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ID PMID Title PublicationDate abstract
32540401 Inhibiting role of long non-coding RNA LINC01197 in inflammation in rheumatoid arthritis t 2020 Sep 15 PURPOSE: Rheumatoid arthritis (RA) is a commonly diagnosed systemic autoimmune disease. Aberrant expression of long non-coding RNAs (lncRNAs) is closely linked to the development of RA. This study was conducted to explore the functions of the lncRNA LINC01197 in RA progression. METHODS: Differentially expressed lncRNAs/microRNAs/mRNAs in patients with RA were analyzed using RNA microarrays. A mouse model with RA was established and RA-fibroblast-like synoviocytes (RA-FLS) were acquired for in vitro experiments. The function of LINC01197 in inflammation and RA progression in mice and its role in the viability of RA-FLS were determined by experiments involving its overexpression or suppression. The sub-cellular localization of LINC01197 was determined and the downstream molecules involved in LINC01197-mediated events were identified. RESULTS: LINC01197 was poorly expressed in the synovial tissues in the RA model mice. Overexpression of LINC01197 reduced RA severity in mice and inhibited proliferation and inflammatory responses as well as promoted apoptosis in RA-FLS. Online predictions and dual luciferase reporter gene assays suggested that LINC01197 could bind to miR-150 and further regulate THBS2 expression. LINC01197 promoted THBS2 expression through miR-150 sponging and inactivated the TLR4/NF-κB signaling pathway, thus alleviating RA inflammation. CONCLUSION: The current study suggested that LINC01197 sponged miR-150 to promote THBS2 expression, leading to TLR4/NF-κB inactivation, and ameliorated RA inflammation. These findings may offer new insights into RA treatment.
31609517 Involvement of Tumor Necrosis Factor Receptor Type II in FoxP3 Stability and as a Marker o 2020 Apr OBJECTIVE: To study the involvement of Treg cells expressing tumor necrosis factor receptor type II (TNFRII) in exerting control of inflammation in experimental models and in the response to anti-TNF treatments in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA). METHODS: The role of TNFRII in Treg cells was explored using a multilevel translational approach. Treg cell stability was evaluated by analyzing the methylation status of the Foxp3 locus using bisulfite sequencing. Two models of inflammation (imiquimod-induced skin inflammation and delayed-type hypersensitivity arthritis [DTHA]) were induced in TNFRII(-/-) mice, with or without transfer of purified CD4+CD25+ cells from wild-type (WT) mice. In patients with RA and those with SpA, the evolution of the TNFRII+ Treg cell population before and after targeted treatment was monitored. RESULTS: Foxp3 gene methylation in Treg cells was greater in TNFRII(-/-) mice than in WT mice (50% versus 36.7%). In cultured Treg cells, TNF enhanced the expression, maintenance, and proliferation of Foxp3 through TNFRII signaling. Imiquimod-induced skin inflammation and DTHA were aggravated in TNFRII(-/-) mice (P < 0.05 for mice with skin inflammation and P < 0.0001 for mice with ankle swelling during DTHA compared to WT mice). Adoptive transfer of WT mouse Treg cells into TNFRII(-/-) mice prevented aggravation of arthritis. In patients with RA receiving anti-TNF treatments, but not those receiving tocilizumab, the frequency of TNFRII+ Treg cells was increased at 3 months of treatment compared to baseline (mean ± SEM 65.2 ± 3.1% versus 49.1 ± 5.5%; P < 0.01). In contrast, in anti-TNF-treated patients with SpA, the frequency of TNFRII+ Treg cells was not modified. CONCLUSION: TNFRII expression identifies a subset of Treg cells that are characterized by stable expression of Foxp3 via gene hypomethylation, and adoptive transfer of TNFRII-expressing Treg cells ameliorates inflammation in experimental models. Expansion and activation of TNFRII+ Treg cells may be one of the mechanisms by which anti-TNF agents control inflammation in RA, but not in SpA.
