Progression Of Structural Damage Research Articles

Current Unmet Needs in Spondyloarthritis.

There was a substantial progress in the field of spondyloarthritis (SpA) in terms of understanding disease mechanisms, early diagnosis, and improved treatment. Nonetheless, several unresolved questions and unmet needs do remain. Although the diagnostic delay in axial SpA is decreasing, it remains one of the longest in rheumatology. Application of referral strategies, as well as correct application and interpretation of imaging finding in the clinical context, is the main key to early diagnosis of axial SpA. Tumor necrosis factor (TNF) alpha and interleukin (IL)-17 represent currently two major treatment targets in SpA, while other promising targets such as IL-23 or IL-6 failed in clinical trials. There is an unmet need for strategy trials to optimize and to individualize treatment in SpA. The role of Janus kinases and their blockade in SpA is still to be explored. TNF blockade showed efficacy in peripheral SpA, and other targets (IL-17 and IL-23) should be investigated in clinical trials. Early, effective, and long-term suppression of inflammation is currently the best method to prevent structural damage progression in the spine in axial SpA, while specific effects of IL-17 blockade and of nonsteroidal anti-inflammatory drugs on new bone formation are still being investigated. This review summarizes the recent advances in diagnosis and treatment of SpA and discusses the current unmet needs in the field.

Determining MRI Inflammation Targets When Considering a Rheumatoid Arthritis Treat-to-Target Strategy: Results of a Randomized, Placebo-Controlled Trial.

IntroductionMagnetic resonance imaging (MRI) is increasingly used in patients with rheumatoid arthritis (RA) to determine residual inflammation after treatment and as a predictor of structural damage progression. Establishing an optimal threshold of inflammatory activity that predicts lower risk of structural damage progression may inform treatment decisions. This post hoc analysis investigated whether patients with RA at low risk of structural damage progression can be identified based on MRI inflammation thresholds.MethodsHand and wrist MRI was performed at baseline, and at months 6 and 12 in a phase 3b, randomized, active-controlled, double-blind trial of abatacept in early RA (AVERT). Pathologies were scored using the OMERACT RA MRI Score. Data were stratified into two risk subgroups (less and more severe inflammation) for structural damage progression (erosion change > 0.5) based on baseline inflammation. In this post hoc analysis, log odds ratios of probability of progression {adjusted for baseline Disease Activity Score in 28 joints [C-reactive protein; DAS28 (CRP)]} were compared between subgroups to test the performance of inflammation thresholds.ResultsThere were 351 randomized and treated patients with baseline MRIs, of whom 276 (78.6%) and 235 (67.0%) had MRIs available at months 6 and 12, respectively. The DAS28 (CRP)-adjusted probabilities of progression from baseline to month 12 based on scores at baseline, and from months 6 to 12 based on month 6 scores, were significantly lower among patients with less inflammation (P < 0.0001–0.0459), independent of clinical disease activity. Predefined thresholds of synovitis ≤ 3 (total score 21), osteitis ≤ 3 (total score 69) and total inflammation score (osteitis double-weighted) ≤ 9 were associated with a lower likelihood of structural damage progression in unadjusted analyses.ConclusionLevels of MRI-determined inflammatory activity below defined thresholds were independently associated with a lower risk of structural damage progression in early RA, providing a potential trial endpoint for levels of inflammation not associated with progression.Trial RegistrationClinicalTrials.gov identifier, NCT01142726.FundingBristol-Myers Squibb.Electronic Supplementary MaterialThe online version of this article (10.1007/s12325-019-01020-6) contains supplementary material, which is available to authorized users.

