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ID PMID Title PublicationDate abstract
30088389 Management of corneal melting in a patient with long-standing rheumatoid arthritis – cas 2016 Corneal melting is a rare ocular complication of rheumatoid arthritis, associated with poor prognosis. Rapid course of the disease and unpredicted treatment response, which depends on a patient general state and disease severity, make every case a challenge and requires a cooperation between ophthalmologists and rheumatologists. We present a case of a 58-year-old woman with corneal melting, who was successfully treated with systemic corticosteroids and methotrexate, along with ocular surgery.
26587663 Impaired NFKBIE gene function decreases cellular uptake of methotrexate by down-regulating 2016 Jul OBJECTIVE: A non-synonymous single nucleotide polymorphism (nsSNP, rs2233434, Val194Ala) in the NFKBIE (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon) gene is known to be a rheumatoid arthritis (RA) susceptibility polymorphism in the Japanese RA population and could be closely associated with nuclear factor kappaB (NF-κB) activity. Inflammation caused by RA is sometimes associated with changes in expression levels of MTX (methotrexate) pathway-related genes. It is of interest to examine whether the NFKBIE gene had any influences on the mode of MTX action. METHODS: Both knockdown of NFKBIE gene expression and overexpression of wild-type NFKBIE and Val194Ala mutation were performed. A transfected human RA synovial cell line was cultured and then gene expressions in the MTX pathway were measured. In addition, we measured the uptake and efflux of MTX derivatives under the NFKBIE knockdown condition. RESULTS: Knockdown of NFKBIE reduced the mRNA for SLC19A1, a main MTX membrane transporter, and the intracellular accumulations of MTX derivatives. Moreover, our experiments also confirmed that overexpression of Val194Ala mutant NFKBIE decreased the SLC19A1 mRNA when compared to that of wild-type NFKBIE. CONCLUSIONS: We suggest that the impairment of NFKBIE gene function can reduce the uptake of MTX into cells, suggesting that the gene is an important factor for the RA outcome.
26652611 Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid ar 2016 BACKGROUND: Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients. AIM: To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RA patients receiving MTX. PATIENTS & METHODS: We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes. RESULTS: We studied 194 RA patients receiving MTX monotherapy. Two FPGS SNPs, rs10987742 and rs10106, were associated with response (p = 0.033 and p = 0.041, respectively). The FPGS rs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Three ABCB1 SNPs, rs868755, rs10280623 and rs1858923, were associated with toxicity (p = 0.025, p = 0.048 and p = 0.031, respectively). CONCLUSION: FPGS and ABCB1 genetic variants can influence the outcome in RA patients receiving MTX monotherapy.
26590174 Value of ultrasonography as a marker of early response to abatacept in patients with rheum 2016 Oct OBJECTIVES: To study the responsiveness of a combined power Doppler and greyscale ultrasound (PDUS) score for assessing synovitis in biologic-naïve patients with rheumatoid arthritis (RA) starting abatacept plus methotrexate (MTX). METHODS: In this open-label, multicentre, single-arm study, patients with RA (MTX inadequate responders) received intravenous abatacept (∼10 mg/kg) plus MTX for 24 weeks. A composite PDUS synovitis score, developed by the Outcome Measures in Rheumatology-European League Against Rheumatism (OMERACT-EULAR)-Ultrasound Task Force, was used to evaluate individual joints. The maximal score of each joint was added into a Global OMERACT-EULAR Synovitis Score (GLOESS) for bilateral metacarpophalangeal joints (MCPs) 2-5 (primary objective). The value of GLOESS containing other joint sets was explored, along with clinical efficacy. RESULTS: Eighty-nine patients completed the 24-week treatment period. The earliest PDUS sign of improvement in synovitis was at week 1 (mean change in GLOESS (MCPs 2-5): -0.7 (95% CIs -1.2 to -0.1)), with continuous improvement to week 24. Early improvement was observed in the component scores (power Doppler signal at week 1, synovial hyperplasia at week 2, joint effusion at week 4). Comparable changes were observed for 22 paired joints and minimal joint subsets. Mean Disease Activity Score 28 (C reactive protein) was significantly reduced from weeks 1 to 24, reaching clinical meaningful improvement (change ≥1.2) at week 8. CONCLUSIONS: In this first international prospective study, the composite PDUS score is responsive to abatacept. GLOESS demonstrated the rapid onset of action of abatacept, regardless of the number of joints examined. Ultrasound is an objective tool to monitor patients with RA under treatment. TRIAL REGISTRATION NUMBER: NCT00767325.
25431327 Can we prevent rapid radiological progression in patients with early rheumatoid arthritis? 2015 Jan The aim of this study is to test the performance of a matrix model to predict rapid radiological progression (RRP) in a study population of early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) patients. A matrix model using baseline CRP, erosion score, autoantibody status, and initial treatment choice to predict RRP (increase ≥5 points in Sharp-van der Heijde score (SHS) in 1 year) was derived from the BeSt study where patients with active RA (1987-criteria) were treated with initial monotherapy or combination therapy, aiming at low disease activity. In the IMPROVED study, patients with early RA (2010 criteria) and UA were initially treated with methotrexate and prednisone aiming at remission. A receiver operating characteristics (ROC) curve was used to assess the discriminative value of the model to predict damage progression in the IMPROVED population. Four hundred thirty-one out of 479 patients with RA and 106/122 with UA could be categorized as high, intermediate, low, or very low risk for RRP. One patient, with a very low risk profile, showed RRP. Thirty-two other patients (5 %) showed radiological progression ≥0.5 point SHS; none had a high risk profile and 22 had a very low risk profile. The area under the curve (AUC) of the ROC curve was 0.56 (95% CI 0.45; 0.68). A matrix model predicting RRP based on risk factors identified in recent onset active RA according to the 1987-criteria performed poorly in recent onset RA (2010 criteria) and UA. It appears that known risk factors for damage progression lose their impact with early remission steered treatment, so that RRP might be considered a phenomenon of the past.
26080569 [Study on biomarker of Tripterygium wilfordii in treatment of rheumatoid arthritis based o 2015 Jan To observe the serum samples and the anti-inflammatory effect of Tripterygium wilfordii in treating RA by using the pharmacokinetic-pharmacodynamic model, make a correlation analysis on concentration-time and effect-time curves, and explore RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in rats by PCR. Methotrexate, tripterine and high-dose T. wilfordii could down-regulate RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in AA rat lymph nodes. The study on PK-PD model showed correlations between inflammatory factors and blood concentration of T. wilfordii. T. wilfordii and its main active constituent tripterine could show the inflammatory effect and treat RA by inhibiting IL-17 cytokine.
27062502 BRONJ in patients with rheumatoid arthritis: a multicenter case series. 2016 Sep OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of various medications (bisphosphonates, anti-resorptive, and anti-angiogenic drugs). ONJ pathogenesis is still unclear although some risk factors have been recognized. Of these, rheumatoid arthritis (RA) has been hypothesized as a potential risk factor for developing ONJ. This observational study will describe a multicenter case series of patients affected with RA and ONJ, and it will attempt to evaluate the association between features of ONJ and pharmacological, systemic, and site variables. METHODS: Demographic, pharmacological, and clinical data from 18 RA patients with ONJ were collected and registered from three Italian centers (i.e., Palermo, Verona, and Padua) from 2004 to 2013. RESULTS: Sixteen (88.9%) patients were in therapy for RA: 9 of 18 (50.0%) with systemic steroids, 3 of 18 (16.7%) with methotrexate, and 4 of 18 (22.2%) with both medications. Two patients were not receiving treatment for RA. All patients took NBPs for secondary osteoporosis (average NBP duration of 69 months, range: 20-130): Fifteen (83.3%) patients were treated with single NBPs, while three (16.7%) with different molecules; one patient was also treated with denosumab. Mandible was affected more frequently (66.7%) than maxilla (33.3%); one patient presented multiple ONJ events. CONCLUSIONS: This is the first multicenter case series in the international literature regarding our topic. Focusing on our data, it could be hypothesized that patients with RA may be more susceptible to ONJ than the majority of osteometabolic patients. In our opinion, it could be important to monitor also denosumab or other biological drug side effects.
26608859 [Efficacy of disease modifying anti-rheumatic drugs on bone destruction in rheumatoid arth 2015 Dec There had been proved the efficacy of preventing bone destruction by using disease modifying anti-rheumatic drugs (DMARDS) such as methotrexate(MTX). A certain combination of DMARDS is more effective than treated alone. But the data about DMARDS combination therapy or DMARDS used mainly in Japan is not abundant, and there needed to establish the evidences of them.
25024096 The new 2010 ACR/EULAR criteria as predictor of clinical and radiographic response in pati 2015 Jan New American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for the classification of rheumatoid arthritis (RA) have recently been proposed. The aim of this cohort study was to examine whether fulfilling these 2010 ACR/EULAR criteria at the first visit has an impact on the clinical course and on the radiographic progression of the disease. For this observational cohort study, we included patients from the Swiss RA registry SCQM with early RA or undifferentiated arthritis (UA, disease duration ≤1 year), as defined by the treating rheumatologist, who had not received any previous disease modifying anti-rheumatic drugs (DMARDs). Patients were categorized into two groups depending on whether or not they fulfilled the 2010 ACR/EULAR criteria (≥6 points vs <6 points) at the first visit. The primary outcome measures were the evolution of the DAS 28 and of radiographic erosions as measured by the Ratingen score over time. Of the 592 patients fulfilling the inclusion criteria, 352 satisfied the 2010 ACR/EULAR criteria at baseline, whereas 240 were not classifiable as definite RA. The ACR/EULAR criteria scores correlated with disease activity at disease onset (R (2) = 0.31). DMARD treatment was subsequently initiated in all patients, mostly with methotrexate (MTX). There were no significant differences in the therapeutic strategies between patients fulfilling or not fulfilling the classification criteria. Six months after inclusion, patients fulfilling the ACR/EULAR criteria developed a 39.1 % reduction of DAS 28 scores, as compared to a 33.6 % reduction in patients not fulfilling the ACR/EULAR criteria (p = 0.0002), independently of their respective treatment strategy. Importantly, the DAS 28 scores were higher in those patients fulfilling the ACR/EULAR criteria (ACR/EULAR positive patients) throughout the observation, as compared to patients not fulfilling those (ACR/EULAR negative patients). Average radiographic progression was higher among ACR/EULAR positive than negative patients (progression of Ratingen score/year 0.50 vs 0.32, resp., p = 0.03) after 3 years of follow-up. Among early RA/UA patients, a score of the 2010 ACR/EULAR criteria sufficient to classify RA selects patients with worse clinical outcome and more radiographic progression.
25797025 Iguratimod for the treatment of rheumatoid arthritis in Japan. 2015 May Iguratimod (IGU), a small-molecule compound, was developed as a disease-modifying antirheumatic drug in Japan. The pharmacological studies showed that inhibition of the production of cytokines and immunoglobulins mainly contributes to its improvement effect on animal arthritis models. The first clinical study of IGU in Japanese patients with rheumatoid arthritis was started in 1992 and Phase III studies were started in 1998. From the results of Phase II studies, a dose-escalating regimen was recommended to relieve the side effects. In a double-blind study comparing the efficacy and safety of the drug with those of placebo and salazosulfapyridine, it was confirmed that IGU was superior to placebo and was not inferior to salazosulfapyridine. Furthermore, a double-blind controlled trial of IGU in combination with methotrexate revealed an efficacious and manageable safety profile. IGU would be widely used as a new option for rheumatoid arthritis treatment and combination drug with methotrexate.
25989246 Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthri 2015 Nov OBJECTIVE: The costs of biologic treatment per patient with rheumatoid arthritis (RA) are approximately 100 times the costs of treatment with a combination of conventional disease-modifying antirheumatic drugs (DMARDs). Despite this, biologic agents have not been proven superior. We compared the effects of combination DMARD therapies with and without biologic agents as therapy for patients with RA. METHODS: Eight randomized controlled trials published in 10 articles were selected from a systematic literature search of 1,674 identified studies and integrated in a meta-analysis. These trials compared combinations of DMARDs versus a tumor necrosis factor (TNF) inhibitor plus methotrexate. Two reviewers independently entered data into standardized extraction forms. The combined effect measures were compared by means of the inverse variance method (continuous data) and the Mantel-Haenszel method (dichotomous data) using a random-effects model. RESULTS: The primary outcome, radiographic progression score, did not differ between the combination DMARD group and the TNF inhibitor group, neither during the second year (-0.09 units [-0.61, 0.44]) of treatment or during the first 2 years (0.66 units [-0.12, 1.43]). There were significant differences in the radiographic progression score, the American College of Rheumatology criteria for 50% improvement (ACR50), and the ACR70 response criteria at 6 months in favor of TNF inhibitor treatment, but these differences were not present in patients treated with an initial steroid course and disappeared at 24 months, irrespective of the use of steroids. CONCLUSION: The difference between DMARD combination treatments, including or excluding TNF inhibitors, is small. Due to the enormous cost differences, RA guidelines should recommend combination DMARD treatment before initiation of TNF inhibitors.
25413735 Remission of rheumatoid arthritis and potential determinants: a national multi-center cros 2015 Feb The aim of this study is to investigate the remission rate of rheumatoid arthritis (RA) in China and identify its potential determinants. A multi-center cross-sectional study was conducted from July 2009 to January 2012. Data were collected by face-to-face interviews of the rheumatology outpatients in 28 tertiary hospitals in China. The remission rates were calculated in 486 RA patients according to different definitions of remission: the Disease Activity Score in 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), the Clinical Disease Activity Index (CDAI), and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition. Potential determinants of RA remission were assessed by univariate and multivariate analyses. The remission rates of RA from this multi-center cohort were 8.6% (DAS28), 8.4% (SDAI), 8.2% (CDAI), and 6.8% (Boolean), respectively. Favorable factors associated with remission were: low Health Assessment Questionnaire (HAQ) score, absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), and treatment of methotrexate (MTX) and hydroxychloroquine (HCQ). Younger age was also predictive for the DAS28 and the Boolean remission. Multivariate analyses revealed a low HAQ score, the absence of anti-CCP, and the treatment with HCQ as independent determinants of remission. The clinical remission rate of RA patients was low in China. A low HAQ score, the absence of anti-CCP, and HCQ were significant independent determinants for RA remission.
25163739 Laboratory biomarkers for guiding therapy with methotrexate in rheumatoid arthritis. 2015 Methotrexate (MTX) is a first-line drug for the treatment of several rheumatic diseases. However, it is difficult to predict the response to this drug based on clinical manifestations. Although different mechanisms of action have been proposed for the antiinflammatory and immunosuppressive effects of MTX, the best characterized are blockade of the de novo synthesis of purines and pyrimidines, which inhibits DNA synthesis, and induction of adenosine release, which downregulates the effector functions of different immune cells. Thus, variants of the enzymes and other molecules involved in these metabolic pathways are expected to play a relevant role in the therapeutic effect or toxicity of MTX in patients with rheumatoid arthritis (RA). Accordingly, polymorphisms of the genes encoding these proteins have been widely associated with the response to or discontinuation of MTX. In addition, variants of the genes involved in the transportation of MTX inside and outside cells and in its metabolism have also been associated with the efficacy or toxicity of this drug in patients with RA. However, published results are contradictory, and no consensus regarding the best laboratory markers of MTX efficacy has been reached. Therefore, additional prospective studies with a large number of patients are necessary to identify the combination of genetic and nongenetic factors that can predict, with a reasonable level of confidence, the efficacy and toxicity of MTX in patients with RA.