32723040 Prevalence and Risk Factors of Carpal Tunnel Syndrome in Japanese Aged 50 to 89 Years. 2020 Sep Background: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy worldwide, but there are few reports investigating its prevalence using subjects diagnosed by both clinical symptoms and nerve conduction studies (NCSs) in a population-based cohort. This study aimed to determine the epidemiology of CTS diagnosed by sensory disturbance findings and NCSs using a randomly sampled resident population. Methods: Subjects aged between 50 and 89 years were randomly sampled from the basic resident registry of a rural Japanese town. Subjects indicating a history of CTS surgery in a written questionnaire were classified as having past CTS. Subjects with both sensory disturbance of the median nerve area and delays in NCSs were diagnosed as having present CTS. Subjects with past or present CTS were judged as affected with CTS. We calculated the prevalence of CTS and investigated for possible risk factors. Results: Seventeen subjects (14 female and 3 male) were affected with CTS among 379 enrolled subjects. Adjusting these results to Japanese population values, the weighted prevalence of CTS was 4.7% (female: 7.2%, male: 1.8%) in the Japanese population aged 50 to 89 years. Statistically significant positive correlations were found between CTS and female, higher BMI, rheumatoid arthritis, and trigger digit. In females affected with CTS, third metacarpal length was significantly shorter than in those without CTS. Conclusions: This epidemiological study clarified the prevalence of CTS among Japanese seniors as 4.7%. Female, higher BMI, rheumatoid arthritis, trigger digit, and shorter third metacarpal length in females were risk factors for CTS.
32020145 Variables associated with subclinical atherosclerosis among rheumatoid arthritis patients 2020 Feb OBJECTIVES: To evaluate the cardiovascular disease (CVD) as demonstrated by carotid intima-media thickness (cIMT) and the cluster risk factors of CVD including traditional and non-traditional, urinary functions, iron buildup, and hemorheology in rheumatoid arthritis (RA) patients of Gulf Cooperative Council (GCC) countries. METHODS: Carotid intima-media thickness was obtained from 216 RA patients, free of atherosclerotic diseases. The correlation between cIMT and the possible CVD risk factors was carried out using regression analysis. Results: The mean cIMT was observed as 0.58±0.11 mm. Mean age was 48±13 years. Univariate analysis revealed a positive association (p less than 0.05) between cIMT and age, body mass index, systolic blood pressure (SBp), and diastolic blood pressure, c-reactive protein (CRP), triglycerides (TG), low-density lipoprotein (LDL), erythrocyte sedimentation rate (ESR), hemoglobin (Hb), hematocrit (Hct), mean cell volume, platelet, monocytes, eosinophils, ferritin, creatinine, and uric acid. Negative relationship was observed between cIMT and glomerular filtration rate (GFR), transferrin, and high-density lipoprotein. Multiple linear regression analysis exhibited a positive association between cIMT and the age, LDL, eosinophil, SBp, and the ESR, whereas, negative connection with the GFR and transferrin. Conclusion: In this study, we found that the eosinophils, and low transferrin, are the potential candidates for the CVD risk factors in RA patients. Fasting blood glucose level was also observed to be a significant risk factor in diabetic as well as non-diabetic RA. The remaining CVD risk factors in RA patients of GCC countries including older age, high SBp, ESR, LDL, and low GFR were similar to the international population.
32313250 Efficacy outcomes in phase 2 and phase 3 randomized controlled trials in rheumatology. 2020 Jun Phase 3 trials are the mainstay of drug development across medicine but have often not met expectations set by preceding phase 2 studies. A systematic meta-analysis evaluated all randomized controlled, double-blind trials investigating targeted disease-modifying anti-rheumatic drugs in rheumatoid and psoriatic arthritis. Primary outcomes of American College of Rheumatology (ACR) 20 responses were compared by mixed-model logistic regression, including exploration of potential determinants of efficacy overestimation. In rheumatoid arthritis, phase 2 trial outcomes systematically overestimated subsequent phase 3 results (odds ratio comparing ACR20 in phase 2 versus phase 3: 1.39, 95% confidence interval: 1.25-1.57, P < 0.001). Data for psoriatic arthritis trials were similar, but not statistically significant (odds ratio comparing ACR20 in phase 2 versus phase 3: 1.35, 95% confidence interval: 0.94-1.94, P = 0.09). Differences in inclusion criteria largely explained the observed differences in efficacy findings. Our findings have implications for all stakeholders in new therapeutic development and testing, as well as potential ethical implications.