Subclinical synovitis measured by ultrasound in rheumatoid arthritis patients with clinical remission induced by synthetic and biological modifying disease drugs

BackgroundRheumatoid arthritis (RA) patients with disease in clinical remission might show subclinical synovitis, which can be related to the progress of structural joint damage. ObjectiveTo determine and compare the degree of synovial inflammation by ultrasound (US) in patients with RA in clinical remission, treated with DMARD or combination therapy with DMARD and anti-TNF. MethodsHospital-based cross-sectional study of 58 patients with RA in sustained remission for at least 6 months by DAS28 <2.6, who attended the Rheumatology Service at the Hospital Universitario de Caracas. Patients underwent clinical, functional, and laboratory assessments. Ultrasound was performed in hands measuring synovial effusion, synovial hypertrophy and power Doppler signal; using a semiquantitative 4-point scale of 0=none to 3=severe. Chi-square and t-test were used to compare the clinical, functional, laboratory and US assessments between the DMARD (N=37) and combination therapy with DMARD and anti-TNF (N=21) groups. A p-value <0.05 was considered statistically significant. ResultsOut of 58 patients, 25.9% had remission by US and 74.1% had synovial effusion or hypertrophy or positive power Doppler signal. Non-significant differences in US synovitis between the two groups were found. ConclusionsPersistent US activity was evident in a high percentage of rheumatoid arthritis patients in clinical remission by DAS28. No differences in subclinical synovitis measured by US were found between patients with DMARD and anti-TNF-induced clinical remission.

Uniaxial tensile failure of multi-core asymmetric sandwich composite structures with bonded repair

Sandwich structures with composite facesheets and multi-core cellularic materials are being used for load-bearing and protection applications against shocks and medium impact loading. These structures are prone to various surface and sub-surface damage during their operational service life. This experimental work explores the repair technology for these hybrid composite structures using adhesively bonded joints. The post repair performance depends upon the adhesive selection, joint design and repair strategy. This paper aims at experimental evaluation of the performance of thermosetting adhesives for graded honeycomb core sandwich composite structures when subjected to quasi-static tensile loading. Failure modes and progression of damage in these hybrid sandwich structures consisting of honeycomb cores and long fiber reinforced polymer matrix composites is analyzed using strain gauge and acoustic emission measurements.

Glucocorticoid Therapy of Multiple Sclerosis Patients Induces Anti-inflammatory Polarization and Increased Chemotaxis of Monocytes

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by the infiltration of mononuclear cells into the CNS and a subsequent inflammation of the brain. Monocytes are implicated in disease pathogenesis not only in their function as potential antigen-presenting cells involved in the local reactivation of encephalitogenic T cells but also by independent effector functions contributing to structural damage and disease progression. However, monocytes also have beneficial effects as they can exert anti-inflammatory activity and promote tissue repair. Glucocorticoids (GCs) are widely used to treat acute relapses in MS patients. They act on a variety of cell types but their exact mechanisms of action including their modulation of monocyte function are not fully understood. Here we investigated effects of the therapeutically relevant GC methylprednisolone (MP) on monocytes from healthy individuals and MS patients in vitro and in vivo. The monocyte composition in the blood was different in MS patients compared to healthy individuals, but it was only marginally affected by MP treatment. In contrast, application of MP caused a marked shift toward an anti-inflammatory monocyte phenotype in vitro and in vivo as revealed by an altered gene expression profile. Chemotaxis of monocytes toward CCL2, CCL5, and CX3CL1 was increased in MS patients compared to healthy individuals and further enhanced by MP pulse therapy. Both of these migration-promoting effects were more pronounced in MS patients with an acute relapse than in those with a progressive disease. Interestingly, the pro-migratory GC effect was independent of chemokine receptor levels as exemplified by results obtained for CCR2. Collectively, our findings suggest that GCs polarize monocytes toward an anti-inflammatory phenotype and enhance their migration into the inflamed CNS, endowing them with the capacity to suppress the pathogenic immune response.

Conventional radiography of the hands and wrists in rheumatoid arthritis. What a rheumatologist should know and how to interpret the radiological findings.

