Axial spondyloarthritis outcomes improved with intravenous secukinumab

Intravenous (IV) secukinumab appears beneficial in the treatment of adults with active axial spondyloarthritis (axSpA), with improvements seen across disease activity, physical function, quality of life, and sleep measures, according to the results of the phase III INVIGORATE-1 trial.

The primary endpoint was met, with a higher percentage of patients receiving IV secukinumab vs placebo achieving an improvement of at least 40 percent in the Assessment of SpondyloArthritis International Society (ASAS40) criteria (with an absolute improvement of ≥2 units on a 10-unit scale in at least three of the four main ASAS domains, with no worsening in the remaining domain) at week 16 (40.9 percent vs 22.9 percent; p<0.0001).  [Arthritis Rheumatol 2024;doi:10.1002/art.42993]

Significant improvements in ASAS40 response occurred as early as week 4 with IV secukinumab, the investigators said.

All secondary efficacy endpoints were likewise met at week 16. Compared with those who received placebo, significantly more IV secukinumab-treated patients showed ASDAS-CRP* major improvement (27.7 percent vs 7.6 percent; p<0.0001), at least a 20-percent improvement in at least five of six ASAS domains (43.9 percent vs 21.8 percent; p<0.0001), ASAS20** (64.0 percent vs 40.5 percent; p<0.0001), ASDAS-CRP inactive disease (15.9 percent vs 3.4 percent; p<0.0001), and ASAS partial remission (14.8 percent vs 4.2 percent; p<0.0001).

IV secukinumab was also associated with significantly greater improvements in BASDAI^† (−2.70 vs −1.69; p<0.0001), BASFI^†† (−2.33 vs −1.39; p<0.0001), SF-36 PCS^‡ (7.70 vs 4.69; p<0.0001), ASQoL^‡‡ (−4.65 vs −2.88; p<0.0001), high-sensitivity CRP (0.39 vs 0.89; p<0.0001), and PSQI^§ (−2.42 vs −1.76; p<0.05) measures compared with placebo.

“By week 24, patients who switched from placebo to secukinumab at week 16 achieved ASAS40 response rates comparable to those in patients originally randomized to secukinumab. [And the] improvements [in secondary endpoints] achieved at week 16 in patients originally randomized to IV secukinumab either further improved or were sustained … through week 52,” the investigators noted.

“The efficacy outcomes observed in this study are consistent with those in previous phase 3 studies that evaluated SC secukinumab for the treatment of patients with axSpA,” they added. [N Engl J Med 2015;373:2534-2548; Arthritis Rheumatol 2021;73:110-120; Arthritis Res Ther 2017;19:285; Rheumatol Ther 2018;5:447-462; Chin Med J (Engl) 2020;133:2521-2531]

Study details and safety

INVIGORATE-1 included 526 patients (mean age 39.5, 65.2 percent male) with active axSpA, which was radiographic in 413 and nonradiographic in 113. These patients were randomly assigned to receive IV secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks, n=264) or IV placebo (n=262) for 16 weeks. After week 16, patients who initially received placebo were switched to IV secukinumab (3 mg/kg every 4 weeks), while those who initially received secukinumab continued treatment through week 52. Safety was evaluated through week 60.

Of the patients, 88.3 percent of patients in the IV secukinumab group and 89.7 percent of those in the IV placebo–secukinumab group completed the 52-week treatment period, and 86.0 percent and 88.9 percent of patients, respectively, completed the entire 60-week study period. The most frequent reasons for discontinuation were adverse events (AEs) and patient decision.

Over 16 weeks of treatment, treatment-emergent AEs (TEAEs) occurred in 38.6 percent of patients with IV secukinumab and 39.1 percent with placebo. COVID-19, diarrhoea, nasopharyngitis, upper respiratory tract infection, and headache were the most common TEAEs. TEAEs led to treatment discontinuation in 1.9 percent of patients in the IV secukinumab group and in 0.4 percent in the placebo group.

The exposure-adjusted incidence rate (EAIR) for TEAEs was 116.4 per 100 patient-years among patients who received any secukinumab during the entire 60-week safety period. The EAIRs for AEs of interest were low for uveitis (1.8 per 100 patient-years), Crohn’s disease (0.8 per 100 patient-years), and ulcerative colitis (0.4 per 100 patient-years). One patient who received IV secukinumab died due to suspected myocardial infarction that was not deemed to be related to the study treatment.

“Safety data were consistent with those in previous reports on subcutaneous secukinumab, and no new safety signals were observed,” the investigators pointed out.

“INVIGORATE-1 is the first randomized, placebo-controlled, phase III study to evaluate the long-term efficacy and tolerability of an all-IV regimen of secukinumab for the treatment of adults with active axSpA,” they said.

In light of the positive findings of INVIGORATE-1, the investigators emphasized that the addition of an IV administration route for secukinumab could provide increased flexibility in disease management for rheumatologists and their patients with axSpA.