Development and validation of the Flare-OA questionnaire for measuring flare in knee and hip osteoarthritis.

OBJECTIVE: Ability to assess flares in osteoarthritis (OA) of the knee and hip (KHOA) is important in clinical care and research. Using mixed methods, we developed a self-reported instrument measuring flare and assessed its psychometric properties. METHODS: We constructed questionnaire items from semi-structured interviews and a focus group (patients, clinicians) by using a dual-language (English-French) approach. A Delphi consensus method was used to select the most relevant items. Patients with OA from Australia, France and the United States completed the preliminary Flare-OA, HOOS, KOOS and Mini-OAKHQOL questionnaires online. We used a factor analysis and content approach to reduce items and determine structural validity. We tested the resulting questionnaire (score 0-100) for internal consistency, convergent and known-groups validity. RESULTS: Initially, 180 statements were generated and reduced to 33 items in five domains (response 0 = not at all, to 10 = absolutely) by Delphi consensus (50 patients, 116 professionals) and an expert meeting. After 398 patients (mean [SD] age 64 [8.5] years, 70.4% female, 86.7% knee OA) completed the questionnaire, it was reduced to 19 items by factor analysis and a content approach (RMSEA = 0.06; CFI = 0.96; TLI = 0.94). The Cronbach's alpha was >0.9 for the five domains and the whole questionnaire. Correlation coefficients between Flare-OA and other instrument scores were as predicted, supporting construct validity. The difference in Flare-OA score between patients with and without flare (31.8) largely exceeded 2 SEM (10.2). CONCLUSION: Flare-OA is a valid and reliable patient-reported instrument for assessing the occurrence and severity of flare in patients with KHOA in clinical research.

Predictors of fatigue and persistent fatigue in early rheumatoid arthritis: a longitudinal observational study, data from the ESPOIR cohort.

OBJECTIVE: To determine, in a cohort of patients with early rheumatoid arthritis (RA), factors associated with fatigue at baseline, describe its evolution over 5 years of follow-up, and determine baseline predictors of persistent fatigue. METHOD: We selected patients fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA included in the ESPOIR cohort. Using bivariable and multivariable logistic regression models, we examined baseline variables associated with baseline fatigue (defined by visual analogue scale fatigue > 20) and baseline predictors of persistent fatigue (if the patient experienced fatigue at all visits during the 5 year follow-up period). RESULTS: We analysed 673 patients; 80.7% reported fatigue at baseline. At baseline, fatigue was associated with female gender, younger age, greater severity of morning stiffness, sleep problems, higher Health Assessment Questionnaire levels, presence of sicca symptoms, history of thyroid problems, and presence of psychological distress (depressive or anxiety symptoms). At 5 years of follow-up, the percentage of fatigued patients who reported fatigue at all time-points since baseline was 24.6% (referred to as 'persistent fatigue'). Independent baseline predictors were presence of sicca symptoms, greater severity of morning stiffness, and psychological distress. CONCLUSIONS: Fatigue is a frequent symptom in RA. The presence of sicca symptoms, greater severity of morning stiffness, and presence of psychological distress at baseline were associated with baseline fatigue and persistent fatigue at 5 years. We did not observe any association between baseline fatigue or persistent fatigue and the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate.

Comparative effectiveness of improvement in pain and physical function for baricitinib versus adalimumab, tocilizumab and tofacitinib monotherapies in rheumatoid arthritis patients who are naïve to treatment with biologic or conventional synthetic disease-modifying antirheumatic drugs: a matching-adjusted indirect comparison.

