Royal Wolverhampton NHS Trust

Therapies with robust visual outcomes and reduced patient and healthcare system treatment burden are needed amidst the rising incidence of neovascular age-related macular degeneration (nAMD). Aflibercept 8 mg is an additional treatment option with demonstrated potential for extended dosing intervals of up to 24 weeks. The objective of this publication is to introduce a clinical care pathway, developed by expert consensus of experienced UK clinicians, to support best practice with aflibercept 8 mg in nAMD. A structured, face-to-face roundtable meeting of 13 UK retina specialists was held on 8 October 2024, organised and funded by Bayer. The expert panel reached consensus following review of key clinical trial data and consideration of current NHS clinical practice to provide guidance on the use of intravitreal aflibercept 8 mg in nAMD. The panel provided recommendations for an aflibercept 8 mg treat-and-extend pathway for both treatment-naïve and previously treated patients with nAMD. Criteria were developed to guide dosing interval extension, reduction or maintenance based on visual acuity and optical coherence tomography imaging. More detailed guidance includes considerations for switching treatments to or from aflibercept 8 mg, monitoring, and discontinuing treatment. Aflibercept 8 mg may offer opportunities for longer treatment intervals and reduced patient and clinic burden compared with first-generation agents. The proposed treatment pathway is practical and accounts for variability in healthcare structures and capacity pressures, providing clinicians with flexibility in implementing these recommendations while addressing patient needs.

OBJECTIVE:Across several clinical specialties, research-active hospitals deliver higher-quality care and achieve better patient outcomes. To date, these associations have primarily been demonstrated using hospital-reported metrics, with limited insight from the patient perspective. This study evaluated, for the first time, the association between research activity within UK inflammatory bowel disease (IBD) hospital services and adult patient-reported quality of care. METHODS:A cross-sectional analysis was conducted using 2023 national IBD UK benchmarking Patient and Service Survey data linked with research recruitment metrics from the National Institute for Health and Care Research Central Portfolio Management System (CPMS) between 2020 and 2022. Patient-reported high-quality care in the preceding 12 months was defined as a response of 'good', 'very good' or 'excellent' on a five-point Likert scale. Research activity was measured by the number of participants recruited to CPMS-registered IBD studies managed by gastroenterology. Associations were assessed using Spearman's correlation and multivariate regression, adjusting for service-level factors. RESULTS:Recruitment data from 32 391 research participants across 176 IBD services were aligned with 11 454 care quality and 13 583 research opportunity patient responses. A positive correlation was observed between IBD service research recruitment volume and the proportion of patients reporting high-quality care (rₛ=0.19, p=0.013). This association remained significant after adjusting for tertiary status, service size, number of consultants and presence of an IBD leadership team (adjusted β (SE)=0.0008 (0.0004); p=0.029). Services recruiting to interventional studies demonstrated higher patient-reported care quality, while those offering research opportunities reported both higher care quality and greater research recruitment. CONCLUSION:IBD service research activity is positively associated with patient-reported care quality. Embedding research engagement within routine service delivery may improve patient experience and support quality improvement. The results have important implications for service design, workforce planning and national research policy.

Secondary central nervous system (CNS) large B-cell lymphoma (SCNSL) occurs in the de novo setting, as a CNS-isolated relapse, or synchronous (concomitant CNS and systemic) relapse. SCNSL is a devastating event without therapeutic consensus. Thus, we aimed to evaluate treatment outcomes in an international cohort. Progression-free survival (PFS), overall survival (OS) and cumulative incidence of relapse (CIR, estimated using competing-risk models) were reported. Prognostic factors were identified in a 6-month landmark multivariate analysis. Outcomes following thiotepa autologous stem cell transplant (ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) delivered at relapse were compared following propensity score matching (PSM). A total of 1139 patients were included in the analysis (de novo: 537; relapsed SCNSL: 602). 2-year PFS estimates were 40.4%, 43.9% and 16.2% for de novo SCNSL, CNS-isolated relapse, and synchronous relapse respectively. Patients with CNS-isolated relapse demonstrated low rates of systemic recurrence (24-month CIR 6%). Thiotepa-ASCT correlated with longer survival in de novo SCNSL (PFS: HR=0.57; P=0.005; and OS: HR=0.62; P=0.023) and CNS-isolated relapses (PFS: HR=0.55; P=0.002; and OS: HR=0.39; P<.0001) in 6-month multivariable landmark analysis. ASCT (thiotepa or non-thiotepa) also associated with improved survival in synchronous relapses (PFS: HR=0.57; P=0.023; and OS: HR=0.48; P=0.019). Higher survival with thiotepa-ASCT compared to CAR-T was observed in survival analyses following PSM (PFS: HR=0.45; P=0.005 and OS: HR=0.41; P=0.014). These data support thiotepa-ASCT in eligible patients, particularly de novo disease and CNS-isolated relapses. CNS-isolated relapse was infrequently associated with systemic recurrence, supporting treatment regimens adopted from primary CNS lymphoma.

In chronic kidney disease it is hypothesised that the association between loss of lean tissue mass (LLTM) and mortality is purely a function of multimorbidity. We conducted a systematic review in CKD patients to quantify the strength of association between LLTM and mortality or frailty surrogates, including hospitalisation and quality of life (QoL). Muscle mass was estimated using different whole-body bioimpedance methods (BI-MM). Searches of electronic databases identified 132 studies for inclusion (147542 dialysis patients; 15378 CKDG3−5 patients; 356 kidney transplant recipients [KTR], with 14429 deaths). From 67 studies reporting unadjusted analyses, 52 (78

Background:Tofacitinib, filgotinib, and upadacitinib are Janus kinase inhibitors (JAKi) that have demonstrated efficacy in ulcerative colitis (UC) against placebo. This study aims to compare the clinical efficacy between these drugs. Methods:This is a multicentered, retrospective cohort study. Patients with UC starting a JAKi were recruited between 2018 and 2024 when starting their first JAKi. Clinical remission and response, based on clinical scores, calprotectin, and endoscopic measurement, were assessed at 3 and 6 months. Both independent and combined variable outcomes were analyzed. Results:Two hundred and seventy patients were included in the analysis, of which 70 (26%) were on upadacitinib, 51 (19%) on filgotinib, and 149 (55%) on tofacitinib. Clinical, biochemical, and endoscopic remission at 6 months was 91%, 71%, and 80% for upadacitinib; 78%, 67%, and 50% for filgotinib; 73%, 51%, and 44% for tofacitinib. Upadacitinib demonstrated significantly greater clinical response (P = .027) and remission (P = .037) rates at 6 months than tofacitinib. Drug persistence at 12 months was 86% for upadacitinib, 72% for filgotinib, and 69% for tofacitinib. Upadacitinib demonstrated significantly greater 6-month remission rates compared to tofacitinib in the bio-exposed cohort (71% vs 52%, P = .022) and in the bio-naïve cohort (93% vs 50%, P = .009). The incidence rates for hospital admissions were 10.2, 21.9, and 14.1 and for colectomies were 6.7, 10.0, and 5.0 per 1000 patient-months at risk for upadacitinib, filgotinib and tofacitinib, respectively. Conclusion:This study demonstrates that upadacitinib is more likely to achieve 6-month response and remission compared to tofacitinib. In both bio-naïve and bio-exposed patients, upadacitinib was more likely to achieve remission at 6 months. The efficacy of JAKi does not appear diminished by prior biologic use.