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ID PMID Title PublicationDate abstract
26003891 Reduced folate carrier 1 gene expression levels are correlated with methotrexate efficacy 2015 Jun Responsiveness to methotrexate (MTX), the "anchor drug" for treating rheumatoid arthritis (RA), varies among individual patients. In this study we investigated the effects of folate transporter gene expression levels on disease activity among 56 Japanese patients with RA who were undergoing MTX therapy. We also assessed gene expression levels for 15 healthy control subjects. The mRNA expression levels of reduced folate carrier 1 (RFC1) and proton-coupled folate transporter (PCFT) in PBMCs from these patients and controls were determined using real-time quantitative polymerase chain reaction (PCR). Compared with PCFT, there were large individual differences in RFC1 mRNA expression levels in both RA patients and healthy controls. RFC1 mRNA expression levels and RA disease activity scores were significantly negatively correlated, as disease activity scores were lower for patients with higher RFC1 mRNA expression levels. However, RFC1 mRNA levels were not correlated with MTX doses. Thus, the clinical efficacy of MTX for Japanese RA patients was associated with the expression level of a folate transporter gene. Increased RFC1 expression may increase MTX uptake by immune cells, such as lymphocytes, and as a result, RA disease activity would be reduced.
25188646 Etanercept-induced sarcoidosis in rheumatoid arthritis: FDG PET findings. 2015 Jan We report the F-FDG PET/CT findings of an etanercept-induced sarcoidosis in a patient with rheumatoid arthritis. A 68-year-old woman with rheumatoid arthritis who had been treated with etanercept and methotrexate showed multiple lung nodules and hilar lymph node swellings on CT. She underwent FDG PET/CT for cancer screening. Intense FDG uptakes were found in the multiple lung nodules, bilateral hilar lymph nodes, a periurethral masslike lesion, and cranial meningeal nodules. A histopathological examination revealed epithelioid granuloma with multinucleated giant cells, which was compatible with sarcoidosis.
26781783 Determinants of methotrexate adherence in rheumatoid arthritis patients. 2016 May In rheumatoid arthritis (RA) patients, weekly intake of methotrexate (MTX) is the basic drug treatment. This observational study aims to investigate how many RA patients are adherent in terms of MTX intake and to identify determinants of non-adherence. Intake of MTX (orally or via injection) was recorded in 129 RA patients with an electronic monitoring system (MEMS(®)) during 16 weeks. In addition, two adherence questionnaires, the Medication Adherence Report Scale (MARS-5) and the Compliance-Questionnaire-Rheumatology (CQR) as well as a visual analogue scale (VAS) measuring MTX adherence, were administered to these patients. As possible determinants of adherence, data on demographics, disease and treatment characteristics, depression, illness cognitions, motivation, and social support were collected. Of all participants, 58 % were fully adherent and 75 % skipped at most one dose during 16 weeks. A better mental health status and suffering from comorbidities had a positive effect on adherence, while living alone had a negative effect. These three predictors explained 30 % of the variance in MTX adherence. Of the three self-report medication adherence measures, the VAS correlated the highest with the results of the electronic monitoring system (r = 0.552, p = 0.01). A relatively high adherence rate was observed in RA patients treated with MTX. The determinants identified by this study could be used to screen patients at risk for non-adherence. A simple VAS scale seems to be an acceptable way for a preliminary screening of MTX adherence.
