Arthritis, Rheumatoid Clinical Trial
— SUNSTAROfficial title:
Abatacept Versus Tocilizumab by Subcutaneous Administration for the Treatment of Rheumatoid Arthritis in TNF Alpha Inhibitor Inadequate Responder Patients: A Randomized, Open-labeled, Superiority Trial
Rheumatoid arthritis (RA) is the most common inflammatory rheumatoid disease in France, affecting 0.3% of the general population. Without effective treatment, the persistent inflammation causes invalidating pain and joint destruction, leading to major functional disability. Biological agents have been proposed for patients with RA who have the most severe form of the disease and that are inadequate responder patients to conventional synthetic Disease-modifying antirheumatic drugs (csDMARDs). TNF inhibitors (TNFi) are historically proposed as the first biological DAMRD for inadequate responder patients to csDMARDs. A diverse therapeutic arsenal has become available in recent years with the development of non-anti-TNFα drugs whose mechanisms of action are different from the classical TNFi. This new biotherapy class includes tocilizumab and abatacept, two drugs recently available for subcutaneous administration that enables ambulatory care for patients who would otherwise require repeated in-hospital care. The role of these new treatments in the therapeutic strategy has been emphasized by studies that demonstrated their efficacy as first-line treatments. However, in clinical practice, TNFi remain the most common first-line treatment for the majority of patients, non-anti-TNFα biological agents being reserved for inadequate responder patients. In second line, several studies have investigated therapeutic strategies for inadequate responder patients to TNFi. Current data suggest that it could be wise to change the therapeutic target after failure of a first-line treatment with TNFi. Data about the comparative efficacy of different biologics proposed after failure of a first-line treatment with TNFi are in progress. Meta-analyses from registries and academic trials conducted in France and The Netherlands suggest that non-anti-TNFα agents would have equivalent or superior efficacy compared with a second TNFi. This finding suggests clinicians to switch for an alternate therapeutic target after failure of a first-line TNFi. Data comparing different non-anti-TNFα biologics in inadequate responder patients to TNFi are scare. Industrial trials have demonstrated sustained biological efficacy of non-anti-TNFα biologics after failure of a TNFi. However, there is very little solid data on the direct comparison between them.
Status | Recruiting |
Enrollment | 224 |
Est. completion date | November 2024 |
Est. primary completion date | September 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - age >18 years - RA according to the ACR/EULAR 2010 criteria - inadequate response to a subcutaneously administered first-line TNFi defined as moderate to high disease activity (DAS28-ESR>3.2 and CDAI>10) after at least 3 months of treatment with a TNFi - beneficiary of the French National Health Insurance Fund - signed informed consent form - for women of childbearing age: effective contraception during treatment period with engagement to continue such contraception for 14 weeks after last administration Exclusion Criteria: - counter-indication for one or other of the two drugs under study - prior failure of the TNFi due to intolerance - receiving =15 mg/day prednisone for more than 4 weeks - pregnant or nursing women |
Country | Name | City | State |
---|---|---|---|
France | Hôpital Avicenne | Bobigny | |
France | CHU de Bordeaux | Bordeaux | |
France | CH de Boulogne-sur-Mer | Boulogne-sur-Mer | |
France | Ch Cahors | Cahors | |
France | CHU de Clermont-Ferrand | Clermont-Ferrand | |
France | CHU de Grenoble Hôpital Sud | Grenoble | |
France | CHD Vendée | La Roche-sur-Yon | |
France | Hôpital Bicêtre | Le Kremlin-Bicêtre | |
France | CHRU de Lille | Lille | |
France | Hôpital Saint-Philibert | Lomme | Hauts De France |
France | Clinique Infirmerie Protestante de Lyon | Lyon | |
France | CHU de Montpellier | Montpellier | |
France | CHU Nice | Nice | |
France | CHU Bichat | Paris | |
France | Hôpital Cochin | Paris | |
France | Hôpital de la Pitié-Salpêtrière | Paris | |
France | Hôpital Lariboisière | Paris | |
France | CHU de Poitiers | Poitiers | |
France | CH René-Dubos | Pontoise | |
France | CHU de Reims | Reims | |
France | CHU Rouen | Rouen | |
France | CHU de Saint-Etienne | Saint-Étienne | |
France | CHU Saint-Etienne | Saint-Étienne | |
France | CHRU de Strasbourg | Strasbourg | |
France | CHU de Tours | Tours | |
France | CH de Valenciennes | Valenciennes |
Lead Sponsor | Collaborator |
