Favorable clinical response and drug retention of anti-IL-6 receptor inhibitor in rheumatoid arthritis with high CRP levels: the ANSWER cohort study

Abstract

Objective

Currently, biological disease-modifying anti-rheumatic drugs (bDMARDs) with different modes of action [tumour necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL-6Ri), or cytotoxic T-lymphocyte antigen 4–immunoglobulin (CTLA4-Ig)] are used in clinical practice to treat rheumatoid arthritis (RA). However, it is unclear which type of bDMARD is the most efficacious for a specific clinical situation. C-reactive protein (CRP) is an acute-phase reactant driven by IL-6 signalling. Here, we aimed to establish whether therapeutic efficacy differs between IL-6Ri and other bDMARDs with alternative modes of action in RA patients according to their CRP level.

Method

RA patients treated with bDMARDs were enrolled from an observational multicentre registry in Japan. Patients were classified into three groups according to baseline CRP tertiles. The overall 3 year retention rates of each bDMARD category were assessed. The Clinical Disease Activity Index (CDAI) was also assessed before and 3, 6, and 12 months after bDMARD initiation.

Results

A total of 1438 RA patients were included and classified into three groups according to tertiles of baseline CRP levels (CRP¹, 0–0.3; CRP², 0.3–1.8; CRP³, 1.8–18.4 mg/dL). In CRP³, the overall 3 year drug retention rates were significantly higher for IL-6Ri than for TNFi and CTLA4-Ig (77.5 vs 48.2 vs 67.3, respectively). No significant difference was evident in terms of CDAI 12 months after bDMARD initiation in CRP¹–CRP³.

Conclusion

IL-6Ri may be a favourable therapeutic option over TNFi and CTLA4-Ig in RA patients with high CRP levels.

Acknowledgements

The authors thank all medical staff at all institutions participating in the ANSWER cohort study for providing data.

Disclosure statement

MH, RW, K Murata, MT, and HI belong to the Department of Advanced Medicine for Rheumatic Diseases, which is supported by Nagahama City, Shiga, Japan, Toyooka City, Hyogo, Japan, and five pharmaceutical companies (Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co. Ltd, UCB Japan Co. Ltd, AYUMI Pharmaceutical Co., and Asahi Kasei Pharma Corp.). MH has received research and/or speaker fees from Bristol-Myers, Eisai, Eli Lilly, and Tanabe-Mitsubishi. MT has received research grants and/or speaker fees from AbbVie GK, Asahi-Kasei Pharma Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Corp., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd, Eisai Co. Ltd, Eli Lilly Japan KK, Pfizer Inc., UCB Japan Co. Ltd, Janssen Pharmaceutical KK, Mitsubishi-Tanabe Pharma Corp., Novartis Pharma KK, and Taisho Pharma Co. Ltd. HI received a research grant and/or speaker fee from Bristol-Myers, Kyocera, Asahi-Kasei, and Eisai. KE is affiliated with the Department of Musculoskeletal Regenerative Medicine, Osaka University, Graduate School of Medicine, which is supported by Taisho. KE has received research grants from AbbVie, Asahi-Kasei, Astellas, Chugai, Eisai, Ono Pharmaceutical, and UCB Japan. KE has received payments for lectures from AbbVie, Asahi-Kasei, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Ono Pharmaceutical, Sanofi, and UCB Japan. AO has received speaker fees from Chugai, Ono Pharmaceutical, Eli Lilly, Mitsubishi-Tanabe, Asahi-Kasei, and Takeda. RH has received a speaker fee from AbbVie. KO has received a research grant and/or speaker fee from AbbVie, Astellas, Bristol-Myers Squibb, Eli Lily, Mitsubishi-Tanabe, Pfizer, and Takeda. The remaining authors have no financial conflicts of interest to disclose concerning this manuscript. The pharmaceutical companies had no role in the design of the study, the collection or analysis of the data, the writing of the manuscript, or the decision to submit the manuscript for publication.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

The study reported in this publication uses the ANSWER cohort, supported by grants from 10 pharmaceutical companies (AbbVie GK, Asahi-Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. Ltd, Eisai Co. Ltd, Janssen Pharmaceutical KK, Ono Pharmaceutical Co., Sanofi, Teijin Healthcare Ltd, and UCB Japan Co. Ltd) and an information technology services company (CAC). This study is conducted as an investigator-initiated study. These companies have no roles in the study design, data collection, data analysis, data interpretation, or writing of the report.