A randomised, controlled trial to compare prednisolone with doxycycline

1. A randomised, controlled trial to compare prednisolone with doxycycline

2. Most common autoimmune blistering disease in Western Europe • Incidence: estimates vary - audit of the Oxfordshire region (2001-4) showed incidence of 33.4 cases/million/year • Oral prednisolone most common treatment in UK (UK DCTN survey) and Germany (30 hospitals) • This is an effective drug but has many side effects, especially severe in this elderly population

3. Rationale for the study: • Clinical equipoise between steroids and tetracyclines for the treatment of bullous pemphigoid. • Question identified by Cochrane systematic review and UK DCTN • Research question: • Is doxycycline sufficiently effective and safe to be used as a first line treatment for bullous pemphigoid? • Primary objectives: • Safety: Measured by the number of significant blisters present at week 6 • Effectiveness: Measured by the number of severe side effects present at one year

4. Multi-centre randomised controlled trial with a pragmatic design which opened in Feb 2009 • 4.5 year recruitment period with a 1 year follow up for each patient – visits at baseline and weeks 3, 6, 13, 26, 39 and 52 • 256 patients will be recruited from UK (approx 45 sites) and Germany (7 sites) • 7 patients recruited at each site over the course of the trial • Investigator is single – blind for the first 6 weeks but after this is free to amend the dose of the trial medication

5. Prednisolone 0.5mg/kg/day (to be given as a single dose each morning) or • Doxycycline 200mg (once a day) • Mometasone furoate (Elocon) cream or ointment (0.1%) permitted as rescue medication. Applied to blisters / lesions for first 3 weeks and weeks 6 - 52of study

6. Aged 18+ and able to give informed consent • Clinical diagnosis of bullous pemphigoid • At least 3 significant blisters or erosions over 2 or more body sites (eg. both legs) which have appeared in the last week • No previous episodes of bullous pemphigoid or treatment for BP in the previous year (topical steroids allowed)

7. Has taken oral treatment for bullous pemphigoid in the last year, or steroids for any other condition in the last 12 weeks (but if the patient is likely to need steroids in the coming year for a chronic condition they should not be randomised) • Mainly or entirely mucosal pemphigoid • Live virus vaccine in the last three months • Any other condition or allergy which precludes the use of either study drug or would deem them unsuitable in the opinion of the investigator • Participating in another clinical trial

8. The research question developed from a thorough literature search supported by clinical impression of experts in the field • Trial developed by the UK DCTN - rigorous process • Funded by the National Institute for Health Research - highly competitive • International collaboration will ensure sufficient recruitment and support from leaders in the field

9. 50 UK sites and 7 German sites • 3 further sites being opened • 201 Patients recruited up to 16th May • Extension bid successful – now recruiting up to September 2013

10. Refer to a dermatologist who is involved with BLISTER OR • Contact the trial manager (Katharine Foster) on 0115 884 4925 • Please don’t prescribe any oral therapy before the patient has been assessed for the trial. You can prescribe Elecon cream or ointment if required. Website: www.blistertrial.co.uk