Darllen yn Gymraeg / Read in English

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Beth benderfynodd Grŵp Asesu Meddyginiaethau Cymru’n Un?

Gellir rhoi infliximab i drin llid difrifol neu sy'n bygwth bywyd yn yr ysgyfaint (niwmonitis) a achosir gan feddyginiaethau a elwir yn atalyddion pwynt gwirio imiwnedd. Mae atalyddion pwynt gwirio imiwnedd yn feddyginiaethau sy'n trin canser trwy ysgogi'r system imiwnedd. Dim ond pan nad yw triniaeth â dosau uchel o steroidau wedi gweithio y gellir defnyddio infliximab i drin y math hwn o niwmonitis.

Bydd infliximab 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 infliximab wedi'i drwyddedu i drin niwmonitis, felly gelwir ei ddefnyddio i drin niwmonitis yn ddefnydd "oddi ar y label". 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.

I gael rhagor o wybodaeth am imiwnotherapi ag atalyddion pwynt gwirio imiwnedd, ewch i: Cancer Research UK - checkpoint inhibitors (Saesneg yn unig)

 

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What did the One Wales Medicines Assessment Group decide?

Infliximab can be given to treat severe or life-threatening inflammation of the lungs (pneumonitis) caused by medicines called immune checkpoint inhibitors. Immune checkpoint inhibitors are medicines that treat cancer by stimulating the immune system. Infliximab can only be used to treat this type of pneumonitis when treatment with high doses of steroids has not worked.

Infliximab 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.

Infliximab is not licensed to treat pneumonitis, so using it to treat pneumonitis 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 about immunotherapy with immune checkpoint inhibitors visit: Cancer Research UK - checkpoint inhibitors

Medicine: infliximab

Indication: treatment of grade 3–4 steroid-refractory pneumonitis induced by immune checkpoint inhibitor (ICI) therapy

Meeting date: 6 December 2025

Criterion: Clinical effectiveness and safety

OWMAG note that there is limited published clinical evidence available for infliximab for the treatment of grade 3–4 steroid-refractory pneumonitis induced by immune checkpoint inhibitor (ICI) therapy and that no randomised controlled trials or comparative studies were identified. Evidence comes from two systematic reviews, four retrospective case series of 15 patients in total and 18 case reports. OWMAG acknowledge the paucity of data to inform comparisons between different second-line immunosuppressive therapy options for this indication. Taking the published evidence as a whole, OWMAG note that between 30-40% of all the patients reported in these studies showed a clinical response to infliximab. OWMAG note the limitations of the evidence and acknowledge that case reports are generally the lowest grade of evidence as they may be subject to selection bias, are difficult to compare, involve small patient numbers, differ in the amount of clinical information given and the outcomes reported, and so may not be generalisable to patients with this condition in Wales. They note that many patients were treated with multiple immunosuppressive agents in addition to steroids making the relative benefit of infliximab difficult to ascertain. OWMAG acknowledge that published clinical guidelines such as those from the European Society for Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO) and the US National Comprehensive Cancer Network (NCCN), which mainly considered the same published clinical evidence, broadly agree in recommended second-line options and all include infliximab; none of these options are licensed for this indication in the UK. OWMAG note that all guideline recommendations on treatment options are based on low-quality evidence, mainly derived from clinical expert opinion and that clinical opinion can also be informed by preference and experience of using specific treatments. OWMAG note the evidence provided by clinical experts, both in the evidence summary report (ESR) and at the meeting, who report that patients who do not respond to intravenous corticosteroid treatment within 48-72 hours require prompt and effective treatment with an additional immunosuppressant to prevent further deterioration. The current treatment options used in NHS Wales is mycophenolate mofetil (MMF) although infliximab or tocilizumab may be used on an individual patient basis. However, MMF takes a couple of weeks to have a clinical effect whereas infliximab is usually fast acting after one dose. Clinicians in Wales report they have significant experience and familiarity with using infliximab for other ICI-induced toxicities and have had experience of using it for pneumonitis with good clinical responses noted. They also confirmed that response rates from their own clinical practice, and those shared by colleagues from elsewhere in the UK, are much higher than those reported in the published literature. OWMAG note that currently clinicians have to request infliximab on an individual patient basis through local processes which takes time and clinical resource; this can cause delay in initiating treatment and can be detrimental to patient outcomes as patients with this condition can deteriorate rapidly and prompt appropriate treatment is essential. Routine all-Wales access to infliximab will help standardise the treatment pathway in Wales, ensure equity and avoid delay in treatment which may lead to better patient outcomes. OWMAG note that all-Wales guidelines are currently in development by the National Immunotherapy Toxicity Sub-Group on the management of ICI-induced toxicities including pneumonitis. OWMAG note that the use of infliximab (in addition to corticosteroids) is associated with an increased risk of infection and deaths due to infectious complications. OWMAG acknowledge that the NHS Wales National Immunotherapy Toxicity Sub-Group advises that infliximab for the treatment of ICI-induced pneumonitis will only be offered to patients who are not at significant risk of autoimmune infections. For older patients who may be more immunosuppressed, tocilizumab would be used in preference to infliximab as it is less immunosuppressive than infliximab. OWMAG consider that the current published evidence for the use of infliximab to treat grade 3-4 pneumonitis is of very low quality, however, it acknowledges that the published evidence is not reflective of the response rates clinicians are reporting in practice. The experts in attendance state that they are in regular dialogue with other UK clinicians treating patients with this toxicity who all report better outcomes with infliximab than those reported in the literature and that clinical practice is quickly evolving in this area and based on real world experience which the published evidence base is not keeping up with. Taking into account the limited published evidence available, the real world experience reported by clinicians and the safety considerations highlighted, OWMAG consider infliximab demonstrates some clinical effectiveness as a treatment option for this indication and that the benefits of its use outweigh the risks.

