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Prior elicitation of the efficacy and tolerability of Methotrexate and Mycophenolate Mofetil in Juvenile Localised Scleroderma

Authors :
Desai, Yasin
Jaki, Thomas
Beresford, Michael W
Burnett, Thomas
Eleftheriou, Despina
Jacobe, Heidi
Leone, Valentina
Li, Suzanne
Mozgunov, Pavel
Ramanan, Athimalaipet V
Torok, Kathryn S
Anderson, Marina E
Anton, Jordi
Avcin, Tadej
Felton, Jessie
Foeldvari, Ivan
Laguda, Bisola
McErlane, Flora
Shaw, Lindsay
Zulian, Francesco
Pain, Clare E
Desai, Yasin
Jaki, Thomas
Beresford, Michael W
Burnett, Thomas
Eleftheriou, Despina
Jacobe, Heidi
Leone, Valentina
Li, Suzanne
Mozgunov, Pavel
Ramanan, Athimalaipet V
Torok, Kathryn S
Anderson, Marina E
Anton, Jordi
Avcin, Tadej
Felton, Jessie
Foeldvari, Ivan
Laguda, Bisola
McErlane, Flora
Shaw, Lindsay
Zulian, Francesco
Pain, Clare E
Publication Year :
2021

Abstract

BackgroundEvidence is lacking for safe and effective treatments for juvenile localised scleroderma (JLS). Methotrexate (MTX) is commonly used first line and mycophenolate mofetil (MMF) second line, despite a limited evidence base. A head to head trial of these two medications would provide data on relative efficacy and tolerability. However, a frequentist approach is difficult to deliver in JLS, because of the numbers needed to sufficiently power a trial. A Bayesian approach could be considered.MethodsAn international consensus meeting was convened including an elicitation exercise where opinion was sought on the relative efficacy and tolerability of MTX compared to MMF to produce prior distributions for a future Bayesian trial. Secondary aims were to achieve consensus agreement on critical aspects of a future trial.ResultsAn international group of 12 clinical experts participated. Opinion suggested superior efficacy and tolerability of MMF compared to MTX; where most likely value of efficacy of MMF was 0.70 (95% confidence interval (CI) 0.34-0.90) and of MTX was 0.68 (95% CI 0.41-0.8). The most likely value of tolerability of MMF was 0.77 (95% CI 0.3-0.94) and of MTX was 0.62 (95% CI 0.32-0.84). The wider CI for MMF highlights that experts were less sure about relative efficacy and tolerability of MMF compared to MTX. Despite using a Bayesian approach, power calculations still produced a total sample size of 240 participants, reflecting the uncertainty amongst experts about the performance of MMF.ConclusionsKey factors have been defined regarding the design of a future Bayesian approach clinical trial including elicitation of prior opinion of the efficacy and tolerability of MTX and MMF in JLS. Combining further efficacy data on MTX and MMF with prior opinion could potentially reduce the pre-trial uncertainty so that, when combined with smaller trial sample sizes a compelling evidence base is available.

Details

Database :
OAIster
Notes :
text, text, text, text, text, text, text, https://eprints.lancs.ac.uk/id/eprint/219765/1, English, English, English, English, English, English, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1438751114
Document Type :
Electronic Resource