The nocebo effect challenges the non-medical infliximab switch in practice.

BACKGROUND: In clinical practice, non-medical switching of biological medication may provoke nocebo effects due to unexplained deterioration of therapeutic benefits. Indication extrapolation, idiosyncratic reactions, and interchangeability remain challenged in clinical practice after biosimilar approval by the European Medicines Agency. The principle of "first do no harm" may be challenged in a patient when switching from originator to biosimilar biological. AIM: To describe the 1-year results of a pragmatic study on infliximab biosimilar implementation in immune-mediated inflammatory disease patients on the basis of shared decision-making under effectiveness and safety monitoring. METHODS: Inflammatory bowel disease and rheumatology patients on infliximab originator were converted to infliximab biosimilar after providing informed consent. Nocebo response patients were monitored after switch back to originator. Linear mixed models were used to analyze continuous endpoints on effectiveness and laboratory outcomes to determine significance (P ≤ 0.05) of change over time after switching. RESULTS: After inviting 146 patients, a group of 125 patients enrolled in the project over time, respectively, 73 Crohn's disease, 28 ulcerative colitis, nine rheumatoid arthritis, ten psoriatic arthritis, and five ankylosing spondylitis patients. No statistically significant changes in effectiveness and safety were observed in any of the indications after a median of 4 infusions in 9 months of study. An overall nocebo response of 12.8% was found among the patients during a minimal observation period of 6 months after the transition to biosimilar infliximab. The overall nocebo response rate did not differ between the studied indications. CONCLUSIONS: In inflammatory bowel disease and rheumatological patients, similar effectiveness and safety were demonstrated on the transition into infliximab biosimilar. In our series, patient empowerment and registration of treatment outcomes delineated biosimilar transition, an approach that hypothetically could reduce nocebo response rates which are relevant to account for regarding biosimilar implementation.

Presence of multiple spondyloarthritis (SpA) features is important but not sufficient for a diagnosis of axial spondyloarthritis: data from the SPondyloArthritis Caught Early (SPACE) cohort.

OBJECTIVES: Concerns have been raised about overdiagnosis of axial spondyloarthritis (axSpA). We investigated whether patients with chronic back pain (CBP) of short duration and multiple SpA features are always diagnosed with axSpA by the rheumatologist, and to what extent fulfilment of the Assessment of SpondyloArthritis International Society (ASAS) axSpA criteria is associated with an axSpA diagnosis. METHODS: Baseline data from 500 patients from the SPondyloArthritis Caught Early cohort which includes patients with CBP (≥3 months, ≤2 years, onset <45 years) were analysed. All patients underwent full diagnostic workup including MRI of the sacroiliac joints (MRI-SI) and radiograph of sacroiliac joints (X-SI). For each patient, the total number of SpA features excluding sacroiliac imaging and human leucocyte antigen B27 (HLA-B27) status was calculated. RESULTS: Before sacroiliac imaging and HLA-B27 testing, 32% of patients had ≤1 SpA feature, 29% had 2 SpA features, 16% had 3 SpA features and 24% had ≥4 SpA features. A diagnosis of axSpA was made in 250 (50%) of the patients: 24% with ≤1 SpA feature, 43% with 2 SpA features, 62% with 3 SpA features and 85% with ≥4 SpA features. Of the 230 patients with a positive ASAS classification 40 (17.4%) did not have a diagnosis of axSpA. HLA-B27 positivity (OR 5.6; 95% CI 3.7 to 8.3) and any (MRI-SI and/or X-SI) positive imaging (OR 34.3; 95% CI 17.3 to 67.7) were strong determinants of an axSpA diagnosis. CONCLUSIONS: In this cohort of patients with CBP, neither the presence of numerous SpA features nor fulfilment of the ASAS classification criteria did automatically lead to a diagnosis axSpA. Positive imaging was considered particularly important in making a diagnosis of axSpA.

Prevalence and clinical significance of lumbosacral transitional vertebra (LSTV) in a young back pain population with suspected axial spondyloarthritis: results of the SPondyloArthritis Caught Early (SPACE) cohort.

OBJECTIVE: To determine in a cohort of young patients with suspected axial spondyloarthritis (axSpA), the prevalence of lumbosacral transitional vertebra (LSTV), its association with local bone marrow edema (BME) and lumbar spine degeneration, and the potential relationship with MRI findings and clinical signs of axSpA. MATERIALS AND METHODS: Baseline imaging studies and clinical information of patients from the SPondyloArthritis Caught Early-cohort (back pain ≥3 months, ≤2 years, onset <45 years) were used. Two independent readers assessed all patients for LSTV on radiography, and BME-like and degenerative changes on MRI. Patients with and without LSTV were compared with regard to the prevalence of MRI findings and the results of clinical assessment using Chi-squared test or t test. RESULTS: Of 273 patients (35.1% male, mean age 30.0), 68 (25%) patients showed an LSTV, without statistical significant difference between patients with and without axSpA (p = 0.327). Local sacral BME was present in 9 out of 68 (13%) patients with LSTV and absent in patients without LSTV (p < 0.001). Visual analogue scale (VAS) pain score and spinal mobility assessments were comparable. CONCLUSIONS: LSTV is of low clinical relevance in the early diagnosis of axSpA. There is no difference between patients with and without LSTV regarding the prevalence of axSpA, pain and spinal mobility, and a BME-like pattern at the pseudoarticulation does not reach the SI joints.

European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.

BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

Signal intensity loss of the intervertebral discs in the cervical spine of young patients on fluid sensitive sequences.

OBJECTIVE: To evaluate the signal intensity (SI) of the intervertebral discs of the cervical spine on magnetic resonance (MR) fluid sensitive sequences, and correlate this to secondary signs of degeneration on MR and radiographs as well as to age. MATERIAL AND METHODS: A total of 265 patients aged ≥16 with back pain (≥3-months, <2-year, onset <45-years) from the SPondyloArthritis Caught Early (SPACE) cohort were included. Sagittal 1.5 T MR images and lateral radiographs of the cervical spine were independently evaluated by two readers for: SI of the intervertebral discs using a grading system based of Pfirrmann (grade 1 normal/bright SI; 2 inhomogeneous/bright SI; 3 inhomogeneous/mildly decreased SI; 4 inhomogeneous/markedly decreased SI; 5 signal void), disc herniation and Modic changes (MRI) and disc space narrowing, osteophytes and sclerosis (radiograph). Readers were blinded for clinical information. Descriptive statistics were used for characteristics and prevalence of findings, and regression analysis was used for age and grades. RESULTS: Of 265 patients (36% male, mean age 30), 221 (83%) patients had 1 to 6 discs (median 4) with decreased SI. Of 1,590 discs, 737 (46%) were grade 1; 711 (45%) grade 2; 133 (8%) grade 3; 8 (1%) grade 4 and 1 (0%) grade 5. Secondary signs of degeneration were rare and seen predominantly in C5-C7 and appear to be related to signal loss grade 3 and 4. CONCLUSION: Low signal intensity of intervertebral discs in absence of secondary degenerative signs in the cervical spine on fluid sensitive MR images might be pre-existing and part of the natural course.

Natural course of bone marrow oedema on magnetic resonance imaging of the sacroiliac joints in patients with early inflammatory back pain: a 2-year follow-up study.

OBJECTIVES: To describe the distribution and evolution over time of bone marrow oedema (BME) on magnetic resonance imaging of the sacroiliac joint (MRI-SIJ) in patients with recent-onset inflammatory back pain (IBP) suspected for axial spondyloarthritis (axSpA). METHOD: A 2-year follow-up study with annual MRI-SIJ was conducted in patients with IBP of duration ≤ 2 years. Each SIJ was divided into quadrants and MRI scores were analysed on a per-patient and per-SIJ quadrant basis. The presence of BME in each SIJ quadrant was recorded. Fulfilment of the Assessment of SpondyloArthritis international Society (ASAS) criteria for axSpA was assessed at baseline and at follow-up. RESULTS: At baseline, 68 patients (38% male; mean age 34.9 ± 10.3 years) were included. BME was visible at baseline in 24 (35%) patients, all fulfilling the ASAS axSpA criteria. Twenty-three of these 24 patients had a follow-up MRI. Not taking into account the baseline MRI, three (13%) of these 23 patients would no longer fulfil the ASAS criteria during follow-up because of subsiding BME. Forty-four (65%) patients had a negative baseline MRI, of whom 39 had a follow-up MRI available. New BME at follow-up meant that three (8%) of these 39 patients now fulfilled the ASAS criteria. At follow-up, baseline BME lesions subsided completely in 47% of SIJ quadrants (range 33-71%) whereas new BME lesions were detected in 8% of SIJ quadrants (range 2-11%). CONCLUSIONS: BME shows a fluctuating course in patients with early IBP suspected for axSpA. This may have an impact on diagnosis and the overall performance of the ASAS axSpA criteria.

New analysis tools for observational studies.

Observational studies, which are very common in rheumatology, usually follow a selected group of patients for a predetermined period of time, or infinitely, with regard to a certain outcome. Such an outcome could be a "score" reflecting an important aspect of the disease (e.g., a disease activity score), or an "event" (e.g., myocardial infarction). Rather than investigating the efficacy of a particular treatment, observational studies serve to investigate clinical associations between different (outcome) variables. Confounding, which may spuriously inflate or reduce the magnitude of a particular association, is an inherent risk in observational studies. The modern analytical approach of an observational study depends on the study question, the study design, and on how the outcome of interest has been assessed. The current article discusses several aspects of the analytical approach and requirements of the database. The focus is on longitudinal analysis, subgroup analysis, and adjustment for confounding. It is concluded that the appropriate analysis of an observational study should be a close collaboration between the clinical researcher with sufficient epidemiological knowledge and the expert statistician with sufficient interest in clinical questions.

Measurement error in the assessment of radiographic progression in rheumatoid arthritis (RA) clinical trials: the smallest detectable change (SDC) revisited.

OBJECTIVES: To evaluate if the mean smallest detectable change (SDC) of multiple time intervals using the Bland & Altman (B&A) levels of agreement (LoA) method is an appropriate surrogate for the generalisability analysis method for estimating the overall SDC of radiological progression in rheumatoid arthritis (RA) trials. Secondly, to compare the SDC based on 95% LoA with the SDC based on 80% LoA, and to investigate the association between SDC and baseline damage and progression. METHODS: Fifteen datasets from randomised controlled trials in RA were scored by 13 experienced readers as pairs according to the modified Sharp/van der Heijde method. The SDC using the 95% and 80% LoA and the generalisability methods was calculated. RESULTS: 21 295 radiographic time points from 7643 patients were included. The mean (range) SDC for the LoA and the generalisability methods was 3.1 (2.3-4.3) and 3.2 (2.3-4.6) units, respectively. The mean ± SD difference between the two methods was -0.13 ± 0.28. The mean SDC including all intervals (n=31) was 3.0 ± 0.7 for 95% LoA and 2.0 ± 0.4 for 80% LoA. No relationship was observed between baseline damage and the SDC, whereas the SDC increased with increasing radiological progression. CONCLUSIONS: The mean of the interval SDCs obtained by the simple LoA method is a valid surrogate for the SDC obtained by complex generalisability methods. The SDC depends on the level of radiographic progression rather than on the level of absolute damage. In addition, the use of an SDC based on 80% rather than on 95% LoA is proposed.

Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study.

OBJECTIVES: To evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPID-axSpA (NCT01087762), an ongoing Phase 3 trial in patients with axial spondyloarthritis (axSpA), including patients with ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA). METHODS: Patients with active axSpA were randomised 1:1:1 to placebo, CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg every 4 weeks (Q4W). In total 325 patients were randomised. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society 20) response at week 12. Secondary outcomes included change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Metrology Index (BASMI) linear. RESULTS: Baseline disease activity was similar between AS and nr-axSpA. At week 12, ASAS20 response rates were significantly higher in CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo (57.7 and 63.6 vs 38.3, p≤0.004). At week 24, combined CZP arms showed significant (p<0.001) differences in change from baseline versus placebo in BASFI (-2.28 vs -0.40), BASDAI (-3.05 vs -1.05), and BASMI (-0.52 vs -0.07). Improvements were observed as early as week 1. Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA subpopulations. Adverse events were reported in 70.4% vs 62.6%, and serious adverse events in 4.7% vs 4.7% of All CZP versus placebo groups. No deaths or malignancies were reported. CONCLUSIONS: CZP rapidly reduced the signs and symptoms of axSpA, with no new safety signals observed compared to the safety profile of CZP in RA. Similar improvements were observed across CZP dosing regimens, and in AS and nr-axSpA patients.

Treating axial and peripheral spondyloarthritis, including psoriatic arthritis, to target: results of a systematic literature search to support an international treat-to-target recommendation in spondyloarthritis.

BACKGROUND: Current recommendations for the management of axial spondyloarthritis (SpA) and psoriatic arthritis are to monitor disease activity and adjust therapy accordingly. However, treatment targets and timeframes of change have not been defined. An international expert panel has been convened to develop 'treat-to-target' recommendations, based on published evidence and expert opinion. OBJECTIVE: To review evidence on targeted treatment for axial and peripheral SpA, as well as for psoriatic skin disease. METHODS: We performed a systematic literature search covering Medline, Embase and Cochrane, conference abstracts and studies in http://www.clinicaltrials.gov. RESULTS: Randomised comparisons of targeted versus routine treatment are lacking. Some studies implemented treatment targets before escalating therapy: in ankylosing spondylitis, most trials used a decrease in Bath Ankylosing Spondylitis Disease Activity Index; in psoriatic arthritis, protocols primarily considered a reduction in swollen and tender joints; in psoriasis, the Modified Psoriasis Severity Score and the Psoriasis Area and Severity Index were used. Complementary evidence correlating these factors with function and radiographic damage at follow-up is sparse and equivocal. CONCLUSIONS: There is a need for randomised trials that investigate the value of treat-to-target recommendations in SpA and psoriasis. Several trials have used thresholds of disease activity measures to guide treatment decisions. However, evidence on the effect of these data on long-term outcome is scarce. The search data informed the expert committee regarding the formulation of recommendations and a research agenda.

Which spinal lesions are associated with new bone formation in patients with ankylosing spondylitis treated with anti-TNF agents? A long-term observational study using MRI and conventional radiography.

OBJECTIVE: To study the relationship of spinal inflammation and fatty degeneration (FD) as detected by MRI and new bone formation seen on conventional radiographs (CRs) in ankylosing spondylitis (AS). METHODS: CRs at baseline, 2 years and 5 years and spinal MRIs at baseline and 2 years of 73 AS patients treated with infliximab in European AS Infliximab Cohort were available. Relative risks (RR) were calculated with a general linear model after adjustment for within-patient variation. RESULTS: In a total of 1466 vertebral edges (VEs) without baseline syndesmophytes, 61 syndesmophytes developed at 5 years, the majority of which (57.4%) had no corresponding detectable MRI lesions at baseline. VEs with both inflammation and FD at baseline had the highest risk (RR 3.3, p=0.009) for syndesmophyte formation at 5 years, followed by VEs that developed new FD or did not resolve FD at 2 years (RR=2.3, p=0.034), while inflammation at baseline with no FD at 2 years had the lowest risk for syndesmophyte formation at 5 years (RR=0.8). Of the VEs with inflammation at baseline, >70% resolved completely, 28.8% turned into FD after 2 years, but only 1 syndesmophyte developed within 5 years. CONCLUSIONS: Parallel occurrence of inflammation and FD at baseline and development of FD without prior inflammation after 2 years were significantly associated with syndesmophyte formation after 5 years of anti-tumour necrosis factor (TNF) therapy. However, the sequence 'inflammation-FD-new bone formation' was rarely observed, an argument against the TNF-brake hypothesis. Whether an early suppression of inflammation leads to a decrease of the risk for new bone formation remains to be demonstrated.

Comparison of characteristics of international and national databases for rheumatoid arthritis: a systematic literature review.

OBJECTIVES: To evaluate current (inter)national registers and observational cohorts in Europe, and to compare inclusion criteria, aims, collected data, and participation in the European League Against Rheumatism (EULAR) repository. METHOD: We performed a systematic search strategy in six literature databases for rheumatoid arthritis (RA). Publications reporting European (inter)national prospective registers/cohorts including > 200 RA patients with at least half a year of follow-up were selected. RESULTS: In total, 417 articles and abstracts were included from four international databases and 39 national databases/cohorts. International databases were of similar design, frequency of data collection and selection criteria and are mostly initiated to monitor and compare clinical patient care among countries. National databases/cohorts vary in aims and inclusion criteria. Half of the national registers are connected to the EULAR repository of databases. CONCLUSIONS: Our findings indicate that, among researchers, there is little awareness of guidelines to set up registers or cohorts and of the existence of the database collaboration network of EULAR.

Optimisation of rheumatic disease assessments in clinical trials, clinical care, and long-term databases.

The assessment of disease in rheumatological diseases is rather complicated, because it may involve different contexts (clinical practice, clinical trials, observational studies, registries, etc.) as well as different domains (disease activity, physical function, radiographic damage, quality of life, etc.). Furthermore, available tools can be comprehensive but also rather condense, may be patient-oriented or rather physician-oriented, and so on. In this article all these levels that may matter in case of a choice of disease assessment tool are discussed, arriving at a conclusion that choosing the appropriate tool for the assessment of disease is not 'cookbook medicine'.

The METEOR initiative: the way forward for optimal, worldwide data integration to improve care for RA patients.

OBJECTIVES: The METEOR (Measurement of Efficacy of Treatment in the 'Era of Outcome' in Rheumatology) initiative aims at improving care for RA patients by assisting rheumatologists in strict monitoring and tight control of disease activity. The state of the art of the METEOR initiative, the technical organisation of the database and future perspectives are described. METHODS: RA patients are followed in the daily practice setting; (follow-up) visits are registered via the tool or upload facility. The METEOR tool is an easy-to-use, stand-alone, web-based program free available to rheumatologists worldwide. The upload facility is developed to meet the wish of many local registries to upload their data into the METEOR database to benefit from benchmark and research facilities without giving up their own registries. Rheumatologists will always have access to full patient details of their own patients. Yet, patient identifying data are stored in an encrypted manner in the METEOR database in order to provide full patient anonymity to all other users. RESULTS: While the tool can be used without IT involvement, the upload facility requires IT support. The incorporation of local registries into the METEOR database is time consuming, requires endeavours as well as technical support of both the local registries and the METEOR organisation, however, the combination of the tool and the upload facility has enabled the successful creation of a strong research database with real life data of 35,000 RA patients with more than 140,000 visits from all over the world! CONCLUSIONS: The METEOR database offers the unique opportunity to study daily practice care as well as dedicated research questions in worldwide real life setting. Moreover, the METEOR's collective experience can be accessed by those who think about initiating patient registries for all sorts of purposes. Consequently, these well-designed registries may help in treating RA patients even more successfully in future.

Gadolinium contrast-enhanced MRI sequence does not have an incremental value in the assessment of sacroiliitis in patients with early inflammatory back pain by using MRI in combination with pelvic radiographs: a 2-year follow-up study.

OBJECTIVES: To evaluate the potential incremental value in detecting sacroiliitis of the T1 post-gadolinium diethylenetriaminepenta-acetic acid (Gd-DTPA) MRI sequence of the sacroiliac joints (SIJ) compared with the combination of short tau inversion recovery (STIR) MRI sequence and pelvic radiographs in patients with inflammatory back pain (IBP) suspected for axial spondyloarthritis. METHODS: A 2-year follow-up study was conducted in patients with IBP of less than 2 years duration. Annual MRI of the SIJ (MRI-SIJ) was performed and scored for bone marrow oedema (BME). Pelvic radiographs were scored according to the modified New York (mNY) criteria. Agreement on the presence of BME detected by the STIR and post-Gd-DTPA sequence and the incremental value of post-Gd-DTPA sequence over STIR plus radiographs was analysed by descriptive methods and kappa statistics. RESULTS: At baseline, 20 (29%) out of 68 patients (38% male; mean (SD) age 34.9 (10.3) years) enrolled had BME both on the STIR and post-Gd-DTPA sequences; 4 patients (6%) on the STIR sequence only; none on the post-Gd-DTPA sequence only (kappa value: 0.87). Fifteen (22%) patients fulfilled the mNY criteria at baseline. Sixty-two (91%) patients had at least 1 follow-up MRI-SIJ. At 2-year follow-up, 2 patients had BME on the post-Gd-DTPA sequence without BME on the STIR sequence. These 2 patients already fulfilled the mNY criteria at baseline. CONCLUSIONS: In this cohort of patients with early IBP, the post-Gd-DTPA sequence of the MRI-SIJ did not have an incremental value in the detection of sacroiliitis compared with the STIR sequence plus pelvic radiographs.

European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies.

BACKGROUND: Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD). METHODS: The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement. RESULTS: Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extra-articular manifestations of PsA. Five overarching principles and a research agenda were defined. CONCLUSION: These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.

HLA-B27 and gender independently determine the likelihood of a positive MRI of the sacroiliac joints in patients with early inflammatory back pain: a 2-year MRI follow-up study.

OBJECTIVES: To describe how inflammation on MRI of the sacroiliac joints in patients with recent-onset inflammatory back pain (IBP) evolves over time, and to study determinants of activity on MRI of the sacroiliac joint. METHODS: A 2-year follow-up study with annual MRI of the sacroiliac joints was conducted in patients with IBP of less than 2 years' duration. Images were scored for bone marrow oedema on short τ inversion recovery and enhancement after administration of gadolinium on T1. RESULTS: Of the 68 patients (38% male; mean age 34.9 ± 10.3 years) enrolled, 44 had a negative baseline MRI. Of these 44 patients, 39 patients had at least one follow-up MRI of whom six patients (15%) developed activity on MRI during follow-up. 24 patients (35%) had an abnormal MRI at baseline. In 23 of these 24 patients follow-up MRI was available. The MRI became negative in seven of these 23 patients (30%) during follow-up. Human leucocyte antigen B27 (HLA-B27) positivity and male gender determined independently the likelihood of a positive MRI at any time point. In an HLA-B27-positive patient the likelihood of a positive MRI during follow-up is 88% if the baseline MRI is positive and 27% if the baseline MRI is negative. In an HLA-B27-negative patient with a negative MRI at baseline the likelihood of a positive MRI during follow-up is less than 5%. CONCLUSIONS: A positive MRI at baseline predicts a positive MRI during follow-up in HLA-B27-positive patients. A negative MRI at baseline in HLA-B27-negative patients strongly predicts a negative MRI during follow-up.

The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general.

OBJECTIVE: To evaluate new classification criteria for peripheral spondyloarthritis (SpA) in patients with SpA with peripheral manifestations only. METHODS: In this Assessment of SpondyloArthritis international Society (ASAS) study, two prespecified sets of criteria were compared against the European Spondylarthropathy Study Group (ESSG) and Amor criteria in newly referred consecutive patients with undiagnosed peripheral arthritis, and/or enthesitis, and/or dactylitis that usually began before 45 years of age. The clinical diagnosis (SpA vs no SpA) made by the ASAS rheumatologist served as reference standard. RESULTS: In all, 24 ASAS centres included 266 patients, with a final diagnosis of SpA being made in 66.2%. After adjustments a final set of criteria showed the best balance between sensitivity (77.8%) and specificity (82.9%): arthritis and/or enthesitis and/or dactylitis plus (A) one or more of the following parameters: psoriasis, inflammatory bowel disease, preceding infection, human leucocyte antigen B27, uveitis, sacroiliitis on imaging, or (B) two or more other parameters: arthritis, enthesitis, dactylitis, inflammatory back pain in the past, family history of SpA. The new criteria performed better than modified versions of the ESSG (sensitivity 62.5%, specificity 81.1%) and the Amor criteria (sensitivity 39.8%, specificity 97.8%), particularly regarding sensitivity. In the entire ASAS population of 975 patients the combined use of ASAS criteria for axial SpA and ASAS criteria for peripheral SpA also had a better balance (sensitivity 79.5%, specificity 83.3%) than the modified ESSG (sensitivity 79.1%, specificity 68.8%) and Amor criteria (sensitivity 67.5%, specificity 86.7%), respectively. CONCLUSIONS: The new ASAS classification criteria for peripheral SpA performed well in patients presenting with peripheral arthritis, enthesitis and/or dactylitis.

Multinational evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative.

OBJECTIVE: To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). METHODS: 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 39,756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA. CONCLUSIONS: Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.

The European ankylosing spondylitis infliximab cohort (EASIC): a European multicentre study of long term outcomes in patients with ankylosing spondylitis treated with infliximab.

OBJECTIVES: To study the long-term efficacy and safety of treatment with infliximab in patients with ankylosing spondylitis (AS) in a real life setting. METHODS: AS patients from 6 European countries who had finished the 2-year trial ASSERT were invited to participate in the open- label investigator-driven study EASIC. At baseline, 2 groups were formed: patients of group 1 had not been treated with infliximab after ASSERT, while those of group 2 had continuously received it. Patients of group 1 were further subdivided in group 1a: patients with a relapse and 1b: in remission. All patients of group 1a and 2 continuously received infliximab for 96 weeks, mean dose 5 mg/kg, intervals 6-8 weeks. Patients of group 1b were also treated in case of relapse. RESULTS: A total of 103/149 patients (69%) were included in EASIC, 1.3 ± 0.9 years after the end of ASSERT: 9 in group 1a, 5 in group 1b and 89 in group 2. Most patients were male (83%), mean age 44 years. Most patients of group 2 completed the trial (86%) vs. only 5 of group 1 (33%) - mostly due to allergic reactions after readministration of infliximab. In total, there were 22 drop-outs due to 6 adverse events, 4 lack of efficacy, 3 planned pregnancy. All standard assessments indicated beneficial values over time, at week 96 significantly better than at baseline of ASSERT. CONCLUSIONS: The majority of patients were continuously and successfully treated with infliximab for 5 years, whereas discontinuation and reintroduction of therapy was less satisfactory due to the frequent occurrence of hypersensitivity reactions. Anti-TNF therapy with infliximab proved to be effective and safe on a long-term basis.