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ID PMID Title PublicationDate abstract
32501149 JAK inhibitors for the treatment of rheumatoid arthritis. 2020 Dec The treatment of rheumatoid arthritis has changed dramatically over the last two decades since the development of biological disease-modifying anti-rheumatic drugs (bDMARDs). Moreover, Janus kinase (JAK) inhibitors became available in 2013. JAK inhibitors are low-molecular-weight compounds, which exert anti-rheumatic effects by suppressing the action of JAK, an intracellular tyrosine kinase. Of note, biologics bind to extracellular proteins and block their activity. The availability of JAK inhibitors that are as effective as bDMARDs, despite the completely different route of administration and mode of action, has enabled the treatment of rheumatoid arthritis to enter a new stage. JAK inhibitors are useful in a variety of cases, including patients who inadequately responded to treatment with methotrexate and/or bDMARDs. Oral administration is convenient for patients. Nevertheless, the drugs should be carefully prescribed as they are metabolized in the liver and kidneys. Attention should also be paid to adverse events, such as infections including herpes zoster. It is necessary to understand the characteristics of JAK inhibitors and use these agents judiciously.
32237476 [Systematic reviews of effects of Tripterygium Glycosides Tablets on pro-inflammatory fact 2020 Feb To systematically evaluate the effects of Tripterygium Glycosides Tablets alone or in combination with methotrexate(MTX) and leflunomide(LEF) on the levels of pro-inflammatory cytokines in patients or animal models with rheumatoid arthritis(RA), and to provide reference for clinical application and related basic research, this study systematically searched databases of CNKI, VIP, WanFang, PubMed, Embase and Cochrane Library, collected relevant clinical or animal experimental studies, used risk assessment tools to evaluate the quality of research, and used Revman 5.3 software to conduct Meta-analysis or descriptive analysis of the outcome indicators included in the literatures. Of the 1 709 papers retrieved, 3 clinical studies and 12 animal experiments were included. The results showed that compared with MTX alone, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of peripheral blood TNF-α(SMD=-8.88,95%CI[-10.77,-6.99],P<0.000 01),IL-1β(P<0.000 01) and IL-6(SMD=-8.63, 95%CI[-10.57,-6.69], P<0.000 01) in RA patients. Compared with LEF alone, the combination of Tripterygium Glycosides Tablets and LEF could not further reduce the expression levels of TNF-α(P=0.20), IL-1β(P=0.17), IL-6(P=0.31). In RA animal model, compared with model group, Tripterygium Glycosides Tablets could reduce the expression levels of peripheral blood IL-1β(SMD=-6.29,95%CI[-9.64,-2.93],P<0.000 2)in peripheral blood(SMD=-1.39,95%CI[-1.77,-1.02],P<0.000 01), joint fluid(P<0.000 01) and paw plasma(P=0.02), and also reduce the expression levels of TNF-α in RA animal model group. Compared with MTX alone, Tripterygium Glycosides Tablets alone reduced the same levels of TNF-α(P=0.42) and IL-6(P=0.08) in joint fluid, while Tripterygium Glycosides Tablets combined with MTX could further reduce the levels of IL-6(P=0.000 1) in joint fluid; compared with LEF alone, Tripterygium Glycosides Tablets have the similar effects on reducing the expression levels of peripheral blood TNF-α(P=0.16), IL-1β(P=0.32), IL-6(P=0.12), while Tripterygium Glycosides Tablets combined with LEF could further reduce the expression levels of TNF-α(P=0.008), IL-1β(P=0.02), IL-6(P<0.000 1) in peripheral blood. Therefore, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of pro-inflammatory cytokines in peripheral blood of RA patients. Tripterygium Glycosides Tablets alone could reduce the expression levels of pro-inflammatory cytokines in peripheral blood and local joint of RA animal models. Tripterygium Glycosides Tablets combined with MTX or LEF could further reduce the express levels of pro-inflammatory cytokines in peripheral blood of RA animal models. Due to the limitation of literature, this conclusion needs to be further validated.
33301475 Comprehensive exploratory autoantibody profiling in patients with early rheumatoid arthrit 2020 BACKGROUND: We sought to identify immunoglobin G autoantibodies predictive of early treatment response to methotrexate, the recommended first-line therapy for patients with newly diagnosed rheumatoid arthritis, and to the interleukin-6 receptor inhibitor biologic tocilizumab, initiated as the first disease-modifying anti-rheumatic drug. MATERIALS AND METHODS: In baseline sera of a subset of patients with newly diagnosed rheumatoid arthritis in the U-Act-Early study, selected based on specific responder/non-responder criteria using the Disease Activity Score assessing 28 joints (DAS28) within the first 20 weeks, we measured immunoglobin G antibody reactivity against 463 protein antigens and performed supervised cluster analysis to identify predictive autoantibodies for treatment response. The analysis subset comprised 56 patients in the methotrexate arm (22 responders, 34 non-responders) and 50 patients in the tocilizumab arm (34 responders, 16 non-responders). For comparison, these analyses were also performed in 50 age- and gender-matched healthy controls. RESULTS: Increased reactivity in responders versus non-responders was found in the methotrexate arm against two antigens-DOT1-like histone lysine methyltransferase (p = 0.009) and tropomyosin (p = 0.003)-and in the tocilizumab arm against one antigen-neuro-oncological ventral antigen 2 (p = 0.039). Decreased reactivity was detected against two antigens in the methotrexate arm-G1 to S phase transition 2 (p = 0.023) and the zinc finger protein ZPR1 (p = 0.021). Reactivity against the identified antigens was not statistically significant in either treatment arm for patients with rheumatoid factor-positive versus-negative or anti-cyclic citrullinated test-positive versus test-negative rheumatoid arthritis (p ≥ 0.06). CONCLUSIONS: Comprehensive profiling of baseline sera revealed several novel immunoglobin G autoantibodies associated with early treatment response to methotrexate and to tocilizumab in disease-modifying anti-rheumatic drug-naive patients with rheumatoid arthritis. These findings could eventually yield clinically relevant predictive markers, if corroborated in different patient cohorts, and may facilitate future benefit in personalised healthcare.
30629813 Cost-Effectiveness of Combination Disease-Modifying Antirheumatic Drugs Versus Tumor Necro 2020 Mar OBJECTIVE: To determine whether intensive combinations of conventional synthetic disease-modifying antirheumatic drugs (csDMARDS) achieve similar clinical benefits more cheaply than high-cost biologics such as tumor necrosis factor inhibitors (TNFi) in patients with active rheumatoid arthritis (RA) whose illness has failed to respond to methotrexate and another DMARD. METHODS: We used within-trial cost-effectiveness and cost-utility analyses from health and social care and 2 societal perspectives. Participants were recruited into an open-label, 12-month, pragmatic, randomized, multicenter, 2-arm, noninferiority trial in 24 rheumatology clinics in England and Wales. Costs were linked with the Health Assessment Questionnaire (HAQ; primary outcome) and quality-adjusted life years derived from 2 measures (Short-Form 36 health survey and EuroQol 5-domain 3-level instrument). RESULTS: In total, 205 participants were recruited, 104 in the csDMARD arm and 101 in the TNFi arm. Participants in the csDMARD arm with poor response at 6 months were offered TNFi; 46 participants (44%) switched. Relevant cost and outcome data were available for 93% of participants at 6-month follow-up and for 91-92% of participants at 12-month follow-up. The csDMARD arm had significantly lower total costs from all perspectives (6-month health and social care adjusted mean difference -£3,615 [95% confidence interval (95% CI) -4,104, -3,182]; 12-month health and social care adjusted mean difference -£1,930 [95% CI -2,599, -1,301]). The HAQ score showed benefit to the csDMARD arm at 12 months (-0.16 [95% CI -0.32, -0.01]); other outcomes/follow-ups showed no differences. CONCLUSION: Starting treatment with csDMARDs, rather than TNFi, achieves similar outcomes at significantly lower costs. Patients with active RA and who meet the National Institute for Health and Care Excellence criteria for expensive biologics can be treated with combinations of intensive csDMARDs in a cost-effective manner.
