Abstract
Background:
Psoriatic arthritis (PsA) is a heterogeneous inflammatory arthritis associated with psoriasis, affecting multiple domains, including peripheral joints, axial skeleton, enthesis, dactylitis, and skin. Several multinational organizations, including European Alliance of Associations for Rheumatology (EULAR), Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), and Pan American League of Associations for Rheumatology (PANLAR), have established treatment recommendations to optimize patient care. However, differences may exist in their guidelines, reflecting methodology regional differences, expert consensus, and evolving evidence.
Design and objectives:
This review compares the treatment recommendations for PsA established by EULAR, GRAPPA, and PANLAR, highlighting similarities, differences, and challenges in achieving standardized treatment strategies worldwide.
Methods:
A comparative literature review analyzing key aspects of each guideline was performed. A systematic evaluation of the latest three multinational treatment recommendations was conducted, focusing on pharmacological and nonpharmacological management approaches. Differences in treatment sequencing, targeted therapies, and emphasis domains were examined.
Results:
While all three organizations emphasize a multidisciplinary and personalized approach to PsA treatment, some variations exist in the preferred sequencing of therapies, the role of targeted synthetic disease-modifying antirheumatic drugs, and the approach to extra-musculoskeletal manifestations. PANLAR provides a regional perspective with emphasis on access constraints, EULAR integrates real-world evidence and long-term safety data, and GRAPPA emphasizes domain-based treatment.
Conclusion:
While PANLAR, EULAR, and GRAPPA guidelines align in core treatment principles, key differences persist, influencing clinical decision-making. Greater international collaboration may enhance the harmonization of treatment recommendations, ensuring optimal patient outcomes globally.
Introduction
Psoriatic arthritis (PsA) is a chronic, immune-mediated inflammatory disease characterized by joint inflammation, enthesitis, dactylitis, axial involvement, and skin/nail manifestations of psoriasis. This condition is classified as part of the spondyloarthritis spectrum and exhibits substantial heterogeneity in its clinical presentation and disease progression. 1 PsA may affect approximately 0.3%–1% of the global population, with a prevalence of 6%–42% among individuals with psoriasis. The incidence of PsA is approximately 6 per 100,000 individuals per year, and the prevalence is approximately 1 per 1000 in the general population.2,3 This condition typically manifests between the ages of 30 and 50 years and equally may affect both genders. Key risk factors include genetic predisposition (HLA-B27, HLA-C*06), 4 environmental triggers, metabolic syndrome, and microbiome alterations. 5 The interplay between genetic susceptibility and immune dysregulation underlies disease pathogenesis, influencing therapeutic responses throughout the whole spectrum of this condition. 6 Previous studies have reported a considerable burden of disease in patients with PsA, with involvement of quality of life associated with disability related to disease activity and its various manifestations. 7
As the understanding of PsA pathogenesis evolves and therapeutic options expand over time, evidence-based treatment recommendations have become increasingly decisive in guiding clinical practice, including those patients refractory to treatment. 8 Given the heterogeneous nature of PsA—encompassing peripheral arthritis, axial involvement, enthesitis, dactylitis, extra musculoskeletal manifestations, and skin/nail disease—a standardized approach to management is essential. 9 Recommendations play a key role in supporting clinicians and rheumatologist by providing evidence-based guidelines for monitoring disease progression and making informed treatment decisions over time. 10
Among the various sets of recommendations available, those proposed by the Pan American League of Associations for Rheumatology (PANLAR), 11 the European Alliance of Associations for Rheumatology (EULAR), 12 and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 13 are among the most recent and widely recognized multinational guidelines around the world. This selection was based on the most recent and widely multinational recommendations, developed through the participation of experts from multiple countries across different regions of the world, looking for a broad geographic representation. Although all guidelines share the common goal of improving patient care and are based on similar body of scientific evidence, variations in treatment recommendations among different organizations are not uncommon. Factors contributing to these discrepancies include differences in methodological approaches, interpretation of available data, weighting of clinical outcomes, prioritization of treatment strategies, and the composition of expert panels. Additionally, regional and national variations in healthcare systems, access to medications, and differences in patient populations may influence guideline development.
