There has been a significant increase in the number of treatment options for systemic sclerosis over the past decade, according to one Aussie expert.
There are more treatment options for early diffuse systemic sclerosis to choose from than ever before.
That’s what Professor Mandana (Mandy) Nikpour, director of the Sydney MSK Flagship Research Centre at the University of Sydney, told delegates at the ARA Annual Scientific Meeting in Adelaide earlier this month.
“The management of early diffuse systemic sclerosis, or scleroderma, has really been a changing paradigm over the last 10 years where we have moved from a situation where nothing worked to one were we now have a number of therapeutic options,” Professor Nikpour said.
Methotrexate was the first cab off the rank, where two randomised trials displayed improvements in modified Rodnan skin scores following methotrexate compared to placebo.
“But these trials were conducted many years ago, and they used very low doses [of methotrexate] … much less that what we would be using now, which is about 25mg per week,” Professor Nikpour noted.
Evidence supporting the use of cyclophosphamide in systemic sclerosis was first reported in 2006, where a US study found modest benefits on lung function that were maintained for up to two years relative to placebo. However, a greater number of adverse events were reported in the cyclophosphamide group compared to patients who received placebo.
Research performed a decade later suggested that mycophenolate mofetil was similarly efficacious to cyclophosphamide a treating scleroderma-related interstitial lung disease but was associated with fewer side effects. Mycophenolate subsequently went on to become the standard of care for diffuse scleroderma, Professor Nikpour explained.
The interleukin-6 blocker tocilizumab has also been shown to be safe and effective at preserving lung function in patients with systemic sclerosis.
“In some places in the world, tocilizumab us now used in the context of [scleroderma-related interstitial lung disease], but it is certainly not indicated for that use in Australia, and the evidence for skin [benefits is] really not there,” Professor Nikpour said.
The most frequently cited evidence for rituximabin systemic sclerosis comes from the phase 2 DESIRES trial, a Japanese study that reported two courses of the monoclonal antibody treatment provided sustained improvement in the modified Rodnan skin score for up to 48 weeks. A subsequent study comparing rituximab and cyclophosphamide found the former was non-inferior to the latter at treating lung-related symptoms but had fewer adverse events.
“For this reason, the conclusion was that rituximab should be considered as a therapeutic alternative to cyclophosphamide,” Professor Nikpour explained.
An Australian led-systematic review regarding intravenous immunoglobulin use in systemic sclerosis found that while the 12 studies meeting inclusion criteria were predominantly poorer quality, IVIG reduced skin thickening, muscle and joint pain, gastrointestinal symptoms and quality of life.
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Multiple trials have explored autologous stem cell transplantation in scleroderma, and while each trial had slightly different approaches to transplantation, cyclophosphamide was involved to some extent in all of them.
While effective, stem cell transplantation was associated with a transplant-related mortality rate of 10%. But there were additional factors that must be considered before proceeding with the transplant, according to Professor Nikpour.
“Few centres have expertise in stem cell transplantation for scleroderma. There have been a number done at St Vincent’s in Sydney, and also quite a few done at the RPA in Sydney,” she said.
“But we need to be very careful in the selection of patients who have a poor prognosis, often with significant skin disease but also interstitial lung disease – and catch these patients before they have too much damage, because then they succumb to the complications of the treatment itself.”
There has been little research into the use of CAR T cell therapy for systemic sclerosis, with Professor Nikpour highlighting that high-quality clinical trials in the CAR T cell space were required before this option could be considered more seriously.
What does it all mean?
Professor Nikpour suggested that patients with early diffuse systemic sclerosis should be treated with mycophenolate in the first instance, with methotrexate also being a suitable option.
Rituximab or cyclophosphamide should be considered in patients with severe skin involvement and major organ activity, while autologous stem cell transplants were also an option in patients with severe skin disease and interstitial lung disease – although Professor Nikpour hoped the need for stem cell transplants would decrease as the therapeutic repertoire continued to expand.
There was little to no evidence supporting the use of corticosteroids in systemic sclerosis.
ARA 25 was held at the Adelaide Convention Centre from 3-6 May.
