The Association Between Serum Drug Concentration and a Flare in Rheumatoid Arthritis Patients Tapering TNF Inhibitors
Abstract
1. Introduction
2. Results
2.1. Patients
2.2. ADL and ETN Serum Concentrations During Tapering
2.3. ADL and ETN Serum Concentrations During a Flare
2.4. ADAs Targeting ADL
3. Discussion
3.1. Main Findings
3.2. Pharmacokinetics
3.3. Immunogenicity
3.4. Strengths and Limitations
4. Materials and Methods
4.1. Patients
4.2. Outcome Measures and Assessments
4.3. Measurement of Serum Drug Concentrations
4.4. Measurement of Anti-Drug Antibodies (ADAs)
4.5. Statistics
5. Conclusions and Future Directions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
TNFi | Tumor necrosis factor inhibitor |
RA | Rheumatoid arthritis |
ADAs | Anti-drug antibodies |
ADL | Adalimumab |
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Characteristics | All RA Patients (N = 111) | Tapering ADL First, Followed by MTX (N = 22) | Tapering MTX First, Followed by ADL (N = 24) | Tapering ETN First, Followed by MTX (N = 32) | Tapering MTX First, Followed by ETN (N = 33) |
---|---|---|---|---|---|
Demographic | |||||
| 57 (11.3) | 59 (8.9) | 52 (10.8) | 58 (10.3) | 58 (13.5) |
| 26 (24–29) | 25 (25–30) | 26 (24–28) | 27 (24–30) | 25 (23–29) |
| 69 (62) | 11 (50) | 17 (70) | 20 (63) | 21 (63) |
| 5.7 (3.9–8.5) | 7.1 (4.2–9.0) | 6.0 (3.1–9.1) | 5.7 (4.0–8.5) | 4.7 (2.5–70 |
Clinical | |||||
| 56 (50) | 13 (72) | 12 (57) | 16 (55) | 15 (46) |
| 70 (63) | 12 (67) | 15 (71) | 20 (69) | 23 (74) |
| 1.0 (0.49) | 1.0 (0.44) | 1.1 (0.6) | 1.0 (0.53) | 0.9 (0.35) |
| 8 (3–15) | 6 (2–18) | 5.5 (2–12) | 9.5 (4.5–16) | 8 (5–14) |
| 2 (1–5) | 2 (1–5) | 1.8 (1–5) | 2 (1–8) | 3 (1–5) |
| 47 (42) | 12 (54) | 13 (54) | 11 (34) | 11 (33) |
| 20 (15–25) | 15 (14–25) | 15 (10–25) | 22 (15–25) | 25 (15–25) |
| - | 9.5 (5.5–10.5) | 7.4 (4.7–9.8) | 2.3 (1.8–3.0) | 2.4 (1.9–3.2) |
Adalimumab | Etanercept | ||||||
---|---|---|---|---|---|---|---|
Drug Level (mg/L) | OR | (95% CI) | p Value | Drug Level (mg/L) | OR | (95% CI) | p Value |
Low * (<1.81) | - | - | - | Low * (<0.283) | - | - | - |
Medium (1.81–6.06) | 0.29 | (0.09–0.92) | 0.036 | Medium (0.283–2.24) | 1.35 | (0.47–3.92) | 0.57 |
High (>6.06) | 0.37 | (0.14–0.98) | 0.046 | High (>2.24) | 2.14 | (0.86–5.32) | 0.10 |
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Layegh, Z.; Hooijberg, F.; Boekel, L.; Looijen, A.E.M.; van Mulligen, E.; Loeff, F.C.; Dijk, L.; Dolhain, R.J.E.M.; Rispens, T.; Wolbink, G.J.; et al. The Association Between Serum Drug Concentration and a Flare in Rheumatoid Arthritis Patients Tapering TNF Inhibitors. Pharmaceuticals 2025, 18, 1506. https://doi.org/10.3390/ph18101506
Layegh Z, Hooijberg F, Boekel L, Looijen AEM, van Mulligen E, Loeff FC, Dijk L, Dolhain RJEM, Rispens T, Wolbink GJ, et al. The Association Between Serum Drug Concentration and a Flare in Rheumatoid Arthritis Patients Tapering TNF Inhibitors. Pharmaceuticals. 2025; 18(10):1506. https://doi.org/10.3390/ph18101506
Chicago/Turabian StyleLayegh, Zohra, Femke Hooijberg, Laura Boekel, Agnes E. M. Looijen, Elise van Mulligen, Floris C. Loeff, Lisanne Dijk, Radboud J. E. M. Dolhain, Theo Rispens, Gertjan J. Wolbink, and et al. 2025. "The Association Between Serum Drug Concentration and a Flare in Rheumatoid Arthritis Patients Tapering TNF Inhibitors" Pharmaceuticals 18, no. 10: 1506. https://doi.org/10.3390/ph18101506
APA StyleLayegh, Z., Hooijberg, F., Boekel, L., Looijen, A. E. M., van Mulligen, E., Loeff, F. C., Dijk, L., Dolhain, R. J. E. M., Rispens, T., Wolbink, G. J., & de Jong, P. H. P. (2025). The Association Between Serum Drug Concentration and a Flare in Rheumatoid Arthritis Patients Tapering TNF Inhibitors. Pharmaceuticals, 18(10), 1506. https://doi.org/10.3390/ph18101506