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ID PMID Title PublicationDate abstract
31820689 Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblastlike Synoviocytes in 2020 BACKGROUND: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. OBJECTIVE: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. METHODS: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. RESULTS: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1β secretion in RA-FLS. CONCLUSION: Melittin may be useful in preventing damage to the joints during accidental local stimulation.
32023342 Interleukin-17 in rheumatoid arthritis: Trials and tribulations. 2020 Mar 2 Interleukin-17A (IL-17A) is a pro-inflammatory cytokine with well-characterized biological effects on stromal cell activation, angiogenesis, and osteoclastogenesis. The presence of this cytokine in the inflamed joints of patients with rheumatoid arthritis (RA), together with compelling data from in vitro and experimental arthritis models demonstrating its pro-inflammatory effects, made this cytokine a strong candidate for therapeutic targeting. Clinical trials, however, have shown relatively modest success in RA as compared with other indications. Guided by recent insights in IL-17 biology, this review aims to explore possible reasons for the limited clinical efficacy of IL-17A blockade in RA, and what we can learn from these results going forward.
32171982 Novel 1H-pyrazolo[3,4-d]pyrimidin-6-amino derivatives as potent selective Janus kinase 3 ( 2020 May Selective JAK3 inhibitors have been shown to have a potential benefit in the treatment of autoimmune disorders. Here we report the identification of a series of pyrazolopyrimidine derivatives as potent JAK3 inhibitors that exploit a unique cysteine (Cys909) residue in JAK3. Most of these compounds (13k, 13n and 13 t), displayed stronger anti-JAK3 kinase activity and selectivity than tofacitinib. Furthermore, the most active inhibitor 13t (IC(50) = 0.1 nM), also exhibited favourable selectivity for JAK3 in a panel of 9 kinases which contain the same cysteine. In a series of cytokinestimulated cellular analysis, compound 13 t, could potently block the JAK3-STAT signaling pathway. Further biological studies, including cellular antiproliferative activity assays and a rat adjuvant-induced arthritis model for in vivo evaluation, also indicated its efficacy and low toxicity in the treatment of rheumatoid arthritis. The results of these experimental explorations suggested that 13t is a promising lead compound for the development of selective JAK3 inhibitor with therapeutic potential in rheumatoid arthritis.
31691828 The effect of methotrexate on tumour necrosis factor concentrations in etanercept-treated 2020 Jul 1 OBJECTIVES: Recently, we demonstrated that early low concentrations of circulating, adalimumab-bound TNF in RA patients treated with adalimumab was associated with future anti-drug antibody formation. Furthermore, low TNF was associated with less frequent baseline MTX use. This is remarkable, because of the anti-inflammatory effects of MTX and a potential inhibiting effect on cytokine production. We hypothesized an indirect effect of non-MTX use on low TNF concentrations via immunogenicity. To investigate the effect of MTX on TNF concentrations independent of anti-drug antibody formation, we measured TNF in RA patients treated with etanercept, a drug with low immunogenicity. METHODS: TNF was quantified in 186 consecutive etanercept-treated RA patients at baseline and at weeks 4, 16 and 28. The dynamics of TNF during etanercept treatment were compared with dynamics recently published for adalimumab. RESULTS: We demonstrated that TNF concentrations at week 4 did not associate with baseline MTX or remission after 28 weeks. Furthermore, median (interquartile range) TNF increased from <112 (<112-<112) pg/ml at baseline to 548 (344-688) pg/ml at week 4 and remained stable at week 16 and 28 [598 (442-756) and 568 (444-755) pg/ml, respectively]. CONCLUSION: Circulating TNF did not associate with MTX usage in etanercept-treated patients. This implies that MTX does not have a direct effect on TNF concentrations in circulation and that the association between early low TNF and non-use of MTX for adalimumab is thus most likely due to anti-drug antibody formation.
