Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
28545554 Whipple's disease mimicking rheumatoid arthritis can cause misdiagnosis and treatment fail 2017 May 25 BACKGROUND: Whipple's disease, a rare chronic infectious disorder caused by Tropheryma whipplei, may present with predominant joint manifestations mimicking rheumatoid arthritis (RA). METHODS: A retrospective single-center cohort study of seven patients was performed. Clinical symptoms were assessed by review of medical charts and Whipple's disease was diagnosed by periodic-acid-Schiff-stain and/or Tropheryma whipplei-specific polymerase-chain-reaction. RESULTS: Median age at disease onset was 54 years, six patients were male. Median time to diagnosis was 5 years. All patients presented with polyarthritis with a predominantly symmetric pattern. Three had erosive arthritis. Affected joints were: wrists (5/7), metacarpophalangeal joints (MCPs) (5/7), knees (5/7), proximal interphalangeal joints (PIPs) (3/7), hips (2/7), elbow (2/7), shoulder (2/7). All patients had increased C-reactive-protein concentrations, while rheumatoid factor and anti-CCP-antibodies were absent, and were initially (mis)classified as RA-patients according to EULAR/ACR-criteria (median DAS28 4.3). Six patients received antirheumatic treatment consisting of prednisone with methotrexate and/or leflunomide, three were additionally treated with at least one biologic agent (abatacept, adalimumab, etanercept, rituximab, tocilizumab). Most patients showed insufficient treatment response. In all patients Tropheryma whipplei was detected in synovial fluid by polymerase-chain-reaction; in three patients the diagnosis of Whipple's disease was further ascertained by periodic-acid-Schiff-staining. Gastrointestinal symptoms and other extra-articular manifestations were absent, mild or non-specific. Treatment was initiated with trimethoprin/sulfamethoxazole in five and doxycycline/hydroxychloroquine in two patients and had to be adapted in five patients. Finally, all patients had good treatment responses with improvement of arthritis and extra-articular manifestations. CONCLUSION: Whipple's disease is rare and can mimic rheumatoid arthritis. Especially patients with seronegative rheumatoid arthritis with a prolonged disease course and insufficient treatment response should be reevaluated for Whipple's disease.
29205926 A retrospective review of the persistence on bDMARDs prescribed for the treatment of rheum 2018 Aug AIM: To describe the persistence of biologic disease modifying anti-rheumatic drugs (bDMARDs) in Australian rheumatoid arthritis (RA) patients, and assess the influence of methotrexate and other conventional DMARD (cDMARD) concomitant medications, and treatment line on bDMARD persistence and glucocorticoids usage. METHOD: RA patients, from the 10% Australian Medicare random sample, aged ≥18 for whom bDMARDs were dispensed were included. Individual sub-cutaneous (SC) anti-tumor necrosis factor-α (anti-TNFα) agents were combined as they were equivalent. RESULTS: Data from 1230 patients were analyzed. For all patients the 12-month persistence rates (based on Kaplan-Meier estimates) were 76% for intravenous (IV) tocilizumab, 63% abatacept (SC/IV), 61% SC-anti-TNFs and 36% IV-infliximab. Persistence rates on first-line bDMARDs were 79% (tocilizumab and abatacept), 64% (SC-anti-TNFs) and 13% (infliximab); rates were sustained for tocilizumab but dropped to 49% for abatacept and 51% for SC-anti-TNFs in the second-line setting. Median treatment persistence was 40 months tocilizumab (95% CI: 30-ND), 33 months abatacept (95% CI: 20-ND); 22 months SC-anti-TNF (95% Cl: 18-27), and 4 months infliximab (95% CI: 2-13). Longer persistence was observed for SC-anti-TNFs and abatacept combined with methotrexate or other cDMARDs. For tocilizumab, persistence was robust with or without concomitant medications. The median oral glucocorticoid doses decreased from 4.1 mg/day (min 0, max 21) to 2.0 mg/day (min 0, max 17.3) over 2 years. CONCLUSIONS: Treatment persistence was longer on tocilizumab followed by abatacept then SC-anti-TNF therapy and was influenced by co-therapy. Glucocorticoid dosage decreased with bDMARD use. This real-world data highlights that persistence on bDMARDs differs according to biologics mode of action and co-therapy.
