From Domains to Decisions: Personalizing PsA Care with Data Save

At EULAR 2025, Dr. Laura Coates (Oxford) took the plenary stage to reframe how we think about treating psoriatic arthritis. The message was clear: in 2025, PsA treatment is no longer about following a linear algorithm; it’s about understanding the unique constellation of domains, comorbidities, and patient factors that shape each clinical decision.

Current treatment guidelines from both EULAR and GRAPPA support a domain-based approach. Patients with peripheral arthritis, polyarticular or oligoarticular, are typically started on csDMARDs, usually methotrexate. But for enthesitis and axial disease, there’s no evidence for csDMARD efficacy; here, biologics or JAK inhibitors should be initiated as first-line therapy. Apremilast remains a treatment option for milder presentations, and cautious tapering may be appropriate for patients in sustained remission. GRAPPA guidance further encourages clinicians to treat as many active domains as possible, rather than focusing on one at a time, a shift toward more holistic, personalized care.

Despite this framework, many patients with early PsA continue to be under-treated. A study by Charlton and colleagues (ACR 2022) found that PsA patients with high disease activity were significantly less likely to receive DMARDs than their RA counterparts. Even when treatment was initiated, monotherapy dominated. Few patients received combination therapy or early biologics, suggesting a lingering inertia in early PsA care.

This stands in contrast to the accumulating evidence that favors early, targeted intervention. In the COMPLETE study, the combination of methotrexate and leflunomide yielded greater PASDAS improvement and more patients achieving low disease activity and VLDA than methotrexate alone, though with more GI side effects and liver enzyme elevations. The SPEED trial (OP0089), presented at EULAR, randomized early poor-prognosis PsA patients to standard step-up methotrexate, combination csDMARDs, or early TNFi (adalimumab). At 24 weeks, both combination and early biologic strategies outperformed step-up monotherapy, but by 48 weeks, early TNFi use was superior. Similarly, the STAMP trial showed that secukinumab plus methotrexate improved ACR50, PASI90, and MDA rates more than methotrexate alone by week 12.

Choosing among targeted therapies is increasingly informed by both domain involvement and comparative data. Head-to-head trials provide some guidance: in SPIRIT-H2H, ixekizumab was non-inferior to adalimumab for joint outcomes and superior for skin. In SELECT-PsA, upadacitinib (15 and 30 mg) outperformed adalimumab across multiple endpoints, including MDA and ACR70. EXCEED showed similar ACR responses for secukinumab and adalimumab, but greater PASI responses with IL-17 inhibition.

Domain coverage, comorbidities, and safety all influence therapy selection. TNFi offers the broadest efficacy across domains and has the longest track record, including utility in IBD and uveitis. IL-17 inhibitors excel for skin, axial disease, and enthesitis, but may not be suitable for patients with IBD. IL-23 inhibitors are effective for skin but lack evidence for axial symptoms. JAK inhibitors bring the convenience of oral dosing and wide domain coverage, but come with safety trade-offs. Dr. Coates presented a visual “choice map” that distilled these factors, highlighting how modern PsA therapy hinges on personalization rather than protocol.

Looking ahead, new agents like bimekizumab, izokibep, deucravacitinib, and icotrokinra are expanding the horizon of PsA care. But while the therapeutic toolkit grows, the goal remains consistent: early inflammation control, treat-to-target principles, and matching the right treatment to the right patient.

As Dr. Coates concluded, treatment selection is becoming increasingly complex, but that complexity, when managed thoughtfully, enables us to do better by our patients.