OP0020 SEX DIFFERENCES IN EFFECTIVENESS OF FIRST-LINE TUMOR NECROSIS FACTOR INHIBITORS IN AXIAL SPONDYLOARTHRITIS; RESULTS FROM FIFTEEN COUNTRIES IN THE EuroSpA RESEARCH COLLABORATION NETWORK

Abstract

BackgroundEvidence reveals sex differences in physiology, disease presentation and response to treatment in axial spondyloarthritis (axSpA). Pooled data from four randomized controlled trials demonstrated reduced treatment efficacy of a tumor necrosis factor inhibitor (TNFi) in females compared to males with ankylosing spondylitis1. However, real-life evidence confirming these data in large cohorts is scarce. We sought to validate prior studies using data from a large multinational cohort based on real-life clinical practice.ObjectivesTo investigate sex differences in treatment response and drug retention rates in clinical practice among patients with axSpA, treated with their first TNFi.MethodsData from biologic-naïve axSpA patients initiating a TNFi in the EuroSpA registries were pooled. In the primary analysis, propensity-score weighting was applied to assess the causal effect of sex on clinically important improvement (CII) according to ASDAS-CRP at 6 months. A generalized linear regression model was used to estimate the causal risk difference (RD) and relative risk (RR) of sex on CII. Possible covariates influencing the outcome were determined a priori and selected based on availability in the database (<20% missing). The final covariates included in the model were country, age and TNFi start year. In the secondary analysis, drug retention was assessed over 24 months of follow-up by Kaplan-Meier curves and log-rank test.ResultsIn total, 6,451 axSpA patients with available data on ASDAS-CRP at baseline and 6 months were assessed for treatment response. Baseline characteristics are shown in the Table 1. In the adjusted analysis, the probability for females to have CII was 15% (RR, 0.85; 95% confidence interval [CI], 0.82 to 0.89) lower compared to males and the difference in probability for having CII was 9.4 percentage points (RD, 0.094; 95% CI, 0.069 to 0.12). The survival analysis included 28,608 axSpA patients with available data on retention rates. The TNFi 6/12/24-month retention rates were significantly lower in females (81%/69%/58%) compared to males (89%/81%/72%), see Figure 1.Table 1.FemaleMaleMean (SD), Median [IQR] or percentagesMean (SD), Median [IQR] or percentagesAge (years)42.0 (12.1)41.4 (12.3)Fulfilment of mNYC66%80%Disease duration (years)2.0 [1.0, 7.0]3.0 [1.0, 9.0]TNFi start year Start 1999-20097.2%9.8% Start 2010-201326%27% Start 2014-201637%36% Start 2017-202030%27%BASDAI, mm59 (20)54 (21)BASFI, mm48 (25)46 (24)ASDAS, units3.5 (0.9)3.5 (1.0)CRP (mg/L)6.7 [2.5, 16.0]11.9 [4.0, 25.0]SJC (0-28)0 [0, 0]0 [0, 0]TJC (0-28)0 [0, 2]0 [0, 1]VAS pain, mm63 (22)59 (24)VAS fatigue, mm65 (25)59 (26)mNYC, modified New York criteria; TNFi, tumor necrosis factor inhibitor; BASDAI, Bath Ankylosing Spondylitis Disease Activity Indexf; BASFI, Bath Ankylosing Spondylitis Functional Index; ASDAS, Ankylosing Spondylitis Disease Activity Score; CRP, C-reactive protein; SJC, swollen joint count; TJC, tender joint count; VAS, visual analogue scale.ConclusionTreatment efficacy and retention rates are lower among female patients with axSpA initiating their first TNFi. Females presented with lower C-reactive protein levels and higher scores on patient reported outcomes at baseline, reflecting differences in disease expression. Recognizing these sex differences is of relevance for customized patient care and may improve patient education.