Prediction of disease flare by biomarkers after discontinuing biologics in patients with rheumatoid arthritis achieving stringent remission
～Combination of blood biomarkers is most useful～
Prof. Hideto Kameda
Our team, consisting of Professor Hideto Kameda and his colleagues at the Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Toho University, found that a combination of two biomarkers in the blood can predict, with high accuracy, the relapse of rheumatoid arthritis (RA) after discontinuing treatment with biological agents that occurs in a high percentage of patients who have been in remission.
Although the rate of RA relapse is high within two years after the discontinuation of biologics, it is difficult to predict the occurrence of relapse based on clinical symptoms and joint ultrasound findings at the time of discontinuation of biologics. The decision to discontinue the administration of expensive biologics due to the economic burden on patients is difficult. This study is expected to make the discontinuation of biologics in RA more appropriate and have a positive impact on the medical economy. The results were published in the journal “Scientific Reports” on March 25, 2021.
Fifty-six percent of patients with RA experienced relapse within 2 years after voluntarily requesting the discontinuation of biologics.
Although it is difficult to predict relapse by conventional clinical and imaging evaluations at the time of the discontinuation of biologics, we found that it can be predicted with high accuracy by a combination of blood biomarkers. Since biologics are expensive, this research result is expected to have a positive impact on the medical economy.
Our team, consisting of Professor Hideto Kameda and his colleagues at the Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Toho University, found that a combination of two biomarkers in the blood can predict, with high accuracy, the relapse of rheumatoid arthritis (RA) after discontinuing treatment with biological agents that occurs in a high percentage of patients who have been in remission.
Prof. Hideto Kameda
Although the rate of RA relapse is high within two years after the discontinuation of biologics, it is difficult to predict the occurrence of relapse based on clinical symptoms and joint ultrasound findings at the time of discontinuation of biologics. The decision to discontinue the administration of expensive biologics due to the economic burden on patients is difficult. This study is expected to make the discontinuation of biologics in RA more appropriate and have a positive impact on the medical economy. The results were published in the journal “Scientific Reports” on March 25, 2021.
Fifty-six percent of patients with RA experienced relapse within 2 years after voluntarily requesting the discontinuation of biologics.
Although it is difficult to predict relapse by conventional clinical and imaging evaluations at the time of the discontinuation of biologics, we found that it can be predicted with high accuracy by a combination of blood biomarkers. Since biologics are expensive, this research result is expected to have a positive impact on the medical economy.
Plasma cytokine profile at baseline as a predictive marker of RA flare after bDMARD discontinuation.
(A) Comparison of patients with sTNFR1 ≤ cut-off (n = 20, solid line) and sTNFR1 > cut-off (n = 14, dotted line).
(B) Comparison of patients with IL-2 > cut-off (n = 12, solid line) and IL-2 ≤ cut-off (n = 8, dotted line) in those with sTNFR1 ≤ cut-off (n = 20).
(C) Comparison of patients with IL-2 > cut-off (n = 7, solid line) and IL-2 ≤ cut-off (n = 7, dotted line) in those with sTNFR1 > cut-off (n = 14).
Key points of the presentation
RA is a persistent and destructive arthritis that causes joint dysfunction, and affects approximately 700,000 Japanese patients. Since 2003, 20%–30% of patients with RA in Japan have been treated with biologics. As a result, the rate of remission (a state in which the disease activity is sufficiently suppressed) has increased. However, because biological agents are expensive, with an annual expenditure of 200,000–400,000 yen, even with a 30% co-payment, the number of patients receiving them is limited by medical guidelines. Previous studies have reported that RA flares up in about half of the patients within a year of discontinuing biologics. Therefore, patients with RA in whom the internationally accepted strict remission criteria for biologics had been maintained for at least three months (median 20 months; only two patients less than six months) and who wished to discontinue biologics due to their high cost were enrolled in this study and were monitored for relapse over a two-year period. Of the 36 patients enrolled between November 2014 and January 2018, 20 (56%) had flare-up of RA within two years of discontinuing biologics, which is similar to previously reported findings. Although it was difficult to predict relapse using conventional methods such as clinical symptoms and joint ultrasound findings at the time of discontinuation of biologics, the combination of two biomarkers in the blood, namely soluble TNF receptor 1 (sTNFR1) and interleukin (IL)-2, could predict the maintenance of remission after discontinuation. (Figure, A and B). When sTNFR1 levels were high, most patients experienced relapse, regardless of IL-2 levels. Based on the results of this study, it is hoped that the discontinuation of biologics in RA will be more appropriate than in the past, leading to a reduction in healthcare costs. In July 2020, we applied for a patent in Japan based on the results of this research.
