Outcomes

The primary endpoint of the study was defined as change in radiographic spinal progression measured by the mSASSS³⁰ over 2 years of treatment. For this assessment, radiographs of the cervical and lumbar spine in lateral view were performed locally at screening (or already available radiographs performed within 24 months before screening) and after 2 years of treatment (week 108 per protocol, week 84 at the earliest for patients who discontinued prematurely). The mean duration between the radiographs and the baseline visit for the patients in the combination therapy group was 0.89 months (95% CI: 0.37 to 1.41), while this was 1.16 months (95% CI: 0.30 to 2.03) for the monotherapy group (p=0.76). Images were centrally stored in a digital and anonymised format and subsequently scored independently by three trained and calibrated readers (FP, MT and VRR), who were blinded for treatment group allocation, the time point of the assessment and all clinical data.

Secondary endpoints included new syndesmophyte formation or progression of existing syndesmophytes, improvement in disease activity, physical function, spinal mobility and health-related quality of life according to the relevant disease outcome measures including ASDAS (CRP based), BASDAI, CRP, BASFI, BASMI, ASAS Health Index, patient global assessment of disease activity and spinal and nocturnal pain on an NRS of 0–10. Safety endpoints included the number of AEs and percentage of patients experienced AE, serious AE (SAE) and events of interest: infections, malignancies, gastrointestinal events (ulceration, bleeding, perforation, gastric outlet obstruction), thrombotic cardiovascular events (myocardial infarction, stroke, pulmonary artery embolism, peripheral arterial of venous thrombosis), renal impairment and hepatic deterioration. The full assessment schedule can be found in the study protocol (online supplemental file 2).