BACKGROUND:IgG4-related disease is a chronic fibroinflammatory condition that can affect virtually any organ system. Glucocorticoid agents are a cornerstone of therapy but are limited by toxic effects, and relapse is common after discontinuation. Obexelimab is a bifunctional monoclonal antibody that inhibits B-cell activity through coengagement of CD19 and FcγRIIb without inducing B-cell depletion. METHODS:In this phase 3, double-blind, randomized, placebo-controlled trial, patients with active IgG4-related disease received subcutaneous obexelimab at a dose of 250 mg or placebo once weekly for 52 weeks. For patients in both groups, glucocorticoids were tapered in a standardized schedule to discontinuation at week 8. The primary end point was the time to the first flare of IgG4-related disease for which rescue therapy was required, as determined by both the investigator and the independent adjudication committee. Key secondary end points included complete remission at week 52 and the cumulative dose of glucocorticoid rescue therapy through week 52. RESULTS:From January 2023 through November 2024, a total of 194 patients underwent randomization (with 97 assigned to each group). The time to the first disease flare that required rescue therapy was significantly longer with obexelimab than with placebo (hazard ratio, 0.44; 95% confidence interval, 0.28 to 0.71; P<0.001); flares were reported in 26 patients (26.8%) in the obexelimab group and in 53 patients (54.6%) in the placebo group. Obexelimab showed a significant benefit over placebo with respect to all the key secondary end points, including complete remission (37.1% vs. 19.6%, P = 0.005) and the cumulative dose of glucocorticoid rescue therapy (329.5 mg vs. 929.8 mg, P = 0.004). Adverse events included arthralgias (in 19.6% of the patients in the obexelimab group vs. 11.3% of those in the placebo group), hypersensitivity (in 16.5% vs. 11.3%), and diarrhea (in 11.3% vs. 6.2%). Serious adverse events occurred in 10.3% of the patients in the obexelimab group and in 18.6% of those in the placebo group. CONCLUSIONS:Among patients with active IgG4-related disease, weekly obexelimab treatment led to a significantly lower risk of disease flare and significantly less glucocorticoid exposure than placebo. (Funded by Zenas BioPharma; INDIGO ClinicalTrials.gov number, NCT05662241.).

OBJECTIVES:Ultrasound of the temporal and axillary arteries is recommended as the first-line imaging test for suspected giant cell arteritis (GCA), but the additional diagnostic yield of facial artery ultrasound (facUS) remains unclear. METHODS:In this retrospective study, patients with suspected GCA who underwent standardised ultrasound of the temporal arteries (tempUS) and axillary arteries (axUS) were included if both facial arteries had also been examined. Clinical, laboratory, sonographic and histopathological data were retrieved from the electronic medical records. The diagnostic accuracy of facUS was determined by ROC-curve analysis and 2x2 contingency tables. Patients with and without facial artery involvement were compared by univariate significance tests. RESULTS:Among 69 included patients, 37 were diagnosed with GCA and 32 with other conditions. FacUS-values >0.7 mm were found in 34 patients (26 GCA, 8 non-GCA) and >1.0 mm in 18 patients (17 GCA, 1 non-GCA). When facUS was added to tempUS and axUS, sensitivity increased to 97.3% (+8.1%) but specificity decreased to 65.6% (-18.8%) when a cutoff >0.7 mm was applied. With a cutoff >1.0 mm, diagnostic accuracy changed only marginally. Eleven patients showed negative tempUS but positive facUS results; five of them were ultimately diagnosed with GCA (three of whom had isolated facial artery involvement). CONCLUSIONS:FacUS provides limited additional diagnostic yield when added to temporal and axillary artery imaging in suspected GCA but may be performed in selected patients with strong clinical suspicion and negative temporal ultrasound findings.

