Table 1 Advantages and limitations of intravenous/subcutaneous (currently in use) and oral (under investigation) administration of anti-tumor necrosis factor-α-acting molecules in inflammatory bowel disease

The modifiable onset of action (IV—immediate, SC—immediate or modified-release)

Invasive and uncomfortable for the patient

Simplicity of administration

The relatively low onset of action

By definition, avoidance of the first-pass effect and 100% bioavailability

Drug administration usually needs a healthcare professional support and guidance

No need for technical healthcare professional support

Bioavailability below 100% and to some extent unpredictable pharmacokinetics due to possible interaction with gastrointestinal fluid content

A high systemic drug concentration is achievable

Usually need for visiting hospital or outpatient (with different frequency)

No need for regular visiting hospital and/or outpatient clinic

First-pass effect (does not refer to the idea of local oral administration aimed at targeting the inflamed intestinal wall)

Systemic mode of action (if needed)

The drug needs to be prepared in sterile conditions (IV)

Comfortable and painless application

Difficult to use in the case of uncooperative and unconscious patients

Possible in uncooperative and unconscious patients

In case of false dosing, higher risk of overdosing

Improved safety issues

Contraindicated in patients with intestinal obstruction

Possible in vomiting patients and the case of intestinal obstruction

Systemic mode of action (if not needed)

Targeted mode of action directly in the inflamed intestinal wall

Possible interference with food products

No direct interference with food

Specific adverse effects (IV—thrombophlebitis, catheter-related bloodstream infection; tissue necrosis—SC)

No or limited systemic exposure (if not needed)

Limited systemic mode of action (if needed)

Immunogenicity and risk of secondary loss of response

Low immunogenicity and lower risk of secondary loss of response

Possibility of overdosing

Costs

The modifiable onset of release and action (depending on drug design)

Biocompatibility and biodegradability (“eco-friendliness”)

Improvement in drug stability (especially in the case of lipid nanoparticles)

Costs