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ID PMID Title PublicationDate abstract
32359360 PET measurement of cyclooxygenase-2 using a novel radioligand: upregulation in primate neu 2020 May 2 BACKGROUND: Cyclooxygenase-2 (COX-2), which is rapidly upregulated by inflammation, is a key enzyme catalyzing the rate-limiting step in the synthesis of several inflammatory prostanoids. Successful positron emission tomography (PET) radioligand imaging of COX-2 in vivo could be a potentially powerful tool for assessing inflammatory response in the brain and periphery. To date, however, the development of PET radioligands for COX-2 has had limited success. METHODS: The novel PET tracer [(11)C]MC1 was used to examine COX-2 expression [1] in the brains of four rhesus macaques at baseline and after injection of the inflammogen lipopolysaccharide (LPS) into the right putamen, and [2] in the joints of two human participants with rheumatoid arthritis and two healthy individuals. In the primate study, two monkeys had one LPS injection, and two monkeys had a second injection 33 and 44 days, respectively, after the first LPS injection. As a comparator, COX-1 expression was measured using [(11)C]PS13. RESULTS: COX-2 binding, expressed as the ratio of specific to nondisplaceable uptake (BP(ND)) of [(11)C]MC1, increased on day 1 post-LPS injection; no such increase in COX-1 expression, measured using [(11)C]PS13, was observed. The day after the second LPS injection, a brain lesion (~ 0.5 cm in diameter) with high COX-2 density and high BP(ND) (1.8) was observed. Postmortem brain analysis at the gene transcript or protein level confirmed in vivo PET results. An incidental finding in an unrelated monkey found a line of COX-2 positivity along an incision in skull muscle, demonstrating that [(11)C]MC1 can localize inflammation peripheral to the brain. In patients with rheumatoid arthritis, [(11)C]MC1 successfully imaged upregulated COX-2 in the arthritic hand and shoulder and apparently in the brain. Uptake was blocked by celecoxib, a COX-2 preferential inhibitor. CONCLUSIONS: Taken together, these results indicate that [(11)C]MC1 can image and quantify COX-2 upregulation in both monkey brain after LPS-induced neuroinflammation and in human peripheral tissue with inflammation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03912428. Registered April 11, 2019.
31479065 Machine-learning-based knowledge discovery in rheumatoid arthritis-related registry data t 2020 Jan Early detection of patients with chronic diseases at risk of developing persistent pain is clinically desirable for timely initiation of multimodal therapies. Quality follow-up registries may provide the necessary clinical data; however, their design is not focused on a specific research aim, which poses challenges on the data analysis strategy. Here, machine-learning was used to identify early parameters that provide information about a future development of persistent pain in rheumatoid arthritis (RA). Data of 288 patients were queried from a registry based on the Swedish Epidemiological Investigation of RA. Unsupervised data analyses identified the following 3 distinct patient subgroups: low-, median-, and high-persistent pain intensity. Next, supervised machine-learning, implemented as random forests followed by computed ABC analysis-based item categorization, was used to select predictive parameters among 21 different demographic, patient-rated, and objective clinical factors. The selected parameters were used to train machine-learned algorithms to assign patients pain-related subgroups (1000 random resamplings, 2/3 training, and 1/3 test data). Algorithms trained with 3-month data of the patient global assessment and health assessment questionnaire provided pain group assignment at a balanced accuracy of 70%. When restricting the predictors to objective clinical parameters of disease severity, swollen joint count and tender joint count acquired at 3 months provided a balanced accuracy of RA of 59%. Results indicate that machine-learning is suited to extract knowledge from data queried from pain- and disease-related registries. Early functional parameters of RA are informative for the development and degree of persistent pain.
