Factors related to immunogenicity of anti-TNF therapy in IBD
| Factor | ADA | Ref. |
|---|---|---|
| Patient-related | ||
| Genetic predisposition: HLA-DRB1*03 | ↑ | 48 |
| Gender: male† | ↑ | 7 31 45 49 |
| Ethnicity: Jewish Ashkenazi | ↓ | 50 |
| BMI: high or low† | ↑ | 45 47 49 |
| CRP: elevated† | ↑ | 7 11 31 32 49 |
| Albumin: low† | ↑ | 7 47 49 |
| Disease-related | ||
| IBD type: (acute severe) UC† | ↑ | 7 17 20 31 |
| TNF load: higher† | ↑ | 51 |
| Endoscopic severity: higher Mayo score in UC† | ↑ | 7 31 |
| Treatment-related | ||
| Concomitant medication: IMM‡ | ↓ | 7 8 10 15 20 23 49 52–54 |
| Dose and frequency: high§ | ↓ | 55 |
| Type of therapy: episodic | ↑ | 15 20 55 |
| Previous medication: prior anti-TNF therapy | ↑ | 28 36 51 |
†Probably related, via undetectable or low drug concentrations due to faster non-immune clearance as a result of higher disease inflammatory burden.
‡Thiopurines, methotrexate.
§In patients not receiving IMM, there was approximately twofold difference in ADA prevalence between 5 and 10 mg/kg doses, suggesting that lower doses were more immunogenic in the absence of IMM.
ADA, antidrug antibodies; BMI, body mass index; CRP, C reactive protein; HLA, human leucocyte antigen; IBD, inflammatory bowel disease; IMM, immunomodulators; TNF, tumour necrosis factor; UC, ulcerative colitis.