AB0654 Drug Survival and Switching Rate of TNF Inhibitors in A Cohort of Patients with Ankylosing Spondylitis with Long Term Follow Up
Authors: K. Klavdianou, A. Lazarini, C. Koutsianas, C. Tsalapaki, K. Thomas, C. Hatzara, K. Antonatou, D. Vassilopoulos
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Although the efficacy of TNF inhibitors (TNFi) in ankylosing spondylitis (AS) is well established, their long term survival (&gt;5 years), baseline prognostic factors for their discontinuation and switching rate have not been adequately studied in daily clinical practice. <h3>Objectives</h3> To estimate the long-term survival, switching rate of TNFi as well as to identify baseline predictors for drug survival in a cohort of patients with AS in real life settings. <h3>Methods</h3> A retrospective systematic chart review of all AS patients treated with TNFi in our Rheumatology Unit from 1/1/2003 to 31/12/2015 was performed. Demographic, clinical and laboratory data were collected and analyzed. Drug survival was estimated by Kaplan-Meier analysis. The impact of several covariates on drug survival was analysed by Cox regression. <h3>Results</h3> 103 AS patients who had received etanercept (ETN, n=41), infliximab (INF, n=33), adalimumab (ADA, n=21), golimumab (GOL, n=7) or certolizumab pegol (CZP, n=1) were included. Patients were predominantly males (67%, n=69) with a mean age of 45±11.8 years and a median disease duration of 7 years. The patients were followed for a median time of 5 years (mean: 5.1±2.6 years). Peripheral arthritis was present in 42% (n=43) and extra-articular manifestations in 26.5% (n=27) of patients. The majority (94%, n=97) received TNFi as monotherapy. The mean overall survival of the first TNFi was 81.2±6.7 months (40% survival after 7 years). ADA demonstrated a longer survival (84±8.5 months) compared both to ETN (53±6 months, p=0.04) and INF (76±11 months, p=0.063). 43 patients (42%) discontinued the 1st TNFi due to adverse events (37%), inadequate response (35%) or other reasons (28%). 10% of patients were lost to follow up. No difference in discontinuation reasons was found among the different TNFi (p=0.125). 33 patients (32%) switched to a second TNFi (ADA: n=23, ETN: n=3, INF: n=3, GOL n=2, CZP n=1). Overall the retention to therapy was better for non-switchers compared to switchers9 to a second TNFi (81.2±6.7 months vs. 42.8±7 months, p=0.086). Specifically for ADA, this difference was statistically significant (p=0.03). Among several baseline variables (age, disease duration, extra-articular manifestations, peripheral arthritis, HLA B27 status), none was predictive for therapy discontinuation. Although lower baseline CRP (HR=0.7, 95% CI: 0.5–1.3), longer disease duration (HR=1.1, 95% CI: 0.9–1.3), concurrent smoking (HR=4.9, 95% CI: 0.9–25) and male gender (HR=4.8, 95% CI: 0.8–26) were associated with higher risk for drug discontinuation, these did not prove to be statistically significant by multivariate analysis. <h3>Conclusions</h3> Only 40% of AS patients remain on their 1st TNFi 7 years after starting treatment. ADA demonstrated longer survival compared to ETN and INF as the 1st TNFi. Approximately one-third of patients switched to a 2nd TNFi which had a shorter survival compared to the 1st. In our patient cohort we did not identify any baseline predictors for longer drug survival. <h3>Acknowledgement</h3> Supported by research grants from the Special Account for Research Grants (S.A.R.G.), National and Kapodistrian University of Athens, Athens, Greece. <h3>Disclosure of Interest</h3> None declared