Rheumatoid arthritis and idiopathic pulmonary fibrosis: a bidirectional Mendelian randomisation study.

BACKGROUND: A usual interstitial pneumonia (UIP) pattern of lung injury is a key feature of idiopathic pulmonary fibrosis (IPF) and is also observed in up to 40% of individuals with rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD). The RA-UIP phenotype could result from either a causal relationship of RA on UIP or vice versa, or from a simple co-occurrence of RA and IPF due to shared demographic, genetic or environmental risk factors. METHODS: We used two-sample bidirectional Mendelian randomisation (MR) to test the hypothesis of a causal effect of RA on UIP and of UIP on RA, using variants from genome-wide association studies (GWAS) of RA (separately for seropositive (18 019 cases and 991 604 controls) and seronegative (8515 cases and 1 015 471 controls) RA) and of IPF (4125 cases and 20 464 controls) as genetic instruments. Sensitivity analyses were conducted to assess the robustness of the results to violations of the MR assumptions. FINDINGS: IPF showed a significant causal effect on seropositive RA, with developing IPF increasing the risk of seropositive RA (OR=1.06, 95% CI: 1.04 to 1.08, p<0.001) which was robust under all models. For the MR in the other direction, seropositive RA showed a significant protective effect on IPF (OR=0.93; 95% CI: 0.87 to 0.99; p=0.032), but the effect was not significant when sensitivity analyses were applied. This was likely because of bias due to exclusion of patients with RA from among the cases in the IPF GWAS, or possibly because our genetic instruments did not fully capture the effect of the complex human leucocyte antigen region, the strongest RA genetic risk factor. INTERPRETATION: Our findings support the hypothesis that RA-UIP may be due to a cause-effect relationship between UIP and RA, rather than due to a coincidental occurrence of IPF in patients with RA. The significant causal effect of IPF on seropositive RA suggests that pathomechanisms involved in the development of UIP may promote RA, and this may help inform future guidelines on screening for ILD in patients with RA.

Short peripheral blood leukocyte telomere length in rheumatoid arthritis-interstitial lung disease.

Shortened telomere lengths (TLs) can be caused by single nucleotide polymorphisms and loss-of-function mutations in telomere-related genes (TRG), as well as ageing and lifestyle factors such as smoking. Our objective was to determine if shortened TL is associated with interstitial lung disease (ILD) in individuals with rheumatoid arthritis (RA). This is the largest study to demonstrate and replicate that shortened peripheral blood leukocytes-TL is associated with ILD in patients with RA compared with RA without ILD in a multinational cohort, and short PBL-TL was associated with baseline disease severity in RA-ILD as measured by forced vital capacity percent predicted.

Counteracting tryptophan metabolism alterations as a new therapeutic strategy for rheumatoid arthritis.

OBJECTIVES: Alterations in tryptophan (Trp) metabolism have been reported in inflammatory diseases, including rheumatoid arthritis (RA). However, understanding whether these alterations participate in RA development and can be considered putative therapeutic targets remains undetermined.In this study, we combined quantitative Trp metabolomics in the serum from patients with RA and corrective administration of a recombinant enzyme in experimental arthritis to address this question. METHODS: Targeted quantitative Trp metabolomics was performed on the serum from 574 previously untreated patients with RA from the ESPOIR (Etude et Suivi des POlyarthrites Indifférenciées Récentes) cohort and 98 healthy subjects. A validation cohort involved 69 established patients with RA. Dosages were also done on the serum of collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) mice and controls. A proof-of-concept study evaluating the therapeutic potency of targeting the kynurenine pathway was performed in the CAIA model. RESULTS: Differential analysis revealed dramatic changes in Trp metabolite levels in patients with RA compared with healthy controls. Decreased levels of kynurenic (KYNA) and xanthurenic (XANA) acids and indole derivatives, as well as an increased level of quinolinic acid (QUIN), were found in the serum of patients with RA. They correlated positively with disease severity (assessed by both circulating biomarkers and disease activity scores) and negatively with quality-of-life scores. Similar profiles of kynurenine pathway metabolites were observed in the CAIA and CIA models. From a mechanistic perspective, we demonstrated that QUIN favours human fibroblast-like synoviocyte proliferation and affected their cellular metabolism, through inducing both mitochondrial respiration and glycolysis. Finally, systemic administration of the recombinant enzyme aminoadipate aminotransferase, responsible for the generation of XANA and KYNA, was protective in the CAIA model. CONCLUSIONS: Altogether, our preclinical and clinical data indicate that alterations in the Trp metabolism play an active role in the pathogenesis of RA and could be considered as a new therapeutic avenue.

Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in polymyalgia rheumatica: an observational study.

OBJECTIVES: Polymyalgia rheumatica (PMR) is an inflammatory disease with a diagnosis that is sometimes difficult to establish. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) might be helpful. We analysed the usefulness of 18F-FDG PET/CT for the diagnosis of PMR. METHODS: This was an observational retrospective study of individuals with PMR who underwent 18F-FDG PET/CT and a control group. We assessed clinical and 18F-FDG PET/CT characteristics. Sixteen sites were studied. The number of sites with significant FDG uptake, the mean maximum standardised uptake value (SUVmax) and the highest SUVmax value were assessed for each patient. RESULTS: Data for 123 patients with PMR (37 with corticosteroids [CSTs] use) were analysed; 85 had new-onset PMR. As compared with the 75 controls, patients with new-onset PMR had higher mean ± SD number of sites with significant FDG uptake (11.3 ± 3.3 vs. 0.9 ± 1.1, p<0.001) and higher SUVmax scores (p<0.001). A cut-off of 5 hypermetabolic sites provided sensitivity of 96.5% and specificity 100%. For the total SUVmax score, a cut-off of 3 had the best sensitivity (92.6%) and specificity (86.1%). As compared with PMR patients using CSTs, those who were CST-naive had significantly higher CRP level (p<0.001), number of sites with significant FDG uptake (p<0.001) and SUVmax scores (p<0.01). In contrast, large-vessel vasculitis was more frequent in patients receiving CSTs than CST-naive patients (27% vs. 8%, p<0.01). CONCLUSIONS: The number of hypermetabolic sites or SUVmax quantification might be useful for PMR diagnosis, and CSTs might affect the results of 18F-FDG PET/CT.

Clinical significance of a self-reported familial occurrence of rheumatoid arthritis among patients with recent-onset arthritis: data from the ESPOIR cohort.

OBJECTIVES: To assess, in patients with recent-onset arthritis, whether a self-reported familial occurrence of rheumatoid arthritis (RA) is associated with a clinical presentation of the disease, final diagnosis, long-term outcome and treatment decisions. METHODS: The study was conducted from data of patients included between 2002 and 2005 in the early arthritis ESPOIR cohort. Patients were recruited on the basis of having at least two swollen joints for >6 weeks and <6 months, no other diagnosis than RA and no previous exposure to glucocorticoids or disease-modifying antirheumatic drugs (DMARDs). Patients were stratified into two groups according to the presence of a self-reported familial occurrence of RA at baseline. Data concerning final diagnosis (2-year visit), long-term outcome (5-year visit) and therapeutic decisions were compared between the 2 groups of patients, using logistic and Cox regression models. RESULTS: At baseline, 115 patients (14.1%) reported a familial occurrence of RA and showed, as compared with the remaining participants, higher prevalence of extra articular manifestations (EAMs) (51.8% vs. 39.6%, p=0.01) and severe EAMs (7.9% vs. 3.1%, p 0.01). Both unadjusted (hazard ratio, 1.57; 95% CI, 1.1-2.21; p = 0.01) and adjusted analysis (hazard ratio, 1.51; 95% CI, 1.06-2.15; p=0.02) identified a higher probability for the initiation of a targeted DMARD over time among patients with a self-reported familial occurrence of RA. CONCLUSIONS: In the specific context of early arthritis, a self-reported familial occurrence of RA is associated with the future decision to initiate a targeted DMARD.

Screening for spondyloarthritis in patients with inflammatory bowel diseases.

Inflammatory bowel diseases (IBDs) can be associated with various musculoskeletal (IBD-MSK) manifestations that could be difficult to classify for gastroenterologists. We aimed to evaluate the characteristics of patients with IBD-MSK and the prevalence of spondyloarthritis (SpA). In this observational cross-sectional study, we included patients with IBD-MSK complaints (peripheral or back pain). All patients underwent a standardized rheumatology evaluation including clinical, biological and imaging evaluations (MRI of spine and sacroiliac joints and ultrasonography of enthesis). We included 183 IBD patients (60.7% women; median [interquartile range] age 45 [36-56] years); 159 (87%) had joint pain. In 43 (23.5%) and 25/175 (14.3%) patients, enthesis abnormalities were found on ultrasonography and sacroiliitis on MRI, respectively. SpA was diagnosed in 54 (29.5%) patients. IBD-related arthralgia and degenerative spine disease were diagnosed in 105 (57.4%) and 72 (39.3%) patients. Sixteen (29.6%) SpA patients initiated a new conventional synthetic disease modifying anti-rheumatic drug (DMARD). A biologic DMARD was initiated in 10 patients or changed in 3. More than half of IBD-MSK patients had IBD-related arthralgia, and about one-third had definite SpA. Ultrasonography of enthesis and systematic MRI of sacroiliac joints seem useful for SpA classification and differential diagnosis in these patients who often have musculoskeletal pain complaints. Therapeutics were changed in most patients, which highlights the need for a multidisciplinary approach for managing IBD with extra-intestinal symptoms.

Salivary gland ultrasonography in patients with connective tissue diseases: a multi-centre observational study.

OBJECTIVE: US of salivary glands (SGUS) is a non-invasive tool that allows for diagnosing primary SS (pSS) or secondary SS (sSS). However, little is known about the prevalence of US findings of SS in other CTDs. The aim of this multi-centre observational study was to evaluate, in CTD patients with or without SS, the prevalence of abnormal SGUS findings and the possible association of the findings with clinical or biological phenotypes. METHODS: B-Mode SGUS was performed by one operator blinded to clinical data. Each SG was semi-quantitatively rated on a scale from 0 to 4 according to the Jousse-Joulin score; a score ≥2 was considered pathological. RESULTS: Data for 194 patients were analysed (pSS, n = 30; sSS, n = 39; other CTDs, n = 77; controls, n = 48). SGUS findings were abnormal in 80%, 67%, 25% and 2% of patients, respectively. Independent of the underlying disease, age and sex, abnormal SGUS findings were significantly associated with presence of anti-SSA antibodies (P < 0.001), pSS (P < 0.001) and sSS (P < 0.01). Among SS patients, abnormal SGUS findings were associated with the presence of hypergammaglobulinemia, anti-SSA antibodies, objective eye dryness and increased anti-nuclear antibody level, with no difference in EULAR SS Disease Activity Index. CONCLUSION: Abnormal SGUS findings were associated with anti-SSA antibody positivity independent of the underlying disease. In SS patients, abnormal findings were associated with immunologic features and mouth involvement. Among CTD patients, SGUS changes may be associated with a particular immune profile.

Interstitial lung diseases associated with mutations of poly(A)-specific ribonuclease: A multicentre retrospective study.

BACKGROUND AND OBJECTIVE: Poly(A)-specific ribonuclease (PARN) mutations have been associated with familial pulmonary fibrosis. This study aims to describe the phenotype of patients with interstitial lung disease (ILD) and heterozygous PARN mutations. METHODS: We performed a retrospective, observational, non-interventional study of patients with an ILD diagnosis and a pathogenic heterozygous PARN mutation followed up in a centre of the OrphaLung network. RESULTS: We included 31 patients (29 from 16 kindreds and two sporadic patients). The median age at ILD diagnosis was 59 years (range 54 to 63). In total, 23 (74%) patients had a smoking history and/or fibrogenic exposure. The pulmonary phenotypes were heterogenous, but the most frequent diagnosis was idiopathic pulmonary fibrosis (n = 12, 39%). Haematological abnormalities were identified in three patients and liver disease in two. In total, 21 patients received a specific treatment for ILD: steroids (n = 13), antifibrotic agents (n = 11), immunosuppressants (n = 5) and N-acetyl cysteine (n = 2). The median forced vital capacity decline for the whole sample was 256 ml/year (range -363 to -148). After a median follow-up of 32 months (range 18 to 66), 10 patients had died and six had undergone lung transplantation. The median transplantation-free survival was 54 months (95% CI 29 to ∞). Extra-pulmonary features were less frequent with PARN mutation than telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC) mutation. CONCLUSION: IPF is common among individuals with PARN mutation, but other ILD subtypes may be observed.

Genotype-Phenotype Relationships in Inheritable Idiopathic Pulmonary Fibrosis: A Greek National Cohort Study.

BACKGROUND: Monogenic and polygenic inheritances are evidenced for idiopathic pulmonary fibrosis (IPF). Pathogenic variations in surfactant protein-related genes, telomere-related genes (TRGs), and a single-nucleotide polymorphism in the promoter of MUC5B gene encoding mucin 5B (rs35705950 T risk allele) are reported. This French-Greek collaborative study, Gen-Phen-Re-GreekS in inheritable IPF (iIPF), aimed to investigate genetic components and patients' characteristics in the Greek national IPF cohort with suspected heritability. PATIENTS AND METHODS: 150 patients with familial PF, personal-family extrapulmonary disease suggesting short telomere syndrome, and/or young age IPF were analyzed. RESULTS: MUC5B rs35705950 T risk allele was detected in 103 patients (90 heterozygous, 13 homozygous, allelic frequency of 39%), monoallelic TRG pathogenic variations in 19 patients (8 TERT, 5 TERC, 2 RTEL1, 2 PARN, 1 NOP10, and 1 NHP2), and biallelic ABCA3 pathogenic variations in 3. Overlapping MUC5B rs35705950 T risk allele and TRG pathogenic variations were shown in 11 patients (5 TERT, 3 TERC, 1 PARN, 1 NOP10, and 1 NHP2), MUC5B rs35705950 T risk allele, and biallelic ABCA3 pathogenic variations in 2. In 38 patients, neither MUC5B rs35705950 T risk allele nor TRG pathogenic variations were detectable. Kaplan-Meier curves showed differences in time-to-death (p = 0.025) where patients with MUC5B rs35705950 T risk allele alone or in combination with TRG pathogenic variations presented better prognosis. CONCLUSION: The Gen-Phen-Re-GreekS in iIPF identified multiple and overlapping genetic components including the rarest, underlying disease's genetic "richesse," complexity and heterogeneity. Time-to-death differences may relate to diverse IPF pathogenetic mechanisms implicating "personalized" medical care driven by genotypes in the near future.

MRI Features Associated With the Detection of Microbial Pathogens by CT-Guided Biopsy in Septic Spondylodiscitis.

OBJECTIVE: The aim of this study was to assess the magnetic resonance imaging (MRI) features associated with microbial pathogen detection by computed tomography (CT)-guided biopsy in patients with suspected septic spondylodiscitis. METHODS: For the last 10-year period, we analyzed the medical records of patients who underwent MRI and CT-guided biopsy for suspected septic spondylodiscitis. Clinical characteristics were recorded. The following MRI features were assessed: edema or contrast enhancement of the intervertebral disc, adjacent vertebrae, epidural and paravertebral space, presence of abscess, and paravertebral edema size. A positive biopsy was defined by pathogen identification on bacterial analysis or the presence of granuloma on histology. Predictors of a positive biopsy were assessed with a logistic regression model. RESULTS: We examined data for 61 patients (34 [56%] male; mean age, 59.9 ± 18.0 years); for 35 patients (57%), CT-guided biopsy was positive for a pathogen. The 4 MRI findings significantly associated with a positive biopsy were epiduritis, greater than 50% vertebral endplate edema, loss of intradiscal cleft, and abscess. The size of paravertebral edema was greater with a positive than negative biopsy (median, 15.9 [interquartile range, 11.3-21.3] vs 7.3 [4.6-12.9] mm; p = 0.004). On multivariable analysis, epiduritis was the only independent predictor of a positive biopsy (adjusted odds ratio, 7.4 [95% confidence interval, 1.7-31.4]; p = 0.006). CONCLUSIONS: Epiduritis and the size of paravertebral edema on MRI are associated with detection of a microbial pathogen in suspected septic spondylodiscitis. For patients without these MRI signs, the need for further investigations such as enriched or prolonged cultures, a second CT-guided biopsy, or even surgical biopsy need to be discussed.

Interleukin 6 receptor inhibition in primary Sjögren syndrome: a multicentre double-blind randomised placebo-controlled trial.

