OP0169 Sarilumab for the treatment of ankylosing spondylitis: Results of a phase 2, randomized. Double-blind, placebo-controlled, international study (align)

Background Sarilumab is the first fully human monoclonal antibody directed against IL-6Rα. Objectives This study evaluated the efficacy and safety of sarilumab in patients with ankylosing spondylitis (AS). Methods Adult patients with active AS for ≥3 months, that were NSAIDs-IR or intolerant, were randomized equally into 6 groups, stratified according to hsCRP (≤1.5 mg/dL or >1.5 mg/dL) and geographic region. The primary endpoint of the study was ASAS20 response at week 12. Results Demographic and disease characteristics were similar across all treatment groups. Mean age 41 yrs, 72% male, and 97% Caucasian, mean duration of disease 8 yrs; 55% hsCRP ≤1.5 mg/dL and 45% hsCRP >1.5 mg/dL. The median back pain, physical function, patient global assessment, and inflammation scores at entry were 7.0, 4.2, 7.0 and 6.5, respectively (0-10 pt-scale). The intent-to-treat (ITT) and safety populations comprised 301 and 300 patients, respectively. Use of concomitant DMARDs was ∼20% in all treatment groups (with ∼11% of pts on MTX). There was no significant difference in ASAS20 response rate between placebo (ASAS20=24.0%) and any of the sarilumab dose groups: there was a numerically higher treatment response at week 12 in the highest dose regimen tested, 150 mg qw (ASAS20=38.0%, p=0.143; Hommel-adjusted p=0.699). Compared to placebo no difference was observed for key secondary efficacy endpoints including ASAS40, the ASAS partial response criteria, and the MRI based score of disease activity (T1 and STIR technique, change from baseline in Berlin-modified ASspiMRI score). Based on stratification parameter, additional subset analyses were conducted to test the effect of baseline hsCRP values on response rate. Patients with hsCRP values above 1.5 mg/dL, treatment with sarilumab achieved a marginally significant higher percentage of ASAS20 response [placebo 18.2% (n=22) versus 50% (n=17), p=0.055], but only in the 150 mg qw group. There was no clear dose relationship for TEAE incidence. Among the most common TEAEs reported in the active treatment arms were infections (non-serious), neutropenia, and ALT increase. Seven (7) patients experienced a treatment-emergent SAE (all in sarilumab treatment groups). Conclusions The study failed to demonstrate the efficacy of sarilumab in patients with AS assessed by ASAS20 response. Sarilumab was generally well-tolerated. In patients with a high baseline hsCRP, a trend was noted in the percentage of patients achieving ASAS20 only in the