Treatment of Systemic Sclerosis-associated Interstitial Lung Disease: Evidence-based Recommendations. An Official American Thoracic Society Clinical Practice Guideline

Abstract

Background: Interstitial lung disease (ILD) is a significant cause of morbidity and mortality in patients with systemic sclerosis (SSc). To date, clinical practice guidelines regarding treatment for patients with SSc-ILD are primarily consensus based. Methods: An international expert guideline committee composed of 24 individuals with expertise in rheumatology, SSc, pulmonology, ILD, or methodology, and with personal experience with SSc-ILD, discussed systematic reviews of the published evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Predetermined conflict-of-interest management strategies were applied, and recommendations were made for or against specific treatment interventions exclusively by the nonconflicted panelists. The confidence in effect estimates, importance of outcomes studied, balance of desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications for health equity were all considered in making the recommendations. This was in accordance with the American Thoracic Society guideline development process, which is in compliance with the Institute of Medicine standards for trustworthy guidelines. Results: For treatment of patients with SSc-ILD, the committee: 1) recommends the use of mycophenolate; 2) recommends further research into the safety and efficacy of (a) pirfenidone and (b) the combination of pirfenidone plus mycophenolate; and 3) suggests the use of (a) cyclophosphamide, (b) rituximab, (c) tocilizumab, (d) nintedanib, and (e) the combination of nintedanib plus mycophenolate. Conclusions: The recommendations herein provide an evidence-based clinical practice guideline for the treatment of patients with SSc-ILD and are intended to serve as the basis for informed and shared decision making by clinicians and patients.

Keywords: SSc-ILD; interstitial lung disease; systemic sclerosis.

Figure 1.

Summary of treatment recommendations for patients with systemic sclerosis–associated interstitial lung disease (SSc-ILD). The SSc-ILD Guideline Committee:

1. 1)

   Recommends the use of mycophenolate to treat patients with