| 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. This advice has been reviewed four times by OWMAG since its issue in 2019 with no new evidence identified to affect the current recommendation. Therefore, this advice will no longer undergo review by OWMAG unless 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 March 2026. It summarises any new evidence available since the last review in November 2023 and patient outcome data collected in the past two years.
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. The NHS England decision has not changed since 2017.
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 in Wales 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.
This is the fourth review of the evidence supporting the One Wales decision (OW13). If this review finds that the latest evidence still supports the decision, we propose that this decision is added to a static list and will not be routinely reviewed.
Current One Wales decision: Recommended as a second or third-line option.
Licence status: Off-label use for this licensed medicine.
Guidelines: Since the last review of this decision in 2023, the European Alliance of Associations for Rheumatology (EULAR) recommendations for the treatment of systemic sclerosis have been published in full (Del Galdo et al., 2025). EULAR recommends that the use of rituximab (or mycophenolate mofetil or cyclophosphamide) should be considered to treat systemic sclerosis-associated interstitial lung disease. These recommendations were considered substantially new by EULAR, compared to the 2017 iteration of the guideline. The level of evidence for these recommendations was 1a and the strength of the recommendations was rated A, indicating that the evidence is strong.
Licensed alternative medicines or Health Technology Assessment advice for alternative medicines: No new medicines or HTA advice reported for this indication.
Effectiveness: AWTTC conducted a literature search to identify new evidence since the previous external review in 2023. We excluded: any studies published before 2024; conference abstracts; case series and case reports; non-English papers; any systematic reviews in which all the included studies were also included in other systematic reviews; studies conducted in patients in regions outside Europe; and studies in which the dose of rituximab used differed from the dose recommended in the One Wales decision (where reported). Our literature search identified six systematic reviews and three studies, including a cost-effectiveness study based on results from the RECITAL trial, mentioned in our last review in 2023. The other two studies were: a retrospective study and a study using real-world evidence from a European registry.
The cost-effectiveness study is discussed below. The systematic reviews and other studies are summarised in the Appendix; including information on the comparators used and the effect size of the primary outcome. It was not always clear if the use of rituximab was second-line or later in the studies, in line with the current One Wales decision.
Studies assessed improvements in lung function by measuring changes in forced vital capacity (FVC), the total volume of air that can be exhaled forcefully after taking a deep breath, and changes in the diffusing capacity of the lungs for carbon monoxide (DLCO), which measures how efficiently the lungs transfer carbon monoxide from inhaled air into your bloodstream.
The largest systematic review and meta-analysis (Zhang et al., 2025) studied rituximab to treat connective tissue disease-associated interstitial lung disease (CTD‑ILD) and included 40 studies. Results showed that rituximab significantly improved forced vital capacity (expressed as a percentage of the predicted value, FVC% [P < 0.05]) and diffusing capacity of the lungs for carbon monoxide (expressed as a percentage of the predicted value, DLCO% [p < 0.01]) compared with the control group who did not receive rituximab.
Two systematic reviews and meta-analyses studied treatments of systemic sclerosis‑associated interstitial lung disease (SSc-ILD) (Anwar et al., 2025 and Wu et al., 2025) and each included two studies that evaluated rituximab. Wu et al. concluded that rituximab and tocilizumab might be the optimal treatments for SSc‑ILD. Tocilizumab ranked highest (surface under the cumulative ranking probability [SUCRA] 0.904) in slowing the deterioration of FVC, followed by rituximab (0.709); rituximab ranked highest in improving DLCO (0.842) followed by mycophenolate mofetil (0.566). In the review by Anwar et al., network analysis comparing cyclophosphamide with placebo and other immunosuppressants seemed to favour cyclophosphamide over rituximab. The analysis showed potential heterogeneity between the included studies (I2 = 0.81), which suggested that the meta-analysis was not robust.
Two systematic reviews were conducted on treatments for rheumatoid arthritis-associated interstitial lung disease (RA-ILD) (Ines et al., 2025 and Fassio et al., 2025). In the review by Ines et al., 2025, meta-analysis concluded that rituximab was effective in managing RA‑ILD: stabilisation or improvement of lung function was seen in more than half of the patient cohorts across all studies (proportion of stabilisation ranged from: 42% to 100% based on pulmonary function tests; 42% to 87.5% by high-resolution computed tomography). The review also concluded that rituximab had an overall acceptable safety profile. In the review by Fassio et al., 2025, meta-analysis supported rituximab, abatacept and nintedanib as promising treatment options for RA-ILD. Pooled pre-post %FVC estimates were associated with stabilisation or improvement for rituximab and meta-analyses showed no significant differences in %DLCO changes with rituximab compared to non‑users of rituximab.
A systematic review by Kouranloo et al., 2025 of treatments for anti-synthetase syndrome-associated interstitial lung disease (ASS-ILD), which included rituximab, showed that improvements in FVC and DLCO of 12.2% and 2.9% respectively were seen with rituximab treatment.