Criterion: Cost-effectiveness

OWMAG opinion OWMAG note that no comparative cost-effectiveness evidence was identified for this use of infliximab, and in the absence of any comparative studies of infliximab for this indication, no cost effectiveness analyses was undertaken by AWTTC. OWMAG consider that the likely costs associated with using infliximab for this indication would be reasonable in considering the potential benefit gained from this intervention.

Criterion: Budget impact

OWMAG opinion OWMAG consider the clinical estimate of patient numbers reported to be reasonable. However, OWMAG note that use of ICI-treatments are likely to increase in future years, treatment-related toxicities including pneumonitis are also likely to increase. Therefore, patient numbers are expected to rise with an accompanying increase in budget impact. OWMAG note additional screening, monitoring and adverse event costs are excluded from the budget impact calculations both for infliximab and for comparator treatments. In particular, clinicians state that from their experience, patients with grade 3-4 pneumonitis unresponsive to steroids will deteriorate and they will require intensive in-hospital treatment for several days or weeks. Infliximab treatment may cause a rapid improvement in pneumonitis symptoms enabling prompt hospital discharge. OWMAG note that the degree of displacement of the comparator treatment MMF is difficult to estimate and that clinicians indicate that some patients would receive MMF and infliximab simultaneously. However, the acquisition cost of MMF is low and has very little effect on the overall budget impact. Also, from the clinical opinion provided, OWMAG note that it’s likely not all patients will receive three doses of infliximab; therefore, the budget impact may be overestimated. OWMAG also acknowledge that the lack of comparative data between treatments means that any additional benefit from infliximab cannot be quantified and taken into account in budget impact calculations. OWMAG consider that the base case provided in the report is a reasonable estimate of the associated cost to NHS Wales.

Criterion: Resource use

OWMAG opinion OWMAG note that infliximab is given by intravenous infusion in a healthcare setting whereas some comparator treatments are taken orally. However, due to the severity of the condition, patients with grade 3–4 ICI-induced pneumonitis are likely to initially be hospital in-patients and so the addition of the first dose of infliximab to the treatment pathway is likely to have a low additional impact. It is expected that subsequent doses can be administered as an outpatient. As previously mentioned, the use of infliximab may shorten hospital stay in comparison to patients receiving MMF alone.

Criterion: Other factors

OWMAG opinion OWMAG acknowledges that pneumonitis is a rare but serious complication of ICI therapy. Pneumonitis is potentially fatal and early assessment and intervention are key as patients with this condition can deteriorate rapidly. Whilst patients will generally accept significant toxicities in order to live longer, effective and early interventions are needed to improve patient quality of life and outcomes. OWMAG also acknowledges the testimony of the patient organisation representative who highlighted the ease of access to infliximab for this indication for patients treated in England. She also highlighted that pneumonitis, which causes patients to struggle for breath, is particularly unpleasant and frightening and that prolonged intensive in-hospital treatment can lead to psychological distress. Both the patient organisation representative and the clinical experts present also mentioned that prompt treatment with infliximab may avoid some long-term or lifelong side effects from the prolonged use of high-dose steroids and from the pneumonitis itself. OWMAG notes that, due to the mechanism of action of ICIs, patients who develop a severe toxicity are much more likely to exhibit a prolonged response to ICI treatment with many patients living ten or more years. This is in contrast to a predicted overall survival of several months before ICI treatments became available. However, clinicians highlight that the effective management of the toxicities that ICI treatments may induce is crucial in being able to realise the benefits these treatments offer. OWMAG recognises that a standardised NHS Wales treatment pathway for pneumonitis unresponsive to steroids will ensure that appropriate and swift second-line immunosuppression treatment can be given which will help avoid unnecessary long-term complications or death. Making infliximab routinely available for this group of patients will avoid potential delays in getting access, freeing up clinician time and enabling prompt and equitable access for patients across Wales. There are no licensed alternative treatment options routinely available.

Final recommendation

OWMAG recommend the use of infliximab for the treatment of grade 3–4 steroid-refractory pneumonitis induced by immune checkpoint inhibitor (ICI) therapy. This recommendation is subject to the development of appropriate start/stop criteria.

Summary of rationale

Although the published evidence to support the use of infliximab for the treatment of ICI induced grade 3-4 pneumonitis where symptoms have not responded to first-line immunosuppression with corticosteroids is limited and of very low quality, OWMAG considers that the real world experience of clinicians using infliximab for this indication, offers additional supportive evidence of its clinical effectiveness. There are no licensed alternative treatment options and international guidelines recommend the use of infliximab for this indication. Allowing routine access to infliximab will help standardise the treatment pathway in Wales and may enable earlier initiation of treatment resulting in improved patient outcomes. Due to the known increased risk of infections associated with infliximab, clinicians in Wales propose using it only in patients who are not at significant risk of autoimmune infections. The review after 12 months will provide the number of patients who have received this treatment in Wales and more evidence on whether this is an effective treatment for this patient population.

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Key findings

Licence status: Infliximab is not licensed for treating grade 3–4 steroid-refractory pneumonitis induced by immune checkpoint inhibitor (ICI) therapy; its use for this indication is off-label.

Clinical evidence: Evidence comes from two systematic reviews, and retrospective case series and case reports. No randomised controlled trials of infliximab in the treatment of ICI induced pneumonitis were identified. Overall, the evidence for the use of infliximab from the case reports and case series is mixed and inconclusive, and of very low quality.

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

Patient factors: Patients would receive the first dose of infliximab in hospital. Infliximab is administered by intravenous infusion over a two-hour period. Due to risk of acute infusion related reactions, patients should be monitored during and for at least one to two hours post infusion.

Cost effectiveness: No cost-effectiveness evidence was identified for this use of infliximab, and in the absence of any clinical studies of infliximab for this indication, no cost‑effectiveness analyses have been undertaken.

Budget impact: The additional use of infliximab is estimated to increase the annual spend associated with this patient group in Wales by [commercial in confidence figure removed] assuming no displacement of the very low cost comparator treatment, mycophenolate mofetil.

Impact on health and social care services: Minimal – due to the severity of the condition, patients with grade 3 or grade 4 ICI induced pneumonitis will already be admitted to hospital with extensive monitoring. The addition of infliximab to the treatment pathway is likely to have a low additional impact.

