Objectives This study aims to assess the performance of a fully automated deep learning (DL) system for detecting active and structural magnetic resonance imaging (MRI) lesions of the sacroiliac joints (SIJs) in axial spondyloarthritis (axSpA), and validate its generalisability across independent clinical trial datasets. Methods A 2-stage automated pipeline was developed to delineate left and right SIJs and detect 5 MRI-defined lesion types: 1 active lesion: bone marrow oedema (BMO), 4 structural lesions: erosions, fat lesions, sclerosis, and ankylosis. Lesions were assessed at the quadrant or joint level using paired T1-weighted and Short Tau Inversion Recovery sequences. Models were trained on the MEASURE 1 trial (132 patients) using consensus-based labels to address multireader variability and evaluated on 2 independent datasets (PREVENT-555 patients; SURPASS-414 patients). Performance was assessed using area under the curve (AUC), balanced accuracy, sensitivity, specificity, and kappa, and interpreted against expert reader evaluations, done according to the Berlin SIJ scoring method. Results Across all datasets, automated SIJ lesion detection against expert evaluations achieved performance comparable with expert interreader agreement. Structural lesions showed the strongest performance, particularly ankylosis (MEASURE 1 AUC: 0.97, SURPASS AUC: 0.99; balanced accuracy: 0.95 and 0.97). Robust results were also observed for erosions and fat lesions. BMO detection showed consistently high AUCs (0.85-0.93) with lower balanced accuracy (0.72-0.74). Model performance generalised across datasets without additional training. Conclusions A fully automated DL-based approach can reliably detect active and structural SIJ MRI lesions in axSpA with robust external validation, supporting its potential use to enhance the consistency and scalability of MRI assessment in clinical trials and observational studies.
Objectives This study aims to evaluate a triage approach prioritising assessment of patients with inflammatory rheumatic and musculoskeletal disease (iRMD) among rheumatology referrals. Methods In this prospective study, 1180 consecutive referrals to a tertiary rheumatology centre underwent a telephone interview (step 1), followed by a 10-minute rheumatologist consultation within 4 weeks (step 2), during which patients were scheduled for comprehensive inpatient assessment (step 3) immediately, within 4 weeks or later. Diagnostic performance and wait times were analysed. Machine learning (ML) models for steps 1 and 2 were retrospectively investigated. Results Among 1180 referred patients, iRMD was suspected in 413 patients (35%) and not suspected in 767 (65%), of whom 52 (4.4%) were considered sufficiently unlikely to have an iRMD to forgo further evaluation. The remaining 1128 patients were scheduled for comprehensive assessment (step 3). Of these, 148 (13.1%) dropped out, whereas 980 patients proceeded. iRMD was diagnosed in 314 patients (32%); 666 (68%) had noninflammatory conditions. Step 2 correctly identified 211 patients with iRMD (sensitivity 67.2%) and 502 patients without iRMD (specificity 75.4%). Mean (SD) time from telephone interview to final assessment was shorter for patients with iRMD than for those without iRMD (33 [30] vs 55 [24] days). The step 1 and step 2 ML models achieved area under the receiver operating characteristic curve (AUC-ROC) values of 0.73 (95% CI: 0.65-0.80) and 0.78 (95% CI: 0.70-0.86), respectively. Conclusions The triage approach accelerated assessment for more than two-thirds of patients with iRMD, while highlighting the necessity of a full workup to capture the one-third of cases otherwise missed. Using ML may further improve triage performance.
OBJECTIVES:Rheumatoid arthritis (RA) is a chronic autoimmune disease in which distinct macrophage (MΦ) endotypes can guide therapy. TLR5, upregulated during disease flares, drives an IL-1β+NFKB1+IFN-γ+STAT4lo MΦ phenotype in blood and synovium that is refractory to tumour necrosis factor (TNF) and IL-6R blockade. This study aimed to identify an alternative strategy to correct inflammation and metabolic dysfunction in these pathogenic MΦs. METHODS:Peripheral blood-derived MΦs and synovial tissue from patients with RA, together with a localised arthritis model, were used to assess responses to succinate dehydrogenase (SDH) inhibition following TLR5 stimulation. We performed bulk RNA sequencing, Seahorse extracellular flux assays, flow cytometry, and multiscale immunofluorescence microscopy spanning whole RA synovium to individual mitochondria. RESULTS:TLR5, SDH, and p65/NFKB1 colocalised in synovial CD14⁺ MΦs and were upregulated in circulation during disease flares. IL-1β+NFKB1+IFN-γ+STAT4lo MΦs elicited by TLR5 stimulation exhibited biphasic metabolic reprogramming, with an early increase in mitochondrial adenosine triphosphate (ATP) production followed by tricarboxylic acid (TCA) cycle disruption, compensatory glycolysis, and SDH upregulation. In contrast to HK2 inhibition, which targets the first step of glycolysis, SDH inhibition within the TCA cycle intercepted TLR5-induced NF-κB/STAT4 signalling and oxidative stress, restoring TCA enzyme expression and mitochondrial function. In localised TLR5-driven synovitis, SDH inhibition attenuated joint inflammation by reducing the population of F4/80⁺IL-1β+iNOS⁺SDH⁺ MΦs and restoring metabolic balance. CONCLUSIONS:SDH functions as a metabolic-immune checkpoint in pathogenic IL-1β+NFKB1+IFN-γ+STAT4lo MΦs in RA. Targeting SDH may concurrently resolve mitochondrial dysfunction and inflammation in patients experiencing disease flares, with synovial enrichment of TLR5, SDH, IL-1β, NFKB1, and IFN-γ serving as predictive biomarkers.
OBJECTIVES:The European Alliance of Associations for Rheumatology (EULAR) recently proposed a framework for 'difficult-to-manage' (D2M) and 'treatment-refractory' disease in psoriatic arthritis (PsA). We explored real-world prevalence and characteristics of patients fulfilling registry-based components inspired by EULAR's framework among patients with PsA initiating biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD). METHODS:Cohort study from 5 Nordic biologics registries with follow-up of patients initiating first b/tsDMARD 1999 to 2020. First (step 1a), 3 cohorts were defined: discontinuation of ≥2, ≥3, or ≥4 b/tsDMARDs, respectively. Additional components were added sequentially to each cohort: (1b) b/tsDMARD-discontinuation reason (inefficacy/side effects); (1c) discontinuation of ≥2 different mechanisms of action (with 1a+1b+1c providing nuanced understanding of switching patterns); (2) problematic signs/symptoms (patient global score ≥ 30 mm); (3) persistent disease activity (tender/swollen joint count ≥1, C-reactive protein [CRP] > 10 mg/L, or Disease Activity index in PSoriatic Arthritis 28-joint counts >14). Treatment-refractory disease required primary/secondary b/tsDMARD inefficacy (not side-effects/intolerability/contraindications), and objective inflammation (tender/swollen joint count ≥ 1, or CRP > 10 mg/L). RESULTS:Among 14,362 patients, discontinuation of ≥2/≥3/≥4 b/tsDMARDs occurred in 36%/18%/10%, respectively, during a median(IQR) follow-up of 6.3 years (2.4-10.7). Applying all components (1a-3), D2M prevalences were 2%/3%/3%, respectively. Corresponding treatment-refractory prevalences were 1.2%/1.2%/0.8%, respectively. Female sex, depression, and opioid use increased with the number of b/tsDMARD discontinuations. CONCLUSIONS:In routine care, multiple b/tsDMARD discontinuations were common. Two percent were D2M, and 1.2% were treatment-refractory, both characterised by a higher prevalence of women, depression, and opioid use. Although our retrospective design did not allow testing of the EULAR definitions, our findings highlight the complexity of D2M and treatment-refractory PsA and underline the need for prospective studies.
OBJECTIVES:The systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) was specifically developed for paediatric Still's disease (SD) and has high construct validity and sensitivity to change, with validated operable thresholds. This study aims to validate the sJADAS10 and its thresholds in adults with SD. METHODS:The study involved adult patients with SD, followed in one unique reference centre. We extracted data necessary to assess disease activity according to the sJADAS10 and 4 other measures developed for adults with SD. As a reference, disease activity was classified as inactive disease (ID) or low disease activity (LDA), moderate disease activity (MDA), and high disease activity (HDA) according to the Rosina definitions. Weighted Cohen's kappa coefficients (wKappa) were used to evaluate the agreement between disease states according to the sJADAS10, the 4 other tools, and the reference. We compared the discriminative power (ID vs LDA/MDA/HDA or ID/LDA vs MDA/HDA) of the different tools by receiver operating characteristic (ROC) curves. RESULTS:Data were available for 129 different visits: according to the reference, 38 corresponded to ID, 19 to LDA, 33 to MDA, and 39 to HDA. The highest agreement with the reference was observed with the sJADAS10: wKappa (0.70) and accuracy (0.77). The sJADAS10 discriminative power was also high, with an area under the ROC curve for ID or a combination of ID and LDA at 0.94 and 0.97. CONCLUSIONS:The present study supports the external validity of the sJADAS10 in adults with SD. The sJADAS10 appears to be a relevant candidate for harmonised disease activity assessment across paediatric and adult SD populations.