This manuscript aims to compare the treatment recommendations for PsA provided by PANLAR, EULAR, and GRAPPA multinational organizations. Although there are several treatment recommendations at the national level and even covering certain regions globally, such as the International League of Associations for Rheumatology recommendations, 14 it was intentionally decided to review these three recommendations for analysis aimed to have a broad geographical representation. By examining the similarities and differences among these three sets of guidelines, we aim to elucidate the rationale behind divergent recommendations and identify areas of consensus within the rheumatology community with interest in the management of PsA and their implications for clinical practice. It is worth noting that methodological differences can significantly shape guideline development. Variability in the scope and rigor of systematic literature reviews, the composition and expertise of consensus panels, regional healthcare, and regulatory frameworks, as well as the timing of evidence synthesis and publication, can all contribute to divergent approaches. These factors may influence a among others, not only the strength and grading of the evidence but also the scope and focus of the final recommendations.
Current management of PsA
The management of PsA has evolved significantly over the past decades, driven by a growing understanding of disease pathophysiology and the development of targeted therapies. 15 PsA is a heterogeneous condition demanding a multidisciplinary and individualized treatment approach. Current management strategies focus on controlling inflammation, preventing structural damage, and improving patients’ quality of life through a combination of pharmacological and nonpharmacological interventions. Management aims to achieve disease remission or low disease activity while addressing musculoskeletal and extra-musculoskeletal manifestations. 16
Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate, are commonly used as first-line therapy, though their efficacy in axial and enthesitis-dominant disease remains limited. Biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) have changed the therapeutic landscape, offering effective options tailored to disease severity, comorbidities, and patient preferences. Biologic therapies targeting tumor necrosis factor (TNF), interleukin-17 (IL-17), and interleukin-23 (IL-23) have modified PsA management, alongside Janus kinase (JAK) inhibitors as an emerging therapeutic option. Additionally, lifestyle modifications, physical therapy, weight control, and patient education 17 play crucial roles in optimizing long-term outcomes and increasing the probability to achieve remission or at least low disease activity. 18
Methods
This study performed a comparative literature review to analyze key aspects of the most recent treatment recommendations for PsA issued by PANLAR, EULAR, and GRAPPA organizations. A systematic evaluation of these guidelines was conducted, focusing on both pharmacological and nonpharmacological management approaches. The analysis included an in-depth examination of treatment sequencing, the role of csDMARDs, bDMARDs, and tsDMARDs, as well as the integration of lifestyle modifications, physical therapy, and patient education. Additionally, particular attention was given to the domains of emphasis within each guideline, including peripheral arthritis, axial involvement, enthesitis, dactylitis, and skin and nail disease. Variations in therapeutic prioritization, treatment escalation strategies, and recommendations for comorbidity management were compared to identify areas of consensus and divergence among the three recommendations.
Results
A comparative analysis of the three treatment recommendations reveals both convergences and divergences in therapeutic approaches.
Overview of PsA treatment guidelines
While all three guidelines emphasize a patient-centered strategy incorporating pharmacological and nonpharmacological interventions, variations exist in treatment sequencing, therapeutic prioritization, and emphasis on specific disease domains. Characteristics of each guideline is depicted in Table 1.
Comparative summary of treatment recommendations and methodological features in psoriatic arthritis guidelines: GRAPPA, EULAR, and PANLAR.
EULAR, European Alliance of Associations for Rheumatology; GRAPPA, Group for Research and Assessment of Psoriasis and Psoriatic Arthritis; IBD, inflammatory bowel disease; JAK, Janus kinase; PANLAR, Pan American League of Associations for Rheumatology.
Methodology
GRAPPA utilized the GRADE method, whereas EULAR followed the Oxford Evidence-Based Medicine categorization following its standard procedures. Meanwhile, PANLAR employed the GRADE-ADOLOPMENT approach, modifying and refining the EULAR recommendations.
Overarching principles
Overarching principles are broad statements that, while not necessarily grounded in direct evidence, reflect strong expert consensus. Both the GRAPPA and EULAR guidelines incorporated overarching principles, whereas the PANLAR guidelines did not. In both sets of guidelines, these principles highlight the importance of shared decision-making between patients and rheumatologists. The updated EULAR guidelines adopted GRAPPA’s earlier recommendation to assess all disease domains. Additionally, both guidelines emphasized a treat-to-target strategy focused on achieving remission and underscored the value of a multidisciplinary care approach. GRAPPA also included two position statements, not based on direct evidence, addressing the use of biosimilars and tapering.
Pharmacological treatment approaches
Conventional synthetic DMARDs
All three guidelines acknowledge the role of csDMARDs, particularly methotrexate, sulfasalazine, and leflunomide, in the treatment of PsA. However, EULAR and PANLAR strongly recommend methotrexate as the preferred first-line option, especially for peripheral arthritis, citing its clinical efficacy in controlling joint inflammation and its potential benefits for skin involvement. GRAPPA, does not establish a strict treatment hierarchy but instead suggests csDMARDs as an option, particularly for patients with milder disease activity. Unlike PANLAR and EULAR, GRAPPA supports a more rapid escalation to biologic therapy when warranted by disease activity.
Biologic DMARDs
The use of bDMARDs, including TNFi, IL-17 inhibitors, IL-23 inhibitors, and IL-12/23 inhibitors (reflecting targeted cytokine categories rather than therapeutic preference), is widely endorsed across all three guidelines. However, some remarks should be mentioned. EULAR does not establish a hierarchy of preference among bDMARDs for the management of joint involvement, as no agent within this class has demonstrated clear superiority over others in terms of efficacy. PANLAR aligns with this recommendation placing additional emphasis on individualizing therapy based on patient characteristics and treatment history. GRAPPA, on the other hand, offers a more flexible approach, allowing for early consideration of IL-17 and IL-23 inhibitors, particularly in patients with predominant skin disease or inadequate response to TNFi.
Another area of divergence is the approach to treatment switching. EULAR recommends switching to an IL-17 or IL-23 inhibitor following TNFi failure, while PANLAR supports a broader range of options, including JAK inhibitors in specific cases although considering caution in patients with cardiovascular or cancer risk. GRAPPA emphasizes shared decision-making, permitting direct transitions between different biologic classes based on patient preference and clinical presentation, which primarily depends on the affected domain.
Targeted synthetic DMARDs
JAK inhibitors have emerged as an important therapeutic option for PsA, particularly in patients with inadequate response to bDMARDs. PANLAR and EULAR endorse JAK inhibitors, such as tofacitinib and upadacitinib, as alternative options when TNFi or IL-17 inhibitors are contraindicated (e.g., side effects) or ineffective (treatment failure). GRAPPA, consistent with its approach, suggests that JAK inhibitors can be considered earlier in treatment sequencing, especially for patients with high disease activity and comorbidities that may exclude bDMARD use. However, all three guidelines (including GRAPPA published before the EMEA warnings applied to all JAKi), recognize the need for cautious use given the potential risks associated with JAK inhibitors, including thromboembolic events and cardiovascular concerns.
Nonpharmacological management
Each guideline emphasizes the importance of nonpharmacological interventions as part of a comprehensive PsA management strategy in clinical practice. PANLAR, EULAR, and GRAPPA advocate for lifestyle modifications, including weight management, physical activity, exercise, and smoking cessation, given their impact on inflammation and treatment response.
Physical therapy and exercise are strongly recommended across all guidelines to maintain joint function and prevent disability, as part of the integrated and interdisciplinary management of PsA and should be recommended based on the patient’s characteristics and disease activity. In the same line, GRAPPA places a greater emphasis on multidisciplinary care, incorporating dermatologists, rheumatologists, and physiotherapists to ensure optimal patient outcomes. EULAR highlights the role of patient education and self-management strategies, while PANLAR includes guidance for integrated and interdisciplinary management by a specialist in physical medicine and rehabilitation.
Disease domain-specific recommendations
PsA is a heterogeneous disease with varying clinical manifestations, and, as mentioned earlier, each guideline provides recommendations tailored to different disease domains.
