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ID PMID Title PublicationDate abstract
27213997 A survey on the medication adherence to methotrexate among rheumatoid arthritis patients t 2016 Jul OBJECTIVES: Methotrexate (MTX) is the most widely used co-therapy among rheumatoid arthritis (RA) patients using biological disease-modifying anti-rheumatic drugs (bDMARDs). However, adherence to MTX treatment remains a concern with estimates of adherence ranging from 59 to 63%. The objective of this study was to assess the self-reported use and adherence to MTX among RA patients treated with self-administered bDMARDs. METHODS: An electronic questionnaire survey was conducted in 68 community pharmacies in Finland. To be included in the present study patients had to be at least 18 years old, be currently using a self-administered bDMARD and be diagnosed with RA. The results are presented as medians with their respective interquartile ranges (IQR) or percentages. RESULTS: Of the 158 pharmacy customers asked to participate, 135 (85%) consented to complete the questionnaire. The included respondents were predominantly female (72%) with a median age of 55 (IQR 44-65) and rheumatic activity of 3 out of 10 (IQR 2-6.5). The majority (91%) of the included respondents were using TNF-inhibitors and 27% of all patients were on biologic monotherapy. MTX was currently used by 45% of the respondents while 50% were past users. Of the current MTX users, 6.8% identified themselves moderately non-adherent to the treatment. MTX-related adverse events were important factors associated with nonadherence and discontinuation of the treatment. CONCLUSIONS: Only 45% of the respondents were currently using MTX co-therapy, but the ones who did were adherent to their treatment. Self-reported adherence may however be subject to social desirability bias and recall bias.
26915672 Identification of novel urinary biomarkers for assessing disease activity and prognosis of 2016 Feb 26 To optimize treatment for rheumatoid arthritis (RA), it is ideal to monitor the disease activity on a daily basis because RA activity fluctuates over time. Urine can be collected routinely at home by patients. Recently, we identified four urinary biomarker candidates-gelsolin (GSN), orosomucoid (ORM)1, ORM2 and soluble CD14 (sCD14)-in RA patients through transcriptomic and proteomic studies. Here, we investigated the clinical significance of the aforementioned urinary biomarker candidates in a prospective manner. For the first time, we found that urinary ORM1, ORM2 and sCD14 levels, but not GSN, were elevated in RA patients and had a positive correlation with the status of the disease activity. In particular, urine tests for ORM 1, ORM 2 and sCD14 efficiently represented the presence of high RA activity without the need for measuring blood markers. In a parallel study, a more rapid radiographic progression over 3 years was observed in patients with higher ORM2 levels. Combined measurements of urinary ORM2 and serum C-reactive protein synergistically increased the predictability of the radiographic progression of RA (odds ratio: 46.5). Collectively, our data provide evidence that blood-free, urinary biomarkers are promising surrogates for assessing disease activity and prognosis of RA. We anticipate that our urinary biomarkers will provide novel candidates for patient-driven measurements of RA activity at home and can shift the paradigm from blood to urine testing in the assessment of RA activity and prognosis in hospitals.
26237971 [Effects of Moxibustion on Expression of STAT 1, SOCS mRNA in Synovium of Rats with Rheuma 2015 Jun OBJECTIVE: To observe the effect of moxibustion on mRNA expression of signal transducers and activators of transcription 1 (STAT 1), suppressors of cytokine signaling (SOCS) in synovium of rheumatoid arthritis (RA) rats, and to investigate its mechanism for relieving RA. METHODS: 40 Wistar rats were equally and randomly divided into control, model, moxibustion, acupuncture and infrared groups (n = 8 in each group). RA model was developed by putting rats in windy, cold and damp room and injection of Freund's complete adjuvant. Bilateral "Shenshu" (BL 23) were stimulated by the respective means for 20 min in duration, once every other day, ten times in total. The swelling degree of voix pedis (perimeter) of rats was measured. The contents of serum interleukin-1 (IL-1) and interleukin-2(IL-2) were detected by radioimmunoassay, and expression of STAT 1, SOCS mRNA in synovium were assessed by RT-PCR. RESULTS: Rats in model group had acute and severe swelling of voix pedis, together with the increase of serum IL-1 content and decrease of IL-2 content, and down-regulation of mRNA expression of both STAT 1 and SOCS in synovium(all P<0. 01). All three modalities of treatment alleviated the swelling and reversed the relevant changes(P<0. 05, P<0. 01) , however, moxibustion produced greater effects than acupuncture or infrared in elevating IL-2 content and up-regulating mRNA expression of both STAT 1 and SOCS. CONCLUSION: Moxibustion achieves the effects of anti-inflammation and joint swelling reduction of RA via decrease of IL-1, increase of IL-2 in serum and up-regulation of STAT 1, SOCS mRNA expression in synovium.