Multigroup comparison using data from a large European Scleroderma Trials and Research (EUSTAR) registry, which included 172 SSc-ILD patients given rituximab, showed comparable efficacy, in terms of the primary outcome (FVC percent predicted), between rituximab, tocilizumab, mycophenolate mofetil and cyclophosphamide (p = 0.101 [Yan et al., 2025]). Data from a retrospective study showed that rituximab given together with mycophenolate mofetil significantly increased FVC more than rituximab alone (p = 0.003 [Barde et al., 2025]).
Safety: No new safety concerns with rituximab were identified.
Cost-effectiveness: In our previous review of this One Wales decision in 2023, we reported results from the RECITAL study, a double-blind, double-dummy phase IIb randomised controlled trial of rituximab versus cyclophosphamide to treat CTD-ILD conducted in the UK. In 2024, the final research report of the RECITAL study (Maher et al., 2024) was published and included a cost‑effectiveness analysis. This is the first relevant cost effectiveness analysis AWTTC has identified for this medicine and indication. The analysis concluded that, based on the results of the RECITAL trial and from a UK healthcare payer perspective, rituximab was more cost effective than cyclophosphamide as a treatment for severe or progressive CTD-ILD.
The cost-effectiveness analysis used costs estimated from the NHS perspective; only direct medical costs were accounted for. Quality-adjusted life-years (QALY) were derived from utility values (EuroQoL-5 dimensions 5-levels; EQ-5D-5L) taken from the RECITAL trial, collected at 24 weeks and 48 weeks.
The primary outcome was cost-effectiveness, defined by costs in GB pounds, QALYs, incremental cost‑effectiveness ratio (ICER) and incremental net monetary benefit (INMB). A strategy was considered cost effective if it was: more effective and less costly (dominant strategy); or more effective and more expensive with an ICER below £30,000.
Key assumptions made in the cost-effectiveness model were:
The analysis showed that after 12 months, rituximab was a dominant strategy over cyclophosphamide, generating a cost saving of £1,110.99 and a gain in quality of life of 0.022 QALYs per patient. Rituximab provided an incremental monetary benefit compared with cyclophosphamide. In probabilistic sensitivity analyses rituximab was cost-effective in 81.4% of 1,000 simulations, and cyclophosphamide was cost‑effective in 18.6% of the simulations, assuming a willingness to pay limit of £30,000. One-way sensitivity analysis showed that the main drivers that influenced the ICER values were outpatient costs and treatment of adverse events in the cyclophosphamide group, alongside the rituximab cost.
Although the drug costs for rituximab treatment were higher than the costs for cyclophosphamide (UK costs), the economic analysis suggested that, when considering the patterns of healthcare interaction undertaken by participants in the RECITAL trial, rituximab is the dominant strategy. Rituximab continued to be cost effective under less favourable assumptions, where parameters with the highest level of uncertainty were varied, assuming a willingness-to-pay limit of £30,000. Rituximab would become not cost-effective compared to cyclophosphamide if the price increased by 5%.
Since the RECITAL trial was started, the patent for rituximab expired, and several cheaper biosimilar versions are available in the UK. The reduced costs of these biosimilar alternatives further enhance the cost of rituximab compared to cyclophosphamide. The cost-effectiveness analysis suggests that using rituximab to treat connective tissue disorder-interstitial lung disease is potentially cost-saving compared to cyclophosphamide.
Budget impact: Nineteen patients in South East Wales have received treatment with rituximab in the 2 years since the last review. Extrapolating these figures for the whole of Wales provides an estimate of approximately 29 patients treated annually. This is slightly higher than the original estimate of 20 patients per year and higher than numbers reported in previous reviews. In the first 2 years following the decision uptake was lower than expected; most likely due to the COVID-19 pandemic. No further information has been provided on which to assess the budget impact.
Impact on health and social care services: Minimal.
Patient outcome data: In the two years since the last review nine patients in Cardiff and Vale UHB have received treatment with rituximab for ILD. [confidential information removed]. In Aneurin Bevan UHB ten patients have received treatment in the past two years, no further outcome information has been provided.
Evaluation of evidence: No significant new evidence has been published that challenges the previous evidence presented. Patient numbers are broadly in line with those in the initial estimation. AWTTC recommends continuing access to rituximab in NHS Wales through the One Wales Medicines process for the second- or third-line treatment of fibrotic interstitial lung disease, as outlined in the recommendation. AWTTC recommends adding this decision to a static list, so that it will no longer be routinely reviewed.
Next review date: This advice has been reviewed four times by OWMAG since its issue in 2019 with no new evidence identified to affect the current recommendation. Therefore, this advice will no longer undergo review by OWMAG unless new evidence becomes available.
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 document history 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). 2026
Copyright AWTTC 2026. 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 | June 2026 |
| Review schedule | No longer under review by OWMAG unless new evidence becomes available |