31996367 Pragmatic randomised controlled trial of very early etanercept and MTX versus MTX with del 2020 Apr OBJECTIVES: We sought to confirm in very early rheumatoid arthritis (ERA) a much greater superiority (30%) of first-line etanercept+methotrexate (ETN+MTX) over treat-to-target MTX (MTX-TT) than previously reported in ERA (14%); and explore whether ETN following initial MTX secures a comparable response to first-line ETN+MTX. METHODS: Pragmatic, open-label, randomised controlled trial of treatment-naïve ERA (≤12 months symptom), Disease Activity Score 28 joint (DAS28)-erythrocyte sedimentation rate (ESR) ≥3.2, rheumatoid factor (RF)+/-anticitrullinated peptide antibody (ACPA) positive or ultrasound power Doppler (PD) if RF and ACPA negative. Subjects were randomised 1:1 to ETN+MTX; or MTX-TT, escalated to ETN if week 24 DAS28-ESR ≥2.6 and intramuscular corticosteroid at protocolised time points. Primary endpoint of week 48 DAS28ESR remission with clinical and imaging secondary endpoints. RESULTS: We randomised 120 patients, 60 to each arm (71% female, 73% RF/84% ACPA positive, median (IQR) symptom duration 20.3 (13.1, 30.8) weeks; mean (SD) DAS28 5.1 (1.1)). Remission rates with ETN+MTX and MTX-TT, respectively, were 38% vs 33% at week 24; 52% vs 38% at week 48 (ORs 1.6, 95% CI 0.8 to 3.5, p=0.211). Greater, sustained DAS28-ESR remission observed with ETN+MTX versus MTX-TT (42% and 27%, respectively; p=0.035). PD was fully suppressed by week 48 in over 90% in each arm. Planned exploratory analysis revealed OR 2.84, 95% CI 0.8 to 9.6) of achieving remission after 24 weeks of ETN administered first line compared with administered post-MTX. CONCLUSIONS: Compared with remission rates typically reported with first-line tumour necrosis factor inhabitor+MTX versus MTX-TT, we did not demonstrate a larger effect in very ERA. Neither strategy conferred remission in the majority of patients although ultrasound confirmed local inflammation suppression. Poorer ETN response following failure of MTX-TT is also suggested. Trial registration number NCT02433184.
32159257 A randomized, double-blind, placebo-controlled clinical trial, evaluating the garlic suppl 2020 Jul AIM: Rheumatoid arthritis (RA), is a prevalent immune-inflammatory disease, which is associated with disabling pain. Oxidative stress might play a role in RA pathogenesis and outcomes. According to the antioxidant properties of garlic, the current study was performed to evaluate the garlic supplement effects on some serum levels of oxidative stress biomarkers, and quality of life in patients with rheumatoid arthritis. METHODS: Seventy women with RA participated in this randomized, double-blind, placebo-controlled, parallel-design trial. The patients were randomly divided into two groups, receiving two tablets of either 500 mg garlic or placebo daily for 8 weeks. Serum levels of total antioxidant capacity (TAC) and malondialdehyde (MDA) and quality of life were determined at baseline and end of week 8. A health assessment questionnaire (HAQ) was used to evaluate the quality of life related to health. RESULTS: Of 70 patients enrolled in the trial, 62 subjects were included in the final analysis. At the end of the study, there was a significant increase in serum levels of TAC in the garlic group as compared with the placebo group (26.58 ± 77.30 nmol of Trolox equivalent/ml vs 16.11 ± 0.92 nmol of Trolox equivalent/mL; P = .026). In addition, MDA levels were significantly decreased in the intervention group compared with the control group (-0.82 ± 1.99 nmol/mL vs 0.36 ± 2.57 nmol/mL; P = .032). Pain after activity and HAQ scores decreased in the garlic group compared with the placebo (-11.96 ± 13.43 mm vs -0.06 ± 13.41 mm; P < .001, 0.17 ± 20 vs 0.05 ± 0.15; P < .001, respectively). CONCLUSIONS: The findings suggest that garlic supplementation for 8 weeks resulted in significant improvements in oxidative stress, HAQ in women with RA.