OBJECTIVES: No immunomodulatory drug has been approved for primary Sjögren's syndrome, a systemic autoimmune disease affecting 0.1% of the population. To demonstrate the efficacy of targeting interleukin 6 receptor in patients with Sjögren's syndrome-related systemic complications. METHODS: Multicentre double-blind randomised placebo-controlled trial between 24 July 2013 and 16 July 2018, with a follow-up of 44 weeks, involving 17 referral centres. Inclusion criteria were primary Sjögren's syndrome according to American European Consensus Group criteria and score ≥5 for the EULAR Sjögren's Syndrome Disease activity Index (ESSDAI, score of systemic complications). Patients were randomised to receive either 6 monthly infusions of tocilizumab or placebo. The primary endpoint was response to treatment at week 24. Response to treatment was defined by the combination of (1) a decrease of at least 3 points in the ESSDAI, (2) no occurrence of moderate or severe activity in any new domain of the ESSDAI and (3) lack of worsening in physician's global assessment on a Visual Numeric Scale ≥1/10, all as compared with enrolment. RESULTS: 110 patients were randomised, 55 patients to tocilizumab (mean (SD) age: 50.9 (12.4) years; women: 98.2%) and 55 patients to placebo (54.8 (10.7) years; 90.9%). At 24 weeks, the proportion of patients meeting the primary endpoint was 52.7% (29/55) in the tocilizumab group and 63.6% (35/55) in the placebo group, for a difference of -11.4% (95% credible interval -30.6 to 9.0) (Pr[Toc >Pla]=0.14). CONCLUSION: Among patients with primary Sjögren's syndrome, the use of tocilizumab did not improve systemic involvement and symptoms over 24 weeks of treatment compared with placebo. TRIAL REGISTRATION NUMBER: NCT01782235.

Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry.

OBJECTIVE: To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA). METHODS: We analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders. RESULTS: Of 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity. CONCLUSIONS: People with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.

Influence of inflammatory and non-inflammatory rheumatic disorders on the clinical and biological profile of type-2 diabetes.

OBJECTIVE: To study the profile of type-2 diabetes (T2D) in patients with RA or OA. METHODS: This observational, multicentre, cross-sectional study included, over a 24-month period, consecutive patients with adult-onset diabetes and RA or OA. We collected demographics, disease activity and severity indices, current treatments for RA and diabetes, history and complications of diabetes. A systematic blood test was performed, assessing inflammatory, immunological and metabolic parameters. The homoeostasis model assessment (HOMA)2-S was used to assess insulin resistance. RESULTS: We included 167 patients with T2D, 118 with RA and 49 with OA. RA and OA patients had severe T2D with suboptimal metabolic control and a biological profile of insulin resistance. Insulin resistance was significantly higher in RA than in OA patients after stratification on age, BMI and CS use [HOMA2-S: 63.5 (35.6) vs 98.4 (69.2), P < 0.001]. HOMA2-S was independently associated with DAS28 [odds ratio (OR): 4.46, 95% CI: 1.17, 17.08]. T2D metabolic control was not related to disease activity and functional impairment, but HbA1c levels were independently associated with bone erosions (OR: 4.43, 95% CI: 1.18, 16.61). Treatment with low-dose CSs was not associated with decreased insulin sensitivity or increased HbA1c levels. Treatment with TNF-α inhibitors was associated with increased insulin sensitivity compared with patients not receiving biologics [101.3 (58.71) vs 60.0 (32.5), P = 0.001]. CONCLUSION: RA patients display severe T2D with inflammation-associated insulin resistance. These findings may have therapeutic implications, with the potential targeting of insulin resistance through the treatment of joint and systemic inflammation.

Refining myositis associated with primary Sjögren's syndrome: data from the prospective cohort ASSESS.

OBJECTIVES: To refine the prevalence, characteristics and response to treatment of myositis in primary SS (pSS). METHODS: The multicentre prospective Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort of 395 pSS patients with ≥60 months' follow-up was screened by the 2017 EULAR/ACR criteria for myositis. Extra-muscular complications, disease activity and patient-reported scores were analysed. RESULTS: Before enrolment and during the 5-year follow-up, myositis was suspected in 38 pSS patients and confirmed in 4 [1.0% (95% CI: 0.40, 2.6)]. Patients with suspected but not confirmed myositis had higher patient-reported scores and more frequent articular and peripheral nervous involvement than others. By contrast, disease duration in patients with confirmed myositis was 3-fold longer than without myositis. Two of the four myositis patients fulfilled criteria for sporadic IBM. Despite receiving three or more lines of treatment, they showed no muscle improvement, which further supported the sporadic IBM diagnosis. The two other patients did not feature characteristics of a myositis subtype, which suggested 'pure' pSS myositis. Steroids plus MTX was then efficient in achieving remission. CONCLUSIONS: Myositis, frequently suspected, occurs in 1% of pSS patients. Especially when there is resistance to treatment, sporadic IBM should be considered and might be regarded as a late complication of this disease.

Current favourable 10-year outcome of patients with early rheumatoid arthritis: data from the ESPOIR cohort.

OBJECTIVE: To report the 10-year outcome of an inception cohort of patients with early rheumatoid arthritis (RA), the ESPOIR cohort, and predictors of outcome. METHODS: From 2003 to 2005, 813 patients were included if they had early arthritis (<6 months) with a high probability of RA and had never been prescribed DMARDs. Multivariate analysis was used to evaluate predictors of outcome. RESULTS: In total, 521 (64.1%) RA patients were followed up for 10 years; 35 (4.3%) died, which appears to be similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174 (33.4%) received at least one biologic DMARD, 13.6% within 2 years. At year 10, 273 (52.4%) patients were in DAS28 remission, 40.1% in sustained remission, 14.1% in drug-free remission, 39.7% in CDAI remission. Half of the patients achieved a health assessment questionnaire-disability index (HAQ-DI) < 0.5. SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 (17.9). Only 34 (6.5%) patients required major joint surgery. A substantial number of patients showed new comorbidities over 10 years. Positivity for anti-citrullinated peptides antibodies (ACPA) was confirmed as a robust predictor of long-term outcome. CONCLUSIONS: We report a very mild 10-year outcome of a large cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients.

Secukinumab and ustekinumab treatment in psoriatic arthritis: results of a direct comparison.

OBJECTIVES: To evaluate the characteristics of patients (pts) with PsA treated by ustekinumab (UST) or secukinumab (SEK) and to compare real-world persistence of UST and SEK in PsA. METHODS: In this retrospective, national, multicentre cohort study, pts with PsA (CASPAR criteria or diagnosis confirmed by the rheumatologist) initiating UST or SEK with a follow-up ≥6 months were included from January 2011 to April 2019. The persistence between SEK and UST was assessed after considering the potential confounding factors by using pre-specified propensity-score methods. Causes of discontinuation and tolerance were also collected. RESULTS: A total of 406 pts were included: 245 with UST and 161 with SEK. The persistence rate was lower in the UST group compared with the SEK group [median persistence 9.4 vs 14.7 months; 26.4% vs 38.0% at 2 years; weighted hazard ratio (HR) = 1.42; 95% CI: 1.07, 1.92; P =0.015]. In subgroup analysis, the persistence rate of SEK associated with MTX was significantly higher than that of UST associated with MTX: HR = 2.20; 95% CI: 1.30, 3.51; P =0.001, in contrast to SEK vs UST monotherapy: HR = 1.06; 95% CI: 0.74, 1.53; P =0.75. Discontinuation due to inefficacy was reported in 91.7% (SEK) and 82.4% (UST) of pts. Discontinuation due to an adverse event was reported in 12.2% (SEK) and 7.7% (UST) of pts. CONCLUSION: In this first study comparing UST and SEK, the persistence of SEK was higher than that of UST in PsA. In subgroup analysis, this difference was only found in association with MTX.

Screening of dental and sinus infections in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is associated with increased risk of infections. Screening for oral (dental and/or sinus) infection could be proposed before biologic disease-modifying antirheumatic drugs (bDMARDs) initiation but is not systematically recommended. The aim of our study was to assess the prevalence of oral infection in RA patients requiring bDMARDs. MATERIALS AND METHODS: This was a monocentric retrospective study. We included patients with RA and active disease requiring bDMARDs. Dental infection and sinusitis were assessed by a stomatologist and otorhinolaryngologist after clinical, panoramic dental X-ray and sinus CT evaluation. Factors associated with oral infections were analysed in uni- and multivariate models, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 223 RA patients (79.4% women, mean disease duration 8.9 ± 8.6 years). The mean age was 54.4 ± 10.9 years and mean Disease Activity Score in 28 joints 5.5 ± 2.6. Systematic dental screening revealed infection requiring treatment before bDMARDs initiation in 46 (20.9%) patients. Sinusitis was diagnosed by the otorhinolaryngologist in 33 (14.8%) patients. Among the 223 patients, 69 (30.9%) had dental and/or sinus infection. On univariate analysis, active smoking was associated with increased probability of oral infection (OR = 2.16 [95% CI 1.02-4.57], P = .038) and methotrexate with reduced probability (OR = 0.43 [95% CI 0.23-0.81], P = .006). On multivariate analysis, no RA variables were associated with oral infection. CONCLUSION: In our study, asymptomatic oral infection was confirmed in one third of RA patients.

Recent advances in rheumatoid arthritis-associated interstitial lung disease.

PURPOSE OF REVIEW: To provide an overview of recent studies that could be helpful in a better understanding of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and to facilitate the clinical management of this severe complication of RA. RECENT FINDINGS: The advances in deciphering the genetic architecture of RA-ILD support the hypothesis of RA-ILD as a complex disease with a complex phenotype encompassing at least the usual interstitial pneumonia (UIP) high-resolution CT pattern and non-UIP. Genetics studies have provided evidence for a shared genetic background in idiopathic pulmonary fibrosis (IPF) and RA-ILD, and more specifically RA-UIP, a disease with high morbidity and mortality. These findings support the rationale for common pathogenic pathways opening new avenues for future intervention in RA-ILD, notably with - drugs that proved active in IPF. In agreement, a recent controlled trial suggests efficacy of nintedanib, an antifibrotic drug, in patients with progressive lung fibrosis, including RA-ILD. However, there is a substantial gap in RA-ILD treatment, notably evaluating the effect of the RA treatments on the ILD course because of no controlled trial yet. SUMMARY: The phenotypical, environmental, and genetic similarities between IPF and RA-ILD have led to a better understanding of the underlying pathogenesis of RA-ILD. Despite the identification of several biomarkers and useful screening tools, several questions remain unanswered regarding the identification of patients with RA at increased risk of ILD and risk of progression. Other substantial gaps are the lack of recommendations for how high-risk patients should be screened and which specific therapeutic strategy should be initiated. International collaborative efforts are needed to address these issues and develop specific recommendations for RA-ILD.

Ultrasound shoulder assessment of calcium pyrophosphate disease with suspected polymyalgia rheumatica.

OBJECTIVES: Polymyalgia rheumatica (PMR) is characterised by inflammatory pain of shoulders and the pelvic girdle that affects older people. Conditions that can mimic PMR include rheumatoid arthritis (RA), spondyloarthritis (SpA) and calcium pyrophosphate disease (CPPD). In this study, we aimed to define the prevalence of CPPD among patients with polymyalgic syndrome with suspected PMR according to recent ACR/EULAR criteria. METHODS: This was an observational study in which we included patients with polymyalgic syndrome (inflammatory pain of shoulders, elevated C-reactive protein (CRP) level, and age >50 years). All patients were tested for RA antibodies and underwent ultrasonography (US) of shoulders [gleno-humeral effusion, biceps tenosynovitis, sub-acromiodeltoid (SAD) bursitis, synovitis and CPPD of the acromio-clavicular (AC) joint and humeral bone erosion]. RESULTS: We included 94 patients with polymyalgic syndrome (mean age 69.4±11.3 years, 67% female); 27 had a diagnosis of RA and 14 SpA. The remaining 52 were considered to have PMR according to ACR/EULAR criteria for PMR; 25 had a diagnosis of CPPD. As compared with PMR patients without CPPD, those with CPPD more frequently had humeral bone erosion (p=0.003), synovitis and CPPD of the AC joint (p<0.0001 for both) and less frequently SAD bursitis (p=0.0098). For PMR diagnosis, the most sensitive US features were SAD bursitis (96.3%) and biceps tenosynovitis (85.2%), despite low specificity. For CPPD diagnosis, CPPD of the AC joint had the best ratio of sensitivity to specificity (sensitivity: 85.2%; specificity: 97.1%). CONCLUSIONS: Detection of CPPD is relatively frequent with suspected PMR. Adding US assessment of the AC joint to usual US screening might help the clinician better distinguish PMR from other conditions, notably CPPD.