Association between HLA DNA Variants and Long-Term Response to Anti-TNF Drugs in a Spanish Pediatric Inflammatory Bowel Disease Cohort
Abstract
:1. Introduction
2. Results
2.1. Patients
2.2. Genotyping and Frequencies
2.3. Association of rs2097432 with Response to Anti-TNF Drugs
2.4. Association between rs2395185 and Response to Anti-TNF Drugs
2.5. Haplotypes of rs2395185 and rs2097432 with Response to Anti-TNF Drugs
2.6. Comparison of Children with Adults with Crohn’s Disease and Treated with IFX
3. Discussion
4. Materials and Methods
4.1. Study Design and Patient Characteristics
4.2. DNA Isolation and Genotyping
4.3. Statistical Analysis
4.4. Ethics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | Overall (n = 340) | Responders (n = 270) | Non-Responders (n = 70) | p Value |
---|---|---|---|---|
Sex | ||||
Male, n (%) | 205 (60.3%) | 168 (82.0%) | 37 (18.0%) | 0.171 |
Female, n (%) | 135 (39.7%) | 102 (75.6%) | 33 (24.4%) | |
Age (years) | ||||
At diagnosis, median (IQR, range) | 11.2 (4.0, 0.7–17.3) | 11.2 (3.8, 0.9–17.3) | 11.0 (5.8, 0.7–16.0) | 0.109 |
At start of treatment, median (IQR, range) | 12.2 (4.1, 1.1–17.5) | 12.3 (4.1, 1.4–17.5) | 12.0 (4.3, 1.1–17.3) | 0.251 |
Months from diagnosis to initiation of therapy, median (IQR, range) | 6.1 (15.9, 0.0–129.6) | 6.1 (15.3, 0–129.6) | 8.9 (18.2, 0.0–125.8) | 0.202 |
Type of IBD | ||||
CD, n (%) | 240 (70.5%) | 201 (83.8%) | 39 (16.3%) | |
UC, n (%) | 93 (27.4%) | 63 (67.7%) | 30 (32.3%) | 0.012 |
IC, n (%) | 7 (2.1%) | 6 (85.7%) | 1 (14.3%) | |
First or second biological treatment | ||||
1st, n (%) | 318 (93.5%) | 259 (81.4%) | 59 (18.6%) | 0.001 |
2nd, n (%) | 22 (6.5%) | 11 (50.0%) | 11 (50.0%) | |
Drug | ||||
Infliximab, n (%) | 228 (67.1%) | 185 (81.1%) | 43 (18.9%) | 0.318 |
Adalimumab, n (%) | 112 (32.9%) | 85 (75.9%) | 27 (24.1%) | |
Concomitant immunomodulator (n = 330) | ||||
Yes, n (%) | 286 (86.7%) | 229 (80.1%) | 57 (19.9%) | 0.843 |
No, n (%) | 44/13.3%) | 36 (81.8%) | 8 (18.2%) | 0.843 |
Type of immunotherapy (n = 283) | ||||
Azathioprine | 266 (81.6%) | 215 (80.8%) | 51 (19.2%) | |
Mercaptopurine | 3 (0.9%) | 2 (66.7%) | 1 (33.3%) | 0.947 |
Methotrexate | 14 (4.3%) | 10 (71.4%) | 4 (28.6%) |
Characteristics | Overall (n = 131) | Responders (n = 77) | Non-Responders (n = 54) | p Value |
---|---|---|---|---|
Sex | ||||
Male, n (%) | 66 (50.4%) | 41 (62.1%) | 25 (37.9%) | 0.480 |
Female, n (%) | 65 (49.6%) | 36 (55.4%) | 29 (44.6%) | |
Age (years) | ||||
At diagnosis, median (IQR, range) | 27.2 (16.4; 10.8–76.7) | 27.7 (18.2; 10.8–76.7) | 26.7 (15.9; 11.7–58.7) | 0.359 |
At start of treatment, median (IQR, range) | 37.4 (18.5; 12.5–81.4) | 36.6 (19; 12.5–81.4) | 35.5 (18.2; 16.2–64.5) | 0.818 |
First or second biological treatment | ||||
1st, n (%) | 119 (90.8%) | 73 (60.3%) | 48 (39.7%) | 0.317 |
2nd, n (%) | 12 (9.2%) | 4 (40%) | 6 (60%) | |
Concomitant immunomodulator (n = 128) | ||||
Yes, n (%) | 68 (51.9%) | 47 (69.1%) | 21 (30.9%) | 0.045 |
No, n (%) | 60 (45.8%) | 30 (50%) | 30 (50%) | |
Type of immunotherapy | ||||
Azathioprine | 54 (79.4%) | 39 (72.2%) | 15 (27.8%) | 0.870 |
Mercaptopurine | 4 (5.9%) | 4 (100%) | 0 (0%) | |
Methotrexate | 7 (10.3%) | 2 (28.6%) | 5 (71.4%) | |
Mycophenolate | 3 (4.4%) | 2 (66.7%) | 1 (33.3%) |
rs2097432 | rs2395185 | Risk Group |
---|---|---|
TT | TT or GT | Low |
CC 1 or CT 1 | TT or GT | Medium |
TT | GG 1 | Medium |
CC 1 or CT 1 | GG 1 | High |
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Salvador-Martín, S.; Zapata-Cobo, P.; Velasco, M.; Palomino, L.M.; Clemente, S.; Segarra, O.; Sánchez, C.; Tolín, M.; Moreno-Álvarez, A.; Fernández-Lorenzo, A.; et al. Association between HLA DNA Variants and Long-Term Response to Anti-TNF Drugs in a Spanish Pediatric Inflammatory Bowel Disease Cohort. Int. J. Mol. Sci. 2023, 24, 1797. https://doi.org/10.3390/ijms24021797
Salvador-Martín S, Zapata-Cobo P, Velasco M, Palomino LM, Clemente S, Segarra O, Sánchez C, Tolín M, Moreno-Álvarez A, Fernández-Lorenzo A, et al. Association between HLA DNA Variants and Long-Term Response to Anti-TNF Drugs in a Spanish Pediatric Inflammatory Bowel Disease Cohort. International Journal of Molecular Sciences. 2023; 24(2):1797. https://doi.org/10.3390/ijms24021797
Chicago/Turabian StyleSalvador-Martín, Sara, Paula Zapata-Cobo, Marta Velasco, Laura M. Palomino, Susana Clemente, Oscar Segarra, Cesar Sánchez, Mar Tolín, Ana Moreno-Álvarez, Ana Fernández-Lorenzo, and et al. 2023. "Association between HLA DNA Variants and Long-Term Response to Anti-TNF Drugs in a Spanish Pediatric Inflammatory Bowel Disease Cohort" International Journal of Molecular Sciences 24, no. 2: 1797. https://doi.org/10.3390/ijms24021797
APA StyleSalvador-Martín, S., Zapata-Cobo, P., Velasco, M., Palomino, L. M., Clemente, S., Segarra, O., Sánchez, C., Tolín, M., Moreno-Álvarez, A., Fernández-Lorenzo, A., Pérez-Moneo, B., Loverdos, I., Navas López, V. M., Millán, A., Magallares, L., Torres-Peral, R., García-Romero, R., Pujol-Muncunill, G., Merino-Bohorquez, V., ... López-Fernández, L. A. (2023). Association between HLA DNA Variants and Long-Term Response to Anti-TNF Drugs in a Spanish Pediatric Inflammatory Bowel Disease Cohort. International Journal of Molecular Sciences, 24(2), 1797. https://doi.org/10.3390/ijms24021797