Background: Patients with inflammatory rheumatic diseases (IRD) are susceptible to influenza infections and their complications. However, they may avoid vaccination for fear of exacerbating their IRD. This study evaluates the 2023/24 influenza vaccine in IRD patients, aiming to provide recommendations for this group in the upcoming season. Methods: In this prospective, longitudinal study, we assessed the self-reported impact of influenza vaccination on patients with IRD. Participants were recruited nationwide between October and December 2023 and completed an online questionnaire after vaccination as well as at three and six months of follow-up. Results: Among 633 patients, 87.5% were female, with a median age of 50.4 (18-84) years. Post-vaccination, 50% experienced injection site pain; 41% reported no side effects. IRD flares occurred in 5%, with 1% requiring changes to immunomodulation. Among 428 patients with follow-up, influenza infections were reported in 38 patients (8.9%), including 10 (2.3%) with reinfections. No severe cases requiring hospitalization were reported. Spondyloarthritis patients had higher susceptibility to influenza (p = 0.002), accounting for 55.3% of infections. IRD flare-ups in the 12 months before vaccination predicted infections (p = 0.002). Conclusions: The 2023/24 vaccine was well tolerated by IRD patients, with no impact on the course of the disease in 95% of cases. Only 9% of patients reported influenza infections, none of which were severe. In light of these findings, physicians are advised to recommend vaccination to eligible IRD patients prior to or in the respective season.

Objective This systematic literature review (SLR) aims to update the evidence regarding therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), building on the previous SLR informing the European Alliance of Associations for Rheumatology (EULAR) points to consider for the management of D2T RA.Methods Three research questions addressed efficacy or safety of treatments in patients with RA with (1) active disease and limited treatment options; (2) active disease with ≥2 prior biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) and (3) poor health-related quality of life and low objective disease activity (non-pharmacological interventions). MEDLINE, Embase and Cochrane Library were searched until July 2025. Meta-analysis and meta-regression were conducted.Results We screened 8589 records and included 131 studies. For research question (RQ)1, evidence on DMARD efficacy and safety was synthesised across a wide spectrum of comorbidities including obesity, cardiovascular disease, history of malignancy and respiratory comorbidities. For RQ2, all b/tsDMARDs except otilimab demonstrated better efficacy than placebo (mostly high risk of bias). Meta-regression showed efficacy was maintained for Janus kinase inhibitors (JAKi) despite increasing number of prior bDMARD failures (1 to ≥3). Safety results confirmed the increased occurrence of infection and malignancy with JAKi. For RQ3, limited evidence suggested orthopaedic surgical intervention as a potential non-pharmacological option in patients with D2T RA.Conclusions This SLR summarised evidence supporting DMARD efficacy/safety across multiple comorbidities. In patients with active RA with ≥2 prior bDMARDs, JAKi offer substantial clinical benefits but require careful risk stratification given cardiovascular and malignancy risks. Furthermore, standardised reporting and dedicated studies on non-pharmacological interventions are urgently needed.PROSPERO registration number CRD42024593584.

OBJECTIVE:To assess the efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with psoriatic arthritis (PsA) who were naive to biologic disease-modifying antirheumatic drugs or received tumor necrosis factor inhibitors. METHODS:In the 52-week (W), double-blind, placebo-controlled, phase 3 POETYK PsA-2 study (NCT04908189), patients were randomized 3:3:1 to deucravacitinib 6 mg daily, placebo, or apremilast 30 mg twice daily (safety reference arm) through W16. From W16 to W52, patients continued receiving deucravacitinib or apremilast or switched from placebo to deucravacitinib. The primary endpoint was American College of Rheumatology 20% improvement in response (ACR20) at W16. Secondary endpoints were analyzed per prespecified order to control for multiplicity. RESULTS:Overall, 729 patients were randomized (312 deucravacitinib, 312 placebo, 105 apremilast). Significantly more patients achieved ACR20 at W16 with deucravacitinib versus placebo (54.2% vs 39.4%; P=0.0002); responses improved beyond W16 and were maintained through W52 (deucravacitinib-deucravacitinib, 62.2%; placebo-deucravacitinib, 67.3%). At W16, significant differences with deucravacitinib versus placebo were observed in hierarchal secondary endpoints of HAQ-DI, PASI-75, SF-36 PCS, and achievement of MDA. At W16, serious adverse events occurred in 1.0%, 1.9%, and 3.8% of patients with placebo, deucravacitinib, and apremilast, respectively. No new safety signals, deaths, or imbalances in cardiovascular events, malignancies, or opportunistic infections occurred through W52. CONCLUSION:Deucravacitinib was well-tolerated in patients with PsA and demonstrated superior efficacy versus placebo across multiple clinical endpoints and patient-reported outcomes, including functional ability and quality of life. Clinical responses and patient-reported outcomes were maintained through week 52.