---|---|
Lille Catholic University |
France,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change from baseline to 6 months of the Clinical Disease Activity Index (CDAI) | The CDAI is a composite score combining clinical items only: Tender 28-joint count, Swollen 28-joint count, Patient Global Disease Activity (PGA), Evaluator"s Global Disease Activity (EGA). This score provides a numerical assessment reflecting disease activity independently of cute phase reactants. It will be measured at baseline and 6 months after inclusion |
6 months | |
Secondary | Change from baseline of the disease activity score | DAS28-ESR and DAS28-CRP: the disease activity score (DAS) is a composite score providing a numerical assessment based on the tender and swollen joint counts, the PGA VAS and the selected acute phase reactant (ESR or CRP). | 3, 6 and 12 months | |
Secondary | Change from baseline of the Clinical Disease Activity Index (CDAI) | The CDAI is a composite score combining clinical items only: Tender 28-joint count, Swollen 28-joint count, Patient Global Disease Activity (PGA), Evaluator"s Global Disease Activity (EGA). This score provides a numerical assessment reflecting disease activity independently of cute phase reactants. | 3 and 12 months | |
Secondary | Change from baseline of the SDAI | the simple disease activity index (SDAI) is a composite score providing a numerical assessment based on the tender and swollen joint count, the PGAVAS, the EGA VAS, and CRP | 3, 6 and 12 months | |
Secondary | Change from baseline in HAQ quality-of-life scores | 3, 6 and 12 months | ||
Secondary | Change from baseline in SF-36 quality-of-life scores | 3, 6 and 12 months | ||
Secondary | Change from baseline in disease self assessment | FLARE-RA score | 3, 6 and 12 months | |
Secondary | Change from baseline in Patient's Pain Assessment (PPA) | 3, 6 and 12 months | ||
Secondary | Change from baseline in PGA visual analogic scale (VAS) | 3, 6 and 12 months | ||
Secondary | Proportion of patients having achieved low disease activity | Low disease activity (LDA) is defined as DAS28-ESR<3.2 (LDA-DAS28-ESR) and CDAI<10 (LDA-CDAI) | 3, 6 and 12 months | |
Secondary | Proportion of patients in good or moderate EULAR therapeutic response | Good or moderate EULAR therapeutic response is defined as at least 0.6-point reduction in DAS28-ESR and final DAS28-ESR<5.1 | 3, 6 and 12 months | |
Secondary | Proportion of patients achieving ACR20 response | ACR20 response correspond to a 20% improvement in the following parameters: number of tender joints; number of swollen joints; 3/5 complementary items (PPA VAS, PGA VAS, EGA VAS, self-administered functional status questionnaire, acute phase reactant) | 3, 6 and 12 months | |
Secondary | Proportion of patients achieving ACR50 response | ACR50 responses correspond respectively to a 50% improvement in the following parameters: number of tender joints; number of swollen joints; 3/5 complementary items (PPA VAS, PGA VAS, EGA VAS, self-administered functional status questionnaire, acute phase reactant) | 3, 6 and 12 months | |
Secondary | Proportion of patients achieving ACR70 response | ACR70 response correspond respectively to a 70% improvement in the following parameters: number of tender joints; number of swollen joints; 3/5 complementary items (PPA VAS, PGA VAS, EGA VAS, self-administered functional status questionnaire, acute phase reactant) | 3, 6 and 12 months | |
Secondary | Rates of treatment persistence | 3, 6 and 12 months | ||
Secondary | Rates of patients presenting at least one adverse events | 3, 6 and 12 months | ||
Secondary | Rates of treatment withdrawals for intolerance | 3, 6 and 12 months | ||
Secondary | Rates of treatment withdrawals for intolerance requiring in-hospital care | 3, 6 and 12 months | ||
Secondary | Rates of cardiovascular events | 3, 6 and 12 months | ||
Secondary | Rates of perturbation of the lipid profile | 3, 6 and 12 months | ||
Secondary | Rates of severe infection requiring in-hospital care | 3, 6 and 12 months | ||
Secondary | Rate of rescue medication use authorized by the protocol and treatment dose of patients achieving treatment persistence | 3, 6 and 12 months | ||
Secondary | Changes in joint US-Doppler synovitis and Doppler hyperemia grade of the hands and wrists | 6 months | ||
Secondary | Changes in Sharp score in hands, wrists and feet X-Ray | 12 months | ||
Secondary | Change in vascular endothelial growth factor (VEGF) levels | At 3 and 6 months | ||
Secondary | Changes in immunoglobulin (quantitative assay) | 6 months | ||
Secondary | Changes in interleukin-6 serum levels | 6 months |
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