27777170 Rheumatoid arthritis, insulin resistance, and diabetes. 2017 Jul Recent progress in the management of rheumatoid arthritis (RA) is turning attention toward comorbidities, such as diabetes. The objectives of this review are to clarify the links between RA and diabetes and to assess potential effects of disease-modifying antirheumatic drugs (DMARDs) on diabetes. The increased insulin resistance seen in RA is closely linked to the systemic inflammation induced by certain proinflammatory cytokines such as tumor necrosis factor α (TNFα) and interleukin-6. The prevalence of type 2 diabetes is increased in patients with RA. Furthermore, certain DMARDs including hydroxychloroquine, methotrexate, TNFα antagonist, and interleukin-1β antagonists seem to improve the markers of glucose metabolism. In contrast, glucocorticoids tend to adversely affect glycemic control, particularly when taken chronically. Consequently, a crucial yet insufficiently applied rule is that cardiovascular risk factors must be sought and treated routinely, particularly as the choice of the DMARD may affect glucose metabolism.
29070455 [Efficacy of internalized RGD-modified echogenic liposomes in diagnosis and treatment in a 2017 Oct 20 OBJECTIVE: To prepare internalized RGD (iRGD) modified echogenic liposomes containing methotrexate (MTX) and indocyanine green (ICG) (iRGD MTX ICG ELIP) and evaluate its targeting efficiency and inhibitory effect combined with ultrasound on synovial cells. METHODS: iRGD MTX ICG ELIP was prepared by the thin film rehydration and freeze-lyophilization method and its general characteristics and acoustic responsiveness were assessed. The targeting effect of the prepared liposome was observed by assessing its cell uptake in vitro. In a mouse model of rheumatiod arthritis, the targeting effect of the prepared liposome was determined by detecting the fluorescence intensity of the drug in arthrosis. The inhibitory effect of iRGD MTX ICG ELIP combined with ultrasound on synovial MH7A cells in vitro were investigated using CCK8 test. RESULTS: The average diameter and zeta potential of iRGD MTX ICG ELIP was 134.4∓17.61 nm and 10.07∓4.28 mV, and the entrapment efficiency of MTX and ICG was (62.56∓0.77)% and (95.13∓0.82)%, respectively. With ultrasound exposure, the release of MTX and ICG from iRGD MTX ICG ELIP increased with the ultrasound intensity and with the exposure time. In HUVECs, the uptake efficiency of iRGD MTX ICG ELIP was 1.89 times higher than that of non targeted MTX ICG ELIP (P<0.05). In vivo imaging of mouse joint with rheumatiod arthritis showed that the fluorescence intensity of iRGD MTX ICG ELIP was significantly stronger than that of the non targeted liposome. CCK8 assay showed that iRGD MTX ICG ELIP combined with ultrasound resulted in a survival rate of MH7A cells of (32.49∓3.04)%, significantly lower than the rate of cells treated with iRGD MTX ICG ELIP but without ultrasound (P<0.05). CONCLUSIONS: iRGD MTX ICG ELIP has a suitable particle size and can effectively target HUVECs and the joints with rheumatiod arthritis. With a good drug entrapment efficiency and acoustic responsiveness, the drug loaded liposome shows enhanced inhibitory effect on MH7A cells combined with ultrasound in vitro, suggesting its potential in the treatment of rheumatoid arthritis.
29228799 Calprotectin in patients with chronic rheumatoid arthritis correlates with disease activit 2018 Feb OBJECTIVE: Calprotectin (myeloid-related protein 8/14) is elevated in inflammatory diseases and a correlation of serum calprotectin and disease activity in rheumatoid arthritis (RA) has been shown. In this study, we investigated plasma calprotectin as a disease marker in patients with chronic RA treated with methotrexate (MTX) monotherapy and compared plasma calprotectin with C-reactive protein (CRP) in this matter. METHODS: Seventy-six patients with chronic RA were included in this open prospective study and of these 40 were included prior to initiation of MTX therapy. The patients were followed with laboratory and clinical parameters for 52-56 weeks. Plasma calprotectin was analyzed at the start of study and at various intervals. Radiographic evaluation was performed at baseline and after 17.2 months and progression in joint destruction was measured with Larsen score. The response to MTX was evaluated according to the American College of Rheumatology criteria. RESULTS: Patients starting MTX treatment had significantly higher levels of plasma calprotectin compared to patients well established on MTX therapy (p = .008). Among the 40 patients naive to MTX, 25 responded to MTX therapy and serum calprotectin decreased significantly in these patients (p = .0007). The radiographic damage showed no relation to calprotectin. CONCLUSIONS: Plasma calprotectin is associated with disease activity in patients with chronic RA and is more strongly correlated to MTX response compared to CRP. The role of calprotectin as a disease marker is promising and the advantages compared to CRP needs to be further investigated.
29166919 Similar short-term clinical response to high-dose versus low-dose methotrexate in monother 2017 Nov 22 BACKGROUND: Aiming at rapid decrease of disease activity, there has been a trend to start with higher doses of methotrexate (MTX) in patients newly diagnosed with rheumatoid arthritis (RA), both as monotherapy and in combination with other antirheumatic drugs. We aimed to study the relationship between clinical response and MTX dose as monotherapy or combination therapy in patients with early RA. METHODS: Disease-modifying anti-rheumatic drug (DMARD)-naive patients with early RA, from a large international observational database, the METEOR database, were selected if MTX was part of their initial treatment. Patients were divided into four groups: MTX monotherapy, MTX + convention synthetic (cs)DMARDs, MTX + glucocorticoids or MTX + biologic (b)DMARDs. MTX dose was dichotomized: low dose ≤10 mg/week; high dose ≥15 mg/week. Linear mixed model analyses for the Disease Activity Score (DAS), DAS in 28 joints (DAS28) and Health Assessment Questionnaire (HAQ) were performed in each medication group, with MTX dose and time as covariates. Outcomes were assessed from baseline until 3-6 months follow up. Associations were adjusted for potential confounding by indication using propensity score (PS) modelling. RESULTS: For patients starting MTX monotherapy (n = 523), MTX + csDMARDs (n = 266) or MTX + glucocorticoids (n = 615), the PS-adjusted effects of MTX dose (high versus low) on the DAS, DAS28 and HAQ were small and not clinically meaningful. Patients starting MTX + bDMARDs were disregarded due to low numbers (n =11). CONCLUSIONS: In patients newly diagnosed with RA, no clinical benefit of high compared to low initial MTX doses was found for MTX monotherapy or for MTX combination therapy with csDMARDs or glucocorticoids.
29224127 Defining and characterizing sustained remission in patients with rheumatoid arthritis. 2018 Apr The objective of this study is to characterize stability and clinical features of patients with rheumatoid arthritis (RA) in sustained remission. Combination therapy with methotrexate and tumor necrosis factor inhibitors (TNFi) has increased remission rates in RA but optimal regimens to maintain remission are unknown. We describe Study of Etanercept And Methotrexate in Combination or as Monotherapy in Subjects with Rheumatoid Arthritis (SEAM-RA) and data from a run-in period of longitudinal observation. Patients in Simplified Disease Activity Index (SDAI) remission (score ≤ 3.3) receiving etanercept and methotrexate were screened and had to maintain remission over 3 run-in visits/24 weeks before randomization to combination therapy or withdrawal of etanercept or methotrexate. Baseline characteristics were examined for predictive factors for maintaining remission. As of November 2016, 141 patients have enrolled; of these, 64 have been randomized, 34 were ineligible after run-in, and 43 are in run-in period; 70% have completed run-in. Enrolled and randomized patients, respectively, had mean (standard deviation [SD]) disease duration 11.0 (8.6) and 12.6 (9.7) years; mean (SD) duration of etanercept use 4.2 (3.8) and 4.9 (4.2) years; mean (SD) methotrexate dose 15.9 (4.8) and 15.5 (4.9) mg/week; and mean (SD) SDAI scores 1.5 (0.9) and 1.4 (0.8). At enrollment, 73% and 63% were in Boolean remission based on 28 joints and 66/68 joints, respectively. No enrollment characteristic predicted successful completion of run-in. Two-thirds of patients considered to be in remission at enrollment sustained remission through 24 weeks. Baseline characteristics of enrolled patients and those who completed run-in were comparable.
28862177 Effect of disease-modifying antirheumatic drug therapy on immune response to trivalent inf 2017 Apr BACKGROUND & OBJECTIVES: Patients with autoimmune rheumatic diseases may be at an increased risk of infection due to disease and use of disease-modifying antirheumatic drug (DMARD) therapy. The present study was done to evaluate the immune response to influenza vaccination in patients with rheumatoid arthritis (RA). METHODS: Fifty one RA patients on stable methotrexate (MTX) therapy (≥15 mg/wk), 51 newly diagnosed DMARD-naïve RA patients and 45 healthy controls received a single dose of inactivated seasonal trivalent influenza vaccine. Blood samples were collected just prior to and four weeks after vaccination. Pre- and post-vaccination antibody titres against the three virus strains were measured by hemagglutination inhibition assay. The impact of age, gender, DMARD treatment and pre-vaccination seroprotection on response to the vaccine was assessed by binary logistic regression analysis for each of the virus strains. RESULTS: Pre-vaccination antibody titres were found to be high in the three study groups for all influenza strains, except for Yamagata strain, the titres for which were low in healthy controls. Trivalent influenza vaccination was found to be safe and stimulated a good antibody response in all study groups. On regression analysis, there was no association of age, gender or MTX therapy with vaccine response, except for Yamagata strain where healthy controls had higher positive immune response (P=0.008; odds ratio - 3.37, 95% confidence interval: 1.36-8.32). INTERPRETATION & CONCLUSIONS: Our results indicated that influenza vaccination was safe in RA patients with no detrimental effect on disease activity. MTX therapy at a dose ≥15 mg/wk did not affect the vaccine response. Presence of high pre-vaccination seroprotective antibody levels in the study population indicates the need for re-examination of recommended annual influenza vaccination in such subgroups of population.
29071964 [Effect of Moxibustion on Serum IL-17 and TNF-α Levels in Collagen-induced Arthritis Rats 2017 Apr 25 OBJECTIVE: To observe the influence of moxibustion on serum interleukin -17 (IL-17) and tumor necrosis factor alpha (TNF-α) levels in collagen-induced arthritis (CIA) rats, so as to study its mechanism underlying improvement of rheumatoid arthritis. METHODS: A total of 40 male Wistar rats were used in the present study, and 8 rats were randomly selected as a normal control group. The other 32 rats were modeled. The primary immunity emulsion was made with mixed Type Ⅱ chicken collagen and complete Freund's adjuvant, and 0.3 mL emulsion (containing 0.3 mg collagen) was injected equally into left pelma, tail root and the back. Seven days after the primary immune, the same procedure was conducted to induce the secondary immunity, and the emulsion was made with mixed Type Ⅱ chicken collagen and incomplete Freund's adjuvant. The whole course of mo-deling lasted 21 days. And then 24 CIA rats were randomly divided into model group, medication group and moxibustion group (n=8 in each group). For those of the moxibustion group, suspended moxibustion with 20 mm distance above "Zusanli"(ST 36)and "Kunlun" (BL 60) was performed for 20 min/acupoint, once daily, alternately on left and right hind limbs for 10 consecutive days. For those of the medication group, gavage of methotrexate (0.1 mg/100 g) was administrated once every 5 days, and totally two times. Left ankle joint diameter and body weight were detected, and X-ray of left tarsus was observed in each group before and after modeling or after treatment. Serum levels of IL-17 and TNF-α were determined by ELISA kits. RESULTS: After modeling, the left ankle diameter and serum concentrations of IL-17 and TNF-α increased (P<0.05), and the body weight decreased (P<0.05) in the model group compared to the control group, combined with the tarsus soft tissue swelling, joint space narrowing, bone destruction seen from the tarsal X-ray. After intervention, the ankle diameter, the serum IL-17 and TNF-α levels decreased (P<0.05), and the body weight increased (P<0.05) in both medication and moxibustion groups compared to the model group; meanwhile the tarsus soft tissue swelling and the bone deformity turned to be improved. There were no significant differences between the medication group and the moxibustion group in above mentioned indexes (P>0.05). CONCLUSIONS: Moxi-bustion is effective in CIA rats, and the mechanism may be related to the reduction of serum IL-17 and TNF-α levels.
