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ID PMID Title PublicationDate abstract
33162271 Risk Factors Contributing to Early Implant Fracture in Silicone Metacarpophalangeal Joint 2021 Mar PURPOSE: To identify the risk factors associated with early implant fracture of silicone metacarpophalangeal (MCP) joint arthroplasty using the volar hinge silicone implant for patients with rheumatoid arthritis. METHODS: We retrospectively reviewed 113 fingers of 31 hands that underwent MCP joint arthroplasty between 2008 and 2014, with a minimum follow-up of 3 years,. An implant fracture within 3 years after surgery was regarded as an early implant fracture. Patient records were reviewed for potential risk factors of age, affected fingers, ulnar drift angle, and range of motion of the MCP joint before surgery and 1 year after surgery. Candidate risk factors were compared at the level of the digit and at the patient level. RESULTS: With fracture of the implants as the end point, Kaplan-Meier estimated survival rate was 74.3% at 3 years and 67.9% at 5 years. Early implant fracture was detected in 29 fingers. Bivariate analyses showed significant associations between early implant fracture and MCP joint arc of motion before surgery, MCP joint flexion range 1 year after surgery, and MCP joint arc of motion 1 year after surgery. Multiple logistic regression analysis showed that increased MCP joint flexion range 1 year after surgery was an independent risk factor for early implant fracture. CONCLUSIONS: Increasing MCP joint flexion range was associated with increased fractures of the implants. We propose that the MCP joint flexion range should be restricted to less than 60° in postoperative rehabilitation; it is necessary to educate the patient to permanently avoid excessive flexion of the MCP joint. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
32601758 Potential of Sonophoresis as a Skin Penetration Technique in the Treatment of Rheumatoid A 2020 Jun 29 Rheumatoid arthritis, a chronic disorder, limits the use of chemical penetration enhancers for a prolonged period of time. Moreover, systemic routes of administration of the first-line drug, methotrexate, have shown undesirable systemic as well as local side effects. The objective of this research was to overcome the limitations associated with treatment of rheumatoid arthritis by utilizing three physical transdermal penetration enhancement techniques namely cold-laser, electroporation, and sonophoresis to deliver methotrexate. Methotrexate patch was prepared using solvent casting method and the ex-vivo release of methotrexate in combination with three physical penetration enhancers (sonophoresis, electroporation, and cold laser) were studied. The best technique was employed in pre-clinical testing in arthritic and control groups of male Wistar rats excluding remaining two techniques. The comparative ex-vivo studies showed that the penetration enhancement of methotrexate is maximum by sonophoresis followed by electroporation and cold laser (sonophoresis > electroporation > cold laser). In pharmacodynamic studies, the reduction in diameter of injected and non-injected paw on day 5 and day 21 for group 4 (ultrasound pre-treated group) was higher as compared to group 3 (group receiving only methotrexate patch). The motility score and the reduction in pain were significantly improved for group 4 than group 3 on both day 5 and day 21 (P ˂ 0.05) which confirmed the faster recovery of animals of group 4 due to penetration enhancement of methotrexate patch by ultrasound treatment. From the results, it can be concluded that sonophoresis along with methotrexate patch has shown a significant effect in the treatment of rheumatoid arthritis.
31654156 Abatacept retention and clinical outcomes in Austrian patients with rheumatoid arthritis: 2020 Apr BACKGROUND: AbataCepT In rOutiNe clinical practice (ACTION; NCT02109666) was a 2-year international observational study of patients with moderate to severe rheumatoid arthritis. METHODS: Baseline characteristics, abatacept retention rates, and clinical outcomes were compared by treatment line in the Austrian cohort of ACTION. RESULTS: Of 100 patients enrolled in Austria, 98 (98.0%) were evaluable: 33/98 (33.7%) biologic naïve and 65/98 (66.3%) with ≥1 prior biologic failure. At baseline, biologic-naïve patients had shorter disease duration and lower concomitant corticosteroid use than biologic-failure patients. Overall crude abatacept retention rate was 60.5% and retention rate was higher in biologic-naïve (65.1%) versus biologic-failure (58.0%) patients. Good/moderate EULAR (European League Against Rheumatism) response rates were 85.7% in biologic-naïve and 100% in biologic-failure patients. CONCLUSIONS: In the Austrian cohort of ACTION, overall abatacept retention at 2 years was high, with higher retention rates in patients receiving abatacept as an earlier treatment line. Good/moderate EULAR response rate was higher in biologic-failure than in biologic-naïve patients.
