Peripheral manifestations contribute significantly to disease activity in adults with spondyloarthritis (SpA), point toward a generally worse prognosis, and play a big role in defining the phenotypic clustering of the heterogenous disease, according to findings from what researchers called the first prospective study “to comprehensively describe the prevalence, clinical patterns, and prognostic implications of peripheral manifestations across the entire SpA spectrum.”
The stratification of patients in the study based on the presence of peripheral manifestations (arthritis, enthesitis, and/or dactylitis) led to the identification of an endotype with unfavorable outcomes, which not only has prognostic value but supports the need for an endotype-based treatment approach rather than one centered on C-reactive protein (CRP) and the Ankylosing Spondylitis Disease Activity Score (ASDAS).
The findings “advocate strongly for the presence of a distinct SpA endotype, based on potentially different immunopathological mechanisms and characterized by high disease activity at initial presentation with lack of substantial improvement upon follow-up,” first author Ann-Sophie De Craemer, MD, of Ghent, Belgium, and colleagues wrote.
Because the diagnostic and prognostic value of peripheral manifestations has not been well studied in SpA in general and in newly diagnosed patients in particular, Dr. De Craemer and associates decided to analyze their impact in 367 patients in the Be-Giant (BelGian Inflammatory Arthritis and spoNdylitis cohorT) cohort, a multicenter, prospective, observational cohort of newly diagnosed patients with SpA in Belgium. The study was published in Rheumatology.
The study population included 257 (70%) patients with axial-predominant SpA (axSpA) as classified by Assessment of Spondyloarthritis International Society criteria and 110 (30%) with peripheral-predominant SpA (pSpA) as defined by ASAS criteria. A total of 52 patients with axSpA had peripheral manifestations at baseline. The mean age of the patients was 34 years, and 52% were male.
The 162 patients with peripheral manifestations included 143 with arthritis, 52 with enthesitis, and 55 with dactylitis.
Two patient clusters emerge from data
In a cluster analysis that used baseline clinical features, the researchers divided the patients into cluster A (of which 242 of 248 were patients with axSpA) and cluster B (of which 104 of 119 were patients with pSpA). Most of the patients with peripheral manifestations were in cluster B (117 of 162 [72%]), compared with cluster A (45 of 162 [28%]).
A longitudinal analysis included 195 patients who completed a minimum 2-year follow-up. The longitudinal analysis identified high- and low-disease activity trajectories in each cluster.
In axSpA-predominant cluster A, patients with “high” trajectory had high disease activity levels at baseline (mean ASDAS-CRP, 3.2) that remained relatively stable, while those in the low-trajectory group (62%) had less disease activity at baseline (mean ASDAS-CRP, 2.0), which then further declined during follow-up.
Patients in the high trajectory in cluster A were more often affected by peripheral manifestations, “which remained a significant predictor in multivariate analysis,” with an odds ratio of 2.4, the researchers noted. In addition, patients with peripheral manifestations were significantly more likely to have persistent high disease activity despite starting biologics earlier than patients without peripheral manifestations (hazard ratio, 2.1).
Patients in pSpA-predominant cluster B showed differences that were similar to those seen in cluster A in terms of high– and low–disease activity trajectories (mean ASDAS-CRP of 3.6 and 2.8, respectively), but among these patients, a high level of disease activity was significantly associated with elevated CRP, rather than with peripheral disease, the researchers said.
The study findings were limited by several factors, including the exclusion of patients who did not complete the follow-up, which reduced the sample size for longitudinal analysis. However, the results were strengthened by the inclusion of patients from the full SpA spectrum, a geographically spread-out patient population, and a study design that mirrored clinical practice, the researchers noted.
The Be-Giant cohort was supported by an unrestricted grant from AbbVie. Several authors reported financial relationships with AbbVie and other pharmaceutical companies.