Treatment of Scleroderma-Associated Interstitial Lung Disease

First-Line Treatment Approach

The American College of Rheumatology conditionally recommends mycophenolate, azathioprine, rituximab, or cyclophosphamide as first-line immunosuppressive options for SSc-ILD, with tocilizumab or nintedanib as additional first-line choices 1
The American College of Rheumatology conditionally recommends against the use of glucocorticoids as first-line treatment in SSc-ILD, due to negative trends in forced vital capacity (FVC) with glucocorticoid use 1
The American College of Rheumatology conditionally recommends mycophenolate mofetil as a preferred agent with comparable efficacy to cyclophosphamide but better tolerability 1
The American College of Rheumatology conditionally recommends cyclophosphamide as a first-line option, particularly for induction therapy in patients at risk for progression 1
The American College of Rheumatology conditionally recommends rituximab as a first-line option for SSc-ILD 1
The American College of Rheumatology conditionally recommends azathioprine as a first-line treatment for SSc-ILD 1
The American College of Rheumatology conditionally recommends tocilizumab as a first-line treatment option for SSc-ILD (and MCTD-ILD) 1
The American College of Rheumatology conditionally recommends nintedanib as a first-line option for SSc-ILD, though it should not be combined upfront with mycophenolate 1

The American College of Rheumatology recommends against the use of leflunomide, TNF inhibitors, abatacept, pirfenidone, JAK inhibitors, and IVIG or plasma exchange as first-line therapy in SSc-ILD 1, 2

For patients with SSc-ILD progression despite first-line treatment, the guidelines recommend continuing to strongly avoid long-term glucocorticoids, and switching to or adding mycophenolate, rituximab, cyclophosphamide, or nintedanib as treatment options 2
The American College of Rheumatology conditionally recommends referral for stem cell transplantation and/or lung transplantation for SSc-ILD progression despite first-line treatment 2

For patients with rapidly progressive SSc-ILD, the guidelines conditionally recommend pulse intravenous methylprednisolone as first-line treatment, and combination therapy options including rituximab, cyclophosphamide, IVIG, mycophenolate, calcineurin inhibitors, or JAK inhibitors 2

A practical algorithmic approach for SSc-ILD treatment includes starting mycophenolate mofetil or cyclophosphamide, and switching to or adding alternative agents if progression occurs 1, 2

The American College of Rheumatology recommends against combining antifibrotics with mycophenolate upfront, unless there is evidence of ILD progression on mycophenolate alone 1
The certainty of evidence is low to very low for all treatment recommendations, reflecting the challenges in conducting high-quality trials in this population 1