Non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) are considered part of the spectrum of axSpA. Patients are classified as nr-axSpA due to the absence of definitive radiographic sacroiliitis, but suffer from similar disease burden as those with AS. NSAIDs are first-line therapy, and only one anti-TNF therapy is approved in the US for nr-axSpA pts with objective signs of inflammation.  Secukinumab (SEC) provides significant and sustained improvement in signs and symptoms of patients with AS2.  PREVENT is the first phase 3 study evaluating the efficacy and safety of SEC 150 mg with (LD) or without loading (NL) in patients with nr-axSpA.
This phase 3, double blind, placebo (PBO)-controlled, multicenter trial included 555 pts (aged ≥18 years) fulfilling the ASAS (Assessment of SpondyloArthritis International Society) classification criteria for axSpA but not the modified New York Criteria, plus abnormal C-reactive protein (CRP) and/or magnetic resonance imaging (MRI), with no radiographic changes in the sacroiliac joints.
Patients were randomized (1:1:1) to subcutaneous SEC 150 mg LD, 150 mg NL, or PBO.
The LD group received SEC 150 mg at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks (q4wk) through week 52.
The NL group received SEC 150 mg at baseline and PBO at weeks 1, 2, and 3, and then SEC 150 mg q4wk starting at week 4.
Analysis used the Net Reclassification Index for binary and the Mixed Model for Repeated Measures for continuous variables.
Endpoints were analyzed according to a statistical hierarchy.
The primary endpoint was ASAS40 response with SEC 150 mg LD in anti-TNF-naïve patients at week 16.
Secondary endpoints included ASAS40 response rates, total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI50, Bath Ankylosing Spondylitis Functional Index (BASFI), Short Form-36 physical component summary (SF-36 PCS), Ankylosing Spondylitis Quality of Life (ASQoL), and ASAS partial remission in the overall population.
94.6% (150 mg LD), 96.2% (150 mg NL), and 94.1% (PBO) patients completed 24 weeks of treatment.
Demographic and baseline disease characteristics were comparable across groups.
The primary and all secondary endpoints were met.
At week 16, ASAS40 in anti-TNF-naïve pts was significantly higher in the SEC 150 mg LD group than PBO patients (Figure).
SEC 150 mg LD and NL also showed significant improvement vs. PBO in all secondary endpoints (BASDAI, BASDAI50, BASFI, sacroiliac joint edema on MRI, high sensitivity-CRP, ASAS partial remission) as well as physical function and quality of life.
Three cases of serious infections/infestations (0.8%), and 1 case of Crohn’s disease (0.3%) were reported with SEC.
No cases of esophageal candidiasis, major adverse cardiovascular events, malignancy or death were reported on any SEC dose up to week 20.
SEC 150 mg LD provided significant improvement in signs and symptoms of nr-axSpA through week 16.
The safety profile of SEC was consistent with the established safety profile across indications
Key messages/Clinical perspectives
PREVENT is the first randomized controlled trial evaluating the efficacy and safety of SEC in patients with nr-axSpA, met the primary endpoint (ASAS40 at week 16) and confirmed the good safety profile of SEC