ACR CONVERGENCE 2021—Although both axial spondyloarthropathy (axSpA) and axial involvement in psoriatic arthritis (axPsA) fall under the umbrella of the seronegative spondyloarthropathies, the differences between axSpA and axPsA affect their management. During a session of ACR Convergence 2021, three experts helped attendees better understand the distinctions and their implications.
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Nigil Haroon, MD, PhD, DM, FRCPC, co-director of the Spondylitis Program at the University Health Network, and associate professor of medicine and rheumatology, University of Toronto, Canada, began the session by discussing the prevalence of axial involvement in SpA and PsA.
“It’s difficult to gauge the true prevalence of axial involvement in SpA and PsA due to the lack of uniform definition,” said Dr. Haroon. “Because of the way axial involvement is defined, the prevalence of axSpA and axPsA may vary. If you look at spondylitis in PsA, about 30% of these patients do not have sacroiliitis and are HLA-B27 negative. But they do have predominant spinal involvement. It’s easy to see how these patients may be missed when assessing the true burden of axial involvement in PsA using the variable definitions currently available for axPsA.”
AxSpA and axPsA also differ in their phenotypes. Dr. Haroon noted that in axPsA, syndesmophytes tend to be bulkier and asymmetric, with earlier neck involvement. On the other hand, syndesmophytes in axSpA are finer and more symmetric.1 Severe and symmetrical sacroiliitis, ligamentous ossification and bamboo spine are more common in axSpA. These differences have been confirmed by studies examining radiologic changes in classic ankylosing spondylitis vs. other seronegative spondyloarthropathies. However, he took care to note that almost all the studies we have to answer this question are cross-sectional.2
Dr. Haroon next discussed the pathological basis of axSpA and axPsA.
“We know that there is variability in treatment response, depending on what clinical manifestations are present—uveitis, psoriasis or axial disease, for example—but why do they exist?” he asked. “The main genetic overlap between ankylosing spondylitis and PsA seems to be HLA-B27, but genetic studies alone don’t explain why axSpA and axPsA behave differently. HLA-B27 negative axPsA looks completely different from HLA-B27 positive axPsA. Isolated spondylitis is much more common in the former.”3
Anna Molto, MD, PhD, Cochin Hospital, Paris, spoke next, focusing on the clinical presentation of axSpA and axPsA. “Psoriatic spondylitis and axial PsA are actually not new concepts and were introduced as early as 1988.4 So is axSpA with skin psoriasis and peripheral arthritis different than axPsA?” she asked. “These are more or less different words to describe the same clinical phenotype.”
Disease burden seems comparable between axSpA and axPsA.5 Dr. Molto concluded, “In my opinion, the take-home message is that there are some phenotypical differences between the two, particularly in imaging at the cervical spine, but the burden of disease is comparable. It is very important that we do not forget to check the spine in our PsA patients.”
Some phenotypical differences between axial spondyloarthropathy (axSpA) and axial involvement in psoriatic arthritis (axPsA) exist, particularly in imaging at the cervical spine, but the burden of disease is comparable, according to Anna Molto, MD, PhD.
Atul Deodhar, MD, MRCP, professor of medicine, Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, Portland, Ore., closed out the session with insights into the treatment of axSpA and axPsA.
“In 2021, we are fortunate to have data to support the efficacy of several different therapeutic options—biologics, as well as Janus kinase inhibitors—for axSpA and non-radiographic axSpA,” said Dr. Deodhar. “Overall, response rates seem to be similar among classes, although head-to-head trials are yet to be conducted.”
However, Dr. Deodhar drew attention to the fact that interleukin (IL) 12/23 inhibition has not proved helpful in ankylosing spondylitis, with both ustekinumab and risankizumab failing to show benefits.6,7
“Why might this be?” he asked. “Cells that secrete IL-23 are more common in the peripheral skeleton than the axial skeleton, which may explain these discrepancies. IL-23 may also not be that important in the pathogenesis of osteitis, the predominant lesion in axSpA. Also, there are IL-23 independent cells that secrete IL-17, a dominant pro-inflammatory cytokine important in axSpA pathology.8 So IL-23 inhibition doesn’t work well in axSpA, but would it work in axPsA?”
Recent trials examining the efficacy of ustekinumab and guselkumab have shown benefit in axPsA.9,10 IL-17 inhibition with secukinumab and ixekizumab has also shown promise.11,12 “Our new direction is confirming whether drugs that work for axSpA work for axPsA patients too. [Because] these two entities are not identical, drugs that work well for one may not work well for the other and vice versa,” Dr. Deodhar said.
Dr. Deodhar was careful to highlight weaknesses of axPsA studies, thus far. “First, there is often no specific information about how the diagnosis of axPsA was made and no classification criteria were used [because] none exist. Some studies lack imaging requirements of any kind, and others have heterogeneous imaging findings. Lastly, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) are outcome measures created specifically for ankylosing spondylitis and not axPsA,” he noted.
Regarding future directions, Dr. Deodhar was pleased to share that the Assessment in Ankylosing Spondylitis (ASAS) working group and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) are collaborating to develop formal axPsA classification criteria in the Axial Involvement in Psoriatic Arthritis Cohort (AXIS).13
“Studies to ‘molecularly’ characterize axPsA vs. PsA patients have also commenced,” he said.
Some of the differences between axSpA and axPsA have clinical and therapeutic implications, although the burden of disease for patients is similar. Work to create formal axPsA classification criteria is underway, as are therapeutic clinical trials targeted specifically to axPsA patients. It’s critical to remember to assess for axial involvement in PsA patients, given its prevalence and morbidity.
Samantha C. Shapiro, MD, is an academic rheumatologist and an affiliate faculty member of the Dell Medical School at the University of Texas at Austin. She received her training in internal medicine and rheumatology at Johns Hopkins University, Baltimore. She is also a member of the ACR Insurance Subcommittee.
- Jurik AG. Imaging the spine in arthritis—a pictorial review. Insights Imaging. 2011 Apr;2(2):177–191.
- Helliwell PS, Hickling P, Wright V. Do the radiological changes of classic ankylosing spondylitis differ from the changes found in the spondylitis associated with inflammatory bowel disease, psoriasis and reactive arthritis? Ann Rheum Dis. 1998 Mar;57(3):135–140.
- Poddubnyy D, Jadon DR, van den Bosch F, et al. Axial involvement in psoriatic arthritis: An update for rheumatologists. Semin Arthritis Rheum. 2021 Aug;51(4):880–887.
- Hanly JG, Russell ML, Gladman DD. Psoriatic spondyloarthropathy: A long term prospective study. Ann Rheum Dis. 1988 May;47(5):386–393.
- Benavent D, Plasencia C, Poddubnyy D, et al. Unveiling axial involvement in psoriatic arthritis: An ancillary analysis of the ASAS-perSpA study. Semin Arthritis Rheum. 2021 Aug;51(4):766–774.
- Baeten D, Østergaard M, Wei JCC, et al. Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: Results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study. Ann Rheum Dis. 2018 Sep;77(9):1295–1302.
- Deodhar A, Gensler LS, Sieper J, et al. Three multicenter, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of ustekinumab in axial spondyloarthritis. Arthritis Rheumatol. 2019 Feb;71(2):258–270.
- Siebert S, Millar NL, Mcinnes IB. Why did IL-23p19 inhibition fail in AS: A tale of tissues, trials or translation? Ann Rheum Dis. 2019 Aug;78(8):1015–1018.
- Helliwell P, Gladman DD, Poddubnyy D, et al. Efficacy of guselkumab, a monoclonal antibody that specifically binds to the p19-subunit of IL-23, on endpoints related to axial involvement in patients with active PsA with imaging-confirmed sacroiliitis: Week-24 results from two phase 3, randomized, double-blind, placebo-controlled studies [OP0054]. Ann Rheum Dis. 2020;79(Suppl 1).
- Helliwell PS, Gladman DD, Chakravarty SD, et al. Effects of ustekinumab on spondylitis-associated endpoints in TNFi-naïve active psoriatic arthritis patients with physician-reported spondylitis: Pooled results from two phase 3, randomised, controlled trials. RMD Open. 2020 Feb;6(1):e001149.
- Deodhar A, Gladman D, Bolce R, et al. Ixekizumab efficacy in patients with psoriatic arthritis presenting with symptoms indicative of axial involvement [abstract 1347]. Arthritis Rheumatol. 2021 Oct;73 (suppl 10).
- Baraliakos X, Gossec L, Pournara E, et al. Secukinumab in patients with psoriatic arthritis and axial manifestations: Results from the double-blind, randomised, phase 3 MAXIMISE trial. Ann Rheum Dis. 2021 May;80(5):582–590.
- Poddubnyy D. Axial involvement in psoriatic arthritis cohort (AXIS) [NCT04434885]. ClinicalTrials.gov. 2020 Jun 17.