27908307 Evolution of imaging findings, laboratory and functional parameters in rheumatoid arthriti 2017 Jan OBJECTIVES: To investigate the efficacy and safety of anti-TNF-α agent treatment compared to non-biologic DMARDs in rheumatoid arthritis patients. METHODS: 82 consecutive patients, 29 males, 53 females, aged 42-79, diagnosed with RA and suitable for anti-TNF-α treatment composed two study groups: 42 with pre-existing rheumatoid arthritis-related interstitial lung disease (RA-ILD) and 40 without RA-ILD. Respective control groups consisted of 44 patients with pre-existing RA-ILD and 44 patients without RA-ILD, treated with non-biologic DMARDs. All patients underwent chest high resolution computed tomography (HRCT), pulmonary function tests (PFTs) and peripheral blood biomarkers at baseline and after one year of treatment. RESULTS: There was a significant decrease of air trapping extent and bronchial wall thickening after treatment in RA-ILD and RA-non ILD study groups (p<0.05). This was accompanied by a statistically significant improvement of maximum mid-expiratory flow (MMEF75-25), RV and RV/TLC in both study groups (p<0.05). In the RA-ILD study group ILD extent scores remained unchanged after anti-TNF-α treatment. None of the RA-non ILD group developed new-onset ILD. In both RA-ILD and RA-non ILD control groups, HRCT findings and PFTs did not differ significantly at the one-year follow-up study. Methotrexate (MTX) regression analysis showed in both RA-ILD study and control groups a negative correlation between MTX dose and ILD extent score at one-year and between MTX dose and air trapping extent at baseline and after one year of treatment. CONCLUSIONS: Anti-TNF-α treatment, in contrast to non-biologic DMARDs, there was an improvement of small airways disease. There was no new-onset ILD or exacerbation of preexisting-ILD, especially in patients treated with anti-TNF-α agents, supporting the efficacy and favourable safety profile of this treatment in RA patients.
28277784 Association Between MTHFR C677T Polymorphism and Methotrexate Treatment Outcome in Rheumat 2017 May PURPOSE: Methotrexate (MTX) is one of the most widely used disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis (RA). However, its efficacy in RA patients is variable and unpredictable. Methylene tetrahydrofolate reductase (MTHFR) is an important enzyme in the MTX pathway and is involved in folate metabolism and DNA synthesis. Several studies have examined the association between the MTHFR C677T polymorphism and MTX toxicity and efficacy in RA, but their conclusions remain controversial. MATERIALS AND METHODS: We conducted a comprehensive literature search of the PubMed, Embase, and Cochrane Library databases to identify studies reporting an association between the MTHFR C677T single nucleotide polymorphism and MTX response in RA patients. RESULTS: We identified 16 studies reporting MTX efficacy in 2373 RA cases, and 25 studies reporting MTX toxicity in 4063 RA cases. The pooled data analysis indicated that the MTHFR C677T polymorphism was associated with increased toxicity, but not efficacy, of MTX in RA patients. Further stratification based on ethnicity revealed an association between the MTHFR 677TT genotype and overall MTX toxicity in East Asian and Caucasian patient populations. In addition, RA patients with the MTHFR C677T polymorphism who were supplemented with folic acid displayed significantly elevated risk for MTX toxicity. CONCLUSION: Our study indicated that the MTHFR C677T polymorphism could be used as a predictor of MTX toxicity in RA patients. However, large randomized prospective studies will be required to effectively replicate and validate these findings.
28817201 Exposure-Response Modeling and Power Analysis of Components of ACR Response Criteria in Rh 2017 Sep Population pharmacokinetic/pharmacodynamic (PK/PD) models were developed to quantitate the exposure-response relationships using continuous longitudinal data on American College of Rheumatology (ACR) subcomponents, that is, tender-joint count (TJC), swollen-joint count (SJC), C-reactive protein, patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, and patient's assessment of physical function for 5 biologics approved for use in rheumatoid arthritis. The models were then used to simulate the time courses of clinical outcomes following different treatment regimens. The relative sensitivity of the 7 subcomponents was assessed using Monte Carlo simulation-based power analysis. The developed population PK/PD models adequately described the relationship between serum concentrations and changes in ACR subcomponents. The trial simulation and subsequent power analysis showed that SJC and TJC appeared to be more sensitive than the other 5 ACR subcomponents to detect treatment effect over placebo/methotrexate. These 7 ACR subcomponents had similar power in detecting the treatment difference between different doses. In addition, the continuous measures of ACR subcomponents did not appear to be more sensitive than binary measures.
26878896 Ocular surface findings in patients with rheumatoid arthritis under methotrexate or biolog 2017 Mar PURPOSE: To evaluate the ocular findings in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX) or MTX with biological agents. METHODS: One hundred and twelve eyes of 56 patients with RA and treated with MTX or MTX with biological agents were included in the study. Patients were divided into two groups using DMARDs only (group 1) and patients using DMARDs and biologic agents together (group 2). In both groups; Schirmer's II test, tear film break-up time (tBUT), central corneal thickness (CCT), corneal volume (CV), intraocular pressure (IOP) measurement, and anterior segment and fundus examinations of the eye with slit lamp were carried out. Ocular surface disease index (OSDI) score questionnaire were performed. RESULTS: Thirty-eight patients with a mean age of 53.00 ± 8.19 years were in group 1 and 18 patients with a mean age of 51.00 ± 9.54 years were in group 2. The mean duration of RA was 6.89 ± 7.96 years in group 1 and 5.70 ± 9.00 years in group 2. There was a statistically significant difference between two groups with tBUT, CCT, CV, IOP (p < 0.05) and there was no significant difference with age, sex, disease duration, disease activity, and Schirmer's II test (p > 0.05). The disease duration showed a significant moderate negative correlation with CCT and CV in group 2 (p < 0.05). CONCLUSIONS: Although tBUT values were significantly higher in the combination treatment group, CCT and CV values were significantly lower. Due to the decrease in corneal thickness, IOP was determined to be significantly lower.
27142240 Impact of methotrexate dose on efficacy of adalimumab in Japanese patients with rheumatoid 2017 Jan OBJECTIVE: Upper limit of methotrexate (MTX) for patients with rheumatoid arthritis (RA) was recently increased from 8 to 16 mg/week in Japan. We therefore examined the effect of concomitant MTX dose on the efficacy of adalimumab (ADA) in clinical practice. METHOD: Sixty-one consecutive RA patients treated with ADA were followed for minimum 52 weeks and retrospectively compared by MTX dose; patients receiving concomitant MTX of 10 mg/week or more (MTX ≥10 mg group) and <10 mg/week (MTX <10 mg group). Disease activity and remission were evaluated by the disease activity score 28 (DAS28) criteria. RESULTS: The MTX ≥10 mg group consistently showed better improvement in DAS28 and resulted in more patients (52.8%) with DAS28-remission compared with the MTX <10 mg group (26.1%). Multivariate analysis showed that MTX ≥10 mg had a significant effect on DAS28 remission with odds ratio of 5.12. ADA retention rate was 72.2% in MTX ≥10 mg group compared with 52.0% in MTX <10 mg group. Discontinuation of ADA due to adverse events were comparable in the MTX ≥10 mg and MTX <10 mg groups (11.1% vs. 12.0%). CONCLUSIONS: These findings support the critical role of concomitant MTX in the efficacy of ADA, and recommend use of MTX ≥10 mg in Japanese RA patients.
27452207 Evidence-based recommendations for the diagnosis and management of rheumatoid arthritis fo 2017 Sep AIM: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease leading to joint damage, functional disability, poor quality of life and shortened life expectancy. Early diagnosis and aggressive treatment are a principal strategy to improve outcomes. To provide best practices in the diagnosis and management of patients with RA, the Thai Rheumatism Association (TRA) developed scientifically sound and clinically relevant evidence-based recommendations for general practitioners, internists, orthopedists, and physiatrists. METHODS: Thirty-seven rheumatologists from across Thailand formulated 18 clinically relevant questions: three for diagnosis, 10 for treatments, four for monitoring, and one for referral. A bibliographic team systematically reviewed the relevant literature on these topics up to December 2013. A set of recommendations was proposed based on the results of systematic reviews combined with expert opinions. Group consensus was achieved for all statements and recommendations using the nominal group technique. RESULTS: A set of recommendations was proposed. For diagnosis, either American College of Rheumatology (ACR) 1987 or ACR/European League Against Rheumatism 2010 classification criteria can be applied. For treatment, nonsteroidal anti-inflammatory drugs, glucocorticoid, and disease-modifying antirheumatic drugs, including antimalarials, methotrexate and sulfasalazine are recommended. Physiotherapy should be suggested to all patients. Tight control strategy and monitoring for efficacy and side effects of treatments, as well as indications for referral to a rheumatologist are provided. CONCLUSIONS: These evidence-based recommendations provide practical guidance for diagnosis, fundamental management and referral of patients with RA for non-rheumatologists. However, it should be incorporated with clinical judgments and decisions about care for each individual patient.
