Variability in TNF Inhibitor Response Across Joint Locations: A Multi-Registry Study

Breaking Down the Study: Why It Matters

·         Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease that affects both the axial and peripheral joints, along with entheses and other musculoskeletal structures.

·         While tumor necrosis factor inhibitors (TNFi) have been widely used as first-line biologic therapy in PsA, their efficacy may differ based on the joint location affected.

·         The complexity of PsA, coupled with variations in inflammatory processes across different musculoskeletal sites, raises the question of whether certain regions respond better to TNFi treatment than others.

·         This study, leveraging data from nine European registries under the EuroSpA collaboration, aims to explore the differential response to TNFi across distinct joint locations in PsA patients.

·         Understanding these variations could help optimize treatment decisions and improve disease management.

Inside the Research: How Scientists Uncovered the Truth

The study analyzed real-world data from patients initiating their first TNFi therapy across nine national registries in Europe. Patients included in the study had confirmed PsA diagnoses and were assessed for treatment response over a defined follow-up period.

The primary outcomes measured were:

·         Changes in disease activity scores specific to different joint locations.

·         Response rates in peripheral joints, axial joints, entheses and dactylitis.

·         Comparison of treatment efficacy across these sites.

Disease activity was evaluated using standardized clinical measures, including the Disease Activity Score for 28 joints (DAS28), Ankylosing Spondylitis Disease Activity Score (ASDAS), and other PsA-specific indicators. Advanced statistical methods were used to analyze treatment response differences across joint locations.

New Findings: How TNF Inhibitors Perform Across Joint Types

Patient Cohort

·         A large cohort of PsA patients was included from various European populations.

·         The majority of patients were TNFi-naïve before initiating therapy.

·         Disease duration, severity and baseline joint involvement varied across patients.

The Big Picture: What the Data Tells Us

1. Peripheral Joints Show Better Response than Axial Joints

   • Patients with predominant peripheral joint involvement showed significant improvement in disease activity scores after TNFi therapy.

   • In contrast, axial involvement demonstrated a more modest response, suggesting TNFi may be less effective in axial PsA compared to peripheral arthritis.

2. Variability in Enthesitis and Dactylitis Response

   • Enthesitis and dactylitis, hallmark features of PsA, showed mixed responses to TNFi.

   • While some patients experienced marked improvement, others exhibited persistent symptoms despite treatment.

   • The variability may be due to differences in local inflammatory mechanisms and drug penetration at these sites.

3. Early Treatment Leads to Better Outcomes

   • Patients who initiated TNFi therapy earlier in the disease course had superior responses, particularly in peripheral joints.

   • Delayed treatment was associated with lower response rates, reinforcing the need for timely intervention.

4. Differences in Response Based on Specific TNFi Agents

   • Some TNFi agents appeared to perform better in axial disease, while others had stronger effects in peripheral arthritis.

   • Future studies are needed to confirm whether specific TNFi molecules have differential effects based on joint location.

The study’s findings underscore the heterogeneity of PsA and the need for a personalized treatment approach based on joint involvement patterns. While TNFi remain an effective option for many PsA patients, their efficacy varies significantly depending on the region affected.

Potential Explanations for Variability

·         Differences in tissue inflammation and vascularization may influence drug distribution and efficacy at different joint locations.

·         Genetic and immunological variations in PsA subtypes could affect individual responses to TNFi.

·         Delayed treatment initiation in certain cases might contribute to a suboptimal response, particularly in axial disease.

These insights highlight the necessity for joint-specific treatment strategies. Physicians should consider alternative biologic agents, combination therapies, or targeted interventions for patients with inadequate TNFi responses, especially in axial disease and enthesitis.

Clinical Implications

·         Early identification of predominant joint involvement can help tailor TNFi selection and treatment strategies.

·         Peripheral arthritis may respond well to TNFi, but alternative biologics (e.g., IL-17 inhibitors) might be considered for axial disease.

·         Combination approaches, including NSAIDs, physical therapy, or adjunctive immunomodulators, may benefit non-responders.

The Future of Psoriatic Arthritis Treatment

·         This large-scale registry-based study provides compelling evidence that TNFi efficacy in PsA is not uniform across different joint locations.

·         Peripheral joints show the most robust improvement, while axial joints and enthesitis exhibit variable responses.

·         These findings emphasize the importance of personalized treatment strategies based on joint-specific disease activity.

·         Further research is needed to optimize therapy selection and improve long-term patient outcomes.

By - Eeshan Aggarwal

Reference:

Ciurea, A., Kissling, S., Götschi, A. et al. Differences in the response to TNF inhibitors at distinct joint locations in patients with psoriatic arthritis: results from nine European registries. Arthritis Res Ther 27, 18 (2025). https://doi.org/10.1186/s13075-025-03488-w