Multivariable adjusted HRs for ADA development during anti-TNF therapy
| Variable | aHR (95% CI) | |
| Categorical | Continuous | |
| Antibiotics (primary exposure variables) | ||
| Cephalosporins | 1.97 (1.58 to 2.44) | 1.23 (1.17 to 1.28) |
| Penicillin-BLIs | 1.40 (1.13 to 1.74) | 1.11 (1.05 to 1.17) |
| Metronidazole | 0.88 (0.70 to 1.10) | 0.99 (0.96 to 1.04) |
| Penicillins | 0.79 (0.64 to 0.98) | 0.90 (0.83 to 0.97) |
| Macrolides | 0.36 (0.16 to 0.82) | 0.62 (0.37 to 1.03) |
| Fluoroquinolones | 0.20 (0.12 to 0.35) | 0.50 (0.39 to 0.65) |
| Secondary effects (confounders) | ||
| Adalimumab vs infliximab | 0.53 (0.43 to 0.66) | 0.53 (0.43 to 0.66) |
| Crohn’s vs UC | 0.67 (0.52 to 0.87) | 0.64 (0.49 to 0.83) |
| Previous anti-TNF (yes vs no) | 1.52 (1.23 to 1.88) | 1.55 (1.25 to 1.90) |
| Hospitalisations (yes vs no) | 0.89 (0.79 to 1.00) | 1.01 (0.97 to 1.05) |
| Surgeries (yes vs no) | 1.18 (0.90 to 1.54) | 1.03 (0.80 to 1.32) |
| Albumin (per increase of 1 g/dL) | 0.94 (0.74 to 1.19) | 1.01 (0.79 to 1.27) |
| CRP (per increase of 1 mg/dL) | 1.03 (1.02 to 1.04) | 1.04 (1.03 to 1.04) |
| Corticosteroids (yes vs no) | 1.16 (0.90 to 1.49) | 1.10 (0.85 to 1.41) |
| Methotrexate (yes vs no) | 0.86 (0.54 to 1.23) | 0.78 (0.54 to 1.14) |
| Thiopurines (yes vs no) | 0.67 (0.54 to 0.83) | 0.65 (0.52 to 0.80) |
Data are shown for Cox proportional hazards models. Rows represent the covariates incorporated in the model and ordered as primary exposures of interest or secondary effects. Antibiotic classes were incorporated as time dependent covariates as either categorical variables defined as any use of specific class during the time period (3 years) in one model or as continuous variables defined as total sum of dispensations of antibiotics from this class during the same period in the second model.
ADA, anti-drug antibodies; aHR, adjusted HR; anti-TNF, anti-tumour necrosis factor ; BLI, beta lactamase inhibitors; CRP, C reactive protein; UC, ulcerative colitis.