The Bullous Pemphigoid Steroids and Tetracyclines (BLISTER) Study
Professor Hywel Williams discusses the results of the BLISTER trial (duration: 3mins 30sec)
6 MAR 2017 - We are pleased to announce that the BLISTER study has now been published in The Lancet.
The University of Nottingham have issued a Press Release to accompany the publication of the results.
Bullous pemphigoid is a condition which results in tense, itchy blisters on the skin. In the BLISTER Study we assessed whether doxycycline (a member of the tetracycline family of antibiotics) was a useful alternative to prednisolone (a corticosteroid) for treating bullous pemphigoid.
Chief Investigator: Professor Hywel Williams, University of Nottingham
Lead Clinician: Professor Fenella Wojnarowska, University of Oxford.
The trial was run in collaboration with the Nottingham Clinical Trials Unit (NCTU), the UK Dermatology Clinical Trials Network (UK DCTN) and the Medical Research Council Clinical Trials Unit (MRC CTU).
The study team would like to thank all the patients who took part in the BLISTER study and all the staff at the recruiting sites, without whom this trial would not have been possible.
1. What is bullous pemphigoid?
Bullous pemphigoid is a skin condition affecting mainly elderly people, which results in tense, itchy blisters and painful skin erosions that can affect the whole body. It is an auto-immune disease where the immune system makes antibodies against he area between the top layer of skin (epidermis) and the next layer (dermis).
2. What treatments did the BLISTER study test?
Steroid tablets are commonly used to treat bullous pemphigoid. They work quite well, but can cause very serious side effects. Antibiotic tablets are also used to treat bullous pemphigoid. They aren't thought to work as well as steroids, but their side-effects are less serious.
The BLISTER study was a randomised controlled trial which tested the antibiotic doxycycline (200 mg daily) against the steroid prednisone (0.5mg/kg/day) to see how safe the treatments are, and how well they work.
3. How many patients took part?
Fifty four UK hospitals and seven German hospitals took part in the study. In total, 253 patients were recruited into the study, 132 patients received doxycycline and 121 received prednisolone.
4. What did the studies involve?
Participants were randomly allocated (by chance) to either take doxycycline tablets or prednisolone tablets. After 6 weeks, participants could switch their treatment or change the dose of prednisone. Hospital visits happened at week 3, week 6 and then at least every 3 months for 1 year, regardless of how long participants took the study medication.
Participants knew which medication they were using, however their doctor did not. This meant that the treatment response could be assessed in an unbiased way. The treatments were assessed by (i) counting the number of blisters present after 6 weeks of treatment and (ii) looking at the side effects that occurred, and how serious they were.
5. What were the key results?
After 6 weeks of treatment, almost three-quarters (74%) of people in the doxycycline group had a good treatment response (3 or fewer blisters) compared with 91% in the prednisolone group. Over a year of treatment, 4 in 10 people experienced serious side effects who started on prednisolone compared to 2 in 10 who started on doxycyline. The results were about the same for people who had mild, moderate or severe bullous pemphigoid.
6. What do the findings of the BLISTER study mean?
Although more people starting on prednisolone had a good treatment response than those on doxycycline, they also experienced significantly more severe side effects. It should be kept in mind that although fewer participants starting on doxycycline had a good treatment response (compared to those starting on prednisone), many participants – nearly three quarters – did have a good response. Additionally, these participants did not experience as many severe, life threatening or fatal side effects. This study gives doctors and patients another option for bullous pemphigoid treatment. Doxycycline, although not quite so effective in the short term, is a significantly safer treatment in the long term.
Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial. Williams, Wojnarowska, Kirtschig et al. The Lancet. 2017.
A randomised controlled trial to compare the safety, effectiveness and cost effectiveness of doxycycline (200 mg/day) with oral prednisolone (0.5 mg/kg/day) for initial treatment of bullous pemphigoid: the Bullous Pemphigoid Steroids and Tetracyclines (BLISTER) Trial. Chalmers JR, Wojnarowska F, Kirtschig G, Mason J, Childs M, Whitham D, et al. Health Technol Assess 2017;21(10)
The value of the pragmatic-explanatory continuum indicator summary wheel in an ongoing study: the bullous pemphigoid steroids and tetracyclines study. Bratton DJ, Nunn AJ, Wojnarowska F, Kirtschig G, Sandell A, Williams HC. Trials. 2012;13:50.
When inferiority meets non-inferiority: implications for interim analyses. Bratton DJ, Williams HC, Kahan BC, Phillips PP, Nunn AJ. Clin Trials. 2012;9(5):605-609.
A randomised controlled trial to compare the safety and effectiveness of doxycycline (200 mg/day) with oral prednisolone (0.5 mg/kg/day) for initial treatment of bullous pemphigoid: A protocol for the Bullous Pemphigoid Steroids and Tetracyclines (BLISTER) Trial. Chalmers JR, Wojnarowska F, Kirtschig G, et al. Br J Dermatol. 2015;173(1):227-34.
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