학술논문
Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial
Document Type
Academic Journal
Author
Williams, Hywel C; Wojnarowska, Fenella; Kirtschig, Gudula; Mason, James; Godec, Thomas R; Schmidt, Enno; Chalmers, Joanne R; Childs, Margaret; Walton, Shernaz; Harman, Karen; Chapman, Anna; Whitham, Diane; Nunn, Andrew J; Adams, J; Akhras, V; Anstey, A; Barnard, C; Bell, H; Blackford, S; Brocker, E; Carmichael, A; Coelho, R R; Craig, F; Davies, K; Ellis, R; English, J; Glaser, R; Groves, R; Gunthert, C; Hampton, P J; Hepburn, N; Hugel, R; Hussain, K; Ingram, J; Layton, A M; Levell, N J; Lewis, V; Malhomme, H; Omerod, A; Patel, G; Rallan, R; Ravenscroft, J; Santander, H; Steinbrink, K; Sticherling, M; Thomas, C; Vatve, M; van Beek, N; Venning, V; Veysey, E; Wachsmuth, R; Wahie, S; Walker, B; Walsh, M; Wee, J; Westmoreland, M; Wong, G; Ferguson, Adam; Verpetinske, Indre; Duarte-Williamson, Emilia; Antony, Fiona; Bower, Chris; Gawkrodger, David; Taghipour, Kathy; Dunnill, M G S; Waters, Alex; Bottomley, Walter; Wright, Andrew; Sterling, Jane; Azam, Adzura; Gibbs, Sam; Luger, Thomas; Salvary, Ingrid; Lovell, Chris; Ilchyshyn, Andrew; Gibbon, Karen; Nik, Marinella; Charles-Holmes, Robert; Lavery, A Lloyd
Source
The Lancet. April 22, 2017, Vol. 389 Issue 10079, 1630
Subject
Language
English
ISSN
0140-6736
Abstract
To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1016/S0140-6736(17)30560-3 Byline: Prof Hywel C Williams, DSc [hywel.williams@nottingham.ac.uk] (a,*), Prof Fenella Wojnarowska, PhD (b), Gudula Kirtschig, MD (a,c), Prof James Mason, PhD (d), Thomas R Godec, MSc (e), Prof Enno Schmidt, MD (f), Joanne R Chalmers, PhD (a), Margaret Childs (g), Prof Shernaz Walton, MD (h), Karen Harman, DM (i), Anna Chapman, MSc (j), Diane Whitham (g), Prof Andrew J Nunn, MSc (e), J Adams, V Akhras, A Anstey, C Barnard, H Bell, S Blackford, E Brocker, A Carmichael, R R Coelho, F Craig, K Davies, R Ellis, J English, R Glaser, R Groves, C Gunthert, P J Hampton, N Hepburn, R Hugel, K Hussain, J Ingram, A M Layton, N J Levell, V Lewis, H Malhomme, A Omerod, G Patel, R Rallan, J Ravenscroft, H Santander, K Steinbrink, M Sticherling, C Thomas, M Vatve, N van Beek, V Venning, E Veysey, R Wachsmuth, S Wahie, B Walker, M Walsh, J Wee, M Westmoreland, G Wong, Adam Ferguson, Indre Verpetinske, Emilia Duarte-Williamson, Fiona Antony, Chris Bower, David Gawkrodger, Kathy Taghipour, M G S Dunnill, Alex Waters, Walter Bottomley, Andrew Wright, Jane Sterling, Adzura Azam, Sam Gibbs, Thomas Luger, Ingrid Salvary, Chris Lovell, Andrew Ilchyshyn, Karen Gibbon, Marinella Nik, Robert Charles-Holmes, A Lloyd Lavery Summary Background Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. Methods We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0*5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3--9, 10--30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids ( Findings Between March 1, 2009, and Oct 31, 2013, 132 patients were randomly assigned to doxycycline and 121 to prednisolone from 54 UK and seven German dermatology centres. Mean age was 77*7 years (SD 9*7) and 173 (68%) of 253 patients had moderate-to-severe baseline disease. For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18*6% (90% CI 11*1--26*1) 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% (22 of 121) for those starting doxycycline and 36% (41 of 113) for prednisolone (mITT), an adjusted difference of 19*0% (95% CI 7*9--30*1), p=0*001. Interpretation Starting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term. Funding NIHR Health Technology Assessment Programme. Author Affiliation: (a) Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, UK (b) Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK (c) Institute of General Medicine and Interprofessional Care, University of Tubingen, Tubingen, Germany (d) Warwick Medical School, University of Warwick, Coventry, UK (e) Medical Research Council Clinical Trials Unit at University College London, London, UK (f) Department of Dermatology, University of Lubeck, Lubeck, Germany (g) Nottingham Clinical Trials Unit, Nottingham Health Science Partners, Nottingham, UK (h) Dermatology Department, Hull Royal Infirmary, Hull, UK (i) Dermatology Department, Leicester Royal Infirmary, Leicester, UK (j) Dermatology Department, Queen Elizabeth Hospital, Greenwich, London, UK * Correspondence to: Prof Hywel C Williams, Centre of Evidence Based Dermatology, University of Nottingham, King's Meadow Campus, Nottingham NG7 2NR, UK (footnote)[Dagger] Listed at the end of the Article