A 3-arm, randomized, open-label, parallel active controlled, multicenter international study to compare the response of ultrasound-assessed synovitis to baricitinib, alone and combined with methotrexate versus etanercept in rheumatoid arthritis patients with inadequate response to methotrexate. Searching for synovium predictors of response.
- Conditions
- M06Other rheumatoid arthritis
- Registration Number
- DRKS00027537
- Lead Sponsor
- Fundación Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz (FIIS-FJD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 186
1.Patient able to provide written informed consent
2.Mentally competent to understand and willing to undergo the scheduled study procedures, including study questionnaires as established in the protocol.
3.Female or male, from 18 to 75 years of age at the moment of informed consent signature.
4.Patient with RA diagnosed according to 2010 ACR/EULAR Classification Criteria for RA.
5.Moderate to severe disease activity (according to Disease Activity Score for 28 joints (DAS28) = 3.2).
6.Inadequate response to MTX, which must have been received during, at least, 3 months prior to baseline visit and be on a stable dose of = 25 mg/week.
7.Patients who fulfils the pre-requisites for biologic and targeted synthetic disease modifying antirheumatic drugs (DMARD) therapy according to National recommendations/regulations (eg, absence of active infections, absence of latent tuberculosis, recommendations regarding previous cancer, vaccination recommendations,…).
8.Written acceptance to use highly effective contraception i.e. intrauterine device (IUD); hormonal therapy (progestin alone or combined with estrogen) associated with inhibition of ovulation such as oral pill, injection, implant, transdermal patch or vaginal ring; tubal ligation, partner’s vasectomy; or sexual abstinence for the entire duration of study participation including six months after stop of study treatment.
1.Patient considered by the investigator to be unsuitable for the study treatment and/or rescue medication (RM) based on the prescription drug labeling, their medical history, physical examination, concomitant medication (CM) and concomitant systemic diseases.
2.Complications during the period prior to randomisation, in the investigator's opinion.
3.Hypersensitivity or allergy to the study medication.
4.Patients taking any concomitant medication, which could be susceptible to interact with the study drugs.
5.Patients in treatment with any medication that could affect the evaluation of the study treatment’s efficacy. DMARDs other than methotrexate are not allowed at study inclusion. If the patient has received other DMARD, eg hidroxicloroquine, leflunomide, sulphasalazine,....These drugs must have been stopped at least 3 months before inclusion. Regarding NSAID or corticosteroids, concomitant stable doses of nonsteroidal anti-inflammatory drugs, analgesics for pain relief if necessary. or corticosteroids (= 7.5mg of prednisone or the equivalent daily) will be allowed during the trial period.
6.Patients on anticoagulant treatment
7.Pregnant or lactating women.
8.Patients and/or female partners of male patients not using highly effective method of birth control i.e. intrauterine device (IUD); hormonal therapy (progestin alone or combined with estrogen) associated with inhibition of ovulation such as oral pill, injection, implants, transdermal patch or vaginal ring; tubal ligation, partner’s vasectomy; or sexual abstinence.
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Efficacy: The primary outcome considered in this trial is the decrease in join inflammation detected by MSKUS (B-mode and Doppler mode synovitis).<br>Safety: Safety evaluation will be assessed through physical examination, possible adverse events (related or not to the treatment under study) and analytical parameters. During each study visit all the safety variables must be recorded in medical records and e-CRF.
- Secondary Outcome Measures
Name Time Method Time-point of significant change in B-mode and Doppler synovitis according to treatment group (4 weeks, 12 weeks, 24 weeks).<br>-Presence and amount of subclinical B-mode and Doppler synovitis in patients reaching DAS28-defined clinical remission and low disease activity at 4 weeks, 12 weeks and 24 weeks, according to treatment group.<br>-Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) at 4 weeks, 12 weeks and 24 weeks, according to treatment group.<br>- For applicable patients, correlation between presence of MSKUS- assessed synovitis, synovial histological alterations and the presence of proinflammatory citokines (TNF, IL6, IL1, COX2, MCP1, RANKL, OPG…) in serum and synovial tissue, at baseline in all patients and after 12 weeks in patients classified as non-<br>responders, according to treatment group.<br>-Changes in PROM as assessed by the Health Assessment Questionnaire–Disability Index (HAQ-DI), from baseline to 24 weeks.