31740964 Maternal rheumatoid arthritis and systemic lupus erythematosus and risk of cryptorchidism 2020 Aug 1 OBJECTIVES: RA and SLE are the most prevalent autoimmune rheumatic diseases affecting young women. Both diseases are characterized by systemic inflammation that may affect placental function and fetal development during pregnancy, and both diseases are associated with adverse pregnancy and child outcomes. We investigated the associations between maternal RA or SLE and the two genital malformations, cryptorchidism and hypospadias. METHODS: In this nationwide register-based study including all male singleton live births in Denmark from 1995 to 2016, we assessed the occurrence of cryptorchidism and hypospadias according to the prenatal disease-state of the mothers. Using Cox proportional hazards models we calculated adjusted hazard ratios, accounting for varying age at diagnosis. RESULTS: Among 690 240 boys, 1026 had a mother with RA and 352 had a mother with SLE. We found adjusted hazard ratios of 1.72 (95% CI: 1.15; 2.57) for cryptorchidism among boys born to mothers with RA and 1.46 (95% CI: 0.69; 3.06) for boys born to mothers with SLE, compared with the general population. As the number of hypospadias cases was low, multivariate analysis was not feasible. The crude hazard ratios were 0.51 (95% CI: 0.16; 1.58) and 1.00 (95% CI: 0.25; 4.03) for RA and SLE, respectively. CONCLUSION: Boys born to mothers with RA had higher risk of cryptorchidism, compared with unexposed boys. Boys born to mothers with SLE showed a similar tendency, however with less precision of the estimate. No conclusion could be reached on the risk of hypospadias, due to the low number of events.
32917682 B cells polarize pathogenic inflammatory T helper subsets through ICOSL-dependent glycolys 2020 Sep B cells constitute abundant cellular components in inflamed human tissues, but their role in pathogenesis of inflammatory T helper (T(H)) subsets is still unclear. Here, we demonstrate that B cells, particularly resting naïve B cells, have a previously unrecognized helper function that is involved in shaping the metabolic process and subsequent inflammatory differentiation of T-cell receptor-primed T(H) cells. ICOS/ICOSL axis-mediated glucose incorporation and utilization were crucial for inflammatory T(H) subset induction by B cells, and activation of mTOR was critical for T cell glycolysis in this process. Consistently, upon encountering ICOSL(+) B cells, activated effector memory T(H) cells from patients with rheumatoid arthritis or systemic lupus erythematosus spontaneously differentiated into inflammatory T(H) subsets. Immunotherapy using rituximab that specifically depleted B cells in patients with rheumatoid arthritis efficiently abrogated the capabilities of memory T(H) cells to incorporate and use glucose, thereby impairing the pathogenic differentiation of inflammatory T(H) subsets.
32506853 "Wang-Bi tablet, a patented Chinese medicine, maintains the balance of Th1/Th2 in mice wit 2020 Jun OBJECTIVE: To investigate the pharmacological mechanism of Wang-Bi tablets (WBTs), a Chinese patented medicine, in rheumatoid arthritis (RA) using mice with collagen-induced arthritis (CIA). METHODS: A mouse model of CIA was induced using bovine type Ⅱ collagen. WBT treatment was administered and efficacy was evaluated. The levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), and interleukin-4 (IL-4) were examined using an enzyme-linked immunosorbent assay, and the proportions of Th1 and Th2 were detected using flow cytometry. T-bet and GATA-binding protein 3 (GATA3) expression were demonstrated using Western blot analysis. RESULTS: Paw swelling and the arthritis index decreased significantly following WBT treatment. Histopathological analysis revealed markedly alleviated damage to synovium tissue in the WBT and methotrexate treatment groups. WBT regulated the production of IFN-γ, IL-2, and IL-4 and modulated Th1 and Th2 cell populations, which might have been induced by the attenuation of Th1 and Th2 cell differentiation through a decrease in the expression of T-bet and an increase in the expression of GATA3 in the synovial tissue in CIA mice. CONCLUSION: These results indicate that WBT may produce a therapeutic effect on CIA through maintaining the balance of Th1/Th2 cells, which could result in a decrease in the autoinflammatory disorder observed in RA.