Innovation and/or advantages: Infliximab offers an additional treatment option for some patients in this group. Clinicians in Wales suggest that the specificity of the immunosuppressive activity of infliximab might offer an advantage over other immunosuppressive agents with a broader spectrum of activity which may be detrimental to the ongoing control of the cancer targeted by ICI treatment.

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Background

Clinicians in Wales consider there is an unmet need for treatment of grade 3–4 steroid refractory pneumonitis induced by immune checkpoint inhibitor (ICI) therapy. They have identified a cohort of patients who might benefit from infliximab treatment. Infliximab was considered suitable for assessment though the One Wales medicines process following agreement by the AWMSG Scrutiny Panel.

The All Wales Therapeutics and Toxicology Centre (AWTTC) sought opinions from clinical experts in Wales. Clinical experts expressed a need for a clear treatment strategy or clinical guideline to manage ICI-induced pneumonitis in Wales. A small number of patients with steroid-refractory ICI-induced pneumonitis in Wales have received infliximab (off label) through local agreements. A One Wales decision would ensure equity of access to infliximab across the country to treat steroid-refractory ICI induced pneumonitis..

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Target group

The indication considered is the treatment of steroid-refractory grade 3–4 pneumonitis induced by immune checkpoint inhibitors.

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Marketing authorisation date

Not applicable for this indication, off-label. 

Infliximab is not licensed for the treatment of steroid-refractory grade 3–4 pneumonitis induced by ICIs. There are no plans to license infliximab for the indication under consideration. 

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Dosing information

The dose proposed by clinicians in Wales is 5 mg/kg by intravenous infusion over a 2-hour period at Week 0. This dose is the recommended infliximab dose for the majority of licensed indications1. Patients should be observed for at least 1–2 hours post-infusion for acute infusion-related reactions. A second, and third dose may be given, 2 and 6 weeks later. In some cases, a shorter interval may be required between doses and specialist advice should be sought from the immunotherapy team. This is the same dosing regimen as for the treatment of ICI-induced enterocolitis (OW21) and myocarditis (OW31).

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Clinical background

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Incidence

The incidence of any grade ICI-induced-pneumonitis in clinical studies is about 4% for anti-PD-1 therapies, 2% for anti-PD-L1 inhibitors and <1% for anti-CTLA-4 inhibitors; the incidence of high-grade pneumonitis is about 1%⁵. It is more frequent with anti-PD-L1/anti-CTLA-4 combination therapy versus monotherapy (10% versus 1%-5%, respectively)⁵.

The National Immunotherapy Toxicity Sub-Group estimate that approximately 12 patients with steroid-resistant grade 3–4 ICI-induced pneumonitis across Wales would be eligible for treatment with infliximab each year.

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Current treatment options and relevant guidance

The European Society for Medical Oncology (ESMO) guideline for the management of toxicities from immunotherapies recommends that first-line treatment for pneumonitis of grade 3 and above is with intravenous methylprednisolone at 1–2 mg/kg/day followed by steroid tapering over 6 to 8 weeks if respiratory symptoms improve⁵. For patients who have not responded to intravenous steroids within 72 hours, the addition of either infliximab (5 mg/kg, one dose, every two weeks if needed), tocilizumab (8 mg/kg, one dose, every two weeks if needed) or intravenous immunoglobulin (IVIG) (2 g/kg over 2–5 days) is recommended. Other options, such as mycophenolate mofetil (MMF) (1 g twice daily) or cyclophosphamide can be considered after individual assessment on a case-by-case basis. Additionally, the ESMO guidelines state that if symptoms are life-threatening, first-line therapy with tocilizumab or infliximab, in addition to intravenous corticosteroids, is advocated as soon as possible⁵.

