FRI0092 New algorithm to approach ra patients receiving biologic therapies: Introducing immunogenicity assessment in the eular guidelines
Authors: S. Garcês, J. Canas-da-Silva, L. Aarden, J. Demengeot
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In the last years, the "treat to target" strategy revealed the importance of tight control of disease activity in RA patients<sup>1</sup>. To reach clinical remission or at least low disease activity as soon as possible, this strategy, now part of the EULAR guidelines, requires therapeutic combinations and/or fast switches between different therapies<sup>2</sup>. Over the last years it became clear that drug immunogenicity is one of the main mechanism behind biologic therapeutic failure<sup>3-4</sup>. How to integrate the notion of drug immunogenicity in clinical practice remains to be formally established. We conducted a systematic review of the Literature with a meta-analysis evaluating the clinical implications of drug immunogenicity<sup>5</sup>. Based on the information retrieved we designed a new algorithm which introduces immunogenicity assessment in the EULAR guidelines for the management of RA patients receiving biologic therapy. <h3>Objectives</h3> We assessed the influence of adherence to our proposed algorithm on therapeutic responses and low disease activity rates in a prospective cohort of RA patients treated with biologics. <h3>Methods</h3> We conducted a prospective cohort study over 2-years evolving 106 consecutive RA patients, 92% female, with a mean age of 55±13 yrs and mean disease duration of 6±4 yrs. Patients had been submitted to biologic therapy by a mean period of 4±3 years. Serum drug trough levels were assessed by ELISA and anti-drug antibodies (ADA) by an optimized Bridging ELISA, which we previously compared with a fluid-phase RIA. Clinicians were blind for the tests results. Therapeutic response and low disease activity were defined according to the EULAR guidelines. <h3>Results</h3> At the study onset 22 patients were receiving Infliximab (36.4% anti-infliximab pos), 33 Adalimumab (27.3% anti-adalimumab pos) and 49 Etanercept (0% anti-etanercept pos). Patients with detectable ADAs had undetectable serum drug trough levels and lower therapeutic responses rates (37.5% vs 76.9%, p=0.001 for Infliximab and 33.3 vs 66.7%, p=0.02 for Adalimumab). Not a single patient with detectable ADAs had low disease activity. During follow-up period, therapeutic decision coincident with our proposed algorithm concerned 48.6% of the patients (Group 1), however with a décalage median (IQR) time of 249 days (116-388). Therapeutic decisions were discordant with our algorithm for 51.4% of the patients (Group 2). A significant higher proportion of patients in Group 1, when compared to Group 2, reached therapeutic response at 3 months (97.9% vs 52.2%, p=0.001) and at 12 months (71.4% vs 13% p=p=0.000). Moreover, a significant higher proportion of patients in Group 1 achieved low disease activity at 3 months (71.4% vs 13%, p=0.000) and at 12 months (58.8% vs 3.8%, p=0.000). Considering drug direct costs only, we evaluated that about 1 million euros were spent inefficiently in this cohort over 2 years. <h3>Conclusions</h3> Our study strongly suggests that including immunogenicity assessment in EULAR guidelines will allow the design of more cost-effective strategies, tailored to each RA patient receiving biologic therapy. <h3>References</h3> Schipper LG et al. Ann Rheum Dis 2011;Dec30. Smolen JS et al. Ann Rheum Dis 2010;69:964-75. Bartelds et al. JAMA 2011;305:1460-8. Jamnistski et al. Ann Rheum Dis 2011; 70:284-8. EULAR 2012 Abstract: EULAR12-3348. <h3>Disclosure of Interest</h3> None Declared