Machine-learning predicted and actual 2-year structural progression in the IMI-APPROACH cohort.

In the Innovative Medicine's Initiative Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) knee osteoarthritis (OA) study, machine learning models were trained to predict the probability of structural progression (s-score), predefined as >0.3 mm/year joint space width (JSW) decrease and used as inclusion criterion. The current objective was to evaluate predicted and observed structural progression over 2 years according to different radiographic and magnetic resonance imaging (MRI)-based structural parameters.

Clinical outcomes of biliary drainage of malignant biliary obstruction due to colorectal cancer metastases: A systematic review.

Background And Aims: Malignant biliary obstruction is an ominous complication of metastatic colorectal cancer (mCRC). Biliary drainage is frequently performed to relieve symptoms of jaundice or enable palliative systemic therapy, but effective drainage can be difficult to accomplish. The aim of this study is to summarize literature on clinical outcomes of biliary drainage in mCRC patients with malignant biliary obstruction.

A randomised, open-label trial to assess the optimal treatment strategy in early diffuse cutaneous systemic sclerosis: the UPSIDE study protocol.

Introduction: Systemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease associated with high morbidity and mortality, especially in diffuse cutaneous SSc (dcSSc). Currently, there are several treatments available in early dcSSc that aim to change the disease course, including immunosuppressive agents and autologous haematopoietic stem cell transplantation (HSCT). HSCT has been adopted in international guidelines and is offered in current clinical care.

Complex Machine-Learning Algorithms and Multivariable Logistic Regression on Par in the Prediction of Insufficient Clinical Response to Methotrexate in Rheumatoid Arthritis.

The goals of this study were to examine whether machine-learning algorithms outperform multivariable logistic regression in the prediction of insufficient response to methotrexate (MTX); secondly, to examine which features are essential for correct prediction; and finally, to investigate whether the best performing model specifically identifies insufficient responders to MTX (combination) therapy. The prediction of insufficient response (3-month Disease Activity Score 28-Erythrocyte-sedimentation rate (DAS28-ESR) > 3.2) was assessed using logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, and extreme gradient boosting (XGBoost).

EULAR definition of difficult-to-treat rheumatoid arthritis.

Background: Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis (RA) remain symptomatic. These patients can be considered to have 'difficult-to-treat RA'. However, uniform terminology and an appropriate definition are lacking.

Initiating tocilizumab, with or without methotrexate, compared with starting methotrexate with prednisone within step-up treatment strategies in early rheumatoid arthritis: an indirect comparison of effectiveness and safety of the U-Act-Early and CAMERA-II treat-to-target trials.

Objectives: Methotrexate (MTX), often combined with low moderately dosed prednisone, is still the cornerstone of initial treatment for early rheumatoid arthritis (RA). It is not known how this strategy compares with initial treatment with a biological. We therefore compared the effectiveness of tocilizumab (TCZ), or TCZ plus MTX (TCZ+MTX) with MTX plus 10 mg prednisone (MTX+pred), all initiated within a treat-to-target treatment strategy in early RA.

Series: Pragmatic trials and real world evidence: Paper 6. Outcome measures in the real world.

Results from pragmatic trials should reflect the comparative treatment effects encountered in patients in real-life clinical practice to guide treatment decisions. Therefore, pragmatic trials should focus on outcomes that are relevant to patients, clinical practice, and treatment choices. This sixth article in the series (see Box) discusses different types of outcomes and their suitability for pragmatic trials, design choices for measuring these outcomes, and their implications and challenges.

Differences between serum polar lipid profiles of male and female rheumatoid arthritis patients in response to glucocorticoid treatment.

Objective: As there are pharmacological differences between males and females, and glucocorticoid (GC) treatment is associated with increased cardiovascular mortality rate in rheumatoid arthritis (RA) patients, it is important to study serum polar lipid profiles of male and female patients in response to GC therapy. Gender differences may require an adjustment to the treatment strategy for a selection of patients.

Methods: Serum samples from 281 RA patients were analysed using a targeted lipidomics platform.

Determining the Lowest Optimally Effective Methotrexate Dose for Individual RA Patients Using Their Dose Response Relation in a Tight Control Treatment Approach.

Objective: To determine the optimal methotrexate dose in individual patients and to explore whether this optimal dose and the level of disease activity at that dose could be predicted.

