Spine School: Axial Manifestations of Psoriatic Arthritis

EULAR 2022 (VIRTUAL)—Psoriatic arthritis (PsA) is known for its ability to affect patients in many domains and manifest with enthesitis, uveitis, dactylitis and peripheral synovitis. At the 2022 Congress of the European Alliance of Associations for Rheumatology (EULAR), Philip Helliwell, MA, PhD, DM, FRCP, professor of clinical rheumatology at the University of Leeds and honorary consultant rheumatologist for the Bradford Hospitals NHS Trust, Leeds, England, discussed the importance of recognizing the axial manifestations of this disease and treating these symptoms.

In the original classification of Moll and Wright, the spondyloarthritides included such conditions as ankylosing spondylitis, PsA, reactive arthritis, Behçet’s disease, arthritis associated with inflammatory bowel disease (IBD) and Whipple’s disease.¹ These conditions shared many features, including sacroiliitis, asymmetric large joint arthritis, inflammation of the bowel, iritis, mucocutaneous ulcerations and erythema nodosum.

A number of years later, Dr. Helliwell, along with Dr. Wright, published a new classification set that eliminated Behçet’s disease and Whipple’s disease as part of this cadre and added unclassified spondyloarthritis.² These concepts of disease continue to evolve, and the distinctions between diseases have been refined, helping clinicians separate patients into more specific subtypes.

Radiographic Features

Dr. Helliwell went on to describe work he published in the 1990s on the differing radiographic features of axial disease seen in various forms of spondyloarthritis. Whereas the sacroiliitis of ankylosing spondylitis and IBD was noted to typically be severe and symmetrical, conditions like PsA and reactive arthritis were found to often be associated with unilateral or bilateral asymmetrical sacroiliitis. Comparing ankylosing spondylitis and IBD with PsA and reactive arthritis, the former were more frequently associated with symphysis, osteoporosis, lumbar straightening, apophyseal joint involvement, bridging syndesmophytes and ligamentous ossification.³

Not only do radiographic differences exist between PsA and other conditions with axial disease, but in PsA the clinical presentation of axial disease less often includes classical features of inflammatory back pain.

Dr. Helliwell explained that inflammatory back pain includes pain in the hips or buttocks that improves with activity and worsens with rest, occurs at night, is responsive to non-steroidal anti-inflammatory drugs and involves at least 30 minutes of morning stiffness.

A study by Feld et al. notes that axial involvement in PsA can often be asymptomatic, with only about 45% of patients with PsA and axial disease in this study reporting inflammatory back pain symptoms.⁴

Genetics & Phenotypes

Dr. Helliwell also described the interesting genetics of PsA. The HLA-C:06:02 allele is associated with the highest genetic risk of psoriasis, compared with the HLA-B27, HLA-C12–HLA-B38, and HLA-C06–HLA-B57 haplotypes, which are also associated with PsA. Interestingly, the prevalence of HLA-B27 in PsA is much lower than that seen in ankylosing spondylitis, with prevalence of 20% vs. 80%, respectively.

In the axial form of PsA, the HLA-B27:05:02 allele is associated with symmetrical sacroiliitis, and the HLA-B:08:01–HLA-C:07:01 haplotype is associated with asymmetric sacroiliac involvement.⁵

Putting all of this information together, Dr. Helliwell posited that two phenotypes of axial inflammatory arthritis exist: the classical phenotype and the alternative phenotype. Dr. Helliwell further opined that the majority of patients with axial spondyloarthritis will tend to demonstrate the classical phenotype of disease, but the majority of patients with axial involvement in PsA will demonstrate the alternative phenotype. He explained that such distinctions are essential for clinicians to make because this helps with proper classification of disease and selection of appropriate treatment for patients. (Editor’s note: For more on this topic, see “Axial Disease in Psoriatic Arthritis.”)

Axial disease has not been assessed in most randomized clinical trials of PsA, & thus it has been challenging to create evidence-based recommendations for this manifestation.

Treatments

When treatment options are considered, it is important to note that axial disease has not been assessed in most randomized clinical trials of PsA, and thus it has been challenging to create evidence-based recommendations for this manifestation.

Several reasons exist for the absence of clinical trials of axial disease in PsA. These reasons include lack of a validated definition of axial involvement in PsA, lack of a validated outcome measure for the assessment of treatment, the fact that a minority of patients in PsA clinical trials have axial involvement, leading to underpowered assessment of this domain, and the cost and time associated with the serial radiographs and magnetic resonance imaging studies that would be needed to comprehensively assess disease.

Dr. Helliwell did cite a phase 3b study from Baraliakos et al. that evaluated the effect of secukinumab in patients with PsA and axial manifestations. In this double-blind, placebo-controlled, multi-center trial, nearly 500 patients were randomized to receive 300 mg of secukinumab, 150 mg of secukinumab or placebo weekly for four weeks and then every four weeks thereafter for 52 weeks. Patients receiving the 300 mg and 150 mg doses of secukinumab showed significantly improved Assessment of SpondyloArthritis International Society 20 (ASA20) responses at week 12 compared with patients receiving placebo.⁶

Because secukinumab is an inhibitor of interleukin (IL) 17A and this interleukin is closely linked to the actions of IL-23, it is reasonable to ask if IL-23 inhibition would also be effective in treating axial involvement in PsA. However, Dr. Helliwell noted that studies on IL-23 inhibition have demonstrated less successful results, perhaps because it has been shown that cells in the spine are capable of producing IL-17 without IL-23. He did indicate, however, that more studies on IL-23 and Il-12 inhibition may be warranted to see if groups of patients could benefit from such treatments.

In Sum

Dr. Helliwell concluded his lecture with a few take-home points: 1) Heterogeneity of axial involvement in PsA exists, and both the classical and alternative phenotypes of axial disease should be kept in mind; 2) such heterogeneity may relate at least in part to the presence or absence of the HLA-B27 allele; and 3) further studies are needed to define axial PsA and to determine treatment responses in patients with the alternative phenotype of disease. It is through such studies, Dr. Helliwell noted, that his conception of the classical vs. alternative phenotypes of axial disease in PsA and other spondyloarthritic conditions can best be assessed as a conceptual framework.

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Jason Liebowitz, MD, completed his fellowship in rheumatology at Johns Hopkins University, Baltimore, where he also earned his medical degree. He is currently in practice with Skylands Medical Group, N.J.

References

1. Wright V, Moll JMH. Seronegative Polyarthritis. Amsterdam, North-Holland Pub. Co., 1976.
2. Helliwell P, Wright V. Seronegative spondarthritides. Baillieres Clin Rheumatol. 1987 Dec;1(3):491–523.
3. 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.
4. Feld J, Ye JY, Chandran V, et al. Is axial psoriatic arthritis distinct from ankylosing spondylitis with and without concomitant psoriasis? Rheumatology (Oxford). 2020 Jun 1;59(6):1340–1346.
5. Feld J, Chandran V, Haroon N, et al. Axial disease in psoriatic arthritis and ankylosing spondylitis: A critical comparison. Nat Rev Rheumatol. 2018 Jun;14(6):363–371.
6. 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.