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Beth benderfynodd Grŵp Asesu Meddyginiaethau Cymru’n Un?

Gellir rhoi vedolizumab i drin llid yn y llwybr treulio (enterocolitis) a achoswyd gan driniaeth canser gyda meddyginiaethau a elwir yn atalyddion pwynt gwirio imiwnedd. Gellir rhoi vedolizumab os yw'r symptomau'n ddifrifol ('gradd 3') neu'n bygwth bywyd ('gradd 4') ac nad ydynt wedi ymateb i corticosteroidau (steroidau) neu infliximab, neu os yw triniaeth infliximab yn anaddas. Gellir rhoi vedolizumab hefyd ar gyfer symptomau enterocolitis graddau 3-4 sy'n ymateb i steroidau ar y dechrau, ond yna'n gwaethygu pan fydd y dos steroid yn cael ei leihau ac nad ydynt wedi ymateb i driniaeth ddilynol gydag infliximab, neu os nad yw infliximab yn addas.

Gellir rhoi vedolizumab yn lle infliximab i drin symptomau enterocolitis cymedrol ('gradd 2') nad ydynt wedi ymateb i steroidau neu sy'n gwaethygu pan fydd y dos steroid yn cael ei leihau.

Bydd vedolizumab  ar gael i gleifion cymwys sydd wedi cofrestru gyda phractis meddyg teulu yng Nghymru, hyd yn oed os oes angen iddynt dderbyn eu triniaeth y tu allan i Gymru.

Nid yw vedolizumab wedi'i drwyddedu i drin enterocolitis, felly os caiff ei ddefnyddio i drin enterocolitis fe’i gelwir yn ddefnydd “all-drwydded”. Pan gaiff meddyginiaeth ei defnyddio yn “all-drwydded”, rhaid i'ch meddyg esbonio'n glir i chi y risgiau a'r manteision o gymryd y feddyginiaeth. Dylai eich meddyg roi gwybodaeth glir i chi, siarad â chi am eich opsiynau a gwrando'n ofalus ar eich barn a'ch pryderon. Darllenwch ein taflen wybodaeth i gleifion am ddefnydd di-drwydded ac all-drwydded o feddyginiaethau.

Mae Grŵp Asesu Meddyginiaethau Cymru'n Un ac AWTTC yn adolygu'r penderfyniad hwn yn rheolaidd i weld a oes unrhyw dystiolaeth newydd a allai effeithio ar y penderfyniad hwn.

Am ragor o wybodaeth, ewch i: Checkpoint inhibitors | Types of immunotherapy | Cancer Research UK (Saesneg yn unig)

 

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What did the One Wales Medicines Assessment Group decide?

Vedolizumab can be given to treat inflammation of the digestive tract (enterocolitis) that has been caused by cancer treatment with medicines called immune checkpoint inhibitors. Vedolizumab can be given if the symptoms are severe (‘grade 3’) or life‑threatening (‘grade 4’) and have not responded to corticosteroids (steroids) or infliximab, or if infliximab treatment is unsuitable. Vedolizumab can also be given for enterocolitis symptoms grades 3–4 that respond to steroids at first, but then flare when the steroid dose is reduced and have not responded to follow-up treatment with infliximab, or if infliximab is not suitable.

Vedolizumab can be given as an alternative to infliximab to treat moderate enterocolitis symptoms (‘grade 2’) that have not responded to steroids or that flare when the steroid dose is reduced.

Vedolizumab will be available to eligible patients who are registered with a GP practice in Wales, even if they need to receive their treatment outside Wales.

Vedolizumab is not licensed to treat enterocolitis, so using it to treat enterocolitis is called “off-label” use. When a medicine is used “off-label”, your doctor must clearly explain to you the risks and benefits of taking the medicine. Your doctor should give you clear information, talk with you about your options and listen carefully to your views and concerns. Read our patient information leaflet about unlicensed and off-label use of medicines.

The One Wales Medicines Assessment Group and AWTTC review this decision regularly to see if there is any new evidence that may affect this decision.

For more information on immune checkpoint inhibitors visit: Checkpoint inhibitors | Types of immunotherapy | Cancer Research UK

Medicine: vedolizumab (Entyvio^®)

Indication: Reassessment of OW22 to extend the indication to include grade 2 enterocolitis when symptoms have not responded to first-line immunosuppression with corticosteroids or in patients who are corticosteroid-dependent requiring multiple challenges with corticosteroids, and for enterocolitis grades 3-4 requiring multiple challenge with corticosteroids when symptoms have not responded to infliximab or when infliximab is unsuitable.

Meeting date: 19 August 2024

Criterion: Clinical effectiveness and safety

OWMAG opinion OWMAG note that the current One Wales decision (OW22) recommends vedolizumab to treat ICI-induced enterocolitis grade 3–4 where symptoms have not responded to first-line immunosuppression with corticosteroids and infliximab, or when infliximab is unsuitable. This reassessment is in response to the12-month review of OW22 which identified change to the European Society for Medical Oncology (ESMO) guidelines for treating ICI-induced enterocolitis. The One Wales Medicines Assessment Group (OWMAG) proposed that, in accordance with the new treatment guidelines, vedolizumab should be reassessed to include the treatment of ICI-induced grade 2 enterocolitis that had not responded first-line immunosuppression with corticosteroids. This proposal was supported by Welsh clinicians who also requested that patients with grades 2–4 enterocolitis who are corticosteroid-dependent requiring multiple challenges with corticosteroids be included in the expanded indication being considered. OWMAG note that there is limited new clinical effectiveness evidence to that already presented and considered as part of the original assessment and the 12-month review. New evidence presented that includes grade 2 enterocolitis is limited and consists of 3 retrospective studies and interim results of an ongoing clinical trial. For the treatment of grade 2 enterocolitis, the group notes that vedolizumab dosage used (when reported) was consistent with the 300 mg dose recommended in national and international guidelines while dosing schedule frequency varied with generally no more than three doses received. However, results were generally reported for the mixed colitis group (grades 1-4) with no stratification by grade and the treatment pathway varied between studies with vedolizumab given only after failure of infliximab in some.  All studies showed a clinical benefit in terms of enterocolitis symptom improvement and partial or complete response to treatment with vedolizumab and reflected the results of previous studies. OWMAG also considered some real-world data submitted by Welsh clinicians and evidence provided by clinical experts, both in the ESR and at the meeting, who reported positive clinical outcomes for patients they had treated with vedolizumab. OWMAG noted that vedolizumab is the preferred treatment of choice over infliximab for grade 2 enterocolitis unresponsive to corticosteroids in the ESMO guidelines. This is due to its established gut-specificity which is particularly beneficial for the treatment of ICI-induced enterocolitis and, although it takes longer to elicit a response than infliximab, time to treatment success is less critical for moderate (i.e. grade 2) enterocolitis. Clinicians highlighted that the majority of patients with grade 2 enterocolitis unresponsive to steroid treatment progress to grade 3.  At this point, such patients will become eligible for treatment with infliximab or vedolizumab via OW21 and OW22. Allowing use of vedolizumab earlier in the pathway prevents the worsening of symptoms and lessens steroid burden by allowing rapid steroid weaning. Clinicians also highlight that 90% of patients with grade 2 enterocolitis who are successfully treated with either infliximab or vedolizumab are able to resume their cancer treatment with ICIs; this compares to 25-33% of patients with grade 3 enterocolitis. The detrimental impact of the prolonged use of high dose corticosteroids was also discussed; this can result in a range of serious adverse events including some that are irreversible, prevention or delay of cancer-related treatments or surgery and a decrease in quality of life. Clinicians also highlight that some patients with enterocolitis are steroid-dependent and require multiple treatment courses with steroids for relapses. They note concerns regarding the increase risk of steroid-related adverse events due to repeated exposure and would welcome the option to use vedolizumab for these patients to prevent future relapses and lessen steroid burden. OWMAG note that no new safety signals have been observed for the use of vedolizumab to treat ICI-induced enterocolitis. OWMAG considers that the evidence provided demonstrated clinical effectiveness.

Criterion: Cost-effectiveness

OWMAG opinion There is no published cost‑effectiveness evidence available for vedolizumab for the extended indication. OWMAG considered the cost-consequence analysis, threshold analysis and scenario analyses presented. The group acknowledged the limited scope of the analyses in terms of capturing all costs and effects, in particular longer term costs and effects. Clinicians shared their experiences in treating this patient group, suggesting that: the majority of patients not responding to corticosteroids would progress to grade 3 if grade 2 patients are treated successfully, then approximately 90% can be rechallenged with ICI compared with 25% or 33% of patients who experience grade 3 ICI-induced enterocolitis Grade 3 patients tend to be treated as day-cases rather than in-patients Monitoring is intensive for patients with steroid burden ICI-induced enterocolitis is very different to ulcerative colitis (UC), and that unlike UC, it is reversible with limited treatment options. Therefore, they would expect that the likely expected gain in benefits would be higher for patients with ICI-induced enterocolitis. The group also identified there was insufficient evidence presented to compare the value of vedolizumab with infliximab for the treatment of grade 2 enterocolitis, and to be confident that the anticipated additional benefits justified the additional anticipated extra costs.  OWMAG were unable to reach a decision on cost-effectiveness.

Criterion: Budget impact

OWMAG opinion OWMAG consider the clinical estimate of patient numbers reported to be reasonable. Clinicians in Wales estimate that 2 extra patients with grade 2 enterocolitis would be eligible for treatment with vedolizumab per year in addition to the 10 patients with grade 3–4 enterocolitis estimated in the original assessment, thereby giving 12 patients in total. This compares to the 5 patients treated with vedolizumab for grades 2-4 enterocolitis in Wales in 2023. The group note that mortality rates and additional screening and monitoring for bacterial, viral and fungal infections and adverse event costs have not been included in the budget impact. OWMAG acknowledge that a proportion of patients with grade 2 ICI-induced enterocolitis in Wales are already receiving vedolizumab through local agreement routes. Also, as ICI usage grows, it is acknowledged that patient numbers are anticipated to increase over the coming years, resulting in additional budgetary impact in Wales. This will be monitored as part of the review process. OWMAG consider that the base case provided in the report is a reasonable estimate of the associated cost to NHS Wales.

Criterion: Other factors

OWMAG opinion OWMAG acknowledges that although grade 2 colitis is milder than grade 3, it can still significantly impact patients’ quality of life. This may include malnutrition, poor sleep, inability to work, lethargy and chronic dehydration. In addition, OWMAG also acknowledge that long term and/or high dose steroid exposure is associated with increased risk of a wide range of adverse effects including infections, fractures, high blood sugar, cardiovascular and cerebrovascular events and that there are clinical, cost and quality of life benefits in reducing steroid burden and repeated exposure to corticosteroids. It was noted that many patients are elderly and these effects may be more severe. The use of vedolizumab may help a rapid wean from steroids. OWMAG also considers that earlier intervention and resolution of enterocolitis enables resumption of cancer treatment with ICIs for the majority of patients which offers an increased possibility of durable outcomes.   As vedolizumab targets the gut and has no identified systemic immunosuppressive activity, clinicians suggest this may offer potential benefits over infliximab, especially for patients with high disease burden and fewer cancer treatment options. There are no licensed alternative treatment options routinely available.

Final recommendation

OWMAG recommends that the existing recommendation for the use of off-label vedolizumab (Entyvio®) for the treatment of ICI-induced grade 3-4 enterocolitis where symptoms have not responded to first line immunosuppression with corticosteroids and infliximab, or when infliximab is unsuitable and as outlined in OW22 be updated to include the expanded indication considered in this reassessment. Therefore, the updated recommendation is as follows: Vedolizumab can be made available within NHS Wales: for the treatment of ICI-induced grade 3-4 enterocolitis, where symptoms have not responded to first line immunosuppression with corticosteroids and infliximab or when infliximab is unsuitable for the treatment of ICI-induced grade 3–4 enterocolitis in patients who are corticosteroid-dependent requiring multiple challenges with corticosteroids when symptoms have not responded to infliximab or when infliximab is unsuitable as an option for the treatment of ICI-induced grade 2 enterocolitis, where symptoms have not responded to first line immunosuppression with corticosteroids or for patients who are corticosteroid-dependent requiring multiple challenges with corticosteroids This recommendation is subject to the development of appropriate start/stop criteria.

Summary of rationale

There is some limited evidence to support the use of vedolizumab as an clinically effective option for the treatment of ICI-induced grade 2 enterocolitis, where symptoms have not responded to first line immunosuppression or who are steroid-dependent and require multiple treatment courses with steroids for relapses and for the treatment of ICI-induced grade 3–4 enterocolitis in patients who are corticosteroid-dependent requiring multiple challenges with corticosteroids when symptoms have not responded to infliximab or when infliximab is unsuitable. There are no licensed alternative treatment options and recent updates to international guidelines recommend the use of vedolizumab for the treatment of grade 2 enterocolitis unresponsive to corticosteroids. Allowing the use of vedolizumab earlier in the pathway may prevent the worsening of symptoms, lessen steroid burden by allowing rapid steroid weaning, allow resumption of ICIs to treat the patient’s cancer and maintain or improve the quality of life. There was insufficient evidence to recommend using vedolizumab, which has a higher acquisition cost, before infliximab for patients with grade 2 disease. Therefore, vedolizumab is recommended as an option and clinicians should be mindful of both the associated costs and benefits of both treatments before agreeing which treatment to use. A proportion of the extended patient population in Wales is already receiving this treatment via local agreement routes, supporting the extension on an All Wales basis would ensure equity of access. The review after 12 months will provide more clarity around patient numbers and the number of doses of vedolizumab administered.

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Key findings

Licence status: Vedolizumab (Entyvio^®) is not licensed for treating immune checkpoint inhibitor (ICI) induced grade 2–4 enterocolitis, when symptoms have not responded to first‑line immunosuppression with corticosteroids or require multiple challenge with corticosteroids. The use of vedolizumab for this indication is off-label.

Clinical evidence: The clinical evidence for the use of vedolizumab in this setting comes from an ongoing clinical trial, a systematic review with meta‑analysis, and retrospective studies (one of which had been included in the systematic review). The level of evidence available was limited but showed a clinical benefit in terms of overall survival and sustained clinical remission compared with infliximab.

Safety: No new safety signals have been observed for vedolizumab in this indication.

Patient factors: Vedolizumab is administered by intravenous infusion over 30 minutes. Patients should be monitored during and for two hours post‑infusion for the first two infusions. For subsequent infusions, one-hour monitoring post‑infusion is sufficient.

Cost effectiveness: There are no published studies on the cost-effectiveness of vedolizumab in combination with oral corticosteroids for treating ICI-induced grade 2 enterocolitis, when symptoms have not responded to first-line immunosuppression with corticosteroids or require multiple challenges with corticosteroids. AWTTC cost analyses identified that this intervention is associated with an incremental cost of [commercial in confidence figure removed].

AWTTC threshold analysis, with a limited cost perspective, identified that treatment with vedolizumab in combination with corticosteroids would require an improvement of [commercial in confidence figure removed] quality-adjusted life years (QALYs) over a lifetime horizon to be considered cost-effective. There is insufficient evidence to inform a decision on cost-effectiveness.

Budget impact: Clinicians consulted by AWTTC estimate that 12 people in Wales per year would be likely to be eligible to receive vedolizumab in this setting. It is assumed that people would have three vedolizumab doses, within a single year. This is associated with an annual cost of [commercial in confidence figure removed]. The number of eligible patients is likely to increase over time as more people receive ICIs. The budget impact is subject to uncertainty.

Impact on health and social care services: Patients with ICI-induced grade 3–4 enterocolitis in Wales are currently receiving vedolizumab through a One Wales recommendation (OW22) issued in February 2023. Patients with grade 2 colitis may receive vedolizumab through local agreements.

Innovation and/or advantages: Vedolizumab may reduce the need for more invasive interventions for this condition, and may improve patients’ quality of life and allow them to be discharged earlier. Vedolizumab treatment may help patients to receive subsequent cancer treatments, titrate steroids down, and carry on with their lives at home. Managing the toxicity of cancer treatments improves the chance for cancer to be cured for this cohort of patients.

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Background

In 2023 AWTTC reviewed the One Wales recommendation to use vedolizumab to treat ICI-induced enterocolitis grade 3–4 that has not responded to first-line immunosuppression with corticosteroids and infliximab, or when infliximab is unsuitable. The review identified a change to the European Society for Medical Oncology (ESMO) guidelines for treating ICI-induced colitis, to include vedolizumab as an option to treat moderate (grade 2) ICI-induced enterocolitis. Clinical experts expressed an interest in revising the One Wales advice to broaden the patient group to include grade 2 disease, and to include patients with grade 2–4 disease whose condition is settling and re‑flaring and requires multiple steroid escalations.

The One Wales Medicines Assessment Group (OWMAG) proposed that, in accordance with the new treatment guidelines, vedolizumab should be reassessed for the broader indication of treating ICI-induced grade 2 enterocolitis that had not responded to corticosteroid treatment, and grades 2–4 enterocolitis that require multiple challenges with corticosteroids.

The All Wales Therapeutics and Toxicology Centre (AWTTC) sought opinions from clinical experts in Wales, who said the incidence of ICI-induced enterocolitis will increase over the next few years as the use of cancer immunotherapies increases. Clinical experts expressed a need for effective ICI toxicity management and supported the reassessment of vedolizumab for the proposed broader indication.

Patients with ICI-induced grade 2 enterocolitis in Wales currently receive vedolizumab through local agreements. In the absence of other licensed treatments, a One Wales decision would ensure equity of access to this treatment across the country.

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Target group

The indication under consideration is an extension to the current recommendation to include the treatment of ICI-induced grade 2 enterocolitis, when symptoms have not responded to first-line immunosuppression with corticosteroids, or in patients with grades 2–4 enterocolitis who are corticosteroid-dependent requiring multiple challenges with corticosteroids.

The current One Wales advice (OW22) recommends vedolizumab for the treatment of immune checkpoint inhibitor induced grade 3–4 enterocolitis, where symptoms have not responded to first-line immunosuppression with corticosteroids and infliximab, or when infliximab is unsuitable¹.

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Marketing authorisation date

Not applicable, off-label. Vedolizumab (Entyvio^®) is not licensed for the treatment of ICI-induced grade 2 enterocolitis, when symptoms have not responded to first-line immunosuppression with corticosteroids or to multiple challenges with corticosteroids, or for ICI-induced grade 3–4 enterocolitis when infliximab is ineffective or unsuitable.

The marketing authorisation holder of vedolizumab (Entyvio^®) [commercial in confidence information removed].

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Dosing information

The recommended dose is 300 mg administered intravenously on weeks 0, 2 and 6².

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Clinical background

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Incidence

Incidence of ICI-induced enterocolitis will vary greatly depending on the ICI treatment and dosage used⁶. Incidence of all grade diarrhoea is estimated to be 10% and 33% with anti‑programmed cell death protein (PD)‑1 and anti‑cytotoxic T‑lymphocyte-associated protein (CTLA)‑4 treatment, respectively. Incidence of all grade colitis is estimated to be 2% and 7%, respectively. Incidence of grade 1–4 and severe (grades 3–4) colitis is estimated to be 1.2% and 0.2%, respectively, with anti‑PD‑1 treatment, 0.3% and 0.04% with anti‑PD‑L1 treatment, and 11.2% and 4.9% with anti‑CTLA‑4 treatment⁶. The proportion of people who develop steroid-refractory colitis is not known but has been estimated to be between 33.3% and 66.6% of those receiving anti‑CTLA‑treatment and approximately 12.5% of those receiving anti‑PD‑1 treatment⁷.

Clinicians consulted by AWTTC estimated that twelve people in Wales per year would be likely to be eligible to have vedolizumab for ICI-induced grade 2–4 enterocolitis that has not responded to corticosteroids or when infliximab is unsuitable.

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Current treatment options and relevant guidance

Treatment of ICI-induced grade 2 enterocolitis that has not responded to corticosteroids or infliximab is currently treated off-licence in Wales with vedolizumab through local agreements. Treatment of ICI-induced grade 3–4 enterocolitis unresponsive to corticosteroids or infliximab is treated in Wales by vedolizumab under the One Wales recommendation OW22¹.

Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up were updated in 2022⁸. Vedolizumab and infliximab are recommended for grade 2–4 enterocolitis refractory to corticosteroids, with infliximab recommended for more severe forms of disease and vedolizumab for moderate disease. This seems to be due to vedolizumab taking longer to elicit a response and therefore being less suitable when time to treatment success is critical. The updated ESMO guidelines also include the option of switching between biologics, or considering a higher dose of infliximab (10 mg/kg) for refractory colitis⁸. The current One Wales recommendation states that vedolizumab may be used if a patient’s condition is not responsive to corticosteroids for grade 3–4 enterocolitis. Vedolizumab may be used for patients whose condition is unresponsive to infliximab or for whom infliximab is not appropriate.

Several national and international guidelines have been on published on this topic with some variations in their recommendations^3,4,9-11. Generally, for patients with grade 3–4 enterocolitis, early introduction of vedolizumab or infliximab should be considered in addition to steroids in patients with high‑risk features on initial endoscopy examination or severe ulcerative presentation on colonoscopy. Treatment may also be started where there is no response to high‑dose steroids usually within two to three days^3,4,9,11 but up to five days¹⁰. This includes patients with pre‑existing inflammatory bowel disease (IBD) and, for this patient group, the need for ongoing maintenance infusions of infliximab or vedolizumab should be discussed case by case¹¹. Pre‑existing IBD is not a contraindication to receiving ICIs according to the BSG, who advise prompt assessment of disease activity before starting an ICI, regular monitoring during treatment and rapid treatment escalation in the event of relapse³.

Clinical experts advise that patients would initially have clinical review and investigations including routine blood tests, stool cultures and faecal calprotectin. They would then undergo radiology assessment and start primary immunosuppression with intravenous methylprednisolone followed by endoscopy. If the enterocolitis had not resolved and either infliximab was contraindicated or the enterocolitis had not responded to infliximab (up to three doses) then vedolizumab would be considered (up to three doses).

Clinicians in Wales say that there may be a role for the use of vedolizumab to treat refractory grade 2 colitis. In addition, clinicians have identified a group of patients whose condition is settling and re-flaring and requires multiple steroid escalations; these patients might benefit from earlier treatment with vedolizumab. Clinicians would therefore welcome the option to use vedolizumab for patients with grade 2 refractory ICI-induced enterocolitis, and for patients whose condition requires multiple steroid challenges and who may benefit from earlier treatment with vedolizumab.

For patients receiving intravenous corticosteroids, or for patients with high‑risk endoscopic features, screening for tuberculosis, varicella zoster virus, HIV and hepatitis B and C should take place in anticipation of treatment escalation; however, this should not delay treatment initiation³.

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Summary of evidence on clinical effectiveness

For the review of the OW22 recommendation and for reassessment of the broader use of vedolizumab to include grade 2 enterocolitis, AWTTC conducted a literature search for additional evidence. AWTTC excluded studies that had very small numbers of patients, or in which the grade of enterocolitis was not specified by treatment. Evidence identified included three retrospective studies and interim results from an ongoing clinical trial. All are discussed below.

Efficacy

Real world data: [Confidential data removed]

Safety

Discussion

Most of the evidence for the off-label use of vedolizumab to treat ICI-induced grade 2–4 enterocolitis, where symptoms have not responded to first-line immunosuppression with corticosteroids, comes from retrospective studies and two NMAs. When compared to infliximab, vedolizumab may be associated with lower rates of multiple hospitalisations and recurrent infection. When reported, vedolizumab dosage used was consistent with that recommended in national and international guidelines (300 mg; three infusions). Patient selection and grading, as well as outcome measurements are inconsistently reported across the studies due to the nature of their design and limitations in the most widely used grading tool CTCAE. It is therefore difficult to assess efficacy by symptom grade.

Clinical experts state that vedolizumab, for this indication, is given to patients who are usually mid‑treatment or post‑treatment for cancer (specifically those cancers that are indicated for ICI treatment such as melanoma or lung cancers). The indication is rare, given that immunotherapy is a relatively new treatment option for a growing number of cancer indications. The incidence is expected to rise as the use of immunotherapy does. This will lead to more hospital stays and, as such, it is imperative that NHS Wales is able to offer ICI immunotherapy safely. Clinicians state that ICIs offer the possibility of cure for patients with stage IV metastatic disease which is a paradigm shift for cancer care. In melanoma, where ICI has been used for the longest duration, 6.5-year data show that 49% of patients are still alive with more than 75% treatment-free²². To be able to offer patients the possibility of durable outcomes, clinicians feel it is imperative they can manage toxicity effectively with treatments such as vedolizumab.

It is reported that the early use of immunotherapies such as vedolizumab and infliximab to treat ICI-induced enterocolitis may ensure a more favourable overall patient outcome when compared to steroids alone as immunotherapy use is associated with a shortened course of steroid treatment²³. A retrospective review by Wang et al. (2018) assessing the impact of ICI-induced diarrhoea and colitis and their immunosuppressive treatment on patient outcomes found that patients who received long duration of steroid treatment (> 30 days) had a numerically higher infection rate than those who received steroid for shorter duration (40.4 vs. 25.8%; p = 0.160). Likewise, long duration of steroid without infliximab was associated with increased risk of infection compared to short duration of steroid with infliximab (42.9% vs. 14.3%; p = 0.089)²³.

Clinicians have stated that there are some patients who require multiple treatment courses with steroids for relapses and note concerns regarding the increase risk of steroid-related adverse events due to repeated exposure^24-30. They would welcome the option to use vedolizumab in this patient group to with the aim to prevent future relapses. One retrospective study specifically reported use in patients who were corticosteroid dependent and/or had partially refractory ICI-induced enterocolitis. The majority of patients had grade 1 diarrhoea (n = 5) and all were able to taper their steroid dose down, median time to steroid-free remission being 56 days¹⁷.

Patients with grade 2 enterocolitis who are unresponsive to corticosteroids are likely to progress to stage 3 disease. At this point they will become eligible for treatment with either infliximab or vedolizumab under the One Wales recommendations OW21 and OW22^1,31. Higher doses of corticosteroids are associated with a greater risk of fractures, developing diabetes/hyperglycaemia, cataracts, glaucoma, cardiovascular and cerebrovascular events. Psychiatric disturbances are also more common with higher dose corticosteroid use²⁷. In addition, cumulative doses of corticosteroids are associated with an increased risk of fractures, high blood sugar, cataracts, weight gain, skin and sleep problems³². Short-term oral corticosteroid use has cumulatively been associated with osteoporosis, hyperglycaemia and muscle weakness, even when given for <7 days²⁹. Allowing use of vedolizumab earlier in the pathway may prevent the worsening of symptoms requiring hospitalisation, lessen steroid burden and maintain or improve the quality of life for these patients.  

Infliximab blocks TNF-alpha, reducing inflammatory response throughout the body and this reduces the efficacy of the immunotherapy cancer treatment. However, vedolizumab works only in the bowel and thus has the advantage of not affecting the efficacy of the cancer treatment. The BSG state that the gut-selective mechanism of action of vedolizumab, which would not be anticipated to interfere with the efficacy of ICI therapy, might be an especially attractive option for ICI-induced enterocolitis³.

Clinicians suggest vedolizumab has further additional benefits. Infliximab induces widespread immunosuppression thus increasing the risk of latent and serious infections, whereas vedolizumab targets the gut and has no identified systemic immunosuppressive activity². Therefore, vedolizumab is likely to present fewer risks of complications from treating ICI-induced enterocolitis. Clinicians state that there is increasing evidence to support the use of vedolizumab in older patients who are particularly at risk from opportunistic infections secondary to immunosuppression with infliximab. Much of the supporting data has been extrapolated from IBD evidence³³. However, prescribers should be aware of the potential increased risk of opportunistic infections or infections for which the gut is a defensive barrier². The SmPC states that vedolizumab should not to be initiated in patients with active, severe infections until the infections are controlled. Caution should be exercised when considering the use of vedolizumab in patients with a controlled chronic severe infection or a history of recurring severe infections. Patients should be monitored closely for infections before, during and after treatment².

The National Institute for Health and Care Excellence (NICE) recommends vedolizumab for the treatment of moderately to severely active ulcerative colitis in adults (TA342)³⁴. NICE recommends vedolizumab for treating moderately to severely active Crohn's disease only if a TNF-alpha inhibitor has failed or a TNF-alpha inhibitor cannot be tolerated or is contraindicated (TA352)³⁵. It is acknowledged that the acute treatment strategy for ICI-induced enterocolitis may follow a similar pathway to the treatment for Crohn’s and ulcerative colitis. However, there are differences in terms of patient and disease characteristics, the length of treatment, morbidity and mortality rates. Therefore, comparing the use of vedolizumab for these indications and trying to predict clinical and cost effectiveness for ICI-induced enterocolitis from the data used for Crohn’s and ulcerative colitis is subject to significant uncertainty.

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Cost-effectiveness evidence

An AWTTC literature review did not identify any cost-effectiveness studies of vedolizumab for treating ICI-induced grade 2 enterocolitis, when symptoms have not responded to first-line immunosuppression with corticosteroids or require multiple challenge with corticosteroids.

Cost-consequence analysis

An AWTTC cost-consequence analysis compares the cost of intravenous vedolizumab in combination with oral corticosteroids in the treatment of ICI-induced grade 2 enterocolitis with standard of care. Standard of care in this setting consists of symptomatic management with oral corticosteroids at 40–60 mg/day.

The cost-consequence analysis includes the costs of vedolizumab procurement and administration. The analysis adopts a life-time horizon and an NHS Wales/Personal and Social Services perspective. The analysis accounts for the costs and outcomes associated with the acute disease in addition to considering longer term clinical and cost impacts. The recommended dose of vedolizumab is 300 mg given intravenously on Weeks 0, 2 and 6; this is in addition to corticosteroids.

Cost of intervention and comparator

The confidential NHS Wales contract price for vedolizumab 300 mg is [commercial in confidence figures removed] excluding VAT.

The administration cost for the delivery of vedolizumab is sourced from the NHS reference costs 2021/22 with cost code SB12Z used for the first administration and SB15Z for additional delivery. The first administration cost is £207.59. Subsequent delivery is costed at £326.46³⁶. The delivery of three doses of vedolizumab with administration costs equals [commercial in confidence figure removed] excluding VAT. The delivery costs of corticosteroids are assumed equal in the intervention and comparator arm the net intervention cost is therefore [commercial in confidence figure removed] excluding VAT.

Comparative clinical effectiveness

The summary of evidence on clinical effectiveness section outlines the clinical literature searches from which the effectiveness outcomes included in the cost‑consequence analysis, are taken. Clinical outcomes associated with vedolizumab for grade 2 enterocolitis are broad and evidence is heterogenous. Three studies across the severity grade (grades 1–4) found that vedolizumab showed a clinical benefit in terms of symptom improvement or symptom response (complete or partial). Evidence from a network meta-analysis calculates the pooled response rate of vedolizumab in combination with corticosteroids to be 88% (95% CI: 62% to 100%)¹⁹. There is a lack of evidence as to the clinical efficacy for patients in the comparator arm who continue treatment with corticosteroids and who are corticosteroid dependent.

The curative potential of vedolizumab may allow for a reduction in continued oral corticosteroid use, either in reduction of dose for those achieving partial response or in treatment discontinuation for those with complete response. The Summary of evidence on clinical effectiveness section outlines the wide range of adverse events associated with continued oral corticosteroids. Steroid burden is associated with an increase in continued care costs estimated to be £165 in 2007 per patient per year; the cost inflated using the PSSRU inflation indexes to 2022/23 prices is £252³⁷. This cost was calculated by applying the oral corticosteroid relative risk of seven adverse events to the prevailing incidence rate and then multiplying by associated costs³². Fractures were the main cost driver across the seven discrete adverse events. The seven adverse events are chosen due to the availability of relative risk estimates as opposed to severity ranking or incidence rates.

In addition to the seven relative risks included in the steroid burden economic study there is an increased infection risk associated with prolonged steroid use. A retrospective study pooling colitis grade 2 and 3 identified a relationship between longevity of steroid treatment and infection rates. The study findings suggest that early intervention with infliximab in combination with corticosteroids offers favourable outcomes compared to a longer duration of steroid without infliximab with infection rates of 14.3% and 42.9%, respectively; this finding was not statistically significant²³.

Adverse events associated with vedolizumab which were very common (observed in greater than 1 in 10 patients) have been listed in the safety section of the clinical review; they are nasopharyngitis, headache and arthralgia².

Clinical experts highlighted benefits in terms of a reduction in symptoms and an overall increase to patient health­­-related quality of life (HRQoL). This HRQoL impact is described in the patient organisation submission in terms of a disruption to usual activities and pain or discomfort. In addition to the curative impact on enterocolitis, a reduction in continued oral steroid use may also have an overall net HRQoL impact.

ESMO guidance and clinical experts have highlighted the need for hospital monitoring for grade 3–4 enterocolitis³⁸. Welsh clinical experts suggest that intervention at grade 2 with vedolizumab in combination with corticosteroids may reduce progression to grade 3–4 and therefore result in a lower overall hospitalisation rate. The prudent healthcare element to the use of vedolizumab for the treatment of grade 2 ICI enterocolitis is centred upon the timely treatment which avoids progression to more severe grades of enterocolitis. Clinical experts have informed that patients with grade 2 who are unresponsive to steroids may progress to grade 3–4 at which point they can routinely access vedolizumab. The proportion of patients who would progress from grade 2 to grade 3–4 is unknown. Offering treatments with a high partial/full curative rate may avoid subsequent progression or exacerbation. The cost-consequence analysis is summarised in Table 1.

Table 1. Vedolizumab cost-consequence analysis (opens image in new tab)

Threshold analysis

Using this net cost of vedolizumab, AWTTC conducted a threshold analysis to estimate the minimum required quality-adjusted life year (QALY) gain required for vedolizumab to be deemed cost-effective. Applying a cost-effectiveness threshold of £20,000 per quality-adjusted life year to the net intervention cost of [commercial in confidence figure removed] requires a QALY gain of [commercial in confidence figure removed]. A disease burden QALY is calculated to contextualise the threshold; this consists of disease duration and health-related quality of life (HRQoL) decrement.

An AWTTC literature review identified a recent study that reports a median time to resolution with grade 2 colitis of 52 days¹²; however, no direct evidence of impact on HRQoL for this indication was identified.

An alternative method to inform the scale of disease burden is to utilise literature from comparable conditions. An AWTTC literature search identified one relevant publication reporting no significant difference between ICI colitis and two conventional inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) for a range of quality of life measures³⁹. A subsequent targeted literature review was therefore undertaken to search for evidence on the HRQoL burden of ulcerative colitis and Crohn’s disease. Two publications were identified, offering relevant data.

The HRQoL decrement associated with ICI enterocolitis is the difference between the immunotherapy patient cohort HRQoL and those experiencing ICI colitis. Mapping EQ-5D figures from an assessment of ulcerative colitis patients in remission compared to moderate or severe disease status suggests a HRQoL decrement of 0.20⁴⁰. Applying the median grade 2 colitis duration of 52 days offers a QALY decrement of 0.028.

Alternative HRQoL figures are offered by NICE TA342 which reported estimates of 0.88 for ulcerative colitis remission and 0.42 for active disease³⁴. Applying the median duration of 52 days to the utility decrement of 0.46 results in a disease burden estimate of 0.065.

An alternative approach to estimating the HRQoL decrement associated with ICI colitis was undertaken to assess the robustness of the previous HRQoL decrement estimation approach. A targeted literature search aimed to identify publications on the EQ-5D burden of adverse events in patients undergoing immunotherapy, one paper was identified which reports the disutility associated with treatment-related adverse events of any grade as −0.005⁴¹. This generic adverse event disutility can be multiplied by the median duration of 52 days to offer a QALY reduction of 0.001.

The disease burden estimates of 0.028 and 0.065 incorporate evidence which is specific to ulcerative colitis as opposed to the more general approach of adverse events; the disease specific estimates are considered more plausible. 

Scenario analyses

AWTTC undertook scenario analyses to assess the influence of key variables and assumptions. The comparator in the base case is the continuation of oral corticosteroids, a plausible comparator is infliximab. The recommended dose of infliximab is 5 mg/kg⁴². A second dose may be repeated 14 days later, with a maximum of three infusions to be given (weeks 0, 2 and 6). The ESMO guidelines recommend considering a higher dose of 10 mg/kg to treat refractory colitis⁸.

NHS Wales prescribing figures from 2023 for infliximab 100 mg are used to calculate a weighted average procurement cost; details are offered in Appendix 1. The weighted average cost per 100 mg vial is [commercial in confidence figure removed] (excluding VAT). Administration of infliximab incurs the same cost as vedolizumab. The average patient weight is included according to an equal gender distribution at 77.25 kg^43,44. The scenario assumes three cycles of infliximab 5 mg/kg with no vial sharing which cost a total of [commercial in confidence figure removed]. The intervention cost of vedolizumab is [commercial in confidence figure removed] resulting in a net intervention cost of [commercial in confidence figure removed].

The QALY burden in the main analysis uses a HRQoL decrement of 0.20 with a duration of 52 days to offer a QALY reduction of 0.028. Varying the duration by ±20% results in a QALY burden of 0.034 when increased by 20% and by 0.024 when decreased by 20%. There is a high level of uncertainty in the assumptions and figures used to calculate the QALY burden approach. Caution should be applied when incorporating this metric into decision making.

Cost-effectiveness evidence limitations

• There are no published cost-effectiveness studies for this intervention.
• The clinical effectiveness estimate is reported without the context of a comparator curative rate; this is due to the uncertainty as to the curative rate for patients who have previously not responded to corticosteroids. There may be patients achieving partial/total symptom reduction with oral steroids who continue treatment with corticosteroids and who are corticosteroid dependent.
• The cost consequence analysis is limited to intervention and administration costs. The cost impact of adverse events and ongoing healthcare resource use are not included as there is insufficient supporting evidence. Total costs are therefore underestimated for the intervention and the comparator.
• The meta-analysis informing the clinical evidence pools studies from across the disease grade, including grade 1–4¹⁹. Including other disease grades may be misleading if there is a significant interaction between severity and curative rates. There is evidence suggesting that less severe grades respond more quickly to therapeutic intervention¹².
• The time horizons in the included clinical studies are insufficient to capture any potential intermediate or longer-term clinical effects; this prohibits drawing any robust conclusions as to the lifetime cost-effectiveness.  
• The HRQoL estimates are sourced from ulcerative colitis, whilst the equality of impact is supported by the published evidence; direct immune checkpoint inhibitor-induced enterocolitis data would be preferred, and therefore the estimates should be treated with caution. A further limitation is equality of impact evidence, in that the data was collected during the SARS-CoV-2 pandemic where impacts to daily routines may have masked the influence of the study health conditions.
• The burden of disease data is highly uncertain; the three estimates of the impact of enterocolitis in this patient group are inconsistent. This uncertainty and heterogeneity mean it is not possible to draw robust conclusions.
• The time to symptom resolution for grade 2 ICI-induced enterocolitis figure of 52 days includes the broader population and not those who have not responded to first‑line immunosuppression. The time horizon may be longer in those who are less likely to respond to steroid treatment.
• Outcomes include evidence from clinical opinion in the absence of published literature. Whilst clinical expert opinion is an important component in the evidence hierarchy it is more susceptible to bias and uncertainty than well conducted randomised control trials.

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Budget impact

Clinicians in Wales estimate that 2 extra patients with grade 2 enterocolitis would be eligible for treatment with vedolizumab per year in addition to the 10 patients with grade 3–4 enterocolitis estimated in the original assessment, thereby giving 12 patients in total.

The vedolizumab treatment regimen is typically 300 mg given intravenously on weeks 0, 2 and 6. It is assumed that people would have three vedolizumab doses, received within a single year. Medicine and administration costs for this regimen are shown in Table 2.

Table 2. Estimated annual costs for vedolizumab per patient in Wales (opens image in new tab)

The total annual costs for 12 patients are given in Table 3.

Table 3. Estimated annual costs for vedolizumab for 12 patients in Wales (opens image in new tab)

Budget impact issues

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Additional factors

Prescribing unlicensed medicines

Vedolizumab (Entyvio^®) is not licensed to treat this indication and is therefore prescribed ‘off label’. Prescribers should consult their relevant guidelines on prescribing unlicensed medicines before any off-label medicines are prescribed.

  

Care has been taken to ensure the information is accurate and complete at the time of publication. However, the All Wales Therapeutics and Toxicology Centre (AWTTC) do not make any guarantees to that effect. The information in this document is subject to review and may be updated or withdrawn at any time. AWTTC accept no liability in association with the use of its content. An Equality and Health Impact Assessment (EHIA) has been completed in relation to this assessment and this found there to be a positive impact. 

Information presented in this document can be reproduced using the following citation: All Wales Therapeutics & Toxicology Centre. Evidence Status Report. Reassessment of vedolizumab for the treatment of immune checkpoint inhibitor induced enterocolitis OW22. 2024.
Copyright AWTTC 2024. All rights reserved.

