ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1469

Therapeutic Strategy In Patients With Rheumatoid Arthritis and Insufficient Response To a 1st Anti-TNF: Results of the Multicenter Randomized Controlled “ROC” Trial

Jacques-Eric Gottenberg1, Olivier Brocq2, Aleth Perdriger3, Slim Lassoued4, Jean-Marie Berthelot5, Daniel Wendling6, Liana E. euller-Ziegler7, Martin Soubrier8, Christophe Richez9, Bruno Fautrel10, Arnaud L. Constantin11, Xavier Mariette12, Jacques Morel13, Melanie Gilson14, Grégoire Cormier15, Jean Hugues Salmon16, Stephanie Rist17, Frédéric Liote18, Hubert Marotte19, Christine Bonnet20, Christian Marcelli21, Jeremie Sellam22, Olivier Meyer23, Elisabeth Solau-Gervais24, Sandrine Guis25, Jean-Marc Ziza26, Charles Zarnitsky27, Isabelle Valckenaere28, Olivier Vittecoq29, Alain Saraux30, Yves-Marie Pers31, Martine Gayraud32, Gilles Bolla33, Pascal Claudepierre34, Marc Ardizzone35, Emmanuelle Dernis36, Maxime A. Breban37, Olivier Fain38, Jean-Charles Balblanc39, Ouafaa Aberkane1, Marion Vazel1, Christelle Back1, Elodie Perrodeau40, Philippe Ravaud41 and Jean Sibilia42, 1Strasbourg University Hospital, Strasbourg, France, 2Hospital of Princesse Grâce de Monaco, Monaco, France, 3Rheumatology, Hôpital Sud, Rennes, France, 4Cahors Hospital, Cahors, France, 5Rheumatology Unit, Nantes University Hospital, Nantes, France, 6Rheumatology, University Hospital, Besancon, France, 7Service de Rhumatologie, L Archet Hospital (University), Nice CEDEX 3, France, 8Rheumatology, CHU CLERMONT-FERRAND, Clermont-Ferrand, France, 9Pellegrin Hospital, Bordeaux, France, 10Rheumatology, UPMC - Paris 6 University, Paris, France, 11Rheumatology, Purpan University Hospital, Toulouse, France, 12Rheumatology Service, Bicêtre University Hospital, Le Kremlin Bicetre, France, 13Montpellier University Hospital, Montpellier, France, 14CH Grenoble Hopital Sud, Grenoble, France, 15CHD Les Oudairies, LA ROCHE SUR YON, France, 16Reims Hospital, Reims, France, 17Rheumatology, Orleans Hospital, Orleans, France, 18Hôpital Lariboisière, Paris, France, 19INSERM U1059 and University Hospital, Hôpital Nord, Saint-Etienne, France, 20department of Rheumatology, CHU Dupuytren Limoges, Limoges, France, 21Rheumatology Department, Caen University Hospital, CAEN, France, 22Rheumatology, Hopital Saint-Antoine, Pierre et Marie Curie University Paris 6, AP-HP, 75012, France, 23Rheumatology, Hopital Bichat, Paris, France, 24Poitiers University Hospital, Poitiers, France, 25Rheumatology1, CRMBM UMR CNRS 7339, Aix Marseille Univ; AP-HM, Marseille, France, 26Rheumatology, Croix Saint Simon Hospital, Paris, France, 27Rheumatology, CH du Havre, Le Havre, France, 28Nancy University Hospital, Nancy, France, 29RouenUniversity Hospital, Rouen, France, 30Rhumatologie, CHU de la Cavale Blanche, Brest Cedex, France, 31Department of Immuno-Rhumatology, CHU Lapeyronie, Montpellier, France, 32Institut Montsouris, Paris, France, 33Cannes Hospital, Cannes, France, 34Rheumatology, Henri Mondor Teaching Hospital, AP-HP, Créteil, France, 35Mulhouse Hospital, Mulhouse, France, 36Le Mans Hospital, Le Mans, France, 37Ambroise Paré Hospital (AP-HP), and Versailles Saint Quentin en Yvelines University, Boulogne-Billancourt, France, 38Internal Medicine, Jean Verdier Hospital, Bondy, France, 39Rheumatology, Centre Hospitalier Général de Belfort, Belfort, France, 40Epidemiology, Hotel Dieu, Paris, France, 41Epidemiology, Hopital Hotel Dieu, Paris Descartes University, Paris, France, 42Rheumatology, CHU Hautepierre, Strasbourg, France

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy II

Session Type: Abstract Submissions (ACR)

Background/Purpose: TNF inhibitors often represent the 1st biologic prescribed to patients with rheumatoid arthritis (RA). Approximately one third of patients fail to respond. However, therapeutic strategy in patients with insufficient response to a 1stanti-TNF is not codified.