Peripheral arthritis
Methotrexate remains the cornerstone of initial therapy for peripheral arthritis in the PANLAR and EULAR guidelines, with early transition to biologic therapy if treatment goals are not achieved. GRAPPA’s more flexible approach allows for direct initiation of bDMARDs in patients with severe peripheral arthritis, particularly those with high disease burden or poor prognostic factors. PANLAR goes further by stating the option of a combination of methotrexate and leflunomide as conditionally recommended in adults with active peripheral arthritis in other therapies are contraindicated or not available. Contrary to GRAPPA guidelines, PANLAR did not include sulfasalazine within the csDMARDs based on the insufficient evidence, especially related to skin and joint involvement.
Axial disease
PANLAR, EULAR, and GRAPPA recommendations share common ground in emphasizing NSAIDs as first-line therapy for axial involvement in PsA. All three guidelines also advocate for bDMARDs targeting TNF or IL-17 in cases of axial disease. However, key differences arise in their approaches. EULAR provides a robust evidence-based framework with an algorithm specifically addressing axial disease. GRAPPA, however, suggests that IL-17 inhibitors may be considered as an alternative first-line option, given emerging evidence supporting their efficacy in axial involvement. Unlike EULAR, PANLAR, and GRAPPA mentions JAK inhibitors as an option to consider for axial disease after failing bDMARDs and considering risk assessment. Additionally, PANLAR recommend the use of JAK inhibitors as an additional option in patients with PsA and predominantly active axial disease having an insufficient response to NSAIDs.
Enthesitis and dactylitis
While all guidelines recommend early treatment for enthesitis and dactylitis, the preferred therapeutic approach varies. PANLAR and EULAR advocate for initial NSAID use, followed by biologic therapy when symptoms are persistent. GRAPPA provides greater flexibility in therapeutic selection, supporting the use of TNFi, IL-17, IL-12-23i, or IL-23 inhibitors earlier in the treatment course for refractory enthesitis and dactylitis. GRAPPA provided a conditional recommendation for methotrexate in the treatment of active enthesitis. This marks a shift from previous guidelines, which did not recommend methotrexate due to insufficient evidence. The revision was based on expert consensus and new findings from the SEAM-PsA trial, which indicated that methotrexate’s efficacy in treating enthesitis was comparable to that of etanercept. 19 Dactylitis management mirrors polyarthritis strategies, with csDMARDs like methotrexate recommended initially, escalating to biologics for persistent symptoms.
Skin and nail disease
Given the frequent coexistence of psoriasis, all three guidelines address dermatologic involvement. While EULAR and PANLAR do not provide direct treatment recommendations for skin manifestations, they refer to dermatology guidelines for guidance. In contrast, GRAPPA strongly recommends topical agents as the first-line treatment for patients with limited body surface area involvement. For those with more extensive psoriasis or cases unresponsive to topical therapies, GRAPPA strongly advocates for phototherapy, oral treatments (such as methotrexate, ciclosporin, PDE4 inhibitors, and JAK inhibitors), and bDMARDs (including TNF inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, and IL-23 inhibitors).”
Comorbidity and extra musculoskeletal manifestations
PsA is frequently associated with comorbid conditions, including cardiovascular disease, metabolic syndrome, and extra-musculoskeletal manifestations such as inflammatory bowel disease (IBD), and uveitis. PANLAR, EULAR, and GRAPPA all highlight the importance of screening for and managing comorbidities. EULAR and GRAPPA provides specific guidance on treatment modifications in the presence of extra musculoskeletal manifestations. For instance, in patients with a history of IBD, TNFi, IL-12/23 inhibitors, or JAKi are favored over IL-17 inhibitors due to efficacy and safety concerns. PANLAR similarly stresses the importance of cardiovascular risk assessment when prescribing JAK inhibitors, whereas GRAPPA takes a broader approach, emphasizing shared decision-making based on individual patient profiles.
Treatment sequencing and escalation strategies
A critical distinction among the three guidelines lies in treatment sequencing and escalation. EULAR provides a structured stepwise approach, advocating for sequential use of csDMARDs, bDMARDs, and tsDMARDs based on disease activity and response to prior therapies. PANLAR follows a similar structured approach but incorporates regional considerations, including drug availability and healthcare infrastructure at the country level. GRAPPA, in contrast, offers a more flexible treatment paradigm, allowing for earlier initiation of targeted therapies and a more individualized approach to treatment escalation.
