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

Authors :
Desai Y
Jaki T
Beresford MW
Burnett T
Eleftheriou D
Jacobe H
Leone V
Li S
Mozgunov P
Ramanan AV
Torok KS
Anderson ME
Anton J
Avcin T
Felton J
Foeldvari I
Laguda B
McErlane F
Shaw L
Zulian F
Pain CE
Source :
AMRC open research [AMRC Open Res] 2021 Sep 09; Vol. 3, pp. 20. Date of Electronic Publication: 2021 Sep 09 (Print Publication: 2021).
Publication Year :
2021

Abstract

Background: Evidence 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.<br />Methods: An 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.<br />Results: An 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.<br />Conclusions: Key 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.<br />Competing Interests: Competing interests: DE Research grants and consultancy fees from SOBI, Lilly, Pfizer; JA grants and consultancy fees from Novartis, Roche, Gebro Rest of authors no disclosures<br /> (Copyright: © 2021 Desai Y et al.)

Details

Language :
English
ISSN :
2517-6900
Volume :
3
Database :
MEDLINE
Journal :
AMRC open research
Publication Type :
Academic Journal
Accession number :
38708070
Full Text :
https://doi.org/10.12688/amrcopenres.13008.1