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, leading to joint damage and bone destruction. Conventional radiography (CR) of the hands and wrists has been, for many years, the primary imaging modality used to diagnose and monitor RA. On the other hand, many investigators in clinical trials and observational studies used CR of the hands and wrists to demonstrate drug effectiveness and structural damage progression. The purpose of this review is to discuss the evaluation and interpretation of the hands and wrists by CR in RA patients and the radiographic changes occurring in a specific joint. Thus, the literature was reviewed until January 2019 for studies regarding RA radiological evaluation of the hands and wrists, as well as radiological progression using CR. The assessment of joint pathology in RA patients should begin with CR which is the best imaging modality to evaluate any subtle changes occurring at the bone level. Once high-quality radiographs are obtained in appropriate views/projections, then an accurate evaluation can often be made without any further imaging studies. Therefore, CR is a valuable tool for RA screening. It is an easy-to-perform technique and gives important information assisting in differentiating between RA from other arthritides. In contrary CR does not provide good information when early RA changes start to appear, such as synovial inflammation or other soft-tissue structural changes. Nevertheless, it still remains the most commonly used imaging tool in rheumatology and has a number of advantages: it is easily available in most rheumatologists and readily accessible in most patients. It is inexpensive and relatively safe. It provides immediate information and can be interpreted easily by the requested rheumatologist. Finally, the data are reproducible and can be used for serial evaluation and follow-up.

Effectiveness of seismic strengthening to repeated earthquakes in historic urban contexts

PurposeThe purpose of this paper is to discuss the dynamics of the evolution of damage to the residential buildings within the city walls of Norcia during the six-month seismic swarm that hit Central Italy in the period 24th August 2016 to end of January 2019. This is accomplished by comparing the damage recorded by the Italian Civil Protection usability form (AEDES form) during this period after each event.Design/methodology/approachFirst, these outputs are compared with a qualitative assessment conducted by means of omnidirectional camera (ODC) imagery collected on site by the authors, to explore the ability of this technology to support post-earthquake damage assessment. The damage level attributed with these two techniques is then further compared with the output of the analytical vulnerability assessment method FaMIVE, which allows to correlate damage to vulnerability. Specifically, the objective is to investigate the efficacy and performance of historic and recent strengthening interventions.FindingsResults show that there is a good correspondence between AeDES and ODC assessments for low to medium damage grades (DG). Discrepancies in higher DGs are discussed in light of the different levels of information that can be recorded by using the two tools. The efficacy of strengthening is also well captured by the FaMIVE method. The procedure estimates a decrease of almost 40, 25 and 20 per cent of the total number of buildings failing out-of-plane, respectively, for the three seismic events considered, when restraining elements are in action.Research limitations/implicationsThe analysis conducted in this work make use of deterministic values of Norcia’s masonry fabric characteristics that have been found in literature, thus implying that neither the probabilistic aspects nor the related uncertainties have been properly investigated and addressed. However, this limitation is to be considered within the more general context of the legislation for the preservation of historic buildings which limits substantially any type of semi-destructive tests, hence limiting the reliability of the values available in literature. This in turn affects the decisions informing the design and implementation of strengthening interventions which can be confidently considered reliable and effective.Originality/valueThe paper addresses for the first time a systematic investigation of damage progression in historic masonry structures, part of urban aggregates in heritage cities. The current urban fabric is discussed in view of historic building codes as the basis for determining the present seismic vulnerability of the historic city centre of Norcia. The study provides new data sets for the city of Norcia and develops a statistical correlation between cumulative damage and analytical vulnerability functions for heritage buildings exposed to a swarm of earthquakes. The analytical assessment of the effect of historic strengthening is totally novel.

Low rates of radiographic progression of structural joint damage over 2 years of baricitinib treatment in patients with rheumatoid arthritis

ObjectivesTo evaluate radiographic progression of structural joint damage over 2 years in patients with rheumatoid arthritis from baricitinib clinical trials who were disease-modifying antirheumatic drug (DMARD)–naïve or had an inadequate...

