RMD Open最新文献

Objective: Postmarketing safety data of avacopan, the first Food and Drug Administration (FDA) approved drug in a decade for antineutrophil cytoplasmic antibody-associated vasculitis (AAV), are currently limited. This study aims to conduct a comprehensive real-world evaluation of its adverse events (AEs).

Methods: The FDA Adverse Event Reporting System was comprehensively reviewed and analysed. Disproportionality analysis was conducted to evaluate the significance of avacopan-related AEs at both system organ class (SOC) and preferred terms (PTs) levels. Time-to-onset (TTO), Weibull shape parameter (WSP) analysis and cumulative incidence analyses were performed to explore the temporal patterns of AE occurrence. Additionally, subgroup analyses based on gender and age were undertaken.

Results: A total of 3150 reports of avacopan-related AEs were identified. 8 positive SOC signals and 92 positive PT signals were detected, including 34 previously unrecognised PTs. None was classified as a high clinical priority. The median TTO was 48 days. Overall WSP analyses suggested an early failure type pattern, while event-specific analyses demonstrated heterogeneous temporal patterns. Patients aged≥65 years had a higher cumulative incidence of AEs. Hepatobiliary events were the leading ones, with a predominance of reports involving female and geriatric (≥65 years) patients.

Conclusion: Avacopan demonstrated a favourable safety profile in patients with AAV in real-world settings. The overall AE risk increased with age, while hepatobiliary events were particularly more frequent among geriatric and female patients. Our study uncovered previously unrecognised AEs as well. These findings highlighted the need for risk-informed and AE-specific monitoring strategies to support individualised management.

Objective: Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis and primarily affects the joints. While therapeutic advances have substantially reduced the risk of long-term disability, concerns remain regarding disease-related morbidity. Therefore, we aimed to evaluate incidence, prevalence, mortality rates (MRs), standardised mortality ratios (SMRs) and causes of death in RA in north-eastern Italy from 2012 to 2020.

Methods: A retrospective population-based study was conducted in the Veneto region (4.8 million residents) using linked data from the population registry, healthcare co-payment exemptions, hospital discharge records and mortality data. Prevalence and incidence rates were stratified by age and sex. SMRs were calculated by comparing patients with RA to the general population. Causes of death were classified by the International Classification of Diseases Tenth Revision (ICD-10).

Results: We identified 37 996 patients with RA (prevalence 0.54%) and 12 875 incident cases (incidence rate 33.1/100 000). Incidence was twice as high in females. Among prevalent cases, 7 435 deaths occurred (MR 32.2/1000), while among incident cases there were 1288 deaths over the 8-year study period (MR 21.3/1000). The median age at death was 83 (77-88) years. The overall SMR was 1.28 (95% CI 1.21 to 1.35), higher in patients under 45 years of age (2.15, 95% CI 0.93 to 4.24). Leading causes of death were cardiovascular diseases (37.1%), cancer (20.6%) and infections (10.9%).

Conclusions: This study provides updated data on epidemiology and mortality of RA in Italy, offering insights for healthcare planning and resource allocation. The analysis of causes of death provides additional perspectives for a multidimensional approach to disease management.

Objectives: To assess the frequency and extent of work ability impairment and explore differences in its degree in relation to sociodemographic, clinical and patient-reported factors in patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA).

Methods: This cross-sectional analysis used data from the prospective RABBIT-SpA cohort, including patients aged 18-65 years with physician-confirmed axSpA or PsA. Work ability was assessed in both the axSpA and PsA cohorts using the Work Ability Index (WAI; 7-49 points, higher scores=better work ability), categorised as good/excellent (≥37) or moderate/poor (≤36) according to validated cut-offs. Patients were grouped as employed with good/excellent WAI, employed with moderate/poor WAI or non-employed. Descriptive analyses were conducted.

Results: 2655 patients were analysed (axSpA: 1366; PsA: 1276). In the axSpA cohort, 80% were employed, with 70% reporting moderate/poor WAI (mean 31.6, SD: 7.6). Among patients with PsA, 69% were employed, of whom 71% reported moderate/poor WAI (mean 31.4, SD: 8.1).For both the axSpA and PsA cohorts, compared with individuals with good/excellent WAI, those who were non-employed or had moderate/poor WAI were more often female, older, obese, smokers and had fewer years of education.Individuals with lower inflammatory markers, fewer comorbidities and lower disease activity were mainly in the good/excellent WAI group, while non-employed individuals showed the poorest clinical and patient-reported factors, followed by those with moderate/poor WAI.