Methods: Data from CAMERA II trial comparing MTX and MTX with 10 mg of prednisone both in a tight control treatment strategy in early RA was used. For each patient a curve for disease activity over time was fitted and the MTX dose after which further step-up did not result in relevant improvement in disease activity anymore was determined the 'lowest optimally effective MTX dose (LOED)'.

Predicting the 10-year risk of hip and major osteoporotic fracture in rheumatoid arthritis and in the general population: an independent validation and update of UK FRAX without bone mineral density.

Objectives: FRAX incorporates rheumatoid arthritis (RA) as a dichotomous predictor for predicting the 10-year risk of hip and major osteoporotic fracture (MOF). However, fracture risk may deviate with disease severity, duration or treatment. Aims were to validate, and if needed to update, UK FRAX for patients with RA and to compare predictive performance with the general population (GP).

Personalized biological treatment for rheumatoid arthritis: a systematic review with a focus on clinical applicability.

Objectives: To review studies that address prediction of response to biologic treatment in RA and to explore the clinical utility of the studied (bio)markers.

Methods: A search for relevant articles was performed in PubMed, Embase and Cochrane databases. Studies that presented predictive values or in which these could be calculated were selected.

The Epidemiology of Hip and Major Osteoporotic Fractures in a Dutch Population of Community-Dwelling Elderly: Implications for the Dutch FRAX® Algorithm.

Background: Incidence rates of non-hip major osteoporotic fractures (MOF) remain poorly characterized in the Netherlands. The Dutch FRAX® algorithm, which predicts 10-year probabilities of hip fracture and MOF (first of hip, humerus, forearm, clinical vertebral), therefore incorporates imputed MOF rates. Swedish incidence rate ratios for hip fracture to MOF (Malmo 1987-1996) were used to perform this imputation.

Does disease activity add to functional disability in estimation of utility for rheumatoid arthritis patients on biologic treatment?

Objective: Treatment in general is mostly directly aimed at disease activity, and measures such as the DAS28 might therefore present important additional information. Our aim was to develop and validate a model that uses a combination of disease activity (DAS28) and HAQs to estimate EuroQoL 5-dimension scale (EQ5D) utilities.

Methods: Longitudinal data from a cohort study in RA patients from the Utrecht Rheumatoid Arthritis Cohort study Group (Stichting Reumaonderzoek Utrecht) who started treatment with a biologic drug were used for mapping and validation.

Contribution of the subjective components of the disease activity score to the response to biologic treatment in rheumatoid arthritis.

Objective: A significant proportion of patients with rheumatoid arthritis do not respond adequately to biologic treatment. We hypothesized that lack of response to (biologic) disease-modifying antirheumatic drugs (DMARDs) is high in patients in whom the subjective, patient-reported component of the Disease Activity Score 28 (DAS28) is high at baseline. The primary aim of our present study was to investigate the contribution of the more subjective versus the objective components of the DAS28 to response to biologic agents in RA patients, as well as the changes in this contribution over time.

Mortality in British hip fracture patients, 2000-2010: a population-based retrospective cohort study.

Background: Data on recent trends in mortality after hip fracture are scarce. Aims were therefore to examine secular trends in all-cause and cause-specific mortality post hip fracture and to compare this to the general population from 2000 to 2010.

Methods: Population-based cohort study within the United Kingdom Clinical Practice Research Datalink and linked to cause of death data for 57.

Generalization and extrapolation of treatment effects from clinical studies in rheumatoid arthritis.

Objective: Pragmatic clinical trials have been proposed as a solution for nongeneralizability of randomized clinical trial (RCT) results. We investigated whether treatment effects of pragmatic clinical trials are indeed generalizable to clinical practice and how efficacy estimates from published RCTs can be translated to daily practice populations.

Methods: Data from pragmatic clinical trials of the Utrecht Rheumatoid Arthritis Cohort and the observational Nijmegen Early Rheumatoid Arthritis inception cohort were used.

Identifying phenotypes of knee osteoarthritis by separate quantitative radiographic features may improve patient selection for more targeted treatment.

Objective: Expression of osteoarthritis (OA) varies significantly between individuals, and over time, suggesting the existence of different phenotypes, possibly with specific etiology and targets for treatment. Our objective was to identify phenotypes of progression of radiographic knee OA using separate quantitative features.

