Plain language summary, December 22, 2025
First, I would like to acknowledge the support of Arthritis Australia and The Australian Rheumatology Association Research Fund Private Practice Grant for 2025. Without this support, it would not have been possible to undertake this project. It is my hope that this work will help to open up more therapeutic options for patients with EGPA across the world.
EGPA (eosinophilic granulomatosis with polyangiitis) is a rare type of inflammatory disease that often targets blood vessels (hence, it is a form of vasculitis). EGPA is driven by a type of immune cell called the eosinophil, which under ordinary circumstances is thought to predominantly be involved in protecting us against parasites such as tapeworm. When one considers how a microscopic cell might defend against a large organism such as a tapeworm, it is not hard to immediately conclude that the eosinophil must be capable of producing some pretty toxic chemicals (they can). Usually, eosinophils are one of the least common cells in the blood. In EGPA there are too many of them and their toxic products cause damage to the body.
Why eosinophils become overactive in EGPA is now known, however it is fairly clear that they are central to the disease process. EGPA most commonly initially presents as severe asthma and sinusitis. Patients are typically dependent on steroids for management – until it becomes clear that their condition is not just straightforward asthma and sinusitis. EGPA typically causes the formation of polyps in the sinuses, leading to loss of sense of smell. In the lungs, an eosinophilic pneumonia can develop (not due to infection – due to too many eosinophils). EGPA is not limited to the airways however. It often damages nerves, causing ‘mononeuritis multiplex’ – where a peripheral nerve (ie: to the arm of leg) loses all function. A common presentation of mononeuritis multiplex is ‘foot drop’ where the nerve that takes instructions from the brain to the muscles around the ankle and foot just stop working. If that sounds serious, it can get worse: EGPA can attack the heart (myocarditis) and the kidneys (glomerulonephritis). It can also attack the skin, causing rashes as well as the gut (vasculitis of the gut can look like inflammatory bowel disease). It can also attack the joints and is a cause of inflammatory arthritis.
It is because EGPA can attack the joints that rheumatologists are often involved in managing EGPA. For that reason, I became involved in treating a patient with EGPA in 2020 and my experience then led to the project that was supported by Arthritis Australia and the Australian Rheumatology Association in 2025.
Prednisolone and other corticosteroids have been and remain the current mainstay of initial therapy for EGPA. Historically, those with serious organ involvement have been subsequently
treated with cyclophosphamide. Later came rituximab, however neither were sufficiently effective to replace the corticosteroids, that patients remained dependent upon. These traditional approaches were complicated by serious toxicity from the treatments themselves, never mind the EGPA.
In recent years there have been major advances: biologics targeting the eosinophils themselves have transformed the treatment of EGPA. First mepolizumab, then benralizumab have led to significant improvements in disease control, allowing patients to reduce their corticosteroid doses, though typically patients remain dependent on corticosteroids (typically oral, but also inhaled). Rituximab and cyclophosphamide are still required in many patients who present with critical organ involvement. Despite recent developments, most patients with EGPA remain dependent on corticosteroids. Long-term corticosteroid use is associated with an increased risk of serious infection, heart attack, stroke, diabetes mellitus, hypertension, glaucoma, cataract, osteoporosis, avascular necrosis, obesity and death, amongst other potential side effects. Further developments are required to reduce patients’ corticosteroid requirements. This study was initiated to determine whether JAK inhibitors may be of potential utility.
My patient in 2020 was initially unable to access mepolizumab and so I looked for ways to help his respiratory physician tackle both the EGPA and simultaneously address his inflammatory arthritis. My patient was already receiving Ustekinumab for peripheral spondyloarthritis and I had a number of alternative options funded by the PBS that were available to him. The newest at that time was tofacitinib – a Janus Kinase inhibitor (JAK inhibitor). The JAK enzymes (JAK1, JAK2, JAK3 and TYK2) control over 50 biochemical pathways in the body. Tofacitinib inhibits all four enzymes, but is most specific for JAK1 and JAK3. There was almost nothing in the literature to guide me – except one study in mice with eosinophilic pneumonia who had been successfully treated with a novel JAK3 inhibitor. I wasn’t ‘experimenting’ on my patient in recommending tofacitinib – I was just recommending an existing approved and funded medication for his inflammatory arthritis that I explained, just might also help his eosinophilic disease.
