DAS28-γGT for the prediction of major cardiovascular events in rheumatoid arthritis: results from the ESPOIR cohort.

OBJECTIVE: To validate the predictive value of the DAS28 γ-glutamyl transferase (DAS28-γGT) for the occurrence of major cardiovascular (CV) events (MACE) in the 'Etude et Suivi des Polyarthrites Indifférenciées Récentes' ESPOIR cohort. METHODS: Analysis of 13-year outcome from the ESPOIR cohort. RA patients with missing data for baseline γGT activity and those not followed-up to 1 year were excluded. Baseline DAS28-γGT was calculated using the following formula: 0.56*√TJ-28 + 0.28 * √SJ-28 + 2*ln(γGT) + 0.014 * GH. Our primary outcome was the merit of the DAS28-γGT in predicting the occurrence of MACE. RESULTS: Among the 696 patients [536 women, mean (s.d.) age of 49 (12) years], 34 MACE were recorded, with a mean time to event of 71 (44) months. Receiver operating characteristic curve analysis indicated that a DAS28-γGT >9.4 had the best sensitivity and specificity for the diagnosis of MACE during the observation period. DAS28-γGT >9.4 was predictive of the occurrence of MACE, with a hazard ratio (HR) of 3.11 (95% CI 1.41, 5.43). Multivariate Cox analyses confirmed higher DAS28-γGT (HR 2.44, 95% CI 1.05, 5.64) together with age (HR 1.04, 95% CI 1.01, 1.07) and diabetes mellitus (HR 4.12, 95% CI 1.55, 10.95) as independent predictors of MACE. There was a dose effect of the DAS28-γGT for MACE-risk prediction, which was in line with the application of the Framingham risk score. CONCLUSION: The DAS28-γGT was identified in this large prospective cohort as an independent predictor of MACE in patients with RA. The DAS28-γGT is a simple and useful tool to evaluate CV risk in routine and warn the clinician about the CV risk burden in patients with RA.

How do patient reported outcome measures affect treatment intensification and patient satisfaction in the management of psoriatic arthritis? A cross sectional study of 503 patients.

OBJECTIVES: The ASSIST study investigated prescribing in routine psoriatic arthritis (PsA) care and whether the patient reported outcome: PsA Impact of Disease questionnaire (PsAID-12), impacted treatment. This study also assessed a range of patient and clinician factors and their relationship to PsAID-12 scoring and treatment modification. METHODS: Patients with PsA were selected across the UK and Europe between July 2021-March 2022. Patients completed the PsAID questionnaire, with the results shared with their physician. Patient characteristics, disease activity, current treatment methods, treatment strategies, medication changes and patient satisfaction scores were recorded. RESULTS: 503 patients recruited. 36.2% had changes made to treatment, 88.8% of this had treatment escalation. Overall, the mean PsAID-12 score was higher for patients with treatment escalation; the PsAID-12 score was associated with odds of treatment escalation (OR: 1.58; p< 0.0001). However, most clinicians reported PsAID-12 did not impact their decision to escalate treatment, instead supporting treatment reduction decisions. Physician's assessment of disease activity had the most statistically significant effect on likelihood of treatment escalation, (OR = 2.68, per 1-point score increase). Escalation was more likely in patients not treated with biologic therapies. Additional factors associated with treatment escalation included: patient characteristics, physician characteristics, disease activity and disease impact. CONCLUSION: This study highlights multiple factors impacting treatment decision making for individuals with PsA. PsAID-12 scoring correlates with multiple measures of disease severity and odds of treatment escalation. However, most clinicians reported the PsAID-12 did not influence treatment escalation decisions. PsAID scoring could be used to increase confidence in treatment de-escalation.

An international multi-centre analysis of current prescribing practices and shared decision-making in psoriatic arthritis.

OBJECTIVES: Shared decision-making (SDM) is advocated to improve patient outcomes in Psoriatic arthritis (PsA). We analysed current prescribing practices and the extent of SDM in PsA across Europe. METHODS: The ASSIST study was a cross-sectional observational study of PsA patients aged ≥18 years attending face-to-face appointments between July 2021-March 2022. Patient demographics, current treatment and treatment decisions were recorded. SDM was measured by the clinician's effort to collaborate (CollaboRATE questionnaire) and patient communication confidence (PEPPI-5 tool). RESULTS: 503 patients were included from 24 centres across the UK, France, Germany, Italy and Spain. Physician- and patient-reported measures of disease activity were highest in the UK. Conventional synthetic DMARDs constituted a higher percentage of current PsA treatment in UK than continental Europe (66.4% vs 44.9%), which differed from biologic DMARDs (36.4% vs 64.4%). Implementing treatment escalation was most common in the UK. CollaboRATE and PEPPI-5 scores were high across centres. Of 31 patients with low CollaboRATE scores (<4.5), no patients with low PsAID-12 scores (<5) had treatment escalation. However, of 465 patients with CollaboRATE scores ≥4.5, 59 patients with low PsAID-12 scores received treatment escalation. CONCLUSIONS: Higher rates of treatment escalation seen in the UK may be explained by higher disease activity and a younger cohort. High levels of collaboration in face-to-face PsA consultations suggests effective implementation of the SDM approach. Our data indicate that, in patients with mild disease activity, only those with higher perceived collaboration underwent treatment escalation. Prospective studies should examine the impact of SDM on PsA patient outcomes. TRIAL REGISTRATION: clinicaltrials.gov, NCT05171270.

Performance of a diagnostic score for gouty arthritis: results from a cohort of acute arthritis suspected of being septic.

Septic arthritis (SA) and gout are the main suspected etiologies of acute monoarthritis. Differentiating them is essential because SA is an emergency. The performance of a gout diagnostic score developed by Janssens et al. was investigated in a cohort of patients with acute arthritis suspected of being septic. This was an ancillary study of a single-center cohort of patients with suspected SA. Patients were classified into three groups according to the final diagnosis (gout, SA or other diagnosis). We assessed the performance of the score (sensitivity [Se], specificity [Sp], positive and negative predictive value [PPV, NPV], area under the receiver operating characteristic [ROC] curve) for the diagnosis of gouty arthritis. In total, 138 patients were included: 28 (20.3%) had gout, 42 (30.4%) SA, and 68 (49.3%) another diagnosis. The median diagnostic score was 7.0 [4.5; 8.8] for patients with gout, 3.5 [2.5; 6.0] for those with SA and 3.0 [2.0-5.0] for those with another diagnosis. With a score threshold of ≥ 8, the Se for a diagnosis of gout was 28.6%, Sp 96.4%, PPV 66.7%, and NPV 84.1%. With a threshold of ≤ 4, the Se was 82.1%, Sp 64.5%, PPV 37.1%, and NPV 93.4%. The area under the ROC for the diagnostic score was 0.79. The performance of the clinico-biological score of Janssens et al. for a diagnosis of gout applied to a cohort of patients with acute arthritis and suspected of being septic was poor. Joint aspiration remains necessary to differentiate SA from another etiology.

Comparison of the cardiovascular risk profile of rheumatoid arthritis versus hand osteoarthritis patients.

It is clear that there is an increased cardiovascular (CV) risk in rheumatoid arthritis (RA) as a result of systemic inflammation. Hand osteoarthritis (HOA) patients, also have an increased CV risk, but the causes are still debated. Our objective was to compare CV risk factors and risk scores between HOA and RA patients. Thirty-five HOA patients were matched by age (< 3 years) and sex to 35 RA patients in a case-control study. We compared their CV risk profiles and their risk of occurrence of CV events at 10 years using the risk equations SCORE1, SCORE2, and QRISK3. There was a significant increase in SCORE1, SCORE2, but not in QRISK3 in the RA group compared to the HOA group, provided that the multiplication coefficient for RA was applied. This increase was found to no longer be significant for SCORE1 when RA patients have low disease activity (DAS28 ≤ 3.2; n = 8). There was no difference between groups in the frequency of metabolic syndrome, blood pressure, abdominal circumference, body mass index, uricemia, triglyceridemia, HDL cholesterolemia, or pain intensity. Conversely, HOA patients had higher LDL cholesterol and fasting blood glucose levels, in the main analysis and in the subgroup of moderate/high RA activity patients (DAS28 > 3.2; n = 26). We found a higher CV risk in RA compared to HOA patients with moderate/high disease activity. The increased CV risk reported in OA remains to be confirmed in HOA, but these patients appear to have a pro-atherogenic lipid and glycemic profile.

Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry.

OBJECTIVES: To describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD). METHODS: Physician-reported registry of I-RMD and non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections. Data were analysed descriptively. RESULTS: The study included 5121 participants from 30 countries, 90% with I-RMDs (n=4604, 68% female, mean age 60.5 years) and 10% with NI-RMDs (n=517, 77% female, mean age 71.4). Inflammatory joint diseases (58%), connective tissue diseases (18%) and vasculitis (12%) were the most frequent diagnostic groups; 54% received conventional synthetic disease-modifying antirheumatic drugs (DMARDs), 42% biological DMARDs and 35% immunosuppressants. Most patients received the Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna. In fully vaccinated cases, breakthrough infections were reported in 0.7% of I-RMD patients and 1.1% of NI-RMD patients. I-RMD flares were reported in 4.4% of cases (0.6% severe), 1.5% resulting in medication changes. AEs were reported in 37% of cases (37% I-RMD, 40% NI-RMD), serious AEs in 0.5% (0.4% I-RMD, 1.9% NI-RMD). CONCLUSION: The safety profiles of SARS-CoV-2 vaccines in patients with I-RMD was reassuring and comparable with patients with NI-RMDs. The majority of patients tolerated their vaccination well with rare reports of I-RMD flare and very rare reports of serious AEs. These findings should provide reassurance to rheumatologists and vaccine recipients and promote confidence in SARS-CoV-2 vaccine safety in I-RMD patients.

Development and validation of a self-administered questionnaire measuring essential knowledge in patients with rheumatoid arthritis.

To develop and validate a questionnaire assessing patient knowledge in rheumatoid arthritis (RA). Knowledge considered essential for patients with RA was identified through a series of Delphi rounds among rheumatologists, health professionals (HPs), patients, and then reformulated to construct the knowledge questionnaire. Cross-sectional multicenter validation was performed in 12 rheumatology departments to assess internal validity (Kuder-Richardson coefficient), external validity, acceptability, reproducibility (Lin's concordance correlation coefficient) and sensitivity to change (difference in total score before and after patient education sessions). Associations between patient variables and knowledge levels were evaluated. RAKE (RA Knowledge questionnairE) is a self-administered 45-item questionnaire scored 0-100, with a 32-item short-form survey assessing knowledge of disease, comorbidity, pharmacological treatments, non-pharmacological treatments, self-care and adaptative skills. Of 130 patients included in the validation study, 108 were women. Acceptability was good with < 5% missing data. Internal validity coefficient was 0.90. Mean (standard deviation) long-form score was 72.8 ± 17.8, with lower scores in comorbidity and self-care and higher scores in adaptive skills. Reproducibility was good (0.86 [0.80; 0.92]). RAKE score was positively correlated with the patients' level of education and the HPs' opinion on the patients' knowledge. RAKE score showed good sensitivity to change: 66.8 ± 16.4 then 83.8 ± 12.7, representing a hedges effect size of 1.14 [95% CI 0.73; 1.55]. RAKE is an updated questionnaire assessing essential knowledge for patients with RA to enhance self-management according to current guidelines and the patients' perspective. RAKE can usefully inform patient education interventions, routine care and research.

Relation between auditory difficulties and bortezomib-induced peripheral neuropathy in multiple myeloma: a single-center cross-sectional study.

PURPOSE: Bortezomib is a neurotoxic drug used in multiple myeloma and responsible for chemotherapy-induced peripheral neuropathy (CIPN). In a previous cross-sectional study, CIPN prevalence was about 26.9% in 67 patients. A second data analysis was performed to explore the relation between CIPN and auditory difficulties. METHODS: Based on 66 multiple myeloma patients from a single center, auditory difficulties were assessed with a self-questionnaire and compared to sensory CIPN (QLQ-CIPN20 questionnaire), patients' characteristics and anticancer treatments. RESULTS: The prevalence of auditory difficulties was about 42.4% (95% CI [30.6-55.2]) of the 66 patients analyzed and was higher in patients with CIPN than without (82.4% vs. 28.6%, p < 0.001). Auditory difficulties were not related to the characteristics of patients and treatments. The severity of auditory difficulties were correlated to CIPN severity (spearman's coefficient: 0.49, p = 0.009). Odds-ratio of auditory difficulties (multivariable analysis adjusted for sensory CIPN, recreation or professional noise exposure, gender, age, and treatments) was significantly associated with CIPN (18.7, 95% CI [3.0-117.1], p = 0.002). CONCLUSION: This relation between CIPN and auditory difficulties raises concerns about hearing safety in multiple myeloma patients treated by bortezomib. TRIAL REGISTRATION NUMBER: NCT03344328.

MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease.

BACKGROUND: Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA. METHODS: Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls. RESULTS: Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7×10-17). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7×10-35) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3×10-49). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4×10-5), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5×10-6). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone. CONCLUSIONS: We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Société Française de Rhumatologie and others.).

Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial.

OBJECTIVES: To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC). METHODS: Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive. INTERVENTIONS: (1) TC/T2T: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2) UC: visits every 12 weeks and treatment at the rheumatologist's discretion. MAIN OUTCOME: Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed. STATISTICAL ANALYSIS: Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC. RESULTS: 160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC. CONCLUSION: TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective. TRIAL REGISTRATION NUMBER: NCT03043846.

Impact of disease activity and treatments on ovarian reserve in patients with rheumatoid arthritis in the ESPOIR cohort.

OBJECTIVES: Patients with RA have a higher prevalence of infertility than the general population. This study sought to examine the impact of RA disease activity and treatments on ovarian reserve measured by serum anti-Müllerian hormone (AMH) levels in the ESPOIR cohort. We sought to better define the indications for fertility preservation. METHODS: Patients and serum analysis data were derived from the French national cohort ESPOIR. Enrolled patients (n = 102; 18-37-year-olds) fulfilled ACR/EULAR 2010 criteria for RA. Serum AMH levels were measured at T0, T6, T12, T24 and T36 months post-diagnosis. The impacts of RA activity (DAS28 and CRP level) and treatments (MTX only or with other medications) were evaluated at each study visit. RESULTS: A gradual decrease in patients' serum AMH levels was observed over time, in line with the descending curve described for healthy women. Serum AMH levels of RA patients in comparison with the values considered normal for age did not reveal any significant differences (P > 0.05). We did not observe any impact of RA treatments. We demonstrated an inverse correlation between AMH variation and disease activity (DAS28: r = -0.27, P = 0.003; CRP: r = -0.16, P = 0.06). CONCLUSION: This is the first study to determine serum AMH levels of a large cohort of RA patients over 36 months. Rapid disease activity control appears to be required to limit changes in the ovarian reserve. Fertility preservation is not likely to be necessary if inflammation is promptly controlled. CLINICALTRIALS.GOV IDENTIFIER: NCT03666091.

Evaluation of the impact of a nurse-led program of patient self-assessment and self-management in axial spondyloarthritis: results of a prospective, multicentre, randomized, controlled trial (COMEDSPA).

OBJECTIVE: To evaluate the impact of a nurse-led program of self-management and self-assessment of disease activity in axial spondyloarthritis. METHODS: Prospective, randomized, controlled, open, 12-month trial (NCT02374749). Participants were consecutive axial spondyloarthritis patients (according to the rheumatologist) and nurses having participated in a 1-day training meeting. The program included self-management: educational video and specific video of graduated, home-based exercises for patients; and self-assessment: video presenting the rationale of tight monitoring of disease activity with composite scores (Ankylosing Spondylitis Disease activity Score, ASDAS/Bath Ankyslosing Spondylitis Disease Activity Index, BASDAI). The nurse trained patients to collect, calculate and report (monthly) ASDAS/BASDAI. Treatment allocation was by random allocation to this program or a comorbidities assessment (not presented here and considered here as the control group). RESULTS: A total of 502 patients (250 and 252 in the active and control groups, respectively) were enrolled (age: 46.7 (12.2) years, male gender: 62.7%, disease duration: 13.7 (11.0) years). After the one-year follow-up period, the adherence to the self-assessment program was considered good (i.e. 79% reported scores >6 times). Despite a lack of statistical significance in the primary outcome (e.g. coping) there was a statistically significant difference in favor of this program for the following variables: change in BASDAI, number and duration of the home exercises in the active group, and physical activity (international physical activity score, IPAQ). CONCLUSION: This study suggests a short-term benefit of a nurse-led program on self-management and self-assessment for disease activity in a young axial spondyloarthritis population in terms of disease activity, exercises and physical activity.

Cardiovascular events and change in cholesterol levels in patients with rheumatoid arthritis treated with tocilizumab: data from the REGATE Registry.

OBJECTIVES: Rheumatoid arthritis (RA) is responsible for excess mortality mainly due to cardiovascular disease. Studies have found elevated cholesterol levels in RA patients who received tocilizumab (TCZ). We studied the occurrence of major cardiovascular events in RA patients who received TCZ in current practice. We also analysed cholesterol level changes in these patients. METHODS: Data were collected from the French REGATE Registry, a multicentre observational study including patients with RA treated with TCZ. All cardiovascular complications were analysed. Changes in cholesterol levels were studied. Factors associated with major adverse cardiac and cerebrovascular events were analysed by multivariate analysis, estimating odds ratios and 95% confidence intervals. RESULTS: During an exposure time of 5591 patient-years (PYs), 35 cardiovascular events occurred in 33 patients, corresponding to an incidence of 0.63/100 PYs. The incidence of ischaemic stroke and cardiac ischaemia was 0.41 and 0.21/100 PYs. Age and personal history of cardiovascular events were identified as risk factors associated with cardiovascular events: OR=1.06 [95% CI 1.02-1.09] and 4.10 [1.90-8.83]. Female sex was a protective factor (OR=0.29 [95% CI 0.14-0.64]). Glucocorticoids may play a role but was not statistically significant. All cholesterol variables were increased in level after the third month of treatment with TCZ, with a 15.4%, 18.9% and 13.4% increase for total cholesterol, LDL-C and HDL-C, at 3 months. CONCLUSIONS: In current practice, cardiovascular events occurring under TCZ treatment is in the range of what is expected in RA patients despite a global increase in cholesterol levels.

Concomitant fibromyalgia in primary Sjögren's syndrome in the French ASSESS cohort: comparison of the ACR 1990 and ACR 2016 criteria, FiRST questionnaire and physician's opinion.

OBJECTIVES: Dryness, fatigue, and pain are classic symptoms in primary Sjögren's syndrome (pSS) but are also common in fibromyalgia (FM). We compared the characteristics of FM assessed by different criteria (American College of Rheumatology (ACR) 2016 and 1990 criteria), physician's opinion and Fibromyalgia Rapid Screening Tool (FiRST) questionnaire) in a cohort of patients with pSS. METHODS: Eight hospital departments tested 134 patients with pSS according to AECG criteria from the Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort. RESUKLTS: FM was present in 19%, 18%, 20%, and 29% of cases according to ACR 2016, ACR 1990 criteria, physician's opinion and the FiRST questionnaire, respectively. FM criteria-positive patients had higher EULAR SS Patient-Reported Index (ESSPRI) score, but not higher EULAR SS Disease Activity Index (ESSDAI) score. The objective measurements of dryness and the use of corticosteroids and immunosuppressive drugs did not differ between FM positive and negative patients. Regarding the ESSPRI dryness and fatigue subscale scores, depression and anxiety scores and the use of anxiolytics and antidepressants, the FiRST questionnaire exhibited a higher difference between positive and negative patients than ACR 2016 criteria. ACR 1990 and physician's opinion were somewhere in the middle. ACR 2016 exhibited moderate agreement with ACR 1990 (κ=0.52) and the physician's opinion (κ=0.60) and poor agreement with FiRST (κ=0.39). CONCLUSIONS: The FM criteria identified pSS patients with higher ESSPRI scores but not higher ESSDAI systemic disease scores. Agreement between the different FM criteria was moderate, and the characteristics they described did not fully coincide.

Therapeutic education improves rheumatoid arthritis patients' knowledge about methotrexate: a single center retrospective study.

To assess, by means of a questionnaire, the effectiveness of a therapeutic education session on rheumatoid arthritis patients' knowledge about methotrexate. Retrospective study of data collected in routine care. STROBE guidelines were used. Rheumatoid arthritis patients treated with methotrexate had a therapeutic education session conducted by a rheumatology nurse at time 0 and 6 months after. They completed a questionnaire to assess their knowledge about methotrexate before the first therapeutic education session and 6 and 12 months after. A score from 0 to 100 was calculated based on 20 questions. A total of 66 patients were enrolled (50 women), with a mean age of 57 years, median disease duration of 4 years, and methotrexate treatment duration of 2 years. The knowledge score improved 6 months after the first therapeutic education session and was unchanged at 12 months. Significant improvement was observed in knowledge about the need for contraception, the contraindication of trimethoprim, the maximum dose not to be exceeded, reduction in alcohol consumption, and the value of combining folic acid with methotrexate. Knowledge about the risk of hypersensitivity pneumonitis did not improve. Skills related to the need for and timing of laboratory testing and contraception were evaluated using two role-playing situations. None of the skills improved. A therapeutic education session improves patients' knowledge about methotrexate at 6 months.

Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: A prospective multicohort study of the ABIRISK consortium.

BACKGROUND: Biopharmaceutical products (BPs) are widely used to treat autoimmune diseases, but immunogenicity limits their efficacy for an important proportion of patients. Our knowledge of patient-related factors influencing the occurrence of antidrug antibodies (ADAs) is still limited. METHODS AND FINDINGS: The European consortium ABIRISK (Anti-Biopharmaceutical Immunization: prediction and analysis of clinical relevance to minimize the RISK) conducted a clinical and genomic multicohort prospective study of 560 patients with multiple sclerosis (MS, n = 147), rheumatoid arthritis (RA, n = 229), Crohn's disease (n = 148), or ulcerative colitis (n = 36) treated with 8 different biopharmaceuticals (etanercept, n = 84; infliximab, n = 101; adalimumab, n = 153; interferon [IFN]-beta-1a intramuscularly [IM], n = 38; IFN-beta-1a subcutaneously [SC], n = 68; IFN-beta-1b SC, n = 41; rituximab, n = 31; tocilizumab, n = 44) and followed during the first 12 months of therapy for time to ADA development. From the bioclinical data collected, we explored the relationships between patient-related factors and the occurrence of ADAs. Both baseline and time-dependent factors such as concomitant medications were analyzed using Cox proportional hazard regression models. Mean age and disease duration were 35.1 and 0.85 years, respectively, for MS; 54.2 and 3.17 years for RA; and 36.9 and 3.69 years for inflammatory bowel diseases (IBDs). In a multivariate Cox regression model including each of the clinical and genetic factors mentioned hereafter, among the clinical factors, immunosuppressants (adjusted hazard ratio [aHR] = 0.408 [95% confidence interval (CI) 0.253-0.657], p < 0.001) and antibiotics (aHR = 0.121 [0.0437-0.333], p < 0.0001) were independently negatively associated with time to ADA development, whereas infections during the study (aHR = 2.757 [1.616-4.704], p < 0.001) and tobacco smoking (aHR = 2.150 [1.319-3.503], p < 0.01) were positively associated. 351,824 Single-Nucleotide Polymorphisms (SNPs) and 38 imputed Human Leukocyte Antigen (HLA) alleles were analyzed through a genome-wide association study. We found that the HLA-DQA1*05 allele significantly increased the rate of immunogenicity (aHR = 3.9 [1.923-5.976], p < 0.0001 for the homozygotes). Among the 6 genetic variants selected at a 20% false discovery rate (FDR) threshold, the minor allele of rs10508884, which is situated in an intron of the CXCL12 gene, increased the rate of immunogenicity (aHR = 3.804 [2.139-6.764], p < 1 × 10-5 for patients homozygous for the minor allele) and was chosen for validation through a CXCL12 protein enzyme-linked immunosorbent assay (ELISA) on patient serum at baseline before therapy start. CXCL12 protein levels were higher for patients homozygous for the minor allele carrying higher ADA risk (mean: 2,693 pg/ml) than for the other genotypes (mean: 2,317 pg/ml; p = 0.014), and patients with CXCL12 levels above the median in serum were more prone to develop ADAs (aHR = 2.329 [1.106-4.90], p = 0.026). A limitation of the study is the lack of replication; therefore, other studies are required to confirm our findings. CONCLUSION: In our study, we found that immunosuppressants and antibiotics were associated with decreased risk of ADA development, whereas tobacco smoking and infections during the study were associated with increased risk. We found that the HLA-DQA1*05 allele was associated with an increased rate of immunogenicity. Moreover, our results suggest a relationship between CXCL12 production and ADA development independent of the disease, which is consistent with its known function in affinity maturation of antibodies and plasma cell survival. Our findings may help physicians in the management of patients receiving biotherapies.

French survey on the crossed needs on sexual health for chronic inflammatory rheumatism patients and healthcare professionals.

Patients with Inflammatory Chronic Rheumatic disease have approximately three times more sexual dysfunction than the healthy population. However, health professionals do not dare to discuss the subject with them, largely because they do not feel educated on the subject. To define the educational needs in the sexual health of health professionals involved in patient education and those of patients with Inflammatory Chronic Rheumatic disease. This French multicenter cross-sectional online study included health professionals involved in patient education and patients with Inflammatory Chronic Rheumatic disease. Two surveys were designed to assess, both of them the specific needs. They were filled out anonymously online with a secured server. The influence of professionals and patients' characteristics on their sexual health needs were tested. 57 health professionals and 239 patients answered. 71,6% of the patients reported sexual difficulties and 79,9% had never discussed them with health professionals. To facilitate discussion, the health professionals most often wanted a colleague specialized in sexual health in their team (59,7%) and access to tools (52,6%). The patients' primary expectations were psychological support (65.7%), information (51.9%), and referral to specialists if needed (43.1%). The topics the health professionals and patients considered most useful were adverse effects of treatment and impact of rheumatism on sexuality and body image. 70,2% of the health professionals felt they needed training. This survey demonstrates the need to offer educational training to health professionals designed to enable them to address and discuss sexual health issues and give their patients appropriate advice.

Comparing patient-perceived and physician-perceived remission and low disease activity in psoriatic arthritis: an analysis of 410 patients from 14 countries.

BACKGROUND: The objective was to compare different definitions of remission and low disease activity (LDA) in patients with psoriatic arthritis (PsA), based on both patients' and physicians' perspectives. METHODS: In ReFlap (Remission/Flare in PsA; NCT03119805), adults with physician-confirmed PsA and >2 years of disease duration in 14 countries were included. Remission was defined as very low disease activity (VLDA), Disease Activity index for PSoriatic Arthritis (DAPSA) ≤4, and physician-perceived and patient-perceived remission (specific question yes/no), and LDA as minimal disease activity (MDA), DAPSA <14, and physician-perceived and patient-perceived LDA. Frequencies of these definitions, their agreement (prevalence-adjusted kappa), and sensitivity and specificity versus patient-defined status were assessed cross-sectionally. RESULTS: Of 410 patients, the mean age (SD) was 53.9 (12.5) years, 50.7% were male, disease duration was 11.2 (8.2) years, 56.8% were on biologics, and remission/LDA was frequently attained: respectively, for remission from 12.4% (VLDA) to 36.1% (physician-perceived remission), and for LDA from 25.4% (MDA) to 43.9% (patient-perceived LDA). Thus, patient-perceived remission/LDA was frequent (65.4%). Agreement between patient-perceived remission/LDA and composite scores was moderate to good (kappa range, 0.12-0.65). When patient-perceived remission or LDA status is used as reference, DAPSA-defined remission/LDA and VLDA/MDA had a sensitivity of 73.1% and 51.5%, respectively, and a specificity of 76.8% and 88.0%, respectively. Physician-perceived remission/LDA using a single question was frequent (67.6%) but performed poorly against other definitions. CONCLUSION: In this unselected population, remission/LDA was frequently attained. VLDA/MDA was a more stringent definition than DAPSA-based remission/LDA. DAPSA-based remission/LDA performed better than VLDA/MDA to detect patient-defined remission or remission/LDA. Further studies of long-term outcomes are needed.

Management of inflammatory rheumatic conditions in the elderly.

The number of elderly people with chronic inflammatory rheumatic diseases is increasing. This heterogeneous and comorbid population is at particular risk of cardiovascular, neoplastic, infectious and iatrogenic complications. The development of biotherapies has paved the way for innovative therapeutic strategies, which are associated with toxicities. In this review, we have focused on the scientific and therapeutic changes impacting the management of elderly patients affected by RA, SpA or PsA. A multidimensional health assessment resulting in an integrated therapeutic strategy was identified as a major research direction for improving the management of elderly patients.