Search

Objectives: To investigate whether HLA alleles, other than HLA-B27, influence predisposition to spondyloarthropathy (SpA) in multiplex families.Methods: Seventy French families with at least two affected SpA members were recruited. Patients, and their first degree relatives were typed for HLA-A, B, C, and DR, and extended HLA haplotypes were determined. The distribution of HLA-A, C, and DR alleles carried on HLA-B27+ haplotypes in SpA families was compared with the distribution of these alleles among HLA-B27+ haplotypes in the French general population. Contribution to SpA susceptibility of HLA-A, B, C, and DR alleles, other than HLA-B27, was tested by transmission disequilibrium test. The contribution of HLA alleles to specific presentation features of SpA was examined.Results: Frequencies of HLA-A, C, and DR alleles carried on HLA-B27+ haplotypes from SpA families were comparable with those seen in the French population, except for DR13 which was overrepresented among patients (pcorr<0.001). Most interestingly, the HLA-DR4 allele was transmitted in excess to patients with SpA, independently of linkage to HLA-B27 (pcorr=0.05), and in a direction opposite to that for HLA-B27+ unaffected siblings (pcorr=0.01). Finally, the distribution of HLA alleles was not related to the presentation feature of SpA.Conclusion: HLA predisposition to familial SpA appears not to be limited to HLA-B27, but some HLA-DR alleles also have a significant influence. In particular, HLA-DR4 contributes significantly to a genetic predisposition to SpA, which may have implications in our understanding of SpA pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: To explore how patients with chronic inflammatory rheumatic diseases (CIRDs) coped with their disease during the COVID-19 pandemic and to identify possible predictive factors of SARS-CoV-2 infection in this population., Methods: Patients followed in a single rheumatology department in France or registered on the Spondy+ platform, a secure e-health platform for spondyloarthritis patients, were invited to complete a questionnaire focused on their experiences around COVID19 symptoms, testing and medications access during the lockdown period. Descriptive statistics were used to report questionnaire's results. Factors associated with COVID-19 or with treatment discontinuation were assessed by logistic regression., Results: We obtained 655 answers from the 2,081 contacted patients: 474 with spondyloarthritis, 129 with rheumatoid arthritis and 52 with psoriatic arthritis. The population was predominantly female (61.8%) with a mean age of 51.0±13.4 years. Incidence of COVID-19 was 6.9% (95%CI: 5.1-9.2%), including 12 confirmed and 33 highly suspicious cases. No death was observed and five patients needed to be hospitalized. Factors independently associated with an increased risk of infection were SARS-CoV-2 exposure, younger age and non-smoking. More than 30% of the patients suspended or decreased the dosage of one of their drugs during the lockdown period. This was followed in 63.4% of them by increased disease activity. Modifications were mostly motivated by fear of contagion (79.3%)., Conclusion: We did not observe any increase of incidence or severity of COVID-19 in patients suffering of the 3 most common CIRDs. This survey also adds evidence of the safety of anti-rheumatic drugs use regarding COVID-19., (Copyright © 2020 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objective: The contribution of environmental factors to spondyloarthritis (SpA) course remains poorly characterized. We previously reported a possible triggering of disease flares by stressful life events and vaccination. The objective of the present study was to specify the types of vaccine and life event that may influence disease activity., Methods: A prospective cohort of adult SpA was followed for two years. Patients logged on to a secured website every month to complete a standardized auto-questionnaire. They reported whether they had been exposed to stressful life events, vaccinations or other environmental factors. Patients were asked to rate the distress resulting from exposure to life events on a numerical rating scale (NRS: 0-10). Primary outcome variable was the variation of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) measured on two consecutive connections. Months where an event occurred were compared to months without events. The cut-off value of 1 is defined as the minimal clinically important variation for the BASDAI., Results: The 272 enrolled SpA patients returned 3,388 questionnaires. Months where an abrupt and unexpected traumatic event occurred were associated with a significant increase of BASDAI of 0.57 [95%CI: 0.29; 0.85] (P<0.001). The higher the rating of distress, the larger the impact on BASDAI, reaching a clinically meaningful increase of 0.99 [0.17; 1.82] for a VNS≥9. The effect of stressful events on BASDAI persisted during a median of 3 months. No other environmental factor was significantly associated with BASDAI variations., Conclusion: Among stressful life events, abrupt and unexpected events were associated with transient worsening of disease activity in SpA, which reached a clinically meaningful increase for the highest rating of distress. Association between vaccines and disease flare was not confirmed., (Copyright © 2018 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: To estimate the number of patients with severe spondyloarthritis (SpA) in France, describe their comorbidities and document and value their healthcare resource consumption., Methods: Data were retrieved from an insurance claims database covering a 1/97 random sample of the French population. All patients benefiting from full insurance coverage ("ALD") for severe SpA in 2012 (including cases with structural damage and/or frequent flares) were identified, together with a control group frequency-matched by age and gender. Severe comorbidities were documented through ALD categories. Healthcare resource consumption was documented and valued from the payer's perspective. Rates of comorbidities and costs were compared in SpA patients versus controls using non-parametric testing., Results: Overall, 827 patients with ALD status for severe SpA were identified (control group: n=2.481), corresponding to a prevalence rate of 0.18% [0.17-0.19] for SpA with ALD in the general population. Severe comorbidities more frequent in patients with SpA than in controls included inflammatory bowel disorders (odds ratio: 15.0 [6.2-36.2]), hypertension (2.5 [1.6-3.9]), atrial fibrillation (4.3 [1.9-9.6]) and major depressive disorder (2.1 [1.3-3.6]). Mean per capita annual direct healthcare expenditure was 3.6 [3.2-4.1]-fold higher in SpA patients (€6,122 [€5,838-€6,406]) than in controls (€1,682 [€1,566-€1,798]). Extrapolating to all patients in France, total healthcare cost attributable to severe SpA patients was €391 [€355-€426] million, with medication accounting for 53.8% of this cost., Conclusions: The burden of severe SpA in France is substantial, due to the high prevalence, high direct costs and associated comorbidities., (Copyright © 2018. Published by Elsevier Masson SAS.)