32264838 Phenotypic variability in a child with Felty's syndrome: a case report. 2020 Apr 7 BACKGROUND: Felty's syndrome (FS) is characterized by the triad of rheumatoid arthritis (RA), splenomegaly and neutropenia. The arthritis is typically severe and virtually always associated with high-titer rheumatoid factor. The presence of persistent neutropenia is generally required to make the diagnosis. Most patients diagnosed with FS are aged 50-70 years and have had RA for more than 10 years. It is rarely seen in patients with juvenile idiopathic arthritis (JIA), with only five cases having been reported throughout the world. CASE PRESENTATION: The present study describes the case of a 14-year-old female with a seven-year history of polyarticular JIA, presenting with splenomegaly, hepatomegaly, cholestasis and thrombocytopenia. However, she occasionally developed neutropenia. Titers of rheumatoid factor and anti-CCP were persistently high, and the antinuclear antibody titer was 1:320, while the antibody results for anti-dsDNA and anti-Sm were negative. Serum levels of IgA, IgG, IgM and IgE were all persistently elevated, and the ratio of CD19(+) lymphocytes in the subgroups of lymphocytes was persistently high. The level of complements was normal. No STAT3 and STAT5B mutations were found by next-generation sequencing. The patient did not respond to methotrexate, prednisolone, hydroxychloroquine (HCQ), sulfasalazine and etanercept but was responsive to rituximab. CONCLUSIONS: JIA, thrombocytopenia and splenomegaly are the most common and important features in six children with FS, while persistent neutropenia is not seen in all these patients. No complement deficiency has been found in children with FS so far. Manifestations of FS without neutropenia may be extremely rare. There are differences between adults and children in the clinical and laboratory features of FS.
32868798 Efficacy of methotrexate and etanercept biosimilar rhTNFR:Fc in Chinese patients with acti 2020 Aug 31 Rheumatoid arthritis is a chronic inflammatory disease which could lead to severe joint damage and disability. This study was performed to determine the efficacy and safety of methotrexate (MTX) therapy combined with maintenance or discontinuation of etanercept biosimilar rhTNFR:Fc in active rheumatoid arthritis patients in Chinese patients. In this controlled, randomized and open-label study, 89 patients with active rheumatoid arthritis were enrolled at 7 institutions in China between September 2010 and May 2011. In a period of 52 weeks, patients were randomly assigned to one of three treatment groups: MTX plus rhTNFR:Fc for 52 weeks, MTX plus rhTNFR:Fc for 24 weeks, or MTX monotherapy. The primary endpoint was the joint damage evaluated by change from baseline (CFB) of van de Heijde modified Total Sharp Score (mTSS). Intention-to-treat population were used for analysis. A total of 89 enrolled patients were eligible for this study, of whom 32 were assigned to MTX plus rhTNFR:Fc52 group, 31 to MTX plus rhTNFR:Fc24, and 26 to MTX monotherapy. Only one patient was lost to follow up in the MTX plus rhTNFR:Fc24 group. The mTSS CFB was lower in the rhTNFR:Fc pooled group (combination of data in the MTX plus rhTNFR:Fc52 group and MTX plus rhTNFR:Fc24 group) comparing with MTX monotherapy at week 24 and 52 (P = 0.03 and P < 0.01). Additionally, ACR50 and ACR70 response rates were both higher in the rhTNFR:Fc pooled group than MTX monotherapy (P < 0.05). Combination of MTX and rhTNFR:Fc in patients with active rheumatoid arthritis could effectively inhibit joint structure damage.
