Clinical trial NCT04147026: Prediction Medical Device for Rheumatoid Arthritis (PREDIRA)
Official title: PRediction mEdical DevIce for Rheumatoid Arthritis: Scale-up of Unique Predictive Online Platform Highly Improving the Quality of Life of Rheumatoid Arthritis' Patient by Personalised and Efficient Biotherapies Prescription
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Arthritis, Rheumatoid
Keywords: Biological therapy
Predictive software
Quality of life
Lead sponsor: Hospital San Carlos, Madrid
Sponsor class: OTHER
First posted: 2019-10-31
Enrollment: 180
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: The study is a prospective, phase III, controlled, multicenter, and randomized in 2 parallel groups, single-blind (patient) with binded outcome assessment clinical trial.

* Intervention arm: Prescription of biotherapy (rituximab, adalimumab, abatacept) using SinnoTest® software
* Control arm: Prescription of biotherapy without the SinnoTest® software which corresponds to current practice (all biotherapies).
Primary purpose: TREATMENT

Brief summary: Rheumatoid arthritis (RA) is one of the leading chronic inflammatory rheumatism, with a prevalence of about 0.4% of the population.

First-line therapy with synthetic disease modifying anti-rheumatic drugs (including methotrexate) is insufficiently effective in 40% of cases. These patients are then treated with biotherapies. The use of these bio-drugs increases each year, becoming a public health issue and a considerable economic burden. Besides, their growth is just beginning, as they are among the major purveyors of pharmacy innovations.

There are about ten bio-drugs currently on the market for rheumatoid arthritis with an average annual treatment cost of 8 to 12 K € per patient. This cost is 20 times higher than that of synthetic disease modifying anti-rheumatic drugs. However, among patients treated with biotherapies, clinical practice shows that about one-third will not respond to the selected drug. In the case of non-response, practitioners currently have no choice but to perform an empirical rotation between the different treatments, because no tool capable of predicting the response or non-response to these molecules is currently available.

The study is a prospective, phase III, controlled, multicenter, and randomized, single-blind (patient) clinical trial.

* Intervention arm: Prescription of biotherapy (rituximab, adalimumab, abatacept) using SinnoTest® software
* Control arm: Prescription of biotherapy without the SinnoTest® software which corresponds to current practice (all biotherapies).

In addition, a sub study will be carried out within this trial to analyse the proteomic profile of the patients included and their modification throughout the study.

To study the clinical and pharmacoeconomic impact after 6 months of the use of the SinnoTest® predictive tool in patients with rheumatoid arthritis who have failed to a first anti-TNF biologic agent compared to usual care.


Eligibility criteria: Inclusion Criteria:

* Patients over 18 years old and under 70 years old,
* Patients with RA, defined according to the ACR / EULAR 2010 or ACR 1987 criteria,
* Patients failing a first anti-TNF, defined as:
* Ineffectiveness (which is defined as a DAS28-ESR ≥3.2 and an inadequate response to iTNF according to the usual rheumatologist, which generally includes one or more of the following conditions: persistent swollen and tender joints, persistence of disease activity according to the overall evaluation of the patient, high levels of acute phase reactants and/or dependence of analgesics, nonsteroidal anti-inflammatory drugs or corticosteroids); or
* Toxicity(defined as the appearance of any adverse event that the patient's rheumatologist relates to the medication and requires discontinuation),
* Effective contraception for patients of childbearing potential (oral contraceptive, intrauterine device, implant, spermicide, surgical sterilization or abstinence),
* Patients able to read and understand the modalities of the protocol,
* Patients who have dated and signed the informed consent form of the trial,
* Stability of treatments (no change) between the selection visit and the inclusion visit (M0).

Exclusion Criteria:

* Patients with a contraindication to any bDMARD or methotrexate,
* Patients included in another therapeutic evaluation study during this trial,
* Surgical intervention programmed during the trial,
* Patients with difficulties in understanding the Spanish language,
* Patients cannot be followed up 6 months,
* Psychosocial instability incompatible with regular monitoring (homelessness, addictive behaviour, antecedent of psychiatric pathology or any other comorbidity that would make it impossible for free and informed consent or limit adherence to the protocol),
* Breastfeeding and/or pregnancy. Although there are bDMARD that can be used in pregnancy, since SinnoTest can recommend one that discourages this condition, it is decided to exclude the inclusion of pregnant women.

Primary outcomes:
measure: Incremental Cost Utility ratio at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Budget impact analysis at 6 and 12 months
timeFrame: 12 months
measure: Software's predictive model performance
timeFrame: 6 months
measure: Description of the variation of the proteomic profile between M0 (biotherapy start date) and M6 (6 months visit)
timeFrame: Inclusion and 6 months
Other outcomes:
measure: Incremental Cost Effectiveness ratio at 6 months
timeFrame: 6 months
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario de La Paz
Study officials:
affiliation: Hospital San Carlos, Madrid
name: Benjamín Fernández-Gutiérrez, MD, 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.
citation: Freites-Nunez D, Baillet A, Rodriguez-Rodriguez L, Nguyen MVC, Gonzalez I, Pablos JL, Balsa A, Vazquez M, Gaudin P, Fernandez-Gutierrez B. Efficacy, safety and cost-effectiveness of a web-based platform delivering the results of a biomarker-based predictive model of biotherapy response for rheumatoid arthritis patients: a protocol for a randomized multicenter single-blind active controlled clinical trial (PREDIRA). Trials. 2020 Aug 31;21(1):755. doi: 10.1186/s13063-020-04683-7.