In the Multicenter Randomized Controlled Rotation or Change Trial, a Non-TNF Targeted Therapy Has a Higher Efficacy Than a Second Anti-TNF at 3, 6 and 12 Months

Jacques Gottenberg¹, Olivier Brocq², Aleth Perdriger³, Slim Lassoued⁴, Jean-Marie Berthelot⁵, Daniel Wendling⁶, Liana Euller-Ziegler⁷, Martin Soubrier⁸, Christophe Richez⁹, Bruno Fautrel¹⁰, Arnaud Constantin¹¹, Xavier Mariette¹², Jacques Morel¹³, Mélanie Gilson¹⁴, Gregoire Cormier¹⁵, Jean Hugues Salmon¹⁶, Stephanie Rist Bouillon¹⁷, Frederic Lioté¹⁸, Hubert Marotte¹⁹, Christine Bonnet²⁰, Christian Marcelli²¹, Jeremie Sellam²², Olivier Meyer²³, Elisabeth Solau-Gervais²⁴, Sandrine Guis²⁵, Jean Marc Ziza²⁶, Charles Zarnitsky²⁷, Isabelle Chary-Valckenaere²⁸, O Vittecoq²⁹, Alain Saraux³⁰, Yves-Marie Pers³¹, Martine Gayraud³², Gilles Bolla³³, Pascal Claudepierre³⁴, Marc Ardizzone³⁵, Emmanuelle Dernis Labous³⁶, Maxime A. Breban³⁷, Olivier Fain³⁸, Jean Charles Balblanc³⁹, Ouafaa Aberkane⁴⁰, Marion Vazel⁴⁰, Christelle Back⁴⁰, Elodie Perrodeau⁴¹, Jean Sibilia⁴² and Philippe Ravaud³², ¹Hautepierre, Strasbourg, France, ²Hospital Center Princesse Grâce, Monaco, Monaco, ³Service de Rhumatologie, CHU de Rennes, Rennes, France, ⁴Rheumatology, Cahors, France, ⁵Rheumatology, University Hospital, Nantes, France, ⁶Université de Franche-Comté, Besançon, France, ⁷Rheumatology, Nice, France, ⁸Rheumatology department CHU Clermont-Ferrand, Clermont-Ferrand, France, ⁹Rheumatology, Bordeaux, France, ¹⁰Rheumatology, AP-HP Pitié-Salpêtrière Hospital / Pierre and Marie Curie University Paris 6 GRC-08 (EEMOIS), Paris, France, ¹¹Rheumatology, CHU Purpan - Hopital Pierre-Paul Riquet, Toulouse, France, ¹²Université Paris-Sud, AP-HP, Hôpitaux Universitaires Paris-Sud, Paris, France, ¹³Department of rheumatology, Lapeyronie Hospital and Montpellier University, Montpellier, France, ¹⁴Hospital Center, Grenoble, France, ¹⁵Rheumatology, La Roche Sur Yon, France, ¹⁶Hôpital Maison Blanche, Rheumatology, REIMS, France, ¹⁷Rhumatologie, Hopital La Source, La Source, France, ¹⁸Rheumatology, Lariboisière, France, ¹⁹INSERM 1059 / LBTO, Université de Lyon, Saint-Etienne; Rheumatology Department, Saint-Etienne, France, ²⁰Rheumatology, CHU Dupuytren, Limoges, France, ²¹Rheumatology, Caen, France, ²²Rheumatology, PARIS, France, ²³Rheumatology, Hopital Bichat, Paris, France, ²⁴Rhumatologie, University Hospital, Poitiers, France, ²⁵Rheumatology, Marseille, France, ²⁶Hopital Croix-Saint-Simon, Paris Cedex 20, France, ²⁷Rheumatology, Le Havre, France, ²⁸Rheumatology, Nancy, France, ²⁹University Hospital, Rouen, France, ³⁰Rheumatology, Brest, France, ³¹Rheumatology, Montpellier, France, ³²Rheumatology, Paris, France, ³³Rheumatology, Cannes, France, ³⁴Rheumatology, Université Paris Est Créteil, Créteil, France, ³⁵Rheumatology, Centre Hospitalier de Mulhouse, Mulhouse, France, ³⁶Réseau Hôpital et Ville en Rhumatologie (RHEVER) Network, Paris, France, ³⁷Rheumatology, A. Paré University Hospital, Boulogne-Billancourt, France, ³⁸Internal Medicine Department, Saint Antoine Hospital, Paris, France, ³⁹Rheumatology, Belffort, France, ⁴⁰Rheumatology, Strasbourg, France, ⁴¹Epidemiologist, Paris, France, ⁴²Department of Rheumatology, Strasbourg University Hospital, Strasbourg, France

Meeting: ACR/ARHP Annual Meeting 2015

Date of first publication: September 29, 2015

Keywords: Biologic drugs, randomized trials and rheumatoid arthritis (RA)

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis-Small Molecules, Biologics and Gene Therapy V: Immunogenecity

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose:

As many as one third of patients show insufficient response to their first TNF inhibitor (TNF-insufficient response, TNF-IR). The lack of efficacy of one anti-TNF drug does not preclude the potential efficacy of another anti-TNF drug. Alternatively, switching to a non-TNF-targeted therapy is also a rationale strategy. These 2 strategies (a second anti-TNF agent or a non-TNF targeted therapy) have only been compared in scarce observational studies in TNF-IR patients. However, no randomized controlled trial has compared the efficacy of a non-TNF-targeted biologic and a second anti-TNF drug in TNF-IR patients. We previously presented the preliminary results at 6 months. We now present the final 12 month-results of the trial.

