It’s the first biologic to have a significant steroid-sparing effect on the debilitating and life-threatening disease.
Adults with moderate to severe bullous pemphigoid have achieved sustained disease remission with dupilumab, a pivotal study has found.
The new study is being hailed as a breakthrough, as it is the first biologic to have a significant steroid-sparing effect on the debilitating and life-threatening disease.
Dupilumab is currently listed on the Pharmaceutical Benefits Scheme (PBS) in Australia for the treatment of patients aged 12 years and above with severe atopic dermatitis who have failed to respond to optimally prescribed topical treatments.
Sydney dermatologist Professor Dedee Murrell, head of the Department of Dermatology at St George Hospital and the University of NSW, has been involved in the design and conduct of the international trial since the outset.
She told Rheumatology Republic the findings were a “huge step forward”, particularly for elderly patients with many comorbidities.
“Even though the quality-of-life data isn’t here yet [this is still being prepared for future publication], anecdotally, you know that reducing steroids equates to better quality of life, not to mention the fact that reducing the burden of blisters improves quality so, I think this is a ground breaker,” she said.
The trial, known as the ADEPT pivotal study, met the primary and all key secondary endpoints evaluating its investigational use in adults with moderate-to-severe disease. In the trial, five times more dupilumab patients achieved sustained disease remission compared to those on placebo.
Sustained disease remission was defined as complete clinical remission with completion of oral corticosteroids taper by week 16 without relapse and no rescue therapy use during the 36-week treatment period.
In the ADEPT study, 106 adults with moderate-to-severe BP were randomized to receive dupilumab 300 mg (n=53) every two weeks after an initial loading dose or placebo (n=53), along with standard-of-care oral corticosteroids (OCS). During treatment, all patients underwent a protocol-defined OCS tapering regimen if control of disease activity was maintained.
For the primary endpoint, 20% of dupilumab patients experienced sustained disease remission at 36 weeks compared to 4% for placebo. For the components comprising the primary endpoint – with patients having to achieve all components – efficacy among patients receiving dupilumab compared to placebo included:
- Absence of disease relapse after patient completed OCS taper: 59% vs. 16%
- Absence of need for rescue therapy during treatment period: 42% vs. 12%
- Achievement of complete remission and off OCS by week 16: 38% vs. 27% (not significant)
For selected secondary endpoints, results for dupilumab compared to placebo were statistically significant as follows:
- Patients achieving ≥90% reduction in disease severity: 41% vs. 10%
- Patients achieving clinically meaningful itch reduction: 40% vs. 11%
- Secondary endpoints assessing decreased OCS use, and time to use of rescue medications, also favoured dupilumab and were significant
- Reduction in disease severity from baseline: 77% vs. 51%
- Reduction in itch from baseline: 52% vs. 27%
- Days of complete remission off OCS: 40 vs. 13
Overall rates of adverse events (AEs) were 96% (n=51) for dupilumab and 96% (n=51) for placebo. AEs more commonly observed with dupilumab compared to placebo in more than three patients included peripheral oedema (n=8 vs. n=5), arthralgia (n=5 vs. n=3), back pain (n=4 vs. n=2), blurred vision (n=4 vs. n=0), hypertension (n=4 vs. n=3), asthma (n=4 vs. n=1), conjunctivitis (n=4 vs. n=0), constipation (n=4 vs. n=1), upper respiratory tract infection (n=3 vs. n=1), limb injury (n=3 vs. n=2), and insomnia (n=3 vs. n=2). There were no AEs leading to death in the dupilumab group and 2 AEs leading to death in the placebo group.
Professor Murrell said the clinically meaningful reduction in itch was a significant result.
“The dupilumab is holding these people, and they’ve only really measured them out to eight weeks for the outcome that they were looking for, because that was part of the definition,” she said.
“Another thing is that this is such a safe treatment that’s approved for basically young children, six months and up with bad eczema.
“Eczema is a type two immune response disease, and they’ve discovered that bullous pemphigoid, at the other end of the age spectrum, is another type two response, and it’s often a cause of old age eczema.”
She said it was possible that people in nursing homes diagnosed as having eczema could in fact have undiagnosed bullous pemphigoid.
“They don’t think of it until it gets so bad that the blisters come and then people are stuck in nursing homes with itching. They’re just giving them steroids. They’re not investigating them,” said Professor Murrell.
“There’s probably a lot of them around, especially people with diabetes … if we could manage these people, recognise them earlier, and treat them with dupilumab then they hopefully wouldn’t end up with these horrible blisters, infections and death, because the mortality is about 20% in one year this disease.
“This is breakthrough stuff.”