Methods: Separate radiographic features of OA were measured by Knee Images Digital Analysis (KIDA) in individuals with early knee OA (the CHECK cohort: Cohort Hip & Cohort Knee), at baseline and at 2-year and 5-year followup.

Quantitative radiographic features of early knee osteoarthritis: development over 5 years and relationship with symptoms in the CHECK cohort.

Objective: To evaluate whether computer-assisted, interactive digital analysis of knee radiographs enables identification of different quantitative features of joint damage, and to evaluate the relationship of such features with each other and with clinical characteristics during 5-year followup in early osteoarthritis (OA).

Methods: Knee radiographs from the Cohort Hip and Cohort Knee (CHECK) study, including 1002 individuals with early OA complaints, were evaluated for different measures with knee images digital analysis (KIDA). To aid definition of different radiographic features of OA, principal component analysis of KIDA was used.

Impact of self-reported comorbidity on physical and mental health status in early symptomatic osteoarthritis: the CHECK (Cohort Hip and Cohort Knee) study.

Objective: To describe the relationship between comorbidity (absolute number as well as the presence of specific comorbidities) and pain, physical functioning and mental health status of participants with early symptomatic OA of the hip or knee.

Methods: In the Netherlands, a prospective 10-year follow-up study was initiated by the Dutch Arthritis Association in participants with early symptomatic OA of the hip or knee: CHECK (Cohort Hip and Cohort Knee), which consists of 1002 individuals. At baseline, linear regression analysis was used to determine the influence of comorbidity on the outcome variables: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, WOMAC physical functioning, Medical Outcomes Study Short Form 36 (SF-36) Physical Component Summary and Mental Component Summary.

Overview and analysis of treat-to-target trials in rheumatoid arthritis reporting on remission.

Objectives: To present an updated overview of tight control studies with a fixed treatment target ('treat-to-target'), reporting on (sustained) remission in rheumatoid arthritis (RA).

Methods: A search of the electronic databases Medline (PubMed), Embase and Cochrane was performed in July 2012 to identify trials and studies addressing tight control with treat-to-target reporting on (sustained) remission, regardless of definition or duration. Next to a narrative overview of the identified studies, a formal meta-analysis was performed pooling study results of studies comparing the effects of a tight control and treat-to-target strategy arm with those of a usual care strategy.

COX-2-selective NSAIDs and risk of hip or knee replacements: a population-based case-control study.

Disease models of osteoarthritis (OA) have shown that COX-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs, coxibs) may have beneficial effects on cartilage. Clinical or epidemiological evidence for this potential association is scarce. The objective of this study was to evaluate the risk of hip or knee replacement in users of coxibs compared to nonselective NSAIDs.

Increase of body mass index in a tight controlled methotrexate-based strategy with prednisone in early rheumatoid arthritis: side effect of the prednisone or better control of disease activity?

Objective: To clarify whether increase of body weight in patients with early rheumatoid arthritis (RA) upon administration of prednisone is a side effect of prednisone or a result of better control of disease activity, we examined the association of prednisone and disease activity with a subsequent change in body mass index (BMI).

Methods: In the Computer Assisted Management in Early Rheumatoid Arthritis Trial-II, patients ages ≥18 years with early RA (disease duration <1 year and no prior use of disease-modifying antirheumatic drugs) had been randomized to a methotrexate (MTX)-based tight control strategy with either 10 mg of prednisone (MTX + prednisone) or placebo (MTX + placebo). The MTX + prednisone group had lower disease activity, but gained more weight than the MTX + placebo group (mean ± SD 2.

Performance of a multi-biomarker score measuring rheumatoid arthritis disease activity in the CAMERA tight control study.

Objectives: To evaluate the performance of individual biomarkers and a multi-biomarker disease activity (MBDA) score in the early rheumatoid arthritis (RA) patient population from the computer assisted management in early rheumatoid arthritis (CAMERA) study.

Methods: Twenty biomarkers were measured in the CAMERA cohort, in which patients were treated with either intensive or conventional methotrexate-based treatment strategies. The MBDA score was calculated using the concentrations of 12 biomarkers (SAA, IL-6, TNF-RI, VEGF-A, MMP-1, YKL-40, MMP-3, EGF, VCAM-1, leptin, resistin and CRP) according to a previously trained algorithm.