Conclusion: Around 25% of patients of working age with axSpA and PsA were non-employed and two-thirds of employed patients reported moderate/poor work ability. The results underline the importance of enhanced focus on occupational health in rheumatology to identify at-risk patients early.

Background: Tumour necrosis factor α (TNFi) and interleukin 17 (IL-17) inhibitors have demonstrated efficacy and safety in psoriatic arthritis (PsA) therapy through head-to-head randomised controlled trials, but evidence from real-world clinical practice (RWE) remains limited.

Methods: Adalimumab vs Ixekizumab Real-world Effectiveness is a multicentre cohort study, aimed at comparing the effectiveness of these drugs in a 'real-world' PsA population. The primary outcome consisted of mixed-effects models comparing Disease Activity in Psoriatic Arthritis (DAPSA) and Psoriasis Areas and Severity Index (PASI) over 12 months in both treatment groups. Remission outcomes (DAPSA; Minimal Disease Activity (MDA)) were analysed using time-dependent Cox models adjusted for confounders.

Results: A total of 437 patients (42% on adalimumab (ADA); 57% on ixekizumab (IXE)) were enrolled. At baseline, the ADA group mainly showed axial and nail involvement, while the IXE group was mostly biologic disease-modifying antirheumatic drug (bDMARD)-experienced and had higher C reactive protein levels and worse functional status.The DAPSA score improved in both groups, and between-treatment differences in DAPSA pathways over time were not significant. Probabilities of achieving DAPSA remission or MDA did not differ by drug at 12 months. PASI improved similarly in both groups, but IXE showed a greater early reduction from baseline at 3 months. DAPSA remission and MDA were primarily associated with male sex, absence of nail psoriasis, higher PASI, fewer prior bDMARDs and better functional status.

Conclusions: This RWE study showed that ADA and IXE provide similar 12-month joint outcomes, while IXE showed a faster skin response. Baseline demographic and clinical features affect the chance of remission, highlighting the importance of personalised treat-to-target approaches in PsA.

Objectives: We compared mean and artery-specific pericoronary adipose tissue attenuation (PCATa) between rheumatoid arthritis (RA) patients and controls and examined whether clinical factors and coronary plaque burden were associated with PCATa similarly in both groups. We also explored differences in PCATa around plaque-free arteries between RA and controls.

Methods: This cross-sectional analysis included 147 patients with RA and 118 age-matched and sex-matched controls with complete coronary CT angiography data. PCATa and plaque counts (total, non-calcified, mixed or calcified) were assessed at a single time point. Models adjusted for age, sex, cardiovascular risk factors and epicardial adipose tissue volume.

Results: Mean and artery-specific PCATa around right coronary (RCA) and left circumflex (LCx) arteries were higher in RA than controls (B=0.35 (95% CI 0.12 to 0.58), B=0.39 (95% CI 0.14 to 0.63) and B=0.25 (95% CI 0.03 to 0.48), respectively). Mean PCATa was higher in males than females (p<0.01). Age and dyslipidaemia influenced PCATa differently in RA versus controls (p for interaction=0.032 and 0.021). Mean and LCx-PCATa were associated with total and mixed plaque counts in RA but not in controls (p for interaction=0.040 and 0.021, respectively). Per-artery PCATa did not differ between RA and controls without atherosclerosis. Among participants with atherosclerosis, PCATa around plaque-free LCx and RCA vessels was higher in RA than controls (p<0.05).

Conclusions: PCATa was higher in RA than controls. Mean PCATa was higher in men and associated with coronary atherosclerosis in RA but not in controls. PCATa differences around plaque-free LCx and RCA vessels between RA and controls were observed among participants with plaque elsewhere.

Objectives: To assess the clinical and imaging characteristics associated with fibroblast activation detected by ⁶⁸Gallium-labelled fibroblast activation protein inhibitor positron emission tomography/CT (⁶⁸Ga-FAPI-PET/CT) in patients with psoriasis and whether ⁶⁸Ga-FAPI uptake correlates with the risk of progression to psoriatic arthritis (PsA).

Methods: Psoriasis patients with arthralgia underwent ⁶⁸Ga-FAPI-PET/CT and were followed up prospectively. ⁶⁸Ga-FAPI uptake was assessed at 71 articular sites and patients with ≥1 joint with ⁶⁸Ga-FAPI uptake and PET/CT Joint Index≥2 were considered FAPI positive. The associations between FAPI uptake and clinical and ultrasound (US) findings were investigated. Survival analyses were conducted to assess the association between ⁶⁸Ga-FAPI uptake and progression to PsA.

