arthritis classification criteria: results from a very early arthritis cohort

ObjectiveTo determine how the European League Against Rheumatism (EULAR) definition of erosive disease (erosion criterion) contributes to the number of patients classified as rheumatoid arthritis (RA) according to the 2010...

A Role for Soluble IL-6 Receptor in Osteoarthritis.

Interleukin-6 (IL-6) is one of several pro-inflammatory cytokines present at elevated levels in the synovial fluid of individuals with confirmed clinical diagnosis of rheumatoid arthritis (RA) and osteoarthritis (OA). The mechanism of action of IL-6 was shown to involve its capacity to interact with a membrane-bound IL-6 receptor (mIL-6Rα), also known as the “classical” IL-6 pathway, or through its interaction with a soluble IL-6 receptor (sIL-6R) termed the “trans-signaling” pathway. Activation of downstream signaling is transduced via these IL-6 receptors and principally involves the Janus Kinase/Signal Transduction and Activators of Transcription (JAK/STAT) signaling pathway that is further regulated by glycoprotein-130 (gp130) interacting with the IL-6/mIL-6R complex. Phosphorylation of STAT proteins via JAK activation facilitates STAT proteins to act as transcription factors in inflammation. However, the biological function(s) of the sIL-6R in human chondrocytes requires further elucidation, although we previously showed that exogenous sIL-6R significantly suppressed the synthesis of neutrophil gelatinase-associated lipocalin (NGAL) in the immortalized line of human chondrocytes, C28/I2. NGAL was shown to regulate the activity of matrix metalloproteinase-9 (MMP-9), whose activity is crucial in OA for the destruction of articular cartilage. The “shedding” of sIL-6R from the plasma membrane is carried out by a family of enzymes known as A Distintegrin and Metalloproteinase (ADAM), which are also elevated in OA. In this paper, we have systematically reviewed the role played by IL-6 in OA. We have proposed that sIL-6R may be an important target for future drug development in OA by ameliorating cartilage extracellular protein degradation.