31631316 Autoimmune blistering diseases provoked during the treatment of chronic inflammatory disea 2020 May BACKGROUND: To investigate the clinical course of autoimmune blistering diseases (AIBDs) following treatment with biologic agents (BAs) for chronic inflammatory diseases. METHODS: A comprehensive review of available, published literature was performed using PubMed and CINAHL search engines. Diagnostic criteria of AIBD included positive direct immunofluorescence studies and/or positive serology with clinically suggestive features. RESULTS: A total of 22 cases of AIBDs provoked by the use of BAs were found. The most commonly implicated agents were tumor necrosis factor-alpha inhibitors (n = 14). The mean age of onset of AIBD was 59.4 years (median 61.5 years, range 31-82). Average time to onset of AIBD following initiation of the suspected BA was 33.7 ± 43.8 weeks (range 3 days to 152 weeks). Psoriasis was the most common associated condition for which the BA was prescribed (n = 11), followed by rheumatoid arthritis (n = 6) and ulcerative colitis (n = 5). Of the 21 cases reporting AIBD outcome, 17 reported remission or complete resolution upon stopping treatment with the involved BA. Four cases reported continued bullae formation without worsening of disease following cessation of the BA or systemic corticosteroids used to treat the AIBD. Five cases rechallenged the patient with the involved BA and four of the five reported recurrence, often with quicker onset and more severe symptoms. CONCLUSIONS: BAs may be suspected in patients developing AIBD while being treated for chronic inflammatory diseases. A majority of cases resolve upon cessation of the offending agent.
32681006 Dopamine induces in vitro migration of synovial fibroblast from patients with rheumatoid a 2020 Jul 17 Preventing synovial fibroblast (SF) migration into the adjacent cartilage is a desirable therapeutic target in rheumatoid arthritis (RA). As previous studies demonstrated that RASF and SF from osteoarthritis (OA) patients express dopamine receptors (DR), aim of the present study was to investigate the impact of dopamine on mobility of fibroblasts from patients with chronic arthritides. Synovial tissue and fibroblasts were obtained from RA and OA patients. Immunohistochemistry was performed for all DR-subtypes in the invasion zone. Migration- and motility-assays were performed under DR-stimulation. Cytokines were evaluated using ELISA. Expression of DRs was evaluated by flow cytometry, and DR activation was measured by xCELLigence real-time analysis. All DRs were expressed in RA invasion zone. Migration and motility of RASF and OASF were increased after DR stimulation in patients ≤ 75 years old. Synovial fibroblasts from older RA patients (> 75 years old) expressed lower levels of D1-, D2- and D4-DR than patients ≤ 75 years old. DR activation was not altered in older patients. Our results suggest a possible involvement of dopamine on migration of fibroblasts from arthritis patients. Therefore, the synovial dopaminergic pathway might represent a potential therapeutic target to interfere with progressive joint damage in RA patients.
32778954 Designing a new bispecific tandem single-chain variable fragment antibody against tumor ne 2020 Aug 10 Rheumatoid arthritis disease is a chronic auto-immune inflammatory disease that mainly causes synovial joint inflammation and cartilage destruction. The tumor necrosis factor-α (TNF-α) is a pivotal cytokine that plays an important role in rheumatoid arthritis. The treatments focusing on a single cytokine inhibition are clinically able to produce meaningful responses in only about half of the treated patients due to multiple cytokines involved in this disease. In the present study, a bispecific tandem single-chain variable fragment was designed in order to suppress both human tumor necrosis factor-α and interleukin-23 (IL23) as a potential therapeutic drug candidate for this disease. To do so, at first, eight bispecific tandem single-chain variable fragment models were built against tumor necrosis factor-α and interleukin-23 cytokines with different domain orders by the homology modeling, and then 50 ns molecular dynamics simulation was performed for each one and then structural properties were exploited. The MD simulation results indicate the fact that the domains' order strongly affects tandem single-chain variable fragment properties, and in overall, the fragment V(L)AIL23+Linker+V(H)AIL23+linker+V(L)ATNF+Linker +V(H)ATNF +His6 (V(L) and V(H) are light and heavy chain variable fragments and AIL23 and ATNF are anti-interleukin 23 and anti-tumor necrosis factor-α, respectively, and His6 is the six histidine) not only separated antibody domains accurately but also had better stability and solvation free energy. Therefore, this structure can be considered as an effective potential drug for rheumatoid arthritis. It is expected that the findings of this research could shed a light on the treatment approaches of the rheumatoid arthritis disease.