BACKGROUND AND AIMS:Inflammatory myopathies (IMs) are a group of autoimmune diseases characterized by progressive symmetric muscle weakness and various extramuscular manifestations. Cardiac involvement in IM has been associated with worse outcomes, but evidence to support specific screening and management algorithms for cardiac comorbidities in IM is still limited. METHODS:For this observational study, 37 adult IM patients recruited from the rheumatology outpatient clinic at Ludwig-Maximilians-University Hospital between August 2023 and January 2025 completed a questionnaire on IM characteristics, management, clinical events, and cardiac disease. Self-reported data were verified and complemented using clinical records. The main study endpoints included the incidence of cardiomyopathy, documented cardiac arrhythmias, and myocardial infarction following the diagnosis of IM. RESULTS:The median age at last follow-up was 60 years and 35.1% were male. The most common cardiac symptoms reported by study participants included dyspnoea (45.9%), congestion/oedema (40.5%), palpitations (32.4%), and chest pain (18.9%). Arterial hypertension was diagnosed in 27% after IM had been established. Supraventricular and ventricular arrhythmias were documented in 10.8% and 5.4%, respectively. Echocardiography was performed in all study participants, revealing left ventricular diastolic dysfunction in 35.1%. Severe structural heart disease and cardiac adverse events, including acute myocardial infarction, severe valvular disease, and left ventricular systolic dysfunction, were documented only in isolated cases of IM. CONCLUSIONS:Cardiac symptoms, risk factors, and structural abnormalities are prevalent in a substantial proportion of patients with IM. Routine cardiologic assessment, including echocardiography, may be advisable. Further evidence from prospective longitudinal studies is needed to optimize screening algorithms and multidisciplinary management.

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory condition. While few diagnostic scores are established, none exist to predict both clinical course and time-point specific outcome of sHLH patients so far. We present a machine learning (ML)-based tool to predict Initial Disease Severity (IDS; defined as admission to intensive care units (ICU) OR death < 90 days without ICU admission) and mortality across different time points in sHLH patients. 167 adult sHLH patients from six study centers across three European countries were included retrospectively. Clinical and demographic features, course, survival, and laboratory data were assessed. Random forest models were trained with two sets of eight clinical and laboratory features: one to predict IDS, and five to predict mortality at distinct time points (30, 60, 90, 180 or 365 days). After calibration, the models were tested against hold-out test sets containing n = 32 (IDS) or n = 43 (mortality) sHLH patients. Overall, the models demonstrated strong discriminatory ability, overall performance, and accurate prediction of risk. Serum levels of the soluble interleukin-2 receptor (sIL-2R) and albumin (for IDS) or sIL-2R and platelet counts (for mortality prediction) showed the strongest contributions to the models’ predictions. The HLH-Risk-Calculator is an exploratory tool predicting the clinical course of sHLH. External validation is critical to assess its validity, applicability, and robustness for real-world use. To this end, the calculator is available at www.hlh-risk-calculator.com for research use only, and is currently not intended for clinical decision-making.

OBJECTIVE:Immune checkpoint inhibitors (ICIs) induce a broad range of immune-related adverse events (irAEs), including rheumatic manifestations. Evidence from dedicated rheumatology cohorts on the clinical spectrum, severity, treatment, and outcomes of rheumatic irAEs (rh-irAEs) remains limited. We aimed to describe clinical phenotypes, treatment, and outcomes of rh-irAEs in a national registry. METHODS:The German ERIN Registry (Registry for the Documentation of Rheumatic Immunotherapy-Related Adverse Events) is a multicenter observational registry of adults receiving ICIs. Rh-irAEs were classified using a rheumatology-oriented phenotype-based framework. Variables included demographics, oncological characteristics, treatments, and outcomes. Severity was graded by Common Terminology Criteria for Adverse Events version 5.0. Univariate analyses identified predictors of second-line systemic therapy. RESULTS:As of January 1, 2026, 60 patients (56.7% men; median age 66 years) were included. Predominant malignancy was melanoma (40.0%). The leading phenotype was rheumatoid arthritis-like polyarthritis (41.7%), followed by polymyalgia rheumatica-like (18.3%) and peripheral spondyloarthritis-like syndrome (11.7%). Axial spondyloarthritis (axSpA)-like syndrome occurred in younger patients. Rh-irAEs were moderate or severe in 90%; 23.3% required hospitalization and 38.3% led to permanent ICI discontinuation. Systemic glucocorticoids (GCs) were used in 85.0%; 58.3% were GC-refractory and 53.3% required second-line immunomodulatory therapy. Complete remission was achieved in 33.3% and partial remission in 51.7%. Oncological progression occurred in 15.0% overall and in 28.1% of patients requiring second-line therapy. Male sex was the strongest predictor of second-line systemic therapy. CONCLUSION:Rh-irAEs in a rheumatologists-referred population were more severe than previously described, with frequent ICI discontinuation and escalation beyond GCs. Male sex was associated with treatment escalation. An underrecognized axSpA-like phenotype occurred in younger patients, warranting further study.

OBJECTIVES:This study aims to provide an update of the European Alliance of Associations for Rheumatology (EULAR) rheumatoid arthritis (RA) management recommendations addressing the most recent insights. METHODS:An International Task Force was formed with a wide expertise and solicited 2 systemic literature research activities on the safety and efficacy of disease-modifying antirheumatic drugs (DMARDs). New evidence was discussed, considering the update from 2022. A voting process was applied to each item. Levels of evidence and strengths of recommendation were assigned, and participants voted on the levels of agreement. RESULTS:The task force agreed on 5 overarching principles and reduced the number of recommendations to 9 concerning use of conventional synthetic DMARDs (methotrexate [MTX], leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b)DMARDs (tumour necrosis factor inhibitors [adalimumab, certolizumab pegol, etanercept, golimumab, infliximab], abatacept, rituximab, tocilizumab, sarilumab, including biosimilars) and targeted synthetic [ts]DMARDs (namely the Janus kinase inhibitors [JAKi] tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target), and tapering following clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were considered. Initially, MTX ideally in combination with short-term GCs is recommended; upon insufficient response after 3 to 6 months, a bDMARD should be added; after careful consideration of risks, including MACEs, malignancies and/or thrombo-embolic events, JAKi may also be considered. If the first bDMARD (or JAKi) fails, any other bDMARD (from another or the same class) or JAKi (considering risks) is recommended. With sustained remission, DMARDs may be tapered, but caution is required as stopping often leads to a flare. Levels of evidence and levels of agreement were high for most recommendations. CONCLUSIONS:These updated EULAR recommendations provide consensus on RA management based on currently available evidence regarding efficacy, safety, and cost.

OBJECTIVES:Giant cell arteritis (GCA) is the most common primary systemic vasculitis and is nowadays commonly diagnosed using vascular ultrasound. Whether repeated ultrasound is helpful in disease management is unclear. METHODS:We conducted a retrospective analysis of 100 patients diagnosed with GCA between 01/2016 and 12/2022. High-resolution ultrasound was performed to assess vasculitic wall thickening in superficial temporal, facial, and axillary arteries at diagnosis and during follow-up. Patients were treated according to current standards, with tocilizumab treatment initiated within 6 months after diagnosis in 38 patients. The course of wall thickening in the different vascular segments was recorded. Patients with and without complete normalisation of wall thickening were compared. The impact of tocilizumab treatment on vessel wall remodelling and the potential benefit of repeated ultrasound examinations for the diagnosis of relapsing disease were assessed. RESULTS:In the overall cohort (63% females, mean age 72.8±8.9 years), one, two or three arterial territories were affected in 31, 50 and 17 patients. Follow-up ultrasound examinations showed a significant reduction in wall thickening over time: superficial temporal arteries -0.42 mm, facial arteries -0.35 mm, axillary arteries -0.36 mm. Normalisation of wall thickening occurred in 32.6% (superficial temporal arteries), 53.1% (facial arteries), and 35.5% (axillary arteries), with some differences in clinical characteristics between patients with and without complete sonographic remission. Patients treated with tocilizumab showed a slightly faster early reduction in mean intima-media thickness which was lost over time. Repeated ultrasound showed a significant increase in maximum IMT (at least +0.3 mm) in 3.6% of the superficial temporal arteries, 18.4% of the facial arteries, and 21.4% of the axillary arteries in patients with relapsing disease. CONCLUSIONS:Our results help to interpret repeated IMT measurements of the affected cranial and extracranial arteries in patients with GCA undergoing treatment. Repeated ultrasound examinations appear to be of limited diagnostic value in the diagnosis of relapsing GCA.