26404390 Treatment of rheumatoid arthritis by molecular-targeted agents: efficacy and limitations. 2015 Nov Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation due to unknown causes. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological DMARDs (bDMARDs), and tofacitinib, a targeted sDMARD, can be used to treat RA. In clinical trials, molecular-targeted therapies showed a significant reduction in RA symptoms and provided pain relief for patients with active RA. Even if patients did not show clinical improvement with combination therapy with a bDMARD and methotrexate (MTX), some patients showed a significant inhibition in structural damage. The clinical efficacies of tofacitinib were shown to be equivalent to adalimumab, a bDMARD, in patients with RA treated with MTX. MTX is the first-line agent for the treatment of RA. Higher doses of MTX might be needed to maintain the effects of bDMARDs. Patients receiving some bDMARDs have been shown to have a higher risk for serious infections; thus, pre-screening for infections is important before beginning treatment with bDMARDs. The rates of patients maintaining targeted levels of disease activity after stopping bDMARDs are relatively low. It is uncertain whether remission or low disease activity can be maintained after stopping molecular-targeted therapies. The development of bDMARDs and targeted-molecular sDMARDs has provided a wide range of treatment options for RA. Patients with active RA should be treated with a treat-to-target strategy after assessment of risks and benefits.
26865601 Sustained improvements in MRI outcomes with abatacept following the withdrawal of all trea 2016 Aug OBJECTIVES: To assess structural damage progression with subcutaneous abatacept (ABA) in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial following abrupt withdrawal of all rheumatoid arthritis (RA) medication in patients achieving Disease Activity Score (DAS)-defined remission or low disease activity. METHODS: Patients with early, active RA were randomised to ABA plus methotrexate (ABA/MTX) 125 mg/week, ABA 125 mg/week or MTX for 12 months. All RA treatments were withdrawn after 12 months in patients with DAS28 (C reactive protein (CRP)) <3.2. Adjusted mean changes from baseline in MRI-based synovitis, osteitis and erosion were calculated for the intention-to-treat population. RESULTS: 351 patients were randomised and treated: ABA/MTX (n=119), ABA (n=116) or MTX (n=116). Synovitis and osteitis improved, and progression of erosion was statistically less with ABA/MTX versus MTX at month 12 (-2.35 vs -0.68, -2.58 vs -0.68, 0.19 vs 1.53, respectively; p<0.01 for each) and month 18 (-1.34 vs -0.49 -2.03 vs 0.34, 0.13 vs 2.0, respectively; p<0.01 for erosion); ABA benefits were numerically intermediate to those for ABA/MTX and MTX. CONCLUSIONS: Structural benefits with ABA/MTX or ABA may be maintained 6 months after withdrawal of all treatments in patients who have achieved remission or low disease activity. TRIAL REGISTRATION NUMBER: NCT01142726; Results.
26784398 Remaining Pain in Early Rheumatoid Arthritis Patients Treated With Methotrexate. 2016 Aug OBJECTIVE: To investigate the frequency of remaining pain in early rheumatoid arthritis (RA) after 3 months of treatment with methotrexate as the only disease modifying antirheumatic drug, with a special focus on patients with a good clinical response. METHODS: The study base was cases reported to a population-based early RA cohort who had followup data from the Swedish Rheumatology Quality Register (n = 1,241). The Disease Activity Score in 28 joints European League Against Rheumatism (EULAR) response criteria were used to evaluate clinical response to treatment as good, moderate, and no response. The primary end point was remaining pain at the 3-months followup visit, defined as pain >20 mm on a 100-mm visual analog scale (VAS). RESULTS: Remaining pain in spite of a EULAR good response at followup was associated with higher baseline disability, using the Health Assessment Questionnaire (adjusted odds ratio [OR] 2.2 [95% confidence interval (95% CI) 1.4-3.4] per unit increase), and less baseline inflammation, using the erythrocyte sedimentation rate (adjusted OR 0.81 [95% CI 0.70-0.93] per 10-mm increase). Similar associations were detected for remaining pain at followup in spite of low inflammatory activity, defined as a C-reactive protein level <10. Increase in VAS pain during the treatment period was observed in 19% of the whole cohort, with frequencies in the EULAR response groups of 9% (good response), 15% (moderate response), and 45% (no response). CONCLUSION: These results are in line with the hypothesis that a subgroup of early RA patients exhibits pain that is not inflammatory mediated, where alternative treatment strategies to traditional antiinflammatory medications need to be considered.
27271301 Dry Olive Leaf Extract in Combination with Methotrexate Reduces Cell Damage in Early Rheum 2016 Oct The effects of co-administration of dry olive leaf extract (DOLE) with standard methotrexate (MTX) therapy on the parameters of cell damage and inflammation in patients with early and long-term rheumatoid arthritis (RA) were evaluated at baseline, 3 and 6 weeks. Patients were assigned to groups: the early phase RA group on MTX monotherapy (E MTX), and the two RA groups that received co-treatment with DOLE and MTX: early (E MTX + DOLE) and long-term phase patients (L-t MTX+ DOLE). Baseline values indicated increased parameters of cell damage and disruption of redox balance in all groups. After three weeks the E MTX + DOLE group maintained high catalase activity, exhibited decrease of lipid peroxidation and protein damage indicators-thiols and nitrites, while levels of DNA damage and pro-inflammatory interleukin-6 were significantly reduced. In E MTX group catalase activity remained unaltered while significant lipid peroxidation and DNA damage reductions were seen only after six weeks. L-t MTX + DOLE group showed only modest alterations of cell damage parameters during six weeks. Combined administration of DOLE with MTX contributes to faster reduction of cell damage, restores oxidative balance and improves interleukin-6 suppression during high disease activity in early phase RA, but not in long term patients. Copyright © 2016 John Wiley & Sons, Ltd.
26259617 Efficacy and safety results from a Phase 3, randomized, placebo-controlled trial of subcut 2016 Nov AIM: The efficacy and safety of golimumab + methotrexate (MTX) were evaluated in Chinese patients with active rheumatoid arthritis (RA) despite MTX therapy. METHODS: Chinese patients (n = 264) were randomly assigned (1 : 1) to receive subcutaneous injections of placebo + MTX with crossover to golimumab 50 mg + MTX at week 24 (Group 1) or to golimumab 50 mg + MTX (Group 2) every 4 weeks. Group 1 patients with inadequate response entered blinded early escape to golimumab 50 mg + MTX at week 16. At least a 20% improvement in the American College of Rheumatology (ACR20) criteria at week 14 was the primary endpoint. Other assessments included the 28-joint count Disease Activity Score using C-reactive protein (DAS28-CRP) and Health Assessment Questionnaire-Disability Index (HAQ-DI) through week 52. Adverse events (AEs) were monitored through week 56. RESULTS: ACR20 response at week 14 was significantly higher in Group 2 (40.9% [54/132]) compared with Group 1 (15.9% [21/132]; P < 0.001). Greater proportions of patients in Group 2 compared with Group 1 had a DAS28-CRP response at week 14 (65.2% vs. 30.3%, P < 0.001) or ACR20 response at week 24 (42.4% vs. 15.9%, P < 0.001), and Group 2 had a significantly greater change in HAQ-DI at week 24 (-0.26 vs. 0.15, P < 0.001). After week 24, the proportion of patients achieving ACR20 in Group 1 approached that in Group 2. Through week 16, 23.5% of Group 1 and 26.7% of Group 2 patients reported AEs. Among golimumab + MTX-treated patients, 50.2% and 4.2% had ≥ 1 AE or serious AE, respectively, through week 56. No unexpected safety signals were observed. CONCLUSION: Among MTX-experienced Chinese patients with active RA, a significantly greater proportion of patients receiving golimumab + MTX had improvements in the signs and symptoms of RA compared with MTX monotherapy. Safety findings were consistent with previous studies of golimumab in patients with RA.
