Arthritis affects various joints differently, despite systemic inflammatory cues.2 In people with rheumatoid arthritis, transcriptomic variances identified in synovial fibroblasts from various joint sites have been shown to translate into joint-specific phenotypes with distinct characteristics and responsiveness to cytokines.2,3 These findings suggest that different joints may potentially respond variably to specific immunosuppressive treatments. To expand on this, Ciurea and colleagues set out to investigate whether joints at different anatomical locations in people with PsA might respond differently to treatment with a tumour necrosis factor inhibitor (TNFi). The results have been released in an abstract at the 2024 EULAR congress in Vienna.
The research was based on real-life data from several European registries collaborating in the EuroSpA network – and over 1,700 PsA patients starting a first TNFi. The primary outcome was time to first resolution of joint swelling on an individual joint level based on the 28-joint count, assessed at baseline and at various timepoints over 2 years.
At baseline, the mean number of swollen and tender joints at baseline was 4.8 and 7.4, respectively, with a mean disease activity score using the C-reactive protein (DAS28-CRP) of 4.7. When looking at joints of the upper limb – with the proximal interphalangeal joint of the third digit (PIP3) as a reference – a significantly higher rate of resolution of joint swelling was observed for the elbow and the shoulder. In contrast, a lower rate of resolution of joint swelling was found for the wrist in relation to the PIP3 joint. However, there was no evidence for a difference in resolution of joint swelling in the knee as compared to the elbow.
The results suggest that the clinical response to a TNFi in PsA appears to depend on joint location – at least in terms of time to the first resolution of joint swelling. This approach also indirectly identified those joints that were less likely to resolve despite TNFi treatment, suggesting that local factors might impact treatment effectiveness at specific joints – such as mechanical factors or specific synovial fibroblast phenotypes. This new work suggests a need for future analyses to explore whether joint-specific responses in PsA are associated with distinct therapeutic modes of action.
Source
Ciurea A, et al. Differential joint-level responses to TNF inhibitors in psoriatic arthritis: A collaborative European observational cohort study. Presented at EULAR 2024; OP0034.
Ann Rheum Dis 2024; DOI: 10.1136/annrheumdis-2024-eular.2535.
References
1. Gossec L, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update. Ann Rheum Dis 2024; DOI: 10.1136/ard-2024-225531.
2. Frank-Bertoncelj M, et al. Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions. Nat Commun 2017;8:14852.
3. Elhai M, et al. The long non-coding RNA HOTAIR contributes to joint-specific gene expression in rheumatoid arthritis. Nat Commun 2023;14:8172.
About EULAR
EULAR is the European umbrella organisation representing scientific societies, health professional associations and organisations for people with rheumatic and musculoskeletal diseases (RMDs). EULAR aims to reduce the impact of RMDs on individuals and society, as well as improve RMD treatments, prevention, and rehabilitation. To this end, EULAR fosters excellence in rheumatology education and research, promotes the translation of research advances into daily care, and advocates for the recognition of the needs of those living with RMDs by EU institutions.