Results: 45 patients with psoriasis were enrolled, 37 of whom (82%) were FAPI positive. FAPI-positive psoriasis patients had significantly higher body mass index (BMI) (p=0.036) and Disease Activity Score 28-C reactive protein (p=0.033) compared with FAPI-negative patients. ⁶⁸Ga-FAPI uptake was most frequent in large joints and mechanically stressed sites and was more likely in the presence of low-grade synovial hyperplasia (OR: 1.77, 95% CI 1.08 to 2.89), entheseal Power Doppler (OR: 3.80, 95% CI 1.66 to 8.72) and concomitant osteoarthritis (OA). FAPI-positive patients showed a higher risk of progression to PsA compared with FAPI-negative patients (HR 7.1, 95% CI 0.9 to 53.6) (log-rank p=0.028). Only 1/8 patients with psoriasis (12.5%) without ⁶⁸Ga-FAPI uptake developed PsA, as opposed to 18/37 (49%) of FAPI-positive patients.

Conclusions: In psoriasis patients with arthralgia, ⁶⁸Ga-FAPI uptake, indicating fibroblast activation, is associated with higher BMI, more pain, subclinical US changes and concomitant OA. Pathological ⁶⁸Ga-FAPI uptake at articular sites was indicative of higher risk of progression to PsA in our cohort, suggesting fibroblast activation as a crucial step to develop PsA.

Background: Anifrolumab is approved for adults with moderate-to-severe active systemic lupus erythematosus (SLE) based on Randomised clinical trials (RCTs). While randomised pivotal RCTs have demonstrated their efficacy and safety, real-world evidence (RWE) remains limited.

Objectives: To describe the clinical characteristics, effectiveness and safety of anifrolumab in clinical practice and to assess findings from published observational studies.

Methods: Multicentre study of patients with SLE classified according to EULAR/American College of Rheumatology (ACR) 2019. Data were collected from medical records up to 30 April 2025. Variables included demographic characteristics, clinical and serological features, prior and concomitant therapies, disease activity indices including the SLE Disease Activity Index 2000 (SLEDAI-2K), SLE Disease Activity Score (SLE-DAS) and Physician Global Assessment (PGA), damage and disease control measures including the Systemic Lupus International Collaborating Clinics/ACR Damage Index, Lupus Low Disease Activity State (LLDAS) and Definitions of Remission in SLE (DORIS) remission and the association with adverse events (AEs). A review of published observational studies was also conducted.

Results: We included 206 patients (183 women; mean age 44.6±12.6 years) from 54 Spanish centres. The most common indications for anifrolumab were cutaneous (61.7%), musculoskeletal (48.5%) and haematological (27.2%).A rapid and sustained improvement was observed in disease activity (SLEDAI-2K, SLE-DAS, PGA), LLDAS, DORIS remission, serological markers (anti-double-stranded DNA, C3/C4) and corticosteroid tapering. Organ damage remained stable. After a mean follow-up of 7.5±5.3 months, the most frequent AEs were herpes zoster (n= 5), respiratory infections (n= 6) and headache (n= 3). Twenty patients discontinued treatment. These results were consistent with published observational studies.

Conclusion: In this large RWE cohort, anifrolumab demonstrated early and sustained clinical benefit, a favourable safety profile and a significant corticosteroid-sparing effect. These findings reinforce the evidence from CT and support the incorporation of anifrolumab into routine care for patients with SLE.

Introduction: Interstitial lung disease (ILD) is a serious extra-articular manifestation of rheumatoid arthritis (RA) associated with increased morbidity and mortality. The pulmonary safety of biologic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) in RA-associated ILD (RA-ILD) remains uncertain. This systematic review and meta-analysis aimed to assess the effect of bDMARDs and tsDMARDs on ILD progression in RA, focusing on pulmonary function test (PFT) parameters-forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO)-and, when available, high-resolution computed tomography (HRCT) outcomes.

Methods: PubMed and Cochrane databases were searched up to 2025 for controlled trials and observational studies, including patients with RA fulfilling the 1987 ACR or 2010 ACR/EULAR criteria. Studies reporting longitudinal changes in PFTs or HRCT after bDMARD or tsDMARD treatment were included. Meta-analyses were conducted using the inverse variance method (RevMan V.5.4.1) for pooled estimates of FVC and DLCO.

