Clinical trial NCT04117165: Assessment of the Clinical and Medico-economic Impact of SinnoTest® in Patients With Rheumatoid Arthritis
Official title: 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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Arthritis, Rheumatoid
Biological Therapy
Keywords: predictive software
quality of life
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2019-10-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective clinical trial, phase III, randomized in 2 parallel groups, multicentric, controlled (prescription with SinnoTest® software versus prescription without SinnoTest® software), single-blind
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Clinical benefit of using SinnoTest® software at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Clinical benefit of using SinnoTest® software at 1 year
timeFrame: 1 year
measure: Comparison of the response delay to a bDMARD and the number of bDMARDs prescribed during 12 months in both arms.
timeFrame: 1 year
measure: Performance of the software predictive model on the new clinical data from the trial at 6 months and 1 year
timeFrame: 6 months and 1 year
measure: Comparison of the variation in the proteomic profile between M0 (biotherapy start date) and M6
timeFrame: Inclusion and 6 months
measure: Cost-utility analysis that will compare the 2 groups at 1 year from the community's perspective.
timeFrame: 1 year
measure: 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.
timeFrame: 1 year
measure: Budget impact analysis from the point of view of Health Insurance at 3 and 5 years.
timeFrame: 3 and 5 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: Chu Amiens
city: Besançon
country: France
facility: CHU J Minjoz
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin - CHU de Bordeaux
city: Brest
country: France
facility: CHU Cavale Blanche
city: Caluire-et-Cuire
country: France
facility: Clinique de l'infirmerie protestante
city: Clermont-Ferrand
country: France
facility: Hôpital G. Montpied
city: Dijon
country: France
facility: CHU DIJON Hôpital le Bocage
city: Grenoble
country: France
facility: Grenoble University Hospital
city: Montpellier
country: France
facility: CHU Montpellier Hôpital Lapeyronie
city: Nantes
country: France
facility: CHU NANTES - Hôtel Dieu
city: Paris
country: France
facility: APHP Groupe hospitalier Pitié-Salpêtrière
city: Paris
country: France
facility: APHP Hôpital Cochin
city: Rouen
country: France
facility: CHU Rouen Hôpital bois-guillaume
city: Saint-Étienne
country: France
facility: CHU Saint-Etienne
city: Strasbourg
country: France
facility: CHU Strasbourg Hôpital HAUTEPIERRE
city: Toulouse
country: France
facility: Hôpital PURPAN
Study officials:
affiliation: University Hospital, Grenoble
name: Philippe GAUDIN, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.