Detail Article

Informations générales (source: ClinicalTrials.gov)

Numéro NCT

NCT03227419 En recrutement IDF

Titre

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 (SUNSTAR)

Type

Interventional

Pathologie

Arthrite
Polyarthrite rhumatoïde

Phase

Phase 4

Promoteur

Lille Catholic University (Voir sur ClinicalTrials)

Date de début

janvier 2018

Date de fin

novembre 2024

Dernière mise à jour

29 juin 2024

Résumé

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.

Détail

Voir le détail 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 as well as progressive structural damage resulting in major joint deformity. Biologic agents are taking on an increasingly important role in the management of patients with an inadequate response to conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). Biological DMARD (bDMARD) therapy consists in the use of monoclonal antibodies or fusion proteins, administered intravenously or subcutaneously. The earliest developed biologic agents have been available for more than 15 years. Tumor necrosis factor alpha (TNFα), a pro-inflammatory cytokine, was the first cytokine successfully targeted by a biologic agent for RA treatment. TNF inhibitors (TNFi) are historically proposed as the first bDAMRD for inadequate responder patients to csDMARDs. More recently non-anti-TNFα drugs have emerged, with other biological targets such as interleukin-6 receptor (tocilizumab) or B- (rituximab) and T-lymphocytes (abatacept) that are implicated in the inflammatory response. Initially administered strictly intravenously, these drugs are now available in formulations adapted to subcutaneous administration, which allows ambulatory care for patients who otherwise would require repeated in-hospital care. National and international guidelines, especially those issued in 2013 by the European League Against Rheumatism (EULAR) and also in 2013 by the French Society of Rheumatology now recommend first-line treatment not only with TNFi but also with non-anti-TNFα biologic agents. However, in routine practice, most clinicians preferably prescribe TNFi for the first-line regimen, reserving non-anti-TNFα drugs to TNFi inadequate responder patients. There is a growing body of research focusing on first-line biologic agents but there is very little solid data on the direct randomized comparison between them. Actually, all three of the published studies have systematically compared a non-anti-TNFα biomedication versus TNFi (one study with a blinded design and two open studies). The therapeutic strategy that should be adapted after failure of a TNFi regimen has also been investigated. Those studies favor non-anti-TNF drugs over an alternate TNFi. There is adequate evidence of the efficacy of the different non-anti-TNFα biologic agents versus placebo after TNFi failure. In other hands, industrial trials have not provided any comparative data between drugs. An academic trial from The Netherlands using medico-economic performance as the primary outcome found no difference in efficacy between abatacept and rituximab (a non-anti-TNFα drug administered exclusively intravenously) after failure of a TNFi. Meta-analyses using data from care networks have not reported any difference between different non-anti-TNFα drugs after failure of a TNFi. Data from national registries have provided interesting complementary information since in everyday practice these agents are generally used after failure of at least one TNFi. The Danish registry thus suggests that the therapeutic response would be better with tocilizumab than with abatacept. This observation was confirmed by an analysis of French registries data presented at the American College of Rheumatology (ACR) congress in November 2016 showing that tocilizumab exhibits superiority for treatment persistence over 2 years. These results were fully in agreement with the findings of the French ROC trial comparing intravenous administration of a second anti-TNFα drug versus a non-anti-TNFα agent after failure of an anti-TNFα drug that suggested a superiority of tocilizumab over abatacept in the subgroup of patients given a non-anti-TNFα agent. A recent Bayesian network meta-analysis showed better efficacy in the non-anti-TNFα groups for ACR20 in patients who responded insufficiently to an anti-TNFα. Subcutaneous formulations have been recently developed for both tocilizumab and abatacept. Subcutaneous administration is important because it enables ambulatory care for a substantial number of patients who to date are recurrently hospitalized in day-care units for their intravenous infusions. Excepting specific situations, the subcutaneous formulation will be favored for a large majority of patients because of economic as well as practical considerations. Phase III trials have demonstrated the equivalence of the intravenous versus subcutaneous routes of administration focusing on efficacy and tolerance. The subcutaneous formulation is now also available for routine administration of both tocilizumab and abatacept. Nevertheless, despite large-scale industrial trials on drug equivalence, data issuing from clinical practice suggest a potential difference in the behavior of these two formulations which needs to be explored. Rituximab is apart in the treatment strategy because of its exclusive intravenous administration at spaced intervals and because it is used for specific patient profiles (extra-articular involvement, history of neoplasia, rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity). There is no perspective for the development of a subcutaneous formulation of rituximab for RA patients. Furthermore, the routine treatment schedule for rituximab (one-time injections at a mean interval of 9 months) would compromise comparison, especially short-term comparison, with other subcutaneous treatments. These findings illustrate the need for a new multicentric, prospective, randomized trial designed to demonstrate the superiority of tocilizumab over abatacept in patients exhibiting inadequate response to a first anti-TNFα. A direct comparison of subcutaneous formulation is the need for the promising route of administration for future ambulatory care. Fermer le détail

Etablissements

Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données
HOPITAL NOVO	PERTUISET	En recrutement IDF	04/07/2024 11:05:06	Contacter
Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
AP-HP - Hôpital Avicenne	Luca SEMERANO, MD	En recrutement IDF		Contact (sur clinicalTrials)
AP-HP - Hôpital Bichat	Sébastien OTTAVIANI, MD	En recrutement IDF		Contact (sur clinicalTrials)
AP-HP - Hôpital Cochin	Jérôme AVOUAC, MD, Pr	En recrutement IDF		Contact (sur clinicalTrials)
Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
Ch Cahors - Cahors - France	Slim LASSOUED, MD	En recrutement		Contact (sur clinicalTrials)
CH de Boulogne-sur-Mer - Boulogne-sur-Mer - France	Renaud DESBARBIEUX, MD	En recrutement		Contact (sur clinicalTrials)
CH de Valenciennes - Valenciennes - France	Xavier DEPREZ, MD	En recrutement		Contact (sur clinicalTrials)
CHD Vendée - La Roche-sur-Yon - France	Grégoire CORMIER, MD	En recrutement		Contact (sur clinicalTrials)
CHRU de Lille - Lille - France	René-Marc FLIPO, MD, Pr	En recrutement		Contact (sur clinicalTrials)
CHRU de Strasbourg - Strasbourg - France	Jacques-Eric GOTTENBERG, MD, Pr	En recrutement		Contact (sur clinicalTrials)
CHU de Bordeaux - Bordeaux - France	Marie-Elise TRUCHETET, MD	En recrutement		Contact (sur clinicalTrials)
CHU de Clermont-Ferrand - Clermont-Ferrand - France	Martin SOUBRIER, MD, Pr	En recrutement		Contact (sur clinicalTrials)
CHU de Grenoble Hôpital Sud - Grenoble - France	Athan BAILLET, MD, Pr	En recrutement		Contact (sur clinicalTrials)
CHU de Montpellier - Montpellier - France	Jacques MOREL, MD, Pr	En recrutement		Contact (sur clinicalTrials)
CHU de Poitiers - Poitiers - France	Elisabeth GERVAIS, MD, Pr	En recrutement		Contact (sur clinicalTrials)
CHU de Reims - Reims - France	Jean-Hugues SALMON, MD	En recrutement		Contact (sur clinicalTrials)
CHU de Saint-Etienne - Saint-Étienne - France	Hubert MAROTTE, MD	En recrutement		Contact (sur clinicalTrials)
CHU de Tours - Tours - France	Isabelle GRIFFOUL, MD	En recrutement		Contact (sur clinicalTrials)
CHU Nice - Nice - France	Véronique BREUIL, MD, Pr	En recrutement		Contact (sur clinicalTrials)
CHU Rouen - Rouen - France	Olivier VITTECOQ, MD, Pr	En recrutement		Contact (sur clinicalTrials)
CHU Saint-Etienne - Saint-Étienne - France	Hubert MAROTTE, MD	En recrutement		Contact (sur clinicalTrials)
Clinique Infirmerie Protestante de Lyon - Lyon - France	André BASCH, MD	En recrutement		Contact (sur clinicalTrials)
Hôpital Bicêtre - Le Kremlin-Bicêtre - France	Xavier MARIETTE, MD, Pr	En recrutement		Contact (sur clinicalTrials)
Hôpital de la Pitié-Salpêtrière - Paris - France	Bruno FAUTREL, MD, Pr	En recrutement		Contact (sur clinicalTrials)
Hôpital Lariboisière - Paris - France	Pascal RICHETTE, MD, Pr	En recrutement		Contact (sur clinicalTrials)
Hôpital Saint-Philibert - 59462 - Lomme - Hauts De France - France	Tristan Pascart, MD, PhD	En recrutement		Contact (sur clinicalTrials)

Critères

Genre

Tous

Nombre d'inclusion

Critère d'inclusion

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

Critère de non inclusion

- 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

NCT03227419 - 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 (SUNSTAR)

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