32265899 Neuro-Immune Circuits Regulate Immune Responses in Tissues and Organ Homeostasis. 2020 The dense innervation of the gastro-intestinal tract with neuronal networks, which are in close proximity to immune cells, implies a pivotal role of neurons in modulating immune functions. Neurons have the ability to directly sense danger signals, adapt immune effector functions and integrate these signals to maintain tissue integrity and host defense strategies. The expression pattern of a large set of immune cells in the intestine characterized by receptors for neurotransmitters and neuropeptides suggest a tight neuronal hierarchical control of immune functions in order to systemically control immune reactions. Compelling evidence implies that targeting neuro-immune interactions is a promising strategy to dampen immune responses in autoimmune diseases such as inflammatory bowel diseases or rheumatoid arthritis. In fact, electric stimulation of vagal fibers has been shown to be an extremely effective treatment strategy against overwhelming immune reactions, even after exhausted conventional treatment strategies. Such findings argue that the nervous system is underestimated coordinator of immune reactions and underline the importance of neuro-immune crosstalk for body homeostasis. Herein, we review neuro-immune interactions with a special focus on disease pathogenesis throughout the gastro-intestinal tract.
32423478 Multi-HLA class II tetramer analyses of citrulline-reactive T cells and early treatment re 2020 May 18 BACKGROUND: HLA class II tetramers can be used for ex vivo enumeration and phenotypic characterisation of antigen-specific CD4+ T cells. They are increasingly applied in settings like allergy, vaccination and autoimmune diseases. Rheumatoid arthritis (RA) is a chronic autoimmune disorder for which many autoantigens have been described. RESULTS: Using multi-parameter flow cytometry, we developed a multi-HLA class II tetramer approach to simultaneously study several antigen specificities in RA patient samples. We focused on previously described citrullinated HLA-DRB1*04:01-restricted T cell epitopes from α-enolase, fibrinogen-β, vimentin as well as cartilage intermediate layer protein (CILP). First, we examined inter-assay variability and the sensitivity of the assay in peripheral blood from healthy donors (n = 7). Next, we confirmed the robustness and sensitivity in a cohort of RA patients with repeat blood draws (n = 14). We then applied our method in two different settings. We assessed lymphoid tissue from seropositive arthralgia (n = 5) and early RA patients (n = 5) and could demonstrate autoreactive T cells in individuals at risk of developing RA. Lastly, we studied peripheral blood from early RA patients (n = 10) and found that the group of patients achieving minimum disease activity (DAS28 < 2.6) at 6 months follow-up displayed a decrease in the frequency of citrulline-specific T cells. CONCLUSIONS: Our study demonstrates the development of a sensitive tetramer panel allowing simultaneous characterisation of antigen-specific T cells in ex vivo patient samples including RA 'at risk' subjects. This multi-tetramer approach can be useful for longitudinal immune-monitoring in any disease with known HLA-restriction element and several candidate antigens.
32598771 [Frequency of sarcopenia and factors associated with lean mass in women with rheumatoid ar 2020 Jun 5 AIM: To evaluate the frequency of sarcopenia (SP) according to EWGSOP2 criteria and factors associated with low lean mass in women with rheumatoid arthritis (RA). MATERIALS AND METHODS: 79 women (aged 4075 years) with RA were enrolled in the study. We analyzed clinical data: age, body mass index (BMI), disease duration, methotrexate use, glucocorticoid use, anthropometric measurements, C-reactive protein level, disease activity score in 28 joints-erythrocyte sedimentation rate, bone mineral density (BMD) of the lumbar spine, femur neck, total hip and body composition by Dual energy X-ray absorptiometry. Also, muscle strength and functional tests were performed. We analyzed the correlation between disease parameters and low lean mass with the Spearman method. RESULTS: 73 (92%) patients had low muscle strength, 20 (25%) patients had low muscle strength and low lean mass, among them 9 (11%) also had functional disability. There was no correlation between the age of patients and the presence of SP, while the duration of RA in women with SP was significantly greater (p=0.006). There were significant correlations between lean mass and body mass index, glucocorticoids used, methotrexate doses, creatinine and urea acid serum concentration, bone mineral density and falls number. CONCLUSION: According EWGSOP2 confirmed sarcopenia was found in 25% RA patients, among them 11% women had severe sarcopenia. Lean mass correlated with the factors related to the disease itself and some general clinical parameters, which requires further study.
