Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis: the RRRR study, a randomised controlled trial.

The aim of this study is to determine whether the 'programmed' infliximab (IFX) treatment strategy (for which the dose of IFX was adjusted based on the baseline serum tumour necrosis factor α (TNF-α)) is beneficial to induction of clinical remission after 54 weeks and sustained discontinuation of IFX for 1 year. In this multicentre randomised trial, patients with IFX-naïve rheumatoid arthritis with inadequate response to methotrexate were randomised to two groups; patients in programmed treatment group received 3 mg/kg IFX until week 6 and after 14 weeks the dose of IFX was adjusted based on the baseline levels of serum TNF-α until week 54; patients in the standard treatment group received 3 mg/kg of IFX. Patients who achieved a simplified disease activity index (SDAI) ≤3.3 at week 54 discontinued IFX. The primary endpoint was the proportion of patients who sustained discontinuation of IFX at week 106. A total of 337 patients were randomised. At week 54, 39.4% (67/170) in the programmed group and 32.3% (54/167) in the standard group attained remission (SDAI ≤3.3). At week 106, the 1-year sustained discontinuation rate was not significantly different between two groups; the programmed group 23.5% (40/170) and the standard group 21.6% (36/167), respectively (2.2% difference, 95% CI -6.6% to 11.0%; p=0.631). Baseline SDAI <26.0 was a statistically significant predictor of the successfully sustained discontinuation of IFX at week 106. Programmed treatment strategy did not statistically increase the sustained remission rate after 1 year discontinuation of IFX treatment.

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Competing interests: YT has received consulting fees, speaking fees and/or honoraria from AbbVie GK; Chugai Pharmaceutical Co Ltd; Daiichi-Sankyo Co Ltd; Bristol-Myers, Mitsubishi Tanabe Pharma Co; Astellas Pharma Inc; Takeda Pharmaceutical Co Ltd; Pfizer Japan Inc; Teijin Pharma; Asahikasei Pharma Corp; YL Biologics; Sanofi KK: Janssen Pharmaceutical KK; Eli Lilly Japan KK and GlaxoSmithKline KK and has received research grants from Mitsubishi Tanabe Pharma Co; Takeda Pharmaceutical Co, Ltd; Daiichi Sankyo Co Ltd; Chugai Pharmaceutical Co Ltd; Bristol-Myers KK; MSD KK; Astellas Pharma Inc; AbbVie GK; Eisai Co Ltd K Oba has received honoraria from Takeda Pharmaceutical Co Ltd; Ono Pharmaceutical Co Ltd; Eisai Co Ltd; Chugai Pharmaceutical Co Ltd; Daiichi- Sankyo Co Ltd. TT has received grants from Astellas Pharma Inc and Pfizer Japan, Inc; Chugai Pharmaceutical Co Ltd; Daiichi Sankyo Co Ltd; Takeda Pharmaceutical Co Ltd; AbbVie GK; Asahikasei Pharma Corp; Mitsubishi Tanabe Pharma Co; Pfizer Japan Inc; Eisai Co Ltd; AYUMI Pharmaceutical Co; Nipponkayaku Co Ltd; Novartis Pharma KK; Shionogi AbbVie GK; AYUMI Pharmaceutical Co; Eisai Co Ltd; Gilead Sciences, Inc; GlaxoSmithKline KK; Sanofi KK; Taiho Pharmaceutical Co Ltd; Mitsubishi Tanabe Pharma Co; Diaichi Sankyo Co Ltd; Chugai Pharmaceutical Co Ltd; Taisho Pharmaceutical Co Ltd; Eli Lilly Japan KK; Novartis Pharma KK; Boehringer-ingelheim Co Ltd; Nipponkayaku Co Ltd; Pfizer Japan Inc; Bristol–Myers KK; Janssen Pharmaceutical KK; UCB Japan Co Ltd. TM received research grants and/or speaking fees from Asahikasei Pharma Corp; Astellas Pharma Inc; AYUMI Pharmaceutical Corporation; Bristol-Myers Squibb; Chugai Pharmaceutical Co Ltd; Diaichi-Sankyo Co Ltd; Eisai Co Ltd; Eli Lilly Japan KK; Mitsubishi-Tanabe Pharma Co; MSD KK; Nippon Kayaku Co Ltd; Pfizer Japan Inc; Sanofi KK; Takeda Pharmaceutical Co Ltd. TK has received speaking fees from AbbVie GK; ASKA Pharmaceutical Co Ltd; Astellas Pharma Inc; Bristol-Myers KK; Chugai Pharmaceutical Co Ltd; Diaichi-Sankyo Co Ltd; Eisai Co Ltd; Mitsubishi Tanabe Pharma Co; Pfizer Japan Inc; Teijin Pharma; UCB Pharma and consulting fees from Bristol-Myers KK; Eli Lilly Japan KK; Pfizer Japan Inc; Diaichi-Sankyo Co Ltd; Sanofi KK. SH has received research grants from Eli Lilly Japan KK; UCB Pharma; consultancy fee from Bristol-Myers Squibb; Celgene KK; Janssen Pharmaceutical KK; Novartis Pharma KK and speaker’s fees from AbbVie GK; Asahikasei Pharma Corp; Astellas Pharma Inc; AYUMI Pharmaceutical Co; Bristol-Myers Squibb; Chugai Pharmaceutical Co Ltd; Eisai Co Ltd; Eli Lilly Japan KK; Janssen Pharmaceutical KK; Kissei Pharmaceutical Co Ltd; Pfizer Japan Inc; Sanofi KK; Takeda Pharmaceutical Co Ltd; Mitsubishi Tanabe Pharma Co; UCB Pharma. ET has received lecture fees or consulting fees from Asahi Kasei pharma co; Bristol Myers Squibb; Chugai Pharmaceutical Co Ltd; Diaichi Sankyo Co Ltd; Eisai Co Ltd; Janssen Pharmaceutical KK; Nippon Kayaku Co Ltd; Pfizer Japan Inc; Takeda Pharmaceutical Co Ltd; Taisho Toyama Pharmaceutical Co Ltd; UCB Pharma. YK has received grants or speaking fees from AbbVie GK; Astellas Pharma Inc; AYUMI Pharmaceutical Co; Bristol-Myers Squibb; Chugai Pharmaceutical Co Ltd; Eisai Co Ltd; Eli Lilly Japan KK; Hisamitsu Pharmaceutical Co Inc; Janssen Pharmaceutical KK; Novartis Pharma KK; Pfizer Japan Inc; Sanofi KK; Takeda Pharmaceutical Co Ltd; Mitsubishi Tanabe Pharma Co; UCB Pharma. KN has received speaking fees from UCB Pharma; Astellas Pharma Inc; Mitsubishi Tanabe Pharma Co and research grants from Mitsubishi Tanabe Pharma Co; Eisai Co Ltd. KA has received research grants from Asahi Kasei Pharma Co; Chugai Pharmaceutical Co Ltd and honoraria from Astellas Pharma Inc; Eli Lilly Japan KK; Pfizer Japan Inc; Mitsubishi Tanabe Pharma Co Ltd.