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ID PMID Title PublicationDate abstract
28798049 Patient-reported outcomes from a phase 3 study of baricitinib versus placebo or adalimumab 2017 Nov BACKGROUND: To assess the effect of baricitinib on patient-reported outcomes (PROs) in patients with active rheumatoid arthritis and an inadequate response to methotrexate (MTX). METHODS: In this double-blind phase 3 study, patients were randomised 3:3:2 to placebo (n=488), baricitinib 4 mg once daily (n=487), or adalimumab 40 mg biweekly (n=330) with background MTX. PROs included the SF-36, EuroQol 5-D (EQ-5D) index scores and visual analogue scale, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity (PtGA), patient's assessment of pain and Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis (WPAI-RA), and measures collected in electronic patient daily diaries: duration and severity of morning joint stiffness (MJS), Worst Ttiredness and Worst Joint Pain. The primary study endpoint was at week 12. Treatment comparisons were assessed with logistic regression for categorical measures or analysis of covariance for continuous variables. RESULTS: Compared with placebo and adalimumab, baricitinib showed statistically significant improvements (p≤0.05) in HAQ-DI, PtGA, pain, FACIT-F, SF-36 physical component score, EQ-5D index scores and WPAI-RA daily activity at week 12. Improvements were maintained for measures assessed to week 52. Statistically significant improvement in patient diary measures (MJS duration and severity), worst tiredness and worst joint pain were observed for baricitinib versus placebo and adalimumab at week 12 (p≤0.05). CONCLUSIONS: Baricitinib provided significantly greater improvement in most PROs compared with placebo and adalimumab, including physical function MJS, pain, fatigue and quality of life. Improvement was maintained to the end of the study (week 52). TRIAL REGISTRATION: NCT01710358.
27632985 The Relationship Between Focal and Generalized Bone Loss in Rheumatoid Arthritis. 2017 OBJECTIVE: To determine if there is an association between focal and systemic bone loss in patients with RA. METHODS: Bone loss is a hallmark finding in rheumatoid arthritis (RA) and manifests as localized, periarticular and systemic bone loss. RA patients were selected from the Consortium of Rheumatology Researchers of North America (CORRONA) database. Multiple logistic regression models were constructed to assess the association between the presence or absence of erosions and T-scores at the lumbar spine (LS) and total hips and adjusted for age, gender, body mass index (BMI), medications and disease activity indices. RESULTS: Data on erosions and T-scores were available in 3,898 and 5,099 subjects, respectively. Patients with erosions had a significantly lower LS T-scores (-0.9) compared to RA patients without erosions (p=0.0002). Similarly, the mean total hip T-scores were significantly lower in patients with (-1.4) compared to subjects without erosions (-1.0) (p<0.01). The odds of having no erosion increased by 21% for each 1-unit increase in LS T-score and 46% for each 1 unit increase in hip Tscore. Patients with erosions were significantly younger (p<0.01) had a lower BMI (p<0.01) and higher DAS28 scores than those without erosions. More patients with erosions were on anti-TNF therapy, disease modifying drugs and osteoporosis medications than patients without erosions (p<0.01, 0.003 and 0.0003). CONCLUSION: RA patients with bone erosions have significantly lower T-scores at the LS and hips compared with RA patients without erosions. These data suggest a relationship between localized and generalized bone loss in RA.
