Dupilumab appears attractive for the treatment of refractory EGPA-related asthma and ENT manifestations.
Introduction
ANCA-associated vasculitis (shortened to AAV), is a rare group of diseases of the immune system. It causes damage to small blood vessels. Any part of the body can be affected, but it most often affects the small blood vessels of a person’s kidneys, lungs, joints, nerves, and may cause bleeding in their nose and ears. AAV is very severe, and if left untreated can be life-threating.
AAV is linked to a type of autoantibody called ANCA. An antibody is a protein that in a healthy immune system guards the body from foreign substances, such as viruses or bacteria. But when this goes wrong, autoantibodies can attack a person’s own tissues. ANCA autoantibodies are known to cause damage to small blood vessels.
Eosinophilic granulomatosis with polyangiitis (EGPA) is the rarest type of AAV, affecting less than 20 people in every million. Treatments are available to target a molecule called interleukin-5 and its receptor, but they do not work for everyone – especially people with ear, nose, and throat symptoms. Additionally, sometimes people may have a period of improvement with treatment, but then their signs and symptoms come back – this is called a relapse. In these cases, a different biologic drug called dupilumab may be given. It works by inhibiting the signalling of two different molecules – interleukin-4 and interleukin-13.
What did the authors hope to find?
The authors wanted to see how well dupilumab works for non-vasculitic manifestations of EGPA, such as uncontrolled asthma and ear, nose, and throat symptoms for which they need to take steroids. They also hoped to collect data on the safety of dupilumab in this specific group of people.
Who was studied?
The study included 51 adults with EGPA who had either relapsed disease, or EGPA that did not respond to conventional treatment.
How was the study conducted?
This was a retrospective, observational study. This means the researchers collected information about people’s medical history and lifestyle from their medical records. This allowed researchers to investigate certain links or risks. There was no interventional treatment given to patients as part of the study – only what their doctors had already prescribed for them.
The study was done within a network called the European EGPA Study Group. These doctors had started using dupilumab for people with refractory or relapsing EGPA. The researchers provided the doctors with a form to collect anonymous data and patient information. They then used this information to see how well people responded to the treatment. This was defined according to changes in vasculitis manifestations, asthma and ear, nose, and throat symptoms, as well as the dose of steroid needed to manage the symptoms. The authors also collected information on any side effects.
What were the main findings of the study?
The main finding was that 41% of patients treated with dupilumab achieved a complete response, and 24% achieved a partial response. However, 27% of people did not see a response to dupilumab treatment.
Overall, 35% of people reported an adverse event, including 2 which were serious. Additionally, 31% experienced a relapse, including 10 systemic relapses. These relapses were associated with eosinophilia in the majority of cases – this was due to the presence of too many of a specific type of white blood cell. Efficacy was complete in 41% of patients and partial in 24%.
Are these findings new?
Yes, these results are completely new. No previous study has evaluated the use of dupilumab in people with EGPA.
What are the limitations of this study?
The main limitation of this study was its retrospective design, and the lack of a control group or normal glucocorticoid tapering. This could be associated with a high risk of bias.
What do the authors plan on doing with this information?
The authors hope this original data will help inform the design and objectives of further studies of dupilumab in people with EGPA.
What does this mean for me?
If you have EGPA with uncontrolled asthma, or disabling ear, nose, and throat symptoms, dupilumab may help, and could reduce the dose of steroid medicines you need to take. However, dupilumab is not approved for use in people with EGPA, so this should be done under the supervision of an expert with experience in treating EGPA, who will need to closely monitor clinical and biological signs of relapse.
If you have any concerns about your disease or its treatment, you should talk to your doctor or a healthcare professional involved in your care.
Date prepared: July 2024
Summary based on research article published on: January 2024
From: Summary from Molina B, et al. Dupilumab for relapsing or refractory sinonasal and/ or asthma manifestations in eosinophilic granulomatosis with polyangiitis: a European retrospective study. Ann Rheum Dis 2023;82:1587–1593. doi:10.1136/ard-2023-224756
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