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THU0087 One single infusion of rituximab 1g might be sufficient in the long-term management of rheumatoid arthritis patients responding to a first cycle of rituximab (2 × 1g): Results of a 2-year multi-center randomized controlled trial
  1. M. Dougados1,
  2. B. Combe2,
  3. X. Le Loët3,
  4. J. Tebib4,
  5. J. Sibilia5,
  6. S. Rouanet6,
  7. R. Jourdan7,
  8. X. Mariette8
  1. 1Rheumatology, Paris-Descartes University, Cochin Hospital, Paris
  2. 2Rheumatology, Hopital Lapeyronie, Montpellier
  3. 3Rheumatology, CHU de ROUEN, Rouen
  4. 4Rheumatology, Centre Hosp Lyon Sud, Pierre Benite
  5. 5Rheumatology, Hopitaux Universitaires de Strasbourg, Strasbourg
  6. 6Roche, Boulogne Billancourt
  7. 7Roche, Boulogne-Billancourt cedex
  8. 8Rhumatology, Universite Paris-Sud, Kremlin Bicetre, France

Abstract

Objectives To assess the symptomatic efficacy and the safety profile of 2 dose regimens of rituximab (RTX) in patients (pts) who had a EULAR response 6 months after a 1st cycle of 2 infusions of RTX 1g and who necessitated subsequent therapy

Methods Definite RA (1987 ACR criteria); active disease (DAS >3.2 and either SJC ≥6 and TJC ≥6 or CRP ≥10 mg/l or ESR ≥28 mm/1st hour; refractory or intolerant to at least one aTNF.

Study design: The 1st 24 week-period was a prospective multi-center non-controlled trial followed (from week (W) 24 to W104) by a randomized controlled trial. At W0, the 1st cycle of RTX consisted of 2 x 1g RTX two weeks apart. At W24, pts who experienced a EULAR response were randomized to receive RTX 1g in one single infusion (Arm A) or the licensed dose of RTX 2 x 1g (Arm B) as subsequent retreatment following assessment of disease activity every 6 months (e.g. DAS >3.2).

Outcome measures: DAS28-CRP, number of required cycles of RTX, time to a second retreatment.

Analysis: Non inferiority of Arm A versus (vs) Arm B on the DAS28-CRP Area Under the Curve (AUC) during 104 W, with a non-inferiority margin defined by 20% of the mean DAS AUC of the reference group (δ=444). Main analysis was performed on the per-protocol (PP) and intention to treat (ITT) population using a covariance analysis that included baseline DAS value as covariate.

Results Of the 234 screened pts, 224 received the 1st cycle of RTX. DAS28-CRP changed from 5.8±0.9 to 4.2±1.2 at W24, resulting in a EULAR response in 152 patients (71%). Pts (n=143) were randomized in the 2nd part of the study (ITT: 70/Arm A and 73/Arm B) without any inter-group difference. Following withdrawals and major protocol deviations, the final PP population was 51pts/Arm A and 49/Arm B. The DAS28-CRP AUC at W104 (PP) was 2761±508 in Arm A and 2666±490 in Arm A vs. Arm B, resulting in an adjusted inter-group difference of 51.4 with a 95% CI of [-131.2; 233.9] demonstrating the non-inferiority of retreatment in Arm A vs Arm B. Similar results have been shown for the ITT population. The number of required cycles per year after the first retreatment was similar in both arms (1.0±0.3) as was the estimated median time to a second retreatment using the Kaplan-Meier method (263 and 255 days in Arm A vs B, respectively). During the study the percentage of any and serious adverse events was similar (92% and 29% vs 96% and 37% in Arm A vs B, respectively). The percentage of pts with an IgG level below 6.82 g/L (LLN) at week 104 was 2% (1/48) and 11% (6/53) in Arm A vs B (p=0.12). The percentage of serious infections was 12% (8/66) and 3% (2/68) in Arm A vs B (p=0.05) corresponding to a serious infection rate of 7.2 and 1.5/100 pt-yrs.

Conclusions This study suggests that in case of a EULAR response after a first cycle of 2 infusions of RTX 1g, retreatment with a RTX 1g single infusion provides similar clinical outcomes compared with 2 x 1g infusions. The structural (radiographic) effect of these 2 strategies was not assessed in this study.

Disclosure of Interest M. Dougados Grant/Research support from: Roche, B. Combe Grant/Research support from: Roche, X. Le Loët Grant/Research support from: Roche, J. Tebib Grant/Research support from: Roche, J. Sibilia Grant/Research support from: Roche, S. Rouanet Employee of: Roche, R. Jourdan Employee of: Roche, X. Mariette Grant/Research support from: Roche

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