Multicentre, 26-week, open-label phase 2 trial of the JAK inhibitor filgotinib in Behcets disease, idiopathic inflammatory myopathies and IgG4-related disease: DRIMID study protocol

Introduction
Research into novel therapies for rare, immune-mediated inflammatory diseases (IMIDs) faces significant challenges, including small patient populations, complex clinical trial design and difficulties in patient recruitment. Patients with Behcet’s disease (BD), idiopathic inflammatory myopathies (IIM) and IgG4-related disease (IgG4-RD) typically undergo treatment involving prolonged administration of high-dose glucocorticoids and immunosuppressants. Both are associated with an increased risk of infection. Additionally, glucocorticoids carry long-term toxicity risks. Thus, there is an urgent need to develop more targeted and effective anti-inflammatory treatments. Given the activation of the type 1 interferon pathway in BD, IIM and IgG4-RD, inhibition of the Janus kinase (JAK) STAT pathway emerges as a promising therapeutic strategy. The Drug Rediscovery in IMIDs (DRIMID) consortium aims to conduct a prospective pilot basket trial to investigate the effects of filgotinib, a JAK1 preferential inhibitor approved for ulcerative colitis and rheumatoid arthritis, on disease activity, quality of life and safety in patients with refractory BD, IIM and IgG4-RD.

Methods and analysis
In this investigator-initiated, multicentre, open-label phase 2 study, up to 60 patients with rare IMIDs will be enrolled for a 26-week treatment period with filgotinib 200 mg once daily. The trial consists of two stages, each involving a consecutively treated cohort of up to 20 patients per disease. An interim analysis is conducted between these stages, where the trial will proceed only in diseases showing potential effectiveness. Baseline, 3-month and 6-month assessments will include data on quality of life, disease activity, corticosteroid toxicity and biomarkers. The coprimary endpoints are disease activity and quality of life across and within each disease.

Ethics and dissemination
The study received approval from the Medical Research Ethics Committee in Utrecht, Netherlands. A Data Safety Monitoring Board has been established to monitor the trial’s safety and progress.

Trial registration number
NCT06285539.

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Error in the Results

The Original Investigation titled “Safety and Efficacy of Anti–IL-23 Monoclonal Antibody QX004N for Patients With Psoriasis: A Randomized Clinical Trial,” published online on December 11, 2024, and in the March 2025 issue was corrected to fix an error in the Results. In the text, the number of patients with a baseline Investigator’s Global Assessment score of 3 (moderate) in the QX004N cohort was corrected from “3 of 21” to “21 of 24.” This article was corrected online and in print.

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Jessner Lymphocytic Infiltrate in Anti-HMGCR Myopathy

This case report describes a man in his 50s with type 2 diabetes and hyperlipidemia who was admitted for rash and proximal muscle weakness, pain, and unintentional 15-pound weight loss associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy.

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Real-world outcomes in patients with melanoma brain metastasis: a US multisite retrospective chart review study of systemic treatments

Objective
This study examined real-world treatment patterns and outcomes in patients with melanoma brain metastasis (MBM) treated with first-line immunotherapy consisting of nivolumab plus ipilimumab or anti-programmed death-1 (PD-1) monotherapy (nivolumab or pembrolizumab) or targeted therapy consisting of BRAF/MEK inhibitors.

Design
Retrospective chart review study.

Setting
Academic medical centres, community hospitals and private practice offices.

Participants
Included patients diagnosed with melanoma with brain metastasis in the USA.

Outcome measures
The statistical analysis was descriptive in nature. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared between treatments in a univariate Cox proportional hazards model.

Results
In total, 472 patients with MBM who received first-line nivolumab plus ipilimumab (n=246), anti-PD-1 monotherapy (n=112) or BRAF/MEK inhibitors (n=114) were identified. Patients receiving nivolumab plus ipilimumab, compared with patients receiving anti-PD-1 monotherapy or BRAF/MEK inhibitors, had favourable baseline prognostic factors, such as younger age, fewer or smaller brain metastases, better Eastern Cooperative Oncology Group performance status and less frequently elevated lactate dehydrogenase. Median follow-up times were 15.4 months (range 0.1 to 37.0), 13.3 months (range 0.3 to 36.6) and 13.9 months (range 1.9 to 36.5), respectively. Numerically longer OS was observed with nivolumab plus ipilimumab versus anti-PD-1 monotherapy (HR 0.47, 95% CI 0.34 to 0.67) or BRAF/MEK inhibitors (HR 0.72, 95% CI 0.50 to 1.04) and numerically longer PFS was observed with nivolumab plus ipilimumab versus anti-PD-1 monotherapy (HR 0.74, 95% CI 0.53 to 1.02) or BRAF/MEK inhibitors (HR 0.82, 95% CI 0.60 to 1.12). With nivolumab plus ipilimumab, anti-PD-1 monotherapy and BRAF/MEK inhibitors, 1-year OS rates were 79%, 60% and 72%, respectively; 1-year PFS rates were 68%, 58% and 59%.