Summary of key similarities
Overall, the guidelines reveal more areas of agreement than points of discrepancy. Despite differences in prioritization and sequencing, PANLAR, EULAR, and GRAPPA share several fundamental principles in PsA management: All three guidelines emphasize the importance of early diagnosis and timely initiation of appropriate therapy. Additionally, csDMARDs remain a mainstay in peripheral arthritis, with methotrexate being the preferred initial agent in PANLAR and EULAR. Nonpharmacological interventions, including rehabilitation, physical activity, weight management, psychological support, and multidisciplinary care, are universally supported. In the same way and considering recent data, 20 comorbidity management is a crucial aspect of PsA treatment across all three guidelines.
Summary of main differences
The treatment recommendations exhibit both convergence and divergence in their therapeutic approaches, reflecting distinct methodological frameworks and regional considerations. An important consideration is that many of the discrepancies observed across guidelines are attributable to variations in update timelines frequency and the incorporation of emerging therapeutic data (e.g., bimekizumab, deucravacitinib). Such differences highlight the evolving paradigm of “living” guidelines, which are intended to adapt continuously to emerging evidence, thereby maintaining their clinical relevance and ensuring timely translation of new scientific data into clinical practice.
PANLAR emphasizes a pragmatic, stepwise strategy that accounts for treatment accessibility across diverse healthcare settings, advocating for initial management with NSAIDs and csDMARDs in mild cases, while recommending the early introduction of bDMARDs—specifically TNF and IL-17 inhibitors—in patients with moderate to severe disease. Notably, JAK inhibitors are positioned as a therapeutic option for cases refractory to bDMARDs, underscoring the need for individualized escalation strategies. EULAR, in contrast, integrates a treat-to-target paradigm, prioritizing csDMARDs as first-line therapy, followed by early initiation of bDMARDs, with TNF inhibitors as the preferred option unless contraindications exist. Furthermore, IL-17 and IL-23 inhibitors are recommended for patients with inadequate response to TNF inhibitors, while JAK inhibitors are reserved for refractory cases due to safety concerns. Importantly, EULAR guidelines incorporate comorbidity assessments and patient preferences as central determinants in therapeutic decision-making. GRAPPA adopts a domain-based approach, tailoring treatment selection according to specific PsA manifestations. For peripheral arthritis, TNF, IL-17, and IL-23 inhibitors are prioritized, while axial disease management favors TNF and IL-17 blockade. Enthesitis and dactylitis treatment is optimized with TNFi, IL-17 inhibitors, and JAKi, whereas IL-23 and IL-17 inhibitors are preferred for psoriatic skin involvement. Additionally, tsDMARDs are considered in refractory disease, broadening the spectrum of therapeutic options.
One key difference lies in the prioritization of biologic therapies. While EULAR follows a stepwise approach, favoring TNF inhibitors as the first-choice bDMARD, both PANLAR and GRAPPA allow for earlier use of IL-17 and IL-23 inhibitors, reflecting emerging evidence on their efficacy in PsA. This distinction is particularly evident in axial PsA, where GRAPPA clearly prioritizes IL-17 inhibitors over TNF inhibitors, whereas EULAR recommends bDMARDs targeting TNF, IL-17A, and IL-17A/F, as well as tsDMARDs targeting JAK. However, EULAR notes that IL-17A inhibition is listed first primarily because only one trial (the MAXIMISE trial) 21 has specifically investigated axial PsA, with other therapies included afterward. Similarly, PANLAR recommends the use of a bDMARD (TNFi or IL-17i) or a JAK inhibitor in patients with PsA and predominantly active axial disease who have had an inadequate response to NSAIDs.
Another critical difference involves the placement of JAK inhibitors within treatment algorithms. PANLAR and GRAPPA recognize JAK inhibitors as viable alternatives earlier in the treatment cascade, especially in cases refractory to initial bDMARD therapy, whereas EULAR remains more conservative, reserving JAK inhibitors for later-line use due to safety concerns. Additionally, regional disparities influence guideline frameworks; PANLAR incorporates cost-effectiveness and accessibility restrictions into its recommendations, ensuring feasibility in Latin American healthcare systems, whereas EULAR maintains a more evidence-driven approach, focusing on rigorous clinical trial data without direct consideration of regional limitations. These variations underscore the complexity of establishing universally applicable treatment pathways for PsA and highlight the necessity of integrating both efficacy data and real-world accessibility considerations in developing comprehensive treatment strategies. From this standpoint, GRAPPA recommendations can be seen as more globally representative, as they are not influenced by regional or geographical drug availability or clinical practice variability. This should be considered when contrasting GRAPPA with guidelines developed in more continental context (EULAR, PANLAR).