31781849 Comparison of the efficacy and safety of tofacitinib and filgotinib in patients with activ 2020 Aug OBJECTIVE: We compared the efficacy and safety of tofacitinib and filgotinib in patients with rheumatoid arthritis (RA) showing inadequate response to conventional synthetic (cs) or biologic (b) disease-modifying anti-rheumatic drugs (DMARDs). METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib and filgotinib in combination with methotrexate (MTX) in patients with RA exhibiting inadequate cs- or bDMARD response. RESULTS: Nine RCTs consisting of 5466 patients met the inclusion criteria. We obtained 15 pairwise comparisons, including 11 direct comparisons from 6 interventions. Tofacitinib 10 mg + MTX and filgotinib 200 mg + MTX were among the most effective treatments for active RA showing an inadequate cs- or bDMARD response, followed by tofacitinib 5 mg + MTX, filgotinib 100 mg + MTX, and adalimumab + MTX. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that tofacitinib 10 mg + MTX and filgotinib 200 mg + MTX showed the highest probability of being the best treatment options in terms of ACR20 response rate (SUCRA = 0.898, 0.782), followed by tofacitinib 5 mg + MTX (SUCRA = 0.602), filgotinib 100 mg + MTX (SUCRA = 0.359), adalimumab + MTX (SUCRA = 0.358), and placebo + MTX (SUCRA = 0.001). No significant differences were observed in the incidence of serious adverse events after treatment with tofacitinib + MTX, filgotinib + MTX, adalimumab + MTX, or placebo + MTX. CONCLUSION: In patients with RA exhibiting an inadequate response to cs- or bDMARDs, tofacitinib 10 mg + MTX and filgotinib 200 mg + MTX were the most efficacious interventions and risks of serious adverse events did not differ between tofacitinib and filgotinib groups.
31257076 Use of calcium channel blockers and myocardial infarction in hypertensive patients with rh 2020 Jan BACKGROUND/PURPOSE: Rheumatoid arthritis (RA) should be regarded as a high risk factor for myocardial infarction (MI). In addition to anti-hypertensive effect, calcium channel blockers (CCBs) were frequently used as anti-angina drugs in patients with MI. However, the association between CCBs and MI in RA remains unclear. We investigated whether CCBs could decrease incidence of myocardial infarction in patients with hypertension and RA. METHODS: We identified patients from the Registry for Catastrophic Illness, a nation-wide database encompassing almost all of the RA patients in Taiwan from 1995 to 2008. The primary endpoint was MI and the median duration of follow up was 3,050 days. Propensity score matching and Cox proportional hazards regression models were used to estimate hazard ratios for MI. RESULTS: Among 27,844 patients with hypertension, 17,317 (61.5%) subjects received CCBs (mean age = 58.8 years, 72.1% female). The incidence of MI significantly decreased in patients treated with CCBs (hazard ratio [HR] 0.560; 95% confidence interval [CI] 0.494-0.634). After propensity match, subjects receiving CCBs had significantly lower risk of MI (HR 0.637, 95% CI 0.549-0.740). The protective effect of CCBs therapy was significantly better in patients taking longer duration. Of note, the effect remained robust in subgroup analyses, including dihydropyridine CCBs (HR 0.550; 95% CI 0.466-0.650) and non-dihydropyridine CCBs (HR 0.674, 95% CI 0.588-0.773). CONCLUSION: Therapy of CCBs is associated with a lower risk of MI among hypertensive patients with RA. Hence, the prescription of CCBs may be a compelling indication of BP lowering in RA population.
