Between 15% and 25% of patients with UC will require hospitalisation for an acute severe flare of disease at some stage in the natural history of their disease, often as the index presentation. Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition, characterised by clinical and laboratory assessment using the modified Truelove and Witts criteria.

Management of ASUC should be as per BSG pathway. Please see the flowchart in British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults | Gut (bmj.com).

This guideline supports the prescribing, administration and monitoring of “rescue” or “salvage” therapies for ASUC at FHFT. The use and efficacy of this therapy can depend significantly on the actions taken in the first days of admission.

The decision to start ciclosporin or infliximab for UC must only be taken by a Consultant Gastroenterologist.

Benefits/risks of rescue therapy and colectomy must be fully discussed with the patient. This decision is based on individual assessment and wishes of each patient and will be after 3-5 days treatment with intravenous steroids.

Ciclosporin can provide a viable alternative to colectomy in ASUC. It is commonly used as a bridge to maintenance treatments such as azathioprine or vedolizumab and the two agents will overlap for a number of weeks. Ciclosporin must not be used concurrently with JAK inhibitors or S1P modulators.

Intravenous infliximab can provide a viable alternative to colectomy or ciclosporin in ASUC. It is then continued as maintenance therapy.

The decision to initiate rescue therapy (ciclosporin/infliximab) MUST only be taken by a Consultant in Gastroenterology.

The medical team is responsible for the monitoring of treatment at ward level. Baseline screening should be ordered promptly with the diagnosis of ASUC to avoid delays in administering potential rescue therapy. The Gastroenterology team should ensure a biologics screen is undertaken at the diagnosis of ASUC if not already done, using the “New Gastro Biologics Starter” SmartSet. This includes important additional TB and viral screening (quantiferon, HIV, Hepatitis viruses). Therapy should not be delayed waiting for the results of these tests. A chest x-ray should be completed and reviewed prior to infusion – to rule out infection.

Ciclosporin or infliximab Should be planned to be initiated in-hours where possible (to mitigate any risk of anaphylaxis/infusion related reaction). Where rescue therapy has been prescribed to be administered out-of-hours it should not be delayed without confirming with the prescribing consultant whether it is most appropriate to give or wait to administer the next morning.

Nursing staff should promptly liaise with Pharmacy as soon as the treatment is prescribed to ensure supply is promptly obtained. ASUC should be treated promptly and Blueteq® funding is not required to proceed with supply or administration.

Rescue therapies should only be administered in locations where nursing staff are familiar with the administration and monitoring of these medications and the patient with ASUC (e.g. gastroenterology wards).

The Gastroenterology team should ensure a biologics screen is undertaken at the diagnosis of ASUC (if not already previously done), using the “New Gastro Biologics Starter” SmartSet. This includes important additional TB and viral screening. This remains applicable to the use of ciclosporin as the patient will transition to the use of an alternative immunosuppressant. The results of the viral and TB screen are not required to proceed with rescue therapy.

Screen should include: HepB surface Ag, HepB core Ab, HepC Ab, HIV, VZV, EBV, CMV IgG, TPMT (if not already done previously), quantiferon (or TB elispot if already been on steroids - discuss with lab if organising elispot) and chest X-ray.

An infection screen, including a history for contact with TB and a chest X-ray, should be completed prior to proceeding with rescue therapy.

Ciclosporin is a potent immunosuppressant requiring therapeutic drug monitoring due to its narrow therapeutic index. The use of ciclosporin as a rescue therapy (following non-response to IV corticosteroids) represents practice as endorsed by the British Society of Gastroenterology. This is an unlicensed indication.

Ciclosporin is commonly used as a bridge to maintenance treatments such as azathioprine or vedolizumab and the two agents will overlap for a period whilst this occurs. Ciclosporin should not be used concurrently with JAK inhibitors or S1P modulators.

Baseline Investigations

Contraindications

• Known hypersensitivity to ciclosporin or any excipients

• Known hypersensitivity to polyethoxylated castor oils (anaphylaxis risk with intravenous preparation)

• Concomitant use of tacrolimus

• Low serum cholesterol (increased likelihood of side effects)

• Uncorrected hypomagnesaemia (increased likelihood of seizures)

• Uncontrolled hypertension

• Absolute indication for surgery (perforation, major haemorrhage, toxic megacolon, obstruction).

• Severe infection

Dosage and Administration

Where possible patients should be prescribed oral ciclosporin. If there are concerns around absorption or in instances where an IV load may be useful, intravenous ciclosporin may be used for up to 5 days, but patients should be switched to an oral dose as soon as possible. Ciclosporin has excellent oral bioavailability.

The original drug trials for IV ciclosporin in ASUC administered 2mg/kg as a continuous infusion over 24 hours (unlicensed) which due to stability requires a syringe to be changed every 6 hours if a giving set containing PVC is used. Ciclosporin can alternatively be given as an intermittent intravenous infusion over 2 to 6 hours in a twice daily regimen (switching to PO as soon as practical). This reduces the nursing requirement, provides patient time without the infusion running and avoids the stability issue.

Dosing

• Oral ciclosporin: 2.5mg/kg twice daily (rounded to practical dose). If converting from IV ciclosporin, ensure to account for any prior dose adjustments whilst on IV therapy.

• Intravenous ciclosporin: 1mg/kg over 2-6hours twice daily. Round dose to nearest 5mg.

• Continuous intravenous ciclosporin infusion: 2mg/kg over 24hours. (see Appendix).

When dosing obese patients use the adjusted body weight, rounded to a practical dose, and monitor ciclosporin levels carefully.

The hospital holds stock of Neoral® capsule preparations in the following strengths: 10mg, 25mg, 50mg, and 100mg capsules. Other brands and a liquid form may also be available. For patients starting ciclosporin orally, ensure to round to a practical dose, and prescribe the minimum number of dosage units to make up each dose to aid adherence at discharge.

Adjust dosing based on therapeutic drug levels – see below.

Drug Monitoring (including TDM)

• Take a pre-dose (trough) level on day 4 (ideally prior to morning dose).

• Target induction trough concentration = 150 - 250 ng/mL. Adverse effects are more likely at levels > 300ng/mL

• Target maintenance trough concentration = 100 – 200 ng/mL

• Routine bloods (FBC, U&E, LFT, CRP and Mg) should be taken daily whilst inpatient on ciclosporin.

• After conversion to oral ciclosporin, routine bloods (FBC, U&E, LFT, CRP and Mg) and a trough ciclosporin level should be taken weekly for four weeks until the dose is stable. Once stable, blood tests can be less frequent (2-4weekly), and the monitoring of levels should not be routinely required. A lipid profile should be taken after one month of treatment.

Dose Adjustments

Discuss with Registrar/Consultant prior to any dose amendment.

Intravenous Administration (intermittent infusion)

• Dilute to give a final concentration for infusion of between 500 micrograms in 1mL to 2.5mg in 1ml in sodium chloride 0.9% or glucose 5%. Most doses should be diluted to a final volume of 50mL and given via syringe pump. The infusion should then be run over 2 to 6 hours depending on tolerability.

• Ciclosporin is available in the Trust as 50mg/ml ampoules of concentrate (Sandimmun®). The ampoules should be protected from light, but light protection is not required for prepared infusions of ciclosporin.

• For information regarding continuous infusion – see Appendix.

Clinical Monitoring

Anaphylaxis

• Polyethoxylated castor oil can cause anaphylactic reactions (acute respiratory distress, dyspnoea, wheezing, blood pressure changes, facial flushing).

• Monitor vital observations every 15 minutes for the first hour: blood pressure, pulse, temperature, respiratory rate.

• Repeat vital observations every 30 minutes until the first infusion has finished. Continue to closely observe the patient and monitor for anaphylaxis post infusion.

• If signs of anaphylaxis develop, stop infusion, and follow anaphylaxis protocols.

Adverse Effects

Refer to the SPC for a full list of adverse effects:

On discharge, ensure the patient has sufficient supply of oral ciclosporin, in the appropriate strength capsules, as well as the required blood test monitoring forms and has been referred to IBD CNS.

Interactions

Interactions with ciclosporin are common and are largely mediated through inhibition or induction of CYP enzymes that metabolise ciclosporin – particularly CYP3A4. Ciclosporin is also a CYP3A4 and p-GP inhibitor and its effects on other medicinal products should be carefully considered before prescribing.

A pharmacist should be contacted to check interactions with concurrent medications.

The list below is not exhaustive.

Vaccinations – may be less effective during treatment of ciclosporin. Live attenuated vaccines are contraindicated. Check eligibility criteria for the Shingrix® recombinant vaccine.

Infliximab is a chimeric human-murine monoclonal antibody that binds to TNF alpha – blocking its activity. It is licensed for induction and maintenance of remission in UC.

Baseline Investigations

• full biologic screen (should be taken on admission).

• Ideally use the Gastro – Biologics New Starter Panel in Epic. The result of the viral screen and quantiferon/IGRA is not required prior to proceeding with rescue therapy with infliximab.

• An up-to-date CXR is required to be reviewed prior to treatment to rule out infection (including TB) and should complement a thorough history of exposure to TB.

Contraindications

• Active infection (including tuberculosis)

• Hypersensitivity to infliximab or other murine proteins.

• Moderate to severe heart failure (NYHA III/IV)

Dosing Administration

Discuss with pharmacy to confirm which biosimilar infliximab is being used at time of prescription.

Nursing staff should access Medusa for administration information.

Pre-Medication for Infliximab

Chlorphenamine 10mg IV and paracetamol 1g PO should both be prescribed as pre-medication to be taken 15-30mins prior to infusion. If the patient is already on high dose steroids, further steroid dose is not required.

Refer to the IBD CNS team at initial dose and again at discharge to organise counselling of the patient, follow-up and ongoing infliximab dosing.

The patient should continue IV infliximab until they have shown a good response, at which point they may transition to SC maintenance therapy. This may require more than the usual 2 or 3 IV doses used before the usual transition to SC.

• IV hydrocortisone 100mg QDS should be switched to prednisolone 40mg once daily, reducing by 5mg weekly when safe to do so. Prednisolone 5mg tablets should be prescribed and supplied.

• Consider prescribing Adcal D₃ chewable (1 tablet twice daily) for the duration of steroid course. Patients should have their FRAX score completed to assess for risk of osteoporosis.

• Consider Co-trimoxazole 960mg three times a week as Pneumocystis carinii (PCP) prophylaxis when patient on triple immunosuppressant therapy (steroids, ciclosporin and azathioprine and/or biologic).

• Amino-salicylates (5-ASA) should be reviewed. If there is a plan to start an advanced therapy consideration should be made to stopping oral 5-ASA.

1. National Institute for Health and Care Excellence [NICE] (2019) Ulcerative colitis: management. NG130. Available at: https://www.nice.org.uk/guidance/ng130 (Accessed: 25 March 2025)

2. Lamb, C.A. et al. (2019) 'British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults', Gut, 68: s1-s106. https://doi.org/10.1136/gutjnl-2019-318484 (Accessed: 25 March 2025).

3. Electronic Medicines Compendium (2023) SANDIMMUN Concentrate for Solution for Infusion 50mg/ml. Available at: https://www.medicines.org.uk/emc/product/1036/smpc#gref (Accessed 11 July 2024)

4. Langebrake et al. (2011) 'Drug dosing and monitoring in obese patients undergoing allogenic stem cell transplantation', International Journal of Clinical pharmacy, 33(6), pp. 918-924. Available at: https://doi.org/10.1007/s11096-011-9568-0 (Accessed: 25 March 2025).

5. Ciclosporin intravenous administration monograph – Medusa www.medusa.wales.nhs.uk accessible on line

6. Jiang, C. D. et al. (2021) 'P452 Oral ciclosporin is a convenient, effective and safe rescue therapy in steroid refractory Acute Severe Ulcerative Colitis: A single tertiary centre experience', Journal of Crohn's and Colitis, 15(supplement 1), p. S447. Available at: https://doi.org/10.1093/ecco-jcc/jjab076.576 (Accessed: 25 March 2025).

7. Bumps (2022) Ciclosporin. Available at: Ciclosporin (Accessed: 25 March 2025).

8. UKTIS (2022) Use of ciclosporin in pregnancy. Available at: Use of Ciclosporin in Pregnancy – UKTIS (Accessed: 25 March 2025).

To prescribe a continuous infusion via volumatic pump (divided in 4 doses of 6 hourly infusions).

Prescribe using the ciclosporin for severe ulcerative colitis infusion panel (highlighted).

Use the panel to select an appropriate dose (0.5mg/kg every 6hours (administered over 6 hours).

For obese patients, use adjusted body weight, rounded to a practical dose and monitor ciclosporin levels carefully. For example: for an 80kg patient (total daily dose is 160mg/24hours).

Each dose is then diluted to 50mL of sodium chloride 0.9% and given via an infusion pump over 6hours.

This guideline has been registered with the Trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt, contact a senior colleague or expert. Caution is advised when using guidelines after the review date.

This guideline is for use in Frimley Health NHS Foundation Trust hospitals only. Any use outside this location will not be supported by the Trust and will be at the risk of the individual using it.

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