29325724 Rheumatoid Arthritis, Disease Modifying Agents, and Periprosthetic Joint Infection: What D 2018 Apr The incidence of periprosthetic joint infection (PJI) among patients with rheumatoid arthritis (RA) is 1.6× greater than in patients undergoing the same procedure for osteoarthritis. This higher risk "may" be due to the immunosuppressive therapies for RA patients including corticosteroids, such as prednisone, and disease-modifying antirheumatic drugs (DMARDs), such as methotrexate. There is a debate about the role of DMARDs in increasing the incidence of subsequent PJI. Studies show conflicting results, with some demonstrating no significant increase in the rates of PJI and some finding otherwise. The International Consensus Meeting on PJI recommended that DMARDs should be halted prior to an elective total joint arthroplasty based on their half-life. Moreover, the International Consensus Meeting stated that cessation of immunosuppressant medications should be performed in consultation with and under the direction of the treating physician. In this review, we aimed to provide an introduction to the available treatment options and cover the recommendations on the treatment protocols for RA patients who undergo elective total joint arthroplasty.
28793911 IgG Fc galactosylation predicts response to methotrexate in early rheumatoid arthritis. 2017 Aug 9 BACKGROUND: Methotrexate (MTX) is the standard first-line therapy in rheumatoid arthritis (RA) with variable clinical efficacy that is difficult to predict. The glycosylation status of immunoglobulin G (IgG) is altered in RA and influenced by MTX treatment. We aimed to further investigate if IgG glycosylation in untreated early RA can predict therapeutic response to MTX. METHODS: We used a shotgun proteomic approach to screen for the Fc glycopeptides in the serum of 12 control subjects and 59 untreated patients with early RA prior to and following MTX initiation. MTX treatment response was defined according to the European League Against Rheumatism at a median of 14 weeks (range 13-15) after treatment initiation. Seropositive patients were defined as those testing positive for anticitrullinated protein antibodies and/or rheumatoid factor at baseline (n = 44). Data analysis was performed using uni- and multivariate statistics. RESULTS: We could confirm a low abundance of galactosylated glycans in untreated patients with early RA compared with control subjects that was partially restored by MTX treatment. This was more evident among future nonresponders than among responders to MTX treatment. Results were further validated and confirmed by multivariate statistical analysis of the baseline Fc glycan, proteomic, and clinical data. We found that the ratio between the main agalactosylated (FA2) and main mono- and di-galactosylated Fc glycans (FA2G1 and FA2G2) of IgG1 ranked as the most prominent factor distinguishing responders from nonresponders. A low baseline ratio of FA2/[FA2G1 + FA2G2]-IgG1 was associated with nonresponse (OR 5.3 [1.6-17.0]) and was able to discriminate future nonresponders from responders to MTX therapy with a sensitivity of 70% (95% CI 46-88%) and a specificity of 69% (95% CI 52-83%). For seropositive patients (n = 44), this trend was improved with a sensitivity of 73% (95% CI 45-92%) for nonresponse and a specificity of 79% (95% CI 60-92%). CONCLUSIONS: We show that the FA2/[FA2G1 + FA2G2] of IgG1 is a biomarker candidate that is significantly associated with nonresponding patients and has potential value for prediction of MTX clinical response.