28425837 Calprotectin levels in rheumatoid arthritis and their correlation with disease activity: a 2017 Jun OBJECTIVE: We evaluated the relationship between calprotectin levels and rheumatoid arthritis (RA), and the correlation between plasma/serum calprotectin and RA activity. METHODS: We searched PUBMED, EMBASE, and Cochrane databases and performed meta-analyses comparing plasma/serum or synovial fluid calprotectin levels in RA patients and controls, and correlation coefficients between calprotectin levels and disease activity for 28 joints (DAS28) as well as C-reactive protein (CRP) in RA patients. RESULTS: Sixteen studies including 849 RA patients and 266 controls were available for meta-analysis. Meta-analysis showed that calprotectin levels were significantly higher in the RA group than in the control group (SMD = 2.337, 95% CI = 1.544-3.130, p < 1.0 × 10(-8)). Stratification by rheumatoid factor (RF) status revealed significantly elevated calprotectin levels in the RF-positive RA group compared to that of the RF-negative RA group (SMD = 0.574, 95% CI = 0.345-0.804, p = 9.2 × 10(-7)). Meta-analysis of correlation coefficients identified a significant positive correlation between calprotectin levels and CRP or DAS28 (correlation coefficient for CRP = 0.566, 95% CI = 0.512-0.615, p < 1.0 × 10(-8); correlation coefficient for DAS28 = 0.438, 95% CI = 0.269-0.518, p = 2.5 × 10(-6)). Calprotectin levels in synovial fluid were significantly higher in the RA group than in the control group (SMD = 2.891, 95% CI = 1.067-4.715, p = 0.002). CONCLUSIONS: Our meta-analysis demonstrates that circulating and synovial fluid calprotectin levels are high in patients with RA, and that circulating calprotectin levels positively correlate with RA activity.
28294565 Ankle pathologies in patients with inflammatory rheumatic diseases: a clinical and ultraso 2017 Jun AIM: We determined ankle pathologies in patients with different types of inflammatory rheumatic diseases using high-resolution ultrasonographic (US) images, and compared the findings among the different patient groups. METHODS: The study included 142 randomly selected inflammatory rheumatic disease patients with clinically swollen or painful ankle joints; 69 patients had rheumatoid arthritis (RA), 58 had spondyloarthropathies (SpA) and 15 had gout. Ankle assessment on US included all of the important anatomical structures. The foot function of patients was evaluated using the Foot Function Index (FFI). RESULTS: Among all the patients, 98.6% of joints were tender and 72.9% were swollen; 82.1% joints were pathological on US. Tibiotalar joint synovitis was observed significantly more frequently in the SpA and gout patients (P < 0.05). Tibialis posterior (TP) tenosynovitis was significantly more common in the RA group than in the other groups (P < 0.001). Subtalar and talonavicular joint synovitis were observed more frequently in the early RA group compared to the other groups (P < 0.05). Tibiotalar joint synovitis was observed more frequently > 1 year after RA diagnosis (P < 0.05). Subtalar joint synovitis, TP tenosynovitis, and peroneus tenosynovitis were the best predictors of higher FFI scores in patients with RA (R(2) c = 0.360, F = 11.83, P < 0.000). CONCLUSION: Tendon involvement in our RA patients was observed more frequently than has been previously estimated. TP tenosynovitis appears to be more specific for RA, while Achilles tendinitis is more frequent in axial SpA and reactive arthritis. Tibiotalar joint involvement exhibits a time-dependent significant increase in frequency in patients with RA.
28419440 The role of stromal cells in inflammatory bone loss. 2017 Jul Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation, local and systemic bone loss and a lack of compensatory bone repair. Fibroblast-like synoviocytes (FLS) are the most abundant cells of the stroma and a key population in autoimmune diseases such as RA. An increasing body of evidence suggests that these cells play not only an important role in chronic inflammation and synovial hyperplasia, but also impact bone remodelling. Under inflammatory conditions FLS release inflammatory cytokines, regulate bone destruction and formation and communicate with immune cells to control bone homeostasis. Other stromal cells, such as osteoblasts and terminally differentiated osteoblasts, termed osteocytes, are also involved in the regulation of bone homeostasis and are dysregulated during inflammation. This review highlights our current understanding of how stromal cells influence the balance between bone formation and bone destruction. Increasing our understanding of these processes is critical to enable the development of novel therapeutic strategies with which to treat bone loss in RA.
