Session Information
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Infliximab (IFX), a TNF inhibitor, is one of the most widely used biological disease-modifying antirheumatic drugs. Recent studies indicated that baseline levels of serum TNF-α could be considered as a key indicator for optimal dosing of IFX for treatment of rheumatoid arthritis (RA) to achieve the clinical response and its sustained remission. The Remission induction by Raising the dose of Remicade in RA (RRRR) study (trial registry no;UMIN000005113) was designed to evaluate the clinical remission after 54 weeks of “programmed” treatment, whose dose of IFX for each patient was determined by the baseline serum TNF-α. The sustained remission rate after 1-year discontinuation of IFX was compared to standard treatment of IFX at week 106.
Methods: RRRR study was a randomized, active controlled, multicenter phase 4 study. IFX-naïve RA patients who showed an inadequate response to MTX were randomized 1:1 to the programmed treatment strategy (programmed group) and the standard treatment strategy (standard group).
Patients in programmed group received 3 mg/kg IFX at week 0, 2, and 6. After 14 weeks, a dose of IFX was kept or raised based on baseline levels of serum TNF-α (3 mg/kg for TNF-α < 0.55 pg/mL; 6 mg/kg for 0.55 pg/mL- <1.65 pg/mL; 10mg/kg for 1.65 pg/mL or greater) every 8 weeks until week 54 after enrollment. Patients in standard group received 3mg/kg of IFX from week 0 to 54. If patients showed a simplified disease activity index (SDAI) ≤ 3.3 at week 54, they discontinued IFX. The primary endpoint was the proportion of patients who kept discontinuation of IFX at week 106 (1-year sustained discontinuation rate).
Results: From April 2011 to September 2013, 405 patients were enrolled and 337 patients who completed IFX treatment at week 0, 2, and 6 were randomized to the programmed group (n = 170) and the standard group (n = 167). The patient characteristics in intention-to treat population were similar between groups (Table 1). One hundred and seventeen patients (68.8%) in the programmed group and 112 patients (67.1%) in the standard group completed the 54 weeks IFX treatment after enrollment. At week 54, 39.4% (67/170) in the programmed group and 32.3% (54/167) in the standard group could attain the remission defined by SDAI (p = 0.176) and withdrew IFX treatment.
At week 106, the 1-year sustained discontinuation rate of the programmed group and standard group was 23.5% (40/170) and 21.6% (36/167), respectively (2.2% difference, 95% confidence interval = -6.6 to 11.0%; p = 0.631). No difference was observed in severe infections and other severe adverse events between groups.
Conclusion: Programmed treatment strategy using different dose of IFX based on the baseline levels of serum TNF-α tended to increase the remission rate at week 54, but did not increase the sustained remission rate after 1-year discontinuation of IFX treatment at week 106.
Table1. Patients characteristics
|
Standard group (N = 167) |
Programmed group (N = 170) |
|
|
Age, years, median (range) |
59 (20 to 83) |
58 (20 to 81) |
|
Female, n (%) |
136 (81.4) |
129 (75.9) |
|
Duration of disease, > 3 years, n (%) |
69 (41.3) |
71 (41.8) |
|
Baseline SDAI, mean (SD) |
27.0 (13.1) |
28.2 (14.1) |
|
Tender/painful joint count, mean (SD) |
7.7 (6.4) |
8.7 (6.4) |
|
Swollen joint count, mean (SD) |
7.4 (5.2) |
7.4 (4.9) |
|
Patients’ global assessment VAS, mean (SD) |
49.8 (19.1) |
50.7 (25.1) |
|
Physicians’ global assessment VAS, mean (SD) |
49.0 (19.1) |
48.6 (22.4) |
|
CRP, mg/dL, median (range) |
0.91 (0.0 to 15.1) |
1.0 (0.0 to 20.7) |
|
Baseline DAS28 CRP, mean (SD) |
4.1 (1.0) |
4.2 (1.0) |
|
Baseline TNF-α, < 0.55 pg/dL, n (%) |
55 (32.9) |
51 (30.0) |
|
Baseline TNF-α, 0.55 to < 1.65 pg/dL, n (%) |
61 (36.5) |
68 (40.0) |
|
Baseline TNF-α, > 1.65 pg/dL, n (%) |
51 (30.5) |
51 (30.0) |
|
HAQ-DI score, mean (SD) |
1.0 (0.8) |
1.0 (0.8) |
|
mTSS, median (range) |
8.25 (0 to 318) |
8 (0 to 403) |
|
RF, IU/ml, median (range) |
45.2 (0 to 2301) |
59 (0 to 2050) |
|
Dose of MTX, mg/w, mean (SD) |
10.8 (3.2) |
11.5 (3.3) |
|
SD, standard deviation;SDAI, simplified disease activity index; VAS, visual analog scale; CRP, C-reactive protein; DAS28, disease activity score 28; HAQ-DI, health assessment questionnaire disability index; mTSS, modified total sharp score; RF, rheumatoid factor; |
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To cite this abstract in AMA style:
Tanaka Y, Oba K, Koike T, Miyasaka N, Mimori T, Takeuchi T, Hirata S, Tanaka E, Yasuoka H, Kaneko Y, Murakami K, Koga T, Nakano K, Amano K, Ushio K, Atsumi T, Inoo M, Hatta K, Mizuki S, Nagaoka S, Tsunoda S, Dobashi H, Horie N, Sato N. Sustained Clinical Remission after Discontinuation of Infliximab with a Raising Dose Strategy in Patients with Rheumatoid Arthritis (RRRR study): A Randomized Controlled Trial [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/sustained-clinical-remission-after-discontinuation-of-infliximab-with-a-raising-dose-strategy-in-patients-with-rheumatoid-arthritis-rrrr-study-a-randomized-controlled-trial/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/sustained-clinical-remission-after-discontinuation-of-infliximab-with-a-raising-dose-strategy-in-patients-with-rheumatoid-arthritis-rrrr-study-a-randomized-controlled-trial/