32983142 Synergistic Interaction Between High Bioactive IL-17A and Joint Destruction for the Occurr 2020 Rheumatoid arthritis (RA) remains a cause of morbidity and mortality in many patients while new treatments have changed the face of the disease. Despite the emergence of these new drugs, cardiovascular (CV) diseases remain more frequent in RA patients compared with the general population. However, predictive biomarkers of RA severity and precise guidelines to manage the CV risk in these patients are still lacking. Pro-inflammatory cytokines contribute both to RA and CV pathogenesis. Focusing on IL-17A, high levels of bioactive IL-17A were associated with destruction in RA but also during myocardial infarction. The study aimed to assess the relationship between bioactive IL-17A, destruction and the occurrence of CV events (CVE) in RA patients with a very long follow-up. Thirty-six RA patients were followed between 1970 and 2012 in Lyon, France. They were tested for bioactive IL-17A and clinical and biological characteristics were recorded at baseline. Then, the occurrence of CVE was registered during the follow-up. To study the bioactive fraction of IL-17A, the bioassay used the ability of human umbilical vein endothelial cells to produce IL-8 in presence of RA plasma samples with or without an anti-IL-17A antibody. Bioactive IL-17A level at baseline was higher in RA patients who later experienced a CVE compared to those without (0.77 vs 0.21 ng/ml, p-value = 0.0095, Mann-Whitney test) and synergized with joint destruction (p-value = 0.020, Kruskal-Wallis test). Through its effects on vessels and thrombosis, high levels of bioactive IL-17A could represent a long-term marker of CV risk.
31611249 GM-CSF in inflammation. 2020 Jan 6 Granulocyte-macrophage colony-stimulating factor (GM-CSF) has many more functions than its original in vitro identification as an inducer of granulocyte and macrophage development from progenitor cells. Key features of GM-CSF biology need to be defined better, such as the responding and producing cell types, its links with other mediators, its prosurvival versus activation/differentiation functions, and when it is relevant in pathology. Significant preclinical data have emerged from GM-CSF deletion/depletion approaches indicating that GM-CSF is a potential target in many inflammatory/autoimmune conditions. Clinical trials targeting GM-CSF or its receptor have shown encouraging efficacy and safety profiles, particularly in rheumatoid arthritis. This review provides an update on the above topics and current issues/questions surrounding GM-CSF biology.
32047926 Targeting bioenergetics prevents CD4 T cell-mediated activation of synovial fibroblasts in 2020 Oct 1 OBJECTIVES: We investigated the reciprocal relationship linking fibroblast-like synoviocytes (FLS) and T lymphocytes in the inflamed RA synovium and subsequently targeted cellular metabolic pathways in FLS to identify key molecular players in joint inflammation. METHODS: RA FLS were cultured with CD4 T cells or T cell conditioned medium (CD4CM); proliferation, expression of adhesion molecules and intracellular cytokines were examined by flow cytometry. FLS invasiveness and secreted cytokines were measured by transwell matrigel invasion chambers and ELISA, while metabolic profiles were determined by extracellular Seahorse flux analysis. Gene expression was quantified by real-time quantitative RT-PCR. RESULTS: Our results showed mutual activation between CD4 T cells and FLS, which resulted in increased proliferation and expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 by both CD4 T cells and FLS. Furthermore, interaction between CD4 T cells and FLS resulted in an increased frequency of TNF-α+, IFN-γ+ and IL-17A+ CD4 T cells and augmented TNF-α, IFN-γ, IL-17A, IL-6, IL-8 and VEGF secretion. Moreover, CD4CM promoted invasiveness and boosted glycolysis in FLS while downregulating oxidative phosphorylation, effects paralleled by increased glucose transporters GLUT1 and GLUT3; key glycolytic enzymes GSK3A, HK2, LDHA and PFKFB3; angiogenic factor VEGF and MMP-3 and MMP-9. Importantly, these effects were reversed by the glycolytic inhibitor 2-DG and AMP analogue 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). CONCLUSION: This study demonstrates that CD4 T cells elicit an aggressive phenotype in FLS, which subsequently upregulate glycolysis to meet the increased metabolic demand. Accordingly, 2-DG and AICAR prevent this activation, suggesting that glycolytic manipulation could have clinical implications for RA treatment.