25574939 The effect of social support features and gamification on a Web-based intervention for rhe 2015 Jan 9 BACKGROUND: Rheumatoid arthritis (RA) is chronic systematic disease that affects people during the most productive period of their lives. Web-based health interventions have been effective in many studies; however, there is little evidence and few studies showing the effectiveness of online social support and especially gamification on patients' behavioral and health outcomes. OBJECTIVE: The aim of this study was to look into the effects of a Web-based intervention that included online social support features and gamification on physical activity, health care utilization, medication overuse, empowerment, and RA knowledge of RA patients. The effect of gamification on website use was also investigated. METHODS: We conducted a 5-arm parallel randomized controlled trial for RA patients in Ticino (Italian-speaking part of Switzerland). A total of 157 patients were recruited through brochures left with physicians and were randomly allocated to 1 of 4 experimental conditions with different types of access to online social support and gamification features and a control group that had no access to the website. Data were collected at 3 time points through questionnaires at baseline, posttest 2 months later, and at follow-up after another 2 months. Primary outcomes were physical activity, health care utilization, and medication overuse; secondary outcomes included empowerment and RA knowledge. All outcomes were self-reported. Intention-to-treat analysis was followed and multilevel linear mixed models were used to study the change of outcomes over time. RESULTS: The best-fit multilevel models (growth curve models) that described the change in the primary outcomes over the course of the intervention included time and empowerment as time-variant predictors. The growth curve analyses of experimental conditions were compared to the control group. Physical activity increased over time for patients having access to social support sections plus gaming (unstandardized beta coefficient [B]=3.39, P=.02). Health care utilization showed a significant decrease for patients accessing social support features (B=-0.41, P=.01) and patients accessing both social support features and gaming (B=-0.33, P=.03). Patients who had access to either social support sections or the gaming experience of the website gained more empowerment (B=2.59, P=.03; B=2.29, P=.05; respectively). Patients who were offered a gamified experience used the website more often than the ones without gaming (t91=-2.41, P=.02; U=812, P=.02). CONCLUSIONS: The Web-based intervention had a positive impact (more desirable outcomes) on intervention groups compared to the control group. Social support sections on the website decreased health care utilization and medication overuse and increased empowerment. Gamification alone or with social support increased physical activity and empowerment and decreased health care utilization. This study provides evidence demonstrating the potential positive effect of gamification and online social support on health and behavioral outcomes. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 57366516; http://www.controlled-trials. com/ISRCTN57366516 (Archived by webcite at http://www.webcitation.org/6PBvvAvvV).
27188329 Differential response of serum amyloid A to different therapies in early rheumatoid arthri 2016 May 17 BACKGROUND: The aim was to compare the effect of etanercept (ETN) and conventional synthetic disease-modifying anti-rheumatic drug (DMARD) therapy on serum amyloid A (SAA) levels and to determine whether SAA reflects rheumatoid arthritis (RA) disease activity better than C-reactive protein (CRP). METHODS: We measured SAA and CRP at baseline, 24, 48, and 102 week follow-up visits in 594 patients participating in the Treatment of early RA (TEAR) study. We used Spearman correlation coefficients (rho) to evaluate the relationship between SAA and CRP and mixed effects models to determine whether ETN and methotrexate (MTX) treatment compared to triple DMARD therapy differentially lowered SAA. Akaike information criteria (AIC) were used to determine model fits. RESULTS: SAA levels were only moderately correlated with CRP levels (rho = 0.58, p < 0.0001). There were significant differences in SAA by both visit (p = 0.0197) and treatment arm (p = 0.0130). RA patients treated with ETN plus MTX had a larger reduction in SAA than patients treated with traditional DMARD therapy. Similar results were found for serum CRP by visit (p = 0.0254) and by treatment (p < 0.0001), with a more pronounced difference than for SAA. Across all patients and time points, models of the disease activity score of 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) using SAA levels were better than models using CRP; the ΔAIC between the SAA and CRP models was 305. CONCLUSIONS: SAA may be a better biomarker of RA disease activity than CRP, especially during treatment with tumor necrosis factor (TNF) antagonists. This warrants additional studies in other cohorts of patients on treatment for RA. TRIAL REGISTRATION: (ClinicalTrials.gov identifier: NCT00259610 , Date of registration: 28 November 2005).
