Factors that influence biological survival in rheumatoid arthritis: results of a real-world academic cohort from the Netherlands

• Published in: Clinical rheumatology Vol. 40; no. 6; pp. 2177 - 2183
• Main Authors: van Mulligen, Elise, Ahmed, Saad, Weel, Angelique E. A. M., Hazes, Johanna M. W., van der Helm- van Mil, Annette H. M., de Jong, Pascal H. P.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-06-2021; Springer Nature B.V
• Subjects: Adverse events; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Autoantibodies; Biological products; Body mass index; Brief Report; Citrulline; Humans; Medicine; Medicine & Public Health; Netherlands - epidemiology; Patients; Precision medicine; Remission; Rheumatoid arthritis; Rheumatoid Factor; Rheumatology; Survival; Netherlands; Biological survival; bDMARDs; TNF inhibitor; Rheumatoid arthritis
• ISSN: 0770-3198; 1434-9949
• DOI: 10.1007/s10067-020-05567-6

We aim to explore real-world biological survival stratified for discontinuation reason and determine its influenceability in rheumatoid arthritis (RA) patients. Data from the local pharmacy database and patient records of a university hospital in the Netherlands were used. RA patients who started a biological between 2000 and 2020 were included. Data on age, anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) status, presence of erosions, gender, body mass index, time to first biological, biological survival time, use of csDMARDs, and discontinuation reasons were collected. Of the included 318 patients, 12% started their first biological within 6 months after diagnosis. The median time to first biological was 3.6 years (95% CI, 1.0–7.2). The median survival of the first- and second-line biological was respectively 1.7 years (95% CI, 1.3–2.2) and 0.8 years (95% CI, 0.5–1.0) (
p
= 0.0001). Discontinuation reasons for the first-line biological were ineffectiveness (47%), adverse events (17%), remission (16%), pregnancy (30%), or patient preference (10%). Multivariable Cox regression analyses for discontinuation due to inefficacy or adverse events showed that concomitant use of csDMARDs (HR = 1.32,
p
< 0.001) positively while RF positivity negatively (HR = 0.82,
p
= 0.03) influenced biological survival. ACPA positivity was associated with the inability to discontinue biologicals after achieving remission (HR = 1.43,
p
= 0.023). Second-line TNF inhibitor survival was similar between patients with a primary and secondary non-response on the first-line TNF inhibitor (HR = 1.28,
p
= 0.34). Biological survival diminishes with the number of biologicals used. Biological survival is prolonged if patients use csDMARDs. RF was negatively associated with biological survival. ACPA was negatively associated with the inability to discontinue biologicals after achieving remission. Therefore, tailoring treatment based upon autoantibody status might be the first step towards personalized medicine in RA.
Key Points
•
Prolonged biological survival is a surrogate for treatment effectiveness; however, an increasing amount of patients will taper treatment due to remission, and factors influencing biological survival based on separate reasons for discontinuation have not been explored
.
•
We found that combining a biological DMARD with a conventional synthetic DMARD increases biological DMARD survival. Rheumatoid factor is negatively associated with biological survival. Anti-citrullinated protein antibody is negatively associated with the inability to discontinue the biological when remission was reached.
•
The first step towards personalized medicine might be tailoring of treatment based upon autoantibody status.