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 physician's 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%; physician's 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., (Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: To estimate the prevalence of spondyloarthritis (SpA) in reference to HLA-B27 in the French population., Methods: In 1989, 20 625 employees of the French national gas and electricity company aged 35-50 years were enrolled in the GAZEL cohort. In 2010, 18 757 still active participants were screened by a questionnaire validated for the detection of SpA. Responders with available DNA were retained for further studies. Pelvic radiograph and HLA-B27 typing were performed in all the self-reported cases of SpA or psoriatic arthritis. Self-reported diagnosis was verified by a qualified rheumatologist. HLA-B27 determination was also performed in subjects without any SpA feature., Results: The target population consisted of 6556 responders with available DNA. Their male:female ratio was 3.6 and their mean age was 65.5±3.3 years. A diagnosis of SpA was confirmed in 32 of the 72 self-reported cases, 75% of them being HLA-B27 positive. Estimated SpA prevalence adjusted for sex was 0.43% (95% CI 0.26% to 0.70%). HLA-B27 positivity rate in 2466 healthy controls was 6.9% (95% CI 5.9% to 7.9%). The relative risk of SpA in HLA-B27 positive individuals was 39 (95% CI 17 to 86)., Conclusions: We estimated the prevalence of SpA in the French population in 2010 to 0.43%. With an estimated prevalence of 75.0% in SpA and 6.9% in healthy controls, HLA-B27 increased the disease risk 39-fold, as compared with HLA-B27 negative subjects., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: Spondyloarthritis (SpA) is a group of inflammatory articular disorders sharing a genetic background. The nonsynonymous single-nucleotide polymorphism (SNP) rs11209026 (Arg381Gln) in the IL23R gene has reproducibly been shown to be associated with ankylosing spondylitis (AS). We undertook this study to examine the association between rs11209026 and SpA as a whole, with particular attention devoted to genotype/phenotype correlation., Methods: The SNP rs11209026 was genotyped in a French cohort of 415 patients/372 controls, with replication analysis performed in 383 "trios," each consisting of 1 patient with SpA and both parents. Association analysis was carried out in SpA as a whole group and then separately in AS and non-AS patients. Phenotype/genotype correlations were examined using logistic regression analysis., Results: A significant association between rs11209026 and SpA overall was identified only in the familial data set (odds ratio 0.57, P=0.028). Strong association with AS was observed in both the case-control and familial data sets (P=4.5×10(-4) and P=4.0×10(-3), respectively). In contrast, such association was not detected in the non-AS group. Furthermore, rs11209026 frequency was significantly different between AS and non-AS patients (P=1.5×10(-3)). Phenotype/genotype correlation study revealed that both radiographic sacroiliitis and early age at onset were independently associated with a lower frequency of the rare protective rs11209026 allele A in patients (P=9×10(-3) and P=8×10(-3), respectively)., Conclusion: Our study replicated the robust association between rs11209026 and AS in the French population. However, such association was restricted to AS, as compared to SpA without radiographic sacroiliitis. The fact that it was independently conditional on radiographic sacroiliitis and age at onset suggests that rs11209026 could affect disease severity rather than susceptibility., (Copyright © 2013 by the American College of Rheumatology.)