Discussion
The comparison of management recommendations between PANLAR, EULAR, and GRAPPA highlights the complexities and challenges of developing standardized guidelines for a heterogeneous disease like PsA in an international context. This process requires taking into consideration some differences in terms of sociodemographic population, different health care systems, and conformation of panel experts in the development of the recommendations.
Despite regional and methodological differences, these guidelines share more similarities than discrepancies, as they were formulated during overlapping timeframes, reviewed comparable bodies of evidence in the scientific literature, and used rigorous methodological frameworks. All three guidelines advocate early intervention and a treat-to-target strategy. Collectively, they provide a complementary framework for PsA treatment, reinforcing evidence-based strategies for clinical decision-making worldwide. Importantly, all three guidelines advocate for a comprehensive and patient-centered approach, integrating nonpharmacological interventions alongside emerging targeted therapies in the setting of a multidisciplinary scenario (rheumatology and dermatology).
The development of a globally unified set of recommendations for PsA management offer significant advantages for rheumatologists by standardizing best practices. International organizations such as PANLAR and EULAR play a crucial role in formulating comprehensive guidelines addressing context-specific challenges and incorporating insights from local and global experts in the field. These guidelines ensure that recommendations are adaptable to variations in healthcare infrastructure at country level, access to therapies, and population-specific disease characteristics. Rather than being contradictory, these guidelines can be seen as complementary frameworks that collectively enhance PsA management helping clinicians to integrate the most valuable aspects of each guideline to optimize patient outcomes.
Developing standardized treatment guidelines for PsA presents significant challenges due to the complex and heterogeneous nature of the disease, as well as variations in healthcare systems across different regions. One of the primary obstacles is the disparity in drug availability and accessibility, which can significantly influence treatment choices and the feasibility of implementing international recommendations in diverse healthcare settings. Additionally, the therapeutic landscape for PsA is rapidly evolving, with an increasing number of targeted therapies emerging. 22 The continuous introduction of novel biologic and small-molecule agents complicates the process of formulating stable, long-term guidelines, as recommendations must be frequently updated to reflect the latest evidence. Another critical limitation is the lack of direct head-to-head comparative trials between different biologic and targeted therapies, making it difficult to establish clear treatment hierarchies and optimize sequencing strategies. Furthermore, the heterogeneity of PsA manifestations—including peripheral arthritis, axial disease, enthesitis, dactylitis, and skin involvement—entails an individualized, domain-driven treatment approach. As a result, while existing guidelines aim to provide evidence-based frameworks for clinical decision-making, the complexity of PsA and the evolving nature of its management continue to pose challenges in achieving globally harmonized recommendations.
Finally, it should be acknowledged that both regional and international guidelines have their advantages and disadvantages to clinicians and rheumatologist; however, local country-specific recommendations may be more useful to clinicians in practice, taking into consideration access, availability, cost, and health system heterogeneity. 23 This underscores the reality for rheumatologists balancing the best available evidence with pragmatic considerations, thereby facilitating the effective and context-appropriate implementation of international guidelines.
Conclusions and future perspectives
While PANLAR, EULAR, and GRAPPA guidelines for PsA share core treatment principles, some differences in therapeutic sequencing and domain-based management could be identified. Collaborative efforts to generate high-quality comparative studies and real-world evidence may enhance guideline harmonization worldwide. Ultimately, a unified international recommendation could provide the greatest benefit to rheumatologists. However, regional organizations such as PANLAR prioritize the development of region-specific treatment recommendations within their strategic framework. This approach facilitates the involvement of regional experts who may not be represented in broader international guidelines, often due to membership limitations. In summary, we believe that the PANLAR, EULAR, and GRAPPA recommendations are, in some ways, complementary. We aim this article support rheumatologists and even dermatologist in incorporating the most valuable elements from each set of recommendations into their clinical practice.
