Ten years of METEOR (an international rheumatoid arthritis registry): development, research opportunities and future perspectives

OBJECTIVES: Ten years ago, the METEOR tool was developed to simulate treatment-to-target and create an international research database. The development of the METEOR tool and database, research opportunities and future perspectives are described. METHODS: The METEOR tool is a free, online, internationally available tool in which daily practice visits of all rheumatoid arthritis patients visiting a rheumatologist can be registered. In the tool, disease characteristics, patient- and physician-reported outcomes and prescribed treatment could be entered. These can be subsequently displayed in powerful graphics, facilitating treatment decisions and patient-physician interactions. An upload facility is also available, by which data from local electronic health record systems or registries can be integrated into the METEOR database. This is currently being actively used in, among other countries, the Netherlands, Portugal and India. RESULTS: Since an increasing number of hospitals use electronic health record systems, the upload facility is being actively used by an increasing number of sites, enabling them to benefit from the benchmark and research opportunities of METEOR. Enabling a connection between local registries and METEOR is a well established but time-consuming process for which an IT-specialist of METEOR and the local registry are necessary. However, once this process has been finished, data can be uploaded regularly and relatively easily according to a pre-specified format. The METEOR database currently contains data from >39,000 patients and >200,000 visits, from 32 different countries and is ever increasing. Continuous efforts are being undertaken to increase the quality of data in the database. CONCLUSIONS: Since METEOR was founded 10 years ago, many rheumatologists worldwide have used the METEOR tool to follow-up their patients and improve the quality of care they provide to their patients. Combined with uploaded data, this has led to an extensive growth of the database. It now offers a unique opportunity to study daily practice care and to perform research regarding cross-country differences in a large, worldwide setting, which could provide important knowledge about disease and its treatment in different geographic and clinical settings

Both structural damage and inflammation of the spine contribute to impairment of spinal mobility in patients with ankylosing spondylitis

OBJECTIVE: To study the relationship between spinal mobility, radiographic damage of the spine and spinal inflammation as assessed by MRI in patients with ankylosing spondylitis (AS). METHODS: In this subanalysis of the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy cohort, 214 patients, representing an 80% random sample, were investigated. Only baseline data were used. MRI inflammation was assessed by the AS spinal MRI activity (ASspiMRI-a) score, structural damage by the modified Stoke AS Spine Score (mSASSS) and spinal mobility by the linear definition of the Bath Ankylosing Spondylitis Metrology Index (BASMI). Univariate correlations were calculated on baseline values using Spearman rank correlation. Independent associations between the variables of interest were investigated by multivariate linear regression analysis. Associations with clinical disease activity, C-reactive protein, disease duration, age, gender, body mass index and HLA-B27 status were also investigated. Subanalyses were performed according to disease duration. RESULTS: BASMI correlated moderately well with mSASSS (Spearman's rho=0.6) and weakly with ASspiMRI-a (rho=0.3). A best-fit model for BASMI included both mSASSS (regression coefficient (B)=0.865, p 3 years B was greater for mSASSS than for ASspiMRI-a (0.924 vs 0.156). CONCLUSION: Spinal mobility impairment in AS is independently determined both by irreversible spinal damage and by reversible spinal inflammation. Spinal mobility impairment is more influenced by spinal inflammation in early disease, and by structural damage in later diseas

Effect of certolizumab pegol over 96 weeks of treatment on inflammation of the spine and sacroiliac joints, as measured by MRI, and the association between clinical and MRI outcomes in patients with axial spondyloarthritis.

OBJECTIVE: To report MRI outcomes and explore the relationship between clinical remission and MRI inflammation in patients with axial spondyloarthritis (axSpA) from the RAPID-axSpA trial, including radiographic (r-)axSpA and non-radiographic (nr-)axSpA. METHODS: RAPID-axSpA (NCT01087762) was double-blind and placebo-controlled to week 24, dose-blind to week 48 and open-label to week 204. Patients were randomised to certolizumab pegol (CZP) or placebo. Placebo patients entering dose-blind were rerandomised to CZP. MRIs performed at baseline, weeks 12, 48 and 96 were scored by 2 reviewers independently: Spondyloarthritis Research Consortium of Canada (SPARCC) for sacroiliac (SI) joints; Berlin modification of the Ankylosing Spondylitis spine MRI scoring system for disease activity (Berlin) for spine. Inflammation thresholds: SPARCC≥2; Berlin>2. Remission thresholds: SPARCC<2 (SI joints); Berlin≤2 (spine); Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (<1.3, clinical). RESULTS: Across 163 patients in the MRI set (109 CZP; 54 placebo), week 12 mean changes from baseline in MRI scores were greater for CZP versus placebo: SPARCC: -4.8 (SD 8.6) vs -1.6 (7.8; p<0.001); Berlin: -2.9 (4.2) vs 0.2 (4.8; p<0.001). Improvements were maintained to week 96. Week 12 MRI remission was achieved by 52.6% of patients with baseline MRI inflammation in SI joints, 62.0% in the spine and 37.9% of patients with both. MRI remission rates were sustained to week 96, with similar trends in r-axSpA and nr-axSpA. At week 96, 57.5% vs 65.9% of patients achieving versus not achieving clinical remission had MRI remission. CONCLUSIONS: CZP reduced inflammation in the spine and SI joints in patients with r-axSpA and nr-axSpA, with improvements maintained over 96 weeks. Substantial proportions of patients achieved MRI remission. Concordance between clinical remission and current definitions of absence of MRI inflammation was limited. TRIAL REGISTRATION NUMBER: NCT01087762; Post-results

Clinical practice guidelines for the foot and ankle in rheumatoid arthritis: a critical appraisal

Background: Clinical practice guidelines are recommendations systematically developed to assist clinical decision-making and inform healthcare. In current rheumatoid arthritis (RA) guidelines, management of the foot and ankle is under-represented and the quality of recommendation is uncertain. This study aimed to identify and critically appraise clinical practice guidelines for foot and ankle management in RA. Methods: Guidelines were identified electronically and through hand searching. Search terms 'rheumatoid arthritis', 'clinical practice guidelines' and related synonyms were used. Critical appraisal and quality rating were conducted using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Results: Twenty-four guidelines were included. Five guidelines were high quality and recommended for use. Five high quality and seven low quality guidelines were recommended for use with modifications. Seven guidelines were low quality and not recommended for use. Five early and twelve established RA guidelines were recommended for use. Only two guidelines were foot and ankle specific. Five recommendation domains were identified in both early and established RA guidelines. These were multidisciplinary team care, foot healthcare access, foot health assessment/review, orthoses/insoles/splints, and therapeutic footwear. Established RA guidelines also had an 'other foot care treatments' domain. Conclusions: Foot and ankle management for RA features in many clinical practice guidelines recommended for use. Unfortunately, supporting evidence in the guidelines is low quality. Agreement levels are predominantly 'expert opinion' or 'good clinical practice'. More research investigating foot and ankle management for RA is needed prior to inclusion in clinical practice guidelines

Subtle changes in individual joints result in both positive and negative change scores in a patient: results from a clinical trial in patients with rheumatoid arthritis

Radiographic progression in clinical trials is assessed by interpreting changes in total radiographic joint score, and the reliability of those scores depends on an evaluation of sum scores. It is not known how consistently changes in individual joints are identified by independent readers and in independent readings. Patients and 7255 single joints from 178 patients who participated in the Trial of Etanercept and Methothrexate with Radiographic Patient Outcomes (TEMPO) trial were evaluated. Every image was independently scored twice according to the Sharp-van der Heijde method by two independent readers, so that four scores per joint were available. Absolute agreement and consistency of negative and positive erosion change scores across readers and readings were compared on a per-joint level, as well as on a per-patient level. The number of joints showing a change for erosion was very low in this trial: 691/7255 analysed joints had at least one non-zero change score out of four readings. Absolute agreement between readings was remarkably poor: only 12 joints showed a consistently positive or negative change in all four readings. Change scores in opposite directions in the same joint across independent readings were rare (25 joints). Frequency of opposite joint scores in the same patient (mixed change patterns) was reader dependent. Substantial intra and interreader disagreement in scoring change in individual joints is common. Opposite joint scores in the same patient, however, are rare and reader dependent. Notwithstanding these subtle inconsistencies on the individual joint level, the total Sharp score is a useful and discriminatory outcome measur

Tofacitinib onveiliger dan TNF-α-remmer bij reumatoïde artritis

De JAK-remmer tofacitinib is een relatief nieuw oraal geneesmiddel voor de behandeling van reumatoïde artritis. Elders in het NTvG wordt het artikel van Ytterberg en collega’s besproken (NTvG/D6749). Hierin wordt de ‘ORAL surveillance’-studie beschreven, een onderzoek naar de veiligheid van tofacitinib dat door de Amerikaanse Food and Drug Administration (FDA) werd geëist als voorwaarde voor goedkeuring van het geneesmiddel

Performance of clinical, laboratory and imaging features for diagnosing spondyloarthritis-a systematic literature review and meta-analysis

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Induction of sustained clinical remission in early axial spondyloarthritis following certolizumab pegol treatment: 48-week outcomes from C-OPTIMISE

INTRODUCTION: Achievement of remission is a key treatment goal for patients with axial spondyloarthritis (axSpA). C-OPTIMISE assessed achievement of sustained clinical remission in patients with axSpA, including radiographic (r) and non-radiographic (nr) axSpA, during certolizumab pegol (CZP) treatment, and subsequent maintenance of remission following CZP dose continuation, dose reduction or withdrawal. Here, we report outcomes from the first 48 weeks (induction period) of C-OPTIMISE, during which patients received open-label CZP. METHODS: C-OPTIMISE (NCT02505542) was a two-part, multicenter, phase 3b study in adult patients with early axSpA (r-/nr-axSpA), including a 48-week open-label induction period followed by a 48-week maintenance period. Patients with active adult-onset axSpA, < 5 years' symptom duration, and fulfilling Assessment of SpondyloArthritis international Society classification criteria, were included. During the induction period, patients received a loading dose of CZP 400 mg at weeks 0, 2, and 4, followed by CZP 200 mg every 2 weeks (Q2W) up to week 48. The main outcome of the 48-week induction period was the achievement of sustained clinical remission (defined as an Ankylosing Spondylitis Disease Activity Score [ASDAS] < 1.3 at week 32 and < 2.1 at week 36 [or vice versa], and < 1.3 at week 48). RESULTS: In total, 736 patients (407 with r-axSpA, 329 with nr-axSpA) were enrolled into the study. At week 48, 43.9% (323/736) of patients achieved sustained remission, including 42.8% (174/407) of patients with r-axSpA and 45.3% (149/329) with nr-axSpA. Patients also demonstrated substantial improvements in axSpA symptoms, MRI outcomes and quality of life measures. Adverse events occurred in 67.9% (500/736) of patients, of which 6.0% (44/736) were serious. CONCLUSIONS: Over 40% of patients with early axSpA achieved sustained remission during 48 weeks of open-label CZP treatment. Additionally, patients across the axSpA spectrum demonstrated substantial improvements in imaging outcomes and quality of life following treatment. No new safety signals were identified. TRIAL REGISTRATION: NCT02505542

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes