PREDIRA (PRediction mEdical DevIce for Rheumatoid Arthritis): Scale-up of unique predictive online platform highly improving the quality of life of Rheumatoid Arthritis’ patient by personalized and efficient biotherapies prescription

Abstract

Background: Rheumatoid arthritis (RA) is one of the leading chronic inflammatory rheumatism. Firstline therapy with synthetic disease modifying anti-rheumatic drugs (sDMARD) is insufficiently effective in 40% of cases and these patients are treated with biotherapies. The increases use of these drugs each year is becoming a public health issue with considerable economic burden. This cost is 20 times higher than that of sDMARD. However, among patients treated with biotherapies, clinical practice shows that about one-third will not respond to the selected drug. In non-response cases, practitioners currently have no choice but to perform an empirical switching between different treatments, because no tool capable of predicting the response or non-response to these molecules is currently available.Methods : The study is a prospective, phase III, controlled, multicenter, and randomized, single-blind (patient) clinical trial, including RA patients with a previous failure to anti-TNF therapies. The main objective is the analysis of the clinical and pharmacoeconomic impact after 6 months of treatment.Intervention arm: Prescription of biotherapy (rituximab, adalimumab, abatacept) using SinnoTest® software, a prediction software based on proteomic biomarkers. Control arm: Prescription of biotherapy based on current practice, without the SinnoTest® software (any biotherapy). In addition, a sub study will be carried out within this trial to generate a biobank and further analyze the proteomic profile of the patients and their modification throughout the study.Discussion : This clinical trial study will be the first validation study of a biotherapy response prediction software, bringing personalized medicine into the management of RA. We expect that the findings from this study will bring several benefits for the patient and the Health Care System. Trial registration : The study was registered at clincaltrials.gov (NCT04147026). Registered on 31 October, 2019.Then compare the two arms, using a chi-square test (or Fischer if necessary).Clinical Secondary Objectives. Diagnostic performance indices at 6 months: sensitivity, specificity, positive and negative predictive values, likelihood ratio will be described. The performance of the SinnoTest® will be calculated in the "SinnoTest®" arm by comparing the response predicted by the software and the response observed at 6 months. It will be searched globally, and for each of the biotherapies.Medico-economic primate and secondary objectives. The incremental cost effectiveness ratio at 6 will be calculated from the cost differential of the strategies and the efficiency differential defined by the rate of responder patients in each group. The ICER and the 6 month ICUR will be subjected to a deterministic and probabilistic sensitivity analysis.Statistical analysis of the proteomic sub study. The biomarkers of the proteomic profile will be compared between the Inclusion visit (M0) and the 6-month visit, as well as the differences in both 23 the M0 and M6 visits between the two treatment ...