Trajectory modelling of disease activity in patients with early axial spondyloarthritis (SpA) is feasible, according to findings from a French study derived from the DESIR study cohort (Devenir des Spondyloarthrites Indifférenciées Récentes,ClinicalTrials.gov Identifier: NCT01648907). DESIR is a prospective, multicenter, longitudinal, observational cohort for study of patients with early inflammatory back pain suggestive of emerging SpA. Researchers in the current study identified 5 disease activity trajectories for axial SpA.

Because disease activity of axial SpA can be heterogeneous, change over time, and impact productivity and overall quality of life with worsening of the disease course, a multicenter team of French researchers sought to identify its early evolutionary patterns. The team used the Ankylosing Spondylitis Disease Activity Score (ASDAS) to accomplish this, which measures inflammatory markers — namely C-reactive protein (CRP) – and integrates these measures with patient-reported items.

Of 708 patients in the DESIR cohort, only patients (n=370) who fulfilled the Assessment in Spondyloarthritis Society criteria for axial SpA and had at least 3 ASDAS values on record over the course of the 3 years’ follow-up were included in the study. Group-based trajectory modelling was used, and predisposing factors were identified by univariate and multivariable multinomial regression. A Cox hazard model was used to evaluate work disability over time.


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Average disease duration was 1.6 years, and 5 distinct trajectories were identified: 1.) persistent moderate-disease activity, affecting 36% of the study population; 2.) persistent inactive disease, affecting 18%; 3.) change from very-high-disease activity to inactive disease, affecting 8%; 4.) persistent high-disease activity, affecting 34%; and 5.) persistent very-high-disease activity, affecting 4%.

After adjustment for baseline factors, it was determined that the stable low-disease activity and improving disease trajectories (trajectories #2 and #3) were associated with higher educational level and professional “white collar” employment. Male sex and peripheral joint involvement also were characteristics of trajectory #3. Work disability was more commonly reported over time for patients within trajectory #4 and trajectory #5 (hazard ratio [HR] 5.2, 95% confidence interval [CI] 1.5 to 18.0; and HR=8.0, 95% CI 1.3 to 47.9, respectively).

These results, the researchers pointed out, suggest that more than a third of patients with axial SpA could be enduring moderate- to high-disease activity over the course of years despite the availability of biologic therapies. They noted that further study is needed regarding causality. 

They also questioned whether patients with low-disease trajectories (characteristically well-educated, professional men) were more adherent to therapy or simply more stoic, adding — nevertheless — that clinicians should be aware that low-income female patients may be particularly at risk for poorer disease trajectories.

Summary & Clinical Applicability

More than a third of patients with axial SpA could be enduring moderate- to high-disease activity over the course of years despite the availability of biologic therapies. Development of a disease trajectory that predicts outcomes based on patient characteristics early in the course of the disease is feasible and has the potential to shape therapies for individual patients in the effort to preserve quality of life and work productivity in the most vulnerable.

Limitations

Study limitations include the possibility that subjective patient-reported outcomes in the ASDAS influenced the trajectory definitions more than CRP measures. Also ASDAS trajectories were not adjusted for tumor necrosis factor (TNF) inhibitor use over time, although the researchers argued that ASDAS trajectories inherently include TNF inhibitor use and use can be considered a reflection of the disease course. The study also only assessed outcomes of different disease trajectories in terms of disability and days of sick leave, not in terms of structural damage.

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Reference

  1. Molto A, Tezenas du Montcel S, Wendling D6, Dougados M, et al. Disease activity trajectories in early axial spondyloarthritis: results from the DESIR cohort. Ann Rheum Dis. 2016 Nov 25 [Epub ahead of print]

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