Deep B-lineage-depleting therapies, including chimeric antigen receptor (CAR) T cells and T-cell engagers, can induce prolonged drug-free remissions in patients with refractory systemic autoimmune diseases, prompting deep depletion and ‘immune reset’ as an emerging therapeutic paradigm. However, durable clinical improvement does not by itself establish immune reset, which implies elimination of autoreactive memory and reconstitution of a renewed, self-tolerant immune repertoire. Furthermore, biological evidence for immune reset following CAR T-cell therapies remains limited to date. In this viewpoint, we aim to address what evidence is required before a mechanistic claim of immune reset can be justified. We propose a provisional research agenda that separates clinical outcomes from target-compartment depletion, humoral reconfiguration, molecular quiescence and complete ‘immune reset’. Full ‘immune reset’ should be defined operationally as durable restoration of self-tolerance despite persistent genetic susceptibility and other contributing pathogenic factors, supported by concordant evidence across disease-relevant tissues, B- and T-cell memory, functional antigen specificity and immune reconstitution. Current data are insufficient to establish this state in most patients.
Objectives Low-dose interleukin-2 (IL-2LD) preferentially stimulates regulatory T cells (Treg) over conventional CD4+ T cells (Tconv), controlling inflammation and promoting immune tolerance in autoimmune and other immune-mediated inflammatory diseases. However, IL-2 has pleiotropic functions, and its therapeutic mechanisms of action remain incompletely defined. In addition, the absence of reliable biomarkers of clinical efficacy limits personalised treatment strategies. We therefore aimed to characterise the transcriptomic effects of IL-2LD in Treg and Tconv cells and to identify candidate biomarkers associated with clinical response. Methods We analysed the whole transcriptome of purified Treg and Tconv from 23 patients with various immune-mediated inflammatory diseases, predominantly autoimmune disorders, treated with IL-2LD in the TRANSREG open-label, exploratory basket trial (NCT01988506). Peripheral blood samples were collected at baseline, day 8, and month 3 after the initiation of treatment. Gene network analysis and multivariate modelling were performed to explore underlying immunological mechanisms of clinical efficacy and evaluate candidate biomarkers associated with clinical response. Results IL-2LD induced broad immune transcriptomic changes, predominantly in Treg cells. Beyond expected IL-2-related gene activation, treatment was associated with progressive downregulation of interferon-stimulated genes (ISGs) in both Treg and Tconv cells, including GBP1, IFIT2, IFIT3, and RSAD2. Importantly, a multivariate model based on baseline ISG expression showed promise for predicting clinical response status to IL-2LD. Conclusions These findings demonstrate that IL-2LD not only expands and activates Treg cells but also shapes an anti-inflammatory transcriptomic landscape characterised by ISG downregulation in Treg and Tconv cells. Baseline ISG expression was associated with treatment response, supporting its evaluation as a candidate biomarker for IL-2LD therapy.
