Medication for IBD – What’s new? - SAGES · Medication for IBD – What’s new? ... Your immune system can “react to them” TNF-α ... Patients don’t usually take the drugs

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Diagnosis and Management

Dr K Govender

Gastroenterologist

Medication for IBD – What’s new?

Dr Kugan Govender

Gastroenterologist

Entabeni Hospital

Durban

Inflammatory Bowel Disease (IBD)

Inflammatory Bowel Disease

Inflammation of bowel

No known cause; No cure

CD – Any part of gut / ‘skip’ areas

UC – Colon only / Continuous inflammation

Treatment directed at inflammation anti-inflam

Overview Goals of treatment?

Currently available medications for IBD?

How do we use IBD drugs?

Which treatment to use?

How to optimise current medical therapy?

Newer treatment strategies?

New IBD drugs?

Future concepts?

Goals of Treatment

Doctor

Healing of the intestine

Prevent long-term complications of IBD

Drug safety

Patient

Feel healthy

No drug side effects

Medication that is simple to use

Avoid surgery

Goals of Treatment

Current medications used in IBD

1) Antibiotics: Ciprofloxacin; Metronidazole

- Useful for infective complications of Crohn’s (abscess; peri-anal

disease; fistulae)

2) Corticosteroids (‘Cortisone’): Prednisone; Entocort®

- Short term use; Side effects

- Oral / topical (enema) / Intravenous

- For both UC and Crohn’s

3) 5-ASA (Salicylates): Salazopyrine®; Ascacol®; Pentasa®

- For UC (usual first-line treatment)

- Oral / Suppository / Enema

- Little effect in Crohn’s

Current medications used in IBD

4) Immune-modulators: Azapress®; Azamun®; Puri-Nethol®;

Methotrexate

- Useful in both UC and Crohn’s

- ‘Steroid sparing’

- Takes 2-4 months to work

5) Biologicals (Anti-TNF): Revellex®; Humira®

- For both UC and Crohn’s

- Most effective therapy in IBD

- Reserved for severe disease

Why are they called Biologicals?

Products made from natural sources – human / animal etc

Produced by biotechnology

Expensive to make

Your immune system can “react to them” TNF-α (Tumor necrosis factor) is a key player in the immune response in IBD

Common IBD biologics – are antibodies against TNF-α (therefore Anti-TNF) NB: Risk of infections while on Biologics

Side effects of steroids

AVOID STEROIDS !

How do we use IBD drugs?

2 phases of treatment: 1) Induce Remission - Steroids (Prednisone; Budesonide) - Biologics (Revellex® ; Humira®) 2) Maintain Remission - 5-ASA (Pentasa®; Asacol®) - Immune-modulators (Azapress®; Methotrexate) - Biologics

INDUCTION

MAINTENANCE

Which treatment to use?

Crohn’s or Ulcerative Colitis? Extent (How much bowel involved?) Severity (How bad is it?) Age / Sex Personal preference Other illnesses / chronic disease

How do we optimise current drug therapy?

1) Right drug for the right patient

Individualise treatment Tailor according to your symptoms / severity / extent /

other illnesses / affordability Adequate dosage Try to avoid / reduce steroids

Optimising treatment

2) Optimising 5-ASA treatment (Pentasa®; Asacol®; Mezavant®)

Useful for Ulcerative Colitis Patients don’t usually take the drugs (poor compliance due to frequent dosing) Once daily equivalent to 3 times daily (better compliance) Combining oral tablets with enema / suppository useful Modified release tabs available (Mezavant)

Optimising treatment

3) Optimising use of Azathioprine (and 6-MP)

Thiopurine methyltransferase activity (TPMT) 1 in 300 patients may have severe bone marrow suppression with Azathioprine (Azapress®) TPMT level predicts who will have suppression Low level Cannot use Azathioprine

Optimising treatment

4) Combination therapy

Drugs act together to control disease Biologics + Immune-modulator 5-ASA + Immune-modulator Reduce need for steroids

Reduce overall side effects

Optimising treatment

5) Monitoring disease and predicting flares

Blood markers (CRP)

Stool markers (Calprotectin) Monitoring of Biologic (Anti-TNF levels)

Monitoring of Azathioprine (6-TGN levels)

Newer Treatment Strategies

“Step-up” Treatment Early “Top-down”

‘Step up’ and ‘Top down’ Strategies

Step-up treatment

- Start with steroids / 5-ASA - Then add on immune-modulator if no response - Biological agents later if no response

Strategies

Early top-down

- Start with Biological agent and immune-modulator at outset

- Taper treatment as required

- May be considered for: - Severe disease on presentation - Early onset (<40 yrs) - Extensive disease - Peri-anal / fistulising - Involvement of areas outside of the bowel

Strategies

New drugs for IBD

1) Golimumab (Simponi®) 2) Vedolizumab (Entyvio®) 3) Biosimilars

Golimumab (Simponi ®)

- Human antibody (similar to Humira®)

- Now approved for UC in South Africa

- Subcutaneous injection

- 4 weekly injections

- Similar side effect profile to other biologics

New drugs

Vedolizumab (Entyvio ®)

- Biologic - Not Anti-TNF; Specific drug designed for IBD

- Blocks receptors on inflammatory cells

- Prevents adhesion of the inflammatory cells to the wall of

blood vessels

- Prevents inflammatory cells from reaching the gut mucosa

- Useful in patients who have failed on other treatments

New drugs

Biosimilars

- Generic biologics

- Not available yet

- Lower cost?

- Similar efficacy?

- Greater affordability may make biosimilars available to more patients

New drugs

Future concepts?

“Mongersen” - Oral Biologic agent - Fast acting with response within 2 weeks - Longer trial required

Ongoing trials

Multiple drugs / pathways

Take home messages

Avoid steroids Use of drugs in combination / at correct dose

Markers to predict inflammation / flare

Once daily use of 5-ASA drugs works

Combining oral and topical 5-ASA effective TPMT activity prior to starting Azathioprine Step up vs Top down tailor treatment for individual patient

Vedolizumab – new exciting biologic