32824307 Association of Electronegative LDL with Macrophage Foam Cell Formation and CD11c Expressio 2020 Aug 16 L5, the most negatively charged subfraction of low-density lipoprotein (LDL), is implicated in atherogenesis, but the pathogenic association is relatively unexplored in patients with rheumatoid arthritis (RA). We examined the role of L5 LDL in macrophage foam cell formation and the association of L5 with CD11c expression in THP-1 cells and RA patients. Using quantitative real-time PCR, we determined mRNA expression levels of ITGAX, the gene for CD11c, a marker associated with vascular plaque formation and M1 macrophages in atherogenesis, in 93 RA patients. We also examined CD11c expression on THP-1 cells treated with L5 by flow cytometry analysis and the plasma levels of inflammatory mediators using a magnetic bead array. We found a dose-dependent upregulation of foam cell formation of macrophages after L5 treatment (mean ± SEM, 12.05 ± 2.35% in L5 (10 µg/mL); 50.13 ± 3.9% in L5 (25 µg/mL); 90.69 ± 1.82% in L5 (50 µg/mL), p < 0.01). Significantly higher levels of CD11c expression were observed in 30 patients with a high percentage of L5 in LDL (L5%) (0.0752 ± 0.0139-fold) compared to 63 patients with normal L5% (0.0446 ± 0.0054-fold, p < 0.05). CD11c expression levels were increased in the L5-treated group (30.00 ± 3.13% in L5 (10 µg/mL); 41.46 ± 2.77% in L5 (50 µg/mL), p < 0.05) and were positively correlated with plasma levels of interleukin (IL)-6 and IL-8. L5 augmented the expression of IL-6, IL-8, and tumor necrosis factor-α (TNF-α) on monocytes and macrophages. Our findings suggest that L5 may promote atherogenesis by augmenting macrophage foam cell formation, upregulating CD11c expression, and enhancing the expression levels of atherosclerosis-related mediators.
32701738 A Modified Posterior Approach for Decompression of a Multiloculated Atlanto-axial Cyst Wit 2020 Aug 15 STUDY DESIGN: Case report. OBJECTIVE: To describe a modified posterior approach for decompression and excision of a multiloculated atlanto-axial cyst. SUMMARY OF BACKGROUND DATA: Atlanto-axial cyst with myelopathy is rare. A direct decompression through anterior approach or an indirect decompression through posterior approach has been proposed. We report a rare multiloculated large C1-C2 cyst extending down to C3 body with myelopathy that created a dilemma in choice of approach. A modified posterior approach was adopted for decompression. METHODS: A 72-year-old lady, known case of Rheumatoid arthritis, presented with cervical myelopathy which was rapidly progressive since 2 months being her to wheel chair bound. She had clumsiness of gait and bilateral grip weakness. Both upper and lower extremities had nonfunctional power (medical research council scale grade 2). Deep tendon reflexes were exaggerated. Sensation was reduced in trunk and both extremities. Magnetic resonance imaging and computed tomography scan showed a large multiloculated cyst compressing spinal cord. Here author used modified posterior approach from the right side to access the cyst. The C2 ganglion excision, vertebral artery isolation, and resection of the pars allowed an approach similar to transforaminal decompression in the lumbar spine. A large antero-lateral epidural part of the cyst was excised. The retro-dental cyst was decompressed by puncturing cyst. Biopsy confirmed a synovial cyst. RESULT: The patient showed rapid neurological recovery after surgery. Postoperative magnetic resonance imaging at 3 months showed complete resolution of cyst. At 2-year follow-up, there was a complete neurological recovery with residual spasticity. CONCLUSION: A customized posterior approach allowed near total excision of a rare multiloculated large C1-2 cyst extending to the C3 body. This allowed visualisation anterior to the spinal cord without undue retraction that saved an additional anterior decompression. LEVEL OF EVIDENCE: 5.