Serum miR-21 expression correlates with radiographic progression but also low bone mineral density in patients with ankylosing spondylitis: a cross-sectional study.

Increased expressions of miR-21 have been detected in ankylosing spondylitis (AS) patients. The current study was performed to examine the serum miR-21 expression with radiographic severity in AS patients, which was determined based on the modified New York (NY) criteria for sacroiliac joints assessment and modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) system for spine involvement. Bone mineral density at lumbar 1–4 and femoral neck were examined by dual-energy absorptiometry (DXA). Serum miR-21 expressions were determined by quantitative real-time PCR, and receiver operating characteristic curve analysis was performed to identify the diagnostic value of miR-21 expression levels regarding the NY criteria. Elevated levels of serum miR-21 expressions were detected in AS patients compared with healthy controls. AS patients with modified NY grade 4 showed significantly higher miR-21 expression than grade 3 and grade 2. AS patients with spinal syndesmophytes had significantly higher serum miR-21 expressions than non-syndesmophyte patients. Increased miR-21 expressions were significantly related to the disease radiographic severity. In addition, serum miR-21 expressions were negatively associated with lumbar 1–4 and femoral neck bone mineral density. In summary, serum miR-21 expressions were related to structural damage and radiological progression in AS, indicating that miR-21 may act as a switch between inflammation and new bone information and regulate different signal ways between lesioned enthesis and trabecular bone.

Heberden’s nodes and their association with mri-based knee osteoarthritis: exploratory study from the foundation for the national institutes of health study

Purpose: To explore whether Heberden’s nodes (HNs) could predict MRI-based knee osteoarthritis (OA)-related osseous structural progression. Methods: This is an IRB approved HIPAA compliant study. 575 subjects from Foundation for the National Institute of Health (FNIH) project underwent clinical examination with evaluation of HNs at baseline and knee MRI at baseline and 24-month. The MRI was read according to the semi-quantitative MRI Osteoarthritis Knee Score (MOAKS) and quantitative periarticular bone morphology measures. Adjusted linear/logistic regression models were implemented to assess the association between the presence of HN (HN+) at baseline examination and worsening of MRI-defined osseous structural damages. Results: Comparing subjects with HN (HN+, n=395) and without HN (HN-, N=188), more periarticular bone area expansion in knee joint (adjusted Beta-coefficient (aβCE) (95%CI): 0.33 (0.05 - 0.61)) especially in medial femur (aβCE: 0.40 (0.05 - 0.76)) and lateral femur (aβCE: 0.92 (0.46 - 1.38)), femoral notch (aβCE: 0.31 (0.02 - 0.61)) and lateral trochlea (aβCE: 0.36 (0.08 - 0.64)) were seen in HN+ group over 24-months. However, there was less osteophyte worsening in HN+ subjects in the whole knee joint (adjusted odds ratio (aOR) (95%CI): 0.63 (0.40 - 1.02)), particularly in femur region (aOR: 0.54 (0.31 - 0.95)) compared to HN- group. Conclusions: Presence of HN was associated with the increased MRI-based periarticular bone area expansion while less osteophytes worsening over 24-month in knee joint, especially in the femoral region. HNs have been known as one of the main hallmarks of generalized OA; these preliminary and exploratory findings may suggest distinct pathophysiology for OA-related structural damage progression patterns in subjects with generalized OA. These initial results can initiate more focused investigations to further characterize this particular OA subtype, and tailor specific treatments for these patients’ in the future clinical trials.

Imaging in rheumatoid arthritis: the role of magnetic resonance imaging and computed tomography.