27404695 Serum pentraxin 3 levels are negatively associated with carotid intima media thickness in 2016 Oct 15 BACKGROUND: Pentraxin-3 (PTX3) is a long pentraxin that is supposed to participate in the inflammatory process and in atherosclerosis. AIM: To study PTX3 serum levels in rheumatoid arthritis (RA) patients to know if its serum levels may reflect disease activity and/or subclinical atherosclerosis. METHODS: PTX3 and carotid intima media thickness (IMT) were studied in 85 RA patients (83.5% females, median age of 59years old, median disease duration of 13years) along with its demographic, clinical, serological and lipid profile. For comparison PTX3 was measured in 85 healthy volunteers. RESULTS: PTX3 levels in RA patients were similar to controls (p=0.21) and did not correlate with inflammatory activity measured by ESR (p=0.39) CRP (p=0.18) and DAS28 (p=0.67). Serum PTX3 levels were higher in nonobese RA patients than in obese (BMI vs PTX3 with rho=-0.27; 95%IC=-0.46 to -0.06; p=0.009). In non-obese patients, PTX3 correlated negatively with carotid IMT (rho=-0.40; 95%IC=-0.66 to -0.06; p=0.01) but not in the obese ones (p=0.26). In the obese RA patients there was a negative correlation between PTX3 levels and LDL/HDL ratio (Rho=-0.29; 95%IC=-0.53-0.01; p=0.03). CONCLUSIONS: PTX3 levels do not reflect inflammatory process in RA. However, it exerts a protective role in the process of atherogenesis in non-obese RA patients.
26003199 Interleukin-1β, Interleukin1-Ra, Interleukin-10, and tumor necrosis factor-α polymorphis 2015 Sep OBJECTIVES: The aim of this study was to investigate the role of IL-1β (-511C>T), TNFα (-308 G>A), IL-10 (-1082 G>A) and IL-1RN VNTR polymorphisms in the susceptibility to rheumatoid arthritis (RA) in Tunisians. PATIENTS AND METHODS: Using PCR-based methods, 104 RA patients and 150 healthy controls were investigated. We compared allele and genotype frequencies in RA patients versus controls and analyzed their correlations with erosive form (EF). RESULTS: IL1-RN VNTR A1A3 genotype is associated with higher risk of RA (P=0.012, OR=4.31). Among the cases, males who carry this genotype were more exposed to RA (P=0.044, OR=8, 47). For IL1- β gene, a significantly higher frequency of the -511C/C genotype was observed in RA patients in comparison to controls (P=0.013, OR=2.45). This higher frequency was especially observed in women (P=0,003, OR=3.42). In contrast, IL10-1082G/G genotype was less common in patients (P=0.046, OR=0.46). According to EF, men carrying IL1-RN VNTR A1A3 (P=0.005 OR=5.28) and IL1-β-511C/C (P=0.015 OR=2.61) genotypes develop non EF of RA. Moreover, TNFα-308 A allele (P=0.024, OR=1.84) and A/A genotype (P=0.033, OR=3.1) were positively associated to EF of RA. However, G allele (P=0.024, OR=0.31) and GG genotype (P=0.31, OR=0.031) of the TNFα-308 were protectors. CONCLUSION: Our results indicated that IL-1RN VNTR, IL-1β (-511C>T) and IL-10 (-1082 G>A) are associated with susceptibility to RA, and that IL-1RN VNTR, IL-1β (-511C>T) and TNFα (-308 G>A) are associated with severity of RA.
