To evaluate the mental health burden in rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) using diagnostic and self-reported tools and to examine its associations with current disease activity, patient-reported outcomes and barriers to appropriate care.

Single-centre, cross-sectional, case–control study.

Rheumatology centre of a tertiary care hospital, serving as a referral clinic with outpatient and inpatient care in Czech Republic.

233 patients with rheumatic diseases (113 RA, 120 axSpA) and 170 healthy controls (HC).

Mental disorders (MD) were assessed through a structured psychiatric interview using the International Neuropsychiatric Interview (Mini International Neuropsychiatric Interview) administered by a trained professional and by self-reported questionnaires including the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). Disease activity was evaluated with the Disease Activity Score-28 with C-reactive protein (DAS28-CRP) for RA and the Ankylosing Spondylitis Disease Activity Score with CRP (ASDAS-CRP) for axSpA, alongside patient-reported outcomes (PROs).

At least one MD was present in 24.8% of RA, 31.7% of axSpA and 7.0% of HC (p

Mental disorders in RA and axSpA are closely associated with higher disease activity and unfavourable PROs, while access to and acceptance of psychiatric care remain markedly insufficient. Systematic integration of mental health assessment and management into rheumatology practice is strongly warranted.

Combined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade. Early trials in melanoma with FMT and reinduction of immune checkpoint blockade (ICI) therapy in patients with anti-PD-1-refractory metastatic melanoma were reported in 2021 and demonstrated reinstatement of response to ICI therapy in many patients. Due to anatomical vicinity and the physiological relevance of the gut-liver axis, we hypothesise HCC to be a particularly attractive cancer entity to further assess a potential benefit of FMT in combination with ICI towards increased antitumour immunity. Additionally, HCC often occurs in patients with liver cirrhosis, where liver function is prognostically relevant. There is evidence that FMT may increase hepatic function and therefore could positively affect outcome in this patient population.

This prospective, multicentre, randomised, placebo-controlled, double-blind phase II clinical trial has been designed to assess immunogenicity and safety of FMT via INTESTIFIX 001 combined with A/B in advanced HCC in comparison to A/B with placebo. Primary endpoints are measured as tumour CD8+ T cell infiltration after 2 cycles of treatment with vancomycin, A/B+INTESTIFIX 001 in comparison to vancomycin-placebo, A/B+INTESTIFIX 001-placebo and safety of the therapeutic combination in advanced HCC. INTESTIFIX 001 is an encapsulated FMT preparation by healthy donors with a high alpha-diversity in their gut microbiome for oral administration, manufactured by the Cologne Microbiota Bank (CMB). Sample size was calculated to achieve a specific expected accuracy for the primary immunological endpoint. 48 subjects will be randomised to reach a goal of 42 usable measurements in the modified intention-to-treat set. Subjects will be randomised in a 2:1 ratio to A/B or placebo (28 A/B, 14 placebo).

The study was approved by ethics committee review and the German Federal Ministry of Drugs and Medical Devices. The trial is registered under EU CT no. 2023-506887-15-00. The outcome of the study will be disseminated via peer-reviewed publications and at international conferences.

NCT05690048.