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ID PMID Title PublicationDate abstract
29334721 Efficacy and safety of tocilizumab in Korean patients with active rheumatoid arthritis. 2019 Jul BACKGROUND/AIMS: To investigate the efficacy and safety of tocilizumab (TCZ) humanized anti-interleukin-6 receptor monoclonal antibody, in Korean patients with active rheumatoid arthritis (RA) refractory to conventional disease modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX). METHODS: The main study was a 24-week, randomized, double-blind, controlled trial that was followed by a 48-week, open-labeled, extension phase. TCZ (8 mg/kg) or placebo was intravenously administered every 4 weeks. RESULTS: Those treated with TCZ showed more favorable outcomes in terms of 20% according to the American College of Rheumatology response criteria (ACR20) and ACR50 responses, individual parameters of ACR core set, disease activity score in 28 joints (DAS28) remission, and European League Against Rheumatism (EULAR) response at week 24. These improvements were maintained or increased during the extension period. DAS28 remission at week 72 was associated with EULAR good response at week 12. The patients who experienced any adverse event (AE) were more frequent in the TCZ group compared to the placebo group. Most AEs were mild or moderate in intensity, although TCZ therapy had possible AEs including serious infection, abnormal liver function, and atherogenic lipid profile. CONCLUSION: TCZ infusion add-on is highly efficacious and well-tolerated in Korean patients with active RA refractory to conventional DMARDs including MTX. EULAR good response at week 12 could predict DAS28 remission at week 72.
31506089 Prevalence of feet and ankle arthritis and their impact on clinical indices in patients wi 2019 Sep 11 BACKGROUND: We aimed to evaluate the prevalence of foot and/or ankle arthritis (FAA) and its impact on clinical indices in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study used data from the Korean College of Rheumatology Biologics & Targeted therapy registry to observe clinical outcomes of patients undergoing biologics therapy and conventional therapy. FAA was defined as ≥1 tender or swollen joint in the ankle and/or 1st-5th metatarsophalangeal (MTP) joints. Disease Activity Score 28 (DAS28), Routine Assessment of Patient Index Data 3 (RAPID3), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) were assessed. RESULTS: Among 2046 patients, 598 had FAA. The ankle joint was the most commonly involved joint in FAA (tender joint, 71.4%; swollen joint, 59.5%), followed by the third and second MTP joints. Patients with FAA showed higher DAS28, RAPID3, SDAI, and CDAI scores. FAA presence was significantly associated with non-remission as per DAS28-ESR (odds ratio, 3.4; 95% confidence interval, 2.0-5.8), DAS28-CRP (3.6, 2.4-5.3), SDAI (6.3, 2.8-14.6), CDAI (7.6, 2.4-24.3), and RAPID3 (5.6, 2.7-11.5) indices on adjusting for age, sex, disease duration, presence of rheumatoid factor, presence of anti-cyclic citrullinated peptide antibody, lung disease, use of methotrexate, and previous use of biological disease-modifying anti-rheumatic drugs. Patients with FAA were less likely to achieve remission of SDAI (n = 6, 1.0%) and CDAI (n = 3, 0.5%) than that of DAS28-ESR (n = 21, 3.5%), DAS28-CRP (n = 38, 6.4%), and RAPID3 (n = 12, 2.0%). CONCLUSIONS: FAA represents a severe disease activity and is an independent risk factor for non-remission in patients with RA.
31803498 A quarter of patients time their early rheumatoid arthritis onset differently than physici 2019 OBJECTIVE: Early rheumatoid arthritis (RA) treatment requires timely recognition. This large, multicentre study compared patient-reported vs physician-reported onset of early RA. METHODS: Patients from the Canadian Early ArThritis CoHort with early/suspected RA (persistent synovitis <1 year) completed questionnaires asking about the date of symptom onset; and rheumatologists date of onset for persistent synovitis. Groups with similar reported timing (patient and physician) versus differing timing of 30 days or more were compared. RESULTS: In 2683 patients, the median patient symptom duration (IQR) was 178 days (163) and physician-reported duration was 166 (138). 1940 (72%) patients had similar patient-reported and physician-reported onset (<30 days), whereas 497 (18%) reported onset 30 or more days preceding physicians, and 246 (9%) 30 or more days after physicians. Patients reporting onset preceding physicians had lower baseline Disease Activity Score based on 28 joint count, swollen joint counts and erythrocyte sedimentation rate (p<0.05). Patients reporting onset after physicians were more likely to be rheumatoid factor positive (p<0.001) and had higher anticitrullinated protein antibody titres (p<0.009). Regression showed low income, smoking, fibromyalgia, osteoarthritis and baseline non-methotrexate non-biological disease-modifying antirheumatic drug use were predictors for longer patient-reported symptoms. At 12 months, patients reporting longer symptom duration than physicians had lower rates of Simplified Disease Activity Index remission and higher physician global assessments. CONCLUSION: Over one-fourth of patients reported differences of >1 month in symptom onset from their rheumatologist. Patients with longer symptom durations had less improvement at 1 year, which may be reflective of comorbid musculoskeletal conditions.
31068954 Dynamics of the Type I Interferon Response During Immunosuppressive Therapy in Rheumatoid 2019 Objective: The type I interferon (IFN) response in rheumatoid arthritis (RA) has been extensively studied in relation to therapy with biological DMARDs (bDMARDs). However, the effect of conventional synthetic (cs)DMARDs and glucocorticoids (GCs) on IFN response gene (IRG) expression remains largely unknown, even though csDMARDS are used throughout all disease phases, including simultaneously with biologic therapy. This study was aimed to determine the dynamics of IFN response upon immunosuppressive treatment. Methods: Whole blood was collected in PAXgene tubes from 35 RA patients who received either COBRA therapy (combination of prednisone, initially 60 mg, methotrexate and sulfasalazine) (n = 14) or COBRA-light therapy (prednisone, initially 30 mg, and methotrexate) (n = 21). Expression of 10 IRGs was determined by real-time PCR at baseline (T0), after 4 weeks (T4), and 13 weeks (T13) of treatment. IRG selection was based on the differential presence of transcription factor binding sites (TFBS), in order to study the therapy effect on different pathway components involved in IFN signaling. Results: Seven of the 10 IRGs displayed significant changes during treatment (p ≤ 0.016). These 7 IRGs all displayed a particularly pronounced decrease between T0 and T4 (≥1.6-fold, p ≤ 0.0059). The differences between IRG sensitivity to the treatment appeared related to the presence of TFBS for STAT1 and IRF proteins within the genes. The extent of the decreases between T0 and T4 was similar for the COBRA- and COBRA-light-treated group, despite the differences in drug combination and doses in those groups. Between T4 and T13, however, IRG expression in the COBRA-light-treated group displayed a significant increase, whereas it remained stable or decreased even further in most COBRA-treated patients (comparison of mean fold changes, p = 0.011). A significant association between IRG dynamics and clinical response to therapy was not detected. Conclusions: Immunosuppressive treatment with csDMARDs, in this case a combination of prednisolone, methotrexate and sulfasalazine, substantially downregulates the IFN response in RA patients. The dynamics of this downregulation were partly dependent on the presence of TFBS within the IRGs and the combination and dosages of agents, but they were irrespective of the clinical response to therapy.
31876200 Methotrexate pharmacokinetic is influenced by co-administration of cyclosporin in rheumato 2020 May The aim was to investigate if the pharmacokinetics of methotrexate (MTX) are affected by the addition of cyclosporin (CsA). Forty patients diagnosed with early rheumatoid arthritis (RA) were included in this open prospective study: 20 patients were treated with a dose of 7.5 mg MTX and a dose of 2.5 mg/kg CsA, 20 patients were treated with a dose of 7.5 mg MTX and placebo. Baseline measurements of plasma MTX and erythrocyte MTX were made. Area under the plasma concentration versus time curve (AUC) and other pharmacokinetic variables were estimated by means of a population based software model. Clinical improvement of 20-50-70% according to the American College of Rheumatology (ACR) and adverse events were evaluated ongoing for 52 weeks. We found that mean peak plasma MTX concentration was significantly higher in the MTX + CsA combination treatment group (p = .003). No differences in AUC, erythrocyte MTX or other pharmacokinetic parameters were found between the two treatment groups. Estimated Glomerular Filtration Rate (eGFR) decreased significantly in the MTX + CsA treatment group (p < .001), but no serious adverse events occurred in either of the two groups. In conclusion, CsA added to methotrexate treatment in early RA significantly increased peak-plasma MTX concentration, but other pharmacokinetic parameters and measurements of MTX were unchanged.
