Current and future perspectives on management of systemic sclerosis-associated interstitial lung disease

ABSTRACT

Introduction: Systemic sclerosis (SSc) is a rare and complex connective tissue disease characterized by fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is a common complication of SSc and the leading cause of SSc-related death. No drugs are licensed for the treatment of SSc-ILD.

Areas covered: This review provides an overview of the current treatment of SSc-ILD and a perspective on investigational therapies, focusing on those studied in randomized controlled trials.

Expert opinion: There is substantial room for improvement in the treatment of SSc-ILD. Current treatment focuses on immunosuppressant therapies, particularly cyclophosphamide and mycophenolate. Hematopoietic stem cell transplantation has been shown to improve long-term outcomes, but the risk of treatment-related mortality restricts its use to select patients at specialized centers. Modifying the course of disease to improve outcomes remains the goal for new therapies. Several drugs are under investigation as potential therapies for SSc-ILD, providing hope that the limited treatment armamentarium for SSc-ILD will be expanded and improved in the near future. Expert consensus is needed on how to screen for and monitor SSc-ILD and on when to initiate and escalate therapy.

KEYWORDS:

• Autoimmune diseases
• connective tissue diseases
• rheumatic diseases
• pulmonary fibrosis
• treatment

Article highlights

• SSc is a rare and complex connective tissue disease with an unpredictable clinical course. ILD is a common manifestation of SSc and is the leading cause of death related to SSc.

• There is no established treatment algorithm for SSc-ILD, but patients with advanced or progressive disease generally receive immunosuppression. CYC and MMF are the most commonly used therapies, based on the results of randomized controlled trials.

• Hematopoietic stem cell transplantation (HSCT) has been shown to improve outcomes in patients with rapidly progressive SSc at risk of organ failure, but its use is restricted to highly selected patients treated at specialized centers due to the risk of treatment-related mortality.

• There is a high unmet need for disease-modifying treatments for SSc-ILD with an acceptable side-effect profile. Several therapies are under investigation as treatments for SSc-ILD. Nintedanib has recently been shown to slow the progression of ILD in patients with SSc-ILD, with a side-effect profile that was manageable for most patients.

• The discovery of biomarkers would facilitate the identification of patients most likely to benefit from specific therapies and so enable a precision medicine approach to treatment.

Acknowledgments

Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Melanie Stephens and Wendy Morris of FleishmanHillard Fishburn, London, UK during the preparation of this article. The authors were fully responsible for all content and editorial decisions, were involved at all stages of manuscript development, and have approved the final version.

Declaration of interest

O Distler has/had consultancy relationship and/or has received research funding from Acceleron, Actelion, AnaMar, Bayer, Biogen Idec, Blade Therapeutics, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GlaxoSmithKline, Inventiva, Italfarmaco, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Novartis, Pharmacyclics, Pfizer, Sanofi, Sinoxa and UCB in the area of potential treatments for SSc and its complications, and has a patent mir-29 for the treatment of SSc filed. ER Volkmann has consultancy relationships with Boehringer Ingelheim and has received research grants from the Rheumatology Research Foundation, Scleroderma Foundation, and EMD/Serono. AM Hoffmann-Vold has obtained research support from Boehringer Ingelheim; acted as a scientific consultant for Actelion and Boehringer Ingelheim; and received travel expenses from GlaxoSmithKline, Actelion and Boehringer Ingelheim for activities related to SSc and related diseases. TM Maher has served as a board member, consultant or has worked on clinical trials for: Apellis, Bayer, Biogen ldec, Blade, Boehringer Ingelheim, Bristol-Myers Squibb, Galecto, Galapagos, GlaxoSmithKline, Indalo, Novartis, Respivent, Roche, Trevi and UCB. TM Maher has also, via his institution, received research funding from GlaxoSmithKline and UCB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

Medical writing assistance on this paper was provided by FleishmanHillard Fishburn, London, UK, supported financially by Boehringer Ingelheim. The authors received no remuneration for their work on this paper.