In suspected and diagnosed rheumatoid arthritis (RA), magnetic resonance imaging (MRI) allows detection of all relevant pathologies, such as synovitis, tenosynovitis, bone marrow edema (osteitis), bone erosion and cartilage damage. MRI is more sensitive than clinical examination for monitoring disease activity (i.e., inflammation) and more sensitive than conventional radiography and ultrasonography for monitoring joint destruction. In suspected RA, MRI bone marrow edema predicts development of RA, and in early RA patients, it predicts subsequent structural damage progression. CT is the standard reference imaging modality for visualizing bone damage, including bone erosions in RA, but lacks sensitivity for soft-tissue changes, including synovitis and tenosynovitis. CT has a minimal role in RA clinical trials and practice, except in selected patients where MRI is contraindicated or not available or if crystal arthritis such as gout or pseudo-gout is suspected. MRI has documented utility in diagnosis, monitoring and prognostication of patients with RA and is increasingly used for these purposes in clinical practice and particularly clinical trials.

Progression of Structural Damage in the Sacroiliac Joints in Patients With Early Axial Spondyloarthritis During Long-Term Anti-Tumor Necrosis Factor Treatment: Six-Year Results of Continuous Treatment With Etanercept.

To evaluate radiographic progression in the sacroiliac (SI) joints and to identify its predictors during long-term treatment (up to 6 years) with the tumor necrosis factor (TNF) inhibitor etanercept in patients with early axial spondyloarthritis (SpA). Patients with early axial SpA who were treated with etanercept for up to 6 years in the Etanercept versus Sulfasalazine in Early Axial Spondyloarthritis (ESTHER) trial were selected based on the availability of radiographs of the SI joints. Two readers who were blinded with regard to clinical data scored the radiographs according to the modified New York criteria (range 0-4 per SI joint). A sacroiliitis sum score (total range 0-8) was calculated as the mean of the scores of the 2 readers. Active and chronic inflammatory changes in the SI joints on magnetic resonance imaging (MRI) performed at baseline, year 2, and year 4 were assessed according to the Berlin MRI scoring system. Of the 76 patients originally included in the study, 42 had radiographs of the SI joints available at baseline and at least 1 follow-up time point (year 2, 4, or 6). The mean ± SD change in the sacroiliitis sum score was 0.13 ± 0.73, -0.27 ± 0.76, and -0.09 ± 0.68, in the time intervals baseline to year 2, year 2 to year 4, and year 4 to year 6, respectively. In the longitudinal mixed model analysis, elevated C-reactive protein level (β = 0.58 [95% confidence interval 0.24, 0.91]) and MRI SI joint osteitis score (β = 0.06 [95% confidence interval 0.03, 0.10]) were independently associated with progression of the sacroiliitis sum score. Our findings indicate that long-term anti-TNF therapy decelerates the progression of structural damage in the SI joints. Elevated CRP level and presence of osteitis on MRI were independently associated with radiographic sacroiliitis progression.

Radiographic Progression Inhibition with Intravenous Golimumab in Psoriatic Arthritis: Week 24 Results of a Phase III, Randomized, Double-blind, Placebo-controlled Trial

Evaluate effects of intravenous (IV) golimumab (GOL) on radiographic progression in psoriatic arthritis (PsA). This phase III, randomized, double-blind, placebo-controlled trial (GO-VIBRANT) randomized patients with active PsA to receive IV placebo (n = 239) or IV GOL 2 mg/kg (n = 241) at weeks 0, 4, 12, and 20. Radiographic progression (controlled secondary endpoint) was evaluated as change from baseline at Week 24 in PsA-modified total Sharp/van der Heijde scores (SvdH). The proportions of patients with a change from baseline at Week 24 in the total PsA-modified SvdH exceeding the smallest detectable change (SDC) or > 0 or 0.5 also were determined. Overall, 474 patients (237/arm) contributed radiographic data. Results obtained from the 2 blinded, independent radiographic readers demonstrated good agreement (total score intraclass correlation coefficients: baseline = 0.93, Week 24 = 0.92, Week 24 change score = 0.73). GOL demonstrated significant inhibition of radiographic progression relative to placebo from baseline to Week 24 (mean changes in PsA-modified total SvdH: -0.36 vs 1.95; treatment difference: -2.32; p < 0.001). At Week 24, smaller proportions of GOL- versus placebo-treated patients demonstrated an increase in the total PsA-modified SvdH score exceeding the SDC (8.0% vs 27.0%, respectively; difference: -19.0%; p < 0.001), > 0 (28.3% vs 57.0%, respectively; difference: -28.7%; p < 0.001), or > 0.5 (18.6% vs 41.8%, respectively; difference: -23.2%; p < 0.001). Results were consistent for erosion and joint space narrowing scores, in hands and feet, and in patients with/without baseline concomitant methotrexate use. Prevention of radiographic progression by GOL was independent of clinical response. IV GOL is significantly better than placebo in inhibiting radiographic progression of structural damage in active PsA. [Clinical trial registration number (www.ClinicalTrials.gov): NCT02181673].

Space-time Gaussian models for evaluating corrosion-induced damages in reinforcing bars

Chloride-induced steel reinforcing bars corrosion is a problem of worldwide importance because, in addition to massive industrialization, a majority of human population inhabit marine atmosphere zones where salinity is the main source of built infrastructure deterioration. Reinforced concrete structures vulnerable to chloride-induced corrosion potentially experience two stages of damage, namely non-structural and structural. Till date, with regard to non-uniform corrosion, there is very limited information regarding the significant role played by the non-structural stage of damage in influencing the progression of structural damage. The present work examines the process of non-uniform chloride ingress into concrete due to the existence of the steel bars and its influence on the spatial and temporal variations in the depth of corrosion penetration. Mathematical models in the form of Gaussian functions are proposed to represent space-time variation in corrosion initiation, spatial spread of corrosion penetration depth and corroded bar morphologies, and are compared with literature data. A numerical inverse analysis procedure is introduced to predict space-time evolution of non-structural damage from experimentally observed spatial spread of structural damage. Further, applicability of superposition approach for the evaluation of corrosion-induced stresses around the steel–concrete interface of a corner reinforcing bar is explored and shown to introduce spatial and temporal errors while evaluating structural damages.

Calprotectin strongly and independently predicts relapse in rheumatoid arthritis and polyarticular psoriatic arthritis patients treated with tumor necrosis factor inhibitors: a 1-year prospective cohort study

BackgroundCalprotectin is a biomarker of disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and predicts relapse in juvenile idiopathic arthritis. Higher drug trough serum levels are associated with a good response in patients treated with tumor necrosis factor inhibitors (TNFi). Power Doppler ultrasound synovitis is predictive of relapse and structural damage progression in patients in clinical remission. The purpose of this study was to analyze the accuracy of serum calprotectin levels, drug trough serum levels (TSL), and power Doppler (PD) activity as predictors of relapse in RA and PsA patients in remission or with low disease activity receiving TNFi.MethodsThis was a longitudinal, prospective, 1-year single-center study of 103 patients (47 RA, 56 PsA) receiving TNFi in remission or with low disease activity (28-joint Disease Activity Score (DAS28) ≤ 3.2). The predictive value of serum calprotectin, TNFi TSL, and PD were assessed using receiver operating characteristic (ROC) analyses. To illustrate the predictive performance of calprotectin, TNFi TSL, and PD score, Kaplan-Meier curves were constructed from baseline to relapse. Associations between baseline factors and relapse were determined using Cox regression models. Multivariate models were constructed to analyze the effect of covariates and to fully adjust the association between calprotectin, TNFi TSL, and PD score with relapse. A generalized estimating equation model with an identity link for longitudinal continuous outcomes was used to assess the effect of covariates on TNFi TSL.ResultsNinety-five patients completed 1 year of follow-up, of whom 12 experienced a relapse. At baseline, relapsers had higher calprotectin levels, lower TNFi TSL, and higher PD activity than nonrelapsers. ROC analysis showed calprotectin fully predicted relapse (area under the curve (AUC) = 1.00). TNFi TSL and PD had an AUC of 0.790 (95% confidence interval (CI) 0.691–0.889) and 0.877 (95% CI 0.772–0.981), respectively. Survival analyses and log rank tests showed significant differences between groups according to calprotectin serum levels (p < 0.001), TNFi TSL (p = 0.004), and PD score (p < 0.001). Univariate Cox regression models showed that time-to-remission/low disease activity (hazard ratio (HR) = 1.17, p < 0.001), calprotectin levels (HR = 2.38, p < 0.001), TNFi TSL (HR = 0.47, p = 0.018), and PD score (HR = 1.31, p < 0.001) were significantly associated with disease relapse. In the multivariate analysis, only baseline calprotectin levels independently predicted disease relapse (HR = 2.41, p = 0.002). The generalized estimating equation analysis showed that only disease activity by DAS28-erythrocyte sedimentation rate (ESR) was significantly associated with longitudinal changes in TNFi TSL (regression coefficient 0.26 (0.0676 to 0.0036), p = 0.001).ConclusionTime-to-remission/low disease activity, calprotectin serum levels, TNFi TSL, and PD score were significantly associated with disease relapse. However, only baseline calprotectin serum levels independently predicted disease relapse in RA and PsA patients under TNFi therapy.

