OP0110 Serum tocilizumab trough concentrations are associated with clinical disease activity index scores in adult rheumatoid arthritis patients
Authors: U Arad, O. Elkayam
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Serum trough levels of TNFα inhibitor biologics have been found to be associated with clinical responses in rheumatoid arthritis (RA) patients. It is unknown whether serum trough levels of tocilizumab (TCZ) administered as a fixed dose subcutaneous injection, also associate with clinical disease activity responses. <h3>Objectives</h3> To ascertain whether serum TCZ trough levels at weeks 12 and 24 after beginning treatment with a 162 mg once weekly regimen of SC tocilizumab, were associated with clinical disease activity outcomes in RA patients. <h3>Methods</h3> We analysed data sets from the Israeli branch (TASC, NCT01988012) of the Roche multinational umbrella study TOZURA, which evaluated a SC TCZ treatment regimen of 162 mg once weekly as monotherapy or in combination with methotrexate or other csDMARDs in a real-life clinical setting. The study comprised of 100 patients. A paired-samples T test was used to compare mean serum TCZ levels at week 12 relative to week 24. Clinical disease activity index (CDAI) scores were natural log-transformed in order to achieve normal distribution. Generalised estimating equations were used to evaluate associations between the predictors (TCZ levels, soluble IL-6 receptor (sIL6R) levels) and the study outcomes (CDAI scores, HAQ scores, CDAI remission/low disease activity status, HAQ DI remission). Generalised estimating equations were also used to evaluate associations between age, sex, weight, BMI, baseline CRP levels, serum TCZ and sIL6r serum levels. P values below 0.05 were considered significant. <h3>Results</h3> Serum trough levels of TCZ at week 24 (mean 41.1, SD 23.2) were higher than at week 12 (mean 36.3, SD 18.1). In a univariate analysis, for every increase of 1 microgram/ml in the serum concentration of TCZ there was a corresponding decrease of 1.3% (95% CI: 0.4% to 2.3%) in the CDAI score and for every increase of 100 ng/ml in the serum concentration of sIL6R there was a corresponding decrease of 12.6% (95% CI: 2% to 22%) in the CDAI score. In a multivariate model which included age, sex, visit date and both sIL6R and TCZ levels, only the associated between TCZ levels and CDAI scores remained significant. Similarly, every increase of 10 microgram/ml in the serum concentration of TCZ was associated with an odds ratio of 1.35 (95% CI: 1.07 to 1.72) of being in a state of CDAI remission or low disease activity versus moderate/high disease activity state. TCZ and sIL6R serum levels were not associated with HAQ DI scores. Female sex was associated with an increase of 12.9 microgram/ml in the serum TCZ concentrations (95% CI: 5.9 to 20.0). Also, every increase of 1 BMI unit was associated with a decrease of 1.5 microgram/ml in the serum TCZ concentrations (95% CI: 0.8 to 2.2) and every increase of 1 kg in weight was associated with a decrease of 0.6 microgram/ml in the serum TCZ concentrations (95% CI: 0.3 to 0.9). <h3>Conclusions</h3> In the first year of TCZ treatment with a fixed dose regimen of 162 mg SC injection once a week, serum trough concentrations of TCZ are associated with CDAI scores and a state of CDAI remission/low disease activity. Body weight and BMI are inversely associated with serum TCZ concentrations. These results suggest that personalising the dose of SC TCZ to body weight may improve clinical outcomes of RA disease activity. <h3>Acknowledgements</h3> We thank Roche for the TASC study data sets. <h3>Disclosure of Interest</h3> None declared