33269654 Methotrexate-associated lymphoproliferative disorder with histopathological features of hi 2021 Jan An 84-year-old Japanese woman suffering from rheumatoid arthritis (RA), who had been treated with methotrexate (MTX) for 15 years, was admitted to our hospital for generalised lymphadenopathy, thrombocytopenia, anaemia, elevated aminotransferases, and elevated CRP levels. Pathological findings of cervical lymph node biopsy were compatible with histiocytic necrotising lymphadenitis (HNL). Small lymphocytes positive for Epstein-Barr virus (EBV)-encoded small RNA were detected in the tissue. We suspected a MTX-associated lymphoproliferative disorder (MTX-LPD), withdrew MTX and administered leucovorin (folic acid). The patient's symptoms gradually resolved following discontinuation of MTX. We considered that this patient developed HNL as an MTX-LPD when EBV was reactivated. This is the first case of HNL associated with MTX treatment for RA, which we report here along with clinical course.
32664100 Efficacy and safety of dual filtration plasmapheresis combined with biological agents in a 2020 Jul 10 To investigate the effectiveness of dual filtration plasmapheresis (DFPP), a novel blood purification treatment, as a rapid and sustained disease-modifying therapy for active refractory rheumatoid arthritis (RA).A retrospective cohort study had been conducted. One hundred fifty three patients aged 18 years or older with active refractory RA were treated with DFPP combined with infliximab (IFX), IFX, or glucocorticoid (GC), all the above treatments were combined with methotrexate (MTX).Baseline characteristic of the 153 patients (DFPP: n = 53; IFX: n = 51; GC: n = 49) were similar across groups. The remission rate of CDAI (SDAI) in the DFPP treatment group was significantly higher than that of the IFX and GC group after 3 months of treatment. The remission rate of DFPP treatment group was above 50%, while in IFX and GC group, the rate of CDAI (SDAI) remission was 41.2% (37.3%) and 22.4% (14.2%) after 3 months of treatment.A combination of DFPP and biological agents can quickly induce remission or low disease activity of active refractory RA.
33454678 THE EFFECT OF ATORVASTATINUM IN THE TREATMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS. 2020 OBJECTIVE: The aim: Was to evaluate the effect of 6-month pathogenetic treatment in combination with atorvastatinum on the endothelium function, lipid and adipokine levels, paroxonase activity and activity of inflammatory process in RA patients. PATIENTS AND METHODS: Materials and methods: The study included 55 patients with RA, dividing into two groups depending on the intended therapy. The first group included 33 patients with "traditional" treatment by methotrexate, glucocorticoids, and non-steroid anti-inflammatory drugs. The second group included 22 patients with "traditional" treatment and additionally prescribed of atorvastatinum 20 mg/day. The lipid profile, leptin, adipokine, paroxonase activity. C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) levels, FMDBA and IMT of carotid artery were determined in all participants of the study. Control parameters were recorded before the start, after 1 and 6 months of treatment. RESULTS: Results: The FMDBA has increased by 32% in the second group, compared by only 10.9% in the first group. The dynamics of IMT in the first group was also twice lower than in group with the additional use of atorvastatinum. The leptin levels in the second group significantly decreased by 27% and adiponectin levels increased by 12.8%, than in the first group - by 12.8% and by 7% respectively. The appointment of statins over 6 months resulted in DAS28, TNF-α, ESR and CRP reduction by 15%, 31%, 25% and 21.5% respectively. In the first group the dynamics of indicate rates ranged from 7.8% to 22.5%, and was significantly lower than in the second group. CONCLUSION: Conclusions: As a result of the study, it was found that the appointment of atorvastatinum 20 mg/day during 6 months not only reduces dyslipidemia, but also significantly reduces the inflammatory process and adipokine dysregulation, normalizes serum paraoxonase activity and improves the endothelium function.