Abatacept in combination with methotrexate in Japanese biologic-naive patients with active rheumatoid arthritis: a randomised placebo-controlled phase IV study

ObjectivesTo evaluate efficacy and safety of abatacept+methotrexate (MTX) in biologic-naive, anticitrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) and early erosion versus placebo+MTX.MethodsIn this phase IV, multicentre,...

Role of reproductive and menopausal factors in functional and structural progression of rheumatoid arthritis: results from the SCQM cohort.

To study the relationship between female reproductive and menopausal factors on functional and structural joint damage progression in women with RA. This is an observational cohort study of RA patients enrolled in the Swiss Clinical Quality Management Program for Rheumatoid Arthritis. Information about female hormonal factors, such as pregnancies, menopause and hormonal therapy, were retrospectively retrieved using a specific questionnaire. The primary outcome was functional disability progression (HAQ) and the secondary outcome radiographic joint damage progression. We compared the functional progression between pre- and post-menopausal women using a multilevel regression model for longitudinal data, adjusting for potential confounders, such as baseline age, years of education, disease duration, seropositivity, DAS28 and treatment. A total of 1667 women were analysed, of whom 1025 (61%) were post-menopausal. Participants had a median of 6 HAQ assessments (interquartile range 3-10) during 5.1 (interquartile range 2.2-9.8) years of follow-up. At baseline, post-menopausal women had higher HAQ and erosion scores than pre-menopausal women. The evolution of HAQ scores over time differed between pre- and post-menopausal women (P < 0.001), with a less favourable evolution in post-menopausal women, particularly with earlier age at menopause. Erosion progression did not differ between pre- and post-menopausal women. In women with RA, functional disability progression differed between pre- and post-menopausal women. The more favourable evolution of function in pre-menopausal women was not explained by disease duration, age or radiographic damage.

Clinical and radiologic analysis of on-demand use of etanercept for disease flares in patients with rheumatoid arthritis for 2 years: The RESUME study: A case-control study.

To reduce costs of biological disease-modifying antirheumatic drugs (bDMARDs), we evaluated the efficacy of repeated etanercept (ETN) discontinuation and restarting in rheumatoid arthritis (RA) patients in a case–control study.Thirty-one bDMARD-naive RA patients with moderate to high disease activity received ETN until low disease activity (LDA) was achieved, after which ETN was discontinued. Upon flaring, ETN was readministered with observation every 2 months for 2 years, and radiographically evaluated in comparison with a historical control group treated continuously with ETN. Statistical methods including Fisher exact test, analysis of variance (ANOVA), Kruskal–Wallis test, multiple regression analysis, and Student t test were conducted as appropriate.Thirteen patients with inadequate response to ETN were withdrawn from the study, and 5 had no flare-up after ETN discontinuation. In the remaining 13 patients, ETN was used on-demand to maintain LDA. Multivariate analysis revealed that MTX was significantly correlated with ETN. All 13 patients achieved LDA at final follow-up. Although joint damage progressed in patients using ETN on-demand, structural damage progression in the on-demand group was not significantly different from that in controls.On-demand use of ETN for flaring reduced disease activity but not structural damage in 50% of patients (though not significantly). However, inhibition of joint damage was achieved in 50% of patients after 2 years, supporting on-demand use of ETN as a treatment option for patients with RA who cannot afford bDMARD or targeted synthetic DMARD therapy.

