Early Anti-Drug Antibodies Predict Adalimumab Response in Juvenile Idiopathic Arthritis
Abstract
:1. Introduction
2. Results
2.1. Patients’ Characteristics
2.2. Comparison Between the Response and Non-Response Groups
2.3. Role of Anti-Drug Antibodies in Adalimumab Treatment Response Prediction
2.4. Factors Related to Immunogenicity
2.5. Role of Anti-Drug Antibodies in Predicting Disease Relapse
3. Discussion
4. Materials and Methods
4.1. Study Subjects
4.2. Ethics
4.3. Treatment Response
4.4. Anti-Adalimumab Antibodies
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ANA | Antinuclear antibody |
AUC | Area under curve |
CRP | C-reactive protein |
DMARDs | Disease-modifying anti-rheumatic drugs |
ERA | Enthesitis-related arthritis |
ESR | Erythrocyte sedimentation rate |
HLA-B27 | Human leukocyte antigen B27 |
JIA | Juvenile idiopathic arthritis |
MTX | Methotrexate |
NSAIDs | Non-steroidal anti-inflammatory drugs |
RF | Rheumatoid factor |
SI | Sacroiliac |
TMJ | Temporomandibular joint |
TNF-α | Tumor necrosis factor alpha |
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n = 65 | |
---|---|
Male subjects, n (%) | 40 (61.5) |
Age at diagnosis, mean ± SD, years | 10.47 ± 3.90 |
Disease duration, mean ± SD, years | 7.97 ± 5.53 |
Duration between diagnosis and adalimumab initiation, mean ± SD, years | 3.28 ± 4.97 |
Duration of adalimumab use, mean ± SD, years | 2.64 ± 0.56 |
JIA subtypes, n (%) | |
Oligoarthritis | 1 (1.5) |
Seronegative polyarthritis | 16 (24.6) |
Seropositive polyarthritis | 5 (7.7) |
Enthesitis related arthritis | 42 (64.6) |
Undifferentiated arthritis | 1 (1.5) |
Laboratory parameters, n (%) | |
ANA positive (≥1:80) * | 4 (6.6) |
RF † | 5 (7.9) |
HLA-B27 ‡ | 40 (65.6) |
Previous Medications, n (%) | |
NSAIDs | 62 (95.4) |
Systemic steroids | 55 (84.6) |
Intra-articular glucocorticoid | 25 (38.5) |
Methotrexate | 56 (86.2) |
Sulfasalazine | 30 (46.2) |
Other TNF-α (Etanercept) | 4 (6.2) |
Response Group n = 54 | Non-Response Group n = 11 | p-Value | |
---|---|---|---|
Male subjects, n (%) | 34 (63.0) | 6 (54.5) | 0.601 |
Age at diagnosis, mean ± SD, years | 10.53 ± 3.98 | 10.08 ± 3.62 | 0.791 |
Duration between diagnosis and adalimumab initiation, mean ± SD, years | 2.71 ± 3.65 | 6.52 ± 9.27 | 0.183 |
Duration of adalimumab use, mean ± SD, years | 2.61 ± 5.82 | 2.76 ± 0.46 | 0.972 |
JIA subtypes, n (%) | 0.187 | ||
Oligoarthritis | 1 (1.9) | 0 | |
Seronegative polyarthritis | 13 (24.1) | 3 (27.3) | |
Seropositive polyarthritis | 5 (9.3) | 0 | |
ERA | 35 (64.8) | 7 (63.6) | |
Undifferentiated arthritis | 0 | 1 (9.1) | |
ERA/non-ERA | 35/19 | 7/4 | 1.000 |
