Elizabeth R. Volkmann
DESTIN, Fla. — Stem cell transplantation, rituximab and tocilizumab show considerable promise as treatments for interstitial lung disease in systemic sclerosis among select patients, according to findings presented at the 2018 Congress of Clinical Rheumatology.
“Three areas that have emerged as new therapies include stem cell transplant, rituximab and tocilizumab, and I’m not sure if anyone here has any experience with using these different modalities in scleroderma, but I think there is tremendous promise in all of these agents for carefully selected patients,” Elizabeth R. Volkmann, MD, MS, of the David Geffen School of Medicine at UCLA, told attendees. “Rituximab is something I typically use in patients who have not responded to mycophenolate, and I generally would choose it over cyclophosphamide because of its better safety profile.”
According to Volkmann, patients who undergo stem cell transplantation received granulocyte colony-stimulating factorto mobilize their white blood cells, as well as leukapheresis, and CD34-positive cells are then selected. The patient then receives vigorous conditioning, which typically includes cyclophosphamide and may or may not involve radiation. The CD34-positive cells are then reintroduced.
Stem cell transplantation, rituximab and tocilizumab show considerable promise as treatments for interstitial lung disease in systemic sclerosis among select patients, according to findings at the 2018 Congress of Clinical Rheumatology.
Volkmann noted a European study published in JAMA that compared stem cell therapy with cyclophosphamide, which determined that patients who received stem cell transplant demonstrated increased forced vital capacity relative to those received the conventional drug. Another study, from Sullivan and colleagues, based in the United States and published this year in the New England Journal of Medicine, found an increased rate of respiratory failure among patients treated with cyclophosphamide, compared to those who underwent stem cell transplant.
However, Volkmann cautioned that mortality is a “significant concern” with stem cell therapy, adding that the European study found a 10% mortality rate in the first year. Meanwhile, the U.S. study showed a much lower mortality rate of 3% in its first year, she said.
According to Volkmann, stem cell transplants should be considered in patients with early diffuse skin involvement who are at risk for organ failure, rather than those who have experienced low involvement for several years.
Rituximab (Rituxan, Genentech, Biogen) has also shown promise in scleroderma, demonstrating an ability to help prevent the progression of interstitial lung disease, particularly among patients who have failed in traditional therapies.
In addition, a recent phase 2 trial, comparing tocilizumab (Actemra, Genentech) to placebo, found that the interleukin-6 inhibitor curbed the predicted decline of forced vital capacity at 48 weeks, Volkmann said. She added that a phase 3 study is underway analyzing its efficacy and safety specifically in patients with interstitial lung disease in systemic sclerosis.
“Tocilizumab may have a lung signal; this is not something I use routinely yet,” Volkmann said. “However, the phase 3 study that is about to come out may have some exciting results in this area.” – by Jason Laday
Volkmann R. Interstitial lung disease in connective tissue disease: Existing and emerging therapies. Presented at: Congress of Clinical Rheumatology; May 17-20, 2018; Destin, Fla.
Disclosure: Volkmann reports consulting fees from, and advisory board membership with, Boehringer Ingelheim and Astellas Pharmaceuticals, as well as grants from Boehringer Ingelheim, Genentech Roche and Merck Sereno.