| Status: Supported for use via the One Wales Medicines process | |
Using the agreed starting and stopping criteria, rituximab can be made available within NHS Wales for the second- or third-line treatment of fibrotic interstitial lung disease (not idiopathic pulmonary fibrosis) associated with connective tissue disease or idiopathic fibrotic non-specific interstitial pneumonia in patients where other health technology appraisal‑approved regimens are unsuitable. Rituximab should be prescribed on the basis of lowest acquisition cost. The risks and benefits of the off-label use of rituximab for this indication should be clearly stated and discussed with the patient to allow informed consent. At the latest review of this recommendation in February 2024, the decision by the One Wales Medicines Assessment group was to retain the current advice with no changes required. This advice will be reviewed after two years or earlier if new evidence becomes available. |
Darllen yn Gymraeg / Read in English
Beth benderfynodd Grŵp Asesu Meddyginiaethau Cymru'n Un?
Gellir rhoi rituximab i drin clefyd interstitaidd ffibrotig yr ysgyfaint (ILD) sy'n gysylltiedig â chlefyd meinwe gyswllt, neu â math o niwmonia o'r enw niwmonia interstitaidd amhenodol ffibrotig, pan nad yw triniaethau eraill wedi gweithio. Mae ILD yn gyflwr sy'n effeithio ar y rhwydwaith o feinweoedd yn yr ysgyfaint, gan eu gwneud yn llidus ac wedi'u creithio (ffibrotig). Mae'r meinwe creithiau yn yr ysgyfaint yn mynd yn drwchus ac yn anystwyth, sy'n ei gwneud hi'n anoddach anadlu. Dim ond pan nad yw'r triniaethau arferol wedi gweithio y gellir rhoi rituximab.
Bydd rituximab 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 rituximab wedi'i drwyddedu i drin ILD, felly os caiff ei ddefnyddio i drin ILD 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: Asthma + Lung UK (Saesneg yn unig)
What did the One Wales Medicines Assessment Group decide?
Rituximab can be given to treat fibrotic interstitial lung disease (ILD) associated with a connective tissue disease, or with a type of pneumonia called fibrotic non-specific interstitial pneumonia, when other treatments have not worked. ILD is a condition that affects the network of tissues in the lungs, making them inflamed and scarred (fibrotic). The scar tissue in the lungs becomes thickened and stiff, which makes it harder to breathe. Rituximab may only be given when the usual treatments have not worked.
Rituximab 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.
Rituximab is not licensed to treat ILD, so using it to treat ILD 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 ILD visit: Asthma + Lung UK
Starting criteria: Rituximab may be commenced after evidence of progression on azathioprine and/or mycophenolate mofetil and nintedanib, in line with current National Institute for Health and Care Excellence (NICE) recommendations.1 For some patients nintedanib may be used as adjunctive treatment with rituximab. A request for rituximab should be made following regional interstitial lung disease multi-disciplinary team diagnosis review and treatment recommendation. Rituximab is recommended only in circumstances where other health technology appraisal-approved regimens are unsuitable or treatment has failed.
Progression is defined as:
Patients who satisfy the start criteria will be prescribed rituximab after consultation with the patient and/or carer considering potential adverse effects, cautions and contraindications. This consultation should be recorded in the patient’s notes.
The recommended rituximab treatment dose regimen is 1,000 mg rituximab followed by a second 1,000 mg dose two weeks later administered by intravenous infusion. A further 1 g may be offered within the first 12 months and then annually, according to response.
Monitoring:
Stopping criteria: Treatment with rituximab should be discontinued according to one or more of the following definitions of disease progression:
References:
Health boards will take responsibility for implementing One Wales Medicines Assessment Group decisions and ensuring that a process is in place for monitoring clinical outcomes.
This report was prepared by the All Wales Therapeutics and Toxicology Centre in December 2023. It summarises any new evidence available since the last review in November 2021 and patient outcome data collected in the last 12 months.
Background: Interstitial lung diseases are a heterogeneous group of disorders that cause scarring of the lungs. The scarring causes stiffness in the lungs which makes it difficult to breathe. A small number of people in Wales have interstitial lung disease associated with a connective tissue disease or idiopathic fibrotic non-specific interstitial pneumonia that does not respond to treatment with conventional oral immunosuppressants.
In 2017 NHS England reviewed and concluded not to routinely commission rituximab to treat connective tissue disease-associated interstitial lung disease. Clinicians in Wales considered there to be an unmet need in NHS Wales and identified a cohort of patients who could benefit from rituximab treatment. Based on this unmet need, rituximab was considered suitable for assessment through the One Wales process. In November 2021, the National Institute for Health and Care Excellence (NICE) recommended nintedanib (Ofev®; TA 747) to treat progressive fibrosing interstitial lung diseases. A clinical expert has indicated that although nintedanib is now an option for this patient group, rituximab remains an option for those patients with a predominately inflammatory phenotype where other immunosuppressants are unsuitable. This place in pathway is reflected in the current start/stop criteria.