31630117 Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remis 2020 Jan OBJECTIVES: The aim of this study is to determine whether the 'programmed' infliximab (IFX) treatment strategy (for which the dose of IFX was adjusted based on the baseline serum tumour necrosis factor α (TNF-α)) is beneficial to induction of clinical remission after 54 weeks and sustained discontinuation of IFX for 1 year. METHODS: In this multicentre randomised trial, patients with IFX-naïve rheumatoid arthritis with inadequate response to methotrexate were randomised to two groups; patients in programmed treatment group received 3 mg/kg IFX until week 6 and after 14 weeks the dose of IFX was adjusted based on the baseline levels of serum TNF-α until week 54; patients in the standard treatment group received 3 mg/kg of IFX. Patients who achieved a simplified disease activity index (SDAI) ≤3.3 at week 54 discontinued IFX. The primary endpoint was the proportion of patients who sustained discontinuation of IFX at week 106. RESULTS: A total of 337 patients were randomised. At week 54, 39.4% (67/170) in the programmed group and 32.3% (54/167) in the standard group attained remission (SDAI ≤3.3). At week 106, the 1-year sustained discontinuation rate was not significantly different between two groups; the programmed group 23.5% (40/170) and the standard group 21.6% (36/167), respectively (2.2% difference, 95% CI -6.6% to 11.0%; p=0.631). Baseline SDAI <26.0 was a statistically significant predictor of the successfully sustained discontinuation of IFX at week 106. CONCLUSION: Programmed treatment strategy did not statistically increase the sustained remission rate after 1 year discontinuation of IFX treatment.
33237533 Rapid Onset of Efficacy of Baricitinib in Chinese Patients with Moderate to Severe Rheumat 2021 Jan INTRODUCTION: Baricitinib is an oral, selective inhibitor of Janus kinase which demonstrates clinical efficacy in patients with rheumatoid arthritis (RA). This report aims to analyze the onset time of baricitinib in Chinese patients with moderately to severely active RA who had an inadequate response to methotrexate. METHODS: This post hoc analysis evaluated clinical improvements of Chinese patients treated with baricitinib 4 mg once daily compared with placebo, based on data from a phase 3 study RA-BALANCE. Efficacy measures including American College of Rheumatology 20% (ACR20) response, ACR core set values, Disease Activity Score modified to include the 28 diarthrodial joint count (DAS28) using high-sensitivity C-reactive protein (hsCRP), DAS28-erythrocyte sedimentation rate, Simplified Disease Activity Index, Clinical Disease Activity Index, DAS28-hsCRP ≤ 3.2 response (low disease activity), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated at weeks 1, 2, 4, 8, 12, 14, 16, 20, and 24 (except for FACIT-F evaluated every 4 weeks). A logistic regression model and an analysis of covariance model were used to analyze treatment comparisons of categorical and continuous measures, respectively. RESULTS: Statistically significant (p ≤ 0.05) improvements were observed as early as week 1 or 2 for the baricitinib group compared to placebo in almost all main efficacy measures. For other outcomes including 66 swollen joint count, 68 tender joint count, FACIT-F, and DAS28-hsCRP ≤ 3.2 response rate, differences were evident (p ≤ 0.05) by week 4 in the baricitinib group compared with placebo. Significant improvements in all efficacy measures were sustained through 24 weeks. CONCLUSIONS: Baricitinib demonstrated a rapid onset of efficacy on ACR20 response, ACR core set values, disease activity, and patient-reported outcome improvements in Chinese patients from RA-BALANCE. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02265705.
33128074 Methotrexate osteopathy: five cases and systematic literature review. 2021 Feb INTRODUCTION: Methotrexate (MTX)-related osteopathy is rare, defined by the triad of pain, osteoporosis, and "atypical fractures" when it was first described in the 1970s in children treated with high doses MTX for acute leukemia. Since then, several cases have been reported in patients treated with low-dose MTX for inflammatory diseases. METHODS: A systematic research of cases of MTX-related osteopathy was performed in records of Rheumatology Department of Rennes University Hospital. Data collection focused on demographic data, corticosteroid doses, MTX doses and intake method, cumulative doses, year of diagnosis, fracture location, bone densitometry value, and osteoporosis treatment if necessary. A literature review was also conducted to identify other cases in literature and try to understand the pathophysiological mechanisms of this rare entity. RESULTS: We report 5 cases identified between 2011 and 2019, which represents the largest cohort described excluding oncology cases. Fracture locations were atypical for osteoporotic fractures. All patients improved in the following months with MTX withdrawal. All patients except one were treated with antiresorptives (bisphosphonates, denosumab). Two patients, treated with bisphosphonates, had a recurrence of fracture, once again of atypical location. Twenty-five cases were collected in literature with similar clinical presentation. The cellular studies that investigated the bone toxicity of MTX mainly showed a decrease in the number of osteoblasts, osteocytes, and chondrocytes in the growth plate and an increase in the number and activity of osteoclasts. In vitro, consequences of mechanical stimulation on human trabecular bone cells in the presence of MTX showed an alteration in mechano-transduction, with membrane hyperpolarization, acting on the integrin pathway. In contrast with our report, the cases described in the literature were not consistently associated with a decrease in bone mineral density (BMD). CONCLUSION: MTX osteopathy while rare must be known by the rheumatologist, especially when using this treatment for inflammatory conditions. The mechanisms are still poorly understood, raising the question of a possible remnant effect of MTX on osteo-forming bone cells, potentially dose-dependent. Methotrexate (MTX) osteopathy, described as a clinical triad, pain, osteoporosis, and atypical stress fractures, while rare, must be known by the rheumatologist. Our cohort of 5 cases represent the largest series of the literature. Pathophysiological studies raised the question of a dose-dependent remnant effect of MTX on osteo-forming bone cells.
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.
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.
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.
31393189 Investigation of the predictors of the response to Iguratimod therapy: A post-hoc analysis 2020 Jul Objectives: The treatment response according to patient disease activity during Iguratimod therapy for rheumatoid arthritis has not been sufficiently assessed. A post-hoc analysis of post-marketing surveillance was performed. The treatment effect was evaluated using the European League against Rheumatism (EULAR) response criteria.Methods: Disease Activity Score (DAS) 28 was assessed at various time points. Patients showing a moderate or good response according to the EULAR response criteria at 24 weeks after the start of Iguratimod therapy were considered Responders. Propensity score matching was also performed, after which the factors with the greatest effect on the treatment evaluation were investigated.Results: The mean DAS28 at the start of administration and after 24 weeks was 4.31 and 2.52, respectively, in the Responder and 3.48 and 3.48, respectively, in the Non-responder. After propensity score matching for patient characteristics, the primary factors found to be related to being a Responder were concomitant use of methotrexate (MTX) with Iguratimod, and prior treatment with MTX before the start of Iguratimod.Conclusion: As factors related to the treatment effect, the concomitant use of MTX may contribute to achieving a better effect, and this study has shown that real-world are consistent with the results of clinical trials.
32075469 Distinct decrease in peripheral lymphocytes in EBER-positive cases of MTX-LPD. 2021 Jan OBJECTIVES: To determine the clinical characteristics of methotrexate-associated lymphoproliferative disorder (MTX-LPD). METHODS: In this study, 12 RA patients who developed MTX-LPD were assessed. The peripheral blood lymphocyte (PBL) count at the onset of MTX-LPD was compared to that 6 months before the onset, in Epstein-Barr virus-encoded RNA (EBER)-positive and -negative subgroups. We examined the change in the PBL count after MTX withdrawal. In patients with relapsed LPD, changes in the PBL count before relapse were also examined. RESULTS: Regression of LPD after MTX withdrawal was noted in eight patients. In these patients, the PBL count was decreased at the onset of MTX-LPD compared to 6 months before the onset; the decrease was significantly more prominent in EBER-positive patients. In cases of spontaneous regression of LPD, the PBL count recovered quickly after MTX withdrawal. Four of eight patients showed a recurrence of LPD after they improved following MTX withdrawal. These patients also exhibited a decreased PBL count at recurrence compared to 6 months before recurrence. CONCLUSION: A decrease in the PBL count might be involved in the pathogenesis of MTX-LPD, especially in EBER-positive cases and in patients with LPD relapse after MTX withdrawal following initial improvement.
32076916 Relative efficacy and safety of iguratimod monotherapy for the treatment of patients with 2020 Jul OBJECTIVES: This study aims to compare the efficacy and the safety of the iguratimod with placebo and other disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis. METHODS: Two authors independently searched and selected randomized controlled trials from Cochrane library, Medline (through Pubmed), and Chinese databases, and then assessed the risk of bias (using ROB 2 tool), and graded the certainty of evidence (using the GRADEpro GDT software). We applied the RevMan 5 software for performing meta-analyses of the final consensus data. RESULTS: We identified 12 trials involving 1938 participants. Ten trials had an overall high risk of bias. Although iguratimod had superior efficacy than placebo, the incidence of adverse events was also higher. Inferring to non-inferiority analysis with other DMARD therapy (primarily comprising methotrexate), iguratimod is likely to result in similar treatment response (20% (OR 1.04, 95% CI 0.79 to 1.36), 50% and 70% improvement in American College of Rheumatology criteria) and functional ability at 24 weeks. Although the disease state was slightly better with iguratimod (MD - 0.55, 95% CI - 0.85 to - 0.25), a clinically important improvement was not achieved. Iguratimod may have lower C-reactive protein and erythrocyte sedimentation rate values. Swollen joint count, tender joint count, pain intensity, and patient's and physician's global assessment of disease state may be comparable between the therapies. Both the therapies are likely to have similar odds (OR 0.91, 95% CI 0.67 to 1.26) of adverse events. CONCLUSION: Our evidence suggests that iguratimod may be considered a potential alternative to methotrexate to treat rheumatoid arthritis.Key Points• The Asia Pacific League of Association for Rheumatology (APLAR) has recommended that iguratimod may be used a first-line drug for rheumatoid arthritis in specific cases.• Patients on iguratimod may have similar treatment response, functional ability, disease state, and adverse event profile at 24 weeks compared with those on methotrexate.• Iguratimod may be considered a better alternative to methotrexate in RA patients having high CRP and ESR values.• Future clinical trials in diverse population comparing the efficacy and safety of iguratimod in monotherapy or combination therapy with DMARDs (other than methotrexate) are warranted.
31474599 Comparative Persistence of Methotrexate and Tumor Necrosis Factor Inhibitors in Rheumatoid 2020 Jun 1 OBJECTIVE: The role of methotrexate (MTX) for the treatment of spondyloarthritis (SpA) remains uncertain. Aims were to compare MTX and tumor necrosis factor inhibitor (TNFi) persistence in spondyloarthritis versus rheumatoid arthritis (RA) and to determine whether concomitant conventional synthetic disease-modifying antirheumatic drug (csDMARD) use is associated with improved TNFi persistence in SpA. METHODS: This retrospective cohort study using Optum's deidentified Clinformatics Data Mart Database 2000-2014 identified patients with RA, psoriatic arthritis (PsA), and ankylosing spondylitis (AS) without prior biologic use who were initiating MTX or a TNFi. Cox proportional hazards models compared time to medication discontinuation over the next 2 years between patients with RA, PsA, or AS, adjusting for potential confounders. In similar analyses stratified by disease, Cox models were used to assess whether concomitant use of csDMARD was associated with TNFi persistence. RESULTS: We identified 31,527 MTX initiators (26,708 RA, 2939 PsA, 1880 AS) and 34,651 TNFi initiators (24,134 RA, 6705 PsA, 3812 AS). MTX was discontinued sooner in patients with PsA [adjusted HR (aHR) 1.10, 95% CI 1.04-1.16] and AS (aHR 1.23, 1.16-1.31) versus RA, while TNFi were discontinued at similar rates in RA and AS and discontinued later in PsA (aHR 0.93, 0.89-0.97). Concomitant use of MTX (compared to no csDMARD) was associated with lower rates of TNFi discontinuation in RA (aHR 0.85, 0.80-0.89), PsA (aHR 0.81, 0.74-0.89), and AS (aHR 0.79, 0.67-0.93). CONCLUSION: MTX discontinuation occurs sooner in patients with PsA and AS versus RA. Concomitant use of MTX with a TNFi, however, is associated with improved TNFi persistence in all 3 diseases.