Background The efficacy and safety of tocilizumab (TCZ) is established for the treatment of rheumatoid arthritis (RA). However, when TCZ is used to treat RA patients with an inadequate response to methotrexate (MTX), it is not confirmed whether it is better to continue MTX or not.
Objectives To compare the efficacy and safety of TCZ monotherapy (SWITCH) and TCZ in combination with methotrexate (ADD-ON) in Japanese RA patients with inadequate response to MTX.
Methods The SURPRISE study was a multicentre, prospective, randomized, open-label study. Inclusion criteria were as follows: RA diagnosed by 1987 ACR classification criteria; DAS28-ESR ≥ 3.2; disease duration ≤ 10 years; MTX ≥ 6 mg/week for at least 8 weeks. Patients were randomized to switch to TCZ or to add on TCZ. The primary endpoint was the non-inferiority of combination therapy compared to monotherapy as assessed by the DAS28 remission rate of each group at 24 weeks with a non-inferiority margin of 10% in the per protocol set (PPS). Patients who received ≥1 dose of TCZ were assessed for safety in the full analysis set (FAS). The LOCF method was used to address the missing data on efficacy.
Results 233 patients were randomized: 115 to SWITCH and 118 to ADD-ON. At baseline in FAS, mean DAS28 was 5.2±0.1 and 5.1±0.1, disease duration was 4.0±0.3 and 3.8±0.3 years, MTX was 8.4±0.2 and 8.6±0.2, and HAQ-DI was 1.0±0.1 and 1.1±0.1 in the SWITCH and ADD-ON groups, respectively. DAS28 remission at 24 weeks was 59.4% in SWITCH and 71.6% in ADD-ON in PPS (n=106 in SWITCH; n=109 in ADD-ON). The delta between groups in DAS28 remission rate was 12.1 (95% CI; -1.3 – 25.2) supporting the non-inferiority of ADD-ON to SWITCH. Moreover, ADD-ON was superior to SWITCH in terms of DAS28 remission (71.3% vs 57.7%, P=0.0372) in FAS. The rates of ACR20, 50, and 70 response in each group were 66.7%, 53.2%, and 36.0% in SWITCH and 64.3%, 48.7%, and 27.8% in ADD-ON. CDAI, SDAI, and ACR/EULAR remission rates were 27.0%, 30.6%, and 20.7% in SWITCH and 36.5%, 40.0% and 20.0% in ADD-ON. The differences between groups in ACR response rate, CDAI remission, and SDAI remission were not significant. HAQ-DI and EQ-5D were similar in both groups. Incidences of serious adverse events were 9.9% in SWITCH versus 8.7% in ADD-ON; among these were 7 incidences of serious infection (3 pneumonia, 4 other infections).
Conclusions In Japanese RA patients with inadequate response to MTX, combination therapy was superior to monotherapy in efficacy as assessed using DAS28 criteria. However, results by other criteria were comparable between groups. In early stage RA, TCZ showed high response, and each of the strategies was useful.
Acknowledgements All member of SURPRISE study group.
Disclosure of Interest T. Takeuchi Grant/research support from: Abott, Astellas, Bristol-Myers, Chugai, Daiichi Sankyo, Eisai, Janssen, Mitsubishi Tanabe, Nippon Shinyaku, Otsuka, Pfizer, Sanofi, Santen, Takeda, Teijin, Consultant for: Astra Zeneca, Eli Lilly, Novartis, Mitsubishi Tanabe, Asahi Kasei, Paid instructor for: Abott, Bristol-Myers, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Pfizer, Takeda, Y. Kaneko: None Declared, T. Atsumi Grant/research support from: Kyowa Hakko Kirin, Mitsubishi Tanabe, Chugai, Novartis, Teijin, MSD, Astellas, Sanofi, Takeda, Novo Nordisk, Otsuka, Boehringer Ingelheim, Paid instructor for: Mitsubishi Tanabe, Takeda, Chugai, Pfizer, Y. Tanaka Grant/research support from: Bristol-Myers, MSD, Chugai, Mitsubishi Tanabe, Astellas, Abbott, Eisai, Janssen, Speakers bureau: Mitsubishi Tanabe, Abbott, Eisai, Chugai, Janssen, Santen, Pfizer, Astellas, Daiichi Sankyo, GlaxoSmithKline, Astra Zeneca, Otsuka, Actelion, Eli Lilly, Nippon Kayaku, UCB Japan, Quintiles Transnational, Ono, M. Inoh: None Declared, H. Kobayashi: None Declared, K. Amano Grant/research support from: Chugai, Mitsubishi Tanabe, Astellas, Eisai, Abott, M. Miyata: None Declared, Y. Murakawa Grant/research support from: Teijin, Astellas, Bristol-Myers, Mitsubishi Tanabe, Chugai, Actelion, Takeda, Pfizer, Taisho Toyama, Eisai, Paid instructor for: Santen, Chugai, Kissei, Astellas, Mitsubishi Tanabe, Actelion, Daiichi Sankyo, Takeda, T. Fujii Grant/research support from: Chugai, A. Kawakami Grant/research support from: Chugai, Mitsubishi Tanabe, Pfizer, Takeda, Abott, Eisai, Bristol-Myers, Janssen, Astellas, Santen, Taisho Toyama, Asahi Kasei, Paid instructor for: Chugai, Mitsubishi Tanabe, Pfizer, Takeda, Abott, Eisai, Bristol-Myers, Janssen, Astellas, Santen, Taisho Toyama, Asahi Kasei, H. Yamanaka Grant/research support from: Abbott, Bristol-Myers, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, UCB, Paid instructor for: Abbott, Bristol-Myers, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, UCB, K. Yamamoto Grant/research support from: ImmunoFuture, Inc, N. Miyasaka Grant/research support from: Abbott, Astellas, Banyu, Chugai, Daiichi Sankyo, Eisai, Janssen, Mitsubishi Tanabe, Takeda, Teijin, T. Mimori Grant/research support from: Asahi Kasei, Astellas, Bristol-Myers, Chugai, Eisai, Merck, Mitsubishi Tanabe, Pfizer, Santen, Takeda, Speakers bureau: Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe, Pfizer, Santen, Takeda