Methods:

The “Rotation of anti-TNF Or Change of class of biologic” (ROC) trial (NCT01000441) is a multicenter,investigator-initiated, open, parallel-group, randomized controlled trial. Patients with inadequate response to a first anti-TNF were randomly assigned in a 1:1 ratio to receive a non-TNF-targeted biologic or a second anti-TNF agent. The choice of the biologic prescribed within each randomized group (ie, non-TNF-targeted biologic or a second anti-TNF agent) was left to the treating clinician. The study duration was 48 weeks.

Results:

Week 12

At week 12 (W12), for patients randomized to a non-TNF-targeted biologic (n=146) or a second anti-TNF agent (n=146), 64.2% and 47.8%, respectively, achieved a good or moderate EULAR response (good response: 27.7% and 13.2%, respectively; moderate response: 36.5% and 34.6%, respectively) (OR 2.01, 95% CI [1.23; 3.32], p = 0.005).

Week 24

At W24 (primary outcome), 69.7% and 52.1%, respectively, achieved a good or moderate EULAR response (good response: 39.4% and 21.1%, respectively; moderate response: 30.3% and 31.0%) (OR 2.12, 95%confidence interval [95% CI] [1.31; 3.46], p=0.003). At W24, DAS28-ESR was lower for patients with the non-TNF-targeted biologic than second anti-TNF drug (difference adjusted to baseline value -0.43, 95% CI [-0.72; ‑0.14], p= 0.004). The proportion with low disease activity was 44.6% and 27.9%, respectively (OR 2.09, 95%CI [1.27; 3.43], p= 0.004).

Week 48

At W48, 60.0% of patients treated with a non TNF-targeted biologic and 43.2% of those treated with a second anti-TNF were EULAR responders (good response: 37.7% and 21.2%, respectively; moderate response: 22.3 and 22.0%, respectively) (OR 1.97 (95%CI [1.21; 3.24], p = 0.007). DAS28-ESR was lower for patients with the non-TNF-targeted biologic than second anti-TNF drug (difference adjusted to baseline value -0.38, 95% CI [-0.69; ‑0.08], p= 0.013). The proportion with low disease activity was 40.8% and 23.5%, respectively (OR 2.24, 95%CI [1.32; 3.82], p= 0.003). The proportion with DAS28-ESR remission was 26.9% and 13.6%, respectively (OR 2.34, 95% CI [1.24; 4.39], p= 0.009. Ongoing comparison of radiographic progression and safety will be also presented at ACR.

Conclusion: This randomized controlled trial demonstrated a better efficacy of a non-TNF-targeted biologic than a second anti-TNF agent for TNF-IR patients. This superiority was consistent over time and across numerous outcome criteria.

Disclosure: J. Gottenberg, Abbvie, MSD, Pfizer, UCB, Roche, 9; O. Brocq, None; A. Perdriger, None; S. Lassoued, None; J. M. Berthelot, None; D. Wendling, None; L. Euller-Ziegler, None; M. Soubrier, None; C. Richez, None; B. Fautrel, None; A. Constantin, None; X. Mariette, None; J. Morel, None; M. Gilson, None; G. Cormier, None; J. H. Salmon, None; S. Rist Bouillon, None; F. Lioté, None; H. Marotte, None; C. Bonnet, None; C. Marcelli, None; J. Sellam, None; O. Meyer, None; E. Solau-Gervais, None; S. Guis, None; J. M. Ziza, None; C. Zarnitsky, None; I. Chary-Valckenaere, None; O. Vittecoq, None; A. Saraux, None; Y. M. Pers, None; M. Gayraud, None; G. Bolla, None; P. Claudepierre, None; M. Ardizzone, None; E. Dernis Labous, None; M. A. Breban, None; O. Fain, None; J. C. Balblanc, None; O. Aberkane, None; M. Vazel, None; C. Back, None; E. Perrodeau, None; J. Sibilia, None; P. Ravaud, None.

To cite this abstract in AMA style:

Gottenberg J, Brocq O, Perdriger A, Lassoued S, Berthelot JM, Wendling D, Euller-Ziegler L, Soubrier M, Richez C, Fautrel B, Constantin A, Mariette X, Morel J, Gilson M, Cormier G, Salmon JH, Rist Bouillon S, Lioté F, Marotte H, Bonnet C, Marcelli C, Sellam J, Meyer O, Solau-Gervais E, Guis S, Ziza JM, Zarnitsky C, Chary-Valckenaere I, Vittecoq O, Saraux A, Pers YM, Gayraud M, Bolla G, Claudepierre P, Ardizzone M, Dernis Labous E, Breban MA, Fain O, Balblanc JC, Aberkane O, Vazel M, Back C, Perrodeau E, Sibilia J, Ravaud P. In the Multicenter Randomized Controlled Rotation or Change Trial, a Non-TNF Targeted Therapy Has a Higher Efficacy Than a Second Anti-TNF at 3, 6 and 12 Months [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/in-the-multicenter-randomized-controlled-rotation-or-change-trial-a-non-tnf-targeted-therapy-has-a-higher-efficacy-than-a-second-anti-tnf-at-3-6-and-12-months/. Accessed .

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