OBJECTIVES:T-cell engagers (TCEs) are well-established treatments in haematology; strategies in autoimmune diseases are evolving. As an alternative to high-dose protocols optimising depletion, lower-dose protocols might optimise safety. METHODS:We assessed safety and efficacy of low-dose blinatumomab in a named patient use case series of 15 patients (median age 55) with multidrug-resistant rheumatoid arthritis (MDR-RA) (28-joint disease activity score C-reactive protein 5.0; clinical disease activity index [CDAI] 28). We monitored safety (cytokine release syndrome [CRS]; immune effector cell-related neurotoxicity syndrome [ICANS]), clinical scores, and tissue inflammation via ultrasound and fibroblast activation protein inhibitor (FAPI)-positron emission tomography/computed tomography (PET/CT). B-cell depletion was quantified in blood, synovium, and lymph nodes. RESULTS:CRS (grade 1) occurred in 3 of 15 patients. No ICANS occurred. One patient developed hypogammaglobulinaemia. One fatal cardiovascular event occurred after 1 year; it was adjudicated as unrelated by treating investigators but not independently reviewed. By week 12, disease activity decreased; 9 of 15 patients achieved CDAI low disease activity, and 3 of 15 patients achieved CDAI remission. Synovial B cells were depleted (4 of 5 biopsies) but not in lymph nodes. FAPI PET/CT showed reduced tracer uptake in the involved joints after blinatumomab. Although 14 of 15 patients flared, disease activity remained lower, and responsiveness lasting >3 months to previously failed drugs (Janus kinase inhibitors, abatacept, tumour necrosis factor inhibitors) was observed in 7 of 15 patients. CONCLUSIONS:Short-term control of RA disease activity, depleted synovial B cells, and reduced fibroblast activation on FAPI-PET were observed 3 months after blinatumomab. Flares after blinatumomab responded to previously ineffective disease-modifying antirheumatic drugs in some patients. Low-dose TCE therapy may offer an accessible path to disease control in MDR-RA, although causal inference and generalisability require validation in controlled trials.
OBJECTIVES:This study aimed to investigate the efficacy and safety of filgotinib, a JAK1 preferential inhibitor, in patients with axial spondyloarthritis (axSpA). METHODS:The phase 3 OLINGUITO trial comprises 2 international, randomised, double-blind, placebo (PBO)-controlled studies. Patients with an established diagnosis of radiographic (r) or nonradiographic (nr) axSpA and an inadequate response/intolerance to ≥2 nonsteroidal anti-inflammatory drugs were randomised 1:1 to filgotinib 200 mg or PBO once daily through week (W) 16 (double-blind period; stratified by high-sensitivity C-reactive protein [hs-CRP] level and prior biologic disease-modifying antirheumatic drug [bDMARD] use). After W16, patients received open-label filgotinib 200 mg through W52; patients ≥65 years and/or with prespecified risk factors received response-based dosing (100 or 200 mg). The primary (Assessment of SpondyloArthritis international Society ≥40% response [ASAS40 response]) and secondary efficacy endpoints were assessed at W16. Efficacy and safety were assessed through W52. RESULTS:At W16, the primary endpoint was met in both studies (ASAS40 response rates: r = axSpA [n = 258], 39.5% filgotinib vs 20.9% PBO [P = .001]; nr-axSpA [n = 237], 34.5% vs 17.8% [P = .003], respectively). ASAS40 improvements, irrespective of hs-CRP level/prior bDMARD use, were observed as early as W1. For secondary endpoints, significant improvements were seen in Axial Spondyloarthritis Disease Activity Score and Spondyloarthritis Research Consortium of Canada magnetic resonance imaging sacroiliac joint inflammation in both studies, and in Bath Ankylosing Spondylitis Functional Index and Ankylosing Spondylitis Quality of Life Questionnaire in patients with r-axSpA. Improvements with filgotinib were maintained/increased further through W52. Overall, 2 cases of myocardial infarction (PBO: n = 1; PBO-filgotinib: n = 1), 3 of herpes zoster (PBO-filgotinib), and 4 of malignancies (excluding nonmelanoma skin cancer; filgotinib: n = 3; PBO-filgotinib: n = 1) occurred. CONCLUSIONS:Across the whole spectrum of axSpA, filgotinib provided rapid and significant patient-relevant improvements in axSpA signs and symptoms and was well tolerated.