31972347 A reliable time-series method for predicting arthritic disease outcomes: New step from reg 2020 Jun BACKGROUND AND OBJECTIVE: The interrupted time-series (ITS) concept is performed using linear regression to evaluate the impact of policy changes in public health at a specific time. Objectives of this study were to verify, with an artificial intelligence-based nonlinear approach, if the estimation of ITS data could be facilitated, in addition to providing a computationally explicit equation. METHODS: Dataset were from a study of Hawley et al. (2018) in which they evaluated the impact of UK National Institute for Health and Care Excellence (NICE) approval of tumor necrosis factor inhibitor therapies on the incidence of total hip (THR) and knee (TKR) replacement in rheumatoid arthritis patients. We used the newly developed Generalized Structure Group Method of Data Handling (GS-GMDH) model, a nonlinear method, for the prediction of THR and TKR incidence in the abovementioned population. RESULTS: In contrast to linear regression, the GS-GMDH yields for both THR and TKR prediction values that almost fitted with the measured ones. These models demonstrated a low mean absolute relative error (0.10 and 0.09 respectively) and high correlation coefficient values (0.98 and 0.78). The GS-GMDH model for THR demonstrated 6.4/1000 person years (PYs) at the mid-point of the linear regression line post-NICE, whereas at the same point linear regression is 4.12/1000 PYs, a difference of around 35%. Similarly for the TKR, the linear regression to the datasets post-NICE was 9.05/1000 PYs, which is lower by about 27% than the GS-GMDH values of 12.47/1000 PYs. Importantly, with the GS-GMDH models, there is no need to identify the change point and intervention lag time as they simulate ITS continually throughout modelling. CONCLUSIONS: The results demonstrate that in the medical field, when looking at the estimation of the impact of a new drug using ITS, a nonlinear GS-GMDH method could be used as a better alternative to regression-based methods data processing. In addition to yielding more accurate predictions and requiring less time-consuming experimental measurements, this nonlinear method addresses, for the first time, one of the most challenging tasks in ITS modelling, i.e. avoiding the need to identify the change point and intervention lag time.
32985609 Re-evaluation of serum leptin and adiponectin concentrations normalized by body fat mass i 2020 Sep 28 Leptin and adiponectin are produced mainly in adipocytes and classified as adipocytokines because of their possible involvement in inflammation and immunity. The aim of this study was to elucidate the relationships of these adipocytokines with the disease activities of RA. We examined leptin and adiponectin concentrations and inflammatory markers such as metalloproteinase-3 (MMP-3) in 136 patients with rheumatoid arthritis (RA) (26 males and 110 females, 69.6 ± 9.3 years) and 78 controls (36 males and 42 females, 66.7 ± 15.0 years). Serum leptin and adiponectin concentrations correlated positively (r = 0.565, P < 0.001) and negatively (r = -0.331, P < 0.001) to the amount of body fat, respectively. Serum leptin and adiponectin concentrations normalized by body fat mass were significantly higher in RA than those in controls [leptin, 1.24 (median) ng/mL/kg fat in RA vs. 0.76 ng/mL/kg fat in controls; adiponectin, 0.74 μg/mL/kg fat in RA vs. 0.44 μg/mL/kg fat in controls]. Normalized adiponectin concentrations correlated positively not only to the degree of bone destruction in Steinbrocker classification but also to serum MMP-3 concentrations. Normalized leptin concentrations did not correlate to the degree of bone destruction. We conclude that adiponectin but not leptin may be involved in joint damage in RA.
33290445 TMJ Pain and Crepitus Occur Early Whereas Dysfunction Develops Over Time in Rheumatoid Art 2020 Fall AIMS: To investigate inflammatory mediator levels in TMJ synovial fluid (SF) and blood and to investigate clinical TMJ symptoms in relation to general and TMJ symptom duration in patients with rheumatoid arthritis (RA). METHODS: Examination of 80 TMJs (68 patients; median age 55 years; 85% women) included the following variables: TMJ pain at rest, maximum mouth opening, and palpation; jaw movement capacity; number of painful movements; crepitus; and degree of anterior open bite. Levels of tumor necrosis factor (TNF), TNF soluble receptor II, interleukin 1β, IL-1 receptor antagonist, IL-1 soluble receptor II, and serotonin in TMJ SF and blood; systemic disease activity; and duration of general and TMJ symptoms were assessed. General symptom duration ≤ 2 years was considered early RA. RESULTS: TMJ symptoms predominantly developed within 5 years following general symptom onset. Logistic regression analysis showed that number of involved joints, general pain, maximum mouth opening, anterior open bite, and TNF plasma levels combined explained 46% of the distinction between early and established RA. Furthermore, TMJ pain at rest and maximum mouth opening, contralateral laterotrusion, painful movements, crepitus, and SF TNF levels combined explained 35% of the distinction. In these analyses, higher general pain and maximum mouth opening, TMJ pain on maximum mouth opening, and crepitus were associated with early RA. CONCLUSION: This study indicates that TMJ pain and crepitus in RA usually occur within 2 years following general symptom onset. Pain-related dysfunction and structural changes develop with time. TNF in plasma and TMJ SF are associated with this development. This makes early (clinical) recognition of pain and inflammation important, enabling early treatment to minimize later irreversible damage.
