Efficacy of a Sequential Treatment Strategy in Rheumatoid Arthritis
ConditionRheumatoid Arthritis
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity Hospital, Montpellier
About this trial
In rheumatoid arthritis (RA), the consensual 1st line conventional synthetic disease modifying antirheumatic drugs (csDMARD) of RA is methotrexate (MTX). In case of contra-indication or intolerance to MTX, leflunomide is an alternative. If the treatment target is not achieved with csDMARD strategy, addition of a biological DMARD (TNF inhibitors, anti-Interleukin 6 (anti-IL6)), abatacept, or rituximab) or a targeted synthetic (ts) DMARD (JAK inhibitors) is considered.
Current practice is to start a bDMARD (biologic Disease Modifying Antirheumatic Drugs) and especially TNF inhibitors (etanercept or monoclonal anti-TNF antibodies) with the benefit of hindsight. However, abatacept and TNF inhibitors have demonstrated similar efficacy in patients with insufficient response to csDMARD (AMPLE trial).
Although abatacept has shown a very good tolerance profile that might be superior to other bDMARDs rheumatologists might be reluctant to use it as a first line bDMARD as there is a belief of a slower efficacy compared to other bDMARDs or JAK inhibitors. Indeed, in real world study, compared to TNF inhibitors it seems that discontinuation of abatacept is more related to lack of effectiveness than safety issues.
Investigators have hypothesized that first rapidly controlling the inflammation phase, using TNF inhibitors followed by abatacept to induce an immunological remission would optimize response and tolerance of ACPA positive patients with RA. To demonstrate our hypothesis, the investigaors propose a randomized controlled trial with one arm receiving an induction therapy for 12 weeks with a TNF inhibitor followed by a cell-targeted bDMARD (abatacept) and the other arm, receiving TNF inhibitors.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Aged between 18 or above
Rheumatoid arthritis according to ACR-EULAR 2010 (American College of Rheumatology-European League Against Rheumatism)
ACPA positive
Under methotrexate or leflunomide treatment for at least 3 months
Disqualifiers
Subject unable to read or/and write
Planned longer stay outside the region that prevents compliance with the visit plan
Subject unable to sign informed consent form
Subject not covered by public health insurance
Trial design
Design model
Sequential
Treatments tested in this trial
Abatacept (W12-W48)
DrugThe experimental strategy will evaluate abatacept 125 mg/week following 12 weeks of anti-TNF prescribed in usual care. Concomitant treatment with stable doses of csDMARD, non-steroidal anti-inflammatory drugs, analgesic agents, glucocorticoids (≤10 mg of prednisone or the equivalent per day), or a combination of these drugs will be permitted. Patients will continue to take methotrexate or leflunomide for the duration of the study.
TNF Inhibitor (W12-W48)
DrugIn the control group, the 88 randomized RA patients will be treated with TNF inhibitor subcutaneous for 36 weeks. In case of insufficient response to a first TNF inhibitor at 24 or 36 weeks, a second TNF inhibitor will be proposed.
TNF Inhibitor (W0-W12)
DrugAll included patients will receive TNF inhibitors subcutaneous for 12 weeks.
Treatment groups
220 Participants
are divided into 2 treatment groupsGroup A: ExperimentalExperimental treatment 2 interventions
Group B: ControlActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
Percentage of patients in remission
Percentage of patients in remission defined by DAS28-CRP\<2.6 score during the 36 weeks following randomization. Disease Activity Score-28 with C-Reactive Protein (DAS28-CRP) describes severity of rheumatoid arthritis using clinical and laboratory data, specifically CRP. It includes 4 variables (number of painful joints out of 28 joints, number of swollen joints out of 28 joints, global assessment of the disease by the patient on a Visual Analogue Scale (VAS), markers of inflammation : CRP) A DAS28-CRP score \> 5.1 means high disease activity, DAS28-CRP \< or = 3.2 indicates low disease activity, a DAS28-CRP \< 2.6 indicates disease remission.
Time frame
36 weeks following randomizationSecondary outcomes
1
percentage of patients in remission at 12 weeks after randomization (DAS28-ESR)
Percentage of patients in remission using definition : DAS28-ESR\<2.6, at 12 weeks after randomization Disease Activity Score-28 with Erythrocyte Sedimentation Rate (DAS28-ESR) describes severity of rheumatoid arthritis using clinical and laboratory data, specifically ESR.
Time frame
At 24 weeks visit (corresponding to 12 weeks after randomization)2
percentage of patients in remission at 12 weeks after randomization (CDAI)
Percentage of patients in remission using definition : CDAI≤2.8, at 12 weeks after randomization Clinical Disease Activity Index (CDAI) is a useful clinical composite score. It's the sum of 4 parameters : Swollen 28-Joint + Tender 28-Joint Count + Patient Global disease Activity + Evaluator's Global disease Activity. Remission is defined as an CDAI of ≤2.8, low disease activity as \>2.8 and ≤10, moderate disease activity as \>10 and ≤22 and high disease activity as \>22.
Time frame
At 24 weeks visit (corresponding to 12 weeks after randomization)3
percentage of patients in remission at 12 weeks after randomization (SDAI)
Percentage of patients in remission using definition : SDAI≤3.3, at 12 weeks after randomization Score Disease Activity Index (SDAI) is the sum of 5 parameters: the number of painful joints and synovitis (28 joints are tested) the global assessment of the patient and the therapist on a visual
Time frame
At 24 weeks visit (corresponding to 12 weeks after randomization)4
percentage of patients in remission at 12 weeks after randomization (Boolean)
Percentage of patients in remission using definition: Boolean criteria, at 12 weeks after randomization Boolean criteria of remission are : number of tender and swollen joint, visual analogue scale for global health and CRP all ≤1
Time frame
At 24 weeks visit (corresponding to 12 weeks after randomization)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov