Similarities and differences between axial spondyloarthritis and axial psoriatic arthritis

Abstract

Spondyloarthritis (SpA) covers a group of interrelated disorders which encompasses ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, undifferentiated SpA and so on. About 5%–30% of non-radiographic-axial SpA patients develop AS over 2–30 years.1 Inflammatory spondylitis, known as axial PsA (axPsA) occurs in 25%–70% of patients with PsA, with greater prevalence in patients with longer disease duration.2 In 1 cohort, an estimated 15% of patients with PsA who did not have axial involvement at presentation developed axPsA over 10 years of follow-up.3 Here, we aim to address the similarities and differences between axial SpA and axPsA in the genetics, clinical presentation, imaging and treatment response. Human leukocyte antigen (HLA)-B*27 is a genetic risk factor for both diseases: axPsA and AS. HLA-B*39 (odds ratio [OR] 2.51, 95% CI 1.25–5.01, P = .009),4 HLA-B*27, HLA-B*08, HLA-B*38, and HLA-Cw*07:02 are associated with axPsA (OR 5.0; 95% CI 1.4–25.0, P = .01).5 However, HLA-B*13:02, HLA-B*40:01, HLA-B*40:02, HLA-B*47:01, HLA-B*51:01 are associated with AS. Moreover, interleukin (IL)-23, IL-17 pathway genes are more common in AS whereas IL-13 genes are risk factors for axial PsA. Inflammatory back pain is reported by patients with PsA and by patients with AS, and includes: pain in the hips or buttocks that improves with activity and worsens with rest; pain that occurs at night; pain that is responsive to nonsteroidal anti-inflammatory drugs (NSAIDs); and axial morning stiffness that lasts for more than 30 minutes.3 Fewer patients (45%) with axPsA are symptomatic with inflammatory back pain whereas nearly 100% of AS patients endorse inflammatory back pain symptoms. Similar levels of self-perceived health status, which reflects pain, disease activity and quality of life, were reported for both diseases. These 2 disorders have differing clinical presentations. Compared to AS, axPsA patients can be asymptomatic, have asymmetrical sacroiliitis, present worse degree of peripheral arthritis, and may present with or without sacroiliitis. However, compared to axPsA, AS patients are more likely to be male, younger, and have more limitation of spinal mobility and back pain.6 An international cohort included 244 axPsA patients (25% HLA-B27+) and 198 AS patients (75% HLA-B27+). It was found that HLA-B27 positive patients had higher levels of radiographic damage, more marginal syndesmophytes, and more syndesmophyte symmetry. However, most patients with PsA axial disease were HLA-B27 negative and less frequently had sacroiliac joint involvement.7 These findings emphasize the importance of HLA-B27 status in severity and the phenotypic radiographical expression of disease. These 2 disorders have differing radiographic presentations. Compared to AS, spinal disease in PsA is more frequently unilateral. In addition, syndesmophytes show a larger volume, that is, appear “chunky”. In most cases, PsA axial disease does not follow exactly the course of the anterior longitudinal ligament and does not appear in consecutive vertebrae.8 However, the radiographic images of AS patients usually present with symmetrical erosion and ankylosis of the sacroiliac joints. Moreover, “bamboo spine” can be seen in AS patients.9 As a minority of subjects have axPsA in PsA, spine disease has not been thoroughly assessed in PsA randomized clinical trials (RCTs). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was developed to assess disease activity in AS/axSpA,10 but when applied to other diseases, for example PsA without axial involvement, BASDAI can “indiscriminantly” show elevated values and also improved scores with treatment. Thus, results of this measure in phase 3 PsA trials to try to assess axPsA response need to be considered with caution. According to Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2021 treatment schema, NSAIDs, physiotherapy, simple analgesia, tumor necrosis factor inhibitors, IL-17 inhibitors and Janus kinase inhibitors were strong recommendations for axPsA. These recommendations were largely based on results from trials of these agents in AS trials which were considered “surrogates” for axPsA. The only RCT dedicated to axPsA has been with secukinumab, an IL-17A inhibitor. This medicine showed rapid and significant improvement in Assessment of Spondyloarthritis International Society criteria for 20% improvement (ASAS20) responses through 12 weeks in PsA patients with axial manifestations and inadequate responses to NSAIDs.11 Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were not recommended for both diseases. Regarding IL-12/23i, IL-23i, the GRAPPA recommendations conclude there is not yet sufficient evidence to recommend their use.12 This is partly based on the evidence that ustekinumab, an IL-12/23i and risankizumab, an IL-23i, failed to show differentiation from placebo in AS trials.13 However, in the pooled phase 3 studies of guselkumab in PsA, a sub-study focused on patients considered to have axPsA and evidence of sacroiliitis on X-ray or magnetic resonance imaging (MRI) showed symptomatic benefit in guselkumab treated patients vs placebo14 (Table 1). There are several additional steps on axPsA controversies being taken. First, the AXIS study to develop axPsA classification criteria has begun through an ASAS-GRAPPA collaboration. In addition, a Janssen-sponsored study of guselkumab in axPsA (STAR study) will soon start enrolling, including required sacroiliac/spine MRI abnormalities as part of inclusion criteria. Moreover, an independent-investigator study, to “molecularly” characterize axPsA vs PsA, conducted within the GRAPPA Collaborative Research Networks, is about to commence. To sum up, axial SpA and axPsA have overlapping features but also meaningful differences in genetic, clinical presentation, imaging and immunophenotype. Efforts are underway to develop classification criteria for axPsA to aid research efforts as well as clinical diagnosis and management. Finally, treatments for axial SpA and axPsA are expanding which may improve opportunity to achieve low disease activity or remission.

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