The American Society of Clinical Oncology (ASCO) recommend that if no improvement is noted within 48 hours of high-dose steroid treatment, additional immunosuppression with either infliximab (5 mg/kg), MMF, IVIG or cyclophosphamide should be offered⁴. The Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group guidelines recommend a similar treatment pathway although also include tocilizumab as a second-line immunosuppressant option⁸. The US National Comprehensive Cancer Network (NCCN) guideline recommends treatment with either IVIG or MMF is used in preference to tocilizumab or infliximab due to the increased risk of gastrointestinal perforation with tocilizumab and data for infliximab showing a mixed response for treatment of ICI-induced pneumonitis⁹. It is also stated that MMF is unlikely to improve steroid-unresponsive pneumonitis immediately but may have clinical benefit to avoid steroid dependence¹⁰. Most guidelines also recommend empiric antibiotics in case of infection.

All guidelines highlight that recommendations for all second-line immunosuppression options are based on low quality evidence.

The NHS Wales National Immunotherapy Toxicity Sub-Group is currently developing an all-Wales consensus guideline on the management of ICI-induced toxicities including pneumonitis. Infliximab is their preferred second-line immunosuppressive therapy option for patients who are not at significant risk of autoimmune infections due to familiarity of use for other ICI-induced toxicities, there is some evidence for its effectiveness and there is less concern about its effect on ongoing cancer control than with some other alternative treatments. For older patients who may be more immunosuppressed, tocilizumab would be used in preference to infliximab as it is less immunosuppressive than infliximab. The National Immunotherapy Toxicity Sub- Group states that the treatment and management of this toxicity is complex and currently sub-optimal and routine early access to infliximab and tocilizumab may improve patient outcomes.

Clinicians from [confidential information removed].

Both ESMO and ASCO guidelines recommend that ICI treatment is permanently discontinued for pneumonitis of grade 3 and above^4,5. However, the consensus recommendations from the US SITC Toxicity Management Working Group state that ICI rechallenge may be considered on a case‑by-case basis for grade 3 pneumonitis but only if symptoms and imaging abnormalities resolve⁸.

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Summary of evidence on clinical effectiveness

AWTTC conducted a literature search during 19–24 September 2025 to look for evidence about the use of infliximab to treat steroid-refractory ICI-induced pneumonitis.

Database searches were performed using MEDLINE, EMBASE and the Cochrane Library. Search terms were: infliximab, renflexis, remicade, remsima, inflectra, zessly, flixabi; pneumonitis, pneumonia, (pneumoniti* or lung inflammation* or pulmonary inflammation*), immune checkpoint inhibitors, immune checkpoint inhibit* (immune adj2 checkpoint adj2 (inhibit* or blockade*)), ((ICI or ICIs) adj2 pneumonitis).

The primary outcomes of interest were symptom improvement or resolution in randomised controlled trials, systematic reviews, network meta-analyses, guidelines, case series, case reports, conference abstracts, retrospective studies, health-related quality of life, economic evaluations and adverse events. No date restrictions were applied; results were restricted to English language. Targeted searches of Google and Google Scholar were also performed. Conference abstracts and letters were included. Clinical authors at AWTTC sifted and screened the results of the clinical searches, and health economics authors sifted and screened the results of the searches for economic evaluations and quality of life. See the PRISMA diagram in Appendix 1.

A total of 394 clinical papers were retrieved during the literature search, from which 20 duplicates were removed. 374 clinical papers were screened by inspecting titles only, and 140 papers were screened by inspecting abstract and full text. Twenty-five papers were identified for inclusion in this report; one paper identified from the Google Scholar search was also included.

The literature search identified no clinical trials of infliximab in steroid-refractory ICI‑induced pneumonitis; only systematic reviews, case reports and case series were identified.

In this evidence summary report, we include: two systematic reviews, four case series (15 patients), and 18 case reports or case series where only a single patient was identified (18 patients). We excluded reviews in which all the cases they reported were covered in other reviews; we also excluded case series and case reports that were covered in the two systematic reviews. The included case reports and cohort studies are listed in Appendix 2.

Efficacy

The two systematic reviews searched PubMed (Daetwyler et al. 2024) and Medline, Embase and Cochrane databases (Canadian Agency for Drugs and Technologies in Health (CADTH) 2024). Both reviews were broader searches for treatment of all types of immune therapy-related adverse events (Daetwyler et al. 2024), and for infliximab to treat immune ICI-related toxicities (CADTH 2024).

