Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness—a protocol for a randomised controlled trial (ASTUTE trial)
Introduction Adalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted by the National Institute for Health and Care Excellence guidance. Ophthalmologists believe that adalimum...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2024-01-01
|
| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/14/1/e082246.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850196091423686656 |
|---|---|
| author | Chris A Rogers Andrew Dick Tunde Peto Robert Wilson Pearse A Keane Alastair K Denniston Srilakshmi M Sharma Lucy Culliford Katie Pike Sarah Baos Carlos Pavesio Sarah Wordsworth Barnaby Reeves Annie Folkard Mae Hazell Mandy P Y Lui Nicholas A V Beare |
| author_facet | Chris A Rogers Andrew Dick Tunde Peto Robert Wilson Pearse A Keane Alastair K Denniston Srilakshmi M Sharma Lucy Culliford Katie Pike Sarah Baos Carlos Pavesio Sarah Wordsworth Barnaby Reeves Annie Folkard Mae Hazell Mandy P Y Lui Nicholas A V Beare |
| author_sort | Chris A Rogers |
| collection | DOAJ |
| description | Introduction Adalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted by the National Institute for Health and Care Excellence guidance. Ophthalmologists believe that adalimumab may be effective in a wider range of patients. The Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness (ASTUTE) trial will recruit patients with ANIU who do and do not meet funding criteria and will evaluate the effectiveness and cost-effectiveness of adalimumab versus placebo as an add-on therapy to standard care.Methods and analysis The ASTUTE trial is a multicentre, parallel-group, placebo-controlled, pragmatic randomised controlled trial with a 16-week treatment run-in (TRI). At the end of the TRI, only responders will be randomised (1:1) to 40 mg adalimumab or placebo (both are the study investigational medicinal product) self-administered fortnightly by subcutaneous injection. The target sample size is 174 randomised participants. The primary outcome is time to treatment failure (TF), a composite of signs indicative of active ANIU. Secondary outcomes include individual TF components, retinal morphology, adverse events, health-related quality of life, patient-reported side effects and visual function, best-corrected visual acuity, employment status and resource use. In the event of TF, open-label drug treatment will be restarted as per TRI for 16 weeks, and if a participant responds again, allocation will be switched without unmasking and treatment with investigational medicinal product restarted.Ethics and dissemination The trial received Research Ethics Committee (REC) approval from South Central – Oxford B REC in June 2020. The findings will be presented at international meetings, by peer-reviewed publications and through patient organisations and newsletters to patients, where available.Trial registration ISRCTN31474800. Registered 14 April 2020. |
| format | Article |
| id | doaj-art-3ebaf65170e0472cb04a20868bd1cd4e |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-3ebaf65170e0472cb04a20868bd1cd4e2025-08-20T02:13:32ZengBMJ Publishing GroupBMJ Open2044-60552024-01-0114110.1136/bmjopen-2023-082246Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness—a protocol for a randomised controlled trial (ASTUTE trial)Chris A Rogers0Andrew Dick1Tunde Peto2Robert Wilson3Pearse A Keane4Alastair K Denniston5Srilakshmi M Sharma6Lucy Culliford7Katie Pike8Sarah Baos9Carlos Pavesio10Sarah Wordsworth11Barnaby Reeves12Annie Folkard13Mae Hazell14Mandy P Y Lui15Nicholas A V Beare16University of Bristol, Bristol, UKTranslational Health Sciences, University of Bristol, Bristol, UKCentre for Public Health, Queen`s University Belfast Faculty of Medicine Health and Life Sciences, Belfast, UKMidlands, NHS England, Nottingham, UK1 Moorfields Eye Hospital NHS Foundation Trust, London, UKCentre for Patient Reported Outcome Research, Institute of Applied Health Research, University of Birmingham, Birmingham, UK.Oxford Eye Hospital, John Radcliffe Hospital, Oxford, UKBristol Trials Centre, University of Bristol, Bristol, UKBristol Trials Centre, University of Bristol, Bristol, UKBristol Trials Centre, University of Bristol, Bristol, UKUveitis and Scleritis Service, Moorfields Eye Hospital NHS Foundation Trust, London, UKUniversity of Oxford, University of Oxford, Oxford, UKUniversity of Bristol, Bristol, UKBirdshot Uveitis Society, London, UKBristol Trials Centre, University of Bristol, Bristol, UKBristol Trials Centre, University of Bristol, Bristol, UKUniversity