Novartis (Germany)

Left panel: Scheme of the XPAG-immune thrombocytopenia trial. The dexamethasone (DEX) arm consisted of DEX 40 mg/day for days 1-4 for one to three cycles every 28 days to a maximum of 12 weeks, cycles 2 + 3 were optional. Patients randomised to eltrombopag (ETB) + DEX received eltrombopag in combination with a short course of high-dose DEX beginning on day 1 (40 mg/day during days 1-4). The starting dose of ETB was 50 mg/day for 2 weeks; thereafter, the ETB dose was increased by 25 mg for all patients who did not achieve the target platelet count of ≥50 × 109/L. The ETB tapering was performed by decreasing the dose by 25 mg every 2 weeks to a minimum dose of 25 mg every other day for all patients. Right upper panel: Clinical outcomes in patients treated with first-line ETB + DEX. Patients displayed a qualitatively longer response duration and qualitatively reduced usage of rescue medication. Right lower panel: The immunological T-cell response was different in treatment responders and non-responders. Patients with sustained response (responders) displayed a high T-cell clonality at baseline. Clones are depicted as bubbles (right side).

IntroductionThis is an interim analysis of the long-term effectiveness and safety of canakinumab in the tumor necrosis factor receptor-associated periodic syndrome (TRAPS) cohort of the RELIANCE non-interventional study.MethodsFrom June 2018, the RELIANCE non-interventional study enrolled paediatric (aged ≥ 2 – < 18 years) and adult patients (aged ≥ 18 years) with TRAPS who were receiving canakinumab as part of their routine medical care. Physician- and patient-reported measures of disease activity, dosing patterns and safety were evaluated at baseline and every 6 months until the end-of-study visit.ResultsA total of 21 patients with TRAPS were enrolled by the analysis cut-off date of December 2022, of which 61.9% (13/21) were paediatric patients (< 18 years) and 66.7% (14/21) were female. All patients were pre-treated with canakinumab prior to enrolment (median duration of canakinumab treatment prior to study inclusion: 1.2 years). Disease activity, evaluated by physician-reported (physician’s global assessment, disease remission, C-reactive protein, serum amyloid A) and patient-reported (disease activity, fatigue, impact on social life, autoinflammatory disease activity index diary) measures, was generally well controlled throughout the study. At baseline, the majority of patients (71.4%) were receiving the recommended starting dose (SD) of canakinumab, with a more even distribution between the < SD, SD, and > SD dosing schedules observed from month 6. No serious adverse drug reactions were reported. Patients continued to receive vaccinations during long-term treatment with canakinumab. In total, 85.7% (18/21) of patients met the Eurofever/PRINTO classification criteria for TRAPS, 42.9% (9/21) with the presence of a confirmative TNFRSF1A genotype and 42.9% (9/21) without. In total, 14.3% (3/21) of patients did not meet the classification criteria.ConclusionsData from this interim analysis support the long-term effectiveness and safety of canakinumab for the treatment of TRAPS.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-025-00809-y.

Despite the availability of guidelines and effective escalation therapies, chronic spontaneous urticaria (CSU) is often inadequately treated in Germany. Implementation science can help to transfer evidence-based care into practice. The aim of this work is to analyze practical challenges, develop intervention strategies and simulate their potential impact on patient outcomes. A multi-stage approach with literature research, market research, expert interviews and focus groups with healthcare professionals enabled a comprehensive context analysis. Based on this, intervention strategies were developed and simulated using a patient journey model. The focus was on an educational program and telemedicine monitoring. CSU management is hampered by delayed diagnosis and underutilization of available therapies. Barriers include lack of knowledge of diagnostic tools, lack of referral standards and structural barriers to the use of patient-reported outcomes. Two strategies were proposed: a training program to improve diagnostics and therapy and telemedicine to optimize monitoring. Simulations show that educational measures could increase diagnosis and treatment rates and digital approaches could reduce waiting times. The study systematically identifies barriers in CSU care and uses a patient journey approach to show the potential effects of targeted implementation strategies. Educational measures in particular could significantly improve care.

Personalized treatment in psoriatic arthritis (PsA) remains challenging, particularly in guiding dose escalation decisions. We applied a causal machine learning framework to real-world data from the AQUILA study to evaluate the impact of secuki-numab dose escalation (150 mg to 300 mg) on disease activity and health-related quality of life (HR-QoL). Using double machine learning, we estimated both average and patient-level conditional treatment effects (CATEs) based on 42 baseline variables, including demographics, laboratory values, disease activity, HR-QoL, comorbidities, and prior treatments. Patients receiving the higher dose showed greater improvement in Psoriatic Arthritis Impact of Disease (PsAID) scores compared to the lower dose (mean reduction: 1.81 vs. 1.44). Subgroup analysis revealed a 28% HR-QoL gain in patients with elevated body mass index (BMI) or C-reactive protein (CRP). The model predicted that approximately 75% of patients would benefit from dose escalation. These findings demonstrate the utility and scalability of causal machine learning for quantifying individualized treat-ment effects and guiding personalized treatment decisions in PsA. The approach is transferable to other chronic conditions, supporting more precise, data-driven care in real-world clinical settings.

Background:Cytoreductive therapies have been the standard treatment for patients with high-risk polycythemia vera (PV) for decades. However, approximately 24% of patients treated with hydroxyurea will eventually develop resistance or intolerance to hydroxyurea and need second-line (2L) therapy.Objective:This study compared clinical outcomes of patients with high-risk PV who switched to ruxolitinib as 2L therapy (switchers) versus those who continued first-line (1L) therapy (nonswitchers) after suboptimal response.Design:This was a retrospective, multicenter, noninterventional study.Methods:The primary outcome was event-free survival (EFS), defined as the time between the index date and the earliest event of thrombosis, major bleeding, disease progression, or death. Key secondary outcomes included overall survival (OS), time to and rate of disease progression, rate of thrombosis, and change in spleen size.Results:Overall, 225 patients were included (switchers: 69; nonswitchers: 156). At baseline, >50% of switchers had a prior history of thrombosis (p = 0.006) and PV-related symptoms (p = 0.037) versus nonswitchers. Switchers had a numerically greater reduction in spleen size at 3 years than nonswitchers (−14.4% vs +15.9%; p = 0.107). Compared with nonswitchers, switchers were more likely to experience persistence or presence of new PV-related symptoms as suboptimal response before switching to ruxolitinib (p < 0.001). A greater proportion of nonswitchers required ⩾3 phlebotomies to maintain hematocrit <45% within 1 year (p < 0.001). No significant differences were observed between switchers and nonswitchers in terms of EFS, OS, time to disease progression, and rate of thrombosis. However, switchers had a significantly higher rate of disease progression to myelofibrosis than nonswitchers (p = 0.016).Conclusion:These data demonstrate the heterogeneity in patient characteristics and type of suboptimal responses between switchers and nonswitchers. The results suggest that patients who switched to ruxolitinib had more severe disease or rapid disease progression and that ruxolitinib may provide some clinical benefit in terms of spleen size reduction and hematocrit control.

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern. The use of CSP in the prediction of likely cocrystal stoichiometry was also explored, demonstrating multiple possible approaches. Crystallographic disorder emerged as an important theme throughout the test as both a challenge for analysis and a major achievement where two groups blindly predicted the existence of disorder for the first time. Additionally, large-scale comparisons of the sets of predicted crystal structures also showed that some methods yield sets that largely contain the same crystal structures.