32001864 Prevalence of Periodontitis among Rheumatoid Arthritis Patients Attending Tertiary Hospita 2020 Jan 21 BACKGROUND: Rheumatoid arthritis and Periodontitis both are chronic destructive inflammatory disorders characterized by dysregulation of the host inflammatory response and increase in localized and systemically circulating pro-inflammatory cytokines. The objective of this study was to determine prevalence of periodontitis among Rheumatoid Arthritis patients in our setup. METHODS: A crossectional study was done in 43 cases of diagnosed Rheumatoid Arthritis patients visiting to department of Orthopedics of Bir Hospital during the period of July 2016 to January 2017 were examined for presence of periodontitis and its severity. A descriptive questionnaire was also prepared concerning age, sex, personal history. Parameters to be measured were Plaque Index, Gingival Index, Pocket Depth and Clinical Attachment Level. RESULTS: Prevalence of periodontitis among Rheumatoid Arthritis patients was found to be 86.04% (37) with Mild periodontitis in 9%(4), Moderate periodontitis 56% (24)and severe periodontitis in 21% (9). The commonest age group was 50.41±9. with male to female ratio of 1:3 Conclusions: Periodontitis was common in Rheumatoid Arthritis in our set up. Moderate periodontitis was more frequent. Periodic oral examination of patients with Rheumatoid Arthritis is required to improve periodontal health.
32088801 Treatment strategies are more important than drugs in the management of rheumatoid arthrit 2020 Apr The treatment of inflammatory arthritides has been changed dramatically in the past two decades with the introduction of the biological (b) disease-modifying anti-rheumatic drugs (DMARDs) as well as the targeting synthetic (ts) DMARDs that can be used as monotherapy or in combination with conventional synthetic (cs) DMARDs. The concept of treat to target (T2T) and tight control monitoring of disease activity represents a therapeutic paradigm of modern rheumatology. In rheumatoid arthritis (RA), this treatment approach has proven to be effective in many clinical trials and is now a well-established approach. The most common treatment strategies rely on the combination of csDMARDs (mainly methotrexate, sulfasalazine and hydroxychloroquine). This comes from different studies which compare the outcomes of combination therapies versus csDMARD monotherapy or versus methotrexate plus biologics in early RA patients. Here, we review the literature of the most important T2T studies for RA patients. The results showed that a tight control strategy appears to be more important than a specific drug to control RA. T2T approach aiming for remission or low disease activity can be achieved in early RA patients using less expensive drugs in comparison to newer drugs and this may need to be recognised in the future recommendations for the management of RA. KEY POINTS: • Tight-control and treat-to-target (T2T) strategies are the cornerstone in achieving remission or low disease activity in rheumatoid arthritis (RA) • A plethora of clinical trials has confirmed the efficacy of csDMARDs when the tight-control and T2T strategies are applied • T2T and tight-control strategies are a less expensive option in comparison to newer drugs and may be recognised in the future recommendations for the management of RA. • Treatment decisions and strategies are more important than just the drugs.
33210383 Acute actinomycotic brain abscess in a patient with rheumatoid arthritis. 2020 Dec An autopsy case of acute actinomycotic brain abscess involving a patient with rheumatoid arthritis (RA) is reported. The patient was a 72-year-old man with a seven-year history of RA and pulmonary complications, who acutely developed dysarthria and dysphagia three days before death. Autopsy revealed a fresh, non-encapsulated abscess in the "late cerebritis" stage, measuring 2 cm in diameter, in the white matter of the right parietal lobe. A small number of tiny "sulfur granules" consisting of numerous filamentous bacilli were found within the abscess. The abscess had ruptured to the lateral ventricle and elicited ventriculitis, and mild acute purulent leptomeningitis was also observed. The lung showed chronic interstitial pneumonia/pulmonary fibrosis with bronchiectasis and emphysema, and large sulfur granules were found in the lumens of a few bronchi. Less than 5% of patients with actinomycotic infection develop central nervous system lesions, and actinomycotic brain abscesses make up only 0.6% of all brain abscesses. Actinomycotic brain abscesses usually pursue a protracted clinical course, and well-formed pyogenic membranes are commonly observed. The present case is exceptional in that the very early stage of the cerebral abscess formation was pathologically captured.
