Secukinumab provides sustained improvement in signs and symptoms and low radiographic progression in patients with psoriatic arthritis: 2-year (end-of-study) results from the FUTURE 5 study

Abstract

Objective: Secukinumab provided sustained efficacy, low radiographic progression and consistent safety over 52 weeks in patients with psoriatic arthritis (PsA) in the FUTURE 5 study. Here, we report 2-year (end-of-study) results from this study.

Methods: Adults with active PsA were randomised 2:2:2:3 to receive subcutaneous secukinumab 300 mg load (300 mg), 150 mg load (150 mg), 150 mg no load or placebo at baseline; weeks 1, 2, 3 and 4; and every 4 weeks thereafter. Secukinumab could be escalated from 150 mg to 300 mg starting at week 52, if active signs of disease were observed based on physician's assessment. Assessments at week 104 (2 years) included clinical end points and radiographic damage (mean change in van der Heijde-modified total Sharp score (vdH-mTSS)). Safety analysis included all patients who received ≥1 dose of study medication.

Results: Of the 996 patients randomised, 783 patients (78.6%) completed 2 years of treatment. Improvement in clinical end points was sustained through 2 years. The vdH-mTSS (mean change (SD)) was 0.10 (1.74; 300 mg), 0.52 (2.66; 150 mg) and 0.41 (2.20; 150 mg no load) at 2 years. The proportion of patients with no radiographic progression (change from baseline in vdH-mTSS ≤0.5) at 2 years was 89.5% (300 mg), 82.3% (150 mg) and 81.1% (150 mg no load).

Conclusion: Secukinumab with and without loading regimen provided sustained clinical efficacy and low radiographic progression through 2 years in patients with PsA. No new safety findings were reported.

Trial registration number: NCT02404350.

Keywords: arthritis; biological therapy; cytokines; inflammation; psoriatic.

Figure 1

Patients’ disposition through week 104. Twenty-six patients from placebo groups discontinued on or before week 16 and were not classified as responders or non-responders.

Figure 2

ACR20 and ACR50 responses through 2 years. All data through week 104 calculated using (A) observed and (B) multiple imputation for patients originally randomised to secukinumab 300 mg, 150 mg and 150 mg no loading dose. *In observed data (A), ‘150 mg group’ included patients who were originally randomised and those who had dose escalation and ‘150 mg No load’ group included patients who were originally randomised and those who had dose escalation from week 60 to week 104, where available data after dose escalation were used (not censored). ACR, American College of Rheumatology. n, number of patients in the treatment group with ACR evaluation.

Figure 3

ACR response up to 36–40 weeks after dose escalation from 150 mg to 300 mg. ACR, American College of Rheumatology. Before dose-escalation is defined as the last assessment done on or before a patient took the 300 mg dose. The colors flowing in the background indicate the proportion of patients changing the response over time. Number of subjects evaluated, n=137. First dose-escalation observed at study week 52.

Figure 4

Mean changes in vdH-mTSS scores from baseline through week 104. (A) Overall population, (B) anti-TNF-naïve and (C) anti-TNF-IR. Analyses at weeks 24, 52 and 104 were done by observed data. In the 300 mg dose group there was one outlier (anti-TNF-IR patient) with a very high mTSS change from baseline (week 104 analysis). Analysis was based on the patients with evaluable X-rays at both baseline and week 104. n, number of patients with evaluable X-rays at both baseline and week 104. At each time point, only patients with a value at both baseline and that time point are included. TNF, tumour necrosis factor; vdH-mTSS, van der Heijde-modified total Sharp score.

Figure 5

Cumulative probability plot of vdH-mTSS at week 104. TNF-IR, tumour necrosis factor inadequate response; vdH-mTSS, van der Heijde-modified total Sharp score.300 mg (N=222), 150 mg (N=220), 150 no load (N=222); N: randomised patients; n: number of patients with evaluable X-rays at both baseline and week 104. 150 mg and 150 mg no load groups included 77 and 79 patients with radiographic results, respectively, who had dose escalation at week 52 or later.