Advanced therapy in Inflammatory Bowel Disease (IBD)

Apr 06, 2022

Treatment for IBD has gone through a major revolution with advent of biologic therapy in the 1990s, initially with Remicade to treat fistulising Crohn’s disease.

Medical treatment options have continued to evolve with availability of newer biologics and novel small-molecules. Collectively, these medications are referred to as advanced therapy in IBD. They are targeted therapy with known mechanism of action.

What is a biologic?

Conventional medicine such as paracetamol, antibiotics or prednisone are produced through a chemical reaction process. They are small compounds with precisely known ingredients. These are usually taken orally.

Biologics are medicine produced by a biological process, through living organisms where the active substance produced are called monoclonal antibodies. Antibodies are large complex protein therefore it has to be given as subcutaneous injection or infusion. In the setting of Inflammatory Bowel Disease (IBD), these antibodies are developed to block a certain aspect of the body’s immune system in order to reduce inflammation so healing may take place. Biologics work in a similar fashion as Random Breath Testing (RBT) unit in its specific target. Biologics are the RBTs that remove specific inflammation causing cells or signals out of the circulation, joints, skin or intestines.

Biologics are powerful immunosuppression medications and may be associated with an increased risk of opportunistic infection therefore a screening process is needed prior. This is the first step in which a close collaboration with General Practitioner is important. Blood tests looking for the immune status of preventable infections such as hepatitis B, Herpes zoster or MMR for examples are performed and patients are encouraged to see their GPs to complete the vaccination program where it is safe to do so. We also look for certain past infections which may be reactivated such as Tuberculosis (TB), CMV, EBV, chicken pox. Tuberculosis is one that requires specific treatment prior to initiating biologic.

The advantage of biologic therapy over convention therapy is that the mechanism of action is known and it precisely targeting factors responsible for IBD. Unlike corticosteroids (for example - Prednisone), which affect the whole body and may produce major side effects. Biologic agents act more selectively. These therapies targeted particular proteins that have already been proven to be involved in IBD. Examples include

Anti-Tumour Necrosis Factor (TNFα) Agents

• bind and block a small protein called TNFα that promotes inflammation in the intestine as well as other organs and tissues.
• Examples include: Infliximab, Adalimumab, Golimumab (IV +/- S/C)

Integrin Receptor Antagonists (α4b7)

• prevent the movement of cells that cause inflammation out of circulation and into intestines by blocking a protein on the surface of those cells.
• Example: Vedolizumab (IV +/- S/C)

Interleukin-12 and -23 Antagonist

• targets specific proteins (IL-23 and IL-12) that play a key role in the inflammation process
• Example: Ustekinumab (IV then S/C)

What are small- molecules?

Small-molecules are synthesized like conventional medicine with known chemical structure. Unlike the biologics, they are administered orally and does not develop immunogenic reaction over time. Like biologics, their mechanism of action is known with more predictable side effect. Currently, Tofacitinib (pan-JAK inhibitor) is available for ulcerative colitis. Hopefully a couple more small molecules will be submitted to Therapeutic Goods Administration (TGA) for approval within 12 months.

As more advanced IBD treatment become available, it can be overwhelming to decide which one or combination to start with to achieve the best outcome with minimal side effect. Factors such as patient’s preference, disease location and activity, any extra-intestinal manifestation and concurrent/ past medical history influence which therapy to choose. Preconception, pregnancy and breast feeding also influence the decision on medication choice. Specialised experience gained through internationally renounced advanced IBD fellowship counts in this setting!

A reasonable question I commonly get is ‘Do I have to take medications for ever?’ This a tricky one! My approach is to establish an agreed treatment goal with the patient early on. An open and empowering therapeutic relationship is critical. Understanding what is important to my patients and my ability to explain complicated treatment options in simple terms help to give them an idea what to expect. Treatment plan should be fluid and constantly reassessed.

Dr Thomas Lee provides general gastroenterology service and direct access gastroscopy and colonoscopy through Wollongong and Nowra Private Hospital.

Seaview Clinic @ Wollongong Private Hospital
Phone 4210 7870
Fax 4227 1502
info@seaviewclinic.com.au

South Coast Specialist Health Care @ 5 Moss St Nowra
Phone 4445 3858
Fax 8331 6089
admin@scshc.com.au