OBJECTIVES:To assess complete depletion of B-cell subsets using high-sensitivity flow cytometry (HSFC) across the therapeutic spectrum of rheumatoid arthritis (RA): from good initial rituximab (RTX) responders to poly-refractory RA (failed all biologic or targeted synthetic disease-modifying antirheumatic drug classes). METHODS:Single-centre real-world cohort of 232 RTX-treated RA adults undergoing peripheral blood HSFC assessment at baseline (before the first RTX infusion) and after 2 weeks (2W). Naïve, memory B cells and plasmablasts were quantified; complete depletion was defined as counts < 0.1 cells/µL. One-year response (simplified disease activity index ≤11 within 6 months, maintained for ≥ 12 months) and 5-year RTX persistence (maintained response with no therapeutic change for ≥ 5 years) were assessed. Longitudinal B-cell trajectories with multiple RTX cycles were analysed. RESULTS:2W complete depletion rates were 91% for naïve, 92% for memory B cells, and 69% for plasmablasts. Higher 2W plasmablast counts were associated with lower odds of 1-year response (odds ratio [OR], 0.50; 95%CI, 0.32-0.75; P = .001) and 5-year RTX persistence (OR, 0.48; 95%CI, 0.30-0.79; P = .004); complete plasmablast depletion at 2W was positively associated with both outcomes. Early during disease, poly-refractory RA (n=31; 13%) showed higher 2W memory B-cell levels, and counts were associated with increasing refractoriness (OR, 1.9; 95%CI, 1.3-2.9; P = .003). Across multiple cycles, sustained suppression of memory B cells and plasmablasts were seen in patients showing RTX persistence. CONCLUSIONS:2W plasmablast depletion on HSFC is strongly linked to 5-year RTX retention, while incomplete memory B-cell depletion characterises poly-refractory RA. Thus, responsiveness and refractoriness in RA are linked to B-cell pathology, endorsing HSFC implementation in selecting novel B-cell targeting strategies and early recognition of refractory disease.
OBJECTIVES:The objective of this study is to investigate the safety, biodistribution, and exploratory clinical outcomes of enekinragene inzadenovec (PCRX-201), a high-capacity, nonintegrating, nonreplicating adenovirus serotype 5 vector expressing interleukin-1 receptor antagonist under the control of an inflammation-inducible promoter, in patients with moderate-to-severe knee osteoarthritis. METHODS:This open-label phase 1 trial (NCT04119687) enrolled participants aged 30 to 80 years with symptomatic (Western Ontario and McMaster Universities Osteoarthritis [WOMAC] pain score ≥ 5 and ≤ 9 [0-10-point scale]) and radiographic (Kellgren-Lawrence grade 2-4) knee osteoarthritis. In part 1, participants received a single intra-articular injection of PCRX-201 at 1 of 3 doses (n = 36). In part 2, participants received intra-articular methylprednisolone acetate immediately before PCRX-201 at the same dose (n = 36). Outcomes at week 104 included safety (primary endpoint), biodistribution (secondary endpoint), clinical outcomes (exploratory patient-reported endpoint), and immunogenicity. Data were analysed as observed. RESULTS:Transient treatment-related knee effusion was the most common adverse event and occurred less frequently in participants receiving glucocorticoid pretreatment (13/36 [36.1%]) than in those who did not (22/36 [61.1%]). Very limited biodistribution was detected outside the knee; only 2 participants had detectable PCRX-201 in plasma on days 1 and 4 postinjection. By week 104, 33/72 (45.8%) of participants had discontinued the study; however, those remaining showed sustained improvements with PCRX-201 for the exploratory outcomes of pain, stiffness, and function across doses and groups, regardless of preexisting neutralising antibody levels, with greater improvements observed in the glucocorticoid-pretreated group. CONCLUSIONS:A single intra-articular injection of PCRX-201 demonstrated safety and localised distribution within the knee. Exploratory patient-reported clinical outcomes suggest promise and support further investigation of PCRX-201.
OBJECTIVES:Paediatric-onset immune-mediated inflammatory diseases (IMIDs), including juvenile idiopathic arthritis and related rheumatic diseases, remain genetically undercharacterised. We aimed to define shared and category-specific genetic architecture across paediatric IMIDs, compare signals with adult IMIDs, and identify therapeutic opportunities. METHODS:We analysed 24 paediatric IMIDs classified as autoimmune, polygenic-autoinflammatory, mixed-pattern, or allergic. Genome-wide association analyses included 18,086 cases and 131,019 controls of European ancestry. We estimated single nucleotide polymorphism (SNP)-based heritability, genetic correlations, and polygenic overlap; performed subset-based meta-analysis; and conducted functional annotation, gene prioritisation, pathway and protein network analyses, adult-IMID comparison, and drug-target prioritisation. RESULTS:SNP-based heritability ranged from 28.9% for allergic IMIDs to 61.9% for autoimmune IMIDs. Genetic correlation and polygenic modelling supported partial sharing across categories with category-specific components. Meta-analysis identified 39 genome-wide significant loci outside the Major Histocompatibility Complex (MHC) region, including 15 previously unreported loci; 19 loci were shared between categories. Gene-prioritisation and protein interaction analyses identified a core MHC-centred antigen-presentation network, with category-enriched modules involving complement, innate/barrier pathways, epithelial biology, and type 2 immunity. Enriched pathways included nuclear factor κB signalling, T helper 17 related pathways, Janus kinase-signal transducer and activator of transcription signalling, programmed cell death protein 1/programmed death‑ligand 1, cytotoxic T‑lymphocyte associated protein 4 regulation, and osteoclast differentiation, several of which are relevant to rheumatic diseases. Paediatric IMIDs shared broad polygenic architecture with adult IMIDs, whereas top-ranked genes converged strongly with adult rheumatic diseases. Priority Index analysis identified 178 high-scoring genes, including 43 approved or investigational IMID drug targets. CONCLUSIONS:Paediatric-onset IMIDs share core pathways with adult forms but exhibit distinct genetic architecture shaped by age-specific immune and neurodevelopmental biology. These findings provide a genomic framework for paediatric precision medicine, guiding classification, risk prediction, and therapeutic development.
