Key takeaways:
- Mycophenolate mofetil outperformed methotrexate, steroids and other immunosuppressives in diffuse cutaneous SSc skin and lung outcomes.
- Outcomes were particularly good with a disease duration of 2 years or shorter.
A comparison of immunosuppressive therapies for the treatment of diffuse cutaneous systemic sclerosis found “robust” support for mycophenolate mofetil as the first-line standard of care, according to data published in ACR Open Rheumatology.
The drug was superior to methotrexate, steroids and other immunosuppressive therapies for skin and lung outcomes, and was particularly advantageous for patients with early disease or interstitial lung disease.
“There’s very little known about what drugs are effective in scleroderma,” Robert F. Spiera, MD, director of the scleroderma, vasculitis and myositis center at Hospital for Special Surgery, told Healio. “We have some drugs which have been shown to be helpful for specific disease manifestations, most notably interstitial lung disease, but there hasn’t been a recognized global disease-modifying drug recognized as being effective in systemic sclerosis.”
To address this knowledge gap, Spiera and colleagues conducted a post hoc analysis of RESOLVE-1, a trial that evaluated lenabasum (Corbus Pharmaceuticals), a cannabinoid-2 receptor agonist, for the treatment of diffuse cutaneous SSc. The study was the largest prospective trial to date in this form of the disease, according to Spiera.
RESOLVE-1 allowed patients to use background immunosuppressive treatment at the investigators’ discretion. Because the study ultimately found no significant benefit from lenabasum vs. placebo, its data set “provides a unique opportunity” to compare the outcomes of the background therapies, Spiera and colleagues wrote.
“Different clinicians had different patients on different background therapies,” Spiera said. The treatment groups defined in the post hoc analysis included patients receiving:
- no immunosuppressive therapy;
- mycophenolate mofetil with or without other immunosuppressive therapy;
- methotrexate with or without other immunosuppressive therapy, excluding mycophenolate mofetil;
- steroids with or without other immunosuppressive therapy, excluding mycophenolate mofetil; and
- other immunosuppressive therapies, including azathioprine, hydroxychloroquine, gamma globulin, abatacept (Orencia, Bristol Myers Squibb), tocilizumab (Actemra, Genentech), cyclosporin, cyclophosphamide and rituximab (Rituxan, Genentech).
According to the researchers, the greatest impact on skin disease, assessed via modified Rodnan skin score, was observed among patients with early disease treated with mycophenolate mofetil. Among patients with a disease duration of 2 years or shorter, those treated with mycophenolate mofetil demonstrated a mean –10.8-point change at week 52, while those not given any immunosuppressive therapy had a mean –4.8-point change.
For patients using methotrexate, steroids or “other” immunosuppressive therapies, skin score improvements landed between those in the mycophenolate mofetil and “no immunosuppressive therapy” groups.
Regarding lung function, forced vital capacity results were also “quite different” between mycophenolate mofetil and no immunosuppressive treatment, the researchers wrote. Among patients with a disease duration of 2 years or less, forced vital capacity remained stable over 52 weeks with mycophenolate mofetil. On the other hand, losses were numerically greatest among those who received no immunosuppressive therapy, leading to an approximate 160 mL between-group difference in mean forced vital capacity change at week 52.
Again, forced vital capacity changes in other treatment groups landed between those of patients who received mycophenolate mofetil and no immunosuppressive therapy.
“You seem to be getting a lot of bang for your buck with earlier starts in the disease course” in terms of lung outcomes, Spiera said.
For both skin and lungs, mycophenolate mofetil demonstrated the greatest difference in effect among patients with anti-topoisomerase 1 autoantibodies.
Skin scores improved particularly quickly among patients with anti-RNA polymerase III autoantibodies who received either mycophenolate mofetil or no immunosuppressive therapy, decreasing by six to seven points within 6 months, the researchers wrote. However, improvements progressed more slowly from there through month 12, especially for those not given immunosuppression.
“Treatment with mycophenolate was associated with better outcomes than treatment with any other regimen that did not include mycophenolate,” Spiera said. “It was the first time that this has been shown, I think, in such a robust way.”
The analysis is valuable due to its use of high-quality “trial-level data,” which otherwise would be difficult to obtain through a randomized controlled trial of mycophenolate mofetil due to ethical concerns, Spiera added.
“This was, I thought, pretty compelling evidence, and I feel it has helped contribute to changing the treatment paradigm of patients with systemic sclerosis,” he said.
