Evaluation & Treatment of Systemic Sclerosis-ILD in the New Decade

New Therapies
With last year’s approval of the tyrosine kinase-inhibitor nintedanib and trial results of the antifibrotic agent pirfenidone awaited, it is an exciting time for the treatment of SSc-ILD, said Richard Silver, MD, professor of medicine and pediatrics at the Medical University of South Carolina, Charleston.

“I think we’re on the cusp of a new era of treatment for this very serious complication of scleroderma,” Dr. Silver said.

The recent progress and the promise for even more treatments are a welcome evolution for a sector of the rheumatology field that until only a few years ago had cyclophosphamide, with its long-term safety concerns, as its main option.³

Mycophenolate mofetil, with the publication of the Scleroderma Lung Study II, became another option for patients, as they were able to remain on the drug longer than they could stay on cyclophosphamide, Dr. Silver said.⁴ And last year, the U.S. Food & Drug Administration approved nintedanib, which showed statistically significant improvement in slowing the rate of FVC over a year, compared to placebo, whether or not it was combined with mycophenolate mofetil.⁵

In the Scleroderma Lung Study III trial, researchers are evaluating the efficacy of the up-front combination of mycophenolate mofetil plus pirfenidone, compared to mycophenolate mofetil plus placebo.⁶ Pirfenidone is already approved for idiopathic pulmonary fibrosis.

Rituximab and tocilizumab remain possible options for SSc-ILD patients in the future, but so far the evidence is inconclusive—for instance, in the faSScinate trial of tocilizumab, the primary endpoint of change in skin score wasn’t met, but the data suggested that it tended to stabilize lung function in patients with ILD, Dr. Silver said.⁷

“We need additional trials for both of these agents,” Dr. Silver concluded.

Thomas R. Collins is a freelance writer living in South Florida.

References

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2. Wu W, Jordan S, Becker MO, et al. Prediction  of progression of interstitial lung disease in patients with systemic sclerosis: The SPAR model . Ann Rheum Dis. 2018 Sep;77(9):1326­–1332.
3. Tashkin DP, Elashoff R, Clements PJ, et al. Cyclophosphamide  versus placebo in scleroderma lung disease. N Engl J Med. 2006 Jun 22;354(25):2655–2666.
4. Tashkin DP, Roth MD, Clements PJ, et al. Mycophenolate  mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): A randomised controlled, double-blind, parallel group trial. Lancet Respir Med. 2016 Sep;4(9):708–719.
5. Distler O, Highland KB, Gahlemann M, et al. Nintedanib  for systemic sclerosis-associated interstitial lung disease. N Engl J Med. 2019 Jun 27;380(26):2518–2528.
6. University of California, Los Angeles and Genentech Inc. Scleroderma  lung study III—Combining pirfenidone with mycophenolate (SLSIII)(NCT03221257). ClinicalTrials.gov. 2017 July 18.
7. Khanna D, Denton CP, Lin CJF, et al. Safety  and efficacy of subcutaneous tocilizumab in systemic sclerosis: Results from the open-label period of a phase II randomised controlled trial (faSScinate). Ann Rheum Dis. 2018 Feb;77(2):212–220.