A Phase II randomized controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS)

Deborah J Griffiths-Jones; Yvonne Sylvestre Garcia; W David Ryder; John D Pauling; Frances Hall; Peter Lanyon; Smita Bhat; Karen Douglas; Harsha Gunawardena; Mohammed Akil; Marina Anderson; Bridget Griffiths; Francesco Del Galdo; Hazem Youssef; Rajan Madhok; Barbara Arthurs; Maya Buch; Kim Fligelstone; Mohammed Zubair; Justin C Mason; Christopher P Denton; Ariane L Herrick

doi:10.1093/rheumatology/kead012

A Phase II randomized controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS)

Deborah J Griffiths-Jones, Yvonne Sylvestre Garcia, W David Ryder, John D Pauling, Frances Hall, Peter Lanyon, Smita Bhat, Karen Douglas, Harsha Gunawardena, Mohammed Akil, Marina Anderson, Bridget Griffiths, Francesco Del Galdo, Hazem Youssef, Rajan Madhok, Barbara Arthurs, Maya Buch, Kim Fligelstone, Mohammed Zubair, Justin C MasonChristopher P Denton, Ariane L Herrick^*

^*Corresponding author for this work

Bristol Medical School (THS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

10 Citations (Scopus)

Abstract

Objectives:
Although the painful and disabling features of early diffuse cutaneous SSc (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate-dose prednisolone in early dcSSc.

Methods:
PRedSS set out as a Phase II, multicentre, double-blind randomized controlled trial, converted to open-label during the Covid-19 pandemic. Patients were randomized to receive either prednisolone (∼0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. Co-primary endpoints were the HAQ Disability Index (HAQ-DI) and modified Rodnan skin score (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures reflecting pain, itch, fatigue, anxiety and depression, and helplessness. Target recruitment was 72 patients.

Results:
Thirty-five patients were randomized (17 prednisolone, 18 placebo/control). The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was −0.10 (97.5% CI: −0.29, 0.10), P = 0.254, and in mRSS −3.90 (97.5% CI: −8.83, 1.03), P = 0.070, both favouring prednisolone but not significantly. Patients in the prednisolone group experienced significantly less pain (P = 0.027), anxiety (P = 0.018) and helplessness (P = 0.040) than control patients at 3 months. There were no renal crises, but sample size was small.

Conclusion:
PRedSS was terminated early primarily due to the Covid-19 pandemic, and so was underpowered. Therefore, interpretation must be cautious and results considered inconclusive, indicating the need for a further randomized trial.

Trial registration:
ClinicalTrials.gov, https://clinicaltrials.gov, NCT03708718.

Original language	English
Pages (from-to)	3133-3138
Number of pages	6
Journal	Rheumatology
Volume	62
Issue number	9
Early online date	13 Jan 2023
DOIs	https://doi.org/10.1093/rheumatology/kead012
Publication status	Published - 1 Sept 2023

Bibliographical note

Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Keywords

Humans
Scleroderma, Diffuse/drug therapy
Treatment Outcome
Pandemics
COVID-19
Double-Blind Method
Prednisolone/adverse effects
Pain

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Griffiths-Jones, D. J., Garcia, Y. S., Ryder, W. D., Pauling, J. D., Hall, F., Lanyon, P., Bhat, S., Douglas, K., Gunawardena, H., Akil, M., Anderson, M., Griffiths, B., Del Galdo, F., Youssef, H., Madhok, R., Arthurs, B., Buch, M., Fligelstone, K., Zubair, M., ... Herrick, A. L. (2023). A Phase II randomized controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS). Rheumatology, 62(9), 3133-3138. https://doi.org/10.1093/rheumatology/kead012

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title = "A Phase II randomized controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS)",

abstract = "Objectives: Although the painful and disabling features of early diffuse cutaneous SSc (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate-dose prednisolone in early dcSSc. Methods: PRedSS set out as a Phase II, multicentre, double-blind randomized controlled trial, converted to open-label during the Covid-19 pandemic. Patients were randomized to receive either prednisolone (∼0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. Co-primary endpoints were the HAQ Disability Index (HAQ-DI) and modified Rodnan skin score (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures reflecting pain, itch, fatigue, anxiety and depression, and helplessness. Target recruitment was 72 patients. Results: Thirty-five patients were randomized (17 prednisolone, 18 placebo/control). The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was −0.10 (97.5\% CI: −0.29, 0.10), P = 0.254, and in mRSS −3.90 (97.5\% CI: −8.83, 1.03), P = 0.070, both favouring prednisolone but not significantly. Patients in the prednisolone group experienced significantly less pain (P = 0.027), anxiety (P = 0.018) and helplessness (P = 0.040) than control patients at 3 months. There were no renal crises, but sample size was small. Conclusion: PRedSS was terminated early primarily due to the Covid-19 pandemic, and so was underpowered. Therefore, interpretation must be cautious and results considered inconclusive, indicating the need for a further randomized trial. Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03708718.",

keywords = "Humans, Scleroderma, Diffuse/drug therapy, Treatment Outcome, Pandemics, COVID-19, Double-Blind Method, Prednisolone/adverse effects, Pain",

author = "Griffiths-Jones, \{Deborah J\} and Garcia, \{Yvonne Sylvestre\} and Ryder, \{W David\} and Pauling, \{John D\} and Frances Hall and Peter Lanyon and Smita Bhat and Karen Douglas and Harsha Gunawardena and Mohammed Akil and Marina Anderson and Bridget Griffiths and \{Del Galdo\}, Francesco and Hazem Youssef and Rajan Madhok and Barbara Arthurs and Maya Buch and Kim Fligelstone and Mohammed Zubair and Mason, \{Justin C\} and Denton, \{Christopher P\} and Herrick, \{Ariane L\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.",

year = "2023",

month = sep,

day = "1",

doi = "10.1093/rheumatology/kead012",

language = "English",

volume = "62",

pages = "3133--3138",

journal = "Rheumatology",

issn = "1462-0324",

publisher = "Oxford University Press",

number = "9",

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Griffiths-Jones, DJ, Garcia, YS, Ryder, WD, Pauling, JD, Hall, F, Lanyon, P, Bhat, S, Douglas, K, Gunawardena, H, Akil, M, Anderson, M, Griffiths, B, Del Galdo, F, Youssef, H, Madhok, R, Arthurs, B, Buch, M, Fligelstone, K, Zubair, M, Mason, JC, Denton, CP & Herrick, AL 2023, 'A Phase II randomized controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS)', Rheumatology, vol. 62, no. 9, pp. 3133-3138. https://doi.org/10.1093/rheumatology/kead012

TY - JOUR

T1 - A Phase II randomized controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS)

AU - Griffiths-Jones, Deborah J

AU - Garcia, Yvonne Sylvestre

AU - Ryder, W David

AU - Pauling, John D

AU - Hall, Frances

AU - Lanyon, Peter

AU - Bhat, Smita

AU - Douglas, Karen

AU - Gunawardena, Harsha

AU - Akil, Mohammed

AU - Anderson, Marina

AU - Griffiths, Bridget

AU - Del Galdo, Francesco

AU - Youssef, Hazem

AU - Madhok, Rajan

AU - Arthurs, Barbara

AU - Buch, Maya

AU - Fligelstone, Kim

AU - Zubair, Mohammed

AU - Mason, Justin C

AU - Denton, Christopher P

AU - Herrick, Ariane L

PY - 2023/9/1

Y1 - 2023/9/1

N2 - Objectives: Although the painful and disabling features of early diffuse cutaneous SSc (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate-dose prednisolone in early dcSSc. Methods: PRedSS set out as a Phase II, multicentre, double-blind randomized controlled trial, converted to open-label during the Covid-19 pandemic. Patients were randomized to receive either prednisolone (∼0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. Co-primary endpoints were the HAQ Disability Index (HAQ-DI) and modified Rodnan skin score (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures reflecting pain, itch, fatigue, anxiety and depression, and helplessness. Target recruitment was 72 patients. Results: Thirty-five patients were randomized (17 prednisolone, 18 placebo/control). The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was −0.10 (97.5% CI: −0.29, 0.10), P = 0.254, and in mRSS −3.90 (97.5% CI: −8.83, 1.03), P = 0.070, both favouring prednisolone but not significantly. Patients in the prednisolone group experienced significantly less pain (P = 0.027), anxiety (P = 0.018) and helplessness (P = 0.040) than control patients at 3 months. There were no renal crises, but sample size was small. Conclusion: PRedSS was terminated early primarily due to the Covid-19 pandemic, and so was underpowered. Therefore, interpretation must be cautious and results considered inconclusive, indicating the need for a further randomized trial. Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03708718.

AB - Objectives: Although the painful and disabling features of early diffuse cutaneous SSc (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate-dose prednisolone in early dcSSc. Methods: PRedSS set out as a Phase II, multicentre, double-blind randomized controlled trial, converted to open-label during the Covid-19 pandemic. Patients were randomized to receive either prednisolone (∼0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. Co-primary endpoints were the HAQ Disability Index (HAQ-DI) and modified Rodnan skin score (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures reflecting pain, itch, fatigue, anxiety and depression, and helplessness. Target recruitment was 72 patients. Results: Thirty-five patients were randomized (17 prednisolone, 18 placebo/control). The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was −0.10 (97.5% CI: −0.29, 0.10), P = 0.254, and in mRSS −3.90 (97.5% CI: −8.83, 1.03), P = 0.070, both favouring prednisolone but not significantly. Patients in the prednisolone group experienced significantly less pain (P = 0.027), anxiety (P = 0.018) and helplessness (P = 0.040) than control patients at 3 months. There were no renal crises, but sample size was small. Conclusion: PRedSS was terminated early primarily due to the Covid-19 pandemic, and so was underpowered. Therefore, interpretation must be cautious and results considered inconclusive, indicating the need for a further randomized trial. Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03708718.

KW - Humans

KW - Scleroderma, Diffuse/drug therapy

KW - Treatment Outcome

KW - Pandemics

KW - COVID-19

KW - Double-Blind Method

KW - Prednisolone/adverse effects

KW - Pain

U2 - 10.1093/rheumatology/kead012

DO - 10.1093/rheumatology/kead012

M3 - Article (Academic Journal)

C2 - 36637209

SN - 1462-0324

VL - 62

SP - 3133

EP - 3138

JO - Rheumatology

JF - Rheumatology

IS - 9

ER -

A Phase II randomized controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS)

Abstract

Bibliographical note

Keywords

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