26543364 Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflamm 2015 BACKGROUND: Rheumatoid arthritis (RA) is the most common autoimmune disease in the word, affecting 1% of the population. Long-term prognosis in RA was greatly improved following the introduction of highly effective medications such as methotrexate (MTX). Despite the importance of this drug in RA, 8%-16% of patients must discontinue the treatment because of adverse effects. Last decade, we developed a promising new nanocarrier as a drug-delivery system, lipid-core nanocapsules. OBJECTIVE: The aim of the investigation reported here was to evaluate if methotrexate-loaded lipid-core nanocapsules (MTX-LNC) reduce proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients and even in functional MTX-resistant conditions. We also aimed to find out if MTX-LNC would reduce inflammation in experimentally inflammatory arthritis at lower doses than MTX solution. METHODS: Formulations were prepared by self-assembling methodology. The adjuvant arthritis was induced in Lewis rats (AIA) and the effect on edema formation, TNF-α levels, and interleukin-1 beta levels after treatment was evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during articular infiltration procedures were treated with MTX solution and MTX-LNC. For in vitro experiments, the same dose of MTX was used in comparing MTX and MTX-LNC, while the dose of MTX in the MTX-LNC was 75% lower than the drug in solution in in vivo experiments. RESULTS: Formulations presented nanometric and unimodal size distribution profiles, with D[4.3] of 175±17 nm and span of 1.6±0.2. Experimental results showed that MTX-LNC had the same effect as MTX on arthritis inhibition on day 28 of the experiment (P<0.0001); however, this effect was achieved earlier, on day 21 (P<0.0001), by MTX-LNC, and this formulation had reduced both TNF-α (P=0.001) and IL-1α (P=0.0002) serum levels by the last day of the experiment. Further, the MTX-LNC were more effective at reducing the cytokine production from mononuclear synovial cells than MTX. CONCLUSION: The MTX-LNC were better than the MTX solution at reducing proinflammatory cytokines and T-cell-derived cytokines such as interferon-gamma and interleukin-17A. This result, combined with the reduction in the dose required for therapy, shows that MTX-LNC are a very promising system for the treatment of RA.
27577564 A case of multiple hepatic lesions associated with methotrexate-associated lymphoprolifera 2016 Oct Patients receiving methotrexate (MTX) for the treatment of autoimmune disease are at a high risk of developing lymphoproliferative disorders (LPD), the so-called methotrexate-associated lymphoproliferative disorders (MTX-LPD). We recently performed abdominal ultrasonography (US) in a patient with rheumatoid arthritis (RA) who had developed hepatic dysfunction during the course of MTX therapy; the examination revealed multiple well-demarcated hepatic tumors with slightly irregular borders, the largest one measuring 9 cm in diameter. In view of the finding of portal and hepatic veins perforating the tumor, we suspected a diagnosis of malignant lymphoma and performed a hepatic tumor biopsy. Histopathological examination of the biopsy specimens revealed a diagnosis of diffuse large B-cell lymphoma, and we made a final diagnosis of MTX-LPD. MTX treatment was discontinued, which resulted in rapid resolution of the lesions. Resolution of MTX-LPD can be obtained just by discontinuation of MTX treatment. In patients receiving MTX therapy who are found to have hepatic tumors perforated by the portal vein and/or hepatic vein on abdominal US, it is advisable to perform hepatic tumor biopsy to facilitate differential diagnosis of MTX-LPD and enable a definite diagnosis.
27098382 Reactivation of occult hepatitis B virus infection under treatment with abatacept: a case 2016 Apr 21 BACKGROUND: Abatacept (ABA) is a fusion receptor protein containing the CTLA-4 domain that prevents the activation of naïve T cells by binding the CD80 and CD86 molecules expressed on the surface of dendritic cells, indicated for the treatment of moderate to severe rheumatoid arthritis (RA). There is still little evidence concerning the safety of ABA in RA patients with positive serology for hepatitis virus B (HBV) infection. CASE PRESENTATION: We report the case of a HBV infection reactivation in an ABA-treated male RA patient. The patient (caucasian race, 66-year-old) was diagnosed with RA in Novembre 2010 and in December 2010 he started a treatment with prednisone plus subcutaneous methotrexate. In October 2011, an anti-TNF agent (golimumab) was added but soon discontinued due to an adverse event. At baseline, screening for HBV markers showed a positivity for HBcAb and HBeAb IgG, being HBsAg, HBsAb, HBcAb IgM, HBeAg and HBV DNA negative. Serum amino-transferase (AST and ALT) levels were within the normal range. In January 2012 he was swapped to intravenous treatment with ABA 750 mg/month, that allowed the achievement of a good clinical response and the permanent discontinuation of corticosteroids. In November 2013, laboratory reports showed that he was positive for HBcAb but negative for the remaining HBV markers, and had a slightly increased AST level and, in December 2013, he became HBV DNA positive (326 IU/mL). In January 2014, his HBV DNA levels had further increased and ABA was stopped while maintaining MTX. He started lamivudine 100 mg/day in January 2014. After 1 month of lamivudine, his HBV DNA levels became undetectable (<10 IU/mL) and liver function was normal although RA had been reactivated (DAS28 5.53). Treatment with ABA was therefore resumed with the achievement of a good response after 6 months. The patient is currently being treated with lamivudine 100 mg/day, i.v. ABA 750 mg/month, and MTX 15 mg/week, with a good response (DAS28 2.27 in October 2015), and constantly monitored without any further evidence of HBV infection reactivation. CONCLUSIONS: Although there are still few reports in literature, we suggest caution in HBV- occult carriers RA patients undergoing a treatment with abatacept.
27384438 Clinical manifestations of autoimmune disease-related non-Hodgkin lymphoma: a Korean singl 2016 Sep BACKGROUND/AIMS: Recently, large cohort studies regarding associations between autoimmune disease and lymphomas have been reported in a few Western countries. However, Asian data concerning autoimmune-related lymphomas are limited. Therefore, we evaluated the clinical characteristics and prognostic factors of patients with autoimmune disease-related non-Hodgkin lymphoma (NHL) in a single center in Korea. METHODS: We analyzed the data from 11 patients with autoimmune-related NHL. Patients were categorized into two groups, those with rheumatoid arthritis (RA) and those with non-RA-related NHL. Then patients were re-categorized into a group with methotrexate (MTX) usage and a MTX non-usage group. Histological subtype, MTX duration, autoimmune disease duration, treatment modalities, and other data were collected and analyzed. RESULTS: Our study revealed that older RA patients have a greater likelihood of occurrence of NHL (p = 0.042). We confirmed that MTX duration and cumulative dose of MTX have no significant correlation with autoimmune disease and NHL (p = 0.073). In the management of autoimmune disease-related NHL, all patients were directly treated with systemic chemotherapy instead of employing a wait and watch approach. Overall survival (OS) and progression-free survival (PFS) in all autoimmune disease-related NHL were 100% and 87.5%, with no treatment-related mortality during the 2-year follow-up period of our study. CONCLUSIONS: Our study suggests that patients with RA-NHL are characterized by older age at onset compared to those with non-RA-NHL. Also considering of OS and PFS, intensive treatment strategy instead of delayed watchful managements may be required for autoimmune disease-related NHL including of old age group.
27091836 Methotrexate dosage as a source of bias in biological trials in rheumatoid arthritis: a sy 2016 Sep OBJECTIVES: To evaluate if optimal dose of either oral or injectable regimens of methotrexate (MTX) of 25 mg/week was used in the comparator arms of studies comparing biologic drugs with MTX in rheumatoid arthritis (RA). METHODS: A systematic literature search was carried out in MEDLINE, EMBASE and the Cochrane Library databases for randomised controlled trials comparing biologics with MTX in RA. A systematic review was performed among studies that met predefined criteria focusing on assessment of dose of MTX used in the comparator arm. Study authors were contacted when necessary. Study quality was assessed. RESULTS: A total of 3276 references were identified and 13 trials were included. We obtained maximal dose and regimen for all. The maximal dose of MTX used in the comparator arm of the trials was no more than 20 mg/week in any trial and for all but one trial, MTX was given orally and not by injection. The trial that used an injectable form reached a maximum of 15 mg/week. CONCLUSIONS: A suboptimal dose of MTX was used in biological clinical trials performed in RA, particularly regarding route of administration. This may have biased findings in favour of biological agents.
27787574 Outcome of knee revisions for osteoarthritis and inflammatory arthritis with postero-stabi 2017 Apr PURPOSE: Patients with rheumatoid arthritis (RA) and osteoarthritis (OA) may require revision total knee replacement. Few studies have compared post-operative complications, results and risk of re-revision in RA and OA patients. MATERIAL AND METHODS: Forty-five RA patients who had undergone revision TKA from 1998 to 2010 were selected and matched with 45 OA patients who had revision during the same period. Results of the use of a revision postero-stabilized implant in osteoarthritis were compared to results of its use in inflammatory arthritis. With a mean follow-up of ten years (range, 5-17 years) we determined differences in comorbidities, risk for peri-operative adverse events, functional and radiological results, and risk of subsequent re-revision, between patients suffering from OA versus RA. RESULTS: There were higher comorbidities, post-operative (<30 days) adverse events, and mortality at average ten years FU in RA than in OA patients. The mean overall changes in function scores were greater for the RA revision group when compared with the OA revision group. Taking steroids (Cox's regression, p = 0.001), and methotrexate or TNFα blockers (Cox's regression, p = 0.02) were not significant factors for radiolucent lines in RA and for loosening. At average ten years followup, patients with RA undergoing revision TKAs were not more likely to have a re-revision (4 among 45 patients; 9 %) than patients with OA undergoing revision in our department (7 patients; 15 %). CONCLUSIONS: Similar results for the knee were observed in these two forms of arthritis in spite of the fact that the initial local joint status and general health status are worse in inflammatory rheumatoid arthritis than in "degenerative" osteoarthritis. However, complications were more frequent with RA.
25738333 Discontinuation of disease-modifying anti-rheumatic drugs and clinical outcomes in the Rhe 2015 May OBJECTIVES: The purpose of this analysis was to examine discontinuation and reasons for discontinuation from disease-modifying anti-rheumatic (DMARD) therapies in the RADIUS 2 registry, a long-term, open-label, observational study of patients with moderate to severe rheumatoid arthritis (RA). METHODS: Patients who participated in RADIUS 2 initiated etanercept (ETN) therapy at study entry and were followed for 5 years. In this post hoc analysis, patients who had received ETN continuously from entry to month 4 were categorised by treatment at month 4: ETN monotherapy, ETN+methotrexate (MTX), ETN+MTX+other DMARDs (OTH), or ETN+OTH. Outcomes were assessed at month 4 and at the time of any subsequent treatment change, and included Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire Disability Index (HAQ-DI). RESULTS: Of 3,484 patients analysed (982 ETN; 1,356 ETN+MTX; 537 ETN+MTX+OTH; 609 ETN+OTH), baseline demographic and clinical characteristics were similar across treatments. No treatment change occurred in 62.3%, 49.9%, 33.3%, and 37.1% of ETN, ETN+MTX, ETN+MTX+OTH, and ETN+OTH patients, respectively. The mean time on therapy from month 4 was longer for patients receiving ETN (23.3 months) or ETN+MTX (23.7 months) than those receiving ETN+MTX+OTH (18.0 months) or ETN+OTH (18.3 months). The greatest improvements in CDAI and HAQ-DI were seen in patients who continued on ETN. The most common reasons for discontinuing DMARD therapy were cost and ineffective treatment. CONCLUSIONS: Most patients who had received ≥4 months of ETN continued on ETN throughout the 5-year observation period. Patients with greatest clinical and disability improvements tended to continue on ETN.
25986458 The association between antibody levels before and after 7-valent pneumococcal conjugate v 2015 May 19 INTRODUCTION: The aim of present study is to inverstigate the association between antibody levels after vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) and subsequent serious pneumococcal infections in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients. METHODS: A cohort of 497 patients (RA=248 and SpA=249) received a single dose of PCV7. At vaccination, patients were treated with methotrexate (MTX; n=85), anti-tumour necrosis factor (anti-TNF) + MTX (n=169), anti-TNF monotherapy (n=158) and non-steroidal anti-inflammatory drugs (NSAIDs)/analgesics (n=85). Antibody levels of serotypes 6B and 23B were analyzed before and 4 to 6 weeks after vaccination using standard enzyme-linked immunosorbent assay (ELISA). Serious pneumococcal infections (pneumonia/lower respiratory tract infection, meningitis, sepsis, septic arthritis) occurring within 4.5 years after vaccination were identified in the Skåne Healthcare Register using the International Classification of Diseases, tenth revision (ICD-10) codes. The association between post-vaccination antibody levels and protection against infections and determination of protective cutoff levels was explored using receiver operating characteristic (ROC) curves. Predictors of infection were studied using regression analyses. RESULTS: Eighteen infections were registered in 15 patients before vaccination and 27 infections in 23 patients after vaccination. Patients with serious infections after vaccination had significantly lower post-vaccination antibody titres for both 6B (P=0.04) and 23 F (P=0.04). Post-vaccination antibody levels of at least 1.29 mg/L and 1.01 mg/L for 6B and 23, respectively, were associated with better protection from serious infections. Higher age, concomitant prednisolone but not MTX or anti-TNF were associated with such infections. CONCLUSIONS: Patients with more robust antibody responses after vaccination with pneumococcal conjugate vaccine were less likely to suffer from serious infections. High age and prednisolone at vaccination were associated with putative serious pneumococcal infections in this cohort. TRIAL REGISTRATION NUMBER: EudraCT EU 2007-006539-29 and NCT00828997 . Registered 23 January 2009.
28012023 Oral to subcutaneous methotrexate dose-conversion strategy in the treatment of rheumatoid 2017 Feb Both the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) guidelines recommend the use of methotrexate (MTX) for the treatment of rheumatoid arthritis (RA) when there is no contraindication. While MTX is the foundation of RA therapy (Singh et al. in Arthritis Care Res 64:625-639,2012), absorption saturation compromises its oral bioavailability (BA). Differences in the relative BA of oral versus subcutaneous (SC) MTX demonstrate the need for guidance on successful dose-conversion strategies. This study was designed to compare MTX PK profiles as a result of MTX administration via three different treatment administrations: oral, SC MTX administered via an auto-injector (MTXAI) into the abdomen (MTXAI(ab)) and into the thigh (MTXAI(th)). In this paper, we establish a dose-conversion method based on the BA of MTX from oral and SC administration. SC administration provided higher exposure of MTX than the same dose given orally. Unlike the exposure limitations of oral MTX, dose-proportional exposure was seen with SC MTX.
26606398 Association of Triple Therapy With Improvement in Cholesterol Profiles Over Two-Year Follo 2016 Mar OBJECTIVE: To evaluate long-term changes in cholesterol levels in patients with early rheumatoid arthritis (RA) who were randomized to begin treatment with methotrexate (MTX) monotherapy, MTX plus etanercept, or triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. METHODS: Levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were analyzed in 416 patients participating in the TEAR trial, during 102 weeks of followup. Associations of cholesterol changes with disease activity and drug treatment were evaluated using repeated-measures analysis with mixed-effect linear models to model within-subject covariance over time. RESULTS: Mixed-effect models controlling for traditional cardiovascular (CV) risk factors, TEAR treatment, and baseline prednisone and statin use demonstrated significant inverse associations of RA disease activity with changes in cholesterol over time. Decreases in the 28-joint Disease Activity Score, the C-reactive protein level, or the erythrocyte sedimentation rate were associated with increases in levels of HDL cholesterol, LDL cholesterol, and total cholesterol in all treatment groups (P < 0.001-0.035). Triple therapy was strongly associated with higher levels of HDL cholesterol, lower levels of LDL cholesterol, and higher ratios of total cholesterol:HDL cholesterol (P < 0.001 for all) compared to MTX monotherapy or MTX plus etanercept therapy over the 2-year followup. CONCLUSION: Decreases in RA disease activity over long-term followup were associated with increases in cholesterol levels in patients with early RA treated with either biologic or nonbiologic therapies. The use of triple therapy during 2 years of followup was associated with higher HDL cholesterol levels, lower LDL cholesterol levels, and lower total cholesterol:HDL cholesterol ratios compared to those observed in patients who received MTX monotherapy or MTX plus etanercept combination therapy. Additional studies are needed to assess the effects of these cholesterol changes on CV events in patients with RA.
26670453 Comparison of comorbidities of the Egyptian rheumatoid arthritis patients to the global co 2016 May The aims of this study are to present the results of Egyptian RA patients included in COMORA cohort and compare it to general COMORA cohort, concerning prevalence of comorbidities, and level of application of recommendations related to detection/prevention of comorbidities. Three-hundred eight Egyptian RA patients included in the cross-sectional, observational, multi-center, international study "COMORA", were compared to the total number of 3612 RA patients. The CRF of COMORA was used in all patients. CRF collects demographic and disease characteristics, comorbidities, risk factors, and compliance with recommendations regarding management of comorbidities. Data were analyzed according to COMORA protocol. Egyptian RA patients were significantly younger, had more active disease, and were more functionally disabled. They showed more frequent use of NSAIDs, methotrexate and steroids and significantly lower use of bDMARDs when compared to non-Egyptians. Egyptian patients had the highest ever HCV prevalence, while depression, hypertension, smoking and dyslipidemia were less prevalent in Egyptians. Prevalence of malignancy risk factors was highly deficient among Egyptians; primarily due to lack of screening. Further, following recommendations for monitoring comorbidities is significantly deficient among Egyptian patients. Egyptian patients had more active disease and more functional impairment than the rest of the COMORA cohort; with lower use of bDMARDs, that is possibly related to the economic situation. Also, there is a clear gap in screening and monitoring comorbidities. Awareness among Egyptian healthcare providers (and possibly similar third-world countries) to detect and manage RA-related comorbidities is required.