32925790 Superb microvascular imaging evaluating joint lesion scores in rheumatoid arthritis compar 2020 Sep 11 BACKGROUND: To compare superb microvascular imaging with power Doppler imaging for evaluating joint lesion scores in rheumatoid arthritis based on high quality clinical cohort or case control studies. METHODS: We searched Medline (via PubMed), Web of Science, Cochrane Library, Embase, and Chinese Biomedical Literature Database without restrictions of language and publication status. Two investigators will identify relevant trials, extract data, and appraise risk of bias in each eligible trial. Data will be pooled by either a fixed-effects model or a random-effects model according to the results of heterogeneity identification. The primary outcomes include a semi-quantitative scoring system, through which synovial vascularity intensity was evaluated by means of both power Doppler imaging (PDI) and superb microvascular imaging (SMI). This study will only include high quality clinical cohort or case control studies. Statistical analyses were conducted by STATA version 15.1 software. RESULTS: This meta-analysis included 11 studies. A total of 4342 joints were assessed through both SMI and PDI. The pooled summary odds ratio was 2.12 (95% confidence interval = 1.80-2.51) with statistical significance (z = 8.82, P < .01). In subgroup analyses, the results revealed also that SMI exhibited more sensitive performance in different subgroups. We found no evidence for publication bias (t = 0.55, P = .598). CONCLUSION: Our meta-analysis indicates that SMI ultrasound is more sensitive than conventional PDI in detecting synovitis in RA patients. INPLASY REGISTRATION NUMBER: INPLASY202060089.
32228087 Clinical outcome of posterior-stabilized total knee arthroplasty using an increased flexio 2020 Apr AIMS: To compare patients undergoing total knee arthroplasty (TKA) with ≤ 80° range of movement (ROM) operated with a 2 mm increase in the flexion gap with matched non-stiff patients with at least 100° of preoperative ROM and balanced flexion and extension gaps. METHODS: In a retrospective cohort study, 98 TKAs (91 patients) with a preoperative ROM of ≤ 80° were examined. Mean follow-up time was 53 months (24 to 112). All TKAs in stiff knees were performed with a 2 mm increased flexion gap. Data were compared to a matched control group of 98 TKAs (86 patients) with a mean follow-up of 43 months (24 to 89). Knees in the control group had a preoperative ROM of at least 100° and balanced flexion and extension gaps. In all stiff and non-stiff knees posterior stabilized (PS) TKAs with patellar resurfacing in combination with adequate soft tissue balancing were used. RESULTS: Overall mean ROM in stiff knees increased preoperatively from 67° (0° to 80°) to 114° postoperatively (65° to 135°) (p < 0.001). Mean knee flexion improved from 82° (0° to 110°) to 115° (65° to 135°) and mean flexion contracture decreased from 14° (0° to 50°) to 1° (0° to 10°) (p < 0.001). The mean Knee Society Score (KSS) improved from 34 (0 to 71) to 88 (38 to 100) (p < 0.001) and the KSS Functional Score from 43 (0 to 70) to 86 (0 to 100). Seven knees (7%) required manipulations under anaesthesia (MUA) and none of the knees had flexion instability. The mean overall ROM in the control group improved from 117° (100° to 140°) to 123° (100° to 130°) (p < 0.001). Mean knee flexion improved from 119° (100° to 140°) to 123° (100° to 130°) (p < 0.001) and mean flexion contracture decreased from 2° (0° to 15°) to 0° (0° to 5°) (p < 0.001). None of the knees in the control group had flexion instability or required MUA. The mean KSS Knee Score improved from 48 (0 to 80) to 94 (79 to 100) (p < 0.001) and the KSS Functional Score from 52 (5 to 100) to 95 (60 to 100) (p < 0.001). Mean improvement in ROM (p < 0.001) and KSS Knee Score (p = 0.017) were greater in knees with preoperative stiffness compared with the control group, but the KSS Functional Score improvement was comparable (p = 0.885). CONCLUSION: TKA with a 2 mm increased flexion gap provided a significant improvement of ROM in knees with preoperative stiffness. While the improvement in ROM was greater, the absolute postoperative ROM was less than in matched non-stiff knees. PS TKA with patellar resurfacing and a 2 mm increased flexion gap, in combination with adequate soft tissue balancing, provides excellent ROM and knee function when stiffness of the knee had been present preoperatively. Cite this article: Bone Joint J 2020;102-B(4):426-433.
32541502 Higher serum uric acid levels are associated with reduced risk of hip osteoporosis in post 2020 Jun 12 Although the positive correlation between serum uric acid (UA) levels and bone mineral density (BMD) has been reported in the general population, there are little data regarding the effect of serum UA levels on bone loss in patients with rheumatoid arthritis (RA).We investigated whether increased serum UA levels were associated with a reduced risk of osteoporosis in postmenopausal women with RA.In this retrospective cross-sectional study, 447 postmenopausal female patients with RA and 200 age-matched, postmenopausal healthy controls underwent BMD examination by dual energy x-ray absorptiometry and serum UA levels measurement. Osteoporosis was diagnosed when the T-score was <-2.5.The median UA level in postmenopausal RA patients was found to be significantly lower than that in the healthy women (4 vs 4.1 mg/dL, P = .012) and the frequency of osteoporosis incidence in the lumbar spine, hip, and either site in RA patients was 25.5%, 15.9%, and 32.5%, respectively; the values were significantly higher than those of the controls. After adjusting for confounding factors, a significantly lower risk for osteoporosis of the hip in RA patients was observed within the highest quartile (odds ratio [OR] = 0.37, 95% confidence interval [CI] = 0.16-0.72, P = .021) and the second highest quartile (OR = 0.44, 95% CI = 0.2-0.95, P = .038) of serum UA levels as compared with the lowest quartile, but this association was not found to be consistent with respect to the lumbar spine. Serum UA levels also showed an independently positive correlation with femoral neck BMD (β = 0.0104, P = .01) and total hip BMD (β = 0.0102, P = .017), but not with lumbar BMD.Our data suggest that UA may exert a protective effect on bone loss in RA, especially in the hip.
31675124 Immunopharmacological effect of β-d-mannuronic acid (M2000), as a new immunosuppressive d 2020 May The positive impacts of β-d-mannuronic acid (M2000) on the gene expression of miR-155, its target molecules (SOCS1 and SHIP1), and NF-κB transcription factor were demonstrated in a study using the HEK293-TLR2 cell line. This new drug has been approved as a safe and effective medication by a randomized, multinational, phase III clinical trial on RA patients. The present study aimed to evaluate the oral administration effect of M2000 on the expression levels of the mentioned genes in RA patients. This research was conducted on 12 RA patients and 12 healthy individuals. After extraction of total RNA from PBMCs of patients and synthesis of cDNA, the expression levels of miR-155, SOCS1, SHIP1, and NF-κB genes were measured through quantitative Real-time PCR at baseline and after 12 weeks of M2000 therapy. Our findings showed that the miR-155 gene expression level significantly decreased in the M2000-treated patients compared with the baseline (0.76-fold, with p < .05). The expression levels of SOCS1 and SHIP1 genes significantly increased in the patients treated with M2000 compared with the before treatment (1.46-, 1.54-fold, with p < .01, p < .05, respectively). In addition, it was found that the gene expression level of the NF-κB transcription factor significantly reduced in M2000-treated patients compared with the baseline (0.81-fold, with p < .05). This study showed that the oral administration of M2000 was able to reduce the expression of the miR-155, increase the expression of SOCS1 and SHIP1, and decrease the NF-κB gene expression (Trial Registration Number: IRCT2017100213739N10).
32080313 Local transplantation of adipose-derived stem cells has a significant therapeutic effect i 2020 Feb 20 Adipose-derived stem cells (ADSCs) have anti-inflammatory and regenerative properties. The purpose of this study was to investigate the effect of locally administered ADSCs in a rheumatoid arthritis (RA) mouse model. In an in vivo experiment, single-cell ADSCs and three dimensionally-cultured ADSC spheroids were injected intra-articularly into the knees of RA model mice and histologically assessed. Marked improvement of synovial inflammation and articular cartilage regeneration was found in ADSC-treated mice. Proliferation, migration, and apoptosis assays of synovial fibroblasts incubated with single-cell and spheroid ADSCs were performed. The expression levels of total cytokine RNA in ADSC single cells, spheroids, and ADSC-treated inflammatory synovial fibroblasts were also evaluated by quantitative reverse transcription PCR. ADSCs suppressed the proliferation and migration of activated inflammatory cells and downregulated inflammatory cytokines. TSG-6 and TGFβ1 were significantly upregulated in ADSCs compared to controls and TGFβ1 was significantly upregulated in ADSC spheroids compared to single cells. The apoptosis rate of ADSC spheroids was significantly lower than that of single-cell ADSCs. These results indicated that intra-articular administration of ADSC single cells and spheroids was effective in an RA mouse model, offering a novel approach for the development of effective localized treatments for patients with RA.
31837028 Isoagglutinin-reduced immunoglobulin retains efficacy in mouse models of immune thrombocyt 2020 Feb BACKGROUND: Immunoglobulin therapy including intravenous immunoglobulin (IVIg) has been used as an effective treatment for autoimmune/inflammatory conditions with few side effects. However, high-dose IVIg (1-2 g/kg) has been recognized as a cause of hemolytic anemia in non-blood group O patients. Hemolysis when observed has been due to anti-A/anti-B isoagglutinins contained in the IVIg. Recently, an isoagglutinin-reduced IVIg, whereby the anti-A and anti-B titers have been reduced by immunoaffinity chromatography, has been introduced; however, whether this new product is as efficacious as nonreduced immunoglobulin (Ig) or will result in less IVIg-associated hemolysis has not been resolved. STUDY DESIGN AND METHODS: We used in vitro phagocytosis by monocytes and proinflammatory/anti-inflammatory macrophages, with isoagglutinin-reduced and -nonreduced Ig opsonized group A(1) , B, and A(1) B red blood cells, to estimate clinical significance of the IgG isoagglutinins. We also used immune thrombocytopenia (ITP) and rheumatoid arthritis (RA) mouse models to examine the in vivo efficacy of isoagglutinin-reduced versus -nonreduced Ig on the amelioration of the diseases. RESULTS: In contrast to nonreduced Ig, phagocytosis was largely absent when isoagglutinin-reduced Ig was used at a concentration equivalent to a patient receiving 2 g/kg. The in vivo efficacy of isoagglutinin-reduced versus nonreduced Ig on the amelioration of experimental ITP and RA was similar, indicating no loss of efficacy due to the chromatographic removal of isoagglutinins. CONCLUSION: Isoagglutinin-reduced Ig should have efficacy similar to nonreduced Ig and result in less IVIg-associated hemolysis.
32598774 [Survival of bDMARDs in bionaive patients with rheumatoid arthritis: data from a retrospec 2020 Jun 5 AIM: Analysis of survival on biological therapy in previously bionaive patients with rheumatoid arthritis (RA) during the first year of therapy in real clinical practice. MATERIALS AND METHODS: The retrospective study included 204 adult patients with RA. In the hospital, patients were first prescribed therapy with various biological disease-modifying antirheumatic drugs (bDMARDs): infliximab, adalimumab, etanercept, certolizumab pegol, tocilizumab, abatacept (ABA), rituximab (RTM). Patients were divided by age in accordance with the classification adopted by WHO. Clinical forms of RA were presented: RA, seropositive for rheumatoid factor, RA, seronegative for rheumatoid factor, RA with extra-articular manifestations, adult-oneset Stills disease, juvenile RA. The reasons for the cancellation of bDMARD during the first year of treatment were: insufficient effectiveness (including primary inefficiency), adverse events, administrative reasons, clinical and laboratory remission, death. RESULTS: A year after being included in the study, treatment was continued in 92 (45%) patients and was discontinued in 112 patients. The average time of treatment amounted to 0.750.33 years. The longest duration of treatment was in the RTM and ABA groups (0.920.22 and 0.830.29 years, respectively). In 56 (50%) patients, bDMARD was canceled due to insufficient effectiveness (including primary inefficiency), 28 patients (25%) due to the development of adverse reactions, 19 (17%) patients for administrative reasons, 7 (6.25%) patients due to drug remission. During the first year of therapy, there were 2 (1.75%) deaths due to severe comorbid conditions in patients, one of whom received RTM, the other tocilizumab. CONCLUSION: Study showed that 45% of patients with RA continue treatment with first-time bDMARD for more than 12 months. The most common reason for discontinuation of therapy was its lack of effectiveness. The best survival rate of bDMARDs was observed in RTM and ABA. When selecting bDMARD in each case, it is necessary to take into account the continuity at all stages of treatment.