28427540 High resolution computed tomography pattern of usual interstitial pneumonia in rheumatoid 2017 May PURPOSE: Interstitial lung disease is a common extra-articular manifestation of rheumatoid arthritis (RA-ILD) and is associated with significant morbidity and mortality. However, limited data exist regarding predictors of mortality. We sought to examine the prognostic value of the high-resolution computed tomography (HRCT) patterns in patients with RA-ILD. MATERIALS AND METHODS: RA-ILD patients with HRCT patterns of usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) were identified among a longitudinal cohort of individuals evaluated at National Jewish Health. A total of 158 subjects were included in the study. For each subject, the earliest available HRCT was reviewed independently by two expert thoracic radiologists blinded to clinical data. HRCT patterns were classified as demonstrating definite UIP, possible UIP, or NSIP. Kaplan-Meier curves were generated and survival was compared among the three patterns using a log rank test for trend. RESULTS: One hundred subjects (63%) had HRCT findings classified as definite UIP, 23 (15%) as possible UIP and 35 (22%) as NSIP. No difference in survival was seen between subjects with definite UIP versus those with possible UIP. The combined group of subjects with either definite- or possible UIP had significantly worse survival than those with NSIP (log-rank p = 0.03). CONCLUSIONS: In patients with RA-ILD, patients with either definite UIP or possible UIP have equally poor survival when compared to those with an NSIP pattern.
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.
27550060 Effectiveness of golimumab for rheumatoid arthritis in patients with an inadequate respons 2017 Mar OBJECTIVES: Several biological disease-modifying antirheumatic drugs (bDMARDs) are currently available for the treatment of rheumatoid arthritis (RA). Increasing evidence indicates that second-line bDMARDs are effective for inadequate responders to first-line bDMARDs. However, all previous studies investigated the use of tumor necrosis factor inhibitors (TNFi) as a first-line bDMARD, while investigated the efficacy of second-line bDMARDs after the use of tocilizumab (TCZ), a non-TNFi, as a first-line bDMARD. Thus, we investigated the efficacy of golimumab (GLM) as a second-line bDMARD after treatment with TCZ as a first-line bDMARD. METHODS: The final study population consisted of 26 patients (inadequate responders to TCZ; TCZ group) with moderate or high disease activity (DAS28-ESR ≥3.2) at week 24 of treatment with TCZ as a first-line bDMARD or whose DAS28-ESR score worsened after starting TCZ treatment. These patients could be followed for another 52 weeks or more after the subsequent switch to GLM treatment. For comparison, 19 patients treated with TNFi as a first-line bDMARD and inadequate response to TNFi (TNFi group) were included. RESULTS: The DAS28-ESR score at week 52 after the start of treatment with GLM improved significantly compared with baseline in the TCZ and TNFi groups. However, the TCZ group showed significantly better improvement. Patients in both groups had significantly improved treatment outcomes according to European League Against Rheumatism response criteria, but there was no statistically significant difference among them. The retention rate at week 52 after the start of treatment with GLM was significantly higher in the TCZ group than in the TNFi group (81% vs. 68%, respectively). In addition, no difference was found in the progression of bone destruction determined by the change in van der Heijde modified total Sharp scoring system scores between groups. CONCLUSIONS: GLM was an effective therapeutic option for inadequate responders to TCZ.
27825791 Recommendations by the Spanish Society of Rheumatology for the management of patients diag 2017 May To establish a set of recommendations for the management of patients diagnosed with rheumatoid arthritis (RA) who cannot be treated with methotrexate (MTX) due to contraindications, drug toxicity or lack of adherence, and to establish therapeutic strategies more effective and safer in these RA patients. A qualitative analysis of the scientific evidence available to June 2015. The 2-round Delphi technique of consensus was used to collect and establish expert opinion based on the participants' clinical experience when only low quality evidence was available. A total of eighteen recommendations were developed for the management of this patient profile. Fourteen of these recommendations were related to drug safety aspects. Recommendations on contraindication and toxicity of MTX have been updated. The experts recommend the use of biological monotherapy, a preferred treatment option, in patients whose profiles reveal a contraindication, intolerance or circumstances that prevent us against the use of MTX. There is some high-quality scientific evidence that supports contraindication and establishes certain conditions of MTX use in RA patients with specific clinical profiles.