OBJECTIVES:Pathological ossification leading to spinal ankylosis is a hallmark of ankylosing spondylitis (AS), yet its molecular mechanisms remain poorly understood. We investigated the genetic basis and functional consequences of severe familial AS to identify pathways driving structural progression. METHODS:Genome-wide linkage analysis and whole-exome sequencing were performed in a multiplex family with severe AS. A heterozygous knock-in mouse carrying the identified EXTL3 variant was generated and characterized using microCT, histology, transcriptomics, primary osteoblast and chondrocyte cultures, and biochemical analyses of heparan sulfate (HS) metabolism. RESULTS:A rare missense variant in EXTL3, a key enzyme involved in HS biosynthesis, was identified in affected family members. Extl3mut/+ mice developed sacroiliac structural abnormalities, osteoid accumulation and early joint bridging, together with impaired trabecular bone architecture. Mechanistically, the mutation accelerated chondrocyte hypertrophy while delaying osteoblast maturation and mineralization. These changes were associated with activation of Wnt signalling, increased HS accumulation, enhanced heparanase expression and altered glycosaminoglycan homeostasis. Collectively, these findings identify EXTL3-mediated HS dysregulation as a novel mechanism linking abnormal bone remodelling to pathological ossification. CONCLUSIONS:Our study identifies EXTL3 as a genetic modifier of structural severity in AS and reveals a previously unrecognised role for HS metabolism in pathological ossification. These findings support a model in which HLA-B27 primarily confers disease susceptibility, whereas rare variants such as EXTL3 contribute to structural progression, highlighting HS-related pathways as potential therapeutic targets.
OBJECTIVES:The randomised, double-blind, placebo-controlled, phase 3 Program fOr Evaluation of TYK2 inhibitor Psoriatic Arthritis-1 (POETYK PsA-1) trial evaluated the efficacy, safety, and tolerability of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with PsA naïve to biologic disease-modifying antirheumatic drugs. METHODS:Adults with active PsA, high-sensitivity C-reactive protein concentration ≥ 3 mg/L, and ≥ 1 PsA-related hand and/or foot erosion detectable via radiograph were randomised 1:1 to oral deucravacitinib 6 mg once daily or placebo through week (W) 16. At W16, patients continued receiving deucravacitinib or switched from placebo to deucravacitinib through W52. The primary endpoint was American College of Rheumatology 20% improvement in response (ACR20) at W16. Nonresponder imputation was used for missing data. Efficacy and safety were evaluated through W52. Post hoc rank analysis of covariance was used to evaluate structural damage with no missing data imputation. RESULTS:In 670 patients, a significantly greater proportion of those receiving deucravacitinib vs placebo achieved ACR20 at W16 (54.2% vs 34.1%, P < .001). Responses with deucravacitinib were increased at W52. Patients who switched from placebo to deucravacitinib achieved improvements similar to those in patients who received continuous deucravacitinib. Inhibition of structural damage was observed at W16 and W52. At W16, incidences of serious adverse events (AEs) (deucravacitinib, 1.8%; placebo, 2.4%) and discontinuations due to AEs (2.4%; 1.8%) were low and remained low through W52, without imbalances in cardiovascular events, malignancies, or opportunistic infections. No new safety signals were detected; no deaths occurred. CONCLUSIONS:Deucravacitinib demonstrated superiority vs placebo for clinical responses, patient-reported outcomes, and structural damage inhibition in patients with PsA, with favourable tolerability and safety.
