By Reuters Staff
NEW YORK (Reuters Health) – For patients with bullous pemphigoid, doxycycline as initial treatment provides acceptable short-term blister control and is safer in the long-term than upfront prednisolone, hint results of a new study.
Bullous pemphigoid is the most common autoimmune blistering skin disease and its incidence is on the rise due in part to the aging of the population. Oral prednisolone is the mainstay of treatment but is associated with clinically significant side effects, the researchers note in their March 6 Lancet online report.
Using a non-inferiority study design, the UK Dermatology Clinical Trials Network BLISTER study group tested the hypothesis that 200 mg/day oral doxycycline is not inferior to oral prednisolone (0.5 mg/kg per day) and is safer. The patients were about 77 years old on average and about two-thirds had moderate-to-severe baseline disease.
There were 132 patients in the doxycycline group and 121 in the prednisolone group. The patients were allowed to apply up to 30 g per week of potent topical corticosteroids to localized blisters for the first three weeks, and after six weeks.
The non-inferiority primary effectiveness outcome for the study was the proportion of patients with three or fewer blisters at six weeks. “We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority,” first author Dr. Hywel Williams of University of Nottingham and colleagues explain.
In the modified intention-to-treat analysis, 83 (74%) of 112 patients starting doxycycline had three or fewer blisters at six weeks compared with 92 (91%) of 101 patients starting prednisolone, an adjusted difference of 18.6% favoring prednisolone (upper limit of 90% CI, 26.1%, within the predefined 37% margin).
Underscoring the side effect profile of systemic steroids in bullous pemphigoid, the prednisolone group had a higher rate of related severe, life-threatening, and fatal events at 52 weeks (36% versus 18% with doxycycline; after adjustment for baseline disease severity, the difference was 19.0%; P=0.001). There were 11 treatment-related deaths in the prednisolone arm and three in the doxycycline arm.
“We have shown that a strategy of starting treatment for bullous pemphigoid with doxycycline 200 mg daily produces acceptable short-term effectiveness that resides within our predefined non-inferiority margin, and significant safety gains at 1 year compared with initiating treatment with prednisolone 0.5 mg/kg per day,” Dr. Williams and colleagues write.
“Although we did not find clear evidence that differences between the two treatment strategies varied by baseline disease severity, our study suggests that effectiveness of either strategy is modest for those with severe disease,” they add.
In a linked commentary, Dr. Henry Grantham and co-authors from Newcastle University, Newcastle upon Tyne, UK, write, “The evidence for non-inferiority is subjective, dependent on the definition of the clinically relevant non-inferiority boundary. However, given the natural history of bullous pemphigoid, and previous responses to topical treatment alone, it is rational to deduce that doxycycline is at least partly effective.”
“So how will this trial affect the management of bullous pemphigoid in clinical practice? Importantly, the primary endpoint for effectiveness in this trial was at 6 weeks. So it would seem reasonable to introduce doxycycline initially in combination with potent (or super-potent) topical steroids; if control is inadequate, treatment can then be escalated to systemic steroids (although this was not covered in the trial design),” Dr. Grantham and colleagues offer.
“An alternative strategy identified by the authors as a potential future trial, would be to start all patients on prednisolone to gain initial control, and then consider doxycycline as a potential maintenance treatment, with patients randomly assigned to continuation of oral corticosteroids or doxycycline,” they add.
The study was funded by the NIHR Health Technology Assessment Program. The authors have disclosed no conflicts of interest.
Dr. Williams did not respond to a request for comment by press time.
SOURCE: https://bit.ly/2mpIWm9 and https://bit.ly/2lY9OhO
Lancet 2017.
(c) Copyright Thomson Reuters 2017. Click For Restrictions - https://about.reuters.com/fulllegal.asp
By Reuters Staff
NEW YORK (Reuters Health) – For patients with bullous pemphigoid, doxycycline as initial treatment provides acceptable short-term blister control and is safer in the long-term than upfront prednisolone, hint results of a new study.
Bullous pemphigoid is the most common autoimmune blistering skin disease and its incidence is on the rise due in part to the aging of the population. Oral prednisolone is the mainstay of treatment but is associated with clinically significant side effects, the researchers note in their March 6 Lancet online report.
Using a non-inferiority study design, the UK Dermatology Clinical Trials Network BLISTER study group tested the hypothesis that 200 mg/day oral doxycycline is not inferior to oral prednisolone (0.5 mg/kg per day) and is safer. The patients were about 77 years old on average and about two-thirds had moderate-to-severe baseline disease.
There were 132 patients in the doxycycline group and 121 in the prednisolone group. The patients were allowed to apply up to 30 g per week of potent topical corticosteroids to localized blisters for the first three weeks, and after six weeks.
The non-inferiority primary effectiveness outcome for the study was the proportion of patients with three or fewer blisters at six weeks. “We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority,” first author Dr. Hywel Williams of University of Nottingham and colleagues explain.
In the modified intention-to-treat analysis, 83 (74%) of 112 patients starting doxycycline had three or fewer blisters at six weeks compared with 92 (91%) of 101 patients starting prednisolone, an adjusted difference of 18.6% favoring prednisolone (upper limit of 90% CI, 26.1%, within the predefined 37% margin).
Underscoring the side effect profile of systemic steroids in bullous pemphigoid, the prednisolone group had a higher rate of related severe, life-threatening, and fatal events at 52 weeks (36% versus 18% with doxycycline; after adjustment for baseline disease severity, the difference was 19.0%; P=0.001). There were 11 treatment-related deaths in the prednisolone arm and three in the doxycycline arm.