Structural damage progression in patients with early rheumatoid arthritis treated with methotrexate, baricitinib, or baricitinib plus methotrexate based on clinical response in the phase 3 RA-BEGIN study

The objective of this study was to evaluate structural damage progression based on clinical response in rheumatoid arthritis patients with no or limited prior disease-modifying anti-rheumatic drug treatment receiving the Janus kinase (JAK)1/JAK2 inhibitor baricitinib 4 mg, methotrexate (MTX), or the combination. Data from the phase 3 RA-BEGIN study were analysed post hoc. Proportions of patients with structural damage progression (change from baseline greater than the smallest detectable change in modified total Sharp score) at week 52 were evaluated based on sustained Disease Activity Score for 28-joint count with serum high-sensitivity C-reactive protein (DAS28-hsCRP) ≤ 3.2 or Simplified Disease Activity Index (SDAI) score ≤ 11; no formal statistical comparisons between treatments were performed to test these proportions. Baseline factors associated with risk of structural damage progression, including Clinical Disease Activity Index (CDAI) score, were identified using multivariate analysis. Patients achieving versus not achieving sustained DAS28-hsCRP ≤ 3.2 or SDAI score ≤ 11 were less likely to experience structural damage progression at week 52. In patients achieving these responses, structural damage progression was less likely with baricitinib monotherapy or plus MTX than with MTX monotherapy. In patients not achieving these sustained clinical thresholds, structural damage progression was less likely with baricitinib plus MTX than with either monotherapy. Independent of treatment, baseline factors significantly associated with increased risk of structural damage progression included higher hsCRP and CDAI score, smoking, female sex, and lower body mass index. In conclusion, patients achieving versus not achieving sustained DAS28-hsCRP ≤ 3.2 or SDAI score ≤ 11 were less likely to show structural damage progression, irrespective of treatment.

Sarilumab: A Review in Moderate to Severe Rheumatoid Arthritis

Sarilumab (Kevzara®), a monoclonal antibody against the interleukin-6 (IL-6) receptor, is approved in various countries, including the USA, those of the EU, and Japan, as a subcutaneous treatment administered every 2weeks for moderately to severely active rheumatoid arthritis (RA) in adults who have responded inadequately to, or are intolerant of, one or more DMARDs. In placebo-controlled trials, sarilumab improved the signs and symptoms of RA, as well as physical function and health-related quality-of-life (HR-QOL), when administered in combination with conventional synthetic DMARD (csDMARD) therapy in patients with an inadequate response to methotrexate or an inadequate response to, or intolerance of, at least one tumour necrosis factor (TNF) inhibitor; benefits were sustained over ≤ 3years' therapy in an open-label extension. Sarilumab plus methotrexate inhibited the progression of structural damage in patients who had inadequately responded to methotrexate. As monotherapy in patients who were inappropriate for continued treatment with methotrexate, sarilumab was more effective than adalimumab in reducing the signs and symptoms of RA and improving physical function. The safety profile of sarilumab was consistent with the anticipated effects of IL-6 inhibition. In the minority of patients who tested positive for anti-drug antibodies (ADAs), ADAs did not impact efficacy or increase adverse reactions. Thus, sarilumab extends the available treatment options for adults with moderately to severely active RA who have responded inadequately to, or are intolerant of, at least one DMARD.