Background: Early therapeutic interventions in inflammatory rheumatic diseases have proven successful in inducing drug-free remission. However, such studies are difficult to conduct in axial spondyloarthritis (axSpA), for which a consensus definition of early disease was only recently published, and diagnostic delay amounts up to 8 years [1,2].

Objectives: To evaluate the efficacy of tight control, treat-to-target approach in newly diagnosed, treatment-naïve axSpA patients, following the ASAS-EULAR disease management recommendations [3].

Methods: Prospective, multicenter, 52-week, open-label clinical trial (EudraCT Number: 2017-001728-23). The treatment algorithm strictly followed the current ASAS-EULAR recommendations for axSpA management. Patients were treated with two different NSAIDs in optimal dose for a period of at least 4 weeks. If inactive disease (ASDAS-CRP <1.3) or clinically important improvement (ΔASDAS-CRP score ≥ 1.1 resulting in low disease activity (ASDAS-CRP <2.1)) was not achieved, monotherapy with 50mg golimumab subcutaneous 4-weekly was initiated. Patients were followed until achieving sustained clinical remission (ASDAS-CRP <1.3 at two consecutive visits with 12 weeks interval) or end of trial. Upon achievement of sustained clinical remission, the medication was stopped and the patients were followed in routine clinical practice to evaluate the possibility of maintaining drug-free remission.

Results: Fifty-five patients completed the trial. The mean time from diagnosis to study inclusion was 53 (±52) days, and the patient-reported symptom duration less than one year, as defined by the study inclusion criteria. The patient’s mean age was 28.2 (±6.3) years, 58.6% were male and 86.2% were HLA-B27 positive. Mean ASDAS-CRP was 3.0 (SD 0.9). 76.4% (42/55) had active sacroiliitis on MRI (according to the ASAS definition, central reading) within 3 months prior to inclusion, with mean SPARCC score of 11.9 (SD 10.8). In total, 34 patients (61.8%) achieved sustained clinical remission, with mean ASDAS-CRP of 0.9 (SD 0.2) and 12 patients (21.8%) had low-disease activity at week 52 of the trial (Figure 1). Baseline patient characteristics have been compared between the patients who achieved sustained clinical remission during the study and those who did not. In univariate analysis, only sex and baseline BASDAI score were significantly different between the two groups. Multivariate logistic regression analysis revealed male sex, abstinence from smoking and lower BASDAI score as predictors of remission (Table 1).

Patients who achieved sustained clinical remission were taken off treatment according to the study protocol and followed-up in routine clinical practice. Within 1 year of follow-up, 84.8% of patients experienced a disease relapse exceeding their patient-acceptable symptom state. For patients who achieved remission under NSAIDs treatment, median time to relapse was 61 days (95% CI: 17 to 168), whereas in the golimumab group it was 155 days (95% CI: 98 to 300).

Conclusion: This is the first clinical trial in early axSpA in which sustained inactive disease status is achieved in over 60% of patients. In the group of axSpA with less than 1 year of disease symptoms, male sex, abstinence from smoking and lower BASDAI score at baseline were associated with higher chances of remission. Despite stable inactive disease state successfully induced by medication, drug-free remission in axSpA remains challenging.

REFERENCES: [1] Navarro-Compán, Victoria et al. “ASAS consensus definition of early axial spondyloarthritis.” Annals of the rheumatic diseases, ard-2023-224232. 15 Jun. 2023.

[2] Zhao, Sizheng Steven et al. “Diagnostic delay in axial spondyloarthritis: a systematic review and meta-analysis.” Rheumatology (Oxford, England) vol. 60,4 (2021): 1620-1628.

[3] Ramiro, Sofia et al. “ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update.” Annals of the rheumatic diseases vol. 82,1 (2023): 19-34.

Figure 1.

Treatment efficacy

Table 1. Multivariate logistic regression analysis reveals predictors of remission

Acknowledgements: NIL.

Disclosure of Interests: None declared.