32393150 Non-TNF inhibitor switchers versus TNF inhibitor cyclers from multicentre rheumatoid arthr 2020 Sep To compare therapeutic efficacy of tumour necrosis factor inhibitor (TNFi) cyclers and non-TNFi switchers in patients with rheumatoid arthritis (RA) having inadequate response to previous TNFis (TNF-IR patients) using composite measures including imaging assessment with power Doppler ultrasonography (PDUS). Patients with RA who had inadequate response to one or more previous TNFi agents with moderate or higher disease activity were enrolled. The outcomes of 56 TNF-IR patients were analysed. Patients were divided into 19 TNFi cyclers and 37 non-TNFi switchers (16 abatacept [ABT] and 21 tocilizumab [TCZ] switchers). Retention ratio at 6 months was significantly higher in non-TNFi switchers than in TNFi cyclers (p < .05). Although there was no significant difference, non-TNFi switchers tended to have a larger decrease than TNFi cyclers in efficacy indicators based on clinical disease activity index and PDUS. Multivariate logistic regression analysis identified a following independent factor associated with both EULAR good response and retention of a biologic agent: non-TNFi switch (p < .05 for both). Non-TNFi switchers were shown to have significantly higher percentage of EULAR good response and higher retention than TNFi cyclers. A non-TNFi biologic agent may hence be a preferential next-line treatment for TNF-IR patients.
30784354 Safety profile of baricitinib in Japanese patients with active rheumatoid arthritis with o 2020 Jan Objectives: Baricitinib is a selective oral inhibitor of JAK1/JAK2 for patients with moderately-to-severely active rheumatoid arthritis (RA). Baricitinib's safety profile in Japanese patients was evaluated using six studies (five Ph2/Ph3 trials, one long-term extension study through 01 September 2016) from an integrated database (nine RA studies).Methods: Incidence rates (IRs) or exposure-adjusted IRs (EAIRs) of adverse events (AEs) per 100 patient-years (PY) were calculated using data which included RA patients exposed to any baricitinib dose.Results: Five hundred and fourteen Japanese patients received baricitinib for 851.5 total PY of exposure (median 1.7 years, maximum 3.2). The EAIR of treatment-emergent AEs was 57.4/100PY. There were no deaths; 31 patients had serious infections (IR: 3.6/100PY), 55 herpes zoster (6.5), 0 tuberculosis, 10 malignancies (1.1) including two lymphomas, two major cardiovascular AEs (0.3), one gastrointestinal perforation (0.1), and four deep vein thrombosis (0.5). In Japanese patients, herpes zoster was more frequent than that of patients overall in the integrated database, but the events were considered manageable.Conclusion: In this analysis, baricitinib had acceptable safety profile in Japanese RA patients in the context of demonstrated efficacy. Aside from herpes zoster, baricitinib safety was not notably different between Japanese RA patients and those RA patients in the integrated database.Trial registration: NCT01185353, NCT00902486, NCT01469013, NCT01710358, NCT01721044, NCT01721057, NCT01711359, and NCT01885078 at https://clinicaltrials.gov/.
30057295 Efficacy and safety of glucocorticoids in rheumatoid arthritis: Systematic literature revi 2020 May OBJECTIVES: 1) To systematically and critically review the evidence on the characteristics, efficacy and safety of glucocorticoids (CS) in rheumatoid arthritis (RA); 2) to generate practical recommendations. METHODS: A systematic literature review was performed through a sensitive bibliographic search strategy in Medline, Embase and the Cochrane Library. We selected randomized clinical trials that analyzed the efficacy and/or safety of CS in patients with RA. Two reviewers performed the first selection by title and abstract. Then 10 reviewers selected the studies after a detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. In a nominal group meeting, based on the results of the systematic literature review, related recommendations were reached by consensus. RESULTS: A total of 47 articles were finally included. CS in combination with disease-modifying antirheumatic drugs help control disease activity and inhibit radiographic progression, especially in the short-to-medium term and in early RA. CS can also improve function and relieve pain. Different types and routes of administration are effective, but there is no standardized scheme (initial dose, tapering and duration of treatment) that is superior to others. Adverse events when using CS are very frequent and are dose-dependent and variable severity, although most are mild. Seven recommendations were generated on the use and risk management of CS. CONCLUSIONS: These recommendations aim to resolve some common clinical questions and aid in decision-making for CS use in RA.
