Combination therapy for early rheumatoid arthritis: a treatment holiday perspective

Abstract

To date, the significance of early intervention with methotrexate and biological disease-modifying anti-rheumatic drugs for rheumatoid arthritis (RA) has not been realized. Longitudinal safety and cost have arisen as new concerns. The concept of a treatment holiday, drug discontinuation after achieving remission, may solve these problems. The authors performed a systematic literature review and identified 13 reports from 10 studies (TNF20, BeSt, OPITMA, HIT-HARD, IMPROVED, PRIZE, IDEA, EMPIRE, tREACH and AVERT) for early RA (≤2 years). Eight out of 13 reports (61.5%) were published in 2013 or 2014, indicating emerging interest in recent years. Also, the authors performed a sub-analysis of the HONOR study (n = 51) to compare early (≤2 years) and established RA. The proportions of remission (REM) and low disease activity were higher in early RA (REM: 63.0 vs 33.3%, p = 0.0346; low disease activity: 77.8 vs 45.8%, p = 0.0185). In conclusion, early intervention is beneficial for successful treatment holiday, which may lead to risk and cost reduction. However, further investigation is required.

Keywords:

• disease-modifying anti-rheumatic drug
• drug-free remission
• early intervention
• rheumatoid arthritis
• treatment holiday

Acknowledgements

This study is partly supported by a grant-in-aid by the Ministry of Health, Labor and Welfare. The authors are grateful to their colleagues in their department for contributions to develop the investigation.

Financial & competing interests disclosure

This study was partly supported by a grant-in-aid by the Ministry of Health, Labor and Welfare. Y Tanaka has received grant/research support from Bristol-Myers, Mitsubishi-Tanabe, AbbVie, MSD, Chugai, Astellas, Daiichi-Sankyo; consultant fee from Mitsubishi-Tanabe, Abbott, Abbvie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD, Asahi Kasei; and speakers bureau from Mitsubishi-Tanabe, Abbott, Abbvie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD, Asahi Kasei. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The concept of ‘treatment holiday’, drug discontinuation after achieving remission, has been expected as the next target of current therapeutic strategy in rheumatoid arthritis (RA).

• By a systematic literature review, 13 reports from 10 studies for early RA were found to be eligible, and 8 were published in 2013 or 2014, indicating emerging interest in treatment holiday in recent years.

• A sub-analysis of HONOR study to compare early (≤2 years) and established RA revealed that higher proportion of REM and low disease activity were identified in early RA patients.

• Despite the fact that further investigation is required, early intervention is beneficial for successful treatment holiday, which may lead to risk and cost reduction.