33361714 IL-23/IL-17 axis in the pathogenesis and treatment of systemic lupus erythematosus and rhe 2020 Dec Interleukin-23 (IL-23) and IL-17 are the gatekeepers of CD4+ T helper 17 (Th17) cells where IL-23 is required for the development and expansion of Th17 cells that subsequently produce IL-17 to promote inflammation. Owing to such pro-inflammatory properties, the IL-23/IL-17 axis has emerged as an important mechanism in the pathogenesis of autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In recent years, therapeutic antibodies targeting IL-23 (e.g. ustekinumab, tildrakizumab, guselkumab) or IL-17 (e.g. brodalumab, secukinumab, ixekizumab) have been approved for the treatment of various autoimmune diseases. In this review, we describe the pathogenic mechanisms of IL-23/IL-17 axis in SLE and RA, as well as summarising the findings from phase II and III clinical trials of anti-IL-23/IL-17 therapeutic antibodies in SLE and RA patients. In particular, phase II study has demonstrated that the anti-IL-23 antibody (ustekinumab) confers enhanced treatment outcomes in SLE patients, while anti-IL-17 antibodies (secukinumab and ixekizumab) have shown improved clinical benefits for RA patients in phase II/III studies. Our review highlights the emerging importance of targeting the IL-23/IL-17 axis in SLE and RA patients.
33196874 Occupational mimics of rheumatoid arthritis: hair dye-induced arthritis. 2021 Apr Hair dye (HD) and its component para-phenylenediamine (PPD) are commonly used to enhance beauty and youth. HD is associated with allergic contact reactions and the development of autoimmune phenomena. A 28-year-old woman presented to us complaining of pain and swelling affecting the small joints of the hands bilaterally lasting for 7 weeks. Laboratory evaluation was remarkable only for an increase of acute-phase reactants, while the rest of laboratory tests including serological tests for viruses, as well as immunological tests were negative or within normal limits. She noticed a close correlation between the onset of symmetrical polyarthritis and the use of HD product. Thus, after excluding other possibilities of inflammatory arthritides, the diagnosis of HD-induced arthritis was made. The patient was treated with naproxen, and after 3 weeks, she had a complete clinical response with decrease of acute-phase reactants. Thus, we review and discuss the relevant literature of cases related with the use of HD and arthritis development. This is the first described case of HD-induced arthritis. Physicians must be aware and recognize these symptoms and signs of patients exposed to HD and treat them appropriately.
33385865 Health-related quality of life in early psoriatic arthritis compared with early rheumatoid 2021 Feb OBJECTIVE: Both psoriatic arthritis (PsA) and rheumatoid arthritis (RA) have a significant impact on quality of life, but few reports have compared the two diseases. The current study assessed health-related quality of life (HRQoL) in PsA at diagnosis and after five years compared with early rheumatoid arthritis (RA) and a matched general population. METHODS: Patients with early PsA and early RA included in two Swedish registries with HRQoL data measured by the Medical Outcomes Study Short Form 36 (SF-36) at baseline and at five years follow-up were included. Differences in SF-36 scores compared with the general population were calculated for each patient. Physical function, disease activity, the delay before diagnosis, pain, and general wellbeing were used as explanatory variables. Statistical tests included t-tests and univariate and multivariate linear regression. RESULTS: PsA (n = 166) and RA (n = 133) patients of both sexes had significantly reduced HRQoL at disease onset. After five years, PsA patients still had impairments in several domains of SF-36, whereas RA patients had an almost normalized HRQoL. The time from symptom onset to diagnosis, disease activity, and disability independently contributed to the reduced improvement in PsA. CONCLUSION: Both early PsA and RA are characterized by severely reduced HRQoL. Despite more severe disease at inclusion, normalization of HRQoL is seen in patients with RA but not PsA. This may be due to delay in the diagnosis of PsA or more powerful interventions in RA. Earlier detection, lifestyle intervention, and more aggressive management strategies may be needed for PsA.
