Search

Objectives To investigate the hypothesis that a history of PMR is associated with a more severe and damaging disease course in newly diagnosed GCA patients. Methods This was a retrospective analysis of GCA patients diagnosed between December 2006 and May 2021. We compared vascular ultrasound findings (presence of vasculitis and vascular stenosis) in GCA patients with and without prior PMR. Results Forty-nine of 311 GCA patients (15.8%) had prior PMR in a median of 30.6 (IQR 7.1–67.3) months before GCA diagnosis. Patients with prior PMR more often had large vessel vasculitis (LVV) (51.0% vs 25.0%, P  < 0.001) and stenosis within the vasculitic segments (18.4% vs 3.1%, P  < 0.001) on ultrasound. In multivariable analysis, prior PMR remained significantly associated with LVV (odds ratio 7.65, 95% CI: 2.72, 23.97, P  < 0.001). Polymyalgic symptoms at GCA diagnosis in the patients without prior PMR were not associated with a higher prevalence of LVV (P  = 0.156). Conclusion Patients with a diagnosis of PMR before GCA diagnosis had two times more often large vessel involvement and significant more vasculitic stenoses on ultrasound examination than patients without prior PMR. Pre-existing PMR is an independent risk factor for more extensive and advanced ultrasound findings at GCA diagnosis. The contribution of subclinical vasculitis to disease associated damage should be further studied. [ABSTRACT FROM AUTHOR]

Objective To describe the clinical efficacy of tixagevimab/cilgavimab in pre-exposure prophylaxis in patients at risk of severe coronavirus disease 2019 (COVID-19) and unresponsive to vaccination (anti-severe acute respiratory syndrome coronavirus 2 antibodies <260 binding antibody units/ml) in rheumatology. Methods In this multicentre observational study we included patients with autoimmune or inflammatory diseases who received pre-exposure prophylaxis with tixagevimab/cilgavimab between December 2021 and August 2022. The endpoint was incidence of COVID-19 and its severity. Results Tixagevimab/cilgavimab was administered to 115 patients with a median age of 62 years [interquartile range (IQR) 52–71], chronic arthritis (n  = 53), connective tissue disease (n  = 38) or vasculitis (n  = 11). The main background immunosuppressants were rituximab (n  = 98), corticosteroids [ n  = 62; median dose 5 mg (95% CI 5–8)] and methotrexate (n  = 48). During a median follow-up of 128 days (IQR 93–173), COVID-19 occurred in 23/115 patients (20%) and the omicron variant was identified for the eight genotyped patients. During the study period, the average weekly incidence was 1071/100 000 inhabitants in Île-de-France vs 588/100 000 in our patients. Patients who received a two-injection regimen had a lower risk of infection than those with a single injection [16/49 (33%) vs 5/64 (8%), P  = 0.0012]. The COVID-19-positive patients did not differ from uninfected patients concerning age, comorbidities, underlying rheumatic disease and immunosuppressants. All COVID-19 cases were non-severe. The tolerance of injections was excellent. Conclusion In a population with autoimmune or inflammatory diseases at risk of severe COVID-19 unresponsive to vaccination, pre-exposure prophylaxis withy tixagevimab/cilgavimab was associated with a lower incidence of COVID-19 and no severe infections. [ABSTRACT FROM AUTHOR]

Objective This study aimed to establish prediction models for respiratory-related mortality in microscopic polyangiitis (MPA) complicated by interstitial lung disease (ILD) using clinical characteristics. Methods We enrolled patients with MPA with ILD between May 2005 and June 2021 in a multicentre cohort of Japanese patients with MPA (REVEAL cohort). We evaluated the demographic, clinical, laboratory, radiological findings, treatments and the presence of honeycombing 1 cm above the diaphragm using chest high-resolution CT (HRCT) on admission. We explored the risk factors predictive of respiratory-related mortality. Results Of 115 patients, 26 cases died of respiratory-related diseases during a median follow-up of 3.8 years. Eighteen patients (69%) died due to respiratory infection, three (12%) had diffuse alveolar haemorrhage, and five (19%) had exacerbation of ILD. In univariate analysis, older age, lower percent forced vital capacity (%FVC), lower percent diffusing capacity of carbon monoxide (%DLCO), and the presence of honeycombing in the right lower lobe were identified as risk factors. Additionally, in multivariate analysis adjusted for age and treatment, %FVC, %DLCO and the presence of honeycombing in the right lower lobe were independently associated with respiratory-related mortality. We created prediction models based on the values of %FVC, %DLCO and presence of honeycombing on chest HRCT (termed "MPF model"). The 5-year respiratory-related death-free rate was significantly different between patients with MPA with ILD stratified by the number of risk factors based on the MPF model. Conclusions Our study indicates that the MPF model may help predict respiratory-related death in patients with MPA with ILD. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study was to determine baseline risk factors for requiring immunosuppression and having persistent arthritis in patients with immune checkpoint inhibitor–induced inflammatory arthritis (ICI–inflammatory arthritis). Methods Participants were adults with rheumatologist diagnosed ICI–inflammatory arthritis. The primary outcome was requirement of conventional synthetic (cs) or biologic (b) DMARDs; other outcomes were persistence of inflammatory arthritis >6 months after ICI cessation and requirement of CSs. Logistic regression models evaluated associations between clinical features and primary and secondary outcomes, with adjustment for potential confounders, as appropriate. Results One hundred and twenty-six patients with ICI–inflammatory arthritis were included; 53 patients (42%) required a csDMARD/bDMARD. In the univariate logistic regression analysis, higher clinical disease activity index (CDAI), tenosynovitis, longer symptom duration before first rheumatology visit and longer ICI duration were significantly associated with a higher likelihood of requiring DMARDs; in addition, there was a trend towards those treated with prior chemotherapy being less likely to need DMARDs. After adjustment, tenosynovitis, longer symptom duration and higher CDAI remained associated with requiring DMARDs, while those with prior chemotherapy were significantly less likely to require DMARDs. Combination anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein-4)/PD-1 (Programmed cell death protein-1) therapy and CS use at baseline were associated with a higher risk of persistent inflammatory arthritis. Conclusion Higher levels of disease activity, tenosynovitis and longer symptom duration prior to rheumatology referral were associated with requiring DMARDs for ICI–inflammatory arthritis, while those treated previously with chemotherapy were less likely to require additional immunosuppression. The presence of risk factors for severe disease at baseline may indicate a role for higher initial CS dose, earlier rheumatology referral, and adoption of immunosuppression beyond CSs to improve outcomes. [ABSTRACT FROM AUTHOR]

Objectives To measure the association between SLE remission and scores of patients-reported outcome (PRO) measures. Methods We performed a prospective cohort study of SLE patients with a 2-year follow-up, using Lupus Patient-Reported Outcome (LupusPRO), Lupus Quality of Life (LupusQoL), Systemic Lupus Erythematosus Quality of Life (SLEQOL) and 36-item Short Form (SF-36) questionnaires. Remission was defined as remission off treatment (ROFT) and remission on treatment (RONT) according to the definitions of remission in SLE consensus. Mixed models accounting for repeated measures were used to compare groups as follow: ROFT and RONT vs no remission and lupus low disease activity state (LLDAS) vs no LLDAS. Results A total of 1478 medical visits and 2547 PRO questionnaires were collected during the follow-up from the 336 recruited patients. A between-group difference in PRO scores reaching at least 5 points on a 0–100 scale was obtained in the following domains: lupus symptoms (LLDAS: +5 points on the 0–100 scale, RONT: +9, ROFT: +5), lupus medication (LLDAS: +5, RONT: +8, ROFT: +9), pain vitality (LLDAS: +6, RONT: +9, ROFT: +6) of LupusPRO; role emotional (LLDAS: +5, RONT: +8), role physical (RONT: +7 and ROFT: +7), bodily pain (RONT: +6), mental health (RONT: +5) and social functioning (RONT: +6) of SF-36. In contrast, a between-group difference reaching at least 5 points was not achieved for any of the LupusQoL and SLEQOL domains. Conclusions RONT, ROFT and LLDAS were associated with significant and clinically relevant higher QoL in most PRO domains of the LupusPRO (disease specific) and SF-36 (generic) questionnaires, but not with LupusQoL and SLEQOL disease-specific questionnaires. [ABSTRACT FROM AUTHOR]

