J R Chalmers1, F Wojnarowska2, G Kirtschig1, A J Nunn3, D J Bratton3, J Mason4, K A Foster5, D Whitham5, H C Williams1,6. 1. Centre of Evidence Based Dermatology, University of Nottingham, King's Meadow Campus Lenton Lane, Nottingham, NG7 2NR, U.K. 2. Nuffield Department of Clinical Medicine, Oxford University, Oxford, OX3 7BN, U.K. 3. Medical Research Council Clinical Trials Unit, Aviation House 125 Kingsway, London, WC2B 6NH, U.K. 4. School for Medicine, Pharmacy and Health, Wolfson Research Institute, Durham University, Stockton on Tees, TS17 6BH, U.K. 5. Nottingham Clinical Trials Unit, Nottingham Health Science Partners, C Floor South Block, Nottingham, U.K. 6. Dermatology Department, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, U.K.
Abstract
BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease in older people, and is associated with significant morbidity and mortality. Oral corticosteroids are usually effective but the side-effects are thought to contribute to the high morbidity and mortality rate. Treatment with oral tetracyclines may be effective but high-quality, randomized controlled trials (RCTs) are needed to confirm this. OBJECTIVES: To compare the effectiveness and safety of two strategies for treating BP. METHODS: This is a two-arm, parallel group, 52-week RCT comparing doxycycline with prednisolone for initial treatment of BP. Dose is fixed for the initial 6 weeks of treatment (doxycycline 200 mg daily; prednisolone 0.5 mg kg(-1) daily), after which it can be adjusted according to need. A total of 256 patients with BP will be recruited in the U.K. and Germany. RESULTS: The primary outcomes are: (i) effectiveness (assessor-blinded blister count at 6 weeks) and (ii) safety [proportion of patients experiencing ≥ grade 3 adverse events (i.e. severe, life: threatening or fatal) related to trial medication during the year of follow-up]. Primary effectiveness analysis will be an assessment of whether doxycycline can be considered noninferior to prednisolone after 6 weeks of treatment. Primary safety analysis is a superiority analysis at 12 months. Secondary outcomes include longer-term assessment of effectiveness, relapse rates, the proportion of patients experiencing any grade of adverse events related to treatment, quality of life and cost-effectiveness. CONCLUSIONS: The trial will provide good evidence for whether the strategy of starting BP treatment with doxycycline is a useful alternative to prednisolone.
BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease in older people, and is associated with significant morbidity and mortality. Oral corticosteroids are usually effective but the side-effects are thought to contribute to the high morbidity and mortality rate. Treatment with oral tetracyclines may be effective but high-quality, randomized controlled trials (RCTs) are needed to confirm this. OBJECTIVES: To compare the effectiveness and safety of two strategies for treating BP. METHODS: This is a two-arm, parallel group, 52-week RCT comparing doxycycline with prednisolone for initial treatment of BP. Dose is fixed for the initial 6 weeks of treatment (doxycycline 200 mg daily; prednisolone 0.5 mg kg(-1) daily), after which it can be adjusted according to need. A total of 256 patients with BP will be recruited in the U.K. and Germany. RESULTS: The primary outcomes are: (i) effectiveness (assessor-blinded blister count at 6 weeks) and (ii) safety [proportion of patients experiencing ≥ grade 3 adverse events (i.e. severe, life: threatening or fatal) related to trial medication during the year of follow-up]. Primary effectiveness analysis will be an assessment of whether doxycycline can be considered noninferior to prednisolone after 6 weeks of treatment. Primary safety analysis is a superiority analysis at 12 months. Secondary outcomes include longer-term assessment of effectiveness, relapse rates, the proportion of patients experiencing any grade of adverse events related to treatment, quality of life and cost-effectiveness. CONCLUSIONS: The trial will provide good evidence for whether the strategy of starting BP treatment with doxycycline is a useful alternative to prednisolone.
Authors: An-Wen Chan; Jennifer M Tetzlaff; Peter C Gøtzsche; Douglas G Altman; Howard Mann; Jesse A Berlin; Kay Dickersin; Asbjørn Hróbjartsson; Kenneth F Schulz; Wendy R Parulekar; Karmela Krleza-Jeric; Andreas Laupacis; David Moher Journal: BMJ Date: 2013-01-08
Authors: Yang Zhang; Bin-Jin Hwang; Zhen Liu; Ning Li; Kendall Lough; Scott E Williams; Jinbo Chen; Susan W Burette; Luis A Diaz; Maureen A Su; Shengxiang Xiao; Zhi Liu Journal: Proc Natl Acad Sci U S A Date: 2018-06-04 Impact factor: 11.205
Authors: J M Mason; J R Chalmers; T Godec; A J Nunn; G Kirtschig; F Wojnarowska; M Childs; D Whitham; E Schmidt; K Harman; S Walton; A Chapman; H C Williams Journal: Br J Dermatol Date: 2018-01-15 Impact factor: 9.302
Authors: Hywel C Williams; Fenella Wojnarowska; Gudula Kirtschig; James Mason; Thomas R Godec; Enno Schmidt; Joanne R Chalmers; Margaret Childs; Shernaz Walton; Karen Harman; Anna Chapman; Diane Whitham; Andrew J Nunn Journal: Lancet Date: 2017-03-06 Impact factor: 79.321