25986917 Interplay between patient global assessment, pain, and fatigue and influence of other clin 2015 Jul The interplay between patient-reported outcome measures in rheumatology is not well clarified. The objective of the study was to examine associations on the group level and concordance on the individual patient level between patient global assessment (PaGl), pain, and fatigue as scored on visual analog scales (VAS) in the daily clinic by patients with active rheumatoid arthritis (RA). Associations with other measures of disease activity were also examined. Traditional disease activity data on 221 RA patients with active disease planned to initiate biological treatment were extracted from the Danish DANBIO registry. Associations between VAS PaGl, pain, and fatigue (0-100) were examined using multiple regression analysis. Concordance between the VAS scores was expressed as the bias (mean difference between intra-individual scores) and the 95% lower and upper limits of agreement (LLoA; ULoA) according to the Bland-Altman method. Mean age was 57 ± 14 years, mean Disease Activity Score (DAS28-CRP4) 5.0 ± 0.9, and mean PaGl 63.6 ± 22.6. PaGl was most strongly predicted by pain and fatigue, pain by PaGl and fatigue, and fatigue by PaGl and pain (beta ranging from 0.17 to 0.69, p < 0.01-0.0001). More objective measures were not or far less predictive. LLoA;ULoA [bias] for PaGl vs. pain was -19.1; 29.5 [5.2], for PaGl vs. fatigue -22.8; 28.6 [2.9], and for fatigue vs. pain -29.2; 33.8 [2.3]. In conclusion, PaGl, pain, and fatigue were most strongly explained by each other, not by more objective clinical measures of disease activity and were nearly identical on the group level. On the individual patient level, however, differences between the scores varied considerably. The findings highlight the challenge of understanding and dealing with traditional patient-reported VAS measures when it comes to individual RA patients in the daily clinic.
26173043 Comorbidities in patients with psoriatic arthritis: a comparison with rheumatoid arthritis 2015 Nov AIM: Psoriatic arthritis (PsA) is a chronic, inflammatory disease. The purpose of this study was to examine the association between PsA and comorbid conditions. This is the first study to investigate comorbid diseases in PsA in Turkey. METHODS: This study was performed under the auspices of the Anatolian Group for the Assessment in Rheumatic Diseases (ANGARD) and involved participation by six university research hospitals. Patients diagnosed with and treated for PsA on the basis of clinical, radiological and laboratory findings and expert opinion were monitored using standardized examination methods and jointly prepared forms. Clinical status, accompanying systemic diseases and surgical history were recorded. RESULTS: One hundred and seventy-three patients with PsA (75 male, 98 female, mean age 41.8) and 138 patients with rheumatoid arthritis (RA) (17 male, 121 female, mean age 48.6) and 67 with psoriasis (PsO) (43 male, 24 female, mean age 36.1) were included in the study. No accompanying disease was determined in 72.8% of PsA, 50.0% of RA and 80.6% of PsO groups. In regression analysis, patients with PsA had higher risk for cataract/glaucoma surgery (odds ratio [OR] = 11.99; 95% CI 1.36-105.4, P = 0.025) compared to patients with RA, and higher risk for hypertension (HT) (OR = 4.26; 95% CI 1.27-14.23, P = 0.018) compared to the patients with PsO. CONCLUSION: Patients with PsA have relatively lower frequency of comorbidities like diabetes mellitus, HT and cataract/glaucoma surgery compared to the patients with RA. The increased risk for having cataract/glaucoma surgery in RA compared to PsA may be particularly attributed to the more prevalent glucocorticoid use in RA.
27556040 Effect of Anti-TNF Antibodies on Clinical Response in Rheumatoid Arthritis Patients: A Met 2016 Background. Antitumor necrosis factor (anti-TNF) drugs have been applied for rheumatoid arthritis (RA) treatment; however, patients having anti-drug antibodies (ADAbs) do not benefit from these drugs. The meta-analysis aims to comprehensively assess the relationship between ADAb positive (ADAb+) and anti-TNF response in RA patients. Methods. Observational studies comparing different clinical response between ADAb+ and ADAb negative groups were included. Odds ratio (OR) with its corresponding 95% confidence interval (CI) was used as effect size. Subgroup analyses stratified by TNF inhibitor types and assay methods for ADAb detection were performed. Results. Totally, 10 eligible studies containing 1806 subjects were included. ADAb+ was significantly associated with reduced anti-TNF response to RA at all the time points after follow-up (P < 0.001). Subgroup analysis also supported this significant association (P < 0.05), except for enzyme-linked immunosorbent assay (ELISA) group at 3 months, infliximab (INF) and enzyme-linked immunosorbent assay (ELISA) groups at 6 months, and Immunological Multi-Parameter Chip Technology (IMPACT) group at 12 months. Conclusion. ADAb+ was significantly associated with reduced clinical response in RA patients, and other alternatives should be considered in RA patients presenting ADAb+.