32495356 Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and 2020 Aug WHAT IS KNOWN AND OBJECTIVE: Several clinical trials have attempted to evaluate the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy in patients with active rheumatoid arthritis (RA), but their relative efficacy and safety as monotherapy remain unclear due to the lack of data from head-to-head comparison trials. The relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy for rheumatoid arthritis (RA) were assessed. METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) and examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy relative to placebo in patients with RA. RESULTS AND DISCUSSION: Five RCTs comprising 1547 patients met the inclusion criteria. Compared with placebo, tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy showed a significantly higher American College of Rheumatology 20% (ACR20) response rate. Peficitinib 150 mg monotherapy showed the highest ACR20 response rate (odds ratio, 17.24.39; 95% credible interval, 6.57-51.80). The ranking probability based on the surface under the cumulative ranking curve indicated that peficitinib 150 mg had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by peficitinib 100 mg, filgotinib 200 mg, filgotinib 100 mg, tofacitinib 5 mg, upadacitinib 15 mg, baricitinib 4 mg and placebo. However, the number of patients who experienced serious adverse events did not differ significantly between the JAK inhibitors, except for tofacitinib 5 mg, and placebo. WHAT IS NEW AND CONCLUSION: All five JAK inhibitors-tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib-were efficacious monotherapy interventions for active RA, and differences were noted in their efficacy and safety in monotherapy.
32473705 DTX3L/ARTD9 contributes to inflammation of fibroblast-like synoviocytes by increasing STAT 2020 Jun Deltex-3-like (DTX3L), an E3 ligase, which is also known as B-lymphoma and BAL-associated protein (BBAP), is a member of the Deltex (DTX) family and was originally identified as a binding partner of diphtheria-toxin-like ADP-ribosyltransferase-9 (ARTD9). The present study found that DTX3L and ARTD9 were upregulated in synovial tissues obtained from rheumatoid arthritis (RA) patients compared with those from the controls. Healthy synovial tissues were obtained by arthroscopic biopsy from patients with meniscus injury (n = 10 samples) without a history of RA in the Orthopedic Department of the Affiliated Hospital of Nantong University. FLSs were isolated from RA patients who underwent total knee arthroplasty. We performed dual immunofluorescence staining on DTX3L and ARTD9, and these data strongly demonstrated that DTX3L and ARTD9 were colocalized with fibroblast-like synoviocytes (FLSs) in patients with RA. Furthermore, Western blot assays were performed to confirm that the expression levels of DTX3L and ARTD9 in the FLSs increased in a time-dependent manner and peaked at 24 h after TNF-α stimulation. Further, the inhibition of endogenous DTX3L and ARTD9 expression by RNA interference significantly suppressed the TNF-α-induced MMP-9 and IL-6 expression, as shown by Western blots. In contrast, overexpressing DTX3L and ARTD9 increased the MMP-9 and IL-6 mRNA levels in the TNF-α-stimulated FLSs. Moreover, DTX3L and ARTD9 associated with STAT1 under TNF-α-stimulated conditions to modulate STAT1 nuclear localization and transcriptional activity in an immunofluorescence staining assay. Collectively, our findings provide evidence that DTX3L and ARTD9 contribute to the production of inflammatory cytokines in FLSs from RA patients and may play a key role in the inflammatory process of RA via the STAT1 signal transduction pathway.