OBJECTIVE: To compare improvement in pain and physical function for patients treated with baricitinib, adalimumab, tocilizumab and tofacitinib monotherapy from randomised, methotrexate (MTX)-controlled trials in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)/biologic (bDMARD)-naïve RA patients using matching-adjusted indirect comparisons (MAICs). METHODS: Data were from Phase III trials on patients receiving monotherapy baricitinib, tocilizumab, adalimumab, tofacitinib or MTX. Pain was assessed using a visual analogue scale (0-100 mm) and physical function using the Health Assessment Questionnaire-Disability Index (HAQ-DI). An MAIC based on treatment-arm matching, an MAIC with study-level matching and Bucher's method without matching compared change in outcomes between therapies. Matching variables included age, gender, baseline disease activity and baseline value of outcome measure. RESULTS: With all methods, greater improvements were observed in pain and HAQ-DI at 6 months for baricitinib compared with adalimumab and tocilizumab (p<0.05). Differences in treatment effects (TEs) favouring baricitinib for pain VAS for treatment-arm matching, study-level matching and Bucher's method, respectively, were -12, -12 and -12 for baricitinib versus adalimumab and -7, -7 and -9 for baricitinib versus tocilizumab; the difference in TEs for HAQ-DI was -0.28, -0.28 and -0.30 for adalimumab and -0.23, -0.23 and -0.26 for tocilizumab. For baricitinib versus tofacitinib, no statistically significant differences for pain improvement were observed except with one of the three methods (Bucher method) and none for HAQ-DI. CONCLUSIONS: Results suggest greater pain reduction and improved physical function for baricitinib monotherapy compared with tocilizumab and adalimumab monotherapy. No statistically significant differences in pain reduction and improved physical function were observed between baricitinib and tofacitinib with the MAIC analyses.

Translation and cross-cultural adaptation into Italian of the self-administered FLARE-RA questionnaire for rheumatoid arthritis.

The aim was to provide a translation into Italian with cross-cultural adaptation of the French FLARE-Rheumatoid Arthritis (RA) questionnaire, and to test its acceptability, feasibility, reliability and construct validity in a single-centre cohort study. The French version of the FLARE-RA questionnaire was cross-culturally adapted and translated into Italian following an established forward-backward translation procedure, with independent translations and backtranslations. To validate the Italian version we tested the internal validity with Cronbach's alpha, test-retest reliability with the intraclass correlation coefficient, agreement between assessments with Bland-Altman plots and construct validity with Spearman's correlation coefficients. The questionnaire was tested on 283 consecutive RA outpatients (mean age 56.1±13.9 years, 226/283 females, median disease duration 12.6 years ranging from 0.2 to 70.6). For the global score (11 items) the Cronbach's alpha coefficient was 0.94. The intraclass correlation coefficient was 0.87 (95% CI, 0.76-0.96). The correlation of FLARE-RA global score was 0.59 (95% CI, 0.50-0.66) with the Disease Activity Score on 28 joints, 0.63 (95% CI, 0.55-0.71) with the Simplified Disease Activity Index, 0.77 (95% CI, 0.71-0.83) with the RA Impact of Disease and 0.67 (95% CI, 0.59-0.73) with the Health Assessment Questionnaire. The Italian version of the FLARE-RA is feasible, brief and easy to administer. The translated and cross-cultural adapted showed accordingly to be valid and reliable. This questionnaire has some practical advantages, such as clarity, comprehensiveness, simplicity, and a minimum filling time. The development of cross-cultural adapted questionnaires in different languages is of pivotal importance to obtain standardized and comparable data across countries.

The American English version of the validated French Flare Assessment in RA Questionnaire (FLARE-RA).

OBJECTIVE: To evaluate use of a British English version of the validated French FLARE-RA questionnaire among American English speaking patients. In addition, to create a culturally adapted American English (AmE) FLARE-RA questionnaire and to examine its attributes of patient-reported RA flare status. METHODS: Using standardized cultural adaptation guidelines, we cognitively debriefed 25 American English speaking rheumatoid arthritis (RA) outpatients and created AmE-FLARE-RA with their input. One hundred three additional RA patients were recruited. Patients completed the Routine Assessment of Patient Index Data 3 (RAPID3), patient global visual analogue scale (VAS), AmE-FLARE-RA, and self-reports of flare. Physician global VAS, physician-assessed flare, swollen and tender joint count (TJC), and clinical disease activity index (CDAI) were documented. AmE-FLARE-RA and disease activity measures were compared between patient-reported and physician-reported flare categories. RESULTS: Patients were female (89%), with mean (SD) age 51.1 (± 15.3) years and mean disease duration (SD) 11.9 (± 10.1) years, with 26% in remission/low disease activity. Total AmE-FLARE-RA scores, RAPID3, CDAI, and patient global VAS were significantly higher for both patient-reported flares and physician-reported flares compared with non-flaring patients by self- or physician report (p < 0.05). Total AmE-FLARE-RA scores correlated significantly with RAPID3 (corr = 0.50, p < 0.0001) and with CDAI (corr = 0.45, p < 0.0001). Across "no flares," "one flare," and "several flare" groups, there was a non-significant increase in AmE-FLARE-RA scores (p = 0.07). CONCLUSION: The British English FLARE-RA was successfully adapted for AmE-speaking RA patients. AmE-FLARE-RA significantly correlated with RAPID3 and CDAI and distinguished between patient-reported and physician-reported flares, making it useful to detect flares in American RA patients.Key Points• The American English FLARE-RA (AmE-FLARE-RA) questionnaire is the result of cognitive debriefing with American RA patients using the British English version of the validated French FLARE-RA and incorporates patient-recommended language modifications..• Patients self-reporting flares had significantly higher AmE-FLARE-RA scores, compared with those without flares at the time of visit. AmE-FLARE-RA scores correlate with RAPID3 and CDAI.• There was a non-statistically significant trend using the AmE-FLARE-RA scores when examining patients with no flare, one flare, or several flares.• AmE-FLARE-RA total scores are uniformly elevated (~ 6.0 on a 0-10 scale), regardless of discordance between patient and MD assessment of flare at time of visit (~ 30%).

