Gradual tapering TNF inhibitors versus conventional synthetic DMARDs after achieving controlled disease in patients with rheumatoid arthritis: first-year results of the randomised controlled TARA study.

OBJECTIVES: The aim of this study is to evaluate the effectiveness of two tapering strategies after achieving controlled disease in patients with rheumatoid arthritis (RA), during 1 year of follow-up. METHODS: In this multicentre single-blinded (research nurses) randomised controlled trial, patients with RA were included who achieved controlled disease, defined as a Disease Activity Score (DAS) ≤ 2.4 and a Swollen Joint Count (SJC) ≤ 1, treated with both a conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and a TNF inhibitor. Eligible patients were randomised into gradual tapering csDMARDs or TNF inhibitors. Medication was tapered if the RA was still under control, by cutting the dosage into half, a quarter and thereafter it was stopped. Primary outcome was proportion of patients with a disease flare, defined as DAS > 2.4 and/or SJC > 1. Secondary outcomes were DAS, European Quality of Life-5 Dimensions (EQ5D) and functional ability (Health Assessment Questionnaire Disability Index [HAQ-DI]) after 1 year and over time. RESULTS: A total of 189 patients were randomly assigned to tapering csDMARDs (n = 94) or tapering anti-TNF (n = 95). The cumulative flare rates in the csDMARD and anti-TNF tapering group were, respectively, 33 % (95% CI,24% to 43 %) and 43 % (95% CI, 33% to 53 % (p = 0.17). Mean DAS, HAQ-DI and EQ-5D did not differ between tapering groups after 1 year and over time. CONCLUSION: Up to 9 months, flare rates of tapering csDMARDs or TNF inhibitors were similar. After 1 year, a non-significant difference was found of 10 % favouring csDMARD tapering. Tapering TNF inhibitors was, therefore, not superior to tapering csDMARDs. From a societal perspective, it would be sensible to taper the TNF inhibitor first, because of possible cost reductions and less long-term side effects. TRIAL REGISTRATION NUMBER: NTR2754.

Hydroxychloroquine affects bone resorption both in vitro and in vivo.

We recently showed that patients with primary Sjögren syndrome (pSS) have significantly higher bone mineral density (BMD) compared to healthy controls. The majority of those patients (69%) was using hydroxychloroquine (HCQ), which may have favorable effects on BMD. The aim of the study was to evaluate whether HCQ modulates osteoclast function. Osteoclasts were cultured from PBMC-sorted monocytes for 14 days and treated with different HCQ doses (controls 1 and 5 µg/ml). TRAP staining and resorption assays were performed to evaluate osteoclast differentiation and activity, respectively. Staining with an acidification marker (acridine orange) was performed to evaluate intracellular pH at multiple timepoints. Additionally, a fluorescent cholesterol uptake assay was performed to evaluate cholesterol trafficking. Serum bone resorption marker ß-CTx was evaluated in rheumatoid arthritis patients. HCQ inhibits the formation of multinuclear osteoclasts and leads to decreased bone resorption. Continuous HCQ treatment significantly decreases intracellular pH and significantly enhanced cholesterol uptake in mature osteoclasts along with increased expression of the lowdensity lipoprotein receptor. Serum ß-CTx was significantly decreased after 6 months of HCQ treatment. In agreement with our clinical data, we demonstrate that HCQ suppresses bone resorption in vitro and decreases the resorption marker ß-CTx in vivo. We also showed that HCQ decreases the intracellular pH in mature osteoclasts and stimulates cholesterol uptake, suggesting that HCQ induces osteoclastic lysosomal membrane permeabilization (LMP) leading to decreased resorption without changes in apoptosis. We hypothesize that skeletal health of patients with increased risk of osteoporosis and fractures may benefit from HCQ by preventing BMD loss.

Inadequate response to treat-to-target methotrexate therapy in patients with new-onset rheumatoid arthritis: development and validation of clinical predictors.