of Liverpool, Liverpool, UKIntroduction Adalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted by the National Institute for Health and Care Excellence guidance. Ophthalmologists believe that adalimumab may be effective in a wider range of patients. The Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness (ASTUTE) trial will recruit patients with ANIU who do and do not meet funding criteria and will evaluate the effectiveness and cost-effectiveness of adalimumab versus placebo as an add-on therapy to standard care.Methods and analysis The ASTUTE trial is a multicentre, parallel-group, placebo-controlled, pragmatic randomised controlled trial with a 16-week treatment run-in (TRI). At the end of the TRI, only responders will be randomised (1:1) to 40 mg adalimumab or placebo (both are the study investigational medicinal product) self-administered fortnightly by subcutaneous injection. The target sample size is 174 randomised participants. The primary outcome is time to treatment failure (TF), a composite of signs indicative of active ANIU. Secondary outcomes include individual TF components, retinal morphology, adverse events, health-related quality of life, patient-reported side effects and visual function, best-corrected visual acuity, employment status and resource use. In the event of TF, open-label drug treatment will be restarted as per TRI for 16 weeks, and if a participant responds again, allocation will be switched without unmasking and treatment with investigational medicinal product restarted.Ethics and dissemination The trial received Research Ethics Committee (REC) approval from South Central – Oxford B REC in June 2020. The findings will be presented at international meetings, by peer-reviewed publications and through patient organisations and newsletters to patients, where available.Trial registration ISRCTN31474800. Registered 14 April 2020.https://bmjopen.bmj.com/content/14/1/e082246.full |
| spellingShingle | Chris A Rogers Andrew Dick Tunde Peto Robert Wilson Pearse A Keane Alastair K Denniston Srilakshmi M Sharma Lucy Culliford Katie Pike Sarah Baos Carlos Pavesio Sarah Wordsworth Barnaby Reeves Annie Folkard Mae Hazell Mandy P Y Lui Nicholas A V Beare Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness—a protocol for a randomised controlled trial (ASTUTE trial) BMJ Open |
| title | Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness—a protocol for a randomised controlled trial (ASTUTE trial) |
| title_full | Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness—a protocol for a randomised controlled trial (ASTUTE trial) |
| title_fullStr | Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness—a protocol for a randomised controlled trial (ASTUTE trial) |
| title_full_unstemmed | Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness—a protocol for a randomised controlled trial (ASTUTE trial) |
| title_short | Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness—a protocol for a randomised controlled trial (ASTUTE trial) |
| title_sort | adalimumab vs placebo as add on to standard therapy for autoimmune uveitis tolerability effectiveness and cost effectiveness a protocol for a randomised controlled trial astute trial |
| url | https://bmjopen.bmj.com/content/14/1/e082246.full |
| work_keys_str_mv | AT chrisarogers adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT andrewdick adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT tundepeto adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT robertwilson adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT pearseakeane adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT alastairkdenniston adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT srilakshmimsharma adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT lucyculliford adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT katiepike adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT sarahbaos adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT carlospavesio adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT sarahwordsworth adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT barnabyreeves adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT anniefolkard adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT maehazell adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT mandypylui adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial AT nicholasavbeare adalimumabvsplaceboasaddontostandardtherapyforautoimmuneuveitistolerabilityeffectivenessandcosteffectivenessaprotocolforarandomisedcontrolledtrialastutetrial |