Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease

Table 4 Risk factors at or after the initial Crohn’s disease surgery associated with time to the second Crohn’s disease surgery

Main effects	HR	95%CI	P value	FDR
Immunomodulators1	0.486	0.306-0.773	0.002	0.026
GM-CSF Ab level	3.493	1.430-8.538	0.005	0.030
GM-CSF cytokine level	2.489	1.292-4.796	0.005	0.030
B2 disease behavior2	1.415	0.517-3.874	0.491	0.624
B3 disease behavior3	0.415	0.146-1.176	0.091	0.145
Smoking4	1.286	0.277-5.981	0.743	0.800
ASCA IgG, U/mL	1.318	0.799-2.174	0.270	0.378
Age at diagnosis	0.983	0.963-1.003	0.094	0.145
Clostridium difficile infection	0.035	0.001-1.092	0.051	0.113
antiTNF-α5	1.272	0.662-2.447	0.461	0.615
ATG16L1 polymorphism	1.793	0.982-3.273	0.052	0.113
IRGM polymorphism	0.092	0.004-2.262	0.136	0.201
ASCA IgA, U/mL	0.976	0.755-1.262	0.852	0.852
NOD2 polymorphisms	1.123	0.741-1.702	0.577	0.673
Interactions
GM-CSF Ab level and smoking	0.612	0.454-0.825	0.001	0.026
GM-CSF cytokine level and ATG16L1	0.652	0.480-0.885	0.005	0.030
GM-CSF Ab level and ASCA IgG, U/mL	0.808	0.674-0.968	0.018	0.081
GM-CSF Ab level and ATG16L1	0.719	0.538-0.962	0.023	0.081
B2 disease behavior and Clostridium difficile	21.57	1.456-319.271	0.023	0.081
B2 disease behavior and smoking	1.601	0.318-8.059	0.560	0.673
B3 disease behavior and smoking	5.117	0.966-27.141	0.050	0.113
GM-CSF Ab level and Clostridium difficile	2.865	1.065-7.715	0.033	0.104
GM-CSF cytokine level and Clostridium difficile	0.902	0.325-2.501	0.840	0.852
Smoking and IRGM	0.406	0.145-1.134	0.079	0.145
ASCA IgG, U/mL and IRGM	1.867	0.908-3.835	0.083	0.145
GMCSF cytokine level and antiTNF-α	0.765	0.562-1.041	0.082	0.145
GM-CSF Ab level and antiTNF-α	0.941	0.703-1.260	0.676	0.757
GM-CSF cytokine level and ASCA IgA, U/mL	0.865	0.750-0.997	0.041	0.113

¹Use of Immunomodulators between first and second CD surgery including: Azathioprine, 6-Mercaptopurine, Methotrexate;

²Stricturing behavior (B2) compared to Inflammatory (B1) disease behavior;

³Penetrating behavior (B3) compared to Inflammatory (B1) disease behavior;

⁴Active smoker before the first CD surgery;

⁵Use of Anti-tumor Necrosis Factor-alpha therapy between first and second CD surgery including: Infliximab, Adalimumab. Cox proportional hazard model; A Cox proportional hazard model was fitted with main effects and first-order interactions of clinical and genotype variables. A stepwise variable selection was performed to select the relevant subset of variables. Within the model, P value was adjusted with the cutoff at FDR < 0.05. Model fitting and selection were generated using R 3.1.1 (http://cran.r-project.org). Table 4 displays the P-values for all fitted terms in the final model. GM-CSF Ab: Granulocyte-macrophage colony-stimulating factor auto-antibodies; ASCA: Anti-Saccharomyces cerevisiae antibodies; CD: Crohn’s disease.