31823822 Zoledronic acid ameliorates the effects of secondary osteoporosis in rheumatoid arthritis 2019 Dec 10 BACKGROUND: Secondary osteoporosis may occur in patients with rheumatoid arthritis (RA), causing irreversible joint damage and disability. Bisphosphonates, the recently developed bone resorption inhibitors, have demonstrated significant therapeutic effects on senile and postmenopausal osteoporosis. This study evaluated the efficacy and safety of zoledronic acid (ZOL), with or without methotrexate (MTX), for the prevention and treatment of bone destruction in RA patients. METHODS: We recruited 66 RA patients with symptoms of secondary osteoporosis. They were randomized into three treatment groups-combined treatment with MTX and ZOL, ZOL monotherapy, or MTX monotherapy-in two consecutive 6-month periods. The participants were followed for 12 months. At the end of each treatment period, improvement in disease activity, bone destruction, and fracture risk were evaluated. RESULTS: Combined treatment with ZOL and MTX had significantly better clinical efficacy compared with either ZOL or MTX monotherapy (P < 0.05). The combination significantly improved the lumbar spine and hip BMD and reduced FRAX scores, suggesting that ZOL combined with MTX reduces bone loss and risk of hip fracture in RA patients with secondary osteoporosis. CONCLUSION: ZOL has a synergistic effect when combined with MTX, inhibiting RA disease activity, reducing fracture risk, and improving quality of life in RA patients with secondary osteoporosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800019290. Registered 3 November 2018-Retrospective registered, http://www.chictr.org.cn/showproj.aspx?proj = 31758.
30981868 Is prediction of clinical response to methotrexate in individual rheumatoid arthritis pati 2020 Jan OBJECTIVES: To identify, by a systematic literature review, predictors of clinical response to methotrexate treatment in rheumatoid arthritis patients, which would facilitate personalised treatment. METHODS: PubMed and Embase databases were searched for original articles. Additionally, congress abstracts of European League Against Rheumatism and American College of Rheumatology annual meetings of the past 2 years were screened. Articles describing predictors of clinical response to methotrexate after 3 to 6 months were included, since this reflects the time span used to determine treatment effectiveness and decide on treatment changes in treat-to-target recommendations. RESULTS: Thirty articles were included, containing 100 different predictors and 11 predictive models. Nineteen predictors and 2 predictive models were studied in multiple cohorts. Female gender was found to be a predictor of non-response in two studies (odds ratios 0.55 and 0.54), but these findings could not be replicated in two other studies. In two studies, smoking predicted non-response (adjusted odds ratios 0.35 and 0.60), although this was inconsistent over all response criteria assessed. Rheumatoid factor positivity predicted non-response in two studies (adjusted hazard ratio 0.61, adjusted odds ratio 0.4), but this was not found in three other studies. Heterogeneity in studies prohibited further comparison of predictive values between studies. Additionally, a validated epigenetic model was found (area under the curve 0.90 and 0.91). CONCLUSIONS: No predictors were identified reliably predicting clinical response to methotrexate after 3 to 6 months in the individual patient: clinical predictors were weak. However, a promising epigenetic model was found that needs further validation.