27214046 Changes in Ultrasonographic Vascularity Upon Initiation of Adalimumab Combination Therapy 2016 Nov OBJECTIVE: To assess joint disease activity by ultrasound (US) in patients with rheumatoid arthritis (RA) initiating treatment with adalimumab (ADA) plus methotrexate (MTX). METHODS: Data for this post hoc analysis originated from the MUSICA trial (ClinicalTrials.gov identifier: NCT01185288), which evaluated the efficacy of initiating ADA (40 mg every other week) plus 7.5 or 20 mg/week MTX in 309 patients with RA with an inadequate response to MTX. Synovial vascularization over 24 weeks was assessed bilaterally at metacarpophalangeal joint 2 (MCP2), MCP3, MCP5, metatarsophalangeal joint 5, and the wrists by power Doppler US (PDUS). A semiquantitative 4-grade scale was used. Disease activity was assessed using the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) and Simplified Disease Activity Index (SDAI). The correlation between continuous variables was assessed using Pearson's correlation coefficient. RESULTS: After 24 weeks of treatment with ADA plus MTX, rapid improvements in the mean synovial vascularity score were observed; the greatest improvements were in MCP2 (-0.5), MCP3 (-0.4), and the wrist (-0.4). At week 24, patients with the lowest DAS28-CRP (<2.6) had the lowest mean 5-joint and 3-joint composite synovial vascularity scores. The 5-joint and 3-joint scores were strongly correlated (ρ > 0.9). Synovial vascularity scores correlated poorly with DAS28, swollen joint count in 66 joints (SJC66), SJC28, tender joint count in 68 joints (TJC68), TJC28, Clinical Disease Activity Index (CDAI), SDAI, physician's global assessment, patient's global assessment of pain, and disease duration (ρ < 0.2). Thirty-two (70%) of 46 patients with a DAS28-CRP of <2.6, and 11 (58%) of 19 patients with an SDAI indicating remission had at least 1 joint with a synovial vascularity score of ≥1. CONCLUSION: PDUS detects changes in synovial vascularity in RA patients treated with ADA plus MTX, and residual synovial vascularity in patients in whom clinical disease control has been achieved.
27369643 Immunogenicity of tocilizumab in patients with rheumatoid arthritis. 2017 Jan OBJECTIVE: The immunogenicity of tocilizumab (TCZ) has been poorly studied. We assessed the immunogenicity of TCZ and serum TCZ trough levels in rheumatoid arthritis (RA) patients and the preexisting TCZ-specific CD4+ T cell repertoire in healthy controls. METHODS: Anti-drug antibodies (ADAs) to TCZ and serum TCZ trough levels in RA patients were assessed at different times by ELISA. Frequencies of naive anti-TCZ CD4+ precursors were studied in healthy controls. RESULTS: In total, 91 samples from 40 RA patients were analyzed: 21 patients within the first 6 months after treatment initiation and 19 during follow-up after a mean TCZ treatment duration of 21±13 months. None of the 91 samples showed persistent ADAs to TCZ. Only 3 RA patients showed transient and low titers of anti-TCZ ADAs. Serum TCZ trough levels were associated with neither patient characteristics (gender, body mass index) nor disease activity and were identical for patients with and without co-treatment with methotrexate. Three of 9 healthy donors showed preexisting TZC-specific CD4+ T cells at a low level. CONCLUSION: Serum TCZ trough levels were not affected by patient characteristics. The occurrence of ADAs to TCZ was a rare event. Because healthy donors show the same frequency of naive TCZ-specific and infliximab-specific CD4+ T cell precursors, the low prevalence of ADAs to TCZ might result from interleukin-6 blockade.