Lba0006 Secukinumab Versus Standard-of-Care in Axial Spondyloarthritis: A Randomized Controlled Open-Label Trial for Treat-to-Target Outcomes (Ascalate)

Background: Remission/low disease activity is the primary treatment target in axial spondyloarthritis (axSpA), as per the treat-to-target (T2T) and international management recommendations [1]. Patients who do not respond to non-steroidal anti-inflammatory drugs (NSAIDs) can be treated with biological (b) (TNFi or IL-17i) disease modifying anti-rheumatic drugs (bDMARDs). There is a lack of trials comparing different strategies for achieving remission, making evidence-based recommendations for the choice of a particular drug or strategy for first or second line treatment difficult. Objectives: The aim of the AScalate study was to evaluate efficacy of a treatment strategy using the IL-17i secukinumab (SEC) as the first line bDMARD treatment, along with predefined criteria for treatment escalation (T2T arm) compared with a standard of care approach (SoC arm) over 36 weeks in patients with active axSpA. Methods: Study design and methodology have been previously described [2]. Briefly, this was a randomized, parallel-group, open-label, multicentric study involving patients with active axSpA (also fulfilling ASAS classification criteria) and objective signs of inflammation at screening [positive MRI of sacroiliac joints (SIJ) or spine or elevated quick C-reactive protein (CRP >5 mg/L)]. All patients were naive to b-/ts DMARDs and had an inadequate response to prior NSAID treatment. At baseline, patients were randomized 1:1 into one of two treatment groups: T2T or SoC arms. In the T2T group, patients received SEC 150 mg s.c. weekly until week 4, and then q4w. At week 12, those achieving clinically important improvement (CII) in ASDAS continued the initial treatment, while the remainder (inadequate responders (IR)) received SEC 300 mg s.c. q4w. At week 24, according to the second response assessment (ASDAS CII from baseline), responders continued SEC 150mg or SEC 300mg q4w treatment, and IR switched to adalimumab 40 mg s.c. q2w until Week 36. In the SoC arm, patients received treatment at the investigator's discretion based on the prevailing standard of care. The primary endpoint of the study was the achievement of ASAS40 response at Week 24 with assumed superiority of the T2T over SoC. Secondary and exploratory endpoints included the achievement of ASAS responses as well as ASDAS low disease activity (ASDAS<2.1), ASDAS inactive disease (ASDAS<1.3) and BASDAI50 at Weeks 12, 24, and 36. Results: A total of 398 axSpA patients were screened, and 304 patients were randomized, 155 into the T2T arm and 149 into the SoC arm. The mean (±SD) age was 39.3±12.1 years, with 64% of patients being males. The symptom duration was 11±10.7 years, 73.4% were HLA-B27 positive, and 61.2% had definite radiographic sacroiliitis. Of the 155 patients randomized to the T2T arm, 64 (41.3%) escalated the SEC dose (150 to 300 mg) at week 12, while 44 (28,4%) switched to adalimumab at week 24. In the SoC arm, a total of 115 patients (77.7%) received TNF-i as starting treatment, 16 (10.8%) received IL-17i, while 11 received csDMARDs and 7 (4.7%) were treated without b/csDMARDs over 36 weeks. The primary endpoint was not met as no statistical difference on ASAS40 response achievement was reported between groups at week 24 (OR 0.69, 95% CI 0.43-1.10; p=0.119; Figure 1). Other endpoints exploring clinical response did not report significant difference between arms (see Figure 1). Post-hoc analysis on the time course of response rates in the treatment sequence SEC150-SEC300 of the T2T group showed that dose escalation for non-responders from week 12 (ΔASDAS CII<1.1) changed response pattern (Figure 2) improving response rate at week 24 for 28% of patients of this subgroup. Safety was comparable across the treatment modalities. Conclusion: With the methodology chosen, the AScalate study did not demonstrate superiority of T2T in axSpA over SoC. Observations are consistent with TICOSPA trial [3]. AxSpA patient care was found to be close to T2T strategy in the participating expert centers. SEC dose escalation was beneficial for approximately one third of patients. REFERENCES: [1] Ramiro S, et al. Ann Rheum Dis 2022;0:1–16. [2] Poddubnyy et al. BMJ Open 2020;10:e039059. [3] Molto et al. Ann Rheum Dis. 2021;80(11):1436-1444. Acknowledgements: NIL. Disclosure of Interests: Denis Poddubnyy AbbVie, Lilly, MSD, Novartis, and Pfizer; has received consultation and/or speaker fees from AbbVie, Biocad, BMS, Gilead, GSK, Lilly, MSD, Novartis, Pfizer, Samsung and UCB, Ludwig Hammel: None declared, Philippe Goupille Abbvie, Amgen, Biogen, BMS, Chugai, Fresenius, Galapagos, Janssen-Cilag, Lilly, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, UCB, Fabian Proft: None declared, Julie BLANCHARD: None declared, Berenice Roesler: None declared, Xenofon Baraliakos AbbVie, BMS, Celgene, Chugai, Hexal, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, Sanofi and UCB Pharma.