Assessment of the Clinical and Medico-economic Impact of SinnoTest® in Patients With Rheumatoid Arthritis (SINNO-RA)

Assessment of the Clinical and Medico-economic Impact of SinnoTest®, a Software That Predicts the Effectiveness of Biotherapy Treatments, in Patients With Rheumatoid Arthritis (RA)

Rheumatoid arthritis (RA) is one of the main chronic inflammatory rheumatic diseases (RCI), with a prevalence of about 0.4% of the population.

First-line treatment with immunomodulators (synthetic and biological Disease Modifying Anti-Rheumatic Drugs (sDMARDs) including methotrexate) is not sufficiently effective in 40% of cases. These patients are then treated with biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) called biotherapies. As the use of these bio-drugs increases each year, they become a major public health and economic issue. Their growth is only just beginning, as they are among the major providers of pharmaceutical innovation.

There are about ten bio-drugs currently on the market for rheumatoid arthritis with an average annual treatment cost of 8 to 12 000 euros per patient. This cost is 20 times higher than that of sDMARDs. However, among patients treated with biotherapy, clinical practice shows that approximately one-third (33%) will not respond to the selected bio-drugs.

In the event of non-response, physicians currently have no choice but to rotate empirically between different treatments, as no tools capable of predicting response or non-response to these molecules are currently available. SinnoTest® software, a predictive algorithm for responding to bDMARDs by analyzing proteomic biomarkers, will clarify this choice of prescription for patients with failed RA of a first bDMARD in the anti-TNF family.

Study Overview

• Status: Withdrawn
• Conditions: Arthritis, Rheumatoid; Biological Therapy
• Intervention / Treatment: Diagnostic test: Biotherapy Prescription with SinnoTest® software; Drug: Patient Current Care

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Amiens, France
    • CHU Amiens
  • Besançon, France
    • CHU J Minjoz
  • Bordeaux, France
    • Groupe Hospitalier Pellegrin - CHU de Bordeaux
  • Brest, France
    • CHU Cavale Blanche
  • Caluire-et-Cuire, France
    • Clinique de l'infirmerie Protestante
  • Clermont-Ferrand, France
    • Hôpital G. Montpied
  • Dijon, France
    • CHU DIJON Hôpital le Bocage
  • Grenoble, France
    • Grenoble University Hospital
  • Montpellier, France
    • CHU Montpellier Hôpital Lapeyronie
  • Nantes, France
    • CHU Nantes - Hôtel Dieu
  • Paris, France
    • APHP Hôpital Cochin
  • Paris, France
    • APHP Groupe hospitalier Pitié-Salpêtrière
  • Rouen, France
    • CHU Rouen Hôpital bois-guillaume
  • Saint-Étienne, France
    • CHU Saint-Etienne
  • Strasbourg, France
    • CHU Strasbourg Hôpital Hautepierre
  • Toulouse, France
    • Hôpital Purpan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with Rheumatoid Arthritis defined according to ACR/EULAR 2010 or ACR 1987 criteria.
• Patients in failure (patient insufficiently responding to anti-TNF treatment DAS28 > 3.2 whether related to primary biotherapy failure, loss of efficacy (loss of response) or adverse event) of a first bDMARD of the anti-TNF family (Adalimumab, Infliximab, Etanercept, Certolizumab or Golimumab).
• Stability of synthetic fund processing for 3 months.
• Corticosteroids ≤ 0.1 mg/kg/day without cortisone assault within 3 months.
• Effective contraception for patients with reproductive capacity (oral contraceptive, intrauterine device, implant, surgical sterilization or abstinence).
• Patients who have dated and signed the consent form for the trial.
• Patients affiliated to a social security system.

Exclusion Criteria:

• Contraindication to at least one of the following bDMARDs: Rituximab and/or Abatacept and/or Adalimumab.
• Scheduled surgical intervention during the trial.
• Difficulties in understanding the French language.
• Cognitive function disorders (dementia such as Alzheimer's, etc.).
• Patients who cannot be followed up at 12 months.
• Psycho-social instability incompatible with regular follow-up (homelessness, addictive behavior, a history of psychiatric pathology or any other comorbidity that would make free and informed consent impossible or limit adherence to the protocol).
• Persons referred to in Articles L1121-5 to L1121-8 of the CSP (corresponding to all protected persons: pregnant woman, parturient, breastfeeding mother, persons deprived of liberty by judicial or administrative decision, persons subject to a legal protection measure).
• Patients currently participating in other clinical research or who participated in a clinical trial within one month prior to inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SinnoTest® software; SinnoTest® is a therapeutic guidance device for patients suffering from chronic inflammatory rheumatism, in particular, rheumatoid arthritis. Prescription of bDMARD or their biosimilars is possible.	Diagnostic test: Biotherapy Prescription with SinnoTest® software; The rheumatologist will use the SinnoTest® software to give the best biotherapy to the patient according to the results of the software.
Active Comparator: Patient Current care; Current care of patients with rheumatoid arthritis, based on the recommendations of the French Society of Rheumatology. Prescription of bDMARD or their biosimilars is possible.	Drug: Patient Current Care; The rheumatologist will use the french guidelines of rheumatoid arthritis to choose the more adapted biotherapy treatment to the patient.; Other Names: Biotherapy treatment without SinnoTest®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical benefit of using SinnoTest® software at 6 months	Clinical benefit of using SinnoTest® software in patients with RA who have failed to respond to a bDMARD of the anti-TNF family compared to usual care practice	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical benefit of using SinnoTest® software at 1 year	Patients who respond according to the disease activity criteria from the DAS28 scale	1 year
Comparison of the response delay to a bDMARD and the number of bDMARDs prescribed during 12 months in both arms.	The delay and the number of bDMARDs prescribed before a good response	1 year
Performance of the software predictive model on the new clinical data from the trial at 6 months and 1 year	Description of the properties of the prediction algorithms on the data of the study	6 months and 1 year
Comparison of the variation in the proteomic profile between M0 (biotherapy start date) and M6	Determination of the blood proteomic profile	Inclusion and 6 months
Cost-utility analysis that will compare the 2 groups at 1 year from the community's perspective.	EuroQol five Dimensions questionnaire (EQ-5D-5L). The ratio will therefore be expressed as a cost per QALY earned, which represents the additional cost that will be required to earn a healthy year of life	1 year
Cost-effectiveness analysis that will compare the group with SinnoTest® compared to the group without SinnoTest®, at 1 year from the community's point of view.	Incremental Cost-Effectiveness Ratio (ICER)	1 year
Budget impact analysis from the point of view of Health Insurance at 3 and 5 years.	Measurement of the financial consequences for the Health Insurance of the implementation of SinnoTest® in the context of rheumatoid arthritis at 3- and 5-years' time point.	3 and 5 years

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Investigators: Principal Investigator: Philippe GAUDIN, PhD, University Hospital, Grenoble

Publications and helpful links

General Publications

• Nguyen MVC, Baillet A, Romand X, Trocme C, Courtier A, Marotte H, Thomas T, Soubrier M, Miossec P, Tebib J, Grange L, Toussaint B, Lequerre T, Vittecoq O, Gaudin P. Prealbumin, platelet factor 4 and S100A12 combination at baseline predicts good response to TNF alpha inhibitors in rheumatoid arthritis. Joint Bone Spine. 2019 Mar;86(2):195-201. doi: 10.1016/j.jbspin.2018.05.006. Epub 2018 Jun 6.
• Nguyen MVC, Adrait A, Baillet A, Trocme C, Gottenberg JE, Gaudin P. Identification of cartilage oligomeric matrix protein as biomarker predicting abatacept response in rheumatoid arthritis patients with insufficient response to a first anti-TNFalpha treatment. Joint Bone Spine. 2019 May;86(3):401-403. doi: 10.1016/j.jbspin.2018.09.005. Epub 2018 Sep 19. No abstract available.
• Baillet A, Trocme C, Romand X, Nguyen CMV, Courtier A, Toussaint B, Gaudin P, Epaulard O. Calprotectin discriminates septic arthritis from pseudogout and rheumatoid arthritis. Rheumatology (Oxford). 2019 Sep 1;58(9):1644-1648. doi: 10.1093/rheumatology/kez098.
• Baillet A, Trocme C, Berthier S, Arlotto M, Grange L, Chenau J, Quetant S, Seve M, Berger F, Juvin R, Morel F, Gaudin P. Synovial fluid proteomic fingerprint: S100A8, S100A9 and S100A12 proteins discriminate rheumatoid arthritis from other inflammatory joint diseases. Rheumatology (Oxford). 2010 Apr;49(4):671-82. doi: 10.1093/rheumatology/kep452. Epub 2010 Jan 25.
• Trocme C, Marotte H, Baillet A, Pallot-Prades B, Garin J, Grange L, Miossec P, Tebib J, Berger F, Nissen MJ, Juvin R, Morel F, Gaudin P. Apolipoprotein A-I and platelet factor 4 are biomarkers for infliximab response in rheumatoid arthritis. Ann Rheum Dis. 2009 Aug;68(8):1328-33. doi: 10.1136/ard.2008.093153. Epub 2008 Jul 29.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: September 30, 2019
• First Submitted That Met QC Criteria: October 2, 2019
• First Posted (Actual): October 7, 2019

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: quality of life; predictive software
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: 2019-A01709-48

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No