Results from the Phase 3 INVIGORATE-2 study indicate that intravenous (IV) secukinumab provides rapid improvement in the signs and symptoms of active psoriatic arthritis (PsA). The placebo-controlled trial demonstrated that IV secukinumab led to significantly greater improvements in disease activity, psoriasis, physical function, and quality of life through Week 16 compared to placebo. Patients who switched from placebo to IV secukinumab at Week 16 experienced similar treatment-related benefits.
Efficacy of IV Secukinumab
The study, led by Alan Kivitz, MD, from the Altoona Center for Clinical Research, randomized individuals aged 18 and older with active PsA in a 1:1 ratio to receive either IV secukinumab 6 mg/kg at baseline, followed by 3 mg/kg every 4 weeks (Q4W), or placebo. At Week 16, patients on placebo were switched to IV secukinumab Q4W, while those on IV secukinumab continued their regimen through Week 52. A post-treatment follow-up occurred at Week 60 for safety monitoring.
The primary efficacy outcome was achieving a 50% improvement in the American College of Rheumatology (ACR) response criteria (ACR50) at Week 16. The efficacy and safety of IV secukinumab were evaluated through Weeks 52 and 60, respectively. The study population consisted of 381 patients, with 191 randomized to IV secukinumab and 190 to placebo. Baseline demographics and disease characteristics were balanced between the treatment arms. Most patients were naive to tumor necrosis factor (TNF) inhibitors (86.4% in the IV secukinumab group and 85.3% in the placebo group).
Significant Improvements Observed
The analysis revealed that all primary and secondary efficacy endpoints for secukinumab achieved statistical significance (all adjusted P < .05) compared to 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 observed 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).
Sustained Benefits After Switching
Following 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 both the IV secukinumab (58.0%) and placebo/IV secukinumab (64.0%) cohorts.
Safety Profile
Over the entire treatment period, approximately 63% of individuals who received any IV secukinumab experienced a treatment-emergent adverse event (TEAE). No new or unexpected safety signals were identified with IV secukinumab; however, a single death was reported in the placebo group before Week 16.
Clinical Implications
"The availability of IV secukinumab may be beneficial and would provide additional treatment options for these patients and their physicians," Kivitz and colleagues wrote. They also noted that 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.
Secukinumab, a fully human monoclonal antibody selectively inhibiting proinflammatory cytokine interleukin-17A, is already approved in the United States and Europe for psoriasis, axial spondyloarthritis, and PsA. The availability of an IV formulation offers an alternative to subcutaneous or oral administration, providing flexibility for both patients and physicians.
