Secukinumab 300 mg May Improve PsA or Active Psoriasis More Than 150 mg

Alan J. Kivitz, MD

Credit: Altoona Arthritis and Osteoporosis Center

A new study found certain doses of secukinumab had greater odds of alleviating psoriatic arthritis (PsA) symptoms than placebo.¹

“In general, US patients treated with secukinumab 300 mg and secukinumab 150 mg with loading dose achieved the highest response rates, including ACR50 and ACR70 responses and the proportions of patients showing at least an MCID improvement in the health-related quality-of-life measure HAQ-DI,” wrote investigators, led by Alan J. Kivitz, MD, from the Altoona Center for Clinical Research/Altoona Arthritis and Osteoporosis Center.

PsA is linked to reduced quality of life, physical function, and work productivity. Five FUTURE studies have shown secukinumab, a selective inhibitor of interleukin 17A, provides rapid and significant improvement in the symptoms of PsA and has a favorable safety profile.²

Investigators aimed to compare secukinumab and placebo in challenging-to-treat US patients with PsA.¹ They pooled data from patients enrolled in phase 3 FUTURE 2 – 5 studies, excluding FUTURE 1 due to the study including an intravenous loading dose that is not approved by the US Food and Drug Administration (FDA) or the European Commission (EC) for PsA.

The FUTURE 2 – 5 trials randomized US patients who were in the minority of the total population with a harder-to-treat disease. This means patients may have had a greater body weight, greater tender and swollen joint counts, and a greater likelihood of enthesitis, dactylitis, and prior exposure to tumor necrosis factor inhibitors (TNFi). Patients either received secukinumab 300 or 150 mg with or without a subcutaneous loading dose or placebo.

The team assessed efficacy, health-related quality of life, and safety at week 16. Subgroup analyses examined TNFi status and body mass index (BMI). With logistic regression, they estimated odds ratios for the American College of Rheumatology (ACR) 20/50/70 and Psoriasis Area and Severity Index (PASI) 75/90/100 responses by treatment.

Although 2147 patients were originally randomized, the current pooled analysis only included 279 patients with 55.6% women. Participants had a mean BMI of > 30 kg/m2 and 55.2% had prior TNFi treatment.

Overall, at week 16, patients on secukinumab 300 mg (59.7%; P < .0001) and secukinumab 150 mg with loading dose (43.4%; P < .0001) had significantly greater ACR20 response rates. Patients on secukinumab 150 mg without a loader dose had greater response rates than placebo but was non-significant (32.5%; P = .30).

When evaluating the PASI score at week 16, patients had greater response rates on secukinumab than on placebo, with more improvements on secukinumab 300 mg than secukinumab 150 mg. Compared to placebo (9.1%), more patients on secukinumab had improved nail disease, with mNAPSI75 rates of 36.4, 24.6, and 15% for secukinumab 300, 150, and 150 mg without loading dose, respectively. Patients also had more improvements in health-related quality of life at week 16 when on secukinumab.

Patients responded to secukinumab as early as week 4, and ACR50 and ACR70 responses were greater with any secukinumab dose than placebo. More patients on secukinumab than placebo had a 100% reduction in PsA symptoms.

When evaluating the odds ratio, the findings revealed patients receiving secukinumab 300 mg and 150 mg with loading dose had greater odds of responding to at least 20%, 50%, or 70% of the treatment in tender and swollen joints (ACR 20/50/70) (P < .05) than patients on placebo. This indicates patients on secukinumab 300 mg and 150 mg with loading doses have the greatest clinical response rates. In contrast, Patients on secukinumab 150 mg without loading dose did not have better odds than placebo.

Patients on all doses of secukinumab had greater odds of a ≥ 75% greater reduction in PASI scores from baseline (PASI75) compared to placebo (P < .05). As for a 90% of 100% improvement from baseline on the PSAI score (PASI90 and PASI100), only the secukinumab 300 mg group worked significantly better compared to placebo (P < .05).

Secukinumab was also demonstrated to be as safe as placebo, with the frequency of all treatment-emergent adverse events similar for patients receiving secukinumab 300 mg (51.4%), secukinumab 150 mg with loading dose (54.2%), secukinumab 150 mg without loading dose (55.9%), and placebo (64.4%). The most common adverse events were upper respiratory tract infection, nasopharyngitis, nausea, and sinusitis.

Overall, secukinumab brought rapid improvements in disease activity and quality of life. The results suggest secukinumab 300 mg better improves symptoms of PsA and active psoriasis than secukinumab 150 mg.

The team underlined many limitations, including not adjusting for logistic regression analyses, nominal P values were calculated for hypothesis generation, patients were not stratified based on weight or BMI at randomization, radiographic progression data was only available from FUTURE 5, and patients in all groups had variability in vdH-mTSS scores from baseline to week 24.

“This analysis also suggests that a loading-dose regimen—particularly for patients receiving secukinumab 150 mg—increases the odds of optimal outcomes in US patients with PsA treated with secukinumab,” investigators concluded.

^References

1. Kivitz AJ, Kremer JM, Legerton CW 3rd, Pricop L, Singhal A. Efficacy and Safety of Secukinumab in US Patients with Psoriatic Arthritis: A Subgroup Analysis of the Phase 3 FUTURE Studies. Rheumatol Ther. Published online April 16, 2024. doi:10.1007/s40744-024-00666-1
2. Grossi, G. Patients with PsA Report Improved Outcomes with Secukinumab in Phase 3 Data. HCPLive. February 13, 2022. https://www.hcplive.com/view/patients-psa-improved-outcomes-secukinumab-phase-3-data. Accessed April 17, 2024.