Laboratory parameters, n (%) | |||
ANA positive (≥1:80) $ | 4 (8.1) | 0 | 1.000 |
RF † | 4 (7.7) | 1 (9.1) | 1.000 |
HLA-B27 ‡ | 32 (64.0) | 8 (72.7) | 0.581 |
CRP, mean ± SD, mg/L | 35.68 ± 24.35 | 35.50 ± 27.27 | 0.340 |
ESR, mean ± SD, mm/h | 29.37 ± 17.86 | 31.45 ± 25.15 | 0.971 |
Concomitant medications used, n (%) | |||
NSAIDs | 13 (24.1) | 3 (27.3) | 1.000 |
Systemic steroids | 5 (9.3) | 3 (27.3) | 0.126 |
Methotrexate | 51 (94.4) | 11 (100) | 1.000 |
Sulfasalazine | 8 (14.8) | 4 (36.4) | 0.194 |
Initial joint involvement, n | |||
TMJs | 5 | 4 | 0.038 * |
SI joints | 8 | 3 | 0.379 |
Enthesitis, n (%) | 7 | 0 | 0.592 |
Uveitis, n (%) | 4 | 0 | 1.000 |
Anti-adalimumab antibodies | |||
Detectable, n (%) | 17 (31.5) | 8 (73.7) | 0.023 * |
Concentrations, mean ± SD, ng/mL | 48.89 ± 200.15 | 287.59 ± 444.48 | 0.002 * |
Antibodies ≥ 7.426 ng/mL n = 17 | Antibodies < 7.426 ng/mL n = 33 | p-Value | |
---|---|---|---|
Male subjects, n (%) | 8 (47.1) | 23 (69.7) | 0.118 |
Age at diagnosis, mean ± SD, years | 10.50 ± 3.14 | 10.36 ± 4.14 | 0.900 |
Duration between diagnosis and adalimumab initiation, mean ± SD, years | 4.43 ± 7.54 | 2.63 ± 3.46 | 0.493 |
Duration of adalimumab use, mean ± SD, years | 2.61 ± 0.53 | 2.59 ± 0.64 | 0.935 |
JIA subtypes, n (%) | 0.111 | ||
Oligoarthritis | 0 | 1 (3.0) | |
Seronegative polyarthritis | 6 (35.3) | 9 (27.3) | |
Seropositive polyarthritis | 2 (11.8) | 0 | |
ERA | 8 (47.1) | 23 (69.7) | |
Undifferentiated arthritis | 1 (5.9) | 0 | |
ERA/non-ERA | 8/9 | 23/10 | 0.118 |
Laboratory parameters, n (%) | |||
ANA positive $ (≥1:80) | 2 (12.5) | 2 (6.7) | 0.602 |
RF † | 2 (12.5) | 0 | 0.106 |
HLA-B27 ‡ | 8 (50.0) | 22 (73.3) | 0.114 |
CRP, mean ± SD, mg/L | 36.45 ± 31.01 | 35.14 ± 20.24 | 0.095 |
ESR, mean ± SD, mm/h | 24.00 ± 17.31 | 30.71 ± 17.89 | 0.129 |
Concomitant medications between 0–6 month, n (%) | |||
NSAIDs | 15 (88.2) | 32 (97.0) | 0.264 |
Oral Steroids | 14 (82.4) | 26 (78.8) | 1.000 |
Methotrexate | 17 (100) | 31 (93.9) | 0.542 |
Sulfasalazine | 7 (41.2) | 15 (45.5) | 0.703 |
Initial joint involvement, n | |||
TMJs | 3 | 3 | 0.396 |
SI joints | 2 | 7 | 0.699 |
Enthesitis, n (%) | 0 | 7 (21.2) | 0.080 |
Uveitis, n (%) | 1 (5.9) | 3 (9.1) | 1.000 |
Remission n = 22 | Relapse n = 32 | p-Value | |
---|---|---|---|
Male subjects, n (%) | 16 (72.7) | 18 (56.3) | 0.218 |
Age at diagnosis, mean ± SD, years | 10.36 ± 3.79 | 10.66 ± 4.17 | 0.753 |
Duration between diagnosis and adalimumab initiation, mean ± SD, years | 2.74 ± 3.58 | 2.70 ± 3.77 | 0.677 |
Duration of adalimumab use, mean ± SD, years | 2.50 ± 0.55 | 2.79 ± 0.44 | 0.000 * |
JIA subtypes, n (%) | 0.854 | ||
Oligoarthritis | 0 | 1 (3.1) | |
Seronegative polyarthritis | 5 (22.7) | 8 (25.0) | |
Seropositive polyarthritis | 2 (9.1) | 3 (9.4) | |
ERA | 15 (68.2) | 20 (62.5) | |
Undifferentiated arthritis | 0 | 0 | |
ERA/non-ERA | 15/7 | 20/12 | 0.667 |
Laboratory parameters, n (%) | |||
ANA positive (≥1:80) $ | 0 (0.0) | 4 (14.3) | 0.125 |
RF † | 2 (9.1) | 2 (6.7) | 1.000 |
HLA-B27 ‡ | 14 (66.7) | 18 (62.1) | 0.774 |
CRP, mean ± SD, mg/L | 30.42 ± 18.78 | 39.68 ± 27.55 | 0.224 |
ESR, mean ± SD, mm/h | 26.48 ± 13.98 | 31.40 ± 20.11 | 0.559 |
Concomitant medications used, n (%) | |||
NSAIDs | 2 (9.1) | 11 (34.4) | 0.051 |
Systemic steroids | 0 | 5 (15.6) | 0.072 |
Methotrexate | 19 (86.4) | 32 (100) | 0.062 |
Sulfasalazine | 2 (9.1) | 6 (18.8) | 0.449 |
Initial joint involvement, n | |||
TMJs | 4 | 1 | 0.146 |
SI joints | 2 | 6 | 0.449 |
Enthesitis, n (%) | 2 (9.1) | 5 (15.6) | 0.687 |
Uveitis, n (%) | 2 (9.1) | 2 (6.3) | 1.000 |
Anti-adalimumab antibodies | |||
Antibodies ≥ 7.426 ng/mL, n (%) | 2/17 (11.8) | 8/24 (33.3) | 0.152 |
Concentrations, mean ± SD, ng/mL | 5.10 ± 16.72 | 79.92 ± 258.95 | 0.032 * |
Adalimumab schedule, n | |||
Every other week | 13 | 10 | 0.042 * |
Prolonged interval (>2 weeks) | 9 | 22 |
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Huang, B.-H.; Hsu, J.-L.; Huang, H.-Y.; Huang, J.-L.; Yeh, K.-W.; Chen, L.-C.; Lee, W.-I.; Yao, T.-C.; Ou, L.-S.; Lin, S.-J.; et al. Early Anti-Drug Antibodies Predict Adalimumab Response in Juvenile Idiopathic Arthritis. Int. J. Mol. Sci. 2025, 26, 1189. https://doi.org/10.3390/ijms26031189
Huang B-H, Hsu J-L, Huang H-Y, Huang J-L, Yeh K-W, Chen L-C, Lee W-I, Yao T-C, Ou L-S, Lin S-J, et al. Early Anti-Drug Antibodies Predict Adalimumab Response in Juvenile Idiopathic Arthritis. International Journal of Molecular Sciences. 2025; 26(3):1189. https://doi.org/10.3390/ijms26031189
Chicago/Turabian StyleHuang, Bo-Han, Jr-Lin Hsu, Hsin-Yi Huang, Jing-Long Huang, Kuo-Wei Yeh, Li-Chen Chen, Wen-I Lee, Tsung-Chieh Yao, Liang-Shiou Ou, Syh-Jae Lin, and et al. 2025. "Early Anti-Drug Antibodies Predict Adalimumab Response in Juvenile Idiopathic Arthritis" International Journal of Molecular Sciences 26, no. 3: 1189. https://doi.org/10.3390/ijms26031189
APA StyleHuang, B.-H., Hsu, J.-L., Huang, H.-Y., Huang, J.-L., Yeh, K.-W., Chen, L.-C., Lee, W.-I., Yao, T.-C., Ou, L.-S., Lin, S.-J., Su, K.-W., & Wu, C.-Y. (2025). Early Anti-Drug Antibodies Predict Adalimumab Response in Juvenile Idiopathic Arthritis. International Journal of Molecular Sciences, 26(3), 1189. https://doi.org/10.3390/ijms26031189