The impact was extraordinary. Within a fortnight of starting tofacitinib, my patient was able to cease both his oral prednisolone (he had been on 37.5mg) – and his inhaled steroids! In January 2021 some concerning safety data was published regarding tofacitinib (it, along with other JAK inhibitors now carry a boxed warning regarding cardiovascular and malignancy risk) and my patient stopped treatment – for two weeks. He rang me, in distress. In that short space of time, his sinuses had become congested, his asthma was flaring and he had developed a pustular rash over most of his body. These had failed to respond to 25mg prednisolone. He had performed a blood test that showed that his eosinophil count was just as high as it had been before the tofacitinib. On my advice, he recommenced the tofacitinib and came in to see me the next day. When I saw him, he was relatively well. His sinuses were still congested, but his shortness of breath was largely gone, as was the rash (only a few spots on his lower legs remained). My patient went on to require sinus surgery to remove the polyps that remained symptomatic despite recommencing tofacitinib.
In the years since, my patient has remained on tofacitinib. He has had to withhold it whenever he has an infection or for surgical procedures (this is standard practice). Every time the tofacitinib has been withheld, his EGPA has flared. To mitigate this, his respiratory physician commenced him on mepolizumab (it is now easier to access mepolizumab compared to 2020). Although he has still developed significant symptoms when off tofacitinib, these flares have been less severe than before.
My experience with this patient led to a search for other similar patients, with the idea being that publishing a large series of patients would provide sufficient evidence to support funding for a formal randomized controlled trial of JAKi therapy for EGPA.
I contacted physicians in the following organizations: Asia-Pacific League of Associations for Rheumatology (APLAR) Vasculitis Special Interest Group, the Australia and New Zealand Vasculitis Society, the Canadian Vasculitis Research Network, the European EGPA Study Group, and the Vasculitis Clinical Research Consortium. EGPA is rare however, and inflammatory arthritis is not the most common of complications. It turns out that there were very few similar patients in the world. This project has involved collaborating with colleagues around the world:
Associate Professor Jean-Paul Makhzoum, Université de Montréal, Service de Médecine Interne, Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Canada
Dr Vincent Cottin, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Centre de référence des maladies pulmonaires rares, Service de pneumologie, ERN-LUNG, INRAE, UMR754, F-69000 Lyon, France
Dr Edoardo Conticini, Rheumatology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Italy
Professor Giacomo Emmi, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy; Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Melbourne, Australia
Dr Sam Whittle, Rheumatology Unit, Queen Elizabeth Hospital, Woodville, South Australia
One week after contacting APLAR, one of the co-authors of our study, wrote to me to advise that he had been asked to review a manuscript detailing a series of 11 patients with EGPA treated with tofacitinib. This study (from Fudan University, China) was published by Oxford University Press in the journal, Rheumatology on August 18. Following publication of this study, my immediate reaction was that my project was dead in the water. Having read this paper however it soon became clear that not all was as it appeared. The title of the paper was ‘Tofacitinib in combination with glucocorticoids in the treatment of eosinophilic granulomatosis with polyangiitis: a pilot study of 11 cases’. Reading the detail on each patient it became clear that most of the patients in this study did not actually have EGPA. I discussed the key clinical characteristics of EGPA above. In the Fudan University paper, only three of the 11 patients were reported to have asthma and only four were reported to have sinusitis. The presence or absence of sinonasal polyposis was not described. Three patients were described to have peripheral nerve involvement. Five of the 11 patients had no listed history of asthma, sinusitis or peripheral neuropathy of any type (patients 1, 4, 7, 8, 11). In light of this, my colleagues and I decided that our study was still worth publishing.
We have therefore written a paper describing the experiences of five patients (two are mine, one from Italy, one from France and one from Canada). Four of the five had clearly significant responses to JAK inhibitor therapy, particularly with regard to both lung and gastrointestinal involvement. One of the five patients included in the study did not have active EGPA at the time JAK inhibitor therapy was commenced, but demonstrated an improvement in their arthritis and did not demonstrate any new safety signals. Our results support the design and implementation of a larger randomised controlled trial to further clarify the potential for JAK inhibitor therapy to help patients with EGPA.
I have presented our findings at two conferences:
The 10th Meeting of the European EGPA Study Group on September 18, 2026 (Paris, France)
Australian Rheumatology Association SA/NT annual scientific meeting on November 7, 2026 (Adelaide, South Australia)
We initially submitted our paper to Rheumatology (Oxford University Press) and suggested to the Editor that it would be worth publishing the Fudan University paper alongside ours. Unfortunately, our submission was rejected by the Editor in Chief. We have subsequently resubmitted to The Journal of Rheumatology (Canada).
Yours sincerely,
Dr Paul A.J. Russo
B. MED. SCI (HONS), MBBS, FRACP, FACR
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