Current One Wales decision: Recommended as a second or third-line option.
Licence status: Off-label use for this licensed medicine.
Guidelines: The European Alliance of Associations for Rheumatology (EULAR) recommendations for the treatment of systemic sclerosis have been updated in 2023 to include new recommendations, including the use of rituximab to treat interstitial lung disease in systemic sclerosis (Del Galdo et al., 2023). This is currently available as a conference abstract, the 2023 recommendations have not yet been published in full.
In 2023 the American Thoracic Society published an evidence-based clinical practice guideline for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). It includes a conditional recommendation for giving rituximab to patients with SSc-ILD, balancing a significant reduction in disease progression with no difference in adverse events against the very low-quality evidence (Raghu et al., 2023).
Licensed alternative medicines or Health Technology Assessment advice for alternative medicines: No new treatments have been approved for this indication.
Effectiveness: A literature search by AWTTC identified 5 systematic reviews and 4 studies, which include results from the RECITAL and EVER-ILD studies, mentioned in our previous review in 2021 (see Appendix 1).
Three systematic reviews and meta-analyses studied the use of rituximab to treat connective tissue disease-associated interstitial lung disease. Two meta-analyses reported some improvements in lung function after rituximab treatment; one meta‑analysis found that lung function decreased after rituximab treatment.
One meta-analysis by Macrea et al., 2023 in treatment of SSc-ILD showed clinically significant differences in forced vital capacity in favour of rituximab; although no significant differences between rituximab and placebo were seen in other critical or important outcomes. He et al., 2022 conducted a meta-analysis in the treatment of anti-melanoma differentiation-associated protein 5 dermatomyositis (anti-MDA5 DM) which showed that 71% of patients responded to rituximab.
Studies included in the systematic reviews were generally of low quality, with heterogeneity between studies. There was also some overlap between the studies included in each review.
The RECITAL study results showed rituximab was not superior to cyclophosphamide to treat connective tissue disorder-associated ILD in 101 patients in the UK. Patients in both treatment groups had increased FVC at 24 weeks, and clinically important improvements in patient-reported quality of life. Rituximab was associated with fewer adverse events, and the authors concluded that it should be considered as a therapeutic alternative to cyclophosphamide in people with CTD-ILD who need intravenous therapy (Maher et al., 2023).
The EVER-ILD study results showed that treatment with rituximab and mycophenolate mofetil (MMF) was superior to MMF alone in patients with ILD associated with connective tissue disease or idiopathic interstitial pneumonia (Mankikian et al., 2023).
Safety: Adverse events reported in the studies were consistent with those previously reported: most commonly bacterial and viral infections. No new safety concerns with rituximab were identified.
Cost-effectiveness: No relevant cost-effectiveness analyses were identified in the repeat literature search.
Budget impact: Clinical experts report that 16 patients have started treatment with rituximab in the last year. Only partial data are available for three health boards;, therefore, usage may be slightly higher. In the original assessment it was estimated that 20 patients per year would be started on rituximab for interstitial lung disease, which is comparable to actual usage.
Impact on health and social care services: Minimal.
Patient outcome data: [confidential information removed]
Evaluation of evidence: No significant new clinical evidence has been published that challenges the original recommendation. Since the One Wales recommendation was last reviewed, European and US guidelines for the treatment of systemic sclerosis‑associated interstitial lung disease have been updated to include the use of rituximab. Data provided indicate patient numbers are within the original budget impact estimates and where outcomes are available, have resulted in disease stability or clinical improvement.
Next review date: February 2026
References: a full reference list is available on request.
Disclaimer: This document includes evidence published since the last review or full assessment of this medicine for the indication under consideration. It does not replace the original full evidence status report. Any previous reviews and the original full evidence status report are available from this webpage in the section '
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 the One Wales policy and this found there to be a positive impact. Key actions have been identified and these can be found in the One Wales Policy EHIA document.
Information presented in this document can be reproduced using the following citation: All Wales Therapeutics & Toxicology Centre. Rituximab as second- or third-line treatment of fibrotic interstitial lung disease (not idiopathic pulmonary fibrosis) associated with connective tissue disease or idiopathic fibrotic non-specific interstitial pneumonia (OW13). 2024
Copyright AWTTC 2024. All rights reserved.
Medicine details |
|
| Medicine name | rituximab |
| One Wales decision status | Supported for use via the One Wales Medicines process |
| Reference number | OW13 |
| Decision issue date | August 2019 |
| Date of last review | February 2024 |
| Review schedule | Every 2 years |