27726046 Comparative effectiveness of biologics for the management of rheumatoid arthritis: systema 2017 Jan Our aim was to establish the comparative effectiveness of rheumatoid arthritis (RA) biologics, using a systematic review and network meta-analysis. The systematic review used randomized controlled trials (RCTs) in adults with RA who failed treatment with conventional disease-modifying agents for rheumatoid disease (cDMARDs). We compared the effectiveness of abatacept, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, and rituximab to tocilizumab, a recent biologic with a different mechanism of action (anti-IL-6 receptor). A network meta-analysis (NMA) included the indirect and direct evidence previously selected. In total, 207 articles were included describing 68 RCTs. The NMA showed that tocilizumab monotherapy was superior to standard care (ACR20, OR 13.27, 95 % CrI [3.958, 43.98]; ACR50, 17.45 [10.18, 31.24]; ACR70, 37.77 [7.226, 216.3]; EULAR, 10.42 [1.963, 54.8]); and methotrexate (MTX; ACR50, OR 5.44 [4.142, 7.238]; ACR70, 7.364 [1.4, 30.83]; EULAR, 4.226 [1.184, 15.58]) at 26 weeks. Similarly, the combination of tocilizumab + MTX was significantly better than standard care/placebo and MTX alone for ACR20, ACR50, ACR70, and EULAR at 26 weeks (OR 18.63 [5.32, 66.81]; 24.27 [14.5, 41.91]; 46.13 [10.08, 277]; 14.23 [2.493, 84.02]; 4.169 [2.267, 7.871]; 5.44 [4.142, 7.238]; 8.731 [4.203, 19.29]; 7.306 [4.393, 13.04], respectively). At 52 weeks, compared to MTX alone, tocilizumab + MTX was significantly better for ACR20 and ACR50 response. Few significant differences were found between tocilizumab (alone or in combination) and any other biologics. Results must be considered in context with the limitations of the available evidence. This NMA suggests that tocilizumab was superior to cDMARDs and as effective as other biologics for RA.
28102443 [New options for the practice : Update S1/S2 guidelines on rheumatoid arthritis?]. 2017 Mar Guidelines are important tools for evidence-based pharmacological treatment of patients suffering from rheumatoid arthritis. Recommendations assist physicians in identifying the best form of treatment but ultimately, the final decision is based on joint participation by the patient and physician. Nowadays, general concepts, such as treat to target seem to be more important in rheumatoid arthritis than differencies between various drugs or drug classes. The universal recommendation to use methotrexate as the initial disease-modifying antirheumatic drug (DMARD) is driven more by economic reasons than by scientific data, which is not completely wrong but should be disclosed. For the future, more differentiated recommendations need better individual risk stratification and more distinct profiling of the different substances.
28560470 Cost per response for abatacept versus adalimumab in rheumatoid arthritis by ACPA subgroup 2017 Jul Rheumatoid arthritis (RA) is a chronic inflammatory disorder leading to disability and reduced quality of life. Effective treatment with biologic DMARDs poses a significant economic burden. The Abatacept versus Adalimumab Comparison in Biologic-Naïve RA Subjects with Background Methotrexate (AMPLE) trial was a head-to-head, randomized study comparing abatacept in serum anti-citrullinated protein antibody (ACPA)-positive patients, with increasing efficacy across ACPA quartile levels. The aim of this study was to evaluate the cost per response accrued using abatacept versus adalimumab in ACPA-positive and ACPA-negative patients with RA from the health care perspective in Germany, Italy, Spain, the US and Canada. A cost-consequence analysis (CCA) was designed to compare the monthly costs per responding patient/patient in remission. Efficacy, safety and resource use inputs were based on the AMPLE trial. A one-way deterministic sensitivity analysis (OWSA) was also performed to assess the impact of model inputs on the results for total incremental costs. Cost per response in ACPA-positive patients favoured abatacept compared with adalimumab (ACR20, ACR90 and HAQ-DI). Subgroup analysis favoured abatacept with increasing stringency of response criteria and serum ACPA levels. Cost per remission (DAS28-CRP) favoured abatacept in ACPA-negative patients, while cost per CDAI and SDAI favoured abatacept in ACPA-positive patients. Abatacept was consistently favoured in ACPA-Q4 patients across all outcomes and countries. Cost savings were greater with abatacept when more stringent response criteria were applied and also with increasing ACPA levels, which could lead to a lower overall health care budget impact with abatacept compared with adalimumab.