Secukinumab: A Review of Safety and Efficacy in Psoriatic Arthritis

August 2017 | Volume 16 | Issue 8 | Supplement Individual Articles | 118 | Copyright © August 2017

Peter W. Hashim MD MHS,a Kim A. Papp MD PHD,b Philip J. Mease MDc

aThe Icahn School of Medicine at Mount Sinai, Department of Dermatology, New York, NY bK. Papp Clinical Research and Probity Medical Research, Waterloo, Ontario, Canada cSwedish Hospital Clinical Research Division, Swedish Medical Center, and University of Washington School of Medicine, Seattle, WA

Sharp/van der Heijde score (SHS), a method for assessing erosion and joint space narrowing in the hands and feet of PsA patients, was calculated throughout the study. At week 24, both secukinumab 150 mg and secukinumab 75 mg groups demonstrated less progression of joint erosion and joint space narrowing relative to placebo (P less than .05). The radiographic progression of disease was inhibited regardless of previous anti-TNF use.A 2-year review of the FUTURE-1 trial highlighted the sustained efficacy of secukinumab in the treatment of PsA.15 Results from week 104 showed ACR20 responses of 66.8% in the secukinumab 150 mg group and 58.6% in the 75 mg group (multiple imputation from weeks 28-104). Lack of efficacy was the most common reason for study dropout (5.0% among subjects receiving 150 mg, 6.9% among those receiving 75 mg, and 7.4% in the placebo group).When patients were stratified according to previous anti-TNF therapy, responses were higher in patients who were anti-TNF-naïve. In the secukinumab 150 mg group, anti-TNF-naïve patients achieved an ACR20 rate of 75.2% versus 48.0% in patients with previous anti-TNF exposure. In the 75 mg group, ACR20 rates were 63.7% and 46.9%, respectively. Both groups experienced an inhibition of joint damage, with radiographic analyses showing an absence of disease progression in 84.3% of patients in the secukinumab 150 mg group and 83.8% of patients in the secukinumab 75 mg group. No new safety signals were identified over the extended follow-up period.Three-year data from the FUTURE-1 trial has recently been presented.16 Of the original 606 patients, 435 patients have completed assessments up to week 156. Statistical analyses used multiple imputation for binary variables. At week 156, ACR 20 responses rates were 76.8% in the 150 mg group and 65.2% in the 75 mg group. Previous TNF treatment continues to demonstrate an effect on responses; in the 150 mg group, ACR20 rates were 81.0% for anti-TNF-naïve patients and 61.5% for anti-TNF-exposed patients. In the 75 mg group, ACR20 rates were 67.3% and 55.6% for anti-TNF-naïve and anti-TNF-exposed patients, respectively. Adverse events have been consistent with those previously reported.FUTURE-2 Clinical TrialThe FUTURE-2 trial ( expanded upon the dosing regimens of the FUTURE-1 study. Three hundred ninety-seven patients were evenly randomized to receive either subcutaneous secukinumab 300 mg, 150 mg, 75 mg, or placebo once weekly until week 4 and then every 4 weeks afterwards.17 At week 16, patients were classified as either responders or non-responders based on whether ≥20% improvement in tender and swollen joints had been achieved. Patients receiving placebo were re-randomized to either secukinumab 300 mg or 150 mg at week 24 (in responders) Measeor at week 16 (in non-responders). The primary endpoint was ACR20 response at week 24.Week 24 results showed response rates of 54% in the 300 mg group (P less than .0001 versus placebo), 51% in the 150 mg group (P less than .0001 versus placebo), 29% in the 75 mg group (P=.0399 versus placebo), and 15% in the placebo group. Significant improvements in physical function and quality of life occurred. Candida infections were reported in 11 subjects, all of whom had been part of secukinumab treatment groups; cases were mild-to-moderate and did not lead to study discontinuation.Similar to the FUTURE-1 trial, 2-year data from the FUTURE-2 trial demonstrated long-term safety and efficacy in the treatment of PsA.18 The ACR20 responses were 69.9% in the 300 mg group, 64.7% in the 150 mg group, and 50.1% in the 75 mg group (multiple imputation). The ACR50 responses were 50.8% in the 300 mg group, 36.2% in the 150 mg group, and 28.2% in the 75 mg group.Dactylitis and enthesitis were examined as distinct clinical manifestations in the FUTURE-2 trial. The endpoints evaluating treatment success were the proportion of patients with resolution of dactylitis or enthesitis at weeks 24 and 52, in addition to the change from baseline in dactylitis digit and enthesitis site counts at weeks 24 and 52. Of the 397 subjects randomized in the FUTURE-2 trial, 138 subjects (35%) were affected with dactylitis, and 253 subjects (64%) suffered from enthesitis.Secukinumab administration was associated with the rapid resolution of dactylitis. At week 24, the proportion of patients who experienced a resolution of dactylitis was significantly greater in the 300 mg group (56.5%) and 150 mg group (50.0%) relative to placebo (14.8%; P less than .01 versus secukinumab). These results were sustained over a 52-week period, with both treatment groups demonstrating >60% resolution at that time. Measuring the dactylitis count at week 24, a significant reduction in affected digits was seen in the 300 mg group (-2.56) compared to placebo (-0.97; P less than .05), although statistically significant differences were not reached in the other treatment groups.Enthesitis also showed high rates of resolution with secukinumab treatment. At week 24, 48.2% of affected patients in the 300 mg group reached disease resolution (P less than .01 versus placebo), along with 42.2% in the 150 mg group (P<.05 versus placebo). These rates remained largely stable over the 52-week period. Of note, the treatment improvements in enthesitis and dactylitis were observed regardless of baseline disease severity.


Taken together, the results from FUTURE-1 and FUTURE-2 demonstrate the ability of secukinumab to significantly ameliorate the signs and symptoms of PsA over long-term periods. Clinical