Cédric Lukas

Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis

Objectives: To develop a new index for disease activity in ankylosing spondylitis (ASDAS) that is truthful, discriminative and feasible, and includes domains/items that are considered relevant by patients and doctors. Methods: Eleven candidate variables covering six domains of disease activity, selected by ASAS experts in a Delphi exercise, were tested in a three-step approach, similar to the methodology used for the disease activity score in rheumatoid arthritis. Data on 708 patients included in ISSAS (International Study on Starting tumour necrosis factor blocking agents in Ankylosing Spondylitis) were used. Cross validation was carried out in the OASIS cohort (Outcome in Ankylosing Spondylitis International Study). Results: Principal component analysis disclosed three factors with eigenvalues >0.75: patient assessments, peripheral joint assessments and acute phase reactants. Discriminant function analysis resulted in a correct classification in ∼72% of the cases (prior probability ∼50%). Regression analysis resulted in an index with five variables (total back pain, patient global assessment, duration of morning stiffness, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)). Three additional candidate indices were designed using similar methodology while omitting either ESR or CRP or patient global assessment. All four scores correlated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; r = 0.67–0.80), patient (0.58–0.75) and physician’s global assessment (0.41–0.48) of disease activity. All four candidate ASDAS indices performed better than BASDAI or single-item variables in discriminating between high and low disease activity state, according to doctors as well as patients in the OASIS cohort. Conclusion: The first steps in the development of a new assessment tool of disease activity in AS derived four candidate indices with good face and construct validity, and high discriminant capacity.

EULAR definition of erosive disease in light of the 2010 ACR/EULAR rheumatoid arthritis classification criteria

The aim of this report was to propose a definition for erosive disease in the context of inflammatory arthritis in light of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) criteria for use in clinical practice and studies. A EULAR task force was formed including 16 rheumatologists and one rheumatology fellow. The process was both evidence based and consensus based, and included, between March 2010 and April 2012, analyses of data from two cohorts, two face-to-face meetings, one online voting and one teleconference. The Leiden Early Arthritis Cohort and the French ESPOIR cohort were used for the evidence-based part. The outcome measures, which were initiation of methotrexate therapy, or any disease-modifying antirheumatic drug therapy within the first year of disease and arthritis persistency over 5 years, were studied with the aim to give the best definition of erosive disease. A decision was made to select a definition with a high specificity and focus on patients who did not otherwise fulfil the 2010 ACR/EULAR RA criteria (<6 points). By a unanimous vote the following definition was selected: erosive disease for use in the 2010 ACR/EULAR RA classification criteria is defined when an erosion (defined as a cortical break) is seen in at least three separate joints at any of the following sites: the proximal interphalangeal, the metacarpophalangeal, the wrist (counted as one joint) and the metatarsophalangeal joints on radiographs of both hands and feet. A highly specific definition for erosive disease has thus been formulated.

Recommendations of the French Society for Rheumatology (SFR) on the everyday management of patients with spondyloarthritis

UNLABELLED The management of spondyloarthritis is challenging and has changed with the development of new concepts and treatments. OBJECTIVE To develop practice guidelines for the everyday management of patients with spondyloarthritis (including psoriatic arthritis), by updating previous national and international recommendations, based on a review of recently published data. METHODS A task force and a multidisciplinary literature review group were established. The task force identified the issues that remained unresolved. Based on existing recommendations and recent publications, the task force developed practice guidelines, which were revised by the literature review group and graded according to AGREE. RESULTS Practice guidelines for the management of spondyloarthritis are reported. After a review of the general diagnostic principles, 30 practice guidelines are given: 5 on general principles, 4 on the management strategy, 5 on non-pharmacological treatments, 7 on conventional pharmacological treatments, 6 on biotherapies, and 3 on surgical treatments and follow-up. CONCLUSION The updated practice guidelines reported here constitute a global framework that can guide physicians in the everyday management of spondyloarthritis.

Serum IL-6 and IL-21 are associated with markers of B cell activation and structural progression in early rheumatoid arthritis: results from the ESPOIR cohort

Objective To identify a specific pattern of serum cytokines that correlates with the diagnosis, activity and severity of rheumatoid arthritis (RA) in patients with early RA as well as with the level of serum markers of B cell activation. Methods Serum interleukin (IL)-1β, IL-1 receptor antagonist (IL1-Ra), IL-2, IL-4, IL-6, IL-10, IL-17, IL-21, monocyte chemotactic protein 1 (MCP-1), tumour necrosis factor α and interferon γ levels were measured in the (ESPOIR) Etude et Suivi des POlyarthrites Indifférenciées Récentes early arthritis cohort, which included patients with at least two swollen joints for >6 weeks and <6 months, and no previous corticosteroids or disease-modifying antirheumatic drugs. Serum cytokine levels were compared between patients who met the 1987 American College of Rheumatology criteria for RA (n=578) or had undifferentiated arthritis (UA, n=132) at the 1-year follow-up visit. Results Serum IL-6 and IL-21 were the only cytokines that discriminated RA from UA on univariate analysis. IL-6 level was associated with RA, whereas erythrocyte sedimentation rate and C-reactive protein were not. Higher proportions of rheumatoid factor and anticyclic citrullinated protein (CCP) positivity, levels of markers of B cell activation, and a higher frequency of rapid radiographic progression were observed in patients with RA with detectable IL-6 or IL-21. Multivariate analysis associated IL-6 and anti-CCP levels with radiographic erosions at enrolment with 1-year radiographic progression. Conclusion Serum IL-6 concentration is greater in RA than in UA. Increase in serum IL-6 and IL-21 levels is associated with markers of B cell activation, and IL-6 is associated with radiographic progression in patients with RA.

Favorable effect of very early disease-modifying antirheumatic drug treatment on radiographic progression in early inflammatory arthritis: Data from the Étude et Suivi des Polyarthrites IndifféRenciées récentes (Study and Followup of Early Undifferentiated Polyarthritis)

OBJECTIVE While there is consensus that treatment with disease-modifying antirheumatic drugs (DMARDs) should be started early in patients with inflammatory arthritis, confirmation that radiographic progression is inhibited with early treatment start is scarce. This study was undertaken to compare radiographic progression in patients treated with a DMARD very early in the course of their disease (within 3 months of diagnosis) and those who began DMARD treatment later. METHODS Patients included in the French observational ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes [Study and Followup of Early Undifferentiated Polyarthritis]) cohort were followed up, and radiographic progression after 12 months was assessed. Propensity scores, reflecting the indication to start a DMARD, were obtained by modeling the start of DMARD therapy by disease-specific and demographic variables obtained at baseline, using logistic regression analysis. The influence of very early versus delayed DMARD start on radiographic progression was evaluated by generalized linear regression, with and without adjustment for propensity scores. RESULTS Six hundred sixty-one patients were analyzed. In an unadjusted analysis, patients starting DMARD therapy within 3 months of diagnosis did not show a significant difference in radiographic progression score as compared to those starting DMARD therapy later (1.2 units versus 1.6 units; P = 0.37). Adjustment for the propensity score revealed a statistically significant difference in mean progression (0.8 units versus 1.7 units; P = 0.033). Analysis by propensity score quintile showed a trend suggesting that early treatment was especially beneficial for patients in the fourth and fifth quintiles (worse prognosis). CONCLUSION Our findings indicate that among patients with inflammatory arthritis in daily clinical practice, early initiation of DMARD therapy reduces 12-month radiographic progression. This strengthens the current recommendations for very early initiation of specific therapy in patients with early arthritis.

Risk of herpes/herpes zoster during anti-tumor necrosis factor therapy in patients with rheumatoid arthritis. Systematic review and meta-analysis

BACKGROUND TNF blockers have demonstrated efficacy in inflammatory rheumatic diseases (IRDs). The drugs are associated with a moderate but definite risk of bacterial infection, but risk of viral infection is not clearly known. OBJECTIVE To assess the risk of herpes zoster (HZ) reactivation in patients with rheumatoid arthritis (RA) receiving TNF blockers as compared with DMARDs. METHODS A systematic search of literature up to March 2013 was performed, in MEDLINE, EMBASE, the Cochrane library and abstracts from the ACR and EULAR congresses from 2008 to 2011. Studies were included if they reported the incidence of HZ, respectively, in patients receiving anti-TNF and conventional DMARDs. RESULTS The literature search identified 3446 articles and 88 congress abstracts; a manual search retrieved seven articles. Finally, 26 articles and nine abstracts were included; six articles and one abstract were of meta-analyses estimating the relative risk of HZ in patients with RA with a total follow-up of 163,077 patient-years. From the meta-analyses of data for seven registries, the pooled risk ratio for HZ with TNF blockers was 1.61 [95% CI 1.16-2.23] (P = 0.004). Proportions of severe HZ ranged from 4.9% to 20.9% with TNF-blockers and from 2.0% to 5.5% with conventional DMARDs, in the different registries. CONCLUSIONS This meta-analysis revealed a significantly increased risk of HZ, up to 61%, in patients with IRD receiving TNF blockers. These data raise the issue of systematic prophylactic treatment with known history of HZ or vaccination without this history.

Repair of erosions occurs almost exclusively in damaged joints without swelling

Background Negative radiographic change scores obtained under blinded time-sequence conditions suggest that repair of joints may indeed occur. It is likely that, if repair truly exists, it would be preferentially seen in clinically inactive joints from patients treated with drugs with well-known structural efficacy. Objective To determine whether repair is associated with both the absence or improvement of swelling and with treatment. Patients and methods Radiographs from patients of the TEMPO trial were scored twice by two readers according to the Sharp–van der Heijde score, blinded to both treatment and true time sequence. Single-joint change scores in erosions were coupled with single-joint swelling scores obtained from clinical examination. Consistency of observed improvement across readers and repeat reads was described, and factors expected to increase the likelihood of occurrence of both worsening and improvement of erosion were tested by generalised estimating equations (GEE) modelling. Results In all of the four independent reads, the mean change in erosion score was statistically significantly negative only in the subgroup of joints with absent or improved swelling, when erosions were present at baseline. Multivariate analysis showed that worsening of the erosion score in a joint was significantly increased if that joint was already damaged at study entry, clinical swelling persisted and methotrexate was used instead of etanercept. Repair was associated with improvement of swelling and use of etanercept (p≤0.007 for all associations). Conclusion Repair of erosions almost exclusively occurs in joints with improvement or absence of swelling, in patients treated with etanercept. Progression is seen more frequently in joints with persistent swelling, in patients receiving methotrexate monotherapy, primarily if damage is already present.

Prediction of Radiographic Damage in Early Arthritis by Sonographic Erosions and Power Doppler Signal: A Longitudinal Observational Study

To assess the ability of ultrasonography (US) to predict radiographic damage in early arthritis.

Predictors of radiographic progression in the ESPOIR cohort: the season of first symptoms may influence the short-term outcome in early arthritis

Objectives To determine predictors of short-term radiographic progression in an inception cohort of patients with early arthritis. Methods Patients presenting with synovitis of at least two joints for 6 weeks to 6 months were included in the Etude et Suivi des POlyarthrites Indifferenciées Récentes (ESPOIR) cohort. Univariate analysis was used to determine the relationship between baseline variables and radiographic outcome (assessed by the modified total Sharp score (mTSS)) after 6 and 12 months. Stepwise multiple logistic regression was used to select independent predictive factors. The sensitivity and specificity of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) at baseline in discriminating between erosive and non-erosive disease were determined by receiver operating characteristic (ROC) curves. Results From data available for 736 patients, radiographic progression at 6 months was independently predicted by baseline ACPA, human leucocyte antigen (HLA)-DRB1*01 and/or 04 genes, erythrocyte sedimentation rate and mTSS. Interestingly, the season of onset of the first symptoms was associated with the severity of early arthritis (OR 1.66, 95% CI 1.07 to 2.59, in winter and spring vs summer and autumn). Univariate analysis revealed similar results for season at 12 months (OR 1.68, 95% CI 1.20 to 2.37). The peak of the ROC curves for radiographic outcome occurred with ACPA and RF values similar to the cut-offs provided by manufacturers. Conclusion The authors found the onset of arthritis symptoms during winter or spring associated with greater radiographic progression at 6 months for patients with early arthritis. These data could reinforce the role of environmental factors in the development and outcome of rheumatoid arthritis.

Association of Tobacco Exposure and Reduction of Radiographic Progression in Early Rheumatoid Arthritis: Results From a French Multicenter Cohort

To investigate the initial response to treatment and risk of radiographic disease progression in current smokers (S), ex‐smokers (EX), and nonsmokers (NS) in a prospective early arthritis cohort and to analyze the influence of smoking cessation on arthritis outcome.