Objectives We evaluated the association between anti-ribosomal P antibody (anti-RibP) titres and disease activity in Japanese SLE patients. Methods Eighty patients admitted and treated in Niigata University Hospital for new-onset or flare-up of SLE were included in this retrospective cross-sectional study. Clinical data were obtained from medical records at admission. The anti-RibP index, and cytokine and tryptophan metabolite levels were determined by ELISA. Results Of the 80 SLE patients, 30 had anti-RibP. Anti-RibP presence was associated with a greater prevalence of skin rash and more severe inflammatory responses, demonstrated by higher inflammatory cytokine levels, hypocomplementemia, and accelerated tryptophan metabolism, in younger patients. The serum anti-RibP index was correlated with age at diagnosis, clinical indicators, initial prednisolone dose, and cytokines and tryptophan metabolite levels in univariate analysis. Multivariate analysis showed that the anti-RibP index was independently associated with the initial prednisolone dose and the prevalence of skin rash. The anti-RibP IgGs were mainly the IgG2 and IgG3 subclasses, and anti-RibP IgG3 was associated with hypocomplementemia, higher DAS, accelerated kynurenine pathway activity, and higher proinflammatory cytokine production. The coexistence of anti-dsDNA IgG and anti-RibP IgG2 or IgG3 accompanied higher IL-10 and IFN-α2 levels; furthermore, anti-RibP IgG3 coexistence with anti-dsDNA antibody contributed to the requirement for higher initial prednisolone doses and accelerated kynurenine pathway activity. Conclusion Anti-RibP was associated with clinical manifestations and parameters in SLE, and its index might be a useful indicator of disease severity. Anti-RibP IgG3 was the IgG subclass most strongly associated with the pathogenesis of SLE. [ABSTRACT FROM AUTHOR]

Objectives Frailty is a risk factor for adverse health in SLE. The Fried phenotype (FP) and the SLICC Frailty Index (SLICC-FI) are common frailty metrics reflecting distinct approaches to frailty assessment. We aimed to (1) compare frailty prevalence according to both metrics in women with SLE and describe differences between frail and non-frail participants using each method and (2) evaluate for cross-sectional associations between each metric and self-reported disability. Methods Women aged 18–70 years with SLE were enrolled. FP and SLICC-FI were measured, and agreement calculated using a kappa statistic. Physician-reported disease activity and damage, Patient Reported Outcome Measurement Information System (PROMIS) computerized adaptive tests, and Valued Life Activities (VLA) self-reported disability were assessed. Differences between frail and non-frail participants were evaluated cross-sectionally, and the association of frailty with disability was determined for both metrics. Results Of 67 participants, 17.9% (FP) and 26.9% (SLICC-FI) were frail according to each metric (kappa = 0.41, P  < 0.01). Compared with non-frail women, frail women had greater disease damage, worse PROMIS scores, and greater disability (all P  < 0.01 for FP and SLICC-FI). After age adjustment, frailty remained associated with a greater odds of disability [FP: odds ratio (OR) 4.7, 95% CI 1.2, 18.8; SLICC-FI: OR 4.6, 95% CI 1.3, 15.8]. Conclusion Frailty is present in 17.9–26.9% of women with SLE. These metrics identified a similar, but non-identical group of women as frail. Further studies are needed to explore which metric is most informative in this population. [ABSTRACT FROM AUTHOR]

Objective This study aimed to compare the efficacy and safety of adalimumab (ADA) vs tocilizumab (TCZ) in patients with Takayasu arteritis (TAK). Methods This was a randomized, controlled, open-label study. Forty patients with active and severe TAK were enrolled. They were treated with ADA (n  = 21) combined with glucocorticoids (GCs) and MTX or TCZ (n  = 19) combined with GCs and MTX. The planned follow-up duration was 12 months. The primary end point was the efficacy rate (ER) at 6 months. The secondary end points included ER at 9 and 12 months, relapse rate, GC tapering, adverse effects, and life quality changes during treatment. Results In the intention-to-treat (ITT) population, the ER at 6 months was higher in the ADA group (85.71% vs 52.63%, P  = 0.02). A similar direction of effect was noted in the per-protocol set (89.47% vs 62.50%, P  = 0.06). The percentages of patients who achieved a GC dose of ≤10 mg/day at 6 months were similar between the ADA and TCZ groups (47.37% vs 43.75%, P  = 0.83). The ERs at 9 and 12 months were similar between the two groups (P  > 0.05). During the first 12 months of treatment, the relapse rate and adverse event incidence were comparable between the two groups (ADA vs TCZ: 9.52% vs 10.53%, P  = 0.96; 38.10% vs 47.37%, P  = 0.55, respectively). Conclusion ADA combined with GCs and MTX may be more efficacious than TCZ combined with GCs and MTX among patients with active and severe TAK. Trial registration Clinicaltrials.gov; NCT04300686. [ABSTRACT FROM AUTHOR]

Objectives Assessment of construct validity and reliability of a novel patient-reported outcome (PRO) instrument for assessing the severity and impact of RP in SSc. Methods An international multicentre study validation study of the 27-item Assessment of Systemic Sclerosis-Associated Raynaud's Phenomenon (ASRAP) and 10-item short-form (ASRAP-SF) questionnaires. The relationship between ASRAP questionnaires and demographics, clinical phenotype and legacy instruments for assessing SSc-RP severity, disability and pain was assessed. Repeatability was evaluated at 1 week. Anchor-based statements of health status facilitated assessment of ASRAP thresholds of meaning. Results A total of 420 SSc subjects were enrolled. There was good correlation between ASRAP (and ASRAP-SF) with RP visual analogue scale (VAS) and Scleroderma Health Assessment Questionnaire RP VAS (rho range 0.648–0.727, P  < 0.001). Correlation with diary-based assessment of SSc-RP attack frequency and duration was lower (rho range 0.258–0.504, P  < 0.001). ASRAP questionnaires had good correlation with instruments for assessing disability, hand function, pain and global health assessment (rho range 0.427–0.575, P  < 0.001). Significantly higher ASRAP scores were identified in smokers, patients with active digital ulceration (DU), previous history of DU and calcinosis (P  < 0.05 for all comparisons). There was excellent repeatability at 1 week among patients with stable SSc-RP symptoms (intra-class coefficients of 0.891 and 0.848, P  < 0.001). Patient-acceptable symptom state thresholds for ASRAP and ASRAP-SF were 45.34 and 45.77, respectively. A preliminary Minimally Important Clinical Difference threshold of 4.17 (95% CI 0.53, 7.81, P  = 0.029) was estimated. Conclusion ASRAP and ASRAP-SF questionnaires are valid and reliable novel PRO instruments for assessing the severity and impact of SSc-RP. [ABSTRACT FROM AUTHOR]

Objectives Fibrotic interstitial lung disease (ILD) is a progressive lung disease characterized by loss of lung volume, resulting in a leading cause of death in patients with RA. Crucially, acute exacerbation (AE) of ILD shows higher morbidity and mortality with rapid deterioration of the lungs. However, a quantitative assessment for physiological changes at AE has yet to be performed. This study hypothesized that quantitative assessments of lung volume (LV) accurately indicate disease severity and mortality risk in patients with AE-RA-ILD. Methods This multicentre cohorts study quantitatively assessed physiological changes of RA-ILD at diagnosis (n  = 54), at AE (discovery-cohorts; n  = 20, and validation-cohort; n  = 33), and controls (n  = 35) using 3D CT (3D-CT) images. LV was quantitatively measured using 3D-CT and standardized by predicted forced vital capacity. Results Patients with RA-ILD at diagnosis showed decreased LV, predominantly in lower lobes, compared with controls. Further substantial volume loss was found in upper- and lower lobes at AE compared with those at diagnosis. During AE, decreased standardized 3D-CT LV was associated with a worse prognosis in both cohorts. Subsequently, standardized 3D-CT LV was identified as a significant prognostic factor independent of age, sex and the presence of UIP pattern on CT by multivariate analyses. Notably, a composite model of age and standardized 3D-CT LV successfully classified mortality risk in patients with AE-RA-ILD. Conclusion Volume loss at AE in patients with RA-ILD was associated with increased mortality. Assessing physiological change using standardized 3D-CT might help evaluate disease severity and mortality risk in patients with AE-RA-ILD. [ABSTRACT FROM AUTHOR]

Objectives To analyse the effectiveness, safety and steroid-sparing effect of AZA and MTX as induction of remission and maintenance treatment in eosinophilic granulomatosis with polyangiitis. Methods We retrospectively collected data from 57 patients divided into four groups according to treatment: MTX/AZA as first-line agents (MTX1/AZA1) in non-severe disease or as second-line maintenance therapy (MTX2/AZA2) in severe disease previously treated with CYC/rituximab. During the first 5 years of treatment with AZA/MTX we compared the groups according to: remission rate [defined as R1: BVAS = 0; R2: BVAS = 0 with prednisone ≤5 mg/day; R3 (MIRRA definition): BVAS = 0 with prednisone ≤3.75 mg/day], persistence on therapy, cumulative glucocorticoid (GC) dose, relapse and adverse events (AEs). Results There were no significant differences in remission rates (R1) in each group (63% in MTX1 vs 75% in AZA1, P  = 0.53; 91% in MTX2 vs 71% in AZA2, P  = 0.23). MTX1 allowed R2 more frequently in the first 6 months compared with AZA1 (54% vs 12%, P  = 0.04); no patients receiving AZA1 achieved R3 up to the first 18 months (vs 35% in MTX1, P  = 0.07). The cumulative GC dose was lower for MTX2 vs AZA2 (6 g vs 10.7 g at 5 years, P  = 0.03). MTX caused more AEs compared with AZA (66% vs 30%, P  = 0.004), without affecting the suspension rate. No differences emerged in time-to-first relapse, although fewer patients treated with AZA2 had asthma/ENT relapses (23% vs 64%, P  = 0.04). Conclusion A significant proportion of patients achieved remission with both MTX and AZA. MTX1 had an earlier remission on a lower GC dose but MTX2 had a better steroid-sparing effect. [ABSTRACT FROM AUTHOR]