32994247 Can the adherence to quality of care indicators for early rheumatoid arthritis in clinical 2020 Sep 29 OBJECTIVE: To describe the adherence to quality of care indicators in early rheumatoid arthritis (RA) and to evaluate its impact on the risk of hospitalisation in a real-world setting. DESIGN: Retrospective cohort study. SETTING: Patients with early-onset RA identified from healthcare regional administrative databases by means of a validated algorithm between 2006 and 2012 in the Lombardy region (Italy). PARTICIPANTS: The study cohort included 14 203 early-onset RA (71% female, mean age 60 years). OUTCOME MEASURES: For each patient, a summary adherence score was calculated starting from the compliance to six quality indicators: (1-2) methotrexate or sulfasalazine or leflunomide with/without glucocorticoids, (3-4) other disease-modifying antirheumatic drugs (DMARDs) with/without glucocorticoids, (5) early interruption of glucocorticoids, (6) early clinical assessment.The relationship between low, intermediate and high categories of the summary score and the 12-month risk of hospitalisation for all causes and for RA was assessed. RESULTS: During a follow-up of 1 year, 2609 hospitalisations occurred, of which 704 were for RA (main or secondary diagnosis) and 252 primarily for RA. In a 7-year period (2006-2012), early DMARDs and timely clinical monitoring treatment increased (from 52% to 62% p trend <0.001 and from 25% to 30% p trend 0.009, respectively).Intermediate and high summary adherence score categories (compared with the low category) were related significantly with a lower risk of hospitalisation (adjusted HR 0.85 (95% CI 0.77 to 0.93), p<0.001 and HR 0.76 (95% CI 0.69 to 0.84), p<0.001, respectively). Among the indicators of the adherence score, early DMARD prescription showed the strongest positive impact, while long-term use of glucocorticoids was the worst negative one. CONCLUSION: In early RA, adherence to quality standards of care is associated with a lower risk of hospitalisation. Future interventions to improve the adherence to quality standards of care in this setting should decrease the risk of hospitalisation with a significant impact on individual and population health.
31077451 Ocular complications of tumour necrosis factor alpha inhibitors. 2020 Mar Tumour necrosis factor alpha inhibitors are a relatively recent development and are becoming increasingly common in the management of many chronic inflammatory conditions such as rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis and juvenile idiopathic arthritis. However, their ocular side effect profile is incomplete and poorly recognised, with mostly anecdotal cases reported in the literature. In this report we review the literature regarding ocular side effects associated with tumour necrosis factor alpha blockade.
32656595 Localisation of citrullinated and carbamylated proteins in inflamed gingival tissues from 2021 Mar OBJECTIVES: It has been proposed that citrullination and carbamylation occur in the inflamed periodontium and could be the plausible mechanisms for the generation of antigens involved in the development and progression of RA. The purpose of this study was to determine the presence and location of citrullinated and carbamylated proteins in the gingival tissues and compare their abundance in periodontitis (PD) patients with or without RA. MATERIALS AND METHODS: Gingival tissue samples of healthy (n = 5), PD with RA (n = 5) and PD without RA (n = 5) were collected. Specimens were formalin fixed, paraffin embedded and sectioned at 4 μm. The tissue sections were analysed for the presence of citrullinated and carbamylated proteins by immunohistochemistry. Semi-quantitative analysis was performed to quantify and compare the protein abundance between groups. RESULTS: The number of cells containing citrullinated and carbamylated proteins with higher intensity was markedly increased in gingival tissues from PD with or without RA in comparison with healthy controls. CONCLUSION: Inflamed gingival tissue is a potential source of citrullinated and carbamylated proteins other than synovial tissues. The extent to which the local accumulation of these proteins contributes to the pathogenesis of RA needs further elucidation. CLINICAL RELEVANCE: If PD is a potential source of post-translationally modified proteins, untreated PD should not be taken lightly in the context of RA. Hence, addressing gingival inflammation should be viewed as an important preventive measure in the general population not only for the progression of periodontal disease but also reducing the risk of developing extra-oral comorbidities.
30875456 Comparative Risk of Cardiovascular Events With Biologic and Synthetic Disease-Modifying An 2020 Apr OBJECTIVE: We performed a systematic review and meta-analysis to evaluate the comparative effects of tumor necrosis factor inhibitors (TNFi), non-TNFi biologics, and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on cardiovascular risk in rheumatoid arthritis (RA). METHODS: Using a systematic search through May 8, 2018, we included 14 observational studies in adults with RA treated with TNFi, non-TNFi biologics, tofacitinib, or csDMARDs, reporting the risk of major adverse cardiovascular events (MACE) or stroke. Only studies reporting active comparators were included. We performed random effects meta-analysis and estimated odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: As compared to TNFi, tocilizumab was associated with a decreased risk of MACE (OR 0.59 [95% CI 0.34-1.00]), whereas csDMARDs were associated with an increased risk of MACE (csDMARDs including methotrexate OR 1.45 [95% CI 1.09-1.93]; without methotrexate OR 2.57 [95% CI 1.32-5.00]), without heterogeneity (I(2) = 0%); there was no difference in risk of MACE between abatacept and TNFi (OR 0.89 [95% CI 0.71-1.11]), or between tocilizumab and abatacept (OR 0.81 [0.57-1.16]). Based on 11 cohorts (n = 135,053 patients), as compared to TNFi, csDMARDs were associated with an increased risk of stroke (OR 1.17 [95% CI 1.01-1.36]); there was no difference in risk of stroke between different biologics (tocilizumab versus TNFi OR 0.98 [95% CI 0.59-1.61]; abatacept versus TNFi OR 1.08 [0.86-1.34]; tocilizumab versus abatacept OR 0.73 [95% CI 0.39-1.38]), without heterogeneity (I(2) = 0%). No comparative studies on cardiovascular risk with tofacitinib were identified. CONCLUSION: Based on meta-analysis, as compared to TNFi, tocilizumab may be associated with a reduced risk of MACE, whereas csDMARDs may be associated with an increased risk of MACE and stroke.
32725883 Predictors of long-term clinical remission in rheumatoid arthritis. 2021 Feb AIM: Little is known about possible predictors of long-term survival on biologic disease-modifying antirheumatic drugs (bDMARD) after achievement of deep clinical remission in rheumatoid arthritis (RA) patients. We aimed at assessing factors associated with drug persistence of the first bDMARD in RA patients who achieved Simplified Disease Activity Index (SDAI) remission. METHODS: The clinical charts of RA patients beginning a first bDMARD were retrospectively reviewed, and those who achieved SDAI-based remission were selected for this analysis. Drug retention rate and mean survival time (MST) were estimated using Kaplan-Meier curves, and hazard ratios (HRs) of discontinuing bDMARD were estimated by multivariate Cox-regression models. RESULTS: Eight-six patients were on SDAI remission, and the survival rate of bDMARDs since 'baseline-time' was 82.6% (MST = 77.8 (95% CI: 69-86) months). Once on remission, patients not taking concomitant glucocorticoids had significantly higher survival rate (90.7%, MST = 86.3 (95% CI: 78-95) months) than patients who continued to intake low dose of glucocorticoids (68.8%, MST = 56.9 (95% CI: 45-69) months; P = .008). On the contrary, those patients assuming methotrexate (MTX) had significantly higher survival (87.7% (MST = 81.8 (95% CI: 73-91) months) than patients who were not taking MTX (66.7% (MST = 55.3 (95% CI: 40-71) months) (log-rank 4.72, P = .03). After the achievement of disease remission, stopping glucocorticoids (HR 0.31, 95% CI: 0.10-0.93) and methotrexate co-therapy (HR 0.34, 95% CI: 0.12-0.98) were independently associated with a lower risk of bDMARD discontinuation. CONCLUSIONS: Among RA patients on clinical remission with a first bDMARD, those stopping glucocorticoids and continuing MTX had much longer survival on bDMARD.
32404541 Subcutaneous Tocilizumab Is Effective for Treatment of Elderly-Onset Rheumatoid Arthritis. 2020 May Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic articular and bone manifestations and its pathogenesis is driven by a complex network of proinflammatory cytokines, including tumor necrosis factor and interleukin (IL)-6. Treatment of rheumatoid arthritis (RA) has been standardized by the introduction of a treat-to-target approach. Subcutaneous tocilizumab (TCZ-SC) is a humanized anti-IL-6 receptor monoclonal antibody, and is widely used for refractory RA patients in the clinical settings. However, it remains unknown whether TCZ-SC shows effectiveness for elderly onset RA. The study was aimed to assess the effectiveness and safety of TCZ-SC in elderly-onset rheumatoid arthritis (EORA) patients in daily practice. Fifty-five RA patients were divided into two age groups upon TCZ-SC administration: young (Y) group (< 65 years old, n = 30) and elderly-onset (EO) group (> 65 years old, n = 25). Disease activity score-28 (DAS28) upon TCZ-SC administration (4.84 in EO group vs. 4.41 in Y group) was significantly decreased to 1.94 vs. 1.93 at 3 months and 1.61 vs. 1.75 at 12 months after administration. The clinical remission (DAS28 < 2.6) rate was 75% in EO group vs. 83% in Y group at 3 months and 90% vs. 85% at 12 months. The retention rate at 12 months was 88% in EO group and 92% in Y group without significant difference. The cessation cases of adverse events were two in each group. In conclusion, TCZ-SC showed good clinical effectiveness and safety in EORA patients. TCZ-SC is a useful agent for patients with EORA.
