Adrien Etcheto

Prevalence of comorbidities and evaluation of their screening in spondyloarthritis: results of the international cross-sectional ASAS-COMOSPA study

Background Increased risk of some comorbidities has been reported in spondyloarthritis (SpA). Recommendations for detection/management of some of these comorbidities have been proposed, and it is known that a gap exists between these and their implementation in practice. Objective To evaluate (1) the prevalence of comorbidities and risk factors in different countries worldwide, (2) the gap between available recommendations and daily practice for management of these comorbidities and (3) the prevalence of previously unknown risk factors detected as a result of the present initiative. Methods Cross-sectional international study with 22 participating countries (from four continents), including 3984 patients with SpA according to the rheumatologist. Statistical analysis The prevalence of comorbidities (cardiovascular, infection, cancer, osteoporosis and gastrointestinal) and risk factors; percentage of patients optimally monitored for comorbidities according to available recommendations and percentage of patients for whom a risk factor was detected due to this study. Results The most frequent comorbidities were osteoporosis (13%) and gastroduodenal ulcer (11%). The most frequent risk factors were hypertension (34%), smoking (29%) and hypercholesterolaemia (27%). Substantial intercountry variability was observed for screening of comorbidities (eg, for LDL cholesterol measurement: from 8% (Taiwan) to 98% (Germany)). Systematic evaluation (eg, blood pressure (BP), cholesterol) during this study unveiled previously unknown risk factors (eg, elevated BP (14%)), emphasising the suboptimal monitoring of comorbidities. Conclusions A high prevalence of comorbidities in SpA has been shown. Rigorous application of systematic evaluation of comorbidities may permit earlier detection, which may ultimately result in an improved outcome of patients with SpA.

Clinical presentation of patients suffering from recent onset chronic inflammatory back pain suggestive of spondyloarthritis: The DESIR cohort

OBJECTIVES DESIR is a prospective longitudinal multicentric French cohort of patients with inflammatory back pain suggestive of spondyloarthritis, with a 10-year-follow-up. The purpose is to evaluate the performances of the different sets of classification criteria for axial spondyloarthritis, and to describe the frequency and characteristics of the clinical features of axial spondyloarthritis. METHODS Demographic data and items allowing classification and indices calculation were collected, as well as biologic and imaging data. Baseline data are analyzed. The performance of the several classification criteria sets was evaluated (likelihood ratio) with the physicians diagnosis as external gold standard. For the clinical presentation of axial spondyloarthritis, a descriptive analysis was conducted. RESULTS Seven hundred and eight patients are included. Ninety-two percent of them satisfy at least one set of classification criteria: mNY 26%, Amor 79%, ESSG 78%, ASAS 70%; physicians confidence level 6.8±2.7. 81 and 83% of patients fulfil modified (including MRI) Amor or ESSG criteria. Axial involvement is present in 100% of the cases. NSAIDs are taken by 90%, with an NSAID sore of 50±46. BASDAI over 40 is noted in 60% and elevated CRP in 30% of the cases. HLA-B27 is present in 58%. According to ASDAS CRP levels, 12.7% are in inactive disease, 63% in high disease activity; mean BASFI was 30. Peripheral involvement is present in 57%, with arthritis in 37% of these. Enthesitis is noted in 49% of the patients, and first symptom in 22.5%; anterior chest wall involvement is noted in 44.6%, and dactylitis in 13%. For extra articular manifestations, psoriasis is recorded in 16%, uveitis in 8.5% and IBD in 5.1%. Smoking is present in 36.3% and hypertension in 5.1% of the cases. CONCLUSION These data represent the base of evaluation of the follow-up of this cohort, allowing future specific studies.

Evaluation of serum interleukin-6 level as a surrogate marker of synovial inflammation and as a factor of structural progression in early rheumatoid arthritis: results from a French national multicenter cohort.

Interleukin‐6 (IL‐6) is a key cytokine in rheumatoid arthritis pathogenesis. We aimed to analyze the association between IL‐6 serum levels and joint inflammation at baseline and the correlation of time‐integrated IL‐6 values with structural damage during the first 36 months of early arthritis.

Preliminary definitions of ‘flare’ in axial spondyloarthritis, based on pain, BASDAI and ASDAS-CRP: an ASAS initiative

Introduction Flares may be used as outcomes in axial spondyloarthritis (axSpA) trials or observational studies. The objective was to develop a definition for ‘flare’ (or worsening) in axSpA, based on validated composite indices, to be used in the context of clinical trial design. Methods (1) Systematic literature review of definitions of ‘flare’ in published randomised controlled trials in axSpA. (2) Vignette exercise: 140 scenarios were constructed for a typical patient with axSpA seen at two consecutive visits. Each scenario included a change in one of the following outcomes: pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI plus C-reactive protein (CRP) or Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP. Each Assessment of Spondyloarthritis (ASAS) expert determined if every scenario from a random sample of 46 scenarios was considered a flare (yes/no). Receiver-operating characteristic (ROC) analyses were applied to derive optimal cut-off values. (3) ASAS consensus was reached. Results (1) The literature review yielded 38 studies using some definition of ‘flare’, with 27 different definitions indicating important heterogeneity. The most frequent definitions were based on BASDAI changes or pain changes. (2) 121 ASAS experts completed 4999 flare assessments. The areas under the ROC curves were high (range: 0.88–0.89). Preliminary cut-offs for pain (N=3), BASDAI (N=5) and ASDAS-CRP (N=4) were chosen, with a range of sensitivity 0.60–0.99 and range of specificity 0.40–0.94 against the experts opinions. Conclusions This data-driven ASAS consensus process has led to 12 preliminary draft definitions of ‘flare’ in axSpA, based on widely used indices. These preliminary definitions will need validation in real patient data.

Impaired quality of life in adults with X-linked hypophosphatemia and skeletal symptoms

OBJECTIVE Adults with X-linked hypophosphatemia (XLH) may suffer from skeletal symptoms leading to functional disability. No data on their quality of life (QoL) have been reported so far. Our objectives were to evaluate the QoL and its determinants in XLH adults. PATIENTS AND METHODS We conducted a prospective study in XLH adults, who consulted for musculoskeletal symptoms between 2013 and 2014. We assessed their QoL using HAQ, RAPID3 and SF36, and analysed the variables associated with low QoL. We compared their QoL to that of patients affected with axial spondyloarthritis (ax-SpA) (paired on age and gender), a rheumatologic disorder with a known low QoL. RESULTS Fifty-two XLH adults (37 women (71.1%); mean age 41.8±13.3 years) were included; 44 (84.6%) patients had an altered QoL. Increased age and presence of structural lesions were significantly associated with worse QoL (HAQ, RAPID3) (P<0.05). Presence of enthesopathies was significantly associated with worse RAPID3 (OR=4.45 (1.09-18.29), P=0.038). Treatment with phosphate supplements and vitamin D in XLH adults were significantly associated with a better SF36-mental component score (OR=0.14 (0.03-0.57), P=0.007 and OR=0.26 (0.07-0.98), P=0.047 respectively). QoL was significantly worse in XLH than in ax-SpA adults (VAS pain, SF36-PCS, RAPID3) (P<0.05). CONCLUSION Our study showed i) QoL of XLH adults is altered and significantly worse than that of ax-SpA patients (VAS pain, SF36-PCS and RAPID3), ii) structural lesions and especially enthesopathies are associated with a worse QoL and iii) treatment using phosphate supplements and/or vitamin D is associated with a better mental health score.

Systematic switch from Innovator Infliximab to Biosimilar Infliximab in Inflammatory Chronic Diseases in Daily Clinical Practice: The Experience of Cochin University Hospital, Paris, France

OBJECTIVE To investigate effectiveness of systematic switching treatment from innovator infliximab to biosimilar infliximab, and its associated factors. METHODS In this prospective observational study, all adult patients receiving maintenance therapy with innovator infliximab in Cochin University Hospital were systematically switched to biosimilar infliximab. Effectiveness was assessed by the retention rate of biosimilar infliximab at the time of the third infusion. Sensitivity analyses for effectiveness included changes of disease activity parameters and infliximab trough levels between baseline and the last visit as well as the occurrence of adverse events leading to drug discontinuation. Factors associated with biosimilar infliximab discontinuation at the last visit were explored. RESULTS A total of 260 patients fulfilled the inclusion criteria, including 31 rheumatoid arthritis (RA), 131 axial spondyloarthritis (axSpA) and 64 inflammatory bowel diseases. The retention rate was 85% (221/260 patients) at the time of the third biosimilar infusion. Between baseline and the last visit (mean follow-up of 34 weeks), 59 patients (23%) discontinued biosimilar infliximab, mainly due to experienced inefficacy (n = 47, 80%). No clinical or biological factors were associated with biosimilar discontinuation. No serious adverse events occurred. No change in objective disease activity parameters or infliximab trough levels was detected. However, a significant increase of BASDAI (2.94 ± 2.20 vs. 3.18 ± 2.21, P = 0.046, before vs. after switch, respectively) was observed in patients with axSpA. Innovator infliximab was re-established in 47/59 patients (80%). CONCLUSION No changes in drug trough levels or objective parameters were observed after the systematic switch to biosimilar infliximab in a real clinical practice setting. Only changes in patient-reported outcomes were observed, suggesting attribution effects rather than pharmacological differences.

Evaluation of the impact of concomitant fibromyalgia on TNF alpha blockers’ effectiveness in axial spondyloarthritis: results of a prospective, multicentre study

Objective To describe the prevalence of fibromyalgia (FM) in an axial spondyloarthritis (axSpA) population and to confirm that concomitant FM had a negative impact on tumour necrosis factor blockers’ (TNFb) response. Design Prospective observational study with two visits 3 months apart. Patients Adult patients with AxSpa initiating a TNFb. Study groups FM was defined by the Fibromyalgia Rapid Screening Tool (FiRST) at baseline and also by a sustained positive FiRST (both visits) and by a fulfilment of the 1990 American College of Rheumatology criteria for FM. Statistical analysis Prevalence of FM; evaluation of the impact of a concomitant FM on TNFb response (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50) as primary endpoint), adjusted by factors known to have an impact on TNFb response. Results Among the 508 patients included in the main analysis, 192 (37.8%) were screened at baseline as FM. Percentage of success after 12 weeks of treatment was lower in the FM group for most of the effectiveness endpoints (eg, BASDAI 50: 45.3% vs 54.1% in the FM/not FM groups according to the FiRST), except for the C reactive protein change endpoints which were not different across groups. Conclusion This study confirms that FM coexists in patients with axSpA and that its presence seems to have a negative impact on TNFb response, which seems more related to the self-reported instruments used in its evaluation, rather than a different treatment effect of the molecule in this subgroup of patients.

Bone loss in patients with early inflammatory back pain suggestive of spondyloarthritis: results from the prospective DESIR cohort

OBJECTIVES The objectives of the study were to assess the 2 year BMD changes and their determinants in patients with early inflammatory back pain suggestive of axial spondyloarthritis (SpA) (DESIR cohort). METHODS A total of 265 patients (54% male, mean age 34.4 years) had BMD measurements at baseline and at 2 years. Low BMD was defined as a Z score ≤-2 (at at least one site) and significant bone loss was defined by a decrease in BMD ≥0.03 g/cm(2). Clinical, biological and imaging parameters were assessed over 2 years. RESULTS Thirty-nine patients (14.7%) had low BMD at baseline; 112 patients (42.3%) had a 2 year significant bone loss. One hundred and eighty-seven (70.6%) used NSAIDs at baseline and 89 (33.6%) received anti-TNF therapy over 2 years. In anti-TNF users, BMD significantly increased at the lumbar spine and did not change at the hip site from baseline. In multivariate analysis, baseline use of NSAIDs [odds ratio (OR) 0.38, P = 0.006] had a protective effect on hip bone loss. In patients without anti-TNF treatments, baseline use of NSAIDs (OR 0.09, P = 0.006) and a 2 year increase in BMI (OR 0.55, P = 0.003) had protective effects on hip bone loss, whereas a 2 year increase in fat mass was associated with hip bone loss (OR 1.18, P = 0.046). CONCLUSION Among patients with symptoms suggestive of early axial SpA, 42.3% of patients have significant bone loss over 2 years. Anti-TNF therapy is protective against bone loss and baseline use of NSAIDs has a protective effect on hip bone loss.

A New Correction for Multiple Testing in Gene–Gene Interaction Studies

A major problem in gene–gene interaction studies in large marker panels is how to correct for multiple testing while accounting for the dependence between marker pairs due to the presence of linkage disequilibrium. The “gold standard” approach is to perform permutations of case/control labels. However, this is often not feasible in practice, due to computational demands. Here, we propose a correction based on the effective number of independent tests of interaction between marker pairs. This number depends on the effective number of independent single‐marker tests. We tested its validity using simulated samples, as well as that of another correction of marker pair tests. We showed that our approach was valid while the other correction strongly underestimated the effective number of independent tests. Our method provides estimates of the effective number of independent tests close to those reported in the literature for a Genome‐Wide Interaction Study on a 550K chip. Our correction method is quick and simple, and can be applied whatever the marker panel and the underlying linkage disequilibrium pattern.

Imaging findings suggestive of axial spondyloarthritis in diffuse idiopathic skeletal hyperostosis

To describe the magnetic resonance imaging (MRI) findings in diffuse idiopathic skeletal hyperostosis (DISH) patients and to assess the proportion of DISH patients whose MRI findings would fulfill the Assessment of Spondyloarthritis International Society (ASAS) criteria for a positive MRI of axial spondyloarthritis (SpA).