Results: 18 observational studies including 958 patients (mean age 65 years; 57% female) were analysed. The most frequent ILD patterns were usual interstitial pneumonia (48%) and nonspecific interstitial pneumonia (40%). Data were available for rituximab (six studies), abatacept (4), JAK inhibitors (4), tumour necrosis factor (TNF) inhibitors (1) and tocilizumab (1). Pooled analysis showed no significant overall change in FVC (mean difference -0.85%, 95% CI -2.40 to 0.71; p=0.29) or DLCO (+0.79, 95% CI -0.30 to 1.88; p=0.16).

Conclusion: bDMARDs and tsDMARDs appear to stabilise pulmonary function in RA-ILD, without significant differences between agents. Further prospective studies integrating PFT and HRCT endpoints are needed to better define their pulmonary safety and long-term effects.

Objective: Proactive therapeutic drug monitoring (pTDM) intends to optimise tumour necrosis factor (TNF) inhibitor treatment through regular assessment of drug and antidrug antibody levels, enabling individualised dosing. However, health economic evidence for this strategy is limited. This study aims to evaluate the health benefits and costs of pTDM with infliximab compared with standard therapy.

Methods: Based on the 52-week randomised, controlled, open-label, multicentre Norwegian Drug Monitoring trial (NOR-DRUM) B trial, we estimated the cost-effectiveness of pTDM compared with standard infliximab maintenance therapy in patients with six different immune-mediated inflammatory diseases. For each patient (n=454), we estimated the 12-month healthcare costs, including pharmaceuticals, biochemical tests and other types of resource use. Reported in 2024 Euros, unit costs were based on market prices, diagnosis-related group cost weights and reimbursement schedules. We evaluated health outcomes with quality-adjusted life-years (QALYs), using the EuroQol five-dimension, three-level questionnaire (EQ-5D-3L) and Short Form six-dimension health utility measure (SF-6D). Indicator of cost-effectiveness was the incremental cost-effectiveness ratio, expressed as Euros/QALY, compared with an assumed cost-effectiveness threshold value of €23 755. We assessed sampling uncertainty using the non-parametric bootstrap.

Results: The mean 1-year cost per patient in the pTDM group was lower than in the standard therapy group, with a difference of €592 (95% CI -1304 to 107), while the QALYs based on EQ-5D-3L were 0.0018 higher (95% CI -0.0126 to 0.0165). Based on the bootstrap results, pTDM has a probability of 95% of being cost-effective. In explorative subgroup analyses, pTDM appeared cost-effective for some, but not all diagnoses.

Conclusion: pTDM is very likely a cost-effective treatment strategy for patients with immune-mediated inflammatory diseases on infliximab maintenance therapy.

Trial registration number: NCT03074656.

Objectives: Rheumatoid arthritis (RA) is a disease with a heterogeneous phenotype. Partly, this heterogeneity may be concealed by metrics such as 28-joint disease activity score (DAS28) that may assign similar scores to dissimilar phenotypes. To explore how individual patient profiles may be separated, we developed three classification schemes and compared these with DAS28 in newly diagnosed RA.

Methods: We selected patients aged 18-100 years, newly diagnosed with RA between 2012 and 2022 and registered in the Swedish Rheumatology Quality Register. We devised three alternative classifications based on (i) a subjective-objective decomposition of the DAS28 (seven levels), (ii) clinical experience-based cut-offs for each of the DAS28 components (five levels) and (iii) a data-driven Gaussian Mixture Model (five clusters). For each classification, we calculated descriptive statistics for clinical characteristics, demographic variables and comorbidity histories, and contrasted these with those based on DAS28 categories in our study population.

Results: We identified 6624 patients with complete data on all included variables. In each of the alternative classifications, subjectively dominated and objectively dominated subsets captured differences regarding comorbidity histories not detectable in the DAS28 categories. Across all alternative classifications, subjectively dominated subsets had lower work ability than objectively dominated subsets and included 50%-300% more patients with pain and psychiatric diagnoses prior to RA diagnosis.

Conclusions: Separating subjective and objective dimensions reveals different RA patient profiles that are grouped together by DAS28, demonstrating the extent to which DAS28 is confounded by factors beyond RA disease activity. Disentangling and treating heterogeneous RA patient profiles may therefore require more granular disease activity classification systems.