32745130 Correlations of fatigue in Danish patients with rheumatoid arthritis, psoriatic arthritis 2020 OBJECTIVE: To describe fatigue in relation to disease-specific and socioeconomic factors and to test possible correlations between fatigue and work impairment, quality of life, pain, sleep, depression, and physical functioning in people with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: A questionnaire-based cross-sectional survey collecting patient characteristics such as disease characteristics, socioeconomic factors and patient-reported outcomes (PROs) from patients with RA, PsA and axSpA in Denmark. PRO scales included the FACIT-Fatigue sub-scale, Work Productivity and Activity Impairment scale (WPAI), EuroQol (EQ-5D), Medical Outcomes Study Sleep Scale (MOS), Major Depression Inventory (MDI), and Health Assessment Questionnaire (HAQ). Respondents were recruited via routine visits to the outpatient rheumatology clinic; information on diagnosis, treatment and disease activity was collected from medical journals by trained nurses. RESULTS: 487 patients participated in the study. Fatigue was more present in women, experienced patients, and patients who changed medication in the past 12 months, who were unemployed, who had less education, and who had lower household income. There was no statistically significant difference between mean fatigue in the three diagnostic groups (p = 0.08). Fatigue correlated with all included PROs (Pearson correlation coefficients, p<0.0001). Stratifying for diagnosis and adjusting for socioeconomic factors did not change the conclusion. CONCLUSION: In a stable, representative group of patients with RA, PsA and axSpA, we found significant correlations between fatigue and work impairment, quality of life, pain, sleep, depression and physical functioning. Fatigue cannot be perceived as a single problem, but rather as a symptom that affects broadly.
31990338 Efficacy of rituximab in slowing down progression of rheumatoid arthritis-related intersti 2020 Aug 1 OBJECTIVES: To asses the clinical course in RA-related interstitial lung disease (RA-ILD) patients with and without rituximab (RTX). The influence of other variables was also evaluated. METHODS: A longitudinal multicentre study was conducted in RA diagnosed with ILD from 2007 until 2018 in Madrid. Patients were included in a registry [pNEumology RhEumatology Autoinmune diseases (NEREA)] from the time of ILD diagnosis. The main endpoint was functional respiratory impairment (FI), when there was a decline ≥5% in the predicted forced vital capacity compared with the previous one. Pulmonary function was measured at baseline and in follow-up visits every 6-12 months. The independent variable was therapy with RTX. Covariables included sociodemographic, clinical, radiological and other therapies. Survival techniques were used to estimate the incidence rate (IR) and 95% CI of functional impairment, expressed per 100 patient-semesters. Cox multivariate regression models were run to examine the influence of RTX and other covariates on FI. Results were expressed as the hazard ratio (HR) and CI. RESULTS: A total of 68 patients were included. FI occurred in 42 patients [IR 23.5 (95% CI 19, 29.1)] and 50% of them had FI within 1.75 years of an ILD diagnosis. A multivariate analysis showed that RTX exposure resulted in a lower risk of FI compared with non-exposure [HR 0.51 (95% CI 0.31, 0.85)]. Interstitial pneumonia, glucocorticoids, disease activity and duration also influenced FI. CONCLUSION: RA-ILD patients deteriorate over time, with the median time free of impairment being <2 years. Patients exposed to RTX had a higher probability of remaining free of FI compared with other therapies. Other factors have also been identified.