28084811 Power Doppler signal calibration in the finger joint between two models of ultrasound mach 2017 Oct Background Despite the advantages of ultrasound (US) in the management of rheumatoid arthritis (RA) patients, power Doppler (PD) US may be highly dependent on the type of US machine used. Purpose To present a method to calibrate the PD signal of two models of US machines by use of a flow phantom and finger joints of patients with RA. Material and Methods For the phantom study, the PD signal count was measured in the flow phantom perfusing blood mimicking fluid at various injection rates and pulse repetition frequencies (PRFs). The quantitative PD index was calculated with ImageJ. For the clinical study, the second and third metacarpophalangeal joints of five consecutive patients with RA were examined. The quantitative PD index was measured at various PRFs by use of two models of machine (the same models as the phantom study). Results For the phantom and clinical studies, negative correlations were found between the PRF and the quantitative PD index when the flow velocity was constant and positive correlations between flow velocity and the quantitative PD index at constant PRF. There was a significant difference in the depiction performance of synovial blood flow between the two models, which can be calibrated by adjusting the PRF values derived from the phantom study in each model. Conclusion Signal calibration of pannus vascularity between US machines may be possible by adjusting the PRF value according to flow phantom data. Different US machines can thus provide equivalent examination results concerning the pannus vascularity.
28706201 Genotypic variability based association identifies novel non-additive loci DHCR7 and IRF4 2017 Jul 13 Sero-negative rheumatoid arthritis (RA) is a highly heterogeneous disorder with only a few additive loci identified to date. We report a genotypic variability-based genome-wide association study (vGWAS) of six cohorts of sero-negative RA recruited in Europe and the US that were genotyped with the Immunochip. A two-stage approach was used: (1) a mixed model to partition dichotomous phenotypes into an additive component and non-additive residuals on the liability scale and (2) the Levene's test to assess equality of the residual variances across genotype groups. The vGWAS identified rs2852853 (P = 1.3e-08, DHCR7) and rs62389423 (P = 1.8e-05, near IRF4) in addition to two previously identified loci (HLA-DQB1 and ANKRD55), which were all statistically validated using cross validation. DHCR7 encodes an enzyme important in cutaneous synthesis of vitamin D and DHCR7 mutations are believed to be important for early humans to adapt to Northern Europe where residents have reduced ultraviolet-B exposure and tend to have light skin color. IRF4 is a key locus responsible for skin color, with a vitamin D receptor-binding interval. These vGWAS results together suggest that vitamin D deficiency is potentially causal of sero-negative RA and provide new insights into the pathogenesis of the disorder.
28613016 Number of parity and the risk of rheumatoid arthritis in women: A dose-response meta-analy 2017 Sep AIM: The association between parity and rheumatoid arthritis (RA) risk has been investigated, but results are controversial. Thus, our aim was to systematically analyze the effect of number of parity on the risk of RA in women. METHODS: Relevant published studies were identified using PubMed and embase databases through 1 April 2016. We pooled the relative risks (RR) and 95% confidence intervals (CI) using random-effects models. RESULTS: In all, 12 studies with a total of 2 497 580 participants and 11 521 RA cases were included. A borderline significant inverse association was observed when we compared parity with nulliparity for RA, with summarized RR = 0.90 (95%CI: 0.79-1.02; I(2)  = 58.5%, P(heterogeneity)  = 0.010). In dose-response analysis, we observed a significant nonlinear (P(nonlinearity)  = 0.000) relation between parity number and the risk of RA. Compared with null parity, the pooled RR of RA were 0.89 (95%CI: 0.86-0.93), 0.84 (95%CI: 0.79-0.89), 0.85 (95%CI: 0.79-0.90), 0.88 (95%CI: 0.81-0.95), 0.90 (95%CI: 0.83-0.97), 0.92 (95%CI: 0.84-1.02), and 0.94 (95%CI: 0.83-1.07) for 1, 2, 3, 4, 5, 6, and 7 live births, respectively. Subgroup and sensitivity analyses showed similar associations. No publication bias was found. CONCLUSION: The findings from the current meta-analysis indicate that parity was related to decreased risk of RA. The greatest risk reduction appeared when the parity number reached two. Further studies are warranted to confirm our findings.
