Addition of another disease-modifying anti-rheumatic drug to methotrexate reduces the flare rate within 2 years after infliximab discontinuation in patients with rheumatoid arthritis: An open, randomized, controlled trial

Abstract

Objectives. We examined whether the addition of another conventional disease-modifying anti-rheumatic drugs (DMARDs) to methotrexate (MTX) upon infliximab (IFX) discontinuation in well-controlled rheumatoid arthritis (RA) patients could suppress subsequent disease flare.

Methods. RA patients maintaining DAS28-CRP (Disease Activity Score of 28 joints with C-reactive protein) scores < 2.6 for ≥ 6 months with IFX were randomized either to receive addition of bucillamine (BUC) to MTX (BUC + MTX group; n = 24) or not (MTX group; n = 31) upon discontinuing IFX. The primary endpoint was the flare rate within 2 years of IFX discontinuation.

Results. Six patients discontinuing MTX during the study were excluded from analyses. Seventeen patients (63.0%) experienced flares in the MTX group, which was significantly reduced in the BUC + MTX group (31.8%; p = 0.045). Further, the flare rates differed significantly between remission and non-remission by a Boolean definition upon IFX discontinuation in the MTX group (40.0% vs. 91.7%, respectively; p = 0.014), but they were comparable in the BUC + MTX group. BUC treatment was interrupted in seven patients due to rash, proteinuria and incompliance.

Conclusions. DMARDs combination therapy may be a better treatment strategy than MTX monotherapy for maintaining RA control after successful discontinuation of biological agents.

Keywords:

• Biological agents
• Bucillamine
• DMARD combination
• Flare
• Remission

Acknowledgements

The authors gratefully acknowledge all relevant medical staffs in Saitama Medical Center and Keio University, especially Mrs. Harumi Kondo, for supporting data collection.

Conflict of interest

K Amano has received research grant support from and Astellas, Chugai and Pfizer and speaking honoraria from Abbott, Astellas, Bristol Myers, Chugai, Eizai, Mitsubishi-Tanabe and Pfizer.

T Takeuchi has received research grant support from and Abbott, Astellas, Bristol Myers, Chugai, Daiichi Sankyo, Eizai, Janssen, Mitsubishi-Tanabe, Nippon Shinyaku, Otsuka, Pfizer, Sanofi-aventis, Santen, Takeda, Teijin and speaking honoraria/consultancy fee from Abbott, Astellas, Asahi Kasei, Astra Zeneca, Bristol Myers, Chugai, Eizai, Eli-Lilly, Janssen, Johnson&Johnson, Mitsubishi-Tanabe, Pfizer and Symbio.

H Kameda has received research grant support from and Bristol Myers, Eizai and Pfizer and speaking honoraria/consultancy fee from Abbott, Chugai, Eizai, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Quintiles, Santen and UCB.

M Kishimoto is a full-time employee of Santen Pharmaceutical Co. Ltd.