A recent study published in Arthritis Research and Therapy confirmed the validity of previously identified bone-turnover biomarkers for psoriatic disease-associated arthritis and axial arthritis, making it possible to distinguish among patients with psoriasis, those with psoriatic arthritis (PsA), and those with axial disease vs ankylosing spondylitis (AS).
The Axial Disease in Psoriatic Arthritis Study (ADIPSA) was a cross-sectional comparative study that examined levels of 4 biomarkers — dickkopf 1 (Dkk-1), osteoprotegerin, macrophage colony stimulating factor (M-CSF), and matrix metalloproteinase 3 (MMP-3) — and their associations with physical and clinical disease states. The authors’ goals were threefold: to determine whether the biomarkers are associated with psoriatic arthritis, whether the biomarkers can differentiate PsA from psoriasis without arthritis, and whether the biomarkers can differentiate PsA with (psoriatic spondyloarthritis, PsSpA) and without (peripheral-only PsA, pPsA) axial involvement.
Patients with either PsA or AS were candidates because both are musculoskeletal inflammatory SpAs, characterized by bone resorption via osteolysis and erosion, and therefore PsA and AS would hopefully correlate with turnover biomarkers.
A total of 651 subjects were enrolled: 200 with psoriasis without arthritis, 200 with PsA, 201 with AS, and 50 healthy controls. Patients with PsA and AS were further divided into pPsA (n=127), PsSpA (n=117), and AS (n=157) categories. In addition to providing blood samples, each patient was seen by a rheumatologist who collected data based on patient-reported outcome measures, physical examination parameters, and results of axial radiographs.
Investigators found several correlations of interest. MMP-3 and M-CSF identify arthritis in psoriatic disease, making them potentially useful for screening of PsA in patients with dermatologic psoriasis. In addition, Dkk-1 and osteoprotegerin are associated with axial arthritis, and therefore are useful as screens for axial involvement in PsA, as well as in differentiating PsSpA from AS. Elevated levels of Dkk-1 in PsSpA and AS supported prior hypotheses that this biomarker is indeed dysfunctional in SpA. Finally, that Dkk-1, MMP-3, and M-CSF all display differences between healthy and diseased subjects may allow the generalization that all 3 biomarkers denote pathology.
The authors identified several strengths of ADIPSA, including a large cohort, stringent classification of cases, matching of PsA with healthy controls, complete data for 3 biomarkers, and multivariable regression statistical modeling (allowing control of confounders). Additionally, they feel their results are generalizable because of the unselected nature of participants (lowering selection bias) and the varied ages of subjects, as well as their various stages of disease and levels of disease activity.
Limitations noted by the researchers include a lack of commercially available kits for measuring certain biomarker parameters and a cross-sectional design that had a negative impact on adjustment ability for variables such as body mass index, medication use, disease activity, and other unmeasured confounders. They also recognize that for some patients with undiagnosed PsSpA (currently diagnosed with only pPsA), magnetic resonance imaging or computerized tomography scans may be more reliable than plain axial radiographs for diagnosis.
The ADIPSA study appears to confirm the presence of unique biomarker signatures that are able to help identify patient populations for whom additional investigations may be warranted, particularly spinal imaging studies. These results can help clinicians differentiate between the various disease states considered. This elucidation of pathopyhsiology is certain to aid rheumatologists in their clinical decision making regarding diagnosis and treatment options.
Jadon DR, Sengupta R, Nightingale A, et al. Serum bone-turnover biomarkers are associated with the occurrence of peripheral and axial arthritis in psoriatic disease: a prospective cross-sectional comparative study. Arthritis Res Ther. 2017;19(1):210.