A novel multi-biomarker combination predicting relapse from long-term remission after discontinuation of biological drugs in rheumatoid arthritis

Katsuya Nagatani,Hitoshi Endo,Seiji Minota,Eiji Sakashita

doi:10.1038/s41598-021-00357-9

Katsuya Nagatani, Hitoshi Endo + Show 2 more

Open Access

https://doi.org/10.1038/s41598-021-00357-9

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Journal: Scientific Reports	Publication Date: Oct 21, 2021
Citations: 7	License type: open-access

Affiliation: Jichi Medical University

Abstract

Biological disease modifying anti-rheumatic drugs (bDMARDs) show dramatic treatment efficacy in rheumatoid arthritis (RA). Long-term use of bDMARDs, however, has disadvantages such as high costs and infection risk. Therefore, a methodology is needed to predict any future RA relapse. Herein, we report a novel multi-biomarker combination which predicts relapse after bDMARDs-withdrawal in patients in remission. Forty patients with RA in remission for more than 12 months were enrolled. bDMARDs were withdrawn and they were followed monthly for the next 24 months. Fourteen patients (35%) of 40 in the cohort remained in remission at 24 months, whereas 26 (65%) relapsed at various time-points. Serum samples obtained longitudinally from patients in remission were assessed for the relapse-prediction biomarkers and index from 73 cytokines by the exploratory multivariate ROC analysis. The relapse-prediction index calculated from the 5 cytokines, IL-34, CCL1, IL-1β, IL-2 and IL-19, strongly discriminated between patients who relapsed and those who stayed in remission. These findings could contribute to clinical decision-making as to the timing of when to discontinue bDMARDs in RA treatment.

Highlights

Biological disease modifying anti-rheumatic drugs show dramatic treatment efficacy in rheumatoid arthritis (RA)
Forty patients in remission (DAS28-CRP < 2.3) for at least 1 year by bDMARDstreatment were enrolled and Biological disease modifying anti-rheumatic drugs (bDMARDs) were discontinued at the time of study initiation; 14 patients remained in remission for 2 years and 26 relapsed at some point in time
DAS using 28 joints (DAS28)-CRP is a variation of DAS28 in which serum levels of C-reactive protein replace those of sedimentation rates

Summary

Introduction

Biological disease modifying anti-rheumatic drugs (bDMARDs) show dramatic treatment efficacy in rheumatoid arthritis (RA). The relapse-prediction index calculated from the 5 cytokines, IL-34, CCL1, IL-1β, IL-2 and IL-19, strongly discriminated between patients who relapsed and those who stayed in remission These findings could contribute to clinical decision-making as to the timing of when to discontinue bDMARDs in RA treatment. Since the advent of etanercept in 1998 in the United States and infliximab in 2003 in Japan as the first biological disease modifying anti-rheumatic drugs (bDMARD), treatment of patients with rheumatoid arthritis (RA) has been dramatically changed with unprecedented efficacy. The risk of infection is less, the risks remain; patients as well as their physicians need to be alert to the danger of infection which can be serious and potentially fatal[3] Because of these concerns, patients on bDMARDs and in remission may choose to discontinue them. Several clinical parameters were developed to evaluate RA disease-activity for clinical practice such as the Disease Activity Score (DAS), the modified DAS using 28 joints (DAS28)[5,6,7], the Clinical Disease Activity Index (CDAI)[8], the Simplified Disease Activity Index (SDAI)[9], and the Boolean-based jichi.ac.jp

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