28417529 Cardiovascular risk management in rheumatoid arthritis: A large gap to close. 2018 Mar OBJECTIVE: Rheumatoid arthritis (RA) portends significant cardiovascular morbidity and mortality. We therefore determined how often rheumatologists screened for and managed cardiovascular risk factors in RA patients, and the barriers to doing so. METHODS: We examined 300 patient charts from 10 university-affiliated rheumatology practices, to ascertain if they had been screened, treated and/or referred over a 3-year period. We subsequently distributed a national survey to Canadian rheumatologists to elucidate challenges in performing optimal cardiovascular risk modification. RESULTS: Most patients were screened for hypertension. Forty-one per cent were found to be hypertensive; however, the majority of these patients were neither treated nor referred to another provider for management. A small minority of patients were screened for diabetes and/or hyperlipidaemia, and these were usually not addressed if abnormal. Men were referred more frequently than women. Consistent with these findings, the majority of rheumatologists from the national survey felt that they did not manage cardiovascular risk adequately; 79.4% cited a lack of time as a major barrier, and 82.5% felt that it should be managed by the primary care provider. CONCLUSION: There is marked underdiagnosis and undertreatment of cardiac risk in RA. Several major barriers exist, including lack of time. Most rheumatologists feel that this aspect of care is the responsibility of primary care physicians.
28606965 Low disease activity (DAS28≤3.2) reduces the risk of first cardiovascular event in rheum 2017 Oct OBJECTIVE: Systemic inflammation appears to contribute to the excess risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The objective of this study was to investigate the effect of different levels of disease activity over time, particularly low disease activity and remission, on CVD risk in patients with RA. METHODS: Data from the Nijmegen early RA inception cohort were used. The primary outcome was first CVD events within the first 10 years of follow-up. Cut points of the DAS28 for remission (<2.6) and low (≤3.2), moderate (3.2-5.1) and high (>5.1) disease activity were used. The effect of disease activity on CVD risk was analysed using Cox-proportional hazards regression with DAS28 as a time-dependent covariate and also conventionally with time-averaged DAS28 as the primary dependent variable. RESULTS: Low DAS28 (≤3.2) was significantly associated with a reduced risk of CVD (HR 0.65, 95% CI 0.43 to 0.99) compared with DAS28 >3.2, both when included as a time-dependent covariate and as time-averaged DAS28 ≤3.2 (HR 0.52, 95% CI 0.33 to 0.81). Remission had a modest, non-significant protective effect against CVD (HR 0.67, 95% CI 0.43 to 1.07). CONCLUSION: Results of this study suggest that low disease activity is sufficient to achieve a protective effect against CVD in RA. Apparently, remission defined as DAS28 <2.6 has no additional protective effect against CVD compared with low disease activity. Our results strengthen the use of tight control strategies in daily clinical practice to achieve low stable disease activity or remission in patients with RA as soon as possible.
28405825 Use of bisphosphonate might be important to improve bone mineral density in patients with 2017 Jun Although patients with rheumatoid arthritis (RA) are prone to osteoporosis, tight control of disease activity might have a positive effect on bone metabolism. We aimed to determine whether bisphosphonate use is still important to improve bone mineral density (BMD) in RA patients whose disease activity was tightly controlled and the dose of glucocorticoid was reduced. This study was a sub-analysis of the 10-year prospective cohort TOtal Management Of Risk factors in Rheumatoid arthritis patients to lOWer morbidity and mortality: the TOMORROW which started from 2010. We compared BMD between 192 patients with RA and age- and sex-matched volunteers between 2010 and 2013 using dual-energy X-ray absorptiometry (DXA) in whole body mode. We then determined ratios of changes in BMD (%ΔBMD) to assess factors influencing increases in BMD among the patients using multivariate logistic regression analysis. The BMD was significantly lower in the patients than in the controls at all sites surveyed during 2010 and 2013. The %ΔBMD of the total spine was significantly higher among the patients treated with, than without bisphosphonate (6.2 vs. 1.8%, P = 0.0001). Multivariate logistic regression analysis revealed that use of bisphosphonate was a significant factor contributing to BMD increase (odds ratio 2.13; 95% confidence interval, 1.03-4.38, P = 0.041). Meanwhile, use of biologic agents, reducing glucocorticoid dose, and control of disease activity were not significant factors for gain of BMD. The BMD was lower among patients with RA than non-RA controls. Use of bisphosphonate significantly increased the BMD of the spine in patients over a period of 3 years and was important for maintaining the BMD among patients with RA under the control of inflammation and disease activity.
