Improved Screening and Treatment: New Protocols for Axial Involvement in Psoriatic Arthritis
- Patients with psoriatic arthritis (PsA) and human leukocyte antigen B27 (HLA-B27) positivity, elevated inflammatory markers, radiographic peripheral joint damage, and/or nail psoriasis should be screened more frequently for axial involvement to promote early intervention and prevent permanent joint and spine damage.
- If axial involvement is suspected, patients should have an anterior-posterior (AP) plain radiograph (x-ray) of areas where stiffness or pain is present. If there are no findings on x-ray, magnetic resonance imaging (MRI) of the spine and/or sacroiliac (SI) may show areas of active inflammation.
- After detection of axial involvement, if symptoms are not controlled with nonsteroidal anti-inflammatory drugs (NSAIDs), first-line biologic disease-modifying antirheumatic drug (bDMARD) options would be anti-tumor necrosis factor (TNF) therapies such as etanercept, adalimumab, infliximab, certolizumab pegol, and golimumab. If there is failure with these medications, clinicians can consider interleukin (IL)-17 inhibitor (secukinumab) or IL-12/IL-23 inhibitor (ustekinumab).
- Recent studies suggest upadacitinib may offer superior outcomes when compared to adalimumab, but further long-term data is needed — particularly in patients over the age of 50 — due to the increased risk for major adverse cardiovascular events.
PsA is a chronic inflammatory musculoskeletal disease. Between 25% and 70% of patients with longstanding PsA develop axial disease; patients with axial disease have worse arthritis and psoriasis, more body surface area covered by psoriasis, more nail psoriasis, more clinical enthesitis, and more tender joints than PsA patients without axial disease.1
Micaela F. Bayard, MD, an assistant professor of rheumatology at the Icahn School of Medicine at Mount Sinai in New York City and a double board certified clinician in rheumatology and internal medicine, discussed methods to screen for and treat axial involvement in PsA. Dr Bayard’s clinical areas of focus include ankylosing spondylitis, arthritis, dermatomyositis, gout, osteoarthritis, polymyositis, pseudogout, psoriatic arthritis, rheumatoid arthritis, scleroderma and systemic lupus erythematosus.
Early therapeutic intervention is critical for preventing permanent joint and spine damage in PsA with axial involvement. Are there subsets of patients with PsA who are more likely to develop axial disease and, as a result, should be screened more frequently for axial involvement?
Risk factors for developing axial involvement in PsA include HLA-B27 positivity (blood test), elevated erythrocyte sedimentation rate (ESR), presence of radiographic damage to peripheral joints, and nail dystrophy (nail psoriasis).2
A common presenting symptom of PsA with axial involvement is back pain with inflammatory characteristics.2 How do patients typically describe this back pain?
This kind of inflammatory back pain often presents after periods of inactivity, such as first thing in the morning; the pain often improves with movement, such as stretching or activity, and/or anti-inflammatory medications.
In some cases, patients who have PsA with axial involvement do not present with back pain. How do you recommend screening patients without back pain for inflammatory changes in the axial skeleton?
Patients who have skin psoriasis should be screened for any type of joint stiffness or pain and should be referred to a rheumatologist if they screen positive for these symptoms. When seen by a rheumatologist, they will get a more involved exam to assess axial range of motion and further imaging if there are any findings to suggest axial involvement. Rheumatologists will also use presence and severity of peripheral joint inflammation, enthesitis (inflammation at sites of tendon insertion to bone), and dactylitis (whole digit inflammation) to guide further treatment, even in patients clinically perceived as asymptomatic.
Axial PsA is usually diagnosed based on clinical evaluation and imaging,3 and efforts are currently underway by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the Assessment of Spondyloarthritis International Society (ASAS) to further define axial disease in PsA. Can you review the radiographic workup of patients who have PsA with suspected axial involvement? Furthermore, can you comment on the significance of asymmetrical radiographic sacroiliitis in PsA? What are typical syndesmophyte findings?
Patients suspected of axial involvement should have an AP x-ray of the areas of stiffness and pain; plain film radiography can also be helpful in identifying axial involvement. An MRI of the spine and/or SI joints in patients suspected of axial involvement without findings on x-ray may show areas of active inflammation. For over 70% of axial PsA patients, the sacroiliitis involvement is asymmetric3;this finding can help differentiate axial PsA from ankylosing spondylitis, which is often symmetric. Syndesmophytes, which form in the ligaments of the spine, can create irreversible spinal damage (rigidity) by calcifying ligaments and leading to vertebrae fusion.
Is there prognostic significance to early cervical spine (c-spine) involvement in PsA? How does this affect treatment choices?
Not with the c-spine specifically that I know of, but any axial spine involvement leads to a different treatment path. Unlike peripheral involvement, disease-modifying antirheumatic drug (DMARD) therapy does not have the same ability as anti-TNF therapy to reduce disease activity in axial involvement, and so an inadequate response to initial therapy with 2 different NSAIDs is typically followed by anti-TNF therapy. Some studies suggest HLA-B27 positivity may be linked to more severe disease, defined by earlier age of onset and bilateral sacroiliitis.4
Can you elaborate on HLA-B27 gene variants in the context of prognosis and severity of radiographic changes in axial PsA?
HLA-B27 is a risk factor for the development of ankylosing spondylitis and is reported to correlate with both susceptibility and disease activity. Studies suggest that the presence of HLA-B27 may predict the radiographic phenotype of patients with axial spondyloarthritis (axSpA).5 HLA-B27-positivity in spondyloarthritis is related to osteitis extent and severity.6
How often would you reassess ESR in PsA with suspected axial involvement?
If the ESR appears to correlate with disease activity for a patient, I would definitely asses it upon initial workup, as it would be helpful to send for all follow-ups and during a flare of symptoms to help confirm increased disease activity.
Axial PsA can be associated with extra-musculoskeletal disease, including uveitis and inflammatory bowel disease (IBD).3 Should gastroenterologists and ophthalmologists also be screening patients for PsA? If so, how frequently?
Yes, many of my practice referrals for inflammatory back pain come from dermatology, gastroenterology, and ophthalmology, so it should be a part of the review of symptoms during routine visits, as well as for evaluations during flares.
A recent study suggested that the 30-mg dose of upadacitinib was superior to both adalimumab and placebo in reducing tender and swollen joints at the 12-week mark, while a 15-mg daily dose of upadacitinib was superior only to placebo.7 Can you comment on these findings and their clinical applicability in guiding treatment decisions?
This is an exciting alternative as an oral medication. As an alternative mechanism of action, it may have better efficacy in different PsA subsets, including axial involvement. The concern is understanding the risk factor profile of patients with inflammatory arthritis who are already at increased risk for cardiovascular disease (CVD). Because there are already safety concerns regarding cardiovascular events for patients 50 years and older with cardiovascular risk factors, we must study further what the long-term impact of this class of medications has on patients already at risk for CVD.
Can you review the current recommended bDMARD options for PsA with axial involvement if symptoms are not controlled with NSAIDs?
First-line anti-TNF therapy options include etanercept, adalimumab, infliximab, certolizumab pegol, and golimumab, and treatment choice can be dictated by skin psoriasis and IBD, and/or uveitis activity. If a patient has failed TNF therapy, consider an IL-17 inhibitor (secukinumab) vs an IL-12/IL-23 inhibitor (ustekinumab).
What would indicate that PsA with axial involvement is not well-controlled after a first bDMARD therapy? Can you review your use of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in assessing axial disease activity in PsA with axial involvement, as they were initially developed for axSpA?
Persistent symptoms, increased symptom severity, increased joint involvement, and decreased functional capacity at home or work are all indications that PsA is not well-controlled. I use BASDAI during routine visits to provide another marker of disease activity to compare between visits and therapies. Other helpful indicators include neck and back pain ratings, separate from peripheral joints, as well as overall morning stiffness severity scores.
When should a change in therapeutic drug class be considered (eg, switching from TNF inhibitors or IL-17A inhibitors)? How do the comorbidities mentioned before (uveitis and IBD) affect the bDMARD of choice?
A change in therapy should be considered after 3 to 6 months with no improvement, or even earlier if symptoms are worsening. In patients with active uveitis or IBD, discussions with other specialists, such as ophthalmologists, should be taken into account to choose the best new treatment option — for example, TNF therapy — to benefit both axial and extra-articular symptoms.
This Q&A was edited for clarity and length.
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3. Braga MV, de Oliveira SC, Vasconcelos AHC, et al. Prevalence of sacroiliitis and acute and structural changes on MRI in patients with psoriatic arthritis. Sci Rep. 2020;10(1):11580. doi:10.1038/s41598-020-68456-7
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5. Arévalo M, Gratacós Masmitjà J, Moreno M, et al. Influence of HLA-B27 on the ankylosing spondylitis phenotype: results from the REGISPONSER database. Arthritis Res Ther. 2018;20(1):221. doi:10.1186/s13075-018-1724-7
6. Castillo-Gallego C, Aydin SZ, Emery P, McGonagle DG, Marzo-Ortega H. Magnetic resonance imaging assessment of axial psoriatic arthritis: extent of disease relates to HLA-B27. Arthritis Rheum. 2013;65(9):2274-2278. doi:10.1002/art.38050
7. McInnes IB, Anderson JK, Magrey M, et al. Trial of upadacitinib and adalimumab for psoriatic arthritis. N Engl J Med. 2021;384(13):1227-1239. doi:10.1056/NEJMoa202251
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Reviewed February 2023