32029494 Tuberculosis among patients treated with TNF inhibitors for rheumatoid arthritis, ankylosi 2020 Feb 5 OBJECTIVES: This study aimed to assess the risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) treated with any of the commercially available tumour necrosis factor inhibitors (TNFis) in Slovenia. DESIGN: This is a cohort, registry (biorx.si) cross-linked with the Slovenian National TB Registry. SETTING: National, involving all Slovenian rheumatology centres (six secondary and two secondary/tertiary). PARTICIPANTS: 2429 patients with RA, AS or PsA exposed to at least one TNFi participated in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were age-adjusted and sex-adjusted TB incidence rates (IRs) and the standardised incidence ratios (SIRs) compared with the general population exploring different TNFi exposure windows. The secondary outcome measures were a detailed characterisation of the national latent tuberculosis infection (LTBI) screening and TB chemoprophylaxis protocol implementation. RESULTS: Among the 2429 patients exposed to at least one TNFi for a total of 10 445 (49% RA, 33% AS and 18% PsA) person-years (PY), 99% completed LTBI screening and 6% required TB chemoprophylaxis. Six RA (three adalimumab, three certolizumab), two PsA (two golimumab) and zero AS patients developed TB. Five out of eight had miliary TB, three out of eight had pulmonary TB and two patients died. The age-standardised and sex-standardised TB IR (95% CI) per 100 000 PYs/SIRs (95% CI) compared with the general Slovenian population for the current TNFi exposure were 52 (0 to 110)/6.7 (0.6 to 80), 47 (0 to 110)/6.1 (0.3 to 105), 45 (0 to 109)/5.8 (0.3 to 112) overall, in RA and PsA, respectively. CONCLUSIONS: The TB IR in the Slovenian patients with RA, AS and PsA treated with TNFi was comparable with TB IRs in TB non-endemic countries with less than a tenth of the patients requiring TB chemoprophylaxis.
33127856 Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of th 2020 Oct OBJECTIVE: Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). We report the largest integrated safety analysis of tofacitinib, as of March 2017, using data from phase I, II, III, IIIb/IV and long-term extension studies in adult patients with RA. METHODS: Data were pooled for patients with RA who received ≥1 tofacitinib dose. Incidence rates (IRs; patients with events/100 patient-years [PY]; 95% CIs) of first-time occurrences were obtained for adverse events (AEs) of interest. RESULTS: 7061 patients received tofacitinib (total exposure: 22 875 PY; median [range] exposure: 3.1 [0 to 9.6] years). IRs (95% CI) for serious AEs, serious infections, herpes zoster (all), opportunistic infections (excluding tuberculosis [TB]) and TB were 9.0 (8.6 to 9.4), 2.5 (2.3 to 2.7), 3.6 (3.4 to 3.9), 0.4 (0.3 to 0.5) and 0.2 (0.1 to 0.2), respectively. IRs (95% CI) for malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC and lymphomas were 0.8 (0.7 to 0.9), 0.6 (0.5 to 0.7) and 0.1 (0.0 to 0.1), respectively. IRs (95% CI) for gastrointestinal perforations, deep vein thrombosis, pulmonary embolism, venous thromboembolism, arterial thromboembolism and major adverse cardiovascular events were 0.1 (0.1 to 0.2), 0.2 (0.1 to 0.2), 0.1 (0.1 to 0.2), 0.3 (0.2 to 0.3), 0.4 (0.3 to 0.5) and 0.4 (0.3 to 0.5), respectively. IR (95% CI) for mortality was 0.3 (0.2 to 0.3). IRs generally remained consistent across 6-month intervals to >78 months. CONCLUSION: This represents the largest clinical dataset for a JAK inhibitor in RA to date. IRs remained consistent with previous reports from the tofacitinib RA clinical development programme, and stable over time. TRIAL REGISTRATION NUMBERS: NCT01262118; NCT01484561; NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01059864; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT00413699; NCT00661661.For summary of phase I, phase II, phase III, phase IIIb/IV and LTE studies included in the integrated safety analysis, see online supplemental table 1.