Conclusions
In this real-world study, first-line nivolumab plus ipilimumab appeared to provide benefit versus anti-PD-1 monotherapy and BRAF/MEK inhibitors in patients with MBM, consistent with pivotal trial data. However, the observed benefit may have been due to confounding and selection bias, given that patients receiving nivolumab plus ipilimumab had favourable baseline prognostic factors compared with patients receiving anti-PD-1 monotherapy or BRAF/MEK inhibitors.

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Abstract TP324: Lupus Anticoagulant Is Associated With Acute Recurrence in Cardiogenic Embolic Stroke in Older Patients

Stroke, Volume 56, Issue Suppl_1, Page ATP324-ATP324, February 1, 2025. Background and Purpose:Antiphospholipid antibody syndrome (APS) is a rare cause of cerebral infarction, but the effect of antiphospholipid antibodies (aPL) on the acute phase of ischemic stroke in each stroke subtypes is still unclear, especially in the elderly patients. To clarify this, we compared antiphospholipid antibody levels in patients with acute cerebral infarction with or without recurrence, expansion, or hemorrhagic transformation of infarct in each stroke subtype.Methods:Consecutive ischemic stroke patients in a comprehensive stroke center were screened between April 2013 and April 2024. Inclusion criteria were: 1) admitted 24 hours from the onset, 2) more than 60 years-old on the admission, 3) who had follow-up MRI/CT around one week from the onset, and 4) whose aPL (anti-cardiolipin-beta2-glycoprotein I complex antibody [β2-GPI], anti-cardiolipin antibody [aCL] and lupus anticoagulant [LAC]) measured during the admission for suspected APS. Then, we dichotomized the patients with and without recurrence (R), expansion (E), or hemorrhagic transformation (HT) of infarct upon follow-up MRI/CT findings. We compared clinical features including aPL between the groups by each stroke subtypes based on TOAST classification. Sensitivity and specificity were calculated from receiver operating characteristic (ROC) curve of aPL for predicting R, E, and HT.Results:We screened 2,528 consecutive ischemic stroke patients and 271 patients met the inclusion criteria (60 [22%] cardioembolism (CE), 43 [16%] large-artery atherosclerosis, 29 [11%] small-vessel occlusion and 139 [51%] others). In enrolled patients, 30 (11%) patients showed R, 43 (16%) patients for E and 65 (24%) patients for HT. In CE, CL aCL and LAC were higher in patients with R compared without R (aCL 9.5 vs. 8.0 U/mL,p=0.047; LAC 1.15 vs. 1.01,p=0.006) while aPL were not significantly different in other stroke subtypes. Also, aPL were not significantly different between the patients with and without E or HT. In CE, R increased as LAC became higher (1st tertile vs. 2nd tertile vs. 3rd tertile of LAC: 0 (0%) vs. 1 (6%) vs. 6 (33%),p=0.004). In ROC analysis, the optimal cutoff of LAC for predicting R in CE was 1.12 (area under curve 0.83 [95% confidence interval 0.71-0.94],p=0.006; sensitivity 0.86, specificity 0.82).Conclusions:In CE, LAC was associated with acute recurrence of infarct. LAC should be measured in cardioembolic stroke with recurrence in acute phase.

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Abstract TMP31: Distinguishing Intracerebral Hemorrhage from Acute Cerebral Ischemia in the Prehospital Setting: Development and Validation of the California Acute stroke Subtype PRehospital (CASPR) Scale

Stroke, Volume 56, Issue Suppl_1, Page ATMP31-ATMP31, February 1, 2025. Background:A prehospital, paramedic-administered scale to distinguish intracerebral hemorrhage (ICH) from acute cerebral ischemia (ACI) could improve routing to appropriate centers, enrich field randomized trials with targeted subtype patients, and potentially guide prehospital clinical treatment such as hyperacute blood pressure (BP) lowering. We aimed to create a quickly administered prehospital scale from prospectively performed field assessments.Methods:Two scales were created from NIH Field Administration of Stroke Therapy Magnesium (FAST-MAG) trial data, using logistic regression model with backward stepwise variable selection and retention criterion of p

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Abstract 84: Impact of DOAC plasma levels on Hematoma Expansion in DOAC-associated intracerebral hemorrhage

Stroke, Volume 56, Issue Suppl_1, Page A84-A84, February 1, 2025. Background:Direct oral anticoagulants (DOAC) are associated with an increased risk ofhematoma expansion (HE) in spontaneous intracerebral hemorrhage (ICH). However, thecritical DOAC level influencing this risk remains unclear. This study investigates the impact of DOAC levels on the risk of HE in patients with DOAC-associated ICH.Methods:We conducted a retrospective analysis of patients with DOAC-associated ICH who had DOAC-calibrated anti-Xa or -IIa activity levels measured upon admission. Patients were categorized based on a clinically established cutoff for subtherapeutic DOAC levels (

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