AA amyloidosis secondary to adult onset Still's disease: About 19 cases.

OBJECTIVE: Adult onset Still's disease (AOSD) is an inflammatory disorder characterized by high spiking fever, evanescent rash, polyarthritis, and many other systemic manifestations. Recurrent or persistent disease can lead to AA amyloidosis (AAA). Our objectives were to present 3 French cases and perform a systematic review of the literature, in order to determine the prevalence, characteristics, predisposing factors, and therapeutic response of AOSD-related AAA. METHODS: A systematic literature review was performed by searching MEDLINE from 1971 to 2018. Two independent investigators selected reports of AAA complicating AOSD. New French cases were identified with the help of the Reference Center for rare Auto-Inflammatory Diseases and Amyloidosis (CEREMAIA). Patients with juvenile idiopathic arthritis were excluded. RESULTS: The prevalence of AAA in AOSD was 0.88% (95%CI [0.49-1.28]) based on 45 articles. In addition to 3 new cases from the CEREMAIA, 16 patients were assessed for clinical presentation, risk factors, and therapeutic response of AOSD-related AAA. Mean age at AOSD onset was 29.6 ±â€¯12.6 years, with a mean delay before AAA diagnosis of 16.75±5.8 years. Renal involvement was the most common manifestation of AAA. The majority of patients presented active AOSD at AAA diagnosis. Various treatments of AOSD-related AAA were attempted including corticosteroids and biotherapies. CONCLUSION: AAA is a rare and severe complication that may occur during the course of uncontrolled active AOSD. It could be prevented by early diagnosis and better control of AOSD, with more frequent use of biotherapies.

Cost-effectiveness of five different anti-tumour necrosis factor tapering strategies in rheumatoid arthritis: a modelling study.

Objective: To investigate the cost-effectiveness of five different tumour necrosis factor inhibitor tapering strategies in patients with rheumatoid arthritis (RA) and stable low disease activity, using a modelling design.Method: Using Markov models based on data from the DRESS and STRASS randomized controlled trials, and the Nijmegen RA cohort, five tapering strategies for etanercept and adalimumab were tested against continuation: 1, four-step tapering (DRESS strategy); 2, five-step tapering; 3, tapering without withdrawal; 4, use of a stricter flare criterion; and 5, use of a theoretical predictor for successful tapering. We also examined how well a biomarker should be able to predict in order for strategy 5 to become cost-effective compared to the other strategies.Results: All examined tapering strategies were cost saving (range: EUR 5128 to 7873) but yielded more short-lived flares compared to continuation. The change in utilities compared to continuation was minimal and not clinically relevant (range: -0.005 to 0.007 quality-adjusted life-years). Strategy 1 was cost-effective compared to all other strategies [highest incremental net monetary benefit (iNMB)]. However, there was a large overlap in credible intervals, especially between strategies 1 and 2. Scenario analyses showed that 50% reduction of drug prices would result in the highest iNMB for strategy 2. A biomarker only becomes cost-effective when it is inexpensive and has a sensitivity and specificity of at least 84%.Conclusion: Because our study showed a comparable iNMB for tapering in four or five steps (including discontinuation), we recommend a choice between these strategies, based on shared decision making.

Health resource use and costs of symptomatic knee and/or hip osteoarthritis.

BACKGROUND: Data on the economic consequences of hip and knee osteoarthritis (OA) are scarce. We aimed to estimate the annual direct and indirect costs for patients followed for hip and/or knee OA in the Knee and Hip Osteoarthritis Long term Assessment (KHOALA) cohort. METHODS: The KHOALA cohort, set up from 2007 to 2009, is a French multicenter study of 878 individuals with symptomatic knee/hip OA who were 40-75 years old. Resources used were collected annually for 5 years. Costs were assigned by using official sources and expressed in 2018 euros per patient. RESULTS: The mean annual total costs per patient over the 5-year study period were 2,180 ± 5,305€. The mean annual direct medical costs per patient were 2,120 ± 5,275€ and mean annual indirect costs per patient 180 ± 1,735€ for people of working age. Costs increased slightly over the study period. Drugs were the largest cost share, representing over 50% of all direct costs. However, the proportion attributable to OA drugs accounted for only 10.5% of drug costs. The second cost share was hospitalizations; hip and knee prosthetic surgery accounted for 27% of surgery hospitalization costs. Health professional visits were the third cost share, accounting for 3% of direct medical costs. The median costs induced could be as high as 2 billion €/year (IQR 0.7-4.3) in France. CONCLUSION: Hip and knee OA costs were substantial and increased over the study period in France. However, the costs attributable to OA represented only a small fraction of overall costs.

Moderate alcohol consumption is associated with increased radiological progression in women, but not in men, with early rheumatoid arthritis: results from the ESPOIR cohort (Étude et Suivi des Polyarthrites Indifférenciées Récentes).

OBJECTIVE: We conducted this study to determine whether alcohol consumption influences radiological progression in early rheumatoid arthritis (RA). METHOD: Patients fulfilling the European League Against Rheumatism/American College of Rheumatology 2010 criteria in the early arthritis cohort ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes) were included in this study. Alcohol consumption was collected at baseline and at each visit. We classified alcohol consumption into three groups: abstinent (0 g/day), moderate (≤ 20 g/day for women, ≤ 30 g/day for men), and abuse (> 20 g/day for women, > 30 g/day for men). The primary outcome was the occurrence of radiological progression, defined as an increase ≥ 5 points in the total Sharp/van der Heijde score. We investigated whether alcohol consumption is predictive of radiological progression at 1, 3, and 5 years by univariate and multivariate analysis adjusted for age, baseline erosion, rheumatoid factor, anti-citrullinated peptide antibody, smoking status, body mass index, and treatment with leflunomide or methotrexate and biologics. RESULTS: The study included 596 patients. When considering the influence of gender on the interaction between alcohol consumption and radiological progression, we showed a deleterious effect of moderate consumption in women [odds ratio (OR) = 1.73, 95% confidence interval (CI) 1.01; 2.96, p = 0.045] and a trend towards a protective effect of moderate consumption in men (OR = 0.50, 95% CI 0.21; 1.16, p = 0.106) in multivariate analysis. CONCLUSION: Our data suggest a deleterious effect of moderate consumption of alcohol on radiological progression in women, but not in men, with early RA.

[Discontinuation or tapering strategies of biologics in rheumatoid arthritis in remission]. / Stratégies d'arrêt ou de réduction des biomédicaments dans la polyarthrite rhumatoïde en rémission.

The arrival of new drugs and new therapeutic strategies allowed to reach sustained remission in an increasing number of patients with rheumatoid arthritis. The study of biologic disease-modifying anti-rheumatic drugs (bDMARDs) adaptation strategies is a need to optimize the benefit/risk balance and cost/effectiveness ratio of these molecules. Current recommendations such as EULAR 2016 propose tapering bDMARDs, especially when combined with a csDMARD, when the patient is in remission after stopping persistent glucocorticoids. The analysis of literature comprising 22 studies shows that a bDMARD adaptation is possible in established rheumatoid arthritis when clinico-biological and ultrasound remission is maintained over six months. Priority should be given to a progressive tapering strategy doses controlled by disease activity while maintaining "tight control" to identify and effectively treat a relapse, a retreatment being usually favorable.

Economic considerations and patients' preferences affect treatment selection for patients with rheumatoid arthritis: a discrete choice experiment among European rheumatologists.

OBJECTIVE: To compare the value that rheumatologists across Europe attach to patients' preferences and economic aspects when choosing treatments for patients with rheumatoid arthritis. METHODS: In a discrete choice experiment, European rheumatologists chose between two hypothetical drug treatments for a patient with moderate disease activity. Treatments differed in five attributes: efficacy (improvement and achieved state on disease activity), safety (probability of serious adverse events), patient's preference (level of agreement), medication costs and cost-effectiveness (incremental cost-effectiveness ratio (ICER)). A Bayesian efficient design defined 14 choice sets, and a random parameter logit model was used to estimate relative preferences for rheumatologists across countries. Cluster analyses and latent class models were applied to understand preference patterns across countries and among individual rheumatologists. RESULTS: Responses of 559 rheumatologists from 12 European countries were included in the analysis (49% females, mean age 48 years). In all countries, efficacy dominated treatment decisions followed by economic considerations and patients' preferences. Across countries, rheumatologists avoided selecting a treatment that patients disliked. Latent class models revealed four respondent profiles: one traded off all attributes except safety, and the remaining three classes disregarded ICER. Among individual rheumatologists, 57% disregarded ICER and these were more likely from Italy, Romania, Portugal or France, whereas 43% disregarded uncommon/rare side effects and were more likely from Belgium, Germany, Hungary, the Netherlands, Norway, Spain, Sweden or UK. CONCLUSIONS: Overall, European rheumatologists are willing to trade between treatment efficacy, patients' treatment preferences and economic considerations. However, the degree of trade-off differs between countries and among individuals.

Work-related discussions between French rheumatologists and their rheumatoid arthritis patients.

BACKGROUND: Rheumatoid arthritis (RA) causes significant impairment of physical function, and thus adversely affects patients' ability to work. AIMS: To document how often work limitations are discussed by rheumatologists and RA patients during consultations. METHODS: We conducted an observational study in a sample of French rheumatologists and in a parallel sample of patients recruited by pharmacists. We asked all rheumatologists in France practising in private practice or mixed practice (private practice and hospital) to participate in a telephone survey about their most recent consultation with an RA patient. Randomly selected pharmacists recruited RA patients to complete a questionnaire about their most recent consultation with their rheumatologist. We included patients aged 20-59, with a paid job or unemployed. We calculated the proportion of consultations including work-related discussions in both samples. RESULTS: Of the 1737 rheumatologists contacted, 153 (9%) described consultations with eligible patients. Of the 1200 pharmacists contacted, 39 (3%) recruited 81 RA patients. The proportion of consultations including work-related discussions was 50% [95% confidence interval (CI) 42-58%] in the rheumatologist sample and 52% (95% CI 41-63%) in the patient sample. The most frequent subject of discussion (88%) was physical problems related to work in both samples. CONCLUSIONS: This is the first study to document the proportion of consultations where rheumatologists and their RA patients discuss work. Both specialists and patients reported that work was discussed in one in every two consultations.

Economic impact of lower-limb osteoarthritis worldwide: a systematic review of cost-of-illness studies.

OBJECTIVE: An overview of the economic consequences - overall costs as well as cost breakdown (direct and indirect) - of hip and knee osteoarthritis (OA) worldwide. METHODS: A systematic literature search of EMBASE, MEDLINE, Scopus and Cochrane databases for articles was performed independently by two rheumatologists who used the same predefined eligible criteria. Papers without abstracts and in languages other than English or French were excluded. Extracted costs were converted to an annual cost and to 2013 euros (€) by using the Consumer Price Index of the relevant countries and the 2013 Purchasing Power Parities between these countries and the European Union average. RESULTS: A total of 45 abstracts were selected, and 32 articles were considered for the review. The studied populations were heterogeneous: administrative, hospital and national health survey data. Annual total costs per patient ranged from 0.7 to 12 k€, direct costs per patient from 0.5 to 10.9 k€ and indirect costs per patient from 0.2 to 12.3 k€. The weighted average annual costs per patient living with knee and hip OA were 11.1, 9.5 and 4.4 k€ for total, direct and indirect costs, respectively. CONCLUSIONS: This review highlights the heterogeneity of studies and lack of methodologic consensus to obtain reliable cost-of-illness estimates for lower-limb OA. However, costs induced by the disease seem substantial and deserve to be more extensively explored.

Body mass index and response to tocilizumab in rheumatoid arthritis: a real life study.

Several studies have suggested that obesity could have a negative effect on response to anti-tumor necrosis factor α (anti-TNFα) in rheumatoid arthritis (RA). Little is known about the impact of body mass index (BMI) on other biologic agents. We aimed to evaluate the effect of BMI on response to tocilizumab (TCZ) in RA. RA patients treated with TCZ were included in this multicenter retrospective study. BMI was calculated at the initiation of treatment. After 6 months of treatment, change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate and C-reactive protein level, and tender and swollen joints were analyzed. The primary endpoint was decrease in DAS28 ≥ 1.2. Secondary outcomes were good response and remission by EULAR criteria. At baseline, among 115 RA patients included, the median (interquartile range) BMI was 25.4 (22.0-28.8) kg/m(2). The number of patients with normal weight, overweight, and obesity was 53 (46 %), 37 (32 %), and 25 (22 %), respectively. Baseline characteristics did not differ between the three subgroups of BMI. The median BMI did not differ between responders and non-responders for DAS28 decrease ≥1.2 (25.7 [22.1-29.9] vs 24.9 [22.0-27.1], P = 0.38), EULAR good response (25.9 [22.8-30.0] vs 25.4 [22.0-28.4], P = 0.61), and remission (25.1 [22.5-28.6] vs 25.4 [22.0-28.9], P = 0.76). BMI did not affect the response to TCZ in RA. If confirmed, these results could be helpful for the selection of a biologic agent in obese RA patients.

Identifying patients with rheumatoid arthritis with moderate disease activity at risk of significant radiographic progression despite methotrexate treatment.

OBJECTIVES: To determine the baseline factors predictive of significant radiographic progression (SRP) in patients with moderately active rheumatoid arthritis (RA) despite receiving methotrexate (MTX). METHODS: Patients from the MTX arm of the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) trial with sustained moderate RA (defined as ≥3.2 mean disease activity score in 28 joints ≤5.1 during the last 6 months of the first year) were analysed for SRP (mTSS >3.0 overall) after 2 and 3 years. Baseline predictors for SRP were identified by univariate and multivariate analyses. All variables shown to be significantly associated with SRP were categorised based on clinically relevant cut-offs and tertiles and were included in a matrix risk model. RESULTS: 228 patients were assigned MTX treatment, 210 patients were in the radiographic intention-to-treat population, and 96 of these had sustained moderate RA. SRP occurred in 25 (26%) and 33 (34%) patients after 2 and 3 years of MTX treatment, respectively. Univariate and multivariate analyses found that C reactive protein (CRP) and rheumatoid factor (RF) positivity at baseline were predictive of SRP after 2 and 3 years (p<0.05 for all). The matrix risk model showed that RF positivity and CRP levels >40 mg/L at baseline were significantly associated with SRP after 2 (p<0.05 for both; R(2)=0.24) and 3 years (p<0.05 for both; R(2)=0.22). The baseline erosion score was not found to be predictive of SRP. CONCLUSIONS: Patients with sustained moderate RA despite receiving MTX treatment are at risk of SRP, with both RF positivity and high CRP levels shown to be predictive of this.

Evaluating relationships between symptom duration and persistence of rheumatoid arthritis: does a window of opportunity exist? Results on the Leiden early arthritis clinic and ESPOIR cohorts.

BACKGROUND: A prolonged symptom or disease duration at treatment initiation is associated with unfavourable outcomes in rheumatoid arthritis (RA). It is unknown whether this relation is linear, referring to a common 'the-earlier-the-better principle', or whether a transient time frame in which the disease is more susceptible to treatment exists, referring to a 'window of opportunity'. To elucidate this, we evaluated the shape of the associations of symptom duration with persistence of RA. METHODS: Patients with 1987 RA treated with disease modifying antirheumatic drugs (DMARDs) in the Leiden Early Arthritis Clinic (EAC, n=738) and Evaluation et Suivi de POlyarthrites Indifférenciées Récentes (ESPOIR) (n=533) were studied. Cox proportional hazards regression models using natural cubic splines were performed; the log-HR on DMARD-free sustained remission (the opposite of RA persistence) during 5-year follow-up was plotted against symptom duration. Discrimination was measured using time-dependent receiver operator characteristic curves. Subanalyses were performed stratified for the DMARDs used (methotrexate or other conventional DMARDs) and for anticitrullinated peptide antibody (ACPA). RESULTS: 11.5% (85/738) and 5.4% (29/533) of EAC and ESPOIR RA patients achieved DMARD-free sustained remission. In both cohorts and all analyses, the curves depicting the log-HRs on remission in relation to symptom duration were not linear. The symptom duration with optimal discriminative ability was 14.9 weeks (95% CI 12.3 to 16.0; area under the curve (AUC) 0.61) in the EAC and 19.1 weeks (95% CI 12.3 to 28.0; AUC 0.59) in ESPOIR. For ACPA-positive RA, this was 11.4 weeks (95% CI 7.7 to 79.0; AUC 0.56) and for ACPA-negative RA 15.0 weeks (95% CI 9.7 to 48.7; AUC 0.56). CONCLUSIONS: The association between symptom duration and RA persistence is not linear, suggesting the presence of a confined period in which RA is more susceptible to treatment.

Early tumor necrosis factor α antagonist therapy in everyday practice for inflammatory back pain suggesting axial spondyloarthritis: results from a prospective multicenter french cohort.

OBJECTIVE: To determine the frequency of and factors associated with early tumor necrosis factor α (TNFα) antagonist therapy in everyday clinical practice in patients with suspected axial spondyloarthropathy (SpA). METHODS: We used data from the prospective observational study in the French Devenir des Spondylarthropathies Indifférenciées Récentes (DESIR; Outcome of Recent Undifferentiated Spondylarthropathies) cohort of 708 patients with recent-onset (<3 years) inflammatory back pain (IBP) suggesting axial SpA. TNFα antagonist use was recorded at months 6 and 12 and factors independently associated with TNFα antagonist therapy were identified by multivariate logistic regression. RESULTS: Among the 708 patients (mean age 33.8 years, 46.2% men), 166 (23.4%) patients received TNFα antagonist therapy by month 12, including 120 (73.6%) patients who fulfilled Assessment of SpondyloArthritis international Society (ASAS) axial criteria and 157 (94.6%) who fulfilled at least 1 SpA criteria set; 109 (65.6%) had no sacroiliitis. Factors independently associated with early TNFα antagonist therapy were high Ankylosing Spondylitis Disease Activity Score using the C-reactive protein level (odds ratio [OR]1-point increase 1.60, 95% confidence interval [95% CI] 1.25-2.03, P < 0.001), high physician's global disease activity score (OR 1.37, 95% CI 1.21-1.54, P < 0.001), ASAS nonsteroidal antiinflammatory drug score >50 (OR 1.88, 95% CI 1.24-2.87, P = 0.003), current or past disease-modifying antirheumatic drug use (OR 2.09, 95% CI 1.22-3.59, P = 0.008), systemic corticosteroid use (OR 2.48, 95% CI 1.43-4.34, P = 0.002), and mild to severe radiographic hip abnormalities (OR 9.43, 95% CI 2.11-42.09, P = 0.003). After adjustment on these factors, Achilles enthesis hypervascularization by power Doppler and number of work days missed were associated with TNFα antagonist therapy. CONCLUSION: In the DESIR cohort, approximately one-fourth of patients with recent IBP suggestive of axial SpA were under anti-TNFα therapy after 1 year of followup. All factors associated with this early initiation reflected higher disease activity, refractoriness, or severity, which suggests compliance of French rheumatologists with current treatment guidelines.

[Clinical case of the month. A rare case of arthritis and fever]. / Un cas rare d'arthrite fébrile.

We present the case report ofa 28 year old male presenting with recurrent fever episodes and arthralgia. Based on the presence of an inflammatory syndrome, a hyperferritinemia, a salmon-pink rash and recurrent fever episodes, the diagnosis of an adult onset Still's disease (AOSD) was made. A treatment with corticosteroids was started. During the following years, the corticosteroids could not be tapered. Eventually, a treatment with anakinra, an interleukin 1 (IL-1) receptor antagonist was started, allowing tapering of the corticosteroids. This case report supports the possible role of IL-1 in the pathogenesis ofAOSD, possibly through the inflammasome.