28606961 Long-term outcomes after disease activity-guided dose reduction of TNF inhibition in rheum 2017 Oct OBJECTIVE: Tumour necrosis factor inhibitors (TNFi) are effective in rheumatoid arthritis (RA), but disadvantages include adverse events (AEs) and high costs. This can be improved by disease activity-guided dose reduction (DR). We aimed to assess long-term outcomes of TNFi DR in RA by using 3-year data from the DRESS study (Dose REduction Strategy of Subcutaneous TNF inhibitors study). METHODS: In the intervention phase (month 0-18) of the DRESS study (Dutch trial register, NTR 3216), patients were randomised to DR or usual care (UC). In the extension phase (month 18-36), treatment strategies in both groups converged to continuation of protocolised tight control and allowed dose optimisation. Intention-to-treat analyses were done on flare, disease activity (28 joint count-based disease activity score with C reactive protein (DAS28-CRP)), functioning (health assessment questionnaire-disability index (HAQ-DI)), quality of life (Euroqol 5 dimensions 5 levels questionnaire (EQ5D-5L)), medication use, radiographic progression (Sharp van der Heijde score (SvdH)) and AE. RESULTS: 172/180 patients included in the DRESS study were included in the extension phase. Cumulative incidences of major flare were 10% and 12% (-2%, 95% CI -8 to 15) in DR and UC groups in the extension phase, and 17% and 14% (3%, 95% CI -9 to 13) from 0 to 36 months. Cumulative incidences of short-lived flares were 43% (33 to 52%)%) and 35% (23 to 49%)%) in DR and UC groups in the extension phase, and 83% (75 to 90%)%) and 44% (31 to 58%)%) from 0 to 36 months. Mean DAS28-CRP, HAQ-DI, EQ5D-5L and SvdH remained stable and not significantly different between groups. TNFi use remained low in the DR group and decreased in the UC group. Cumulative incidences of AE were not significantly different between groups. CONCLUSIONS: Safety and efficacy of disease activity guided TNFi DR in RA are maintained up to 3 years, with a large reduction in TNFi use, but no other benefits. Implementation of DR would vastly improve the cost-effective use of TNFi.
28598783 Anti-homocitrullinated protein antibody isotype usage in rheumatoid arthritis and their un 2017 Nov OBJECTIVES: The majority of rheumatoid arthritis (RA) patients express anti-citrullinated protein antibodies (ACPA). Unaffected first-degree relatives of RA patients (FDR) also express ACPA, commonly of the IgA isotype. IgG anti-homocitrullinated/carbamylated protein antibodies (AHCPA) have been detected in both RA and FDR. It is unknown whether other isotypes are expressed. We aim to investigate the AHCPA isotype profile in unaffected FDR of RA patients. METHODS: The enrolled subjects were examined by a rheumatologist. FDR and healthy controls (HC) were excluded if they had swollen joints. Serum AHCPA targeting homocitrullinated fibrinogen was determined using enzyme linked immunoabsorbant assay (ELISA). FDR were genotyped for HLA-DR4 alleles encoding the shared epitope (SE). RESULTS: 125 RA (35 probands), 61 FDR and 40 HC were included. 20% of FDR expressed IgG AHCPA, compared to 30% in RA patients and 5% in HC (p=0.0010 for RA vs. HC). Levels of IgG AHCPA in FDR were similar to RA. FDR rarely expressed IgM (8%) and did not express IgA AHCPA. 20% of RA and 13% of HC subjects expressed IgM, but very few expressed IgA AHCPA (<7% in both groups). AHCPA expression in FDR was not significantly associated with joint symptoms, smoking or SE. CONCLUSIONS: IgG AHCPA is the most commonly expressed isotype in RA and FDR. The significance of IgG AHCPA in FDR is unclear as it was not associated with joint symptoms or other risk factors for RA. Longitudinal studies are needed to determine whether AHCPA is meaningful in populations at risk for RA.