32347300 IL-38 restrains inflammatory response of collagen-induced arthritis in rats via SIRT1/HIF- 2020 May 29 OBJECTIVE: To observe the restraining effect of IL-38 on inflammatory response in collagen-induced arthritis rats (CIA), and to explore the regulatory mechanism of SIRT1/HIF-1α signaling pathway. METHODS: 40 SD rats were randomly divided into Control group, CIA group, CLL group and CLH group, with 10 rats in each group; CIA rat model was established. The effects of IL-38 on arthritis index, inflammatory response, osteogenic factor and angiogenic factor were observed by methods including HE staining, ELISA, immunohistochemical and immunofluorescence. Human synoviocytes were cultured in vitro, and SIRT1 inhibitors were added to detect the expression for relating factors of SIRT1/HIF-1α signaling pathway by Western blot. RESULTS: IL-38 could alleviate CIA joint damage and restrain inflammatory response, could up-regulate the expression of OPG in CIA rats and could down-regulate the expression of RANKL and RANK. IL-38 could restrain the expression of VEGF, VEGFR1, VEGFR2 and HIF. Moreover, we found that IL-38 could up-regulate the SIRT1 expression and down-regulate the HIF-1α, TLR4 and NF-KB p65 expression in CLL and CLH groups. From the treatment of synoviocytes to simulate the CIA model and the treatment of SIRT1 inhibitors, we demonstrated that the inhibitory effect of IL-38 on inflammatory factors and regulation of SIRT1/HIF-1α signaling pathway-related proteins were inhibited. CONCLUSION: IL-38 can restrain the inflammatory response of CIA rats, can promote the expression of osteogenic factors, can inhibit neovascularization, and can alleviate joint damage in rats. The mechanism may be related to the regulation of SIRT1/HIF-1α signaling pathway.
31116052 Related factors, increased mortality and causes of death in patients with rheumatoid arthr 2020 May Objectives: Interstitial lung disease (ILD) is a life-threatening extra-articular manifestation of rheumatoid arthritis (RA). We aimed to clarify the relationship between chronic ILD with a pattern of usual interstitial pneumonia (UIP) or non-UIP and mortality in RA patients.Methods: We retrospectively surveyed information of consecutive RA patients who visited our hospital from 2009 to 2014. The relationship between their mortality and chronic ILD (UIP or non-UIP) detected by high-resolution computed tomography was examined.Results: Of 2702 patients enrolled, 261 (9.7%) had chronic ILD and among these 120 had a UIP pattern. At the onset of RA, the prevalence of chronic ILD was 6%. Patients with chronic ILD had a higher mortality than those without. The most frequent cause of death was pneumonia including acute exacerbation (AE) of chronic ILD. Lung cancer death was frequently identified in deceased patients with chronic ILD with a UIP pattern compared with the other decedents (p=.062). The estimated mortality of lung cancer in patients with chronic ILD with a UIP pattern was five times higher than the general population.Conclusion: RA patients with ILD with a UIP pattern have a high mortality rate and are prone to die of AE or lung cancer.
31776579 Rheumatoid arthritis and risk of spontaneous abortion: a Danish nationwide cohort study. 2020 Aug 1 OBJECTIVES: To investigate the influence of RA or preclinical RA on the risk of spontaneous abortion (SA) while taking age and duration of RA into consideration. METHODS: By linkage of data from Danish national registries, we established a nationwide cohort of pregnancies in Denmark from 1 January 1977 to 31 December 2014. We used multiple logistic regression to estimate; odds ratios (OR) for SA in women with RA or preclinical RA, compared with women without, and OR for SA by maternal age in women with RA or preclinical RA. RESULTS: A total of 2 612 529 pregnancies were included. Women aged <35 years diagnosed with RA <5 years before pregnancy had an increased risk of SA (OR = 1.25 95% CI: 1.07, 1.48), compared with women without RA aged <35. Women at the same age diagnosed with RA ≥5 years before pregnancy had an OR of 1.14 (0.96-1.34), compared with women without. Among women with RA aged ≥35 years and women with preclinical RA at time of pregnancy, no increased risk of SA was found. The risk of SA increased by maternal age in both women with RA, preclinical RA and in women without. CONCLUSION: Among women aged <35 years, the risk of SA was higher in women with RA compared with women without. After the age of 35 years, the risk of SA was no different from that among women without RA, even though the risk of SA increased with increasing age.
30570833 Risk of Hospitalized Infection and Initiation of Abatacept Versus Tumor Necrosis Factor In 2020 Jan OBJECTIVE: We aimed to evaluate the comparative risk of hospitalized infection among patients with rheumatoid arthritis (RA) who initiated abatacept versus a tumor necrosis factor inhibitor (TNFi). METHODS: Using claims data from Truven MarketScan database (2006-2015), we identified patients with RA ages ≥18 years with ≥2 RA diagnoses who initiated treatment with abatacept or a TNFi. The primary outcome was a composite end point of any hospitalized infection. Secondary outcomes included bacterial infection, herpes zoster, and infections affecting different organ systems. We performed 1:1 propensity score (PS) matching between the groups in order to control for baseline confounders. We estimated incidence rates (IRs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) for hospitalized infection. RESULTS: We identified 11,248 PS-matched pairs of patients who initiated treatment with abatacept and TNFi with a median age of 56 years (83% were women). The IR per 1,000 person-years for any hospitalized infection was 37 among patients who initiated treatment with abatacept and 47 in those who initiated treatment with TNFi. The HR for the risk of any hospitalized infection associated with abatacept versus TNFi was 0.78 (95% CI 0.64-0.95) and remained lower when compared to infliximab (HR 0.63 [95% CI 0.47-0.85]), while no significant difference was seen when compared to adalimumab and etanercept. The risk of secondary outcomes was lower for abatacept for pulmonary infections, and similar to TNFi for the remaining outcomes. CONCLUSION: In this large cohort of patients with RA who initiated treatment with abatacept or TNFi as a first- or second-line biologic agent, we found a lower risk of hospitalized infection after initiating abatacept versus TNFi, which was driven mostly by infliximab.
31250758 The Oral Administration Effect of Drug Mannuronic Acid (M2000) on Gene Expression of Matri 2020 BACKGROUND: Rheumatoid Arthritis (RA) is a complex disease involving an unknown number of genes, and affecting a large number of organs, tissues, and sites across the body. It is affecting approximately 1% of the population worldwide. The safety and therapeutic efficacy of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property has been demonstrated under in vitro, in vivo examinations and clinical trials phase 1/11 in Ankylosing Spondylitis (AS) patients in addition to phase I/11 and 111 in Rheumatoid Arthritis (RA) patients. OBJECTIVE: In this study, our goal is to evaluate the therapeutic efficacy of oral administration of M2000 on gene expression of the matrix metalloproteinase (MMP2, MMP9) and tissue inhibitor of metalloproteinase (TIMP1, TIMP2) as inflammatory molecules in the progression of rheumatoid arthritis. METHODS: The study has included 15 RA patients who had an insufficient response to the conventional drug. Therefore, mannuronic acid was used as an additive to the conventional regime. The research was a single-blinded study. The dose of M2000 was 500mg orally twice per day for 12 weeks. There were 15 healthy participants considered as control. Blood samples have been collected from both groups once from the healthy control and twice from RA patients before and after treatment with M2000. The Peripheral Blood Mononuclear Cells (PBMCs) were isolated for assessment of the gene expression level of MMP2, MMP9, TIMP1, and TIMP2 using the real-time PCR method. RESULTS: The gene expression level of MMP2 and MMP9 reported a significant reduction in RA patients after treatment with M2000 compared to before treatment. On the other hand, the gene expression level of TIMP2 demonstrated a significant increase in RA patients after treatment with mannuronic acid compared to before treatment, but there was no significant difference between the group of RA patients before treatment and the control group. Vice versa to other molecules, there was no significant difference in the level of TIMP1 in compression with RA patients before and after treatment. CONCLUSION: our findings proved that the β -D- mannuronic acid) as a novel NSAID with immunosuppressive property has a significant effect on the gene expression level of MMP2, MMP9 and TIMP2 molecules in RA patients.