27281095 Circulating interleukin-6 and rheumatoid arthritis: A Mendelian randomization meta-analysi 2016 Jun Interleukin-6 (IL-6), as a pleiotropic cytokine, has been demonstrated to be closely associated with the pathogenisis of rheumatoid arthritis (RA). However, whether this association is causal or not remains unclear, because of the multifactorial role of IL-6 and related confounding factors. We aimed to evaluate the causal relevance between circulating IL-6 levels and the risk of RA through meta-analytical Mendelian randomization approach. IL-6 gene -174G/C variant was selected as an instrument in this Mendelian randomization meta-analysis. Article identification and data collection were conducted in duplicate and independently by 2 authors. The STATA software was used for data analysis. In total, 15 and 5 articles on the association of the -174G/C variant with RA risk and circulating IL-6 level, respectively, were included. The overall analysis showed that C allelic and GC+CC genotype were significantly with 1.59-fold (95% CI: 1.19-2.14) and 1.63-fold (95% CI: 1.17-2.26) increased risk of developing RA, respectively. Asian populations showed stronger association with 4.55-fold (95% CI: 1.62-12.75), 1.84-fold (95% CI: 1.13-2.99), and 4.69-fold (95% CI: 1.68-13.14) increased RA risk in carriers of -174C allelic, CC, and GC+CC genotype, respectively. Carriers of GC+CC genotype showed significant reduction in the circulating IL-6 level compared with GG carriers (WMD = -0.77; 95% CI: -1.16 to -0.38; P = 0.000) in overall populations. Mendelian randomization presented 6% and 22% increased risk of RA with 0.1 pg/mL reduction of circulating IL-6 level in overall and Asian populations, respectively. This Mendelian randomization meta-analysis demonstrated that the long-term genetically reduced circulating IL-6 level might be causally related to a higher risk of RA, especially in Asian populations.
26090499 Methotrexate, Cyclosporine A, and Biologics Protect against Atherosclerosis in Rheumatoid 2015 INTRODUCTION: The risk of cardiovascular disease is increased in rheumatoid arthritis (RA). A meta-analysis showed increased intima media thickness (IMT) in RA. It has been shown that disease modifying antirheumatic drugs (DMARDs) may influence the progression of atherosclerosis. However, it was suggested that biologics may be more efficient than other DMARDs (including methotrexate--MTX) in protecting against atherosclerosis. OBJECTIVES: The aim of this study was to assess the influence of different RA characteristics and treatment regimens on IMT and atherosclerotic plaques. PATIENTS AND METHODS: 317 RA patients and 111 controls were included in the study. IMT was measured in carotid (CIMT) and femoral (FIMT) arteries. Arteries were screened for the presence of plaques. RESULTS: CIMT, FIMT, and prevalence of plaques were lower in patients treated with methotrexate (MTX) ≥ 20 mg/wk, cyclosporine (CsA), or biologics than in patients treated with lower doses of MTX and other disease modifying antirheumatic drugs. No differences in IMT between patients treated with MTX ≥ 20 mg/wk, biologics, or CsA were found. CONCLUSIONS: We found a beneficial effect of MTX ≥ 20 mg/wk, biologics, and CsA on atherosclerosis. We do not confirm a stronger influence of biologics on IMT compared with therapeutic doses of MTX.
26683321 Serum and synovial cartilage oligomeric matrix protein levels in early and established rhe 2016 Nov OBJECTIVE: To assess cartilage oligomeric matrix protein (COMP) levels in serum and synovial fluid in patients with early and established rheumatoid arthritis (RA), and to correlate the levels with clinical, laboratory and radiological characteristics. PATIENTS AND METHODS: The study included 24 female RA patients. Full medical history was taken, thorough clinical examination and laboratory investigations performed, and body mass index (BMI) recorded. Radiological damage was assessed according to the modified Larsen score. Disease activity score 28 (DAS28) was calculated. The control group comprised 30 age- and gender-matched healthy subjects. Serum and synovial COMP levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Mean patient age was 44.04 ± 10.5 years. Of the 24 patients, 12 had early RA and 12 had established disease with joint destruction; 5 of each group had knee effusion. Serum COMP was significantly higher in patients (19.54 ± 5.47 µg/ml) compared to controls (5.93 ± 1.95 µg/ml; p < 0.001) and was also significantly higher in patients with established disease (23.9 ± 3.1 µg/ml) compared to those in early stages (15.1 ± 3.2 µg/ml; p < 0.001). Synovial COMP was also significantly increased in established compared to early-stage RA (31.2 ± 9.8 µg/ml vs. 51.6 ± 10.4 µg/ml; p = 0.013). Serum and synovial COMP significantly correlated with age, disease duration, BMI, DAS28 and modified Larsen score. On performing regression analysis in RA patients, only BMI could predict the serum level of COMP (p = 0.02). CONCLUSION: COMP is a promising biomarker for disease activity in RA, making it a potential therapeutic target. The obvious correlation with the BMI throws light on the importance of weight control not only in osteoarthritis (OA), but also in RA.
25890307 Working mechanism of a multidimensional computerized adaptive test for fatigue in rheumato 2015 Feb 21 BACKGROUND: This paper demonstrates the mechanism of a multidimensional computerized adaptive test (CAT) to measure fatigue in patients with rheumatoid arthritis (RA). A CAT can be used to precisely measure patient-reported outcomes at an individual level as items are consequentially selected based on the patient's previous answers. The item bank of the CAT Fatigue RA has been developed from the patients' perspective and consists of 196 items pertaining to three fatigue dimensions: severity, impact and variability of fatigue. METHODS: The CAT Fatigue RA was completed by fifteen patients. To test the CAT's working mechanism, we applied the flowchart-check-method. The adaptive item selection procedure for each patient was checked by the researchers. The estimated fatigue levels and the measurement precision per dimension were illustrated with the selected items, answers and flowcharts. RESULTS: The CAT Fatigue RA selected all items in a logical sequence and those items were selected which provided the most information about the patient's individual fatigue. Flowcharts further illustrated that the CAT reached a satisfactory measurement precision, with less than 20 items, on the dimensions severity and impact and to somewhat lesser extent also for the dimension variability. Patients' fatigue scores varied across the three dimensions; sometimes severity scored highest, other times impact or variability. The CAT's ability to display different fatigue experiences can improve communication in daily clinical practice, guide interventions, and facilitate research into possible predictors of fatigue. CONCLUSIONS: The results indicate that the CAT Fatigue RA measures precise and comprehensive. Once it is examined in more detail in a consecutive, elaborate validation study, the CAT will be available for implementation in daily clinical practice and for research purposes.
27585684 Triage of Rheumatology Referrals Facilitates Wait Time Benchmarks. 2016 Nov OBJECTIVE: In 2014 the Canadian Rheumatology Association published wait time benchmarks for inflammatory arthritis (IA) and connective tissue disease (CTD) to improve patient outcomes. This study's aim was to determine whether centralized triage and the introduction of quality improvement initiatives would facilitate achievement of wait time benchmarks. METHODS: Referrals from September to November 2012 were retrospectively triaged by an advanced practice physiotherapist (APP) and compared to referrals triaged by an APP from January to March 2014. Each referral was assigned a priority ranking and categorized into one of 2 groups: suspected IA/CTD, or suspected non-IA/CTD. Time to initial consult and time to notification from receipt of referral were assessed. RESULTS: A total of 558 (n = 227 and n = 331 from 2012 and 2014, respectively) referrals were evaluated with 35 exclusions. In 2012, there were 96 (42.5%) suspected IA/CTD and 124 (54.9%) suspected non-IA/CTD patients at the time of the initial consult. Mean wait times in 2012 for patients suspected to have IA was 33.8 days, 95% CI 27.8-39.8, compared to 37.3 days, 95% CI 32.9-41.7 in suspected non-IA patients. In 2014, there were 131 patients (43%) with suspected IA based on information in the referral letter. Mean wait times in 2014 for patients suspected to have IA was 15.5 days, 95% CI 13.85-17.15, compared to 52.2 days, 95% CI 46.3-58.1 for suspected non-IA patients. Time to notification of appointment improved from 17 days to 4.37 days. CONCLUSION: Centralized triage of rheumatology referrals and quality improvement initiatives are effective in improving wait times for priority patients as determined by paper referral.
25884688 Haptoglobin-α1, -α2, vitamin D-binding protein and apolipoprotein C-III as predictors of 2015 Mar 6 INTRODUCTION: The introduction of tumor necrosis factor-alpha (TNF-α) antagonists has substantially improved patient's clinical outcome in rheumatoid arthritis (RA). However, nearly 20% to 40% of RA patients do not respond to anti-TNF-α treatment strategies. To identify valid predictors of TNF-α antagonist response in RA, serum proteome profiles from responders (R) and non-responders (NR) to etanercept, a soluble recombinant TNF-α receptor/IgG Fc fusion protein receptor, were compared in a prospective cohort study. METHODS: In this clinical study 50 RA patients with inadequate response to conventional DMARDs were included and treated with etanercept. The primary efficacy endpoint was response according to the European League against Rheumatism (EULAR) improvement criteria. Serum samples collected prior to initiation and after six months of etanercept therapy were cleared of the most abundant major proteins by immunoaffinity chromatography. After separation by two-dimensional differential gel electrophoresis (2D-DIGE) and identification by mass spectrometry (MS) data were validated by Western blot analysis. RESULTS: After six months of etanercept treatment 62% (n=31) of RA patients achieved response. Haptoglobin-α1 (Hp-α1) and -α2 (Hp-α2) and vitamin D-binding protein (VDBP) were found to be significantly upregulated in responder sera (P≤0.02) at study entry. In contrast, apolipoprotein C-III (ApoC-III) showed significantly higher levels in non-responders (P=0.0162). At study end ApoA-II, Hp-α1, Hp-α2 and VDBP were identified to be expressed at significantly higher levels (P<0.05) in responder sera. CONCLUSIONS: By application of clinical proteomics in immunodepleted sera we could identify and validate for the first time Hp-α1, -α2, VDBP and ApoC-III as potential biomarkers for prediction of etanercept drug response in RA.
26268815 Association of HLA-DRB1 alleles with clinical responses to the anti-interleukin-17A monocl 2016 Jan OBJECTIVE: To assess whether preliminary findings of associations between the HLA-DRB1*04 and HLA-DRB1* shared epitope (SE) allelic groups and response to the anti-IL-17A mAb secukinumab in RA were reproducible in an independent RA cohort. METHODS: Biologic-naïve subjects (n = 100) with RA by 2010 criteria with tender/swollen joint counts (each ≥6) and high-sensitivity CRP (hsCRP) >10 mg/l were randomized 2:1 to secukinumab 10 mg/kg i.v. or placebo every 2 weeks until week 10. Potential associations with treatment response to secukinumab at week 12 (DAS28-CRP change from baseline by analysis of covariance, ACR20 response rate by logistic regression) were assessed for HLA-DRB1*04 (primary end point), HLA-DRB1*SE and HLA-DRB1 position 11 V/L (HLA-DRB1*pos11 V/L) allelic groups, and baseline levels of hsCRP, RF and anti-CCP. RESULTS: Secukinumab was significantly more effective than placebo in reducing DAS28-CRP (-2.41 vs -0.71; P < 0.0001) and producing ACR20 responses (87.1% vs 25.0%; P < 0.0001) at week 12. The HLA-DRB1*04 allelic group was not significantly related to secukinumab response vs placebo. For change from baseline in DAS28-CRP, HLA-DRB1*SE (P = 0.003) and HLA-DRB1*pos11 V/L (P = 0.002) allelic groups were associated with positive treatment response. Higher RF levels, but not anti-CCP positivity, were significantly associated with DAS28-CRP reductions (P = 0.015) and ACR20 (P = 0.008) responses. Secukinumab was well tolerated. CONCLUSION: Secukinumab significantly reduced signs and symptoms of RA vs placebo. As the HLA-DRB1*SE and HLA-DRB1*pos11 V/L results were driven by lack of placebo response in carriers, the hypothesis of clinical utility for HLA-DRB1* allelic groups in RA anti-IL-17A short-term response prediction could not be corroborated. TRIAL REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov/; NCT01426789.