32240943 Association between IL1B polymorphisms and the risk of rheumatoid arthritis. 2020 Jun Rheumatoid arthritis (RA) is a chronic, inflammatory synovitis dominated systemic disease with unknown etiology. The purpose of this study was to determine the relationship between IL1B polymorphisms and RA risk in a Chinese Han population. Four single-nucleotide polymorphisms (SNPs) of IL1B, rs2853550, rs1143643, rs3136558 and rs16944 were genotyped in 508 RA cases and 494 healthy controls using the Agena MassARRAY method. A genetic model analysis was performed to evaluate the relationships between the variants and RA risk. Haplotype analysis was used to evaluate the potential relationship between the genetic block and RA risk. We determined that rs1143643 was linked to a reduced risk of RA based on the results of the co-dominant model (OR = 0.67, 95%CI: 0.50-0.89, p = 0.006) and the dominant model (OR = 0.73, 95%CI = 0.56-0.96, p = 0.025). On the other hand, rs16944 was associated with an increased risk of RA in the co-dominant model (OR = 1.71, 95%CI = 1.53-1.97, p = 0.029) and the recessive model (OR = 1.41, 95%CI = 1.05-1.88, p = 0.021). Among individuals older than 50 years, we observed that rs2853550 was associated with an increased risk of RA, and that rs1143643 decreased RA risk. Furthermore, rs1143643 was associated with a decreased RA risk in female patients. However, rs16944 increased RA risk in both the co-dominant and the additive models in different age subgroups. In addition, rs16944-GA increased RA risk in males in the co-dominance model and rs16944-AA increased RA risk in females in the additive model. These results suggested that rs2853550, rs1143643, and rs16944 in the IL1B gene are associated with RA risk.
32907617 Interleukin-6 receptor blockade or TNFα inhibition for reducing glycaemia in patients wit 2020 Sep 9 BACKGROUND: Diabetes is common in patients with rheumatoid arthritis (RA). Interleukin (IL)-6 is implicated in both the pathogenesis of RA and in glucose homeostasis; this post hoc analysis investigated the effects of IL-6 receptor vs. tumour necrosis factor inhibition on glycosylated haemoglobin (HbA1c) in patients with RA with or without diabetes. METHODS: Data were from two placebo-controlled phase III studies of subcutaneous sarilumab 150/200 mg q2w + methotrexate or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and a phase III monotherapy study of sarilumab 200 mg q2w vs. adalimumab 40 mg q2w. Patients with diabetes were identified by medical history or use of antidiabetic medication (patients with HbA1c ≥ 9% were excluded from all three studies). HbA1c was measured at baseline and weeks 12/24. Safety and efficacy were assessed in RA patients with or without diabetes. RESULTS: Patients with diabetes (n = 184) were older, weighed more and exhibited higher RA disease activity than patients without diabetes (n = 1928). Regardless of diabetes status, in patients on background csDMARDs, least squares (LS) mean difference (95% CI) in change from baseline in HbA1c for sarilumab 150 mg/200 mg vs. placebo at week 24 was - 0.28 (- 0.40, - 0.16; nominal p <  0.0001) and - 0.42 (- 0.54, - 0.31; nominal p <  0.0001), respectively. Without csDMARDs, LS mean difference for sarilumab 200 mg vs. adalimumab 40 mg at week 24 was - 0.13 (- 0.22, - 0.04; nominal p = 0.0043). Greater reduction in HbA1c than placebo or adalimumab was observed at week 24 with sarilumab in patients with diabetes and/or baseline HbA1c ≥ 7%. There was no correlation between baseline/change from baseline in HbA1c and baseline/change from baseline in C-reactive protein, 28-joint Disease Activity Score, or haemoglobin, nor between HbA1c change from baseline and baseline glucocorticoid use. Medical history of diabetes or use of diabetes treatments had limited impact on safety and efficacy of sarilumab and was consistent with overall phase III findings in patients with RA. CONCLUSIONS: In post hoc analyses, sarilumab was associated with a greater reduction in HbA1c than csDMARDs or adalimumab, independent of sarilumab anti-inflammatory effects. Prospective studies are required to further assess these preliminary findings. TRIAL REGISTRATION: ClinTrials.gov NCT01061736: date of registration February 03, 2010; ClinTrials.gov NCT01709578: date of registration October 18, 2012; ClinTrials.gov NCT02332590: date of registration January 07, 2015.
32385143 Comparative effectiveness of antitumour necrosis factor agents, biologics with an alternat 2020 May BACKGROUND: Multiple biologic and targeted synthetic disease-modifying rheumatic drugs (b/tsDMARDs) are approved for the management of rheumatoid arthritis (RA), including TNF inhibitors (TNFi), bDMARDs with other modes of action (bDMARD-OMA) and Janus kinase inhibitors (JAKi). Combination of b/tsDMARDs with conventional synthetic DMARDs (csDMARDs) is recommended, yet monotherapy is common in practice. OBJECTIVE: To compare drug maintenance and clinical effectiveness of three alternative treatment options for RA management. METHODS: This observational cohort study was nested within the Swiss RA Registry. TNFi, bDMARD-OMA (abatacept or anti-IL6 agents) or the JAKi tofacitinib (Tofa) initiated in adult RA patients were included. The primary outcome was overall drug retention. We further analysed secondary effectiveness outcomes and whether concomitant csDMARDs modified effectiveness, adjusting for potential confounding factors. RESULTS: 4023 treatment courses of 2600 patients were included, 1862 on TNFi, 1355 on bDMARD-OMA and 806 on Tofa. TNFi was more frequently used as a first b/tsDMARDs, at a younger age and with shorter disease duration. Overall drug maintenance was significantly lower with TNFi compared with Tofa [HR 1.29 (95% CI 1.14 to 1.47)], but similar between bDMARD-OMA and Tofa [HR 1.09 (95% CI 0.96 to 1.24)]. TNFi maintenance was decreased when prescribed without concomitant csDMARDs [HR: 1.27 (95% CI 1.08 to 1.49)], while no difference was observed for bDMARD-OMA or Tofa maintenance with respect to concomitant csDMARDs. CONCLUSION: Tofa drug maintenance was comparable with bDMARDs-OMA and somewhat higher than TNFi. Concomitant csDMARDs appear to be required for optimal effectiveness of TNFi, but not for bDMARD-OMA or Tofa.
32928578 Ideal food pyramid for patients with rheumatoid arthritis: A narrative review. 2021 Mar Emerging literature suggests that diet plays an important modulatory role in rheumatoid arthritis (RA) because diet is an environmental factor that affects inflammation, antigen presentation, antioxidant defense mechanisms and gut microbiota. Patients with RA frequently ask their doctors about which diets to follow, and even in the absence of advice from their physicians, many patients are undertaking various dietary interventions. Given this background, the aim of this review is to evaluate the evidence to date regarding the ideal dietary approach for management of RA in order to reduce the counteracting inflammation, and to construct a food pyramid for patients with RA. The pyramid shows that carbohydrates should be consumed every day (3 portions of whole grains, preferably gluten free), together with fruits and vegetables (5 portions; among which fruit, berries and citrus fruit are to be preferred, and among the vegetables, green leafy ones.), light yogurt (125 ml), skim milk (200 ml), 1 glass (125 ml) of wine and extra virgin olive oil; weekly, fish (3 portions), white meat (3 portions), legumes (2 portions) eggs (2 portions), seasoned cheeses (2 portions), and red or processed meats (once a week). At the top of the pyramid, there are two pennants: one green means that subjects with RA need some personalized supplementation (vitamin D and omega 3) and one red means that there are some foods that are banned (salt and sugar). The food pyramid allows patients to easily figure out what to eat.
32452344 Baricitinib in patients with rheumatoid arthritis with inadequate response to methotrexate 2020 Jul OBJECTIVES: This study evaluated the efficacy and safety of baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, in patients with moderately to severely active rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX) therapy. METHODS: In this phase 3, double-blind, 52-week, placebo-controlled study, 290 patients with moderately to severely active RA and inadequate response to MTX were randomly assigned 1:1 to placebo or baricitinib 4-mg once daily, stratified by country (China, Brazil, Argentina) and presence of joint erosions. Primary endpoint measures included American College of Rheumatology 20% response (ACR20) at week 12. Secondary endpoints included changes in Health Assessment Questionnaire-Disability Index (HAQ-DI) and Disease Activity Score for 28-joint counts (DAS28)-high-sensitivity C-reactive protein (hsCRP), Simplified Disease Activity Index (SDAI) score ≤3.3, mean duration of morning joint stiffness, severity of morning joint stiffness numeric rating scale (NRS 0-10), worst tiredness NRS, and worst joint pain NRS at week 12. RESULTS: Most patients (approximately 80%) were from China. More patients achieved ACR20 response at week 12 with baricitinib than with placebo (58.6% vs. 28.3%; p<0.001). Statistically significant improvements were also seen in HAQ-DI, DAS28-hsCRP, morning joint stiffness, worst tiredness, and worst joint pain in the baricitinib group compared to placebo at week 12. Through week 24, rates of treatment-emergent adverse events, including infections, were higher for baricitinib compared to placebo, while serious adverse event rates were similar between baricitinib and placebo. CONCLUSIONS: In patients with RA who had an inadequate response to MTX, baricitinib was associated with significant clinical improvements as compared with placebo.
33348651 A Posteriori Dietary Patterns and Rheumatoid Arthritis Disease Activity: A Beneficial Role 2020 Dec 17 To our knowledge, no studies have investigated the relationship between a posteriori dietary patterns (DPs)-representing current dietary behavior-and disease activity in patients with rheumatoid arthritis (RA). We analyzed data from a recent Italian cross-sectional study including 365 RA patients (median age: 58.46 years, 78.63% females). Prevalent DPs were identified through principal component factor analysis on 33 nutrients. RA activity was measured according to the Disease Activity Score on 28 joints (DAS28) and the Simplified Disease Activity Index (SDAI). Single DPs were related to disease activity through linear and logistic regression models, adjusted for the remaining DPs and confounders. We identified five DPs (~80% variance explained). Among them, Vegetable unsaturated fatty acids (VUFA) and Animal unsaturated fatty acids (AUFA) DPs were inversely related to DAS28 in the overall analysis, and in the more severe or long-standing RA subgroups; the highest score reductions (VUFA: 0.81, AUFA: 0.71) were reached for the long-standing RA. The SDAI was inversely related with these DPs in subgroups only. This Italian study shows that scoring high on DPs based on unsaturated fats from either source provides independent beneficial effects of clinical relevance on RA disease activity, thus strengthening evidence on the topic.
31706010 Cinnamtannin D1 attenuates autoimmune arthritis by regulating the balance of Th17 and treg 2020 Jan The suppression of the abnormal systemic immune response constitutes a primary strategy for treatment of rheumatoid arthritis (RA); toward this end, the identification of natural compounds with immunosuppressive activity represents a promising strategy for RA drug discovery. Cinnamtannin D1 (CTD-1), a polyphenolic compound isolated from Cinnamomum tamala, was previously reported to possess good immunosuppressive activity. However, the beneficial effect of CTD-1 on RA is currently unknown. The aim of this study was to evaluate the anti-arthritic effect of CTD-1 in collagen-induced arthritis (CIA) mice and clarify the underlying mechanisms. CTD-1 treatment significantly alleviated the severity of CIA mice, affording reduced clinical scores and paw swelling, along with reduced inflammatory cell infiltration and cartilage damage in the joints; in addition, the serum levels of IL-17, IL-6, and IL-1β were decreased whereas those of TGF-β and IL-10 were increased. CTD-1-treated mice exhibited lower frequency of Th17 cells and higher frequency of Treg cells compared to those in untreated mice, indicating that the balance of Th17/Treg cells may serve as the target for CTD-1. Consistent with this, in ex vivo assays, CTD-1 inhibited Th17 cell differentiation through the downregulation of phospho-STAT3/RORγt, whereas it promoted Treg differentiation by upregulating phospho-STAT5/Foxp3 in response to the stimulation of collagen type II. Moreover, in an in vitro naïve CD4(+) T cell differentiation assay, CTD-1 directly inhibited Th17 cell differentiation and promoted Treg differentiation, suggesting that CTD-1 regulated the balance of Th17 and Treg cells to inhibit excessive immune response. Furthermore, the regulation effect of CTD-1 on Th17 and Treg cells was dependent on Ahr expression, as this effect was abolished when Ahr was knocked down and was impaired when Ahr was overexpressed. Together, our results indicated that CTD-1 treatment benefits CIA mice by regulating Th17 and Treg differentiation through the inhibition of AHR expression, and suggested a potential application of CTD-1 toward RA treatment.