Corticosteroid-resistant immune-related adverse events: a systematic review (Daetwyler et al. 2024)

This systematic review summarises the available evidence for the treatment recommendations of ICI-induced toxicities including pneumonitis⁷. The review identified six case reports and seven case series with 50 patients treated with infliximab and also reviewed evidence for the use of other immunosuppressive agents, including IVIG, MMF, cyclophosphamide and tocilizumab for pneumonitis.

Most evidence was available for infliximab although results were mixed. For example, low success rates in the range of 25–33% were reported in three retrospective studies. Contrastingly, two retrospective studies indicated negative responses following infliximab treatment. Higher success rates were reported for alternative immunosuppressant treatments but based on less evidence. The fatality rate for patients with steroid-resistant pneumonitis, regardless of which additional suppressive treatment was chosen, was high at 67–100%.

The authors recommended that IVIG, and MMF should be used for steroid-resistant pneumonitis followed by tocilizumab if these fail. However, the treatment recommendations made in this systematic review rely heavily on single case reports and small case series which provide low level evidence and so may be subject to considerable uncertainty. The authors conclude that treatment decisions should be made on an individual basis, taking into consideration all clinical factors, drug availability, and local experience favouring one agent over another⁷.

Infliximab for immune checkpoint inhibitor therapy-related toxicities (CADTH 2024)

CADTH published a rapid review summarising the evidence available for the use of infliximab as treatment for ICI therapy-related toxicities in June 2024, which included ICI-induced pneumonitis³. This review included case reports and case series identified in an earlier systematic review by Daetwyler et al. 2024 plus additional relevant publications.

In total, 18 studies were included; nine case reports and nine cases series giving a total of 74 patients reviewed. Combined analysis of the results from the systematic review and additional studies showed that the complete response rate of infliximab for the treatment of ICI-induced pneumonitis was 28.4%, with 1.4% of patients achieving a partial response and 70.2% showing no response. CADTH concluded that the mixed evidence available meant that the effectiveness of infliximab for the treatment of ICI-induced pneumonitis remains to be determined as prospective evidence is not yet available but that the use of infliximab for the treatment of pneumonitis is an option³.

Case reports

Eighteen cases are listed in Table 2 in Appendix 2, two of which reported other ICI-induced toxicities in addition to pneumonitis^11,12.

The dose of infliximab was specified in ten cases and was most commonly 5 mg/kg (eight cases)^11,13-19. When reported, patients mostly received one dose (eight cases) with two patients receiving two doses^14,19.

For the 16 cases where only pneumonitis was present, infliximab treatment led to improvement of pneumonitis symptoms in nine cases^{14,15,17,18,20-24}. In seven cases infliximab treatment failed to improve pneumonitis^{13,16,19,25-28} and in two of these cases, patients were given additional immunosuppressants after infliximab^19,26. For the two cases with multiple toxicities, infliximab treatment led to improvement of pneumonitis in both cases^11,12.

Case series

Sun et al. (2025) reported four patients failed to show any improvement in their pneumonitis. Two of these patients required further treatment with additional immunosuppressants after receiving infliximab and one other patient died of cancer progression²⁹. Tan et al. (2023) reported two patients who recovered from ICI-induced pneumonitis and had > 1 year survival from symptom onset. However, one patient failed to improve and died of pneumonitis³⁰. Frost et al. (2023) reported six patients with worsening symptoms who failed to show any improvement after treatment with infliximab³¹. Sheshadri et al. (2022) also reported two patients who failed to improve with infliximab and died³².

Safety

Discussion

Infliximab is listed as an option for the treatment of steroid-refractory ICI-induced pneumonitis in a number of international guidelines. However, all guidelines highlight that recommendations for all second-line immunosuppression treatment options are based on low-quality evidence.

In this evidence summary, we identified an additional 33 patients from the published literature not included in the two systematic reviews and two patients from NHS Wales who have received infliximab to treat ICI-induced pneumonitis. Of these 35 patients, 15 had a response to treatment with infliximab, 20 had no improvement and five were given additional immunosuppressants after infliximab. Of the 15 patients who responded to infliximab, four later died; two due to cancer progression; one due to multiple organ failure with an Aspergillus infection and one due to sepsis, likely developing after extended periods of steroid treatment.

The systematic reviews identified have included different case reports although there are some reports that are common to both reviews. The systematic reviews conclude that the evidence for the use of infliximab to treat steroid-refractory ICI-induced pneumonitis is mixed and inconclusive. This conclusion is further supported by the results of the additional cases we have identified where, overall, the evidence for the use of infliximab is mixed, and of very low quality. It is also not clear how many patients had grade 3 or 4 pneumonitis.

There are no clinical studies that evaluated the efficacy of infliximab to treat ICI- induced pneumonitis. Evidence is only available from case reports and case series, and systematic narrative reviews of case reports and case series; overall patient numbers remain low. Case reports are generally the lowest grade of evidence. It is difficult to compare cases; cases may not be generalisable. The amount of information given about each case varies; dose and outcome data vary. In some cases, it is not clear when infliximab was given (if the case was steroid-refractory). Patients often had complex diagnoses, some with multiple immune-related toxicities, and treatment rarely followed clinical guidelines in terms of escalation of additional immunosuppression treatments after inadequate response to first-line steroids.

Although the grade of pneumonitis was not stated in many studies, nearly all case reports are for patients where pneumonitis symptoms were severe. Many patients were treated with a number of immunosuppressive agents in addition to steroids and so the relative benefit of infliximab is difficult to ascertain. The concomitant use of immunosuppressive agents may be expected to have a compounding effect on suppressing the immune system; a number of patients developed infections, some proving fatal, which may have been attributable to this effect.

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Patient submission

We received a submission from the patient organisation Melanoma Focus, commenting on our assessment of infliximab to treat steroid-resistant ICI‑induced pneumonitis. The main points of the submission are listed below.

• There is a growing population of melanoma patients who are younger in age; in the 15–44 years age group, melanoma is the second most common form of cancer in males and the third most common cancer in females.
• Checkpoint inhibitors, alone or in combination, are standard of care for all patients with metastatic melanoma and for high-risk stage II and III melanoma.
• Patients will generally accept significant toxicities to live longer. For metastatic melanoma, the longer-term survival rate is better for those treated with combination treatment. Therefore, patients, if fit enough, will likely be treated with combination therapy at the expense of approximately 60% of patients reporting grade 3–4 toxicities.
• ICIs have revolutionised melanoma care; 50% of patients treated with metastatic disease are now alive at 10 years. However, life‑threatening (grade 3–4) toxicities are reported in 50–60% of patients on combination ICI therapy, and in about 20% of patients on single agent ICI therapy.
• Pulmonary inflammation (pneumonitis) is an increasingly recognised complication of ICI therapy occurring in around 6.6% of treated patients. The most severe toxicity can occur in 2% of patients and its incidence is rising every year.
• Pneumonitis is potentially fatal and early assessment and intervention are key. Standard guidelines for grade 3–4 toxicity recommend initial, high-dose corticosteroid treatment. Patients with pneumonitis often need additional immunosuppression with additional medicines, some of which target different chemicals released as part of the inflammatory process associated with checkpoint inhibitors and include infliximab, tocilizumab and abatacept.
• Melanoma Focus strongly supports the co-creation of guidelines for worsening or refractory pneumonitis under the guidance of respiratory medicine and/or medical oncologist. As patients with this condition can deteriorate rapidly, patients and emergency departments need to be aware to swiftly report symptoms which may suggest possible pneumonitis and that it should be treated appropriately to avoid unnecessary long-term complications or death.

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Ongoing clinical studies

No clinical studies are currently progressing for infliximab in this indication. An open‑label randomised trial (study NCT04438382) using infliximab or IVIG for the treatment of steroid‑refractory pneumonitis (grade 2 or higher) started in 2021, but terminated in 2023 due to difficulties in enrolling patients³⁴.

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Cost-effectiveness evidence

No cost-effectiveness evidence was identified for this use of infliximab, and in the absence of any clinical studies of infliximab for this indication, no cost‑effectiveness analyses have been undertaken.

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Budget impact

Infliximab procurement costs are informed by a confidential NHS Wales contract price with a unit cost of a 100 mg vial ranging between [commercial in confidence figures removed] for the various biosimilars on all-Wales contract. NHS Wales prescribing figures from 2024 for infliximab 100 mg are used to calculate a weighted average procurement cost. The weighted average cost per 100 mg vial is [commercial in confidence figure removed] excluding VAT.

The average patient weight is calculated using population averages with an equal percentage of male and females. The recommended dose of 5 mg/kg for an average patient weight of 79 kg results in 4 vials per dose³⁵. There is an assumption of no vial sharing; wastage is applied. The total infliximab procurement cost for a single dose is [commercial in confidence figure removed] excluding VAT.

The administration cost for the delivery of infliximab is sourced from the NHS reference costs 2023/24 with cost code SB12Z used for the first administration and SB15Z for additional delivery³⁶. The first administration cost is £418. Delivery of subsequent dose is costed at £426. Based on clinical expert opinion, it is assumed patients receive three doses of infliximab at 5 mg/kg, the cost of which is [commercial in confidence figure removed] per patient excluding VAT.

Clinicians in Wales indicate that currently patients with steroid-refractory ICI-induced pneumonitis are predominantly treated with MMF. A typical regimen for MMF is 500 mg twice daily for 3 days increasing to between 1 – 1.5 g twice daily depending on response. Treatment with MMF is continued until the patient has been weaned off steroids and is stable; this is usually between 8-12 weeks after initiation of treatment.

MMF procurement costs are informed by confidential NHS Wales contract prices. The unit cost of MMF for 50 x 500 mg tablets ranges from [commercial in confidence figures removed] excluding VAT. Using the second lowest price of [commercial in confidence figure removed], the maximum acquisition cost of 1.5 mg MMF twice daily for 12 weeks is calculated as [commercial in confidence figure removed].

The National Immunotherapy Toxicity Sub-Group estimate that approximately 12 patients with steroid-resistant grade 3-4 ICI-induced pneumonitis across Wales would be eligible for treatment with infliximab each year.

Table 1. Estimated annual net cost for infliximab in comparison to MMF in Wales (opens image in new tab) 

The introduction of infliximab for the indication under consideration will increase the spend for this patient group. Based on an estimated uptake of 12 patients receiving three doses of 5 mg/kg infliximab, the annual cost of infliximab will be [commercial in confidence figure removed] (excluding VAT). The degree of displacement of the comparator treatment MMF is difficult to estimate as some patients may still receive it alongside infliximab to support steroid taper. However, the low cost of 1.5 mg MMF twice daily for 12 weeks per patient will not significantly affect the overall budget impact; if all patients remain on MMF in addition to receiving treatment with infliximab, the total treatment cost for 12 patients is estimated to be [commercial in confidence figure removed].

Budget impact issues

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Equality and health impact assessment

AWTTC have completed an Equality and Health Impact Assessment in parallel with each development stage of the project. This follows the five ways of working for public bodies, and work to achieving the wellbeing goals, outlined in the Well‑Being of Future Generations (Wales) Act 2015. It is not expected that infliximab will have significant potential negative impact on people based on the protected characteristics of the Equality Act 2010.

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Additional factors

Prescribing unlicensed medicines

Infliximab 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. 

Information presented in this document can be reproduced using the following citation: All Wales Therapeutics & Toxicology Centre. Evidence Status Report. Assessment of infliximab for the treatment of steroid‑refractory pneumonitis induced by immune checkpoint inhibitor (ICI) therapy OW34. 2026.
Copyright AWTTC 2026. All rights reserved.

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• Original assessment: OWMAG recommendation with starting and stopping criteria February 2026 PDF 105KB
• Original assessment: OWMAG decision rationale February 2026 PDF 34KB
• Original assessment: Evidence Status Report December 2025 PDF 194KB
• Original assessment: Equality and Health Impact Assessment February 2026 PDF 129KB