“We have shown that a strategy of starting treatment for bullous pemphigoid with doxycycline 200 mg daily produces acceptable short-term effectiveness that resides within our predefined non-inferiority margin, and significant safety gains at 1 year compared with initiating treatment with prednisolone 0.5 mg/kg per day,” Dr. Williams and colleagues write.
“Although we did not find clear evidence that differences between the two treatment strategies varied by baseline disease severity, our study suggests that effectiveness of either strategy is modest for those with severe disease,” they add.
In a linked commentary, Dr. Henry Grantham and co-authors from Newcastle University, Newcastle upon Tyne, UK, write, “The evidence for non-inferiority is subjective, dependent on the definition of the clinically relevant non-inferiority boundary. However, given the natural history of bullous pemphigoid, and previous responses to topical treatment alone, it is rational to deduce that doxycycline is at least partly effective.”
“So how will this trial affect the management of bullous pemphigoid in clinical practice? Importantly, the primary endpoint for effectiveness in this trial was at 6 weeks. So it would seem reasonable to introduce doxycycline initially in combination with potent (or super-potent) topical steroids; if control is inadequate, treatment can then be escalated to systemic steroids (although this was not covered in the trial design),” Dr. Grantham and colleagues offer.
“An alternative strategy identified by the authors as a potential future trial, would be to start all patients on prednisolone to gain initial control, and then consider doxycycline as a potential maintenance treatment, with patients randomly assigned to continuation of oral corticosteroids or doxycycline,” they add.
The study was funded by the NIHR Health Technology Assessment Program. The authors have disclosed no conflicts of interest.
Dr. Williams did not respond to a request for comment by press time.
SOURCE: https://bit.ly/2mpIWm9 and https://bit.ly/2lY9OhO
Lancet 2017.
(c) Copyright Thomson Reuters 2017. Click For Restrictions - https://about.reuters.com/fulllegal.asp
By Reuters Staff
NEW YORK (Reuters Health) – For patients with bullous pemphigoid, doxycycline as initial treatment provides acceptable short-term blister control and is safer in the long-term than upfront prednisolone, hint results of a new study.
Bullous pemphigoid is the most common autoimmune blistering skin disease and its incidence is on the rise due in part to the aging of the population. Oral prednisolone is the mainstay of treatment but is associated with clinically significant side effects, the researchers note in their March 6 Lancet online report.
Using a non-inferiority study design, the UK Dermatology Clinical Trials Network BLISTER study group tested the hypothesis that 200 mg/day oral doxycycline is not inferior to oral prednisolone (0.5 mg/kg per day) and is safer. The patients were about 77 years old on average and about two-thirds had moderate-to-severe baseline disease.
There were 132 patients in the doxycycline group and 121 in the prednisolone group. The patients were allowed to apply up to 30 g per week of potent topical corticosteroids to localized blisters for the first three weeks, and after six weeks.
The non-inferiority primary effectiveness outcome for the study was the proportion of patients with three or fewer blisters at six weeks. “We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority,” first author Dr. Hywel Williams of University of Nottingham and colleagues explain.
In the modified intention-to-treat analysis, 83 (74%) of 112 patients starting doxycycline had three or fewer blisters at six weeks compared with 92 (91%) of 101 patients starting prednisolone, an adjusted difference of 18.6% favoring prednisolone (upper limit of 90% CI, 26.1%, within the predefined 37% margin).
Underscoring the side effect profile of systemic steroids in bullous pemphigoid, the prednisolone group had a higher rate of related severe, life-threatening, and fatal events at 52 weeks (36% versus 18% with doxycycline; after adjustment for baseline disease severity, the difference was 19.0%; P=0.001). There were 11 treatment-related deaths in the prednisolone arm and three in the doxycycline arm.
“We have shown that a strategy of starting treatment for bullous pemphigoid with doxycycline 200 mg daily produces acceptable short-term effectiveness that resides within our predefined non-inferiority margin, and significant safety gains at 1 year compared with initiating treatment with prednisolone 0.5 mg/kg per day,” Dr. Williams and colleagues write.
“Although we did not find clear evidence that differences between the two treatment strategies varied by baseline disease severity, our study suggests that effectiveness of either strategy is modest for those with severe disease,” they add.
In a linked commentary, Dr. Henry Grantham and co-authors from Newcastle University, Newcastle upon Tyne, UK, write, “The evidence for non-inferiority is subjective, dependent on the definition of the clinically relevant non-inferiority boundary. However, given the natural history of bullous pemphigoid, and previous responses to topical treatment alone, it is rational to deduce that doxycycline is at least partly effective.”
“So how will this trial affect the management of bullous pemphigoid in clinical practice? Importantly, the primary endpoint for effectiveness in this trial was at 6 weeks. So it would seem reasonable to introduce doxycycline initially in combination with potent (or super-potent) topical steroids; if control is inadequate, treatment can then be escalated to systemic steroids (although this was not covered in the trial design),” Dr. Grantham and colleagues offer.
“An alternative strategy identified by the authors as a potential future trial, would be to start all patients on prednisolone to gain initial control, and then consider doxycycline as a potential maintenance treatment, with patients randomly assigned to continuation of oral corticosteroids or doxycycline,” they add.
The study was funded by the NIHR Health Technology Assessment Program. The authors have disclosed no conflicts of interest.
Dr. Williams did not respond to a request for comment by press time.
SOURCE: https://bit.ly/2mpIWm9 and https://bit.ly/2lY9OhO
Lancet 2017.
(c) Copyright Thomson Reuters 2017. Click For Restrictions - https://about.reuters.com/fulllegal.asp