27776599 Comparative utility of interferon-γ release assay, QuantiFERON(®) TB-GIT and T-SPOT(®). 2016 Nov SETTING: National hospital for tuberculosis (TB) and rheumatoid arthritis (RA) in Japan. OBJECTIVE: To compare two interferon-γ release assays (IGRAs), QuantiFERON(®)-TB Gold In-Tube (QFT) and T-SPOT(®).TB (T-SPOT), in RA patients for detecting latent tuberculous infection (LTBI). DESIGN: QFT and T-SPOT were conducted concurrently in 230 prospectively enrolled RA patients. RESULTS: There were no active TB patients. The percentage of QFT- and T-SPOT-positive patients was respectively 8.3% and 5.7%. In patients aged ⩾60 years, these proportions were respectively 12.3% and 7.2%. The percentage of QFT positivity and T-SPOT positivity at age <60 years was respectively 2.2% and 3.3%. After multivariate logistic analysis for QFT positivity, age ⩾60 years and TB suspected based on chest X-ray were selected as independent factors, with adjusted odds ratios of respectively 4.73 and 3.25. No factors were selected for T-SPOT positivity. CONCLUSION: QFT had a higher positivity rate. In the light of the previous estimated rate of LTBI in Japan, both IGRAs underestimate LTBI, and neither IGRA has enough capability to detect LTBI.
26204444 Interleukin 35 Synovial Fluid Levels Are Associated with Disease Activity of Rheumatoid Ar 2015 OBJECTIVES: To study the association of systemic and local interleukin-35 (IL-35) levels in rheumatoid arthritis. METHODS: 37 patients with treatment naïve early RA, 49 with established RA and 29 control patients with osteoarthritis (OA) were studied. Serum and paired synovial fluid samples were analysed for IL-35. Disease activity of RA patients was assessed according to the 28-Joint Count Disease Activity Score (DAS28). RESULTS: The levels of serum IL-35 were significantly higher in patients with treatment naïve early RA compared to those with established disease and control OA subjects. In addition, serum levels of IL-35 significantly decreased 12 weeks after initiation of glucocorticoids and conventional synthetic disease modifying antirheumatic drugs in patients with treatment naïve early RA. Synovial fluid IL-35 levels were significantly higher in RA compared to OA patients, were significantly elevated compared to serum counterparts and correlated with synovial fluid leukocyte count (r=0.412; p<0.01), serum CRP levels (r=0.362; p<0.05) and DAS28 (r=0.430, p<0.01). CONCLUSION: This is the first study showing elevated circulating levels of IL-35 in treatment naïve early RA, its significant decrease after treatment initiation and positive association between increased synovial fluid IL-35 and disease activity in patients with long-lasting RA.
25794569 Cost-utility analysis of tocilizumab monotherapy in first line versus standard of care for 2015 Sep The study aims to evaluate the cost-effectiveness of adding tocilizumab (TCZ) first line to a treatment sequence for patients with active rheumatoid arthritis (RA), who had an inadequate response to one or more traditional synthetic disease-modifying antirheumatic drugs (DMARDs) and are intolerant to methotrexate (MTX), or in whom continued treatment with MTX is considered inappropriate. An individual simulation model was applied to project lifetime costs and outcomes for 10,000 patients from a payer's perspective. The analysis compared the standard treatment pathway (STP) with a similar pathway, where treatment was initiated with TCZ. QALYs were used as primary efficacy outcomes. Efficacy data were obtained from the ADACTA trial and a network meta-analysis. Clinical practice standards were derived from an expert panel of Greek rheumatologists. Results indicate that a treatment sequence starting with TCZ yields 1.17 more QALYs (9.38 vs. 8.21) at an additional cost of €3,744 (€119,840 vs. €86,096) compared with the STP. The incremental cost-effectiveness ratio was €28,837/QALY gained. Probabilistic sensitivity analysis confirms robustness of these findings as consistently below a threshold of €45,000. The results of the analysis suggest that TCZ, when used as a first-line biologic monotherapy, can be a cost-effective treatment option for the management of active RA in patients in need of biologic monotherapy.