30337216 Serum free amino acid levels in rheumatoid arthritis according to therapy and physical dis 2019 Jan BACKGROUND: In presented study the amino acid analysis was performed in serum derived from rheumatoid arthritis patients (RA) according to undertaken therapy and classification of physical disability. The results were compared with previously published data. METHODS: The levels of 31 free amino acids were determined in 50 serum samples derived from RA subjects and 51 controls. The RA patients were divided into two groups according to the therapy (methotrexate/leflunomide, infliximab/adalimumab/etanercept/tocilizumab, prednisolone/NSAID) and classification of physical disability of the patients. Levels of amino acids were measured by LC-MS/MS. The obtained results were subjected to multivariate statistical tests. RESULTS: According to the therapy that was being used, threonine differentiated RA patients treated with methotrexate/leflunomide - infliximab/adalimumab/etanercept/tocilizumab (p = 0.00954) and infliximab/adalimumab/etanercept/tocilizumab - prednisolone/NSAID (p = 0.03109), while tryptophan differentiated RA patients treated with methotrexate/leflunomide - infliximab/adalimumab/etanercept/tocilizumab (p = 0.01723). In the functional classification, arginine differentiated RA samples between class III and IV (p = 0.02332), while glycine differentiated them between class I+II and III of the Steinbrocker functional classification (p = 0.03366). CONCLUSIONS: An analysis of the metabolome profile requires the use of validated bioanalytical methods that are strictly dedicated for this purpose. The obtained results are not accidental (p value less than 0.05), and all of the selected amino acids play an important role in inflammation and immune response. It is suggested that studied amino acids can be considered as a markers for diagnosis of RA and monitoring pharmacotherapy of the disease.
30285533 Safety and effectiveness of high-dose methotrexate (over 8 mg/week) in 2838 Japanese pat 2020 Jan Objectives: To confirm the safety and effectiveness of high-dose (>8 mg/week) methotrexate (MTX) for the treatment of rheumatoid arthritis in Japan.Methods: A postmarketing surveillance program enrolled Japanese patients with rheumatoid arthritis starting on high-dose MTX followed up for 24 or 52 weeks. Analyses for safety, risk factors affecting safety, and effectiveness were conducted.Results: The safety/effectiveness analysis sets included 2838/2779 and 335/326 patients in the 24 and 52-week follow-up groups, respectively. Incidence of adverse drug reactions (ADRs) and serious ADRs was 21.42 and 1.66% in the 24-week and 35.52 and 2.69% in the 52-week groups, respectively. The Disease Activity Score in 28 Joints (DAS28) was significantly decreased as early as four weeks from the start of high-dose MTX; after 24-week (4.09-3.21) and 52-week treatment (3.91-2.80; both p < .001). In a majority of patients at baseline who had high-to-moderate disease activity, the remission rate (defined as DAS28-4ESR <2.6) increased three-fold from 10.6% (baseline) to 33.0% (24-week) compared to patients with low disease activity whose remission rate increased two-fold from 24.0% (baseline) to 53.6% (24 weeks).Conclusion: High-dose MTX was well tolerated in Japanese patients, resulted in improved disease control, and can be considered a step forward in achieving treat-to-target goals.
31830144 Real world, big data cost of pharmaceutical treatment for rheumatoid arthritis in Greece. 2019 INTRODUCTION: Rheumatoid Arthritis (RA) is a highly prevalent autoimmune disease associated with joint inflammation and destruction. Treatment for RA, especially with biologic agents (biologics), improves patient functionality and quality of life and averts costly complications or disease progression. Cost of RA pharmaceutical treatment has rarely been reported on the basis of real-world, big data. This study reports on the real-world, big data RA pharmaceutical treatment cost in Greece. METHODS: The Business Intelligence database of the National Organization for Healthcare Services Provision (EOPYY) was used to identify and provide analytics on patients on treatment for RA. EOPYY is responsible for funding healthcare and pharmaceutical care services for approximately 95% of the population in the country. ICD-10 codes were applied to identify patients with RA and at least one reimbursed prescription between 1 June 2014 and 31 May 2015. RESULTS: 35,873 unique patients were recorded as undergoing treatment for RA. Total reimbursed treatment cost for the study period was €81,206,363.70, of which €52,732,142.18 (64.94%) was for treatment with biologics. Of that cost, €39,724,489.71 (48.32%) accounted for treatment with anti-TNFs and/or methotrexate/corticosteroids. CONCLUSION: Real world, big data analysis confirms that the major driver of RA pharmaceutical cost is, as expected, the cost of treatment with biologics. It is critical to be able to match this cost to the treatment outcome it produces to ensure an optimal, no-waste, evidence-based allocation of healthcare resources to need.
31245906 Prevalence of methotrexate intolerance among patients with rheumatoid arthritis using the 2019 Aug AIM: Methotrexate (MTX) is the anchor drug for the treatment of rheumatoid arthritis (RA). MTX is associated with adverse events that limit its use. The MTX intolerance severity score (MISS) was developed to identify symptoms related to MTX use in juvenile idiopathic arthritis and RA patients. The aim of this study is to translate and validate the MISS in the Arabic language. METHODS: Forward and backward translation of the MISS were performed by two fluent Arabic translators and reviewed by three rheumatologists. Consecutive patients with RA who used MTX for ≥3 months were recruited from two tertiary care centers in Riyadh, Saudi Arabia. A test was considered positive if the patient scored ≥6 points. The internal consistency and stability of the items were evaluated using Cronbach's alpha and the test-retest method. RESULTS: A total of 185 patients were recruited. Of those patients, 158 (85.4%) were female. The mean (±SD) age and disease duration were 49.7 (±12.67) and 8.67 (±7.1) years, respectively. The mean Disease Activity Score of 28 joints was 3.2 (±1.3). Fifty-five (30%) patients were illiterate. Seventy-three (39.5%) patients had a positive MISS. Of those patients, 55 (75.3%) and 18 (24.7%) were using the oral and subcutaneous forms of MTX, respectively. The Arabic MISS had good internal consistency (Cronbach's alpha = 0.792) and a factorable study size for test-retest and factor analysis (Kaiser-Meyer-Olkin = 0.745). CONCLUSION: The Arabic MISS showed validity and good reliability in detecting MTX intolerance in RA patients. MTX intolerance is prevalent among RA patients. Larger studies are needed to confirm these findings.
30511295 MicroRNA-132, miR-146a, and miR-155 as potential biomarkers of methotrexate response in pa 2019 Mar INTRODUCTION: Rheumatoid arthritis (RA) patients have high expression levels of hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p in peripheral blood. We studied if baseline blood levels of these microRNAs (miRNAs) could predict response to methotrexate (MTX). METHODS: RA patients (the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria) with active disease (disease-modifying anti-rheumatic drug (DMARD)-naïve and Disease Activity Score 28 (DAS28) > 3.2) were enrolled. They were treated with MTX by gradually increasing dose up to 25 mg/week. After 4 months, the DAS28 score was calculated and EULAR response was assessed. The hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p levels were measured by real-time qPCR in whole-blood RNA at baseline and 4 months after therapy, using hsa-let-7a-5p as housekeeping gene. Results are expressed as median (interquartile range). RESULTS: The 94 enrolled patients (81 females) had a median age of 40 (17) years, disease duration of (24) months, and DAS28 4.61 (1.11). After 4 months of therapy, 73 were classified as responders and 21 as non-responders. Baseline levels of all three miRNAs were lower in responders than non-responders, hsa-miR-132-3p (- 8.03 (0.70) versus - 7.47 (0.85), P < 0.05), hsa-miR-146a-5p (- 5.11 (0.88) versus - 4.62 (0.90), P < 0.05), and hsa-miR-155-5p (- 7.59 (1.07) versus - 7 (0.72), P = 0.002). Receiver operating characteristic curve analysis showed that all three miRNAs were also good predictors of MTX response, showing the following values: hsa-miR-132-3p (area under curve (AUC) 0.756, P < 0.05), hsa-miR-146a-5p (AUC 0.760, P < 0.05), and hsa-miR-155-5p (AUC 0.728, P = 0.002). CONCLUSION: hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p are potential biomarkers of responsiveness to MTX therapy.
32186107 Effect of adjuvant therapy with electroacupuncture on bone turnover markers and interleuki 2019 Aug OBJECTIVE: To evaluate the effect of electroacupuncture as an adjuvant treatment with first-line medications on bone metabolism biomarkers and interleukin-17 (IL-17) in the peripheral blood of patients with rheumatoid arthritis (RA). METHODS: Sixty RA patients were randomized into three groups. The control group was treated with methotrexate plus leflunomide (MTX+LEF), the acupuncture group was treated with simple needling plus MTX + LEF, and the patients in the electroacupuncture (EA) group were treated with EA plus MTX + LEF. EA or acupuncture was applied every other day for a total of 10 times over a treatment period of 8 weeks. RESULTS: In all three treatment groups, serum levels of the bone metabolism markers PICP, N-MID, and B-ALP were elevated and the concentrations of the inflammatory markers β-CTx, IL-17, CRP, and TRACP-5b were reduced after treatment. These differences were significant for the EA group but not the other groups (P < 0.05). CONCLUSION: EA could effectively reduce the suffering and improve the quality of life of RA patients. It is a promising adjuvant therapy for enhancing the effectiveness of clinical therapeutics.
31161488 Long-term clinical, functional, and cost outcomes for early rheumatoid arthritis patients 2019 Oct OBJECTIVE: To retrospectively compare the long-term clinical, functional, and cost outcomes for early RA patients (symptoms < 1 year) who did or did not achieve early remission in a treat-to-target strategy. METHOD: Five-year data of 471 patients included in the DREAM remission induction cohort were used. Patients were treated according to a pre-specified 28-joint Disease Activity Score (DAS28) remission driven step-up treatment strategy starting with methotrexate, addition of sulfasalazine, and exchange of sulfasalazine for biological medication in case of failure. Two- and 3-year healthcare costs were available for selected subsamples of patients only. RESULTS: DAS28 remission was achieved in 27.7%, 38.2%, and 51.6% of patients at 2, 3, and 6 months, respectively. Achieving DAS28 remission at 2, 3, or 6 months was consistently associated with significantly lower DAS28 and Health Assessment Questionnaire-Disability scores at 1, 3, and 5 years of follow-up (all P values < 0.02). Patients in remission at 2, 3, or 6 months also had significantly lower medication costs per patient over the first 2 and 3 years of treatment, mainly due to lower biologic use, but differences in total healthcare resource costs (hospital admissions plus consultations) were less pronounced. Mean total medication and total healthcare resource costs at 3 years were €1131 and €1757 for patients in remission at 6 months vs. €7533 (P < 0.01) and €2202 (P = 0.09) for those not in remission. CONCLUSION: Achieving early remission was associated with beneficial clinical outcomes for early RA patients and lower costs in the long term. Key Points • Previous studies in rheumatoid arthritis patients have demonstrated that early good response is associated with sustained remission and better long-term clinical outcomes. • This study extents these findings by examining the long-term benefits of achieving early remission on clinical, patient-reported, and economic outcomes in a real-world cohort of patients with very early rheumatoid arthritis treated according to treat-to-target principles. • The findings of this study clearly demonstrate that aiming for early remission in rheumatoid arthritis patients is beneficial in the long-term in terms of better clinical and functional outcomes and lower healthcare costs.
29998824 Prevention of the progressive biochemical cartilage destruction under methotrexate therapy 2019 Mar OBJECTIVES: The aim of the study was to investigate biochemical cartilage composition under methotrexate (MTX) therapy and to intra-individually assess the impact of inflammation severity on cartilage composition by using dGEMRIC MRI in patients with early rheumatoid arthritis (eRA). METHODS: dGEMRIC of MCP joints of the index and middle finger of 28 patients from the AthroMark cohort were examined prior to MTX-therapy as well as after 3 and 6 month. OMERACT RA MRI score and clinical parameters (CRP and DAS28) were registered at any time point. Each patient's second and third MCP joints were dichotomised into the joint with more severe synovitis versus the joint with less severe synovitis according to the RAMRIS synovitis subscore. RESULTS: MCP joints with more severe synovitis ('bad joints') demonstrated significantly lower dGEMRIC values compared to MCP joints with less severe synovitis ('good joints') at time-points 0 and 3 months (p=0.002; p=0.019, respectively). After 6 months of MTX therapy no significant difference of dGEMRIC index was found between good and bad joint (p=0.086). CONCLUSIONS: Under MTX therapy, biochemical cartilage integrity remains stable; no further cartilage destruction occurred if patients were treated early in the course of the disease. In addition, six months of MTX therapy triggered an alignment of dGEMRIC index of MCP joints with initially severe synovitis and less severe synovitis in an intra-individual assessment. This underlines the importance of an early treatment in eRA to reduce further cartilage damage of the inflamed joints.
31099191 Infection risks of rituximab versus non-rituximab treatment for rheumatoid arthritis: A sy 2019 Aug OBJECTIVE: The aim of this study was to assess the differences in infection rates between rituximab (RTX) and non-RTX treatment in patients with rheumatoid arthritis (RA). METHODS: A systematic review and meta-analysis was conducted by searching databases of PubMed, MEDLINE, EMBASE, Web of Science and Cochrane Library through to June 2018. We included studies that compared RTX and non-RTX treatment for patients with RA. Outcome measures were overall infections and serious infections between RTX and non-RTX treatments. RESULTS: A total of 11 articles, including 9502 patients (4595 with RTX treatment and 4907 with non-RTX treatment) met our inclusion criteria. The results demonstrated that RTX-related all infections and serious infections in RA patients were 43.8% and 4.4%, respectively. Pooled analysis showed no significant differences between RTX and non-RTX treatment groups in overall infections rate (43.3% vs 44.9%; odds ratio [OR] = 0.87; 95% CI = 0.70-1.08) and serious infections rate (4.1% vs 4.6%; OR = 1.05; 95% CI = 0.84-1.31). Subgroup analysis also showed no significant differences in overall infections between RTX versus placebo (OR = 0.98, 95% CI = 0.71-1.33); RTX versus tumor necrosis factor inhibitors (TNFi) (OR = 0.47, 95% CI = 0.30-1.73); RTX plus methotrexate (MTX) versus placebo plus MTX (OR = 0.98, 95% CI = 0.77-1.24), and in serious infections between RTX versus placebo (OR = 1.06, 95% CI = 0.36-3.07); RTX versus TNFi (OR = 1.25, 95% CI = 0.96-1.63); RTX plus MTX versus placebo plus MTX (OR = 0.69, 95% CI = 0.39-1.20). CONCLUSION: In patients with RA, RTX treatment has no additional risks for infections over non-RTX treatment.
30620765 Mortality, disability, and healthcare expenditure of patients with seropositive rheumatoid 2019 BACKGROUND: We investigated the mortality and disability rate, as well as the healthcare expenditure, for patients with newly diagnosed seropositive rheumatoid arthritis (RA) who were followed-up for up to 10 years, compared to the general population in Korea. METHODS: We conducted a nationwide population-based study using a National Health Insurance Service-National Sample Cohort of the Korean population, consisting of 1 million individuals who submitted medical care claims between 2002 and 2013. RA was identified using as the International Classification of Diseases code M05 (seropositive RA), with prescription of any disease-modifying anti-rheumatic drug (DMARD). Our analysis was based on the data of 1655 patients with incident seropositive RA and 8275 non-RA controls. The controls were matched to the RA cohort by sex, age at the time of diagnosis, duration of follow-up, geographic region, type of social security, and household income. RESULTS: The most commonly used conventional synthetic DMARDs were hydroxychloroquine (71.30%) and methotrexate (69.5%), with adalimumab being the most commonly used biologic DMARD (2.54%). The mortality rate was significantly higher in the RA than the control group (incidence rate ratio [IRR] 1.29, 95% confidence interval [CI] 1.02-1.64) in the first 10 years after diagnosis. Specifically, mortality due to infectious diseases (IRR 4.41, 95% CI 1.60-12.17) and pneumonia (IRR 3.92, 95% CI 1.46-10.53) was significantly higher in the RA than control group. The disability rate was higher in the RA than control group over the first 10 years of the disease (IRR 2.27, 95% CI 1.77-2.92), which was attributed to a higher incidence of physical disability (IRR 3.81, 95% CI 2.81-5.15). Annual health expenditure was greater for the RA than the control group. CONCLUSIONS: Therefore, the rate of mortality and disability, as well as healthcare expenditure, are higher for patients with RA over the first 10 years of the disease onset, than the general population of Korea. The use of claim data has limited the quality of information and there is a limit to the observation period, and we expect the prospective national-wide multicenter cohort for longer period to overcome these limitations.
31271042 Bubbles in the Box: Recurrent Pneumothorax From Bronchopleural Fistula in Rheumatoid Arthr 2019 Jan When considering rheumatoid arthritis (RA)-associated pulmonary diseases, interstitial lung disease and pleural disease are the most common RA-associated pulmonary manifestations while spontaneous pneumothorax and bronchopleural fistula (BPF) are among the extremely rare ones. To the best of our knowledge, all the previous reports of RA-associated BPFs were attributed to peripherally located pulmonary nodules that necrotized, burst into the pleural cavity, and eventually lead to the fistula formation. However, we hereby present the first case of BPF in an RA patient that formed in the absence of any underlying rheumatic pulmonary nodules. Additionally, our patient was on chronic methotrexate therapy, and there are no data in the literature that suggest methotrexate-induced parenchymal lung disease can predispose to BPF formation. Our report is the first to introduce a probe to further investigate this association.
31660707 Quality of life and clinical outcomes in Polish patients with high activity rheumatoid art 2019 Nov BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease. Therapy is based on disease-modifying agents. Methotrexate (MTX) is used in first-line therapy and, in the case of failure, its alternatives include leflunomide, which was recommended in Poland within the National Health Fund Therapeutic Program. OBJECTIVES: The purpose of the study was to evaluate the parameters of quality of life of Polish patients with high RA activity during treatment with leflunomide. Additional aims were to evaluate the effectiveness and safety of treatment. MATERIAL AND METHODS: We performed a retrospective analysis of the data from the PLUS study. The PLUS study comprised 887 adult patients from 30 centers. During the study patients received leflunomide in a maintenance dose of 20 mg or 10 mg once daily. Before the study, 100 mg of leflunomide had been administered daily for 3 days, followed by a maintenance dose of 20 mg/day or 10 mg/day for at least a month before enrollment. The PLUS study observation time was up to 12 months with 1 control visit every 3 months. The patients' quality of life was assessed with Health Assessment Questionnaire Disability Index (HAQ-DI). Erythrocyte sedimentation rate (ESR), Disease Activity Score (DAS28) and CRP (C-reactive protein) concentration were used to assess the disease activity. RESULTS: Six hundred seventy-nine patients completed the study. The HAQ-DI decreased after 3 months of observation (mean value 1.46 vs baseline 1.63; p = 0.001) and remained stable. The percentage of patients with HAQ-DI less than 1 and greater than 2 increased from 12.2% to 17.8% and decreased from 33.2% to 20.3%, respectively (p < 0.0001); DAS28 progressively decreased on subsequent visits. C-reactive protein and ESR decreased after 3 months and remained stable. Adverse events were observed in 4.4% of patients. CONCLUSIONS: Treatment with standard leflunomide doses is safe and allows for significant clinical improvement.
30963994 Genetic markers associated with clinical and radiographic response in adalimumab plus meth 2019 Sep OBJECTIVES: Biologics, including tumour necrosis factor inhibitors such as adalimumab (ADA), have significantly improved outcomes in rheumatoid arthritis (RA). Because the clinical course of RA and response to therapy may be influenced by the genetic background of the patient, the objective of this retrospective parallel-assigned case-control analysis was to evaluate the associations between candidate genetic markers for RA with clinical and radiographic responses to ADA + methotrexate (MTX) or MTX monotherapy in the Optimal Protocol for Treatment Initiation with MTX and ADA (OPTIMA) study. METHODS: Three candidate genetic markers were tested: HLA-DRB1 shared epitope (SE), interleukin 4 receptor (IL4R) single nucleotide polymorphism (SNP) rs1805010, and Fc gamma receptor IIb (FcgRIIb) SNP rs1050501. Genetic associations with week 26 clinical and radiographic responses during treatment with ADA + MTX or MTX monotherapy were assessed using summary statistics, chi-square or Fisher's exact test, correlation, regression models, and corrected for multiple-comparisons. RESULTS: Low disease activity (p=0.008) and improvement in American College of Rheumatology 20%, 50% and 70% response criteria (p=0.02, 0.01, and 0.02, respectively) were associated with HLA-DRB1 SE copy numbers in the ADA + MTX treatment arm, and the FcgRIIb SNP was a predictor of remission. The IL4R SNP correlated with radiographic progression in patients receiving MTX monotherapy, supporting previous findings. CONCLUSIONS: This pharmacogenetic analysis identified genetic components that contribute to clinical responses to anti-rheumatic therapy.