Clinical Guideline
Golimumab, infliximab and adalimumab in the management of moderately to severely active UC (adults)
Indication Golimumab, infliximab and adalimumab are Anti-TNF drugs which are indicated in patients with moderately to severely active ulcerative colitis as defined by the Truelove and Witt’s criteria who have failed to tolerate or had an inadequate response to conventional treatments as outlined below: Topical and oral aminosalicylates Azathioprine or 6-Mercaptopurine Corticosteroids (including steroid dependency)
Truelove & Witt’s criteria for assessing severity of ulcerative colitis
Mild Moderate Severe Number of bowel Fewer than 4 4–6 6 or more movements per day Plus ≥ 1 features of systemic upset (marked *) Blood in stools No more than small Between mild and Visible blood amounts of blood severe Temp> 37.8 °C * No No Yes
Pulse > 90 bpm * No No Yes
Anaemia * No No Yes
ESR * 30 or below 30 or below Above 30
NICE technology appraisal This treatment has been assessed via NICE technology appraisal 329
Prescribing within Wirral University Teaching hospital The algorithm for prescribing golimumab, infliximab and adalimumab is schematically outlined at the end of this guideline They should be prescribed only by Consultant Luminal Gastroenterologists only
Choice of Drug In accordance with NICE TA 329 the choice of treatment between infliximab, adalimumab or golimumab should be made on an individual basis after discussion between the Consultant Luminal Gastroenterologist and the patient about the advantages and disadvantages of the treatments available. This should take into consideration therapeutic need and whether or not the patient is likely to adhere to treatment. If more than 1 treatment is suitable the least expensive should be chosen.
In patients with prior exposure to infliximab (usually rescue treatment for acute severe colitis) Infliximab should be used first line provided there was no history of non-response or significant side effects
In patients without prior exposure to infliximab, golimumab or adalimumab should be used first line due the lower cost of the drugs and associated costs unless compliance is of concern.
Contraindications Severe active infection
Ulcerative colitis-Golimumab, Infliximab and Adalimumab v1 Principle author: Dr Pritchard Approved by: Wirral Drug & Therapeutics Panel: May 2015 Review Date: May 2018
Moderate to severe heart failure Please see BNF for up to date guidance on cautions and side effects.
Pre-screening Patients being considered for treatment with golimumab, infliximab and adalimumab should be screened for the following conditions: HIV (HIV Ab) Hepatitis B (HBV surface Ag & HBV core Ab) Hepatitis C (HCV Ab) TB (Chest X-ray and TB Elispot test) Varicella (Varicella Ab) If evidence of HIV, Hepatitis B and C, TB is found expert advice should be sought from the appropriate specialists and treatment withheld If evidence of lack of immunity to Varicella is found patients should be considered for vaccination prior to treatment if this is not contraindicated, following European Guidelines (European Crohn’s and Colitis Guidelines: Opportunistic Infections, 2014)
Duration of Treatment Treatment should be given until one of the following occurs (whichever is shorter): Failure of treatment (including surgery, non-response or significant side effects) 12 months
Clinical Assessment Patients should be assessed at 4 months by: Clinical evaluation (Truelove and Witts) Inflammatory markers (Crp and Esr) Faecal calprotectin if appropriate Flexible sigmoidoscopy if appropriate Cessation of treatment and reconsideration of surgery or an alternative agent should be considered in primary non-responders
At 12 months patients should again be re-assessed. If there is clear evidence of ongoing response as determined by clinical symptoms, inflammatory markers (and faecal calprotectin and flexible sigmoidoscopy if appropriate) the risks and benefits of continued treatment should be discussed: In those with stable clinical remission a trial of withdrawal of treatment should be discussed. If treatment is withdrawn but the patient relapses they should have the option to restart In those with ongoing response who wish to continue treatment re-evaluation should take place every 12 months
Dosing Golimumab Induction 200mg at week 0, 100mg at week 2 (subcutaneous injection) Maintenance For patient weight <80kg: 50mg every 4 weeks For patient weight >80kg: 100mg every 4 weeks
Infliximab Induction 5mg/kg at week 0, 2, 6 (intravenous infusion) Maintenance 5mg/kg every 8 weeks
Adalimumab Induction 160mg at week 0, 80mg at week 2 (subcutaneous injection) Maintenance 40mg every 2 weeks Ulcerative colitis-Golimumab, Infliximab and Adalimumab v1 Principle author: Dr Pritchard Approved by: Wirral Drug & Therapeutics Panel: May 2015 Review Date: May 2018
Ulcerative colitis-Golimumab, Infliximab and Adalimumab v1 Principle author: Dr Pritchard Approved by: Wirral Drug & Therapeutics Panel: May 2015 Review Date: May 2018
Algorithm for Anti-TNF Drugs in moderately to severely active UC (adults)
Is there a proven diagnosis of UC without evidence of concurrent infection? IF NO Endoscopic evidence Clarify Diagnosis Histological evidence
If YES. Has there been failure to respond/tolerate conventional treatment at maximal dose? Topical and oral aminosalicylates IF NO Azathioprine and mercaptopurine Maximise Steroids (including steroid dependency) conventional treatments
IF YES. Is there moderetely to severely active UC according to Truelove and Witts Criteria? Stool frequency >4 Blood in stools: moderate or more No features of acute severe colitis as defined by fever, tachycardia and anaemia
Surgery IF YES. Discuss risks and benefits of surgery vs Anti-TNF treatment
Anti-TNF Treatment: Contraindications and Prescreening Ensure no contraindications: Moderate to severe heart failure, severe active infection Prescreening tests: TB/HIV/Hep B/HepC/Varicella (Seek expert help if positive)
Anti-TNF Treatment: Choice of drug The choice of treatment between golimumab, infliximab or adalimumab should be made on an individual basis after discussion between the Consultant Luminal Gastroenterologist and the patient about the advantages and disadvantages of the treatments available. Prior exposure to Infliximab, Infliximab should be used first line if no hx of s/e or non-response Without prior exposure to infliximab, golimumab or adalimumab should be used first line
Anti-TNF Treatment: Dosing Golimumab Induction 200mg at week 0, 100mg at week 2 (subcutaneous injection) Maintenance For patient weight <80kg: 50mg every 4 weeks For patient weight >80kg: 100mg every 4 weeks Infliximab Induction 5mg/kg at week 0,2,6 (intravenous infusion) Maintenance 5mg/kg every 8 weeks Adalimumab Induction 160mg at week 0, 80mg at week 2 (subcutaneous injection) Maintenance 40mg every 2 weeks
Clinical Assessment at 4 months Non-responders Withdraw Clinical evaluation (Truelove and Witts) ● Inflammatory markers (Crp and Esr) Faecal calprotectin if appropriate ● Flexible sigmoidoscopy if appropriate treatment
Responders at 4 months Non-responders Continue drug for 12 months or until treatment failure (including surgery) whichever is first Withdraw
treatment
Clinical Assessment at 12 months Non-responders Clinical evaluation (Truelove and Witts) ● Inflammatory markers (Crp and Esr) Withdraw Faecal calprotectin if appropriate ● Flexible sigmoidoscopy if appropriate treatment In those with stable clinical remission a trial of withdrawal of treatment should be discussed. If treatment is withdrawn but the patient relapses they should have the option to restart In those with ongoing response who wish to continue treatment, they should be re-evaluated every 12 months
Ulcerative colitis-Golimumab, Infliximab and Adalimumab v1 Principle author: Dr Pritchard Approved by: Wirral Drug & Therapeutics Panel: May 2015 Review Date: May 2018