Multiple doses of secukinumab provided sustained improvement of the signs and symptoms of psoriatic arthritis
, according to findings from the phase 3 FUTURE 2 study.
The findings highlighted the clinical benefit and safety of long-term treatment with the interleukin-17A (IL-17A) inhibitor.
Iain McInnes, MD, PhD, and a team of investigators aimed to assess and describe the five-year results on the efficacy and safety of secukinumab 300 mg and 150 mg doses, along with dose escalation, from the FUTURE 2 study. The FUTURE 2 study was a phase 3, double-blind, placebo-controlled study done at 76 centers across Asia, Australia, Canada, Europe, and the US.
McInnes, a professor from the University of Glasgow Institute of Infection, Immunity & Inflammation, and colleagues randomly assigned patients >
18 years old with psoriatic arthritis to either secukinumab (300 mg, 150 mg, or 75 mg) or placebo weekly from baseline and then every 4 weeks starting at week 4.
At week 128, the dose went up from 150 mg to 300 mg and from 75 mg to 150 mg or 300 mg if active signs of the disease were observed.
Patients who received placebo were randomly assigned to subcutaneous secukinumab 300 mg or 150 mg (placebo switchers) every 4 weeks at week 16 (non-responders) or 24 (responders) depending on 20% improvement in American College of Rheumatology (ACR) response.
The team assessed key efficacy endpoints at week 260 (5 years) for 150 mg and 300 mg doses of secukinumab. The assessments included the proportion of patients with ACR20, ACR50, and ACR70 responses and Psoriasis Area and Severity Index (PASI)75 and PASI90 responses. Assessments also contained the mean change from baseline in the Short Form-36 Physical Component Summary, 28-Joint Disease Activity by use of C-reactive protein, Health Assessment Questionnaire Disability Index, and Psoriatic Arthritis Disease Activity Score.
McInnes and the investigative team assessed long-term safety and tolerability of secukinumab by monitoring the frequency of treatment-emergent adverse events and serious adverse events. The investigators also monitored injection site reactions; immunogenicity; abnormal laboratory findings; electrocardiograms; physical examinations; vital signs; and clinical laboratory variables over time <
84 after the last treatment was administered.
When randomized, 65% of patients were naïve to tumor necrosis factor inhibitors and 47% were taking concomitant methotrexate. Among the 397 patients assigned in the FUTURE 2 study, 62% completed 5 years of treatment, including 64% of the patients in the original secukinumab 300 mg group, 65% of those in the 150 mg group, 60% of the 75 mg group, and 61% of the placebo group.
More than half (52%) of 242 patients needed their dose escalated during the study.
ACR responses at 5 years were 71 (74%; ACR20), 50 (52%; ACR50), and 31 (32%; ACR70) of the 96 evaluable patients in the 300 mg cohort, and 67 (70%; ACR20), 41 (43%; ACR50), and 28 (29%; ACR70) of 96 evaluable patients in the secukinumab 150 mg group.
The number of ACR and PASI non-responder decreased from weeks 24-32 and 48-84 after the dose escalated from 150 mg to 300 mg. The proportions of ACR and PASI responders increased.
Throughout the entire five-year treatment period, the most frequent serious adverse event due to treatment was serious infection (exposure-adjusted incidence, 1.7; 95% CI, 1.1-2.5; n = 25) in any group that received secukinumab.
There were no new or unexpected safety signals during the study period.
The results supported the clinical benefit of the IL-17A inhibitor for patients with psoriatic arthritis, with both 150 mg and 300 mg doses of secukinumab providing improvement in signs and symptoms of the condition.
The study, “Long-term efficacy and safety of secukinumab in patients with psoriatic arthritis: 5-year (end-of-study) results from the phase 3 FUTURE 2 study
,” was published online in The Lancet