Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic non-inferiority randomised controlled trial

Williams, Hywel C. and Wojnarowska, Fenella and Kirtschig, Gudula and Mason, James and Godec, Thomas R. and Schmidt, Enno and Chalmers, Joanne and Childs, Margaret and Walton, Shernaz and Harman, Karen and Chapman, Anna and Whitham, Diane and Nunn, Andrew J. (2017) Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic non-inferiority randomised controlled trial. The Lancet, 389 (10079). pp. 1630-1638. ISSN 1474-547X

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Abstract

Background: Bullous pemphigoid (BP) is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline conveys acceptable short-term blister control whilst conferring long-term safety advantages over starting treatment with oral corticosteroids.

Methods: Pragmatic multi-centre parallel-group randomised controlled trial of adults with BP (≥3 blisters ≥2 sites and linear basement membrane IgG/C3) plus economic evaluation. Participants were randomised to doxycycline (200 mg/day) or prednisolone (0·5 mg/kg/day). Localised adjuvant potent topical corticosteroids (<30 g/week) was permitted weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with ≤3 blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of noninferiority. The primary safety outcome was the proportion with severe, life-threatening or fatal treatment-related adverse events by 52 weeks. Analysis used a regression model adjusting for baseline disease severity, age and Karnofsky score, with missing data imputed.

Results: 132 patients were randomised to doxycycline and 121 to prednisolone from 54 UK and 7 German dermatology centres. Mean age was 77·7 years and 68.4% had moderate to severe baseline disease. For those starting doxycycline, 83/112 (74·1%) had ≤3 blisters at 6 weeks compared with 92/101 (91·1%) for prednisolone, a difference of 18·6% favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening and fatal events at 52 weeks were 18·5% for those starting doxycycline and 36·6% for prednisolone (mITT analysis), an adjusted difference of 19·0% (95% CI, 7·9%, 30·1%, p=0·001).

Conclusions: A strategy of starting BP patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control and significantly safer long-term.

Item Type: Article
Additional Information: Issued on behalf of the UK Dermatology Clinical Trials Network BLISTER Study Group
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine
Identification Number: 10.1016/S0140-6736(17)30560-3
Depositing User: Eprints, Support
Date Deposited: 03 Jan 2017 09:44
Last Modified: 05 May 2017 13:17
URI: http://eprints.nottingham.ac.uk/id/eprint/39540

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