Objectives We aimed to investigate the value of deep learning (DL) models based on multimodal ultrasonographic (US) images to quantify RA activity. Methods Static greyscale (SGS), dynamic greyscale (DGS), static power Doppler (SPD) and dynamic power Doppler (DPD) US images were collected and evaluated by two expert radiologists according to the EULAR–OMERACT Synovitis Scoring system. Four DL models were developed based on the ResNet-type structure, evaluated on two separate test cohorts, and finally compared with the performance of 12 radiologists with different levels of experience. Results In total, 1244 images were used for the model training, and 152 and 354 for testing (cohort 1 and 2, respectively). The best-performing models for the scores of 0/1/2/3 were the DPD, SGS, DGS and SPD models, respectively (Area Under the receiver operating characteristic Curve [AUC] = 0.87/0.95/0.74/0.95; no significant differences). All the DL models provided results comparable to the experienced radiologists on a per-image basis (intraclass correlation coefficient: 0.239–0.756, P  < 0.05). The SPD model performed better than the SGS one on test cohort 1 (score of 0/2/3: AUC = 0.82/0.67/0.95 vs 0.66/0.66/0.75, respectively) and test cohort 2 (score of 0: AUC = 0.89 vs 0.81). The dynamic DL models performed better than the static ones in most of the scoring processes and were more accurate than the most of senior radiologists, especially the DPD model. Conclusion DL models based on multimodal US images allow a quantitative and objective assessment of RA activity. Dynamic DL models in particular have potential value in assisting radiologists to improve the accuracy of RA US-based grading. [ABSTRACT FROM AUTHOR]

Objective Leukocyte Ig-like receptor A3 (LILRA3) is a soluble receptor belongs to the immunoglobulin superfamily. Our previous studies demonstrated that LILRA3 is a common genetic risk for multiple autoimmune diseases, including RA. Functional LILRA3 conferred increased risk of joint destruction in patients with early RA. We undertook this study to further investigate the pathological role of LILRA3 in joint inflammation of RA. Methods Soluble LILRA3 was measured by ELISA. LILRA3 plasmids were transfected into human fibroblast-like synoviocytes (FLSs) using electroporation. Activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was determined by western blots. Cytokine transcripts were quantified by real-time PCR. Migratory and invasive capacities of FLSs were evaluated using transwell migration and Matrigel invasion assays. FLS apoptosis was analysed using flow cytometry. Colocalization of LILRA3, LILRB1 and HLA-G in RA-FLSs was visualized by immunofluorescence staining. Results Soluble LILRA3 was specifically expressed in synovial fluid and serum LILRA3 was significantly increased and positively correlated with disease activity/severity in RA patients. LILRA3 induced an increased expression of IL-6, IL-8 and MMP3 in RA-FLSs. In vitro LILRA3 stimulation or overexpression promoted RA-FLS migration and invasion, and enhanced phosphorylation of ERK/JNK. Inhibition of ERK/JNK resulted in suppression of IL-6/IL-8 expression in LILRA3-stimulated RA-FLSs. LILRA3 was co-localized with its homologue LILRB1 and shared ligand HLA-G in RA-FLSs. Conclusion The present study provides the first evidence that soluble LILRA3 is a novel proinflammatory mediator involved in synovial inflammation by promoting RA-FLS activation, migration and invasion, probably through the ERK/JNK signalling pathways. [ABSTRACT FROM AUTHOR]

Objective To investigate pain course over time and to identify baseline and 3-month predictors of unacceptable pain with or without low inflammation in early RA. Methods A cohort of 275 patients with early RA, recruited in 2012–2016, was investigated and followed for 2 years. Pain was assessed using a visual analogue scale (VAS; 0–100 mm). Unacceptable pain was defined as VAS pain >40, and low inflammation as CRP <10 mg/l. Baseline and 3-month predictors of unacceptable pain were evaluated using logistic regression analysis. Results After 2 years, 32% of patients reported unacceptable pain. Among those, 81% had low inflammation. Unacceptable pain, and unacceptable pain with low inflammation, at 1 and 2 years was significantly associated with several factors at 3 months, but not at baseline. Three-month predictors of these pain states at 1 and 2 years were higher scores for pain, patient global assessment, and the health assessment questionnaire, and more extensive joint tenderness compared with the number of swollen joints. No significant associations were found for objective inflammatory measures. Conclusion A substantial proportion of patients had unacceptable pain with low inflammation after 2 years. Three months after diagnosis seems to be a good time-point for assessing the risk of long-term pain. The associations between patient reported outcomes and pain, and the lack of association with objective inflammatory measures, supports the uncoupling between pain and inflammation in RA. Having many tender joints, but more limited synovitis, may be predictive of long-term pain despite low inflammation in early RA. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the long-term impact of immunosuppressive therapeutic agents on antibody response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccination in patients with autoimmune rheumatic diseases (AIRD) in order to propose a strategy for annual vaccination. Methods This prospective multicentre cohort study evaluated the humoral response to second and third BNT162b2 and/or mRNA-1273 vaccines in 382 Japanese AIRD patients classified into 12 different medication groups and in 326 healthy controls (HCs). The third vaccination was administered six months after the second vaccination. Antibody titres were measured using the Elecsys Anti-SARS-CoV-2 S assay. Results The seroconversion rate and antibody titres were lower in AIRD patients than in HCs 3–6 weeks after the second vaccination and 3–6 weeks after the third vaccination. Seroconversion rates were <90% after the third vaccination in patients receiving mycophenolate mofetil and rituximab. Antibody levels after the third vaccination were significantly lower in the groups prescribed TNF inhibitor with or without methotrexate, abatacept and rituximab or cyclophosphamide than those of HCs in a multivariate analysis adjusting for age, sex, and glucocorticoid dosage. The third vaccination induced an adequate humoral response in patients treated with sulfasalazine, bucillamine, methotrexate monotherapy, iguratimod, interleukin-6 inhibitors or calcineurin inhibitors including tacrolimus. Conclusions Repeated vaccinations in many immunosuppressed patients produced antibody responses similar to those observed in HCs. In contrast, annual vaccination in patients receiving TNF inhibitors, abatacept, mycophenolate mofetil and rituximab may require caution. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective To identify determinants of neuropsychiatric (NP) flares in patients with SLE treated for active SLE yet no ongoing severe NPSLE with non-biologic standard therapy plus belimumab or placebo. Methods We analysed data from five phase III trials (BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC, EMBRACE; n  = 3638) after exclusion of patients with baseline NP BILAG A. Factors associated with NPSLE flare, defined as a new NP BILAG A or B, were investigated using Cox regression. In a subgroup analysis, we studied patients with baseline NP BILAG E for determinants of de novo NPSLE flare. Organ damage was assessed using the SLICC/ACR Damage Index (SDI). Results We documented 105 (2.9%) NPSLE flares. In multivariable analysis, male sex (HR = 2.37; 95% CI: 1.31, 4.28; P  = 0.004), baseline NP BILAG B–D (HR = 5.91; 95% CI: 3.86, 9.06; P  < 0.001), and increasing SDI scores (HR = 1.35; 95% CI: 1.21, 1.50; P  < 0.001) were strongly associated with NPSLE flare. Belimumab use yielded no association at any dose or administration form. In analysis of SDI domains, NP damage was the strongest determinant of NPSLE flare (HR = 3.25; 95% CI: 2.72, 3.88; P  < 0.001), holding true for cognitive impairment (HR = 14.29; 95% CI: 9.22, 22.14; P  < 0.001), transverse myelitis (HR = 21.89; 95% CI: 5.40, 88.72; P  < 0.001), and neuropathy (HR = 8.87; 95% CI: 5.59, 14.09; P  < 0.001). Male sex was the strongest determinant of de novo NPSLE flare (HR = 3.26; 95% CI: 1.51, 7.04; P  = 0.003). Conclusion Male sex, NPSLE history, and NP damage were strong determinants of impending NPSLE flare. No clear protection or predisposition was conferred from add-on belimumab. [ABSTRACT FROM AUTHOR]

Objective The main aim of this study was to define the best treatment option for multisystem inflammatory syndrome in children (MIS-C) and to analyse the role of anakinra. Methods This is a multicentre retrospective cohort study. Patients were treated according to the attending physician's decision. The patients were divided into four groups on the basis of the first treatment at time of admittance: (i) IVIG, (ii) IVIG and methylprednisolone (≤2 mg/kg/day), (iii) IVIG with high-dose methylprednisolone (>2 mg/kg/day) and (iv) anakinra with or without IVIG and/or methylprednisolone. Primary outcomes were defined as the presence of at least one of the following features: death, the failure of initial treatment, meaning the need for additional treatment for clinical worsening and cardiac involvement at the end of follow-up. Results Two hundred thirty-nine patients were recruited. At univariate analysis, persistent heart involvement at discharge was more frequent in those not receiving anakinra as initial treatment (3/21 vs 66/189; P  = 0.047). After comparisons between the four treatment regimens, adjusting for the propensity score, we observed that early treatment with anakinra was associated with a lower probability of developing persistent heart disease at the end of follow-up (odds ratio: 0.6; 95% CI: 0.4–1.0). Conclusion We report that early treatment with anakinra is safe and very effective in patients with severe MIS-C. In addition, our study suggests that early treatment with anakinra is the most favourable option for patients with a higher risk of developing a severe disease outcome. [ABSTRACT FROM AUTHOR]

Objectives To determine the effect of antimalarial agents (AMA) and different doses and pharmaceutical forms of belimumab on preventing renal flares in patients with SLE treated for extra-renal disease. Methods We pooled data from the BLISS-52, BLISS-76, BLISS-SC and BLISS-Northeast Asia trials of belimumab (n  = 3225), that included patients with active SLE yet no severe ongoing nephritis. Participants were allocated to receive intravenous belimumab 1 mg/kg, intravenous belimumab 10 mg/kg, subcutaneous belimumab 200 mg, or placebo in addition to standard therapy. We estimated hazards of renal flare development throughout the study follow-up (52–76 weeks) using Cox regression analysis. Results In total, 192 patients developed a renal flare after a median of 197 days. Compared with placebo, the risk of renal flares was lower among patients receiving intravenous belimumab 10 mg/kg (HR: 0.62; 95% CI: 0.41, 0.92; P  = 0.018) and intravenous belimumab 1 mg/kg (HR: 0.42; 95% CI: 0.22, 0.79; P  = 0.007), while no significant association was found for subcutaneous belimumab 200 mg. AMA use yielded a lower hazard of renal flares (HR: 0.66; 95% CI: 0.55, 0.78; P  < 0.001). The protection conferred was enhanced when belimumab and AMA were co-administered; the lowest flare rate was observed for the combination intravenous belimumab 1 mg/kg and AMA (18.5 cases per 1000 person-years). Conclusions The protection conferred from belimumab against renal flare development in patients treated for extra-renal SLE appears enhanced when belimumab was administered along with AMA. The prominent effect of low-dose belimumab warrants investigation of the efficacy of intermediate belimumab doses. Clinical trial identification BLISS-52: NCT00424476; BLISS-76: NCT00410384; BLISS-SC: NCT01484496; BLISS-NEA: NCT01345253. [ABSTRACT FROM AUTHOR]

Objectives To improve the definitions of inflammatory arthritis within the musculoskeletal (MSK) domain of the BILAG-2004 index by incorporating imaging findings and clinical features predictive of response to treatment. Methods The BILAG MSK Subcommittee proposed revisions to the BILAG-2004 index definitions of inflammatory arthritis, based on review of evidence in two recent studies. Data from these studies were pooled and analysed to determine the impact of the proposed changes on the severity grading of inflammatory arthritis. Results The revised definition for severe inflammatory arthritis includes definition of 'basic activities of daily living'. For moderate inflammatory arthritis, it now includes synovitis, defined by either observed joint swelling or MSK US evidence of inflammation in joints and surrounding structures. For mild inflammatory arthritis, the definition now includes reference to symmetrical distribution of affected joints and guidance on how US may help re-classify patients as moderate or no inflammatory arthritis. Data from two recent SLE trials were analysed (219 patients). A total of 119 (54.3%) were graded as having mild inflammatory arthritis (BILAG-2004 Grade C). Of these, 53 (44.5%) had evidence of joint inflammation (synovitis or tenosynovitis) on US. Applying the new definition increased the number of patients classified as moderate inflammatory arthritis from 72 (32.9%) to 125 (57.1%), while patients with normal US (n  = 66/119) could be recategorized as BILAG-2004 Grade D (inactive disease). Conclusions Proposed changes to the definitions of inflammatory arthritis in the BILAG-2004 index will result in more accurate classification of patients who are more or less likely to respond to treatment. [ABSTRACT FROM AUTHOR]

The article looks forward to opportunities for enhanced collaborative landscapes of research in idiopathic inflammatory myopathies (IIM) and calcinosis. It comments on a study which characterized the quantitative and qualitative utility of whole-body computed tomography calcium scoring technique for assessing calcinosis distribution, pattern and burden in dermatomyositis (DM) and proposed IIM-calcinosis subtypes in juvenile and adult DM.

Objectives To estimate the cost-effectiveness of a cognitive behavioural approach (CBA) or a personalized exercise programme (PEP), alongside usual care (UC), in patients with inflammatory rheumatic diseases who report chronic, moderate to severe fatigue. Methods A within-trial cost-utility analysis was conducted using individual patient data collected within a multicentre, three-arm randomized controlled trial over a 56-week period. The primary economic analysis was conducted from the UK National Health Service (NHS) perspective. Uncertainty was explored using cost-effectiveness acceptability curves and sensitivity analysis. Results Complete-case analysis showed that, compared with UC, both PEP and CBA were more expensive [adjusted mean cost difference: PEP £569 (95% CI: £464, £665); CBA £845 (95% CI: £717, £993)] and, in the case of PEP, significantly more effective [adjusted mean quality-adjusted life year (QALY) difference: PEP 0.043 (95% CI: 0.019, 0.068); CBA 0.001 (95% CI: −0.022, 0.022)]. These led to an incremental cost-effectiveness ratio (ICER) of £13 159 for PEP vs UC, and £793 777 for CBA vs UC. Non-parametric bootstrapping showed that, at a threshold value of £20 000 per QALY gained, PEP had a probability of 88% of being cost-effective. In multiple imputation analysis, PEP was associated with significant incremental costs of £428 (95% CI: £324, £511) and a non-significant QALY gain of 0.016 (95% CI: −0.003, 0.035), leading to an ICER of £26 822 vs UC. The estimates from sensitivity analyses were consistent with these results. Conclusion The addition of a PEP alongside UC is likely to provide a cost-effective use of health care resources. [ABSTRACT FROM AUTHOR]

Objectives Although the SLE Disease Activity Score (SLE-DAS) and its definitions to classify disease activity have been recently developed to overcome the drawbacks of the SLE Disease Activity Index 2000 (SLEDAI-2K), the performance of the SLE-DAS for patient-reported outcomes (PROs) has not been fully examined. We aimed to compare SLE-DAS with SLEDAI-2K and validate the classifications of disease activity based on SLE-DAS in terms of PROs. Methods We assessed generic quality of life (QoL) using the Medical Outcome Survey 36-Item Short-Form Health Survey (SF-36), disease-specific QoL using the lupus patient-reported outcome tool (LupusPRO), burden of symptoms using the SLE Symptom Checklist (SSC), patient global assessment (PtGA) and physician global assessment (PhGA). Results Of the 335 patients with SLE, the magnitudes of the mean absolute error, root mean square error, Akaike information criterion, and Bayesian information criterion were comparable for most PROs between the SLE-DAS and SLEDAI-2K. In contrast, SLEDAI-2K had a higher predictive value for health-related QoL of LupusPRO and PtGA than SLE-DAS. Low disease activity, Boolean and index-based remission and categories of disease activity (remission, mild and moderate/severe activity) were significantly associated with health-related QoL in LupusPRO, SSC and PhGA, but not SF-36 or PtGA. Conclusion No clear differences were identified in the use of the SLE-DAS over the SLEDAI-2K in assessing PROs in patients with SLE. The classification of disease activity based on the SLE-DAS was validated against several PROs. SLE-DAS and its categories of disease activity effectively explain some of the PROs. [ABSTRACT FROM AUTHOR]

Objectives Osteoarthritis has been the subject of abundant research in the last years with limited translation to the clinical practice, probably due to the disease's high heterogeneity. In this study, we aimed to identify different phenotypes in knee osteoarthritis (KOA) patients with joint effusion based on their metabolic and inflammatory profiles. Methods A non-supervised strategy based on statistical and machine learning methods was applied to 45 parameters measured on 168 female KOA patients with persistent joint effusion, consecutively recruited at our hospital after a monographic OA outpatient visit. Data comprised anthropometric and metabolic factors and a panel of systemic and local inflammatory markers. The resulting clusters were compared regarding their clinical, radiographic and ultrasound severity at baseline and their radiographic progression at two years. Results Our analyses identified four KOA inflammatory phenotypes (KOIP): a group characterized by metabolic syndrome, probably driven by body fat and obesity, and by high local and systemic inflammation (KOIP-1); a metabolically healthy phenotype with mild overall inflammation (KOIP-2); a non-metabolic phenotype with high inflammation levels (KOIP-3); and a metabolic phenotype with low inflammation and cardiovascular risk factors not associated with obesity (KOIP-4). Of interest, these groups exhibited differences regarding pain, functional disability and radiographic progression, pointing to a clinical relevance of the uncovered phenotypes. Conclusion Our results support the existence of different KOA phenotypes with clinical relevance and differing pathways regarding their pathophysiology and disease evolution, which entails implications in patients' stratification, treatment tailoring and the search of novel and personalized therapies. [ABSTRACT FROM AUTHOR]

Objectives Active RA has been associated with an increased risk of both cardiovascular and peripheral vascular disease. We aimed to compare cerebrovascular changes in patients with and without RA, both with and without a neuropathologic diagnosis of neurodegenerative disease. Methods Patients with RA (n  = 32) who died and underwent autopsy between 1994 and 2021 were matched to non-RA controls (n  = 32) on age, sex and level of neurodegenerative proteinopathy. Routine neuropathologic examination was performed at the time of autopsy. Cerebrovascular disease severity was evaluated using modified Kalaria and Strozyk scales. Clinical dementia diagnoses were manually collected from patients' medical records. Results Prior to death, 15 (47%) RA patients and 14 (44%) controls were diagnosed with dementia; 9 patients in each group (60% and 64%, respectively) had Alzheimer's disease. The prevalence of cerebral amyloid angiopathy, microinfarcts, infarcts or strokes was found to be similar between groups. Patients with RA were more likely to have more severe vascular changes in the basal ganglia by Kalaria scale (P  = 0.04), but not in other brain areas. There were no significant differences in the presence of large infarcts, lacunar infarcts or leukoencephalopathy by Strozyk scale. Among patients with RA and no clinical diagnosis of dementia, the majority had mild–moderate cerebrovascular abnormalities, and a subset of patients had Alzheimer's disease neuropathologic changes. Conclusion In this small series of autopsies, patients with and without RA had largely similar cerebrovascular pathology when controlling for neurodegenerative proteinopathies, although patients with RA exhibited more pronounced cerebrovascular disease in the basal ganglia. [ABSTRACT FROM AUTHOR]

Objectives Self-monitoring and patient-initiated care (PIC) leads to fewer outpatient clinic visits in patients with established RA with low disease activity (LDA) while healthcare outcomes are similar. This study assesses the cost-effectiveness of PIC with self-monitoring. Methods A 12-month randomized controlled trial was performed with 49 patients in the PIC with self-monitoring group (app-group) and 53 in usual care. The usual care group continued with preplanned visits. The app group had one planned follow-up visit after 12 months and monitored their RA disease activity in a smartphone app. Both groups could make additional appointments at liberty. We included adult RA patients with a disease duration of over 2 years, a disease activity score 28 (DAS28) below 3.2 that were stable on medication for at least 6 months. The effect measure, the DAS28, was measured at 12 months and healthcare resource usage and productivity losses were measured at 3, 6, 9 and 12 months. Results There was no significant difference in mean change of DAS28 (-0.04 mean difference, 95% CI: -0.39, 0.30), nor a statistically significant difference in total costs (mean difference €514, 95% CI:-€266, €3690) in the app group compared with the usual care group. The probability that the app was cost-effective was 0.37 and 0.57 at a willingness-to-pay threshold of 0 and 50 000 €/point improvement DAS28, respectively. Conclusion Although rheumatic care costs were significantly lower in the app group, total costs and effects of PIC with self-monitoring were not different from usual care in RA patients with LDA. [ABSTRACT FROM AUTHOR]

The article presents a study which analyzed whether separate dryness assessments could be of value to the European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Patient Reported Index (ESSPRI) in patients with Sjögren's disease (SjD). Topics discussed include baseline characteristics of the included SjD patients from the trial and most important dryness features determining the overall patient-reported dryness.

The article presents a study which analysed predictors in a global sample of patients with idiopathic inflammatory myopathies (IIMs) using data from the second COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. Topics include patients included in the study, patient-reported flares following COVID-19 infection among IIM patients, and factors that were found to significantly increase the risk of flares in univariate analysis.

Objectives Mortality of dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 antibody (anti-MDA5-DM) is alarming, especially during the first several months. Infection is an important cause of early death. As there are no reports regarding the effect of prophylactic use of compounded sulfamethoxazole (coSMZ; each tablet contains 400 mg of sulfamethoxazole and 80 mg of trimethoprim) in anti-MDA5-DM patients, we conducted this study to evaluate the efficacy of coSMZ in reducing the incidence of Pneumocystis jirovecii pneumonia (PJP). Methods Consecutive patients with new-onset anti-MDA5-DM from June 2018 to October 2021 in our centre were retrospectively reviewed for >12 months. They were divided into two groups—coSMZ and non-coSMZ—based on the initial use of prophylactic coSMZ. Mortality and the incidence of severe infection within 12 months were compared between two groups. Results Compared with the non-coSMZ group (n  = 93), the coSMZ group (n  = 121) had lower mortality (18.8% vs 51.1%; P   <  0.001) and a lower incidence of PJP (6.8% vs 15.2%; P  = 0.040) and fatal infection (16.1% vs 3.3%; P  = 0.001) during the first 12 months from diagnosis. After adjusting for age, gender, disease duration, peripheral blood lymphocyte count, anti-MDA5 antibody titres, ground-glass opacity scores and treatments, an inverse association was revealed between the prophylactic use of coSMZ and incidence of PJP [adjusted odds ratio 0.299 (95% CI 0.102–0.878), P  = 0.028]. Conclusion Prophylactic use of coSMZ is an effective and safe way to improve the prognosis of anti-MDA5-DM patients by preventing the incidence of PJP. [ABSTRACT FROM AUTHOR]

Objectives We evaluated sensitivity to change and discriminative abilities of vascular US scores in disease monitoring in the follow-up of a prospective cohort of new-onset cranial and large-vessel (LV) GCA patients. Methods Baseline and follow-up (8 weeks, 24 weeks and 15 months) US of temporal arteries (TA), carotid and axillary arteries (LV) included assessment of halo and measurement of the intima media complex (IMC). Max IMC, max halo IMC, sum IMC, sum halo IMC, mean IMC, halo count and the Southend halo score were calculated. The provisional OMERACT US score, OGUS, was obtained, taking the average of temporal arteries and axillary arteries IMCs divided by their normal cut-off values. Results Baseline US was positive in 44/47 patients (72% TA, 72% LV). Sensitivity to change of all composite US scores containing TAs was evident by week 8 onward. LVs responded poorly and new axillary US lesions emerged in six patients despite clinical remission. The OGUS showed a large magnitude of change and is considered the score least prone to potential bias. All TA-based US scores showed moderate–strong correlation with disease activity markers. OGUS, TA halo count, Southend TA halo score, TA sum IMC and TA mean IMC showed potential to discriminate remission and relapse with area under the curve ≥0.8. Conclusions The OGUS is suggested as an outcome measurement for the assessment of treatment response in clinical trials. The abilities of US scores to discriminate remission and relapse are encouraging and should be further explored. [ABSTRACT FROM AUTHOR]

Objectives Identifying that dysfunction of the IL-23/17 axis underlies PsA has led to the development of effective targeted therapies such as the IL-17A inhibitor secukinumab. As IL-17A stimulates the secretion of neutrophil chemoattractants, such as CXCL8 (IL-8), we examined the effect of secukinumab on neutrophil function in PsA. Methods Nineteen patients with active PsA were treated with secukinumab. Clinical response [PsA Response Criteria (PsARC) and Psoriasis Area and Severity Index (PASI)] and peripheral blood neutrophil function (apoptosis, receptor expression, phagocytosis/killing, chemotaxis and RNA expression) were measured at 12 week intervals for 48 weeks and compared with age- and sex-matched healthy controls. Results At 12 weeks, 12/16 (75%) patients had a PsARC response (100% at 36 weeks) and 10/14 (71%) achieved a 90% PASI response. At baseline, there were no differences in PsA neutrophil reactive oxygen species generation, constitutive or cytokine-delayed apoptosis, chemotaxis or phagocytosis of opsonized Staphylococcus aureus compared with healthy controls. Similarly, there were no differences in these functions from baseline to 12 weeks of therapy. However, surface levels of CD11b/CD18 and CD63 increased and expression of CD16 decreased during therapy. In addition, in a subgroup of early (12 week) responders to secukinumab, RNA sequencing revealed transcriptome changes predicting down-regulation of cytokine signalling and chemotaxis pathways and up-regulation of de novo gene expression pathways, including translation initiation, mRNA catabolism and translation. Conclusion Complex changes in the properties of circulating neutrophils occur with secukinumab treatment in PsA that may indicate altered responsiveness to changes in both local and systemic levels of pro-inflammatory cytokines. However, host defence processes of neutrophils were unaltered. [ABSTRACT FROM AUTHOR]