27932278 Patient-perceived flares in rheumatoid arthritis: A sub-analysis of the STRASS treatment t 2017 Oct OBJECTIVES: Patient's and physician's perspective can differ in rheumatoid arthritis (RA). The aim was to define the concept of patient-reported flares. METHODS: Post-hoc analysis of a randomized controlled trial of a step-down strategy in RA patients treated with anti-TNF, in DAS28-remission for ≥6 months, randomized to either "spacing" or "maintaining" anti-TNF. The occurrence of patient-reported flares (PRF) was evaluated every 3 months for 18 months by: "Over the last 3 months, did you experience symptoms suggestive of disease exacerbation?". Visits with and without PRF were compared, using a linear mixed effects model, in terms of symptoms, disability based on the Health Assessment Questionnaire, quality of life based on Short Form 36 Health Survey and DAS28-based relapses (DBR), defined as an increase of DAS28>0.6 and an absolute value of DAS28>2.6. The agreement between PRF and DBR was measured by the kappa coefficient on repeated data. RESULTS: In all, 137 patients were analyzed: mean age 55±11 years, females 78%, mean RA duration 9.5±8.0 years. Over the 18 months, PRF concerned 27.2% of the 940 available visits. DBR and PRF were observed in 24% and 16% of 940 visits for 137 patients respectively. All the items were associated with PRF with standardized effect size between -0.58 (SF36 PCS) and 0.87 (DAS28). The agreement between PRF and DBR was moderate (κ=0.44). CONCLUSION: The concept of flare refers to more than just RA disease activity.
29273497 Methotrexate in patients with rheumatoid arthritis in Spain: Subanalysis of the AR Excelle 2019 Nov OBJECTIVE: The AR Excellence project evaluates clinical monitoring in patients with rheumatoid arthritis (RA) in Spain. The aim of the study was to analyze the use of methotrexate (MTX) in the AR Excellence cohort and to compare it with current recommendations. PATIENTS AND METHODS: We collected data from RA patients who initiated treatment with MTX. They included demographics, dose and routes of administration, switching among them, highest dose in each route, combinations with other disease-modifying antirheumatic drugs (DMARDs), time to combination with another DMARD (either conventional or biological) and adverse events. RESULTS: Six hundred twenty-five patients with RA (mean age 55 years; 70.6% women) were included, with an average disease duration of 21 months. Ninety percent of the patients initiated treatment with MTX. Therapy was begun with a mean dose of 11mg per week; this initial dose was increased in 58% of the individuals. The average time to reach the full dose of MTX (20mg a week) was 6,67 months. Time to combination of MTX with another DMARD, either synthetic or biological, was 3 months. In all, 67.4% of the patients received oral MTX and the route was subcutaneous in 18.6%. In 12% of the cases, there was a change in the route of administration after a period of 6 months. In 544 patients, folate supplements were added to MTX; MTX-related adverse events were detected in 17.3% of the patients. CONCLUSION: MTX is currently the pivotal treatment in RA. The subanalysis of the AR Excellence project demonstrates that MTX escalation to its full doses is not done with adequate speed. The subcutaneous route is used in a small proportion of patients.
25196086 Hydrogen sulfide acts as a pro-inflammatory mediator in rheumatic disease. 2017 Feb OBJECTIVE: Hydrogen sulfide (H(2) S) is a gaseous mediator produced in the body. In experimental models, endogenously produced H(2) S has been shown to have pro-inflammatory effects. The aim of this study was to investigate whether H(2) S is present in three common rheumatic diseases, rheumatoid arthritis (RA), gout and osteoarthritis (OA) and to determine if H(2) S levels correlate with disease activity. METHODS: Patients with RA, gout, OA, and healthy controls (n = 30 each) were recruited. Plasma and where possible, synovial fluid (SF), were obtained. Levels of H(2) S and interleukin-6 (IL-6) (a known inflammatory marker as a positive control) were determined and assessed for their relationship with disease activity. RESULTS: SF-H(2) S levels were significantly elevated in both RA and gout when compared to respective plasma levels. Plasma levels of H(2) S were not different from those in healthy controls in patients with either RA or gout. In OA, plasma levels of H(2) S were significantly elevated compared to healthy controls. In RA, SF-H(2) S levels correlated with Disease Activity Score (DAS)-28 and tender joint count. CONCLUSION: H(2) S is present in the joint and acts as a pro-inflammatory mediator in rheumatic diseases. H(2) S may be a novel therapeutic target for these conditions.