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References

1. All Wales Therapeutics and Toxicology Centre. Vedolizumab (Entyvio^®) powder for solution for infusion. Reference number: OW22. Assessment information.  Feb 2023. Available at: https://awttc.nhs.wales/accessing-medicines/medicine-recommendations/one-wales-vedolizumab-entyvio-for-ici-induced-enterocolitis-ow22/. Accessed Jun 2024.
2. Takeda UK Ltd. Entyvio^®. Summary of Product Characteristics.  May 2024. Available at: https://www.medicines.org.uk/emc/product/5442/smpc. Accessed May 2024.
3. Powell N, Ibraheim H, Raine T et al. British Society of Gastroenterology endorsed guidance for the management of immune checkpoint inhibitor-induced enterocolitis. The Lancet Gastroenterology and Hepatology. 2020;5:679-697.
4. Schneider BJ, Naidoo J, Santomasso BD et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. Journal of Clinical Oncology. 2021;39(36):4073-4126.
5. Alexander JL, Ibraheim H, Sheth B et al. Clinical outcomes of patients with corticosteroid refractory immune checkpoint inhibitor-induced enterocolitis treated with infliximab. Journal for ImmunoTherapy of Cancer. 2021;9.
6. Nielsen DL, Juhl CB, Chen IM et al. Immune checkpoint Inhibitor–Induced diarrhea and Colitis: Incidence and Management. A systematic review and Meta-analysis . Cancer Treatment Reviews. 2022;109.
7. East of England Priorities Advisory Committee. Infliximab for the management of diarrhoea or colitis associated with Immune Checkpoint Inhibitor (ICPI) therapy.  2019. Available at: https://medicines.bedfordshirelutonandmiltonkeynes.icb.nhs.uk/wp-content/uploads/2020/10/Infliximab-for-colitis-assoc-with-immune-checkpoint-therapyss-1.pdf. Accessed May 2024.
8. Haanen J, Obeid M, Spain L et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Annals of Oncology. 2022;33(12):1217-1238.
9. Thompson JA, Schneider BJ, Brahmer J et al. Management of Immunotherapy-Related Toxicities, Version 1.2020. Journal of the National Comprehensive Cancer Network. 2020;18(3):230-241.
10. Brahmer J, Abu-Sbeih H, Ascierto PA et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events. Journal for ImmunoTherapy of Cancer. 2021;9(6).
11. Amiot A, Laharie D, Malamut G et al. Management of immune checkpoint inhibitor in patients with cancer and pre-existing inflammatory bowel disease: recommendations from the GETAID. Digestive and Liver Disease. 2022;54(9):1162-1167.
12. Nguyen TL, Tew A, Kirton L et al. Evaluation of colitis induced by immune checkpoint inhibitors therapy in melanoma patients by an overall grading scale. Journal of Oncology Pharmacy Practice. 2024;0(0):doi:10.1177/10781552241248057.
13. Dahl EK, Abed OK, Kjeldsen J et al. Safety and efficacy of infliximab and corticosteroid therapy in checkpoint inhibitor-induced colitis. Alimentary Pharmacology & Therapeutics. 2022;56(9):1370-1382.
14. Machado AP, Shatila M, Glitza Oliva IC et al. Impact of selective immunosuppressive therapy on subsequent immune-related adverse events after immune checkpoint inhibitor-induced colitis treatment. American Journal of Clinical Oncology. 2023;46(8):350-365.
15. Wang YH, Varatharajalu K, Shatila M et al. Randomized clinical trial of infliximab versus vedolizumab for immune checkpoint inhibitor related colitis. Presented at Digestive Disease Week. 6-9 May 2023. Gastroenterology. 164 (6 Suppl). DOI: 10.1016/S0016-5085%2823%2903549-7. Accessed May 2024.
16. Abu-Sbeih H, Ali FS, Alsaadi D et al. Outcomes of vedolizumab therapy in patients with immune checkpoint inhibitor–induced colitis: a multi-center study. Journal for ImmunoTherapy of Cancer. 2018;6(142).
17. Bergqvist V, Hertervig E, Gedeon P et al. Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis. Cancer Immunology, Immunotherapy. 2017;66:581-592.
18. Zou F, Faleck D, Thomas A et al. Efficacy and safety of vedolizumab and infliximab treatment for immune‑mediated diarrhea and colitis in patients with cancer: a two-center observational study. Journal for ImmunoTherapy of Cancer. 2021;9.
19. Ibraheim H, Baillie S, Samaan MA et al. Systematic review with meta-analysis: effectiveness of anti-inflammatory therapy in immune checkpoint inhibitor-induced enterocolitis. Alimentary Pharmacology & Therapeutics. 2020;52:1432-1452.
20. M.D. Anderson Cancer Center. NCT04407247: Treatment of Immune Checkpoint Inhibitor-Related Colitis With Infliximab or Vedolizumab: A Randomized Trial. May 2024. Available at: https://clinicaltrials.gov/ct2/show/NCT04407247. Accessed May 2024.
21. University of Copenhagen. NCT04797325: Open Label Randomized Controlled Clinical Trial of Vedolizumab Versus Conventional Treatment for Checkpoint Inhibitor Induced Colitis. Aug 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT04797325. Accessed May 2024.
22. Wolchok JD, Chiarion-Sileni V, Gonzalez R et al. CheckMate 067: 6.5-year outcomes in patients (pts) with advanced melanoma. Journal of Clinical Oncology. 2021;39(15_suppl):9506-9506. Available at: https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.9506.
23. Wang YH, Abu-Sbeih H, Mao E et al. Immune-checkpoint inhibitor-induced diarrhea and colitis in patients with advanced malignancies: retrospective review at MD Anderson. Journal for ImmunoTherapy of Cancer. 2018;6(37):1-13.
24. Waljee AK, Rogers MAM, Lin P et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ. 2017;357:j1415.
25. Min KH, Rhee CK, Jung JY et al. Characteristics of adverse effects when using high dose short term steroid regimen. Korean Journal of Audiology. 2012;16:65-70.
26. Yasir M, Goyal A, and Sonthalia S. Corticosteroid adverse effects. In StatPearls [Internet}. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Jul 2023. Available at: https://www.ncbi.nlm.nih.gov/books/NBK430685/. Accessed Jul 2024.
27. Warrington TP, and Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clinic Proceedings. 2006;81(10):1361-1367.
28. Joseph RM, Hunter AL, Ray DW et al. Systemic glucocorticoid therapy and adrenal insufficiency in adults: a systematic review. Seminars in Arthritis and Rheumatism. 2016;46:133-141.
29. Heaney LG, Schleich F, Korn S et al. Recognising the long-term burden of short course oral corticosteroids. Presented at 2021 ERS International Congress. 5-8 September 2021.  European Respiratory Journal 2021; 58: Suppl. 65, PA3548.
30. National Institute for Health and Care Excellence. Clinical Knowledge Summary: Corticosteroids - oral. .  Jan 2024. Available at: https://cks.nice.org.uk/topics/corticosteroids-oral/management/corticosteroids/. Accessed Jul 2024.
31. All Wales Therapeutics and Toxicology Centre. Infliximab powder for solution for infusion. Reference number: OW21. Assessment information.  Feb 2023. Available at: https://awttc.nhs.wales/accessing-medicines/medicine-recommendations/one-wales-infliximab-for-ici-induced-enterocolitis-ow21/. Accessed Jun 2024.
32. Manson SC, Brown RE, Cerulli A et al. The cumulative burden of oral corticosteroid side effects and the economic implications of steroid use. Respiratory Medicine. 2009;103:975-994.
33. Attauabi M, Hoglünd C, Fassov J et al. Vedolizumab as first-line biological therapy in elderly patients and those with contraindications for anti-TNF therapy: a real-world, nationwide cohort of patients with inflammatory bowel diseases. Scandinavian Journal of Gastroenterology 2021;56(9).
34. National Institute for Health and Care Excellence. Technology Appraisal 342. Vedolizumab for treating moderately to severely active ulcerative colitis.  Jun 2015. Available at: https://www.nice.org.uk/guidance/ta342. Accessed May 2024.
35. National Institute for Health and Care Excellence. Technology Appraisal 352 Vedolizumab for treating moderately to severely active Crohn's disease after prior therapy.  Aug 2015. Available at: https://www.nice.org.uk/guidance/ta352. Accessed May 2024.
36. NHS England. 2021/22 National Cost Collection Data Publication. 2023. Available at: https://www.england.nhs.uk/publication/2021-22-national-cost-collection-data-publication/. Accessed Jun 2024.
37. Personal Social Services Research Unit. Unit costs of health and social care, 2022.  2022. Available at: https://www.pssru.ac.uk/unitcostsreport/. Accessed Jul 2024.
38. Haanen JBAG, Carbonnel F, Robert C et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis,treatment and follow-up. Annals of Oncology. 2017;28(4):119-142.
39. Torkizadeh M, Ibraheim H, Radhakrishnan S et al. Health-related quality of life in patients with checkpoint inhibitor enterocolitis. Presented at BSG Annual Meeting. 8-12 November 2021. Gut. 70 (4 Suppl). PMO-46.
40. Vaizey CJ, Gibson PR, Black CM et al. Disease status, patient quality of life and healthcare resource use for ulcerative colitis in the UK: an observational study. Frontline Gastroenterology. 2014;5(3):183-189.
41. Kaufman HL, Hunger M, Hennessey M et al. Nonprogression with avelumab treatment associated with gains in quality of life in metastatic Merkel cell carcinoma. Future Oncology. 2018;14(3):255-266.
42. Merck Sharp & Dohme (UK) Limited. REMICADE^®. Summary of Product Characteristics.  Jul 2022. Available at: https://www.medicines.org.uk/emc/product/3831/smpc. Accessed Oct 2022.
43. Onaverage. Average Weight of a Man. Available at: https://www.onaverage.co.uk/body-averages/average-weight-of-a-man. Accessed Jun 2024.
44. Onaverage. Average Weight of a Female. Available at: https://www.onaverage.co.uk/body-averages/average-female-weight. Accessed Oct 2024.

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• Reassessment (to include grade 2 enterocolitis): One Wales Interim Decision with starting and stopping criteria September 2024 PDF 56KB
• Reassessment (to include grade 2 enterocolitis): Decision rationale September 2024 PDF 39KB
• Reassessment (to include grade 2 enterocolitis): Evidence Status Report September 2024 PDF 245KB
• Reassessment (to include grade 2 enterocolitis): Equality and Health Impact Assessment September 2024 PDF 142KB 
• Original assessment (grades 3-4 enterocolitis): One Wales Interim Decision with starting and stopping criteria February 2023 PDF 87KB
• Original assessment (grades 3-4 enterocolitis): Evidence Status Report February 2023 PDF 164KB