Objective To determine the effect of a multidisciplinary lifestyle program in patients with RA with low–moderate disease activity. Methods In the 'Plants for Joints' (PFJ) parallel-arm, assessor-blind randomized controlled trial, patients with RA and 28-joint DAS (DAS28) ≥2.6 and ≤5.1 were randomized to the PFJ or control group. The PFJ group followed a 16-week lifestyle program based on a whole-food plant-based diet, physical activity and stress management. The control group received usual care. Medication was kept stable 3 months before and during the trial whenever possible. We hypothesized that PFJ would lower disease activity (DAS28). Secondary outcomes included anthropometric, metabolic and patient-reported measures. An intention-to-treat analysis with a linear mixed model adjusted for baseline values was used to analyse between-group differences. Results Of the 83 people randomized, 77 completed the study. Participants were 92% female with mean (s. d.) age of 55 (12) years, BMI of 26 (4) kg/m2 and mean DAS28 of 3.8 (0.7). After 16 weeks the PFJ group had a mean 0.9-point greater improvement of DAS28 vs the control group (95% CI 0.4, 1.3; P  < 0.0001). The PFJ intervention led to greater decreases in body weight (difference –3.9 kg), fat mass (–2.8 kg), waist circumference (–3 cm), HbA1c (–1.3 mmol/mol) and low-density lipoprotein (–0.32 mmol/l), whereas patient-reported outcome measures, blood pressure, glucose and other lipids did not change. Conclusion The 16-week PFJ multidisciplinary lifestyle program substantially decreased disease activity and improved metabolic status in people with RA with low–moderate disease activity. Trial Registration International Clinical Trials Registry Platform; https://www.who.int/clinical-trials-registry-platform ; NL7800. [ABSTRACT FROM AUTHOR]

Objectives The primary endpoint of the pivotal phase III study of infliximab (IFX) s.c. demonstrated non-inferiority of s.c. to i.v. IFX, based on 28-joint DAS-CRP (DAS28-CRP) improvement at week (W) 22 (NCT03147248). This post-hoc analysis investigated whether numerical differences in efficacy outcomes at W30/54 were statistically significant, using conservative imputation methods. Methods Patients with active RA and inadequate response to MTX received IFX i.v. 3 mg/kg at W0 and W2 (induction) and were randomized (1:1) to IFX s.c. 120 mg every 2 weeks or i.v. 3 mg/kg every 8 weeks thereafter (maintenance). Patients randomized to IFX i.v. switched to IFX s.c. from W30–54. This post-hoc analysis compared efficacy outcomes for s.c. and i.v. groups pre-switch (W30) and post-switch (W54) using last observation carried forward (LOCF) and non-responder imputation (NRI) methods. Results Of 343 randomized patients, 165 (IFX s.c.) and 174 (IFX i.v.) were analysed. At W30, significantly improved outcomes were identified with s.c. vs i.v. IFX for DAS28-CRP/DAS28-ESR/Clinical Disease Activity Index (CDAI)/Simplified Disease Activity Index (SDAI) scores (LOCF); ACR/good EULAR responses, DAS28-CRP/Boolean remission, and DAS28-CRP/DAS28-ESR/CDAI/SDAI low disease activity and remission (LOCF and/or NRI); and minimal clinically important difference in HAQ score (LOCF and NRI). After switching to IFX s.c. from IFX i.v. fewer significant between-group differences were identified at W54. Conclusion IFX s.c. showed improved efficacy at W30 compared with IFX i.v. and the reduced between-group difference in efficacy outcomes at W54 after switching supports the results suggesting benefits of IFX s.c. compared with IFX i.v. at W30. Trial registration ClincialTrials.gov, http://clinicaltrials.gov , NCT03147248, https://clinicaltrials.gov/ct2/show/NCT03147248. [ABSTRACT FROM AUTHOR]

Objectives Nintedanib is an inhibitor of tyrosine kinases that has been shown to slow the progression of interstitial lung disease (ILD), including ILD associated with SSc. The aim of this study was to explore the effect of nintedanib on cardiomyopathy associated with systemic sclerosis (SSc). Methods Twenty consecutively hospitalized patients with SSc-ILD were enrolled and prospectively followed. The rate of change at 6 months in cardiac magnetic resonance (CMR) parametric mapping, including myocardial extracellular volume, was primarily evaluated. Other endpoints included changes in CMR functional parameters, echocardiographic parameters, modified Rodnan skin score, serum biomarkers and pulmonary function test. Results Nintedanib was administered in 10 patients, whereas the other 10 were treated without nintedanib or watched, according to ILD severity and progression. Baseline values of CMR parametric mapping were not different between the two groups. The rate of change at 6 months in myocardial extracellular volume was highly different, almost divergent, between the nintedanib group and the control group (−1.62% vs +2.00%, P  = 0.0001). Among other endpoints, the change in right ventricular ejection fraction was significantly different between the two groups (P  = 0.02), with a preferential change in the nintedanib group. Conclusion Our data indicate beneficial signals of nintedanib on cardiomyopathy associated with SSc. The anti-fibrotic effect of nintedanib might not be limited to the lung. [ABSTRACT FROM AUTHOR]

Objective To analyse the association between the average 'adjusted' Global APS Score (aGAPSS) over time, as a surrogate of disease activity, and change in Damage Index for APS (DIAPS) during follow-up in patients with thrombotic and non-thrombotic APS. Methods Two hundred APS patients (138 primary, 62 associated to other autoimmune diseases) were included. DIAPS change was calculated as the difference between basal DIAPS and DIAPS at the end of follow-up. The aGAPSS was calculated for each patient at baseline and on a yearly basis for up to 6 years (minimum 3 years). The average score per patient was computed and considered the reference aGAPSS. Linear regression models were designed to analyse the association between mean aGAPSS and DIAPS change. Moreover, factors associated to high (increase of DIAPS ≥1 during follow-up) vs low (increase of DIAPS <1 during follow-up) damage accrual were assessed. Results A higher mean aGAPSS value was associated to a DIAPS increase during follow-up (b = 0.04, P  < 0.001) in the multivariate analysis. Higher mean aGAPSS values were found in patients with a DIAPS increase ≥1 during follow-up compared with patients with an increase of <1 point [9.22 (95% CI 7.58, 10.86) vs 6.72 (95% CI 6.0, 7.43), P  = 0.003]. aGAPSS increased the odds a DIAPS increment of ≥1 point during follow-up [OR = 1.12 (95% CI 1.04, 1.21), P  = 0.003]. Conclusions Our data support the utility of longitudinal assessing of the aGAPSS score in predicting damage accrual, measured by DIAPS, in APS. [ABSTRACT FROM AUTHOR]

Objectives To describe the clinical and pathological features of biopsy-proven cutaneous vasculitis (CV) associated with SLE, focusing on diagnosis classification and impact on overall SLE activity. Methods Retrospective multicentric cohort study including SLE patients with biopsy-proven CV identified by (i) data from pathology departments of three university hospitals and (ii) a national call for cases. SLE was defined according to 1997 revised ACR and/or 2019 ACR/EULAR criteria. CV diagnosis was confirmed histologically and classified by using the dermatological addendum of the Chapel Hill classification. SLE activity and flare severity at the time of CV diagnosis were assessed independently of vasculitis items with the SELENA-SLEDAI and SELENA-SLEDAI Flare Index. Results Overall, 39 patients were included; 35 (90%) were female. Cutaneous manifestations included mostly palpable purpura (n  = 21; 54%) and urticarial lesions (n  = 18; 46%); lower limbs were the most common location (n  = 33; 85%). Eleven (28%) patients exhibited extracutaneous vasculitis. A higher prevalence of Sjögren's syndrome (51%) was found compared with SLE patients without CV from the French referral centre group (12%, P  < 0.0001) and the Swiss SLE Cohort (11%, P  < 0.0001). CV was mostly classified as urticarial vasculitis (n  = 14, 36%) and cryoglobulinaemia (n  = 13, 33%). Only 2 (5%) patients had no other cause than SLE to explain the CV. Sixty-one percent of patients had inactive SLE. Conclusion SLE-related vasculitis seems very rare and other causes of vasculitis should be ruled out before considering this diagnosis. Moreover, in more than half of patients, CV was not associated with another sign of active SLE. [ABSTRACT FROM AUTHOR]

Objectives To establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD). Methods A conceptual framework for subclinical, clinical and progressive ILD was provided to 83 experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least four experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥75% of experts agreed. Experts provided information on which items were important in determining classification. Results Forty-four experts (53%) completed the survey. Consensus was achieved on the dimensions of severity (75%, 60 of 80 profiles), risk of progression (71%, 57 of 80 profiles) and progressive ILD (60%, 24 of 40 profiles). For profiles achieving consensus, most were classified as clinical ILD (92%), low risk (54%) and stable (71%). Severity and disease progression overlapped in terms of framework items that were most influential in classifying patients (forced vital capacity, extent of lung involvement on high resolution chest CT [HRCT]); risk of progression was influenced primarily by disease duration. Conclusions Using our proposed conceptual framework, international experts were able to achieve a consensus on classifying SSc-ILD patients along the dimensions of disease severity, risk of progression and progression over time. Experts rely on similar items when classifying disease severity and progression: a combination of spirometry and gas exchange and quantitative HRCT. [ABSTRACT FROM AUTHOR]

Objective To assess associations between the extent of fibrotic interstitial lung disease (ILD) and forced vital capacity (FVC) at baseline and change in FVC over 52 weeks in patients with systemic sclerosis-associated ILD (SSc-ILD) in the SENSCIS trial. Material and methods We used generalized additive models, which involve few assumptions and allow for interaction between non-linear effects, to assess associations between the extent of fibrotic ILD on high-resolution computed tomography (HRCT), and the interplay of extent of fibrotic ILD on HRCT and FVC % predicted, at baseline and FVC decline over 52 weeks. Results In the placebo group (n  = 288), there was weak evidence of a modest association between a greater extent of fibrotic ILD at baseline and a greater decline in FVC % predicted at week 52 [r: –0.09 (95% CI –0.2, 0.03)]. Higher values of both the extent of fibrotic ILD and FVC % predicted at baseline tended to be associated with greater decline in FVC % predicted at week 52. In the nintedanib group (n  = 288), there was no evidence of an association between the extent of fibrotic ILD at baseline and decline in FVC % predicted at week 52 [r: 0.01 (95% CI: -0.11, 0.12)] or between the interplay of extent of fibrotic ILD and FVC % predicted at baseline and decline in FVC % predicted at week 52. Conclusions Data from the SENSCIS trial suggest that patients with SSc-ILD are at risk of ILD progression and benefit from nintedanib largely irrespective of their extent of fibrotic ILD at baseline. Study registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT02597933. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to (i) investigate actual work participation in Belgian spondyloarthritis (SpA) patients compared with the general population, and (ii) identify determinants of work-related outcomes. Material and methods Adult SpA patients from the Ghent University Hospital based Be-GIANT cohort (fulfilling ASAS classification criteria) were cross-sectionally questioned on their socio-economic status and completed a Work Productivity and Activity Impairment questionnaire (May 2018 to May 2019). Results were compared with national and regional data on the general population using indirect standardization. Associations between clinical and job characteristics and work-related outcomes were analysed with logistic regression (having a paid job) and negative binomial hurdle models (sick leave and presenteeism, i.e. restrictions while at work). Results A total of 215/262 (82%) patients of working age (<65 y/o) had a paid job, corresponding to an age- and sex-adjusted employment ratio of 1.00 (95% CI 0.88, 1.14). Patients worked 39.6h (10.5h)/week, and 49% (95% CI 42, 56%) reported sick leave in the previous year, similar to the general population (39.7h/week, 42%). In total, 56% reported presenteeism of median (IQR) 10% (0–20%). In multivariate analysis, functional impairment (BASFI) and health-related quality of life (HRQoL, EuroQoL-VAS) were associated with each work-related outcome, while contextual factors (education, physically demanding job) were positively associated with, respectively, having a paid job and presenteeism. Clinical characteristics showed no independent association with any of these outcomes. Conclusions Evidence from this academic cohort study does not support a work participation gap between SpA patients and the general population, but confirms the role of physical function, overall HRQoL, and education or job type as risk factors for adverse work outcomes. [ABSTRACT FROM AUTHOR]

The prevalence and severity of SLE have been found to vary across populations of different ancestries. This review explores whether these differences can be explained by the genetic aetiology of the condition. Large genetic studies suggest that populations of different ancestry share the same risk loci but individual risk alleles are more common in some, leading to a higher prevalence and severity and an earlier onset of the condition. Despite many of the loci being shared across populations, some have been found to be ancestry specific and these are hypothesized to have undergone differential selective pressure in recent human history. Additionally, the effectiveness of some of the drugs used in SLE has been found to vary across ancestries, which might affect progression of the disease, but it is unclear whether these differences are pharmacogenetic. We concluded that to understand the full role of genetics in the risk, presentation and response to treatment of SLE, larger studies including individuals from a wider representation of ancestries will be required. [ABSTRACT FROM AUTHOR]

Objectives MTX is the recommended first-line treatment for RA associated with folic acid (FA) to reduce side effects related to MTX. Here, we proposed to test a co-administration of MTX with FA in the rat adjuvant-induced arthritis (AIA) on efficacy. Material and methods AIA was induced in female Lewis rats and treated with MTX in three groups. The first group of rats received only MTX (n  = 13), whereas the second received MTX and FA on the same day (n  = 14). The third group received FA one day after MTX (n  = 14). Arthritic index (AI), ankle circumference (AC), ankle microcomputed tomography, and blood tests assessed arthritis severity and MTX tolerance. Results AI and AC were similar in MTX groups at various time points. Bone erosion and bone loss parameters were similar in all groups. MTX-PG1 was found at similar levels in various MTX groups and correlated negatively with arthritis severity. Finally, haematology and metabolic parameters were found at a similar level in MTX groups. Conclusion Co-administration of MTX with FA on the same day did not reduce efficacy compared with FA application one day after MTX. Thus, co-administration of MTX and FA could be more convenient and improve compliance in patients. [ABSTRACT FROM AUTHOR]

Objective The IL-23 p19-subunit inhibitor guselkumab has been previously compared with other targeted therapies for PsA through network meta-analysis (NMA). The objective of this NMA update was to include new guselkumab COSMOS trial data, and two key comparators: the IL-23 inhibitor risankizumab and the Janus kinase (JAK) inhibitor upadacitinib. Material and methods A systematic literature review was conducted to identify randomized controlled trials up to February 2021. A hand-search identified newer agents up to July 2021. Bayesian NMAs were performed to compare treatments on ACR response, Psoriasis Area and Severity Index (PASI) response, modified van der Heijde–Sharp (vdH-S) score, and serious adverse events (SAEs). Results For ACR 20, guselkumab 100 mg every 8 weeks (Q8W) and every 4 weeks (Q4W) were comparable (i.e. overlap in credible intervals) to most other agents, including risankizumab, upadacitinib, subcutaneous TNF inhibitors and most IL-17A inhibitors. For PASI 90, guselkumab Q8W and Q4W were better than multiple agents, including subcutaneous TNF and JAK inhibitors. For vdH-S, guselkumab Q8W was similar to risankizumab, while guselkumab Q4W was better; both doses were comparable to most other agents. Most agents had comparable SAEs. Conclusions Guselkumab demonstrates better skin efficacy than most other targeted PsA therapies, including upadacitinib. For vdH-S, both guselkumab doses are comparable to most treatments, with both doses ranking higher than most, including upadacitinib and risankizumab. Both guselkumab doses demonstrate comparable ACR responses to most other agents, including upadacitinib and risankizumab, and rank favourably in the network for SAEs. [ABSTRACT FROM AUTHOR]

Objective Clinical trials in early diffuse SSc have consistently shown a placebo group response with a declining modified Rodnan skin score (mRSS), with negative outcomes. Our objective was to identify strategies using clinical characteristics or laboratory values to improve trial design. Methods We identified early diffuse SSc patients first seen at the University of Pittsburgh from 1980–2015. Eligible patients had ≥3 visits, with at least two mRSS scores within the first year of follow-up. We performed Kaplan–Meier analyses, group-based trajectory analysis of mRSS scores, followed by multivariable regression analysis and classification tree analysis. We applied the results to the abatacept in early diffuse systemic sclerosis (ASSET) trial outcome data. Results We identified 403 patients with <18 months, and 514 with <36 months disease duration. The median number of mRSS follow-up scores was 14 (interquartile range 8, 25). All methodologic approaches identified skin thickness progression rate, RNA polymerase III (RNAP3) antibody positivity and presence of tendon friction rubs (TFR) as predictors of mRSS trajectory over 5 years of follow-up, and thereby as potential enrichment variables. When applied to the ASSET data, adjustment for both RNAP3 and TFR demonstrated reduction of the placebo mRSS response, particularly at 6 months. A significant difference in the ACR Composite Response Index in Systemic Sclerosis (CRISS) score was found with adjustment by RNAP3 at 6 months, and TFR or RNAP3 at 12 months. Conclusion Adjustment for both RNAP3 and TFR predicts mRSS trajectory and diminished the mRSS decline in ASSET placebo group, and identified significant differences in CRISS. RNAP3, particularly, is a stratification or enrichment approach to improve early diffuse SSc trial design. [ABSTRACT FROM AUTHOR]

The author discusses the study "An Integrated Extrapolation of Long-Term Outcomes in Systemic Lupus Erythematosus: Analysis and Simulation of the Hopkins Lupus Cohort" by P. Watson and colleagues, published in the issue. Topics include negative prognostic impact of severity on variability, enduring effects of systemic lupus erythematosus (SLE) disease activity, and estimated regression coefficients of a random-effects model.

Objectives Behçet's disease (BD) is a unique systemic vasculitis mainly involving veins, in contrast to other vasculitides. Prior studies have shown that pulmonary arteries (PAs) have a similar structure to systemic veins. In this study we aimed to assess PA wall thickness by transthoracic echocardiography (TTE) in BD patients compared with healthy controls (HCs) and patients with non-inflammatory pulmonary embolism (NIPE). Methods Patients with BD (n  = 77) and NIPE (n  = 33) and HCs (n  = 57) were studied. PA wall thickness was measured from the mid-portion of the main PA with TTE by two cardiologists blinded to cases. Results PA wall thickness was significantly lower in HCs [3.6 mm (s. d. 0.3)] compared with NIPE [4.4 mm (s. d. 0.5)] and BD [4.4 mm (s. d. 0.6)] (P  < 0.001 for both). PA wall thickness was similar between BD and NIPE (P  = 0.6). Among patients with BD, PA wall thickness was significantly higher in patients with major organ involvement compared with mucocutaneous limited disease [4.7 mm (s. d. 0.4) vs 3.7 (0.4), P  < 0.001], HCs and NIPE (P  < 0.001 and P  = 0.006, respectively). PA wall thickness was comparable between patients with vascular and non-vascular major organ involvement [4.6 mm (s. d. 0.5) vs 4.7 (0.3), P  = 0.3]. Conclusion We observed that PA wall thickness was significantly higher in BD with major organ involvement compared with patients with only mucocutaneous limited disease, HCs and NIPE. These results suggest that increased PA wall thickness may be a sign of severe disease with major organ involvement in BD. [ABSTRACT FROM AUTHOR]

Objectives Few data are available on the role of emotional distress as a possible mediator of the relationship between coping strategies and the Patient Global Assessment (PGA). This study aims to investigate, in a large cohort of patients affected by RA, the relationship between specific copying strategies and PGA, and the role of emotional distress as a mediator. Methods A total of 490 patients with RA completed a set of standardized assessments including the self-reported PGA, the Coping Orientation to the Problems Experienced (COPE-NVI) and the Hospital Anxiety and Depression Scale (HADS). A mediation analysis was conducted to investigate the role of emotional distress. Results The effect of coping strategies on the PGA score was significantly mediated by the emotional distress for religious (total effect mediated 42.0%), planning (total effect mediated 17.5%), behavioural disengagement (total effect mediated 10.5%), and focus on and venting of emotions (total effect mediated 9.8%). Seven coping strategies (acceptance, positive reinterpretation and growth, active coping, denial, humour, substance use-mental disengagement) resulted directly associated to PGA total score, but no mediation effect was found. The remaining four coping strategies were not associated to the PGA score. Conclusion This study suggests that coping strategies could be an important factor in the perceived disease severity. Consequently, in order to reduce PGA in patients with RA, a useful tool could be represented by the implementation of psychological interventions aiming to modify the specific coping styles. Moreover, to prevent or treat emotional distress seems to further reduce PGA. [ABSTRACT FROM AUTHOR]

Objective To identify predictors for lupus low disease activity state (LLDAS), early-achieved LLDAS and long-term disease activity, and to refine a prognostic stratification tool for use in active SLE patients. Method A total of 245 active SLE patients were enrolled, followed up quarterly from 2014 to 2016. LLDAS-50 was defined as the maintenance of LLDAS for ≥50% of the observed time. LLDAS at 3 months after cohort entry (LLDAS-3mo) was considered an early-achieved LLDAS. Multivariate analysis was performed to identify predictors for LLDAS, early-achieved LLDAS and long-term disease activity. Based on the factors associated with LLDAS, a prognostic stratification tool for LLDAS was established. Results The 2-year probability of achieving LLDAS was 62.9% (154/245). Multivariate analysis-determined renal involvement, haematological involvement and hypocomplementaemia were negative predictors for achieving LLDAS and LLDAS-50. In multivariate logistic analysis, antiphospholipid antibodies positivity, hypocomplementaemia, renal involvement and haematological involvement were identified as negative predictors for achieving LLDAS-3mo. LLDAS-3mo (P  < 0.0001; risk ratio: 47.694; 95% CI: 13.776, 165.127) was a strong predictor for LLDAS-50. The probability of achieving LLDAS, LLDAS-50 and LLDAS-3mo were 88.9% (32/36), 69.4% (25/36) and 41.7% (15/36) in the low-risk group, 65% (65/100), 51.0% (51/100) and 32.0% (32/100) in intermediate-risk group, and 52.8% (57/108), 27.8% (30/108) and 13.0% (14/108) in high-risk group respectively. Significant differences (P  < 0.0001) were observed in the LLDAS Kaplan–Meier estimates for the three risk groups based on the identified risk factors. Conclusion Renal involvement, haematological involvement and hypocomplementaemia were negative predictors of LLDAS achievement and maintenance. LLDAS-3mo was a positive predictor for the long-term sustainment of LLDAS. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to identify biomarkers for radiographic OA severity and progression acting within the inflammation and metabolic pathways. Methods For 3517 Rotterdam Study participants, 184 plasma protein levels were measured using Olink inflammation and cardiometabolic panels. We studied associations with severity and progression of knee, hip and hand OA and a composite overall OA burden score by multivariable regression models, adjusting for age, sex, cell counts and BMI. Results We found 18 significantly associated proteins for overall OA burden, of which 5 stayed significant after multiple testing correction: circulating cartilage acidic protein 1 (CRTAC1), cartilage oligomeric matrix protein (COMP), thrombospondin 4, IL-18 receptor 1 (IL-18R1) and TNF ligand superfamily member 14. These proteins were also associated with progression of knee OA, with the exception of IL-18R1. The strongest association was found for the level of CRTAC1, with 1 s. d. increase in protein level resulting in an increase of 0.09 (95% CI 0.06, 0.12) in the overall OA Kellgren–Lawrence sum score (P  = 2.9 × 10−8) in the model adjusted for age, sex, BMI and cell counts. This association was also present with the severity of OA in all three joints and progression of knee OA and was independent of BMI. We observed a stronger association for CRTAC1 with OA than for the well-known OA biomarker COMP. Conclusion We identified several compelling biomarkers reflecting the overall OA burden and the increased risk for OA progression. CRTAC1 was the most compelling and robust biomarker for OA severity and progression. Such a biomarker may be used for disease monitoring. [ABSTRACT FROM AUTHOR]

Objectives Four-and-a-half LIM domains 1 (FHL1) is a muscle-specific protein. Autoantibodies against FHL1 were recently discovered in adults with idiopathic inflammatory myopathies (IIMs) and were found to be associated with clinical features and outcomes indicative of increased disease severity. Anti-FHL1 autoantibodies have not been described in children. Here, the prevalence and clinical features associated with anti-FHL1 autoantibodies were examined in a large North American cohort of juvenile patients with IIM. Methods Sera from 338 juvenile IIM patients and 91 juvenile healthy controls were screened for anti-FHL1 autoantibodies by ELISA. Clinical characteristics and HLA alleles of those with and without anti-FHL1 autoantibodies were compared among those with juvenile IIM. Results Anti-FHL1 autoantibodies were present in 10.9% of juvenile IIM patients and 1.1% of controls. The frequency of anti-FHL1 autoantibodies among clinical and serologic subgroups did not differ. A higher percentage of Asian patients had anti-FHL1 autoantibodies (11% vs 0.7%; P  = 0.002). Myositis-associated autoantibodies (MAAs) [odds ratio (OR) 2.09 (CI 1.03, 4.32)], anti-Ro52 autoantibodies specifically [OR 4.17 (CI 1.83, 9.37)] and V-sign rash [OR 2.59 (CI 1.22, 5.40)] were associated with anti-FHL1 autoantibodies. There were no differences in other features or markers of disease severity. No HLA associations with anti-FHL1 autoantibodies in Caucasian myositis patients were identified. Conclusion Anti-FHL1 autoantibodies are present in ∼11% of juvenile IIM patients and commonly co-occur with MAAs, including anti-Ro52 autoantibodies. In contrast to adult IIM, anti-FHL1 autoantibodies in juvenile myositis are associated with V-sign rash but not with other distinctive clinical features or worse outcomes. [ABSTRACT FROM AUTHOR]