The concept of difficult-to-treat disease in rheumatology: where next?

New pathogenesis-based therapeutics and evidence-based consensus treatment recommendations, often with predefined treatment goals, have remarkably improved outcomes across many chronic diseases. However, a clinically significant subgroup of patients responds poorly to interventions and show a progressive decline in the disease trajectory, which poses an increasing health-care challenge. Difficult-to-treat approaches exist in several areas of medicine and the need for similar definitions has recently also emerged in rheumatology.

Sustained response to guselkumab regardless of baseline characteristics in patients with active psoriatic arthritis and inadequate response to TNF inhibitors: results from the phase 3b COSMOS clinical trial.

Objectives: To prospectively evaluate the effect of guselkumab through 48 weeks across various clinical outcomes in subgroups of patients with psoriatic arthritis (PsA) and inadequate response to tumour necrosis factor inhibitors (TNFi-IR) from the phase 3b COSMOS trial. Subgroups were defined by baseline demographics, disease characteristics and prior/ongoing therapies.

Methods: Patients with active PsA (tender joint count (TJC) and swollen joint count (SJC) both ≥3) and TNFi-IR were randomised 2:1 to receive guselkumab 100 mg at week 0, week 4, then every 8 weeks through week 44 or to placebo with cross-over to guselkumab 100 mg at week 16 (early escape) or week 24 (planned).

Synovial tissue myeloid dendritic cell subsets exhibit distinct tissue-niche localization and function in health and rheumatoid arthritis.

Current rheumatoid arthritis (RA) treatments do not restore immune tolerance. Investigating dendritic cell (DC) populations in human synovial tissue (ST) may reveal pathways to reinstate tolerance in RA. Using single-cell and spatial transcriptomics of ST biopsies, as well as co-culture systems, we identified condition- and niche-specific DC clusters with distinct functions.

Greater preservation of SARS-CoV-2 neutralising antibody responses following the ChAdOx1-S (AZD1222) vaccine compared with mRNA vaccines in haematopoietic cell transplant recipients.

Whilst SARS-CoV-2 mRNA vaccines generate high neutralising antibodies (nAb) in most individuals, haematopoietic stem cell transplant (HSCT) and chimeric antigen receptor T-cell (CAR-T) recipients respond poorly. HSCT/CAR-T treatment ablates existing immune memory, with recipients requiring revaccination analogous to being vaccine naive. An optimal revaccination strategy for this cohort has not been defined.