Interest of Assessing Anti-Drug Antibodies for the Choice Between a Second Anti-TNF and a Non-TNF-Targeted Biologic in Patients with Inadequate Response to a First Anti-TNF : Results from the Randomized Controlled Trial « Rotation or Change »

Sophie Candon¹, Lucienne Chatenoud¹, 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 Liote¹⁸, Hubert Marotte¹⁹, Christine Bonnet²⁰, Christian Marcelli²¹, Jeremie Sellam¹, Olivier Meyer²², Elisabeth Solau-Gervais²³, Sandrine Guis²⁴, Jean Marc Ziza²⁵, Charles Zarnitsky²⁶, Isabelle Chary-Valckenaere²⁷, O Vittecoq²⁸, Alain Saraux²⁹, Yves-Marie Pers³⁰, Martine Gayraud³¹, Gilles Bolla³², Pascal Claudepierre³³, Marc Ardizzone³⁴, Emmanuelle Dernis Labous³⁵, Maxime A. Breban³⁶, Olivier Fain³⁷, Jean Charles Balblanc³⁸, Elodie Perrodeau³⁹, Jean Sibilia⁴⁰, Philippe Ravaud³¹ and Jacques Gottenberg⁴¹, ¹Rheumatology, PARIS, 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, Hopital Bichat, Paris, France, ²³Rhumatologie, University Hospital, Poitiers, France, ²⁴Rheumatology, Marseille, France, ²⁵Hopital Croix-Saint-Simon, Paris Cedex 20, France, ²⁶Rheumatology, Le Havre, France, ²⁷CHU de Nancy, Rheumatology, Nancy, France, ²⁸University Hospital, Rouen, France, ²⁹Rheumatology, Brest, France, ³⁰Rheumatology, Montpellier, France, ³¹Rheumatology, Paris, France, ³²Rheumatology, Cannes, France, ³³Rheumatology, Université Paris Est Créteil, Créteil, France, ³⁴Rheumatology, Centre Hospitalier de Mulhouse, Mulhouse, France, ³⁵Réseau Hôpital et Ville en Rhumatologie (RHEVER) Network, Paris, France, ³⁶Rheumatology, A. Paré University Hospital, Boulogne-Billancourt, France, ³⁷Internal Medicine Department, Saint Antoine Hospital, Paris, France, ³⁸Rheumatology, Belffort, France, ³⁹Epidemiologist, Paris, France, ⁴⁰Department of Rheumatology, Strasbourg University Hospital, Strasbourg, France, ⁴¹Hautepierre, Strasbourg, France

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: anti-TNF therapy

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: Anti-drug antibodies (ADAs) might result in loss of efficacy to anti-TNF. The impact of ADAs to a 1st anti-TNF on subsequent response to a second biologic has never been assessed in the setting of a randomized controlled trial. The “Rotation of anti-TNF Or Change of class of biologic” (ROC) trial showed a better efficacy at 6 months of a non-TNF-targeted biologic than a second anti-TNF. In a post-hoc analysis, we investigated the potential usefulness of assessing anti-drug antibodies to guide the choice of the second biologic in TNF-IR patients.

Methods: The 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 (abatacept, rituximab or tocilizumab) or a second anti-TNF agent. Anti-TNF drug concentration in serum was measured using solid phase ELISA assays based on the capture of infliximab, adalimumab, golimumab, certolizumab with plate-bound recombinant TNF-a. For infliximab and adalimumab, the detection of anti-drug antibodies (ADAb) was performed by a homemade assay based on the ability of anti-idiotypic antibodies to neutralize anti-TNF drug activity and inhibit its capture by TNF-alpha (Candon S, et al. 2006). For the other anti-TNF, commercial tests were used. (Shikari, Eurobio for anti-etanercept ADAs, Lisa-Tracker kits (Theradiag, France) for anti-golimumab and anti-certolizumab ADAs).

Results: ADAs were assessed in 278 patients. In 19 (6.8%) patients, ADAs could not be detected because of persistent levels of the 1st anti-TNF. No ADA was detected in 227 (81.7%) patients. Presence of ADAs was detected in 32 (11.5%) of patients (anti-adalimumab: 20 patients ; anti-certolizumab : 2 patients ; anti-golimumab : 1 patient ; anti-infliximab: 9 patients). In all these patients with ADAs, blood levels of the 1st anti-TNF were very low or indetectable. Among the 120 patients randomized to a 2d anti-TNF and assessed for ADAs, 12 had ADAs and 108 had no ADA. Among the 139 patients randomized to a non-TNF targeted biologic and assessed for ADAs, 20 had ADAs and 119 had no ADA. In patients with ADAs, change in DAS28-ESR at 6 months adjusted on baseline DAS28-ESR was similar between patients randomized to a second anti-TNF and those randomized to a non-TNF-targeted biologic (median change of 0.45 and 0.45, respectively, P=0.96). In patients without ADA, change in DAS28-ESR at 6 months adjusted on baseline DAS28-ESR was lower in patients randomized to a second anti-TNF than in those randomized to a non-TNF targeted biologic (median change -0.22 and -0.36, respectively, P= 0.003).

Conclusion:

In the ROC trial, only a minority (~ 10%) of TNF-IR patients had ADAs. Interestingly, in TNF-IR patients with an immunogenic response against TNF inhibitors, the response to a second TNF inhibitor did not differ from response to a non-TNF-targeted drug. Therefore, the assessment of ADAs might contribute to guide the choice of a second biologic in TNF-IR patients.

Disclosure: S. Candon, None; L. Chatenoud, None; 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. Liote, 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; E. Perrodeau, None; J. Sibilia, None; P. Ravaud, None; J. Gottenberg, Abbvie, MSD, Pfizer, Roche, BMS, 9.

To cite this abstract in AMA style:

Candon S, Chatenoud L, 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, Liote 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, Perrodeau E, Sibilia J, Ravaud P, Gottenberg J. Interest of Assessing Anti-Drug Antibodies for the Choice Between a Second Anti-TNF and a Non-TNF-Targeted Biologic in Patients with Inadequate Response to a First Anti-TNF : Results from the Randomized Controlled Trial « Rotation or Change » [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/interest-of-assessing-anti-drug-antibodies-for-the-choice-between-a-second-anti-tnf-and-a-non-tnf-targeted-biologic-in-patients-with-inadequate-response-to-a-first-anti-tnf-results-f/. Accessed .

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