TABLE 4.
Cox proportional hazards regression analyses of associations between (2log‐transformed) serum biomarker levels and the risk of (A) progression or recurrence of stricturing disease, (B) progression or recurrence of penetrating disease and (C) CD‐related surgical interventions
| HR per doubling a (95% CI) | Tertiles per biomarker b | |||
|---|---|---|---|---|
| Tertile 1 (low) | Tertile 2 (mid) | Tertile 3 (high) | ||
| A. Stricturing disease | ||||
| C1M | 1.17 (0.79–1.73), p = 0.424 | 0.77 (0.30–1.99), p = 0.768 | 0.51 (0.18–1.44), p = 0.511 | 1.00 (reference) |
| C3M | 0.76 (0.29–1.95), p = 0.563 | 1.06 (0.40–2.85), p = 0.906 | 0.96 (0.34–2.75), p = 0.944 | 1.00 (reference) |
| PRO‐C3 | 0.66 (0.30–1.45), p = 0.301 | 1.43 (0.53–3.85), p = 0.478 | 0.90 (0.31–2.56), p = 0.836 | 1.00 (reference) |
| C3M/PRO‐C3 | 1.16 (0.59–2.30), p = 0.669 | 0.77 (0.30–2.00), p = 0.769 | 0.54 (0.19–1.53), p = 0.542 | 1.00 (reference) |
| C4M | 0.85 (0.36–1.97), p = 0.699 | 1.32 (0.51–3.42), p = 0.562 | 0.63 (0.20–1.99), p = 0.630 | 1.00 (reference) |
| PRO‐C4 | 1.11 (0.56–2.18), p = 0.764 | 0.53 (0.20–1.38), p = 0.193 | 0.54 (0.20–1.49), p = 0.236 | 1.00 (reference) |
| PRO‐C4/C4M | 1.78 (0.53–5.99), p = 0.352 | 0.37 (0.13–1.06), p = 0.063 | 0.54 (0.21–1.40), p = 0.207 | 1.00 (reference) |
| C4G | 1.08 (0.61–1.89), p = 0.800 | 0.86 (0.36–2.07), p = 0.739 | 0.26 (0.07–1.03), p = 0.065 | 1.00 (reference) |
| C6Ma3 | 2.01 (0.89–4.57), p = 0.095 | 0.61 (0.21–1.76), p = 0.360 | 1.19 (0.46–3.09), p = 0.720 | 1.00 (reference) |
| B. Penetrating disease | ||||
| C1M | 1.33 (0.90–1.97), p = 0.154 | 1.00 (reference) | 5.91 (1.31–26.7), p = 0.021 | 4.73 (1.00–22.3), p = 0.049 |
| C3M | 2.18 (0.87–5.47), p = 0.098 | 1.00 (reference) | 0.51 (0.15–1.68), p = 0.265 | 1.48 (0.58–3.77), p = 0.411 |
| PRO‐C3 | 1.16 (0.50–2.69), p = 0.723 | 1.00 (reference) | 0.75 (0.25–2.25), p = 0.609 | 1.21 (0.45–3.26), p = 0.707 |
| C3M/PRO‐C3 | 1.33 (0.69–2.53), p = 0.393 | 1.00 (reference) | 1.17 (0.39–3.49), p = 0.777 | 1.74 (0.62–4.93), p = 0.296 |
| C4M | 1.53 (0.69–3.39), p = 0.297 | 1.00 (reference) | 1.52 (0.53–4.38), p = 0.440 | 1.64 (0.57–4.74), p = 0.365 |
| PRO‐C4 | 2.24 (1.07–4.71), p = 0.033 | 1.00 (reference) | 1.91 (0.62–5.89), p = 0.258 | 2.10 (0.70–6.28), p = 0.184 |
| PRO‐C4/C4M | 4.81 (1.13–20.4), p = 0.033 | 1.00 (reference) | 1.58 (0.52–4.85), p = 0.420 | 1.86 (0.62–5.55), p = 0.266 |
| C4G | 1.71 (1.05–2.81), p = 0.032 | 1.00 (reference) | 0.53 (0.13–2.11), p = 0.366 | 2.66 (1.01–7.01), p = 0.048 |
| C6Ma3 | 2.00 (0.87–4.62), p = 0.104 | 1.00 (reference) | 3.03 (0.95–9.67), p = 0.062 | 2.30 (0.69–7.64), p = 0.175 |
| C. Surgical interventionsc | ||||
| C1M | 1.39 (0.94–2.06), p = 0.099 | 1.00 (reference) | 2.14 (0.66–6.98), p = 0.208 | 3.13 (0.96–10.2), p = 0.059 |
| C3M | 1.24 (0.49–3.12), p = 0.648 | 1.00 (reference) | 0.48 (0.15–1.57), p = 0.226 | 1.19 (0.47–3.01), p = 0.714 |
| PRO‐C3 | 1.01 (0.42–2.44), p = 0.975 | 1.00 (reference) | 0.50 (0.16–1.53), p = 0.223 | 1.05 (0.40–2.72), p = 0.922 |
| C3M/PRO‐C3 | 1.12 (0.56–2.25), p = 0.752 | 1.00 (reference) | 0.70 (0.24–2.01), p = 0.504 | 1.13 (0.42–3.04), p = 0.806 |
| C4M | 1.07 (0.47–2.39), p = 0.879 | 1.00 (reference) | 1.01 (0.36–2.78), p = 0.993 | 1.10 (0.40–3.06), p = 0.854 |
| PRO‐C4 | 1.41 (0.70–2.87), p = 0.340 | 1.00 (reference) | 1.67 (0.58–4.86), p = 0.345 | 1.75 (0.60–5.08), p = 0.304 |
| PRO‐C4/C4M | 2.76 (0.64–11.9), p = 0.173 | 1.00 (reference) | 1.18 (0.40–3.51), p = 0.767 | 1.64 (0.58–4.61), p = 0.352 |
| C4G | 1.00 (0.55–1.80), p = 0.990 | 1.00 (reference) | 0.23 (0.05–1.05), p = 0.058 | 1.46 (0.61–3.54), p = 0.398 |
| C6Ma3 | 2.08 (0.87–5.00), p = 0.101 | 1.00 (reference) | 2.61 (0.88–7.67), p = 0.082 | 1.80 (0.57–5.71), p = 0.320 |
Abbreviations: CI, confidence interval; HR, hazard ratio; MV, multivariable analysis; UV, univariable analysis.
a
Biomarker levels were 2log‐transformed before entry into the model as a continuous predictor, facilitating results interpretation (per doubling).
b
Per biomarker, levels were divided into tertiles with the lowest tertile (Tertile 1) set as a reference standard in the model.