GRAPPA Research Projects: Development of Criteria for Axial Psoriatic Arthritis and Definitions of Complex-to-Manage and Treatment-Refractory Psoriatic Arthritis

The AXIS study

The AXIS study, a collaborative initiative between ASAS and GRAPPA, explores axial involvement in PsA, which has long lacked standardized classification criteria. In 2018-2019, ASAS and GRAPPA agreed to develop such criteria. A literature review and expert consultation identified candidate items potentially indicative of axial involvement.¹ These include, among others, imaging findings (eg, structural damage or bone marrow edema on magnetic resonance imaging [MRI] of the sacroiliac joints and spine), clinical symptoms (eg, inflammatory back pain, good response to nonsteroidal antiinflammatory drugs), and genetic markers (HLA-B27). To rank these candidates in order of their importance for classifying the patient as having axial PsA (axPsA), an online survey was conducted among ASAS and GRAPPA members using the potentially all pairwise rankings of all possible alternatives (PAPRIKA) approach. Experts evaluated hypothetical patient profiles to determine which combinations of features best indicated axial involvement in patients with PsA who met the Classification Criteria for Psoriatic Arthritis (CASPAR). This multicriteria decision analysis helped rank the importance of each item, with an imaging variable ranked higher. However, at that time, no PsA cohort previously existed with a complete set of imaging (ie, radiographs and MRI scan of the sacroiliac joints and spine) to test potential criteria with imaging components.

The recently completed phase of the project, which focused on prospective characterization of the axial domain in patients with PsA, closed this gap. A total of 428 patients were screened, and 409 patients were enrolled across 41 centers in 19 countries.

The next phase involves developing and applying a PsA-specific classification instrument to 23 cases from existing cohorts, using standardized definitions and response forms. Experts will rank these cases by likelihood of axPsA, enabling item reduction and weighting. The refined criteria will then be tested in the full AXIS cohort.

The findings from the AXIS cohort were presented at the American College of Rheumatology (ACR) Convergence 2024,² and a full publication is currently in preparation. The ultimate aim is to establish validated, internationally accepted classification criteria for axPsA, which is expected to be completed in 2026.

GRAPPA consensus definitions for C2M-PsA and TR-PsA

PsA is a complex and heterogeneous condition, often marked by variable responses to treatment and a persistent burden of disease.³ Despite therapeutic advancements, a considerable number of patients continue to experience symptoms, treatment failure, and diminished quality of life due to comorbidities, fatigue, or psychological distress. Although definitions for D2T disease exist for rheumatoid arthritis^4,5 and were recently published for axSpA,⁶ a standardized framework was lacking for PsA until now.

The GRAPPA-led initiative sought to develop consensus-based definitions for 2 key categories: C2M-PsA and TR-PsA. C2M-PsA refers to a broad group with ongoing symptoms from diverse causes, whereas TR-PsA is a narrower subgroup showing clear inflammation despite treatment (Figure). These definitions were formulated through a transparent, international, multistakeholder process involving both clinicians and patients, a scoping literature review,⁷ and 2 surveys.^8,9 They are intended to support clinical decision making, trial design, registry development, and future research.

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Figure.

Concept of complex-to-manage and treatment-refractory PsA. PsA: psoriatic arthritis; b/tsDMARD: biologic/targeted synthetic disease-modifying antirheumatic drug.

Five overarching principles were agreed upon through a Delphi process:

1. PsA requires multidisciplinary care and shared decision making.

2. Management should address all disease domains and be guided by predefined treatment targets.

3. Inadequate response to recommended therapies should prompt reassessment of diagnosis and consideration of contributing factors.

4. C2M-PsA encompasses a broader group with persistent symptoms because of various factors, whereas TR-PsA represents a specific subgroup with objective evidence of inflammation despite multiple treatments.

5. TR-PsA requires confirmation of inflammation through clinical signs, imaging (MRI or musculoskeletal ultrasound scans), or laboratory markers, with alternative causes excluded.

C2M-PsA is therefore defined as a disease state characterized by persistent symptoms despite at least 1 adequate trial of a biologic/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD), with contributing factors such as comorbidities, overlapping conditions, or treatment-related challenges. These elements complicate disease management and affect quality of life, as perceived by the clinician and/or patient. TR-PsA is defined by failure to respond to ≥ 3 PsA therapies (including ≥ 2 b/tsDMARDs with distinct mechanisms of action), persistent symptoms considered problematic by both clinician and patient, and objective evidence of ongoing inflammation.

Both definitions are accompanied by checklists to facilitate clinical application and patient stratification. The final terminology and framework were endorsed by 95.1% of GRAPPA members through formal voting, reflecting strong international consensus. Future steps include full-text publication, clinical trial and guideline implementation, educational dissemination, and ongoing validation using quality indicators.

This initiative represents a significant advancement in PsA care, providing clinicians with a structured approach to identify patients with complex or refractory disease presentations and helping them to select the right management approach.