Methods: The “Rotation of anti-TNF Or Change of class of biologic” (ROC) trial (NCT01000441) is a pragmatic open multicenter randomized controlled trial comparing the initiation of a second anti-TNF or of another class of biologic in patients with inadequate response to a first anti-TNF. Patients were randomly assigned in one of the two groups according to a computer generated randomization list using a block design with variable blocks sizes and a stratification on center. The choice of the second anti-TNF (adalimumab, certolizumab,  etanercept, infliximab) or of the other biologic abatacept, rituximab or tocilizumab) remained at the appreciation of the clinician. Inclusion criteria were: RA according to ACR criteria, insufficient response to 1 anti-TNF, DAS28 equal or greater than 3.2. Primary outcome criteria was EULAR response at 6 months.

Results:

Another class of biologic and a  second anti-TNF were respectively initiated in 146 patients  (abatacept:  35, rituximab: 41, tocilizumab: 70) and in 145 patients (adalimumab:  57; certolizumab: 23; etanercept: 53; infliximab: 8). Baseline characteristics are summarized in Table 1. EULAR response at 6 months was observed in 74.4% of patients (good: 41.8%/moderate response: 32.6%) treated with another class of biologic versus 65.7% (27.1%/38.6%) of those treated with a 2d anti-TNF (OR 1.6 (CI95% [0.9 ; 3.0], p = 0.1).  EULAR good/moderate responses at 6 months were 28.1/34.4%, 28.2/35.9%, 55.7/30.0%, 27.3/43.6%, 31.8/31.8%, 26.9/38.5%, and 12.5/25.0% in patients treated with abatacept, rituximab and tocilizumab, adalimumab, certolizumab, etanercept and infliximab, respectively. Low disease activity (LDA) was observed in 47.1%  of patients who changed of class of biologic vs 33.6% of patients who had a 2d anti-TNF, and DAS28-ESR remission was observed in 29.0 and  20.4% of patients, respectively.

Conclusion:

The ROC trial first demonstrates the efficacy of a second biologic in more than 2 thirds of TNF-IR patients.  At 6 months, the proportion of responders between patients who changed of class of biologic and those who had a second anti-TNF was overall similar. EULAR good response, LDA, DAS remission appeared higher in patients who changed of class of biologic compared to those who had a second anti-TNF. Analyses of clinical efficacy of each biologic,  changes in synthetic DMARDs and corticosteroids, biologic retention rate and radiographic progression at 1 year are ongoing. 

Table 1. Baseline characteristics of patients

 

Other class of   biologic

abatacept, rituximab, tocilizumab, n=146

2d anti-TNF

adalimumab, certolizumab, etanercept, infliximab,n= 145

Age/female sex

58.2 (11.1) / 82.2%

55.9 (13.1)/ 84.1%

Disease duration

10 [4;17.8]

10.5[4;19.2]

RF+/anti-CCP+

84.6/83.3%

77.1/80.0%

Ever smokers

18.5%

19.3%

Duration since 1st   anti-TNF discontinuation , days

17[6-56]

16[7-50.5]

Concomitant corticosteroids

54.8%

51.0%

Synthetic DMARD

76.7%

76.6%

TJC

8[4;12]

6[3;10]

SJC

5[3;8]

4[3;7]

Patient’s activity   VAS

6.2(1.9)

6.3(1.7)

ESR

27[11;50]

22[10;46]

DAS28-ESR

5.2(1.2)

5(1.1)

HAQ

1.3(0.6)

1.3(0.6)

Disclosure:

J. E. Gottenberg,

Abbvie, BMS, MSD, Pfizer, Roche,

5;

O. Brocq,
None;

A. Perdriger,
None;

S. Lassoued,
None;

J. M. Berthelot,
None;

D. Wendling,
None;

L. E. euller-Ziegler,
None;

M. Soubrier,
None;

C. Richez,
None;

B. Fautrel,
None;

A. L. Constantin,
None;

X. Mariette,
None;

J. Morel,
None;

M. Gilson,
None;

G. Cormier,
None;

J. H. Salmon,
None;

S. Rist,
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. 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,
None;

M. A. Breban,
None;

O. Fain,
None;

J. C. Balblanc,
None;

O. Aberkane,
None;

M. Vazel,
None;

C. Back,
None;

E. Perrodeau,
None;

P. Ravaud,
None;

J. Sibilia,
None.

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