Bruno Fautrel1, Thao Pham2, Toni Alfaiate3, Frédérique Gandjbakhch1, Violaine Foltz1, Jacques Morel4, Emmanuelle Dernis5, Philippe Gaudin6, Olivier Brocq7, Elisabeth Solau-Gervais8, Jean-Marie Berthelot9, Jean-Charles Balblanc10, Xavier Mariette11, Florence Tubach12. 1. Pierre et Marie Curie University-Paris 6, Sorbonne Universités, GRC-08 (EEMOIS), Paris, France APHP, Rheumatology Department, Pitié Salpêtrière Hospital, Paris, France. 2. Aix-Marseille University, Marseille, France AP-HM, Rheumatology Department, Sainte Marguerite Hospital, Marseille, France. 3. APHP, Department of Epidemiology and Clinical Research, Hôpital Bichat, Paris, France INSERM CIC-EC 1425, Paris, France. 4. Rheumatology Department, Montpellier 1 University, Lapeyronie Hospital, Montpellier, France. 5. Rheumatology Department, Le Mans Hospital, Le Mans, France. 6. Rheumatology Department, Joseph Fourrier University, Sud Hospital, Grenoble, France. 7. Rheumatology Department, Princess Grace Health Centre, Monaco, Monaco. 8. University of Poitiers, Poitiers, France Rheumatology Department, La Miletrie Hospital, Poitiers, France. 9. University of Nantes, Nantes, France Rheumatology Department, Hotel-Dieu Hospital, Nantes, France. 10. Rheumatology Department, Belfort-Montbeliard Health Center, Belfort, France. 11. Paris Sud University-Paris 11, Le Kremlin Bicêtre, France AP-HP, Rheumatology Department, Bicêtre Hospital, Le Kremlin Bicêtre, France. 12. Aix-Marseille University, Marseille, France University Paris Diderot, Sorbonne Paris Cité, UMR 1123, Paris, France.
Abstract
UNLABELLED: Tumour necrosis factor (TNF)-blocker tapering has been proposed for patients with rheumatoid arthritis (RA) in remission. OBJECTIVE: The trial aims to compare the effect of progressive spacing of TNF-blocker injections (S-arm) to their maintenance (M-arm) for established patients with RA in remission. METHODS: The study was an 18-month equivalence trial which included patients receiving etanercept or adalimumabat stable dose for ≥1 year, patients in remission on 28-joint Disease Activity Score (DAS28) for ≥6 months and patients with stable joint damage. Patients were randomised into two arms: maintenance or injections spacing by 50% every 3 months up to complete stop. Spacing was reversed to the previous interval in case of relapse, and eventually reattempted after remission was reachieved. The primary outcome was the standardised difference of DAS28 slopes, based on a linear mixed-effects model (equivalence interval set at ±30%). RESULTS: 64 and 73 patients were included in the S-arm and M-arm, respectively, which was less than planned. In the S-arm, TNF blockers were stopped for 39.1%, only tapered for 35.9% and maintained full dose for 20.3%. The equivalence was not demonstrated with a standardised difference of 19% (95% CI -5% to 46%). Relapse was more common in the S-arm (76.6% vs 46.5%, p=0.0004). However, there was no difference in structural damage progression. CONCLUSIONS: Tapering was not equivalent to maintenance strategy, resulting in more relapses without impacting structural damage progression. Further studies are needed to identify patients who could benefit from such a strategy associated with substantial cost savings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00780793; EudraCT identifier: 2007-004483-41. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
RCT Entities:
UNLABELLED: Tumour necrosis factor (TNF)-blocker tapering has been proposed for patients with rheumatoid arthritis (RA) in remission. OBJECTIVE: The trial aims to compare the effect of progressive spacing of TNF-blocker injections (S-arm) to their maintenance (M-arm) for established patients with RA in remission. METHODS: The study was an 18-month equivalence trial which included patients receiving etanercept or adalimumab at stable dose for ≥1 year, patients in remission on 28-joint Disease Activity Score (DAS28) for ≥6 months and patients with stable joint damage. Patients were randomised into two arms: maintenance or injections spacing by 50% every 3 months up to complete stop. Spacing was reversed to the previous interval in case of relapse, and eventually reattempted after remission was reachieved. The primary outcome was the standardised difference of DAS28 slopes, based on a linear mixed-effects model (equivalence interval set at ±30%). RESULTS: 64 and 73 patients were included in the S-arm and M-arm, respectively, which was less than planned. In the S-arm, TNF blockers were stopped for 39.1%, only tapered for 35.9% and maintained full dose for 20.3%. The equivalence was not demonstrated with a standardised difference of 19% (95% CI -5% to 46%). Relapse was more common in the S-arm (76.6% vs 46.5%, p=0.0004). However, there was no difference in structural damage progression. CONCLUSIONS: Tapering was not equivalent to maintenance strategy, resulting in more relapses without impacting structural damage progression. Further studies are needed to identify patients who could benefit from such a strategy associated with substantial cost savings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00780793; EudraCT identifier: 2007-004483-41. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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