Treating Systemic Sclerosis Interstitial Lung Disease: Evidence on Best Uses of Newly Approved Drugs

Kimberly Showalter, MD, MS

Interstitial lung disease (ILD) is a frequent complication of systemic sclerosis (SSc) as well as a leading cause of death in this population. Nintedanib (Ofev) and tocilizumab (Actemra) are both recently approved treatments for SSc-ILD; these novel therapies are the focus of this article. Nintedanib is also approved for progressive fibrosing ILD.

Jessica K. Gordon, MD, MS

Clear treatment guidelines, including when to initiate immunosuppressive therapy for SSc-ILD, have not yet been delineated. Scleroderma Lung Study (SLS)-Iestablished that cyclophosphamide is modestly superior to placebo in the treatment of SSc-ILD over 12 months. However, the benefit was not clearly durable when studied without maintenance treatment. SLS-II established that mycophenolate mofetil (MMF) has efficacy similar to cyclophosphamide but with a favorable side-effect profile. At this point, MMF is frequently considered as an initial treatment for ILD in individuals with SSc; cyclophosphamide is considered in some cases. Azathioprine is considered when these medications are contraindicated or not tolerated. Pirfenidone (Esbriet) is an antifibrotic medication that is currently under investigation in SLS-III. Emerging data have also shown a possible benefit of rituximab for SSc-ILD, including a systematic review and meta-analysis and recent randomized, controlled trialFurther data are needed to inform optimal antifibrotic and immunomodulatory strategies for patients with connective tissue disease–associated ILD.