Alan J. Kivitz
CHICAGO — Phase 3 data from the MEASURE 3 trial showed that a 300-mg dose of secukinumab sustained improvements in the signs and symptoms of active ankylosing spondylitis over 3 years without increasing the incidence of adverse events compared with a 150-mg dose.
“Secukinumab [(Cosentyx, Novartis)] is a fully human monoclonal antibody that directly inhibits IL-17A and has demonstrated significant improvement in the signs and symptoms of active AS in several phase 3 studies,” Alan J. Kivitz, MD, founder and medical director of the Altoona Center for Clinical Research, said during a presentation at the ACR/ARHP 2018 Annual Meeting. “We present our end-of-study results at week 156 from the MEASURE 3 study that assessed the highest dose of secukinumab to date in AS.”
The study followed 226 patients with AS, some of whom had active disease despite current or previous use of TNF inhibitors. After receiving a loading dose of 10 mg/kg of IV secukinumab at baseline, week 2 and week 4, patients were randomly assigned to receive 300 mg (n = 76) or 150 mg (n = 74) of secukinumab every 4 weeks thereafter. Another 76 patients were randomly assigned to receive placebo for 16 weeks, then re-randomized to 300 mg (n = 37) or 150 mg (n = 36) of secukinumab every 4 weeks.
By the end of the 3-year study period, 80.5% of patients assigned to 300 mg of secukinumab and 80.9% assigned to 150 mg of secukinumab completed treatment. Novartis previously released findings from the primary analysis, which showed both doses were associated with a 20% or greater improvement in Assessment in Ankylosing Spondylitis (ASAS20).
The current analysis showed that clinical responses with both secukinumab doses were sustained over 156 weeks. Response rates with more stringent clinical endpoints, including ASAS40, were greater in the 300-mg dose group, particularly among patients with previous anti-TNF exposure. By the end of the study, 56.5% of patients assigned to 300 mg achieved ASAS40 vs. 47.7% of patients assigned to 150 mg.
Both the 300-mg dose and 150-mg dose had similar safety profiles. Five patients in each group discontinued treatment due to adverse events, and two patients in each group developed a serious infection. Three patients in the 150-mg group developed a malignant or unspecified tumor vs. one patient in the 300-mg group.
The most common adverse events included nasopharyngitis (n = 27 in each group), headache (n = 14 in the 300-mg group; n = 12 in the 150-mg group), and arthralgia (n = 14 in each group). No deaths or cases of inflammatory bowel disease, ulcerative colitis, or Crohn’s disease were reported.
“In conclusion, 300 mg and 150 mg of secukinumab both provide sustained improvement in the signs and symptoms of active AS,” Kivitz said. “Secukinumab demonstrated a favorable and consistent safety profile throughout the 3 years of treatment.”
Although the study was not powered to demonstrate superiority, Kivitz said another trial is currently assessing whether there is a clinical advantage to raising the dose of secukinumab from 150 mg to a higher dose.
Additional findings from and extension of the MEASURE 1 trial, also presented at the ACR/ARHP 2018 Annual Meeting, showed that secukinumab was safe and effective against multiple features of AS over 5 years. – by Erin Michael
Kivitz, A, et al. Abstract 1869. Presented at: ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.
Disclosures: Kivitz reports being a consultant for AbbVie, Celgene, Genentech, Pfizer, Sanofi/Regeneron and UCB. He also reports serving on a speakers’ bureau for Celgene, Horizon, Merck, Pfizer and Sanofi/Regeneron. The study was sponsored by Novartis Pharma AG.