To give further insights into the safety of SARS-CoV-2 vaccinations in patients with inflammatory rheumatic diseases (IRDs) compared to healthy individuals and to highlight changes over the course of repeated vaccinations. In this single-centre study, SARS-CoV-2 vaccinated IRD patients were recruited from the hospital of the University of Munich. Healthcare workers served as the control group. Adverse events following each vaccination were assessed using questionnaires. Descriptive statistics and non-parametric tests were used to illustrate the differences between IRD patients and the control group. Between January 1, 2021, and Septemper 30, 2022, 235 IRD patients (60.4

Hemophagocytic lymphohistiocytosis (HLH) is an orphan disease characterized by excessive inflammation and poor outcome. We sought to further characterize clinical features, courses, and risk factors of secondary HLH (sHLH) triggered by infection (iHLH). 28 (43.1%) of 65 adult sHLH cases treated at our hospital from 2012–2024 were infection-associated. iHLH patients were mostly male (71.4%). Infectious agents most frequently detected were EBV (57.1%) and leishmania (14.3%). The median time to diagnosis was 13 [6.0;24.8] days. iHLH patients had a mortality rate of 39.3% (median follow-up time: 735 [336;1140] days), worse survival than patients with autoimmune-triggered (hazard ratio: 3.33 (1.01–11.10), p = 0.049), and better survival than patients with paraneoplastic HLH (hazard ratio: 0.19 (0.10–0.84), p = 0.002). Elevated levels of soluble interleukin-2 receptor (sIL2R; > 6,000 I/U), low thrombocyte counts (< 40 G/l), and a history of malignant disease were associated with adverse outcomes. Protracted time to diagnosis was associated with severe disease courses and with leishmaniosis. Further, sIL2R levels correlated positively with prolonged aPTT and thrombocytopenia, and hypertriglyceridemia with elevated INRs. Patients with an elevated sIL2R:ferritin ratio were more likely to have a history of malignant comorbidities. Taken together, sIL2R, thrombocytopenia, and a history of malignant disease are important prognostic factors of iHLH. Patients with high sIL2R levels or hypertriglyceridemia may be at higher risk of bleeding, and patients with elevated sIL2R:ferritin ratios should be assessed for possible malignant comorbidities. Lastly, increased awareness of the disease and newly emerging pathogens (i.e. leishmania) may shorten the time to diagnosis, and thus reduce severe courses of iHLH. Graphical Abstract

Cardiac involvement has been described in many forms of vasculitides and is associated with worse outcomes. However, data on the incidence of structural and arrhythmic heart disease is limited. For this single-center study, we recruited 191 patients with giant-cell arteritis (GCA, n = 109), Takayasu arteritis (TAK, n = 26), polyarteritis nodosa (PAN, n = 3), granulomatosis with polyangiitis (GPA, n = 38), or eosinophilic granulomatosis with polyangiitis (EGPA, n = 15) between August 2023 and January 2025. The primary study endpoint was the incidence of structural or arrhythmic heart disease after the diagnosis of vasculitis. The demographic characteristics of patients diagnosed with vasculitis differed significantly between those with GCA, TAK, PAN, GPA, and EGPA. Arterial hypertension and dyslipidemia at baseline were more prevalent among patients with GCA, while chest pain and signs of congestion were more frequently reported by patients with EGPA. No significant difference between the five main subgroups were found regarding the incidence of documented arrhythmic diseases. Cardiac imaging was performed using echocardiography in 70