OBJECTIVE: To identify and validate clinical baseline predictors associated with inadequate response (IR) to methotrexate (MTX) therapy in newly diagnosed patients with rheumatoid arthritis (RA). METHODS: In U-Act-Early, 108 disease-modifying antirheumatic drug (DMARD)-naive patients with RA were randomised to initiate MTX therapy and treated to target until sustained remission (disease activity score assessing 28 joints (DAS28) <2.6 with four or less swollen joints for ≥24 weeks) was achieved. If no remission, hydroxychloroquine was added to the treatment regimen (ie, 'MTX+') and replaced by tocilizumab if the target still was not reached thereafter. Regression analyses were performed to identify clinical predictors for IR, defined as needing addition of a biological DMARD, to 'MTX+'. Data from the treatment in the Rotterdam Early Arthritis Cohort were used for external validation of the prediction model. RESULTS: Within 1 year, 56/108 (52%) patients in U-Act-Early showed IR to 'MTX+'. DAS28 (adjusted OR (ORadj) 2.1, 95% CI 1.4 to 3.2), current smoking (ORadj 3.02, 95% CI 1.1 to 8.0) and alcohol consumption (ORadj 0.4, 95% CI 0.1 to 0.9) were identified as baseline predictors. The area under the receiver operator characteristic curve (AUROC) of the prediction model was 0.75 (95% CI 0.66 to 0.84); the positive (PPV) and negative predictive value (NPV) were 65% and 80%, respectively. When applying the model to the validation cohort, the AUROC slightly decreased to 0.67 (95% CI 0.55 to 0.79) and the PPV and NPV to 54% and 80%, respectively. CONCLUSION: Higher DAS28, current smoking and no alcohol consumption are predictive factors for IR to step-up 'MTX+' in DMARD-naive patients with new-onset RA. TRIAL REGISTRATION: NCT01034137; Post-results, ISRCTN26791028; Post-results.

Performance of screening tools for psoriatic arthritis: a cross-sectional study in primary care.

Objective: . To compare the screening performance of the Psoriasis Epidemiology Screening Tool (PEST), Psoriatic Arthritis Screening and Evaluation (PASE) and Early Arthritis for Psoriatic Patients (EARP) questionnaires for detecting PsA among psoriasis patients in a primary care setting. Methods: In a cross-sectional study, 473 primary care psoriasis patients at risk for PsA completed the PEST, PASE and EARP questionnaires and were clinically evaluated by a trained research nurse. A PsA case was defined by a rheumatologist according to the CASPAR criteria. Sensitivity and specificity were determined for the PEST and EARP cut-offs (⩾3) and the PASE cut-offs (⩾44 and ⩾47). Results: PsA was diagnosed in 53 patients. The PEST had a sensitivity of 0.68 and a specificity of 0.71. The PASE was validated for two different cut-offs. The cut-off of 47 led to a sensitivity of 0.59 and a specificity of 0.66, whereas the lower cut-off of 44 led to a sensitivity of 0.66 and a specificity of 0.57. For the EARP we found a sensitivity of 0.87 with a specificity of 0.34. Conclusion: The PEST questionnaire has the most favourable trade-off between sensitivity and specificity to screen for PsA. However, as the prevalence of psoriasis and PsA is fairly low in primary care, screening only psoriasis patients with musculoskeletal complaints may be a better allocation of resources.

Best cost-effectiveness and worker productivity with initial triple DMARD therapy compared with methotrexate monotherapy in early rheumatoid arthritis: cost-utility analysis of the tREACH trial.

OBJECTIVE: To evaluate direct and indirect costs per quality adjusted life year (QALY) for different initial treatment strategies in very early RA. METHODS: The 1-year data of the treatment in the Rotterdam Early Arthritis Cohort trial were used. Patients with a high probability (>70%) according to their likelihood of progressing to persistent arthritis, based on the prediction model of Visser, were randomized into one of following initial treatment strategies: (A) initial triple DMARD therapy (iTDT) with glucocorticoids (GCs) intramuscular (n = 91); (B) iTDT with an oral GC tapering scheme (n = 93); and (C) initial MTX monotherapy (iMM) with GCs similar to B (n = 97). Data on QALYs, measured with the Dutch EuroQol, and direct and indirect cost were used. Direct costs are costs of treatment and medical consumption, whereas indirect costs are costs due to loss of productivity. RESULTS: Average QALYs (sd) for A, B and C were, respectively, 0.75 (0.12), 0.75 (0.10) and 0.73 (0.13) for Dutch EuroQol. Highest total costs per QALY (sd) were, respectively, €12748 (€18767), €10 380 (€15 608) and €17 408 (€21 828) for strategy A, B and C (P = 0.012, B vs C). Direct as well as indirect costs were higher with iMM (strategy C) compared with iTDT (strategy B). Higher direct costs were due to ∼40% more biologic usage over time. Higher indirect costs, on the other hand, were caused by more long-term sickness and reduction in contract hours. iTDT was >95% cost-effective across all willingness-to-pay thresholds compared with iMM. CONCLUSION: iTDT was more cost-effective and had better worker productivity compared with iMM.

Adding ultrasound to clinical examination reduced frequency of enthesitis in primary care psoriasis patients with musculoskeletal complaints.

OBJECTIVES: Part of the psoriasis patients with musculoskeletal complaints will have inflammation of the entheses. Entheseal inflammation is difficult to assess by clinical examination only. Therefore, we aimed to determine the frequency of clinically relevant ultrasound inflammation at the most commonly assessed entheses (MASEI; Madrid Sonographic Enthesis Index) in primary care psoriasis patients with one or more tender entheses. METHODS: Adult primary care psoriasis patients with musculoskeletal complaints (tender enthesis or arthritis at physical examination) had an ultrasound examination of seven entheses according to the MASEI. Clinically relevant ultrasound inflammation was defined as active inflammation on ultrasound in combination with at least one clinical feature at the same enthesis. Active ultrasound inflammation contained positive power Doppler signal or in case of the plantar aponeurosis increased thickness. Structural changes entailed calcifications, enthesophytes, increased thickness, hypoechogeneicity indicating irregular fibre structure and erosions. Clinically, an enthesis was scored positive by a tender enthesis at clinical examination, reported pain in the history or self-reported pain in the questionnaires. RESULTS: Of 542 primary care psoriasis patient, 111 patients had tender entheses and/or arthritis. These patients were both clinically and ultrasonographically evaluated. Active ultrasound inflammation accompanied with pain or tenderness at the enthesis was found in 36% of the patients (n=40). Most common were inflammation at the knee (n=11) and at the plantar aponeurosis (n=10). Structural changes were observed in 95% of the psoriasis patients independent of their clinical manifestation. CONCLUSIONS: We found concurrent presence of ultrasound inflammatory changes and clinical symptoms in 36% of the primary care psoriasis patients who had tenderness at one or more entheseal sites.

Study protocol for a cluster randomized controlled trial to evaluate a referral strategy for axial spondyloarthritis in young primary care patients with chronic low back pain; an impact study.

BACKGROUND: Axial spondyloarthritis (axSpA) is a disabling inflammatory joint disease with chronic low back pain (CLBP) as leading symptom. Recognizing axSpA in the large amount of CLBP patients is difficult for general practioners (GP). This evaluation aims to assess the effect of a referral strategy for axSpA in young primary care patients with CLBP by comparing the use of the strategy with usual care. The effect is measured at three different levels; by patient reported outcomes (the clinical effect), process and costs evaluation. METHODS/DESIGN: This study design is a cluster randomized controlled trial with GP as clusters. GPs throughout the Netherlands are invited to participate and randomized to either the intervention or the control group. Patients from participating GPs are invited to participate if they have ever been registered with low back pain, without radiation (ICPC L03) and aged 18-45 years. To be included in the study, patients need to have current low back pain and chronic low back pain (>12 weeks). In the intervention arm a referral strategy for axSpA will be applied in CLBP patients, in the control arm care as usual will be provided for CLBP patients. The referral strategy consists of four easy to use variables. All are questions about the back pain complaints of the patients. Data is prospectively collected in an online database at baseline (T0), 4 months (T1), 12 months (T2) and 24 months (T3). After time point T1 (4 months) patients from the control group will also receive the intervention i.e. the application of a referral strategy for axSpA. The effect of the referral strategy is measured at three different levels, by patient outcomes (e.g. pain scores, quality of life), process measures (e.g. number of axSpA diagnoses by rheumatologists) and by costs (work productivity and health care resources use). Our primary outcome is the Roland Morris Disability Questionnaire after 4 months, secondary outcomes are pain and quality of life. Costs will be assessed before and after the use of the referral strategy, to estimate if the use of the strategy will lead to a reduction in health care costs and improvement in work participation. DISCUSSION: It is anticipated that using the axSpA referral strategy for primary care CLBP patients will increase the quality of life of CLBP patients, will result in more (correct) diagnoses of axSpA by the rheumatologists, and will be cost-effective. Ultimately, the results of this study may contribute to the startup of a national implementation of the axSpA referral strategy to identify timely CLBP patients with axSpA. TRIAL REGISTRATION: NCT01944163 , date of registration; September 6, 2013 (Clinicaltrials.gov).

Treatment decisions and related costs differ significantly depending on the choice of a disease activity index in RA, according to 1987 and 2010 classification criteria.

OBJECTIVE: To evaluate the therapeutic and economic consequences of various disease activity indices (DAIs) in RA according to 1987 and 2010 criteria. METHODS: Data on disease activity states from all sustained visits were assessed from all patients who participate in the treatment in the Rotterdam Early Arthritis Cohort (tREACH) study, a stratified randomized trial to evaluate different treatment strategies in patients with a symptom duration of <1 year. Frequencies of treatment adaptations, based upon exclusive thresholds of various DAIs, were visualized in reclassification tables. The Stuart-Maxwell test was applied to analyse any significant differences between treatment decisions according to the different DAIs. Simulated annual median medication costs were estimated using the tREACH medication protocol with standard national costs. RESULTS: DAIs perform similar in RA according to 1987 and 2010 criteria. A total of 1104 DASs per DAI were available from 296 patients. DAIs differ significantly, compared with DASs, in classifying a patient's disease state. Consequently, treatment intensifications occur more frequently with SDAI, CDAI and DAS-28 usage, compared with DAS. Tapering treatment occurs less frequently with SDAI and CDAI and more frequently with DAS-28 usage. Simulated annual median medication costs are significantly higher if DAS-28, SDAI and CDAI are used compared with DAS usage. CONCLUSION: Usage of various DAIs in a single patient leads to inconsistent disease state categorizations. Consequently, these inconsistencies significantly influence therapeutic decisions and accompanying costs. As DAI usage is imperative to uphold current European League Against Rheumatology (EULAR) treatment recommendations, physicians should consider these therapeutic and economic consequences before choosing a particular DAI.

[Is bone marrow edema a cause of low back pain? A possible role of bacteria]. / Is eindplaatoedeem van wervellichamen een oorzaak van lage-rugpijn?

Lumbar bone marrow edema, also known as Modic type-1 endplate change, has a prevalence of 43% in low back pain populations and 6% in general populations. Besides mechanical factors and genetic predisposition it has been hypothesized that lumbar bone marrow edema is caused by a latent infection of low-virulence anaerobic bacteria in degenerated lumbar intervertebral discs. The hypothesis is supported by the observation that the presence of Cutibacterium acnes is more frequently found in samples of disci with Modic-1 than in discs without and by the positive effects of antibiotics in patients with back pain and Modic-1 as shown in placebo-controlled RCT's. Opponents of the hypothesis argue that the findings of bacteria are most likely a result of contamination during harvesting the samples. We conclude that time has come to make a start in the Netherlands with treatment with antibiotics of a small group of well-selected patients in well-selected clinics.

Progression From Subclinical Inflammation to Overt Spondyloarthritis in First-Degree Relatives of Patients in Association With HLA-B27: The Pre-Spondyloarthritis Cohort.

OBJECTIVE: As first-degree relatives (FDRs) of HLA-B27-positive patients with axial spondyloarthritis (SpA) have an increased risk of developing axial SpA, the objectives were 1) to evaluate the presence of highly specific imaging features as well as clinical signs of SpA at baseline and after 1 year of follow-up, and 2) to describe the evolution toward clinical disease within 1 year of follow-up in a cohort of seemingly healthy FDRs of HLA-B27-positive axial SpA patients. METHODS: The Pre-SpA cohort is a 5-year prospective inception cohort of seemingly healthy FDRs of HLA-B27-positive axial SpA patients. Clinical and imaging features were collected and recorded. RESULTS: At baseline, 19% of the FDRs reported inflammatory back pain, 32% current arthralgia, 3% arthritis (ever), 5% enthesitis (ever), and 1% dactylitis (ever), and 3% had an extraarticular manifestation. C-reactive protein level was elevated in 16%, and erythrocyte sedimentation rate was elevated in 7%. On magnetic resonance imaging (MRI) views of sacroiliac joints, 10% had a Spondyloarthritis Research Consortium of Canada score of ≥2, 4% had a score of ≥5, and 4% had deep lesions. In total, 1% fulfilled the modified New York criteria for radiographic sacroiliitis. Clinical, MRI, and acute phase findings were equally distributed between HLA-B27-positive and -negative FDRs. After 1 year of follow-up, clinical parameters did not change on the group level, but 6% of the FDRs were clinically diagnosed with axial SpA, of whom 86% were HLA-B27-positive. CONCLUSION: Features associated with SpA or imaging abnormalities were found in up to 32% of seemingly healthy FDRs, with an equal distribution between HLA-B27-positive and -negative FDRs. Progression to clinical axial SpA within 1 year of follow-up was mainly observed in HLA-B27-positive FDRs.

Factors that influence biological survival in rheumatoid arthritis: results of a real-world academic cohort from the Netherlands.

We aim to explore real-world biological survival stratified for discontinuation reason and determine its influenceability in rheumatoid arthritis (RA) patients. Data from the local pharmacy database and patient records of a university hospital in the Netherlands were used. RA patients who started a biological between 2000 and 2020 were included. Data on age, anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) status, presence of erosions, gender, body mass index, time to first biological, biological survival time, use of csDMARDs, and discontinuation reasons were collected. Of the included 318 patients, 12% started their first biological within 6 months after diagnosis. The median time to first biological was 3.6 years (95% CI, 1.0-7.2). The median survival of the first- and second-line biological was respectively 1.7 years (95% CI, 1.3-2.2) and 0.8 years (95% CI, 0.5-1.0) (p = 0.0001). Discontinuation reasons for the first-line biological were ineffectiveness (47%), adverse events (17%), remission (16%), pregnancy (30%), or patient preference (10%). Multivariable Cox regression analyses for discontinuation due to inefficacy or adverse events showed that concomitant use of csDMARDs (HR = 1.32, p < 0.001) positively while RF positivity negatively (HR = 0.82, p = 0.03) influenced biological survival. ACPA positivity was associated with the inability to discontinue biologicals after achieving remission (HR = 1.43, p = 0.023). Second-line TNF inhibitor survival was similar between patients with a primary and secondary non-response on the first-line TNF inhibitor (HR = 1.28, p = 0.34). Biological survival diminishes with the number of biologicals used. Biological survival is prolonged if patients use csDMARDs. RF was negatively associated with biological survival. ACPA was negatively associated with the inability to discontinue biologicals after achieving remission. Therefore, tailoring treatment based upon autoantibody status might be the first step towards personalized medicine in RA. Key Points • Prolonged biological survival is a surrogate for treatment effectiveness; however, an increasing amount of patients will taper treatment due to remission, and factors influencing biological survival based on separate reasons for discontinuation have not been explored. • We found that combining a biological DMARD with a conventional synthetic DMARD increases biological DMARD survival. Rheumatoid factor is negatively associated with biological survival. Anti-citrullinated protein antibody is negatively associated with the inability to discontinue the biological when remission was reached. • The first step towards personalized medicine might be tailoring of treatment based upon autoantibody status.

The IMPACT study: A clustered randomized controlled trial to assess the effect of a referral algorithm for axial spondyloarthritis.

BACKGROUND: A substantial number of patients with chronic low back pain (CLBP) have axial spondyloarthritis (axSpA), but early recognition of these patients is difficult for general practitioners (GPs). The Case Finding Axial Spondyloarthritis (CaFaSpA) referral strategy has shown to be able to identify patients with CLBP at risk for axSpA, but its impact on clinical daily practice is yet unknown. OBJECTIVE: To assess the effect of the CaFaSpA referral strategy on pain caused by disability in primary care patients with CLBP. METHODS: Within this clustered randomized controlled trial 93 general practices were randomized to either the CaFaSpA referral model (intervention) or usual primary care (control). In each group primary care patients between 18 and 45 years with CLBP were included. The primary outcome was disability caused by CLBP, measured with the Roland Morris Disability Questionnaire (RMDQ) at baseline and four months. Secondary outcome was the frequency of new axSpA diagnosis. Descriptive analyses were performed, and a linear mixed-effects model was used. RESULTS: In total 679 CLBP patients were included of which 333 patients were allocated to the intervention group and 346 to the control group. Sixty-four percent were female and mean age was 36.2 years. The mean RMDQ score at baseline was 8.39 in the intervention group and 8.61 in the control group. At four months mean RMDQ score was 7.65 in the intervention group and 8.15 in the control group. This difference was not statistically significant (p = 0.50). Six (8%) out of the 75 finally referred patients, were diagnosed with axSpA by their rheumatologist. CONCLUSIONS: The CaFaSpA referral strategy for axSpA did not have an effect on disability after four months caused by CLBP. However, the strategy is able to detect the axSpA patient within the large CLBP population sufficiently. Trial registration number: NCT01944163, Clinicaltrials.gov.

Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial.

BACKGROUND: Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis. METHODS: A multicenter stratified randomized single-blind controlled trial is currently being performed in patients 18 years or older with recent-onset arthritis. Eight hundred ten patients are being stratified according to the likelihood of their developing persistent arthritis. In patients with a high probability of persistent arthritis, we will study combination Disease Modifying Antirheumatic Drug therapy compared to monotherapy methotrexate. In patients with an intermediate probability of persistent arthritis, we will study Disease Modifying Antirheumatic Drug of various intensities. In patients with a low probability, we will study non-steroidal anti-inflammatory drugs, hydroxychloroquine and a single dose of corticosteroids. If disease activity is not sufficiently reduced, treatment will be adjusted according to a step-up protocol. If remission is achieved for at least six months, medication will be tapered off. Patients will be followed up every three months over two years. DISCUSSION: This is the first rheumatological study to base treatment in early arthritis on a prediction rule. Treatment will be stratified according to the probability of persistent arthritis, and different combinations of treatment per stratum will be evaluated. Treatment will be started early, and patients will not need to meet the ACR-criteria for rheumatoid arthritis. TRIAL REGISTRATION: This trial has been registered in Current Controlled Trials with the ISRCTN26791028.

International Consortium for Health Outcome Measurement Set of Outcomes That Matter to People Living With Inflammatory Arthritis: Consensus From an International Working Group.

OBJECTIVE: The implementation of value-based health care in inflammatory arthritis requires a standardized set of modifiable outcomes and risk-adjustment variables that is feasible to implement worldwide. METHODS: The International Consortium for Health Outcomes Measurement (ICHOM) assembled a multidisciplinary working group that consisted of 24 experts from 6 continents, including 6 patient representatives, to develop a standard set of outcomes for inflammatory arthritis. The process followed a structured approach, using a modified Delphi process to reach consensus on the following decision areas: conditions covered by the set, outcome domains, outcome measures, and risk-adjustment variables. Consensus in areas 2 to 4 were supported by systematic literature reviews and consultation of experts. RESULTS: The ICHOM Inflammatory Arthritis Standard Set covers patients with rheumatoid arthritis (RA), axial spondyloarthritis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA). We recommend that outcomes regarding pain, fatigue, activity limitations, overall physical and mental health impact, work/school/housework ability and productivity, disease activity, and serious adverse events be collected at least annually. Validated measures for patient-reported outcomes were endorsed and linked to common reporting metrics. Age, sex at birth, education level, smoking status, comorbidities, time since diagnosis, and rheumatoid factor and anti-citrullinated protein antibody lab testing for RA and JIA should be collected as risk-adjustment variables. CONCLUSION: We present the ICHOM inflammatory arthritis Standard Set of outcomes, which enables health care providers to implement the value-based health care framework and compare outcomes that are important to patients with inflammatory arthritis.

Development and validation of a prognostic multivariable model to predict insufficient clinical response to methotrexate in rheumatoid arthritis.

OBJECTIVE: The objective was to predict insufficient response to 3 months methotrexate (MTX) in DMARD naïve rheumatoid arthritis patients. METHODS: A Multivariable logistic regression model of rheumatoid arthritis patients starting MTX was developed in a derivation cohort with 285 patients starting MTX in a clinical multicentre, stratified single-blinded trial, performed in seven secondary care clinics and a tertiary care clinic. The model was validated in a validation cohort with 102 patients starting MTX at a tertiary care clinic. Outcome was insufficient response (disease activity score (DAS)28 >3.2) after 3 months of MTX treatment. Clinical characteristics, lifestyle variables, genetic and metabolic biomarkers were determined at baseline in both cohorts. These variables were dichotomized and used to construct a multivariable prediction model with backward logistic regression analysis. RESULTS: The prediction model for insufficient response in the derivation cohort, included: DAS28>5.1, Health Assessment Questionnaire>0.6, current smoking, BMI>25 kg/m2, ABCB1 rs1045642 genotype, ABCC3 rs4793665 genotype, and erythrocyte-folate<750 nmol/L. In the derivation cohort, AUC of ROC curve was 0.80 (95%CI: 0.73-0.86), and 0.80 (95%CI: 0.69-0.91) in the validation cohort. Betas of the prediction model were transformed into total risk score (range 0-8). At cutoff of ≥4, probability for insufficient response was 44%. Sensitivity was 71%, specificity 72%, with positive and negative predictive value of 72% and 71%. CONCLUSIONS: A prognostics prediction model for insufficient response to MTX in 2 prospective RA cohorts by combining genetic, metabolic, clinical and lifestyle variables was developed and validated. This model satisfactorily identified RA patients with high risk of insufficient response to MTX.

Work outcome in yet undiagnosed patients with non-radiographic axial spondyloarthritis and ankylosing spondylitis; results of a cross-sectional study among patients with chronic low back pain.

BACKGROUND: To understand the impact of yet undiagnosed non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) on work outcomes in a cohort of patients with long-lasting chronic low back pain (CLBP). METHODS: Data were used from a primary care CLBP cohort that was established to understand the prevalence of nr-axSpA and AS. Clinical characteristics comprised measures of back pain (visual analogue scale), inflammation (C-reactive protein) and physical functioning (Roland Morris Disability Questionnaire (RMDQ)). Worker outcomes comprised a question on employment and the Work Productivity and Activity Impairment (WPAI) questionnaire, distinguishing absenteeism, presenteeism, and overall work impairment in those employed and activity impairment in all patients. For each disease subgroup, employment ratio compared to the general population was assessed by indirect standardization. Factors associated with work productivity were explored by zero inflated negative binomial (ZINB) regression models. RESULTS: Patients with CLBP (n = 579) were included (41% male, mean age 36 years), of whom 71 (12%) were identified as having nr-axSpA and 24 (4%) as having AS. The standardized employment ratios were 0.89 (95% CI 0.84-0.94), 0.97 (95% CI 0.85-1.09) and 0.81 (95% CI 0.56-1.06) for patients with CLBP, nr-axSpA and AS, respectively. Scores for the WPAI subdomains were not significantly different between patients with CLBP, nr-axSpA or AS. The ZINB models showed significant associations between visual analog scale (VAS) score for pain and RMDQ and work productivity. CONCLUSION: The impact of yet undiagnosed nr-axSpA and AS on patients' work outcomes was substantial but was not significantly different from those of patients with long-standing CLBP. Variables significantly associated with reduced work productivity were VAS for pain and RMDQ score.

The Prevalence and Incidence of Axial and Peripheral Spondyloarthritis in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] is a chronic disease which affects up to 0.5% of the population. Various extraintestinal manifestations occur, among which are rheumatic manifestations, grouped together under the name spondyloarthritis. The objective of this systematic review and meta-analysis was to give a systematic overview of the prevalence and incidence of spondyloarthritis in patients with inflammatory bowel disease. METHODS: We systematically searched Embase, Pubmed, OvidSP, Scopus, and Web-of-Science databases from inception to August 2016. All articles that addressed the prevalence or incidence of the different features of spondyloarthritis in adult inflammatory bowel disease patients were included. Methodological quality was assessed using a modified quality assessment tool developed for prevalence studies. RESULTS: A total of 71 studies were included, reporting on the prevalence of sacroiliitis, ankylosing spondylitis, arthritis, enthesitis, and dactylitis. Pooled prevalences were calculated for sacroiliitis (10%; 95% confidence interval [CI] 8-12%), ankylosing spondylitis [3%; 95% CI 2-4%], and arthritis [13%; 95% CI 12-15%]. Geographical area, setting and use of different criteria contribute to the large heterogeneity. Few estimates were available for enthesitis [prevalence range from 1% to 54%] and dactylitis [prevalence range from 0% to 6%]. Only three incidence studies were identified, which report cumulative incidences from 5 to 30 years. CONCLUSIONS: Spondyloarthritis occurs in up to 13% of patients with IBD. Ankylosing spondylitis is the least common [3%] followed by sacroiliitis [10%] and peripheral arthritis [13%].