IV Secukinumab Rapidly Improved Clinical Responses in Psoriatic Arthritis

Alan Kivitz, MD

Credit: Altoona Center for Clinical Research

Results from the Phase 3 INVIGORATE-2 study demonstrated the benefit of intravenous (IV) secukinumab for the rapid improvement of disease signs and symptoms in patients with active psoriatic arthritis (PsA).¹

The placebo-controlled trial revealed IV secukinumab achieved significantly greater improvements in disease activity, psoriasis, physical function, and quality of life through Week 16 versus placebo. Those who switched from placebo to IV secukinumab at Week 16 experienced the same treatment-related benefit.

“Administration of IV secukinumab could provide rheumatologists additional treatment options to help address the individual treatment needs of patients with PsA,” wrote the investigative team, led by Alan Kivitz, MD, Altoona Center for Clinical Research.

PsA is often linked to a reduction in quality of life, given its propensity for chronic pain, reduced physical function and work capacity, and emotional and social impairment.² This patient population faces a notable economic burden, with higher healthcare-related costs and resource utilization than those without PsA.

Secukinumab is a fully human monoclonal antibody selectively inhibiting proinflammatory cytokine interleukin-17A, approved in the United States and Europe for psoriasis, axial spondyloarthritis, and PsA.³ Since most approved treatments for PsA are administered subcutaneously or orally, IV secukinumab’s alternate delivery could prove flexible as a patient and physician treatment option.

The INVIGORATE-2 trial randomized individuals aged ≥18 with active PsA 1:1 to receive IV secukinumab 6 mg/kg at baseline, followed by 3 mg/kg every 4 weeks (Q4W), or placebo.¹ IV secukinumab doses were based on extensive pharmacokinetic analyses and modeling of Phase 2 and 3 data of secukinumab in patients with PsA.

At Week 16, individuals randomized to placebo were switched to IV secukinumab Q4W, while patients randomized to IV secukinumab continued their dosing regimen through Week 52. A post-treatment follow-up visit took place at Week 60 for the safety follow-up period,

For this analysis, the primary efficacy outcome was achieving a 50% improvement in the American College of Rheumatology (ACR) response criteria, with a primary efficacy endpoint at Week 16. The efficacy and safety of IV secukinumab were evaluated through Weeks 52 and 60, respectively.

The full study population (n = 381) was randomized to receive IV secukinumab (n = 191) or placebo (n = 190), with balanced patient demographics and baseline disease characteristics between treatment arms. Most randomized to IV secukinumab (86.4%) and placebo (85.3%) were naive to tumor necrosis factor (TNF) inhibitors. A total of 177 (92.7%) and 170 (89.5%) patients in each treatment group completed treatment period 2, respectively.

Upon analysis, Kivitz and colleagues found all primary and secondary efficacy endpoints for secukinumab achieved statistical significance (all adjusted P <.05) versus placebo. A significantly greater proportion of patients receiving IV secukinumab achieved the primary endpoint of ACR50 response rates at Week 16 compared with placebo (31.4% vs. 6.3%; adjusted P <.0001).

Significantly higher ACR50 responses were identified with IV secukinumab as early as Week 4, with maintenance through Week 16 (P <.0005). Patients treated with IV secukinumab achieved all secondary efficacy endpoints at Week 16 (all adjusted P <.05).

After the switch from placebo to IV secukinumab at Week 16, patients demonstrated rapid improvement in ACR50 response rates. These responses were maintained or improved up to Week 52 in the IV secukinumab (58.0%) and placebo/IV secukinumab (64.0%) cohorts.

Over the entire treatment period, approximately 63% of individuals who received any IV secukinumab experienced a treatment-emergent adverse event (TEAE). Investigators noted no new or unexpected safety signals were identified with IV secukinumab, but a single death was reported in the placebo group before Week 16.

“The availability of IV secukinumab may be beneficial and would provide additional treatment options for these patients and their physicians,” Kivitz and colleagues wrote. “Additional treatment modalities could benefit specific patient populations, such as patients with obesity who are more likely to have higher disease activity and may benefit from tighter control of weight-based treatment.”

References

1. _{Kivitz A, Sedova L, Churchill M, et al. Efficacy and Safety of Intravenous Secukinumab for the Treatment of Active Psoriatic Arthritis: Results From the Randomized, Placebo-Controlled Phase III INVIGORATE-2 Study. Arthritis Rheumatol. Published online September 19, 2024. doi:10.1002/art.42997}
2. _{Lee S, Xie L, Wang Y, Vaidya N, Baser O. Comorbidity and economic burden among moderate-to-severe psoriasis and/or psoriatic arthritis patients in the US Department of Defense population. J Med Econ. 2018;21(6):564-570. doi:10.1080/13696998.2018.1431921}
3. _{Kolbinger F, Di Padova F, Deodhar A, et al. Secukinumab for the treatment of psoriasis, psoriatic arthritis, and axial spondyloarthritis: Physical and pharmacological properties underlie the observed clinical efficacy and safety. Pharmacol Ther. 2022;229:107925. doi:10.1016/j.pharmthera.2021.107925}