Objective: A robust association between polymorphisms in the non-major histocompatibility complex gene ERAP1 and ankylosing spondylitis (AS) in several populations was recently identified. The aim of the current study was to determine the level of association of ERAP1 polymorphisms with spondyloarthritis (SpA) in French/Belgian populations with particular attention to genotype-phenotype correlations., Methods: We studied 734 independent SpA cases and 632 controls from two European cohorts. Five single-nucleotide polymorphisms (SNPs), rs27044, rs17482078, rs10050860, rs30187 and rs2287987 were genotyped, and case-control association analyses were carried using PLINK 1.07 software. Linkage disequilibrium and haplotypes were estimated with Haploview. Analysis was first carried out in SpA as a whole group, and then separately in AS and non-radiographic SpA (non-AS) patients., Results: Consistent with previous studies conducted in AS, rs30187 was the most significantly associated SNP with SpA (p=0.008 in the French, and p=6.46×10(-4) in the Belgian cohorts). In the combined cohorts, this SNP was associated with both AS and non-AS (P(combined)= 3.9×10(-5) and P(combined)= 0.005, respectively). A similar trend was observed with other SNPs. The rs17482078/rs10050860/rs30187-CCT haplotype was significantly associated with increased risk of SpA in both cohorts (P(combined)= 9.08×10(-4)), including AS and non-AS (P(combined)=6.16×10(-4) and P(combined)=0.049, respectively), whereas the -TTC haplotype was associated with reduced risk of SpA, including AS and non-AS (P(combined)=2.36×10(-7), P(combined)= 5.69×10(-6) and P(combined)= 2.13×10(-4), respectively)., Conclusions: This is the first study to show an association between several polymorphisms located in ERAP1 and SpA as a whole. Our findings demonstrate consistent association of the same SNPs and haplotypes with both AS and non-AS subtypes of SpA.

Unlabelled: Power Doppler ultrasound (PDUS) has proved to be a highly sensitive tool for assessing enthesitis in spondyloarthritis (SpA). In patients with a suspected SpA, diagnosis could be improved by detecting enthesitis with PDUS., Objective: To evaluate the performance of PDUS for the diagnosis of SpA alone or combined with other clinical, laboratory and imaging findings in patients consulting for a suspected SpA., Methods: Prospective, multicenter French cohort study (Boulogne-Billancourt, Brest, Caen, Grenoble, Marseille and Nancy). Outpatients consulting for symptoms suggestive of SpA (inflammatory back pain [IBP], arthritis or inflammatory arthralgia [IA], enthesitis or dactylitis [ED], HLA-B27 positive uveitis [B27+U], familiarity for SpA [Fam]) were recruited and followed up for at least 2 years. Sample size was set to 500 patients (for estimated prevalence of SpA of 30±5% after 2 years). At baseline, patients were submitted to standardized physical examination, pelvic X-ray, sacroiliac joints magnetic resonance imaging (MRI), HLA-B typing, and other tests judged useful for diagnosis. For each patient, a blinded PDUS examination of 14 enthesitic sites was performed at baseline and at years 1 and 2. Patients were planned to be followed during 5 years. The diagnosis of SpA ascertained by an experts' committee, blind to PDUS results, after at least 2 years of follow-up, with a revaluation of doubtful patients at 5 years will be used as gold standard for evaluating the diagnostic performance of PDUS and the best diagnostic procedure by combining PDUS, clinical symptoms and other tests., Results: Between January 2005 and September 2007, 489 patients were included (96% of the target population). Nineteen patients (0.2%) retired their informed consensus or were lost to follow-up immediately after their inclusion. At baseline, mean age of the 470 remaining patients was 40 years, mean duration of symptoms was 6.1 years; 42% of them were HLA-B27+ and 63% were female. Primary inclusion criterion was IBP in 53%, IA in 27%, ED in 9%, B27+U in 8% and Fam in 4%. Follow-up is still ongoing., Conclusion: We have set up a unique diagnostic cohort which includes the entire spectrum of SpA manifestations. By using PDUS we expected to improve the diagnostic procedure of SpA., (Copyright © 2012. Published by Elsevier SAS.)

Objective: To examine the recurrence of manifestations belonging to the spectrum of spondylarthropathy (SpA) in first-degree relatives of patients with SpA, and to estimate the recurrence risk ratio., Methods: Parents and siblings of consecutive SpA probands have been thoroughly investigated, including clinical data collection, pelvic x ray and human leukocyte antigen (HLA)-B27 status determination. The diagnosis of SpA was made according to European Spondylarthropathy Study Group and/or the Amor criteria. The recurrence risk ratio lambda(1), which gives an estimate of the weight of genetic factors, was calculated as the ratio of the recurrence risk of SpA in first-degree relatives compared with the population prevalence of SpA. The lambda(non-HLA) was obtained by similar calculations restricted to HLA-B27+ individuals., Results: Most manifestations of SpA were more frequent among the 157 HLA-B27+ relatives of 83 probands than among their 111 HLA-B27- relatives. A diagnosis of SpA was made in 50 relatives of 31 (37%) probands. Recurrence was very similar between parents and siblings, without gender difference, resulting in overall recurrence risk of 12% in first-degree relatives and of 22.7% in HLA-B27+ relatives. The lambda(1) value was 40 and the lambda(non-HLA) value was 6.5, very close to the lambda(HLA) value of 6.25 estimated from linkage study in SpA., Conclusions: A similar recurrence risk of SpA was observed between parents and siblings, consistent with a model of inheritance with no dominance variance and without sex influence. The weight of the non-HLA genetic component was equivalent to that estimated for the HLA locus, and fitted a model of multiplicative interaction between HLA and non-HLA genetic components.

Objective: To update French Society for Rheumatology guidelines regarding the use of tumor necrosis factor alpha (TNFalpha) antagonists for treating patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA)., Methods: We used the method recommended by Shekelle et al. to update the original recommendations: a limited group of experts selected the items that required updating, the relevant literature was critically appraised, and the experts developed new wording for the recommendations, which was then subjected to internal and external validation. As with the original recommendations, three topics were addressed, namely, indications of TNFalpha antagonist therapy, treatment initiation, and treatment adjustment and follow-up., Results: Four criteria should be used to evaluate the indication of TNFalpha antagonist therapy. First, the patient must have a definitive diagnosis of AS or PsA. Thus, patients with AS must meet modified New York criteria or exhibit characteristic involvement of the sacroiliac joints, spine, or peripheral sites documented by radiographs or computed tomography (structural damage) or by magnetic resonance imaging (inflammation). Patients with PsA must meet validated criteria such as the Moll and Wright or CASPAR criteria. The second criterion is active disease for more than 1month, with a BASDAI >or=4 in patients with predominantly axial disease or a tender/swollen joint count >or=3, and with a physician assessment of disease activity of >or=4/10. The third criterion is failure of at least three non-steroidal anti-inflammatory drugs in patients with axial disease or of disease-modifying antirheumatic drug (DMARD) therapy (methotrexate, salazopyrine, or leflunomide) in patients with peripheral disease. Fourth, the patient must be free of contraindications to TNFalpha antagonist therapy. Four recommendations pertain to the initiation of TNFalpha antagonist therapy: a workup should be performed prior to treatment initiation; there is no evidence that one TNFalpha antagonist is more effective than the others, so decisions about drug selection should be shared with the patient and guided by available safety data and the patient's profile; there is no proof that greater effectiveness can be achieved by routinely combining a conventional DMARD; and patients should receive regular standardized follow-up. The last four recommendations deal with adjusting TNFalpha antagonist therapy: the treatment objective is a 2-point or greater improvement in the BASDAI in patients with axial disease and a 30% or greater improvement in the tender/swollen joint counts in patients with peripheral disease; there is no evidence to support the introduction of DMARD therapy in non-responders, who can be switched to another TNFalpha antagonist or, when on infliximab, given higher dosages or more closely spaced injections; patients who fail to tolerate one TNFalpha antagonist can be switched to another TNFalpha antagonist if allowed by the nature of the adverse event; and when a remission is achieved, reduction or discontinuation of concomitant anti-inflammatory therapy should be considered, followed in the event of a prolonged remission by a reduction in the dosage of the TNFalpha antagonist.

Objectives: To develop recommendations for TNFalpha antagonist therapy in patients with spondyloarthropathies., Methods: The Delphi consensus procedure was used to select questions, to which evidence-based answers were sought in the literature. Expert opinion was used when needed to estimate the risks and benefits of TNFalpha antagonists. TNFalpha antagonists exert potent antiinflammatory effects but fail to provide a definitive cure., Results: Recommendations were developed for patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA). The following criteria for TNFalpha antagonist therapy were selected: definitive diagnosis of AS or PsA, active disease for at least 4 consecutive weeks documented during two physician visits, overall physician's assessment of disease activity>/=4/10 and BASDAI>/=4/10 in axial disease or at least three tender and swollen joints in peripheral disease, failure to respond adequately to at least three nonsteroidal antiinflammatory drugs given in optimal dosages for at least 3 months in axial disease or at least one disease-modifying antirheumatic drug (methotrexate, leflunomide, sulfasalazine) for at least 4 months, with local glucocorticoid injections if appropriate, in peripheral disease. Effectiveness and safety should be evaluated by a rheumatologist. The frequency of monitoring depends on the drug. Lack of effectiveness should be defined as inadequate improvement after 6-12 weeks, with a less than two-point decrease in the BASDAI in axial disease or a less than 30% decrease in the tender and swollen joint counts in peripheral disease., Conclusion: These clinical practice recommendations should help rheumatologists in their everyday decisions regarding the use of TNFalpha antagonist therapy in patients with AS or PsA.

This chapter reviews evidence from family and twin studies supporting the strong genetic predisposition of the spondyloarthritides (SpA), which is only partially attributable to the major histocompatibility locus. The current concept of SpA heterogeneity has been challenged by family studies which showed that all articular and extra-articular manifestations were linked together, and most likely to the same genetic factors.

Objective: To evaluate the efficacy and safety of a loading regimen of the anti-tumour necrosis factor alpha (TNF-alpha) antibody infliximab in predominantly axial severe ankylosing spondylitis (AS)., Methods: We enrolled in this study 50 patients (76% males, 87% HLA-B27(+), median age 35 yr, median disease duration 13 yr) with active AS [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >or=30/100 and serum C-reactive protein concentration >or=15 mg/l) despite treatment with a non-steroidal anti-inflammatory drug, and without peripheral arthritis, uveitis or active inflammatory bowel disease. Other disease-modifying anti-rheumatic drugs were discontinued >or=3 months before inclusion and were not allowed during the study. Patients received three infusions of infliximab (5 mg/kg) at weeks 0, 2 and 6 and were monitored clinically and biologically until week 24., Results: Forty-eight patients completed the treatment. In intention-to-treat analysis, all parameters were significantly improved at week 2 and generally reached maximal improvement at week 8. The proportion of responders, defined by a reduction of >or=20% in the global assessment of pain (GAP) or by the AS Assessment Study Group (ASAS 20%) criteria, and the proportion of patients reaching partial remission were 98, 94 and 70% respectively. Relapse, defined as >or=50% loss of maximal GAP improvement, occurred in 73% of completers, with a median delay of 14 weeks after the third infusion. No serious adverse event related to the treatment was observed., Conclusions: This study confirms, in a large group of severely affected AS patients, the remarkable efficacy of infliximab. Relapse usually occurred after discontinuation of the drug, but almost one-third of completers were still free of relapse 4 months after the last infusion.