31140401 Prevalence of calcium pyrophosphate deposition disease in a cohort of patients diagnosed w 2020 Jan OBJECTIVES: We aimed to characterise the clinical and radiographical phenotype of calcium pyrophosphate dihydrate deposition (CPPD) disease in patients initially diagnosed with seronegative RA, and to increase the awareness that CPPD disease can be falsely diagnosed as seronegative rheumatoid arthritis (RA). METHODS: Altogether 435 early seronegative RA patients were clinically diagnosed in a single rheumatology centre and scheduled for a 10-year follow-up. All clinical data were collected and reviewed. CPPD-related arthritis was suspected if a patient had typical radiographical findings and suitable clinical pattern of CPPD or calcium pyrophosphate crystals were found in the synovial fluid. These patients are the subjects of this study. RESULTS: Among 435 seronegative RA patients, 17 patients (3.9%) (baseline mean age 71.2 years, 82% women) with CPPD disease were identified. CPPD resembling clinical patterns in these patients were: chronic CPP crystal inflammatory arthritis (9 patients), acute CPP crystal arthritis (6 patients) and OA with CPPD (2 patients). All had typical radiographical findings of CPPD: Chondrocalcinosis (CC) of triangular fibrocartilage (17 patients [100%]), CC of knee (9 patients [53%]), CC or narrowing of metacarpophalangeal joints (7 patients [41.2%]), CC of metatarsophalangeal joints (4 patients [23.5%]), CC of symphysis pubis (1 patient [5.8%]), CC of glenohumeral joint (1 patient [5.8%]) and scapholunate advanced collapse (5 patients [29.4%]). None of these patients developed typical RA-like erosions. CONCLUSIONS: CPPD disease can mimic seronegative RA at baseline and is important in the differential diagnosis of seronegative arthritis at baseline and during follow-up. The prevalence of CPPD patients in our early seronegative RA patients was 3.9%, the percentage was 7.0% among patients ≥60 years at baseline.
32079570 Differences in the serum metabolome and lipidome identify potential biomarkers for seroneg 2020 Apr OBJECTIVES: The differential diagnosis of seronegative rheumatoid arthritis (negRA) and psoriasis arthritis (PsA) is often difficult due to the similarity of symptoms and the unavailability of reliable clinical markers. Since chronic inflammation induces major changes in the serum metabolome and lipidome, we tested whether differences in serum metabolites and lipids could aid in improving the differential diagnosis of these diseases. METHODS: Sera from negRA and PsA patients with established diagnosis were collected to build a biomarker-discovery cohort and a blinded validation cohort. Samples were analysed by proton nuclear magnetic resonance. Metabolite concentrations were calculated from the spectra and used to select the variables to build a multivariate diagnostic model. RESULTS: Univariate analysis demonstrated differences in serological concentrations of amino acids: alanine, threonine, leucine, phenylalanine and valine; organic compounds: acetate, creatine, lactate and choline; and lipid ratios L3/L1, L5/L1 and L6/L1, but yielded area under the curve (AUC) values lower than 70%, indicating poor specificity and sensitivity. A multivariate diagnostic model that included age, gender, the concentrations of alanine, succinate and creatine phosphate and the lipid ratios L2/L1, L5/L1 and L6/L1 improved the sensitivity and specificity of the diagnosis with an AUC of 84.5%. Using this biomarker model, 71% of patients from a blinded validation cohort were correctly classified. CONCLUSIONS: PsA and negRA have distinct serum metabolomic and lipidomic signatures that can be used as biomarkers to discriminate between them. After validation in larger multiethnic cohorts this diagnostic model may become a valuable tool for a definite diagnosis of negRA or PsA patients.
31768668 Assessment of adherence to disease-modifying anti-rheumatic drugs in rheumatoid arthritis. 2020 Jan OBJECTIVES: This work aimed to assess treatment adherence in rheumatoid arthritis patients with several tools and to identify factors associated with poor adherence. METHOD: Between February and December 2015, 183 patients were included in this cross-sectional study. A homemade 23-item self-questionnaire was filled by patients during an outpatient consultation or a day hospitalization stay. Morisky Medication Adherence Scale (MMAS)-4, MMAS-8 and Girerd scores were extracted from this homemade questionnaire. Medication possession ratio (MPR) was then calculated. For identification of factors associated with nonadherence, patients were divided in two groups according to MMAS-8 results differentiating patients with good or bad adherence to treatments. RESULTS: Of the 183 patients, 59% received a combination of biologic and conventional synthetic disease-modifying drugs, 22% a biological treatment alone, and 19% a conventional DMARD alone. Respectively, 3%, 10%, and 7% were considered as low adherent according to MMAS-4, MMAS-8, and Girerd scores. MPR was calculated for 84/183 patients; 23% were low adherent. The need for a help in preparing the drugs (p = 0.05; OR = 6.12; 95% CI: 0.86 to 268.90) and concomitant diabetes (p < 0.001; OR = 0.045, 95% CI: 0.001 to 0.299) was higher in patients with good adherence. Presence of a patient's relative reminding to take medications was associated with low adherence (p = 0.002; OR = 4.32, 95% CI: 1.41 to 13.11). CONCLUSIONS: This study highlighted the difficulty of assessing treatment adherence in rheumatoid arthritis patients despite four different tools. Objective measures by MPR indicated a higher proportion of poor adherent patients than self-questionnaires.Key Points• Proportion of patients considered as low adherent ranged from 3 to 27% according to the method of evaluation.• The use of a pillbox and/or the preparation of drugs by a patient's relative was associated with good adherence.• The presence of a patient's relative reminding to take medication was associated with low adherence.
31672633 Correlation between albumin to fibrinogen ratio, C-reactive protein to albumin ratio and T 2020 Jan BACKGROUND: The albumin to fibrinogen ratio (AFR) and the C-reactive protein to albumin ratio (CAR) have been served as inflammatory markers. However, their roles in RA remain unclear. We investigated the association of AFR/CAR with the concentration of autoantibodies and Th17 cells in RA. METHODS: A total of 196 RA patients, 200 patients with systemic lupus erythematosus (SLE), and 200 healthy donors (HD) who were admitted to the First Affiliated Hospital of Fujian Medical University were enrolled. The results of FIB, ALB, CRP, anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF) and erythrocyte sedimentation rate (ESR) from RA patients and SLE patients were retrospectively analyzed. The percentage of Th17 cells in peripheral blood of RA patients was detected by flow cytometry, and the relative expression of TNF-α, IL-6 and IL-17A was detected by RT-qPCR. Correlation analysis of AFR/CAR and Th17 cells, CRP, ESR, TNF-α, IL-6 and IL-17A in RA was conducted. RESULTS: Compared with SLE patients and healthy donors (HD), AFR concentration was significantly lower (P < 0.01) in RA patients, while CAR concentration was significantly increased (P < 0.01) in RA patients. AFR showed negative correlation with CRP (r = -0.7103), ESR (r = -0.6542), RF (-0.2219), Th17 cells (r = -0.5952) and IL-17A (r = -0.4681). CAR was positively correlated with CRP (r = 0.9899), ESR (r = 0.605), RF (0.1867), Th17 cells (r = 0.6818), TNF-α (r = 0.3388), and IL-17A (r = 0.2046). CONCLUSIONS: The concentration of AFR in RA patients was reduced, while CAR concentration was increased. AFR and CAR are associated with CRP, ESR, RF, and Th17 cell ratios in RA patients, which can be used as potential indicators for determining RA inflammation.
32732353 Identifying the preferable rheumatoid arthritis subgroups for intervention with the anti-R 2020 Jul OBJECTIVES: To clarify which rheumatoid arthritis (RA) patients benefit most from the anti-receptor activator of nuclear factor-κB ligand antibody denosumab to reduce the progression of joint destruction. METHODS: We pooled patient data from the 12-month, double-blind, placebo-controlled DRIVE (phase II) and DESIRABLE (phase III) studies. In DRIVE, concomitant treatment was limited to methotrexate, salazosulfapyridine and bucillamine. In DESIRABLE, patients could receive any disease-modifying antirheumatic drug. RA patients were randomised to denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or placebo. Efficacy was assessed by van der Heijde-modified total Sharp score (mTSS), bone erosion score (ES) and joint space narrowing score (JSNS). Change in mTSS was assessed in subgroups stratified by risk factors for radiographic damage if the interaction factor was significant. RESULTS: The pooled analysis included 909 patients. Denosumab reduced worsening of mTSS (mean (SD)) at 12 months in the Q6M (0.88 (3.30), p=0.0024) and Q3M (0.66 (2.16), p=0.0002) groups versus placebo (1.50 (3.73)). This reduction in mTSS progression was due to the change in ES (Q6M, 0.44 (1.89), p=0.0006; Q3M, 0.20 (0.86), p<0.0001) versus placebo (0.98 (2.54)); no effect was observed on JSNS. Anti-cyclic citrullinated peptide (CCP) antibodies, glucocorticoid use and baseline ES showed a significant interaction. Denosumab was particularly effective in patients who were anti-CCP antibody positive (p<0.05). Changes in mTSS versus placebo were observed in all denosumab dose groups, regardless of glucocorticoid use and baseline ES. CONCLUSIONS: Denosumab broadly reduced the progression of joint destruction in RA patients with risk factors for radiographic damage such as especially anti-CCP antibody positivity.