27627584 Proteome Analysis of Rheumatoid Arthritis Gut Mucosa. 2017 Jan 6 Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage damage and ultimately impaired joint function. To gain new insight into the systemic immune manifestations of RA, we characterized the colon mucosa proteome from 11 RA-patients and 10 healthy controls. The biopsies were extracted by colonoscopy and analyzed by label-free quantitative proteomics, enabling the quantitation of 5366 proteins. The abundance of dihydrofolate reductase (DHFR) was statistically significantly increased in RA-patient biopsies compared with controls and correlated with the administered dosage of methotrexate (MTX), the most frequently prescribed immunosuppressive drug for RA. Additionally, our data suggest that treatment with Leflunomide, a common alternative to MTX, increases DHFR. The findings were supported by immunohistochemistry with confocal microscopy, which furthermore demonstrated that DHFR was located in the cytosol of the intestinal epithelial and interstitial cells. Finally, we identified 223 citrullinated peptides from 121 proteins. Three of the peptides were unique to RA. The list of citrullinated proteins was enriched in extracellular and membrane proteins and included known targets of anticitrullinated protein antibodies (ACPAs). Our findings support that the colon mucosa could trigger the production of ACPAs, which could contribute to the onset of RA. The MS data have been deposited to ProteomeXchange with identifiers PXD001608 and PXD003082.
26099641 Is there a role for Digital X-ray Radiogrammetry as surrogate marker for radiological prog 2015 Jun 23 INTRODUCTION: The established scoring techniques based on radiographs present limitations in the evaluation of structural integrity due to high effectiveness of innovative therapeutic strategies. The aim of this study was to evaluate the periarticular mineralisation as detected by Digital X-ray Radiogrammetry (DXR) as surrogate marker for structural integrity during the course of rheumatoid arthritis (RA). METHODS: 11 centers throughout Germany contributed data of 94 patients with verified RA. The patients were treated with leflunomide or methotrexate during a mean observation period of 22 months. All patients underwent complete computerized calculations of bone mineral density (BMD) and metacarpal index (MCI) by DXR using digitized hand radiographs. The radiological assessment of disease progression was estimated by the Sharp Score. RESULTS: The Sharp Score revealed no significant change during the study period. DXR-BMD revealed minimal decrease of -1.4 % (leflunomide group) versus a higher reduction of -4.3 % (methotrexate group). Regarding DXR-MCI, a reduction of -2.2 % (leflunomide group) and -4.9 % (methotrexate group) was observed. CONCLUSION: Quantitative data of hand bone mass estimated by the presented DXR-technique may be a complementary precise tool in the identification of RA-related radiographic changes and in the assessment of structural integrity.
26814847 Predicting and verifying outcome of Tripterygium wilfordii Hook F. based therapy in rheuma 2015 Apr 15 Tripterygium wilfordii Hook F. (TwHF) based therapy has been proved as effective in treating rheumatoid arthritis (RA), yet the predictors to its response remains unclear. A two-stage trial was designed to identify and verify the baseline symptomatic predictors of this therapy. 167 patients with active RA were enrolled with a 24-week TwHF based therapy treatment and the symptomatic predictors were identified in an open trial; then in a randomized clinical trial (RCT) for verification, 218 RA patients were enrolled and classified into predictor positive (P+) and predictor negative (P-) group, and were randomly assigned to accept the TwHF based therapy and Methotrexate and Sulfasalazine combination therapy (M) for 24 weeks, respectively. Five predictors were identified (diuresis, excessive sweating, night sweats for positive; and yellow tongue-coating, thermalgia in the joints for negative). In the RCT, The ACR 20 responses were 82.61% in TwHF/P+ group, significantly higher than that in TwHF/P- group (P = 0.0001) and in M&S/P+ group (P < 0.05), but not higher than in M&S/P- group. Similar results were yielded in ACR 50 yet not in ACR 70 response. No significant differences were detected in safety profiles among groups. The identified predictors enable the TwHF based therapy more efficiently in treating RA subpopulations.
27087059 Clinical efficacy and safety maintained up to 5 years in patients with rheumatoid arthriti 2016 Jul OBJECTIVES: To report 5-year efficacy and safety in rheumatoid arthritis (RA) patients with active disease treated with tocilizumab. METHODS: LITHE was a 2-year, randomised, placebo-controlled study of tocilizumab in RA patients (ClinicalTrials.gov, NCT00106535), with an additional 3-year, open-label extension. Patients were randomly assigned to tocilizumab (4 or 8 mg/kg IV) or placebo every 4 weeks + methotrexate. They could receive rescue with tocilizumab from week 16; after week 52, patients could switch to open-label tocilizumab 8 mg/kg. Radiographs were analysed by randomized treatment using the Genant-modified Total Sharp Score (GmTSS). Patients with at least baseline, week 104 and post-week 104 radiographs were included. Clinical and safety data were pooled for all patients who received ≥1 dose of tocilizumab; results are presented from the first tocilizumab dose. RESULTS: 1,149 patients were included with 4,380 patient-years of exposure; 34% received 5 years of treatment. Mean 5-year change in GmTSS revealed greater inhibition of radiographic progression in tocilizumab patients than placebo patients (1.34 vs. 3.02), with the greatest annualised progression rate in year 1. Overall, 53% of tocilizumab and 35% of placebo patients experienced no progression (GmTSS ≤0). Clinical benefit was maintained - determined by ACR response, DAS28-ESR <2.6, EULAR good/moderate response and Boolean remission - as was physical function. The safety profile over 5 years was similar to that over 2 years. CONCLUSIONS: Over 5 years, tocilizumab + MTX inhibited radiographic progression and maintained improvements in signs and symptoms and physical function in MTX-inadequate responders with active disease; no new safety signals occurred.
25992914 Predicted vs. observed radiographic progression in early rheumatoid arthritis (POPeRA): re 2015 OBJECTIVES: The aim of this study was to apply a previously published method for evaluating radiographic progression, namely, predicted vs. observed radiographic progression in early rheumatoid arthritis (POPeRA), to the Swedish pharmacotherapy (SWEFOT) trial. METHOD: In SWEFOT, 487 patients with eRA were given methotrexate (MTX), and non-responders were randomized to group A [triple therapy: MTX+sulfasalazine (SSZ)+hydroxychloroquine (HCQ)] and group B [anti-tumour necrosis factor (anti-TNF) therapy: MTX+infliximab]. Responders continued on MTX. Predicted progression for 343 eligible patients was calculated based on the baseline total Sharp/van der Heijde score (SHS) divided by symptom duration, compared to observed progression at 12 and 24 months. RESULTS: Observed radiographic progression was reduced from predicted by a mean of 50.1% (A), 72.3% (B), and 73.9% (MTX) at 12 months and by 87.2, 89.8, and 87.8% at 24 months, respectively. Among completers, reductions of 56.7% (A) and 76.5% (B) at 12 months and of 91.0% and 96.0% at 24 months, respectively, were observed. At 12 months, there were no significant between-group differences. At 24 months, progression was reduced more in group B than in group A (first quartile difference 8.5% favouring group B) and in MTX [n=316, 89.8% (sd±32.0) vs. 87.2% (±32.2), p=0.021; vs. 87.8% (±27.8), p=0.013, respectively]. CONCLUSIONS: The POPeRA method confirms the original SWEFOT finding in that anti-TNF therapy was statistically marginally superior (2.6%) to triple therapy in preventing radiographic progression at 24 months among initial MTX non-responders. The simulation provided through POPeRA may facilitate comparisons of the relative efficacy of various treatments in preventing radiographic progression.
27769592 Defining the optimal biological monotherapy in rheumatoid arthritis: A systematic review a 2017 Jun OBJECTIVES: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct and indirect comparisons of the treatment effects, while preserving the randomised comparisons within each trial. PROSPERO identifier: CRD42012002800. RESULTS: The analysis comprises 28 trials (8602 patients), including all nine biological agents approved for RA. Eight trials included "DMARD-naïve", and 20 "DMARD-Inadequate responder" (DMARD-IR) patients. All agents except anakinra and infliximab were superior (p < 0.05) to placebo (i.e., no DMARD treatment) with regard to ACR50. Etanercept and rituximab were superior to anakinra (p = 0.018 and p = 0.049, respectively). Tocilizumab was superior to adalimumab (p = 0.0082), anakinra (p = 0.0083), certolizumab (p = 0.037), and golimumab (p = 0.049). No differences among etanercept, tocilizumab, and rituximab were found (p > 0.52). However, because rituximab was evaluated in just 40 patients, our confidence in the estimates is limited. When including only DMARD-IR trials, the same statistical pattern emerged; in addition etanercept and tocilizumab were superior to abatacept. At recommended doses, both etanercept and tocilizumab were superior to adalimumab and certolizumab. No statistically significant differences among biological agents were found with respect to discontinuation due to adverse events (p > 0.068). CONCLUSIONS: Evidence from randomised trials suggests that most biological agents are effective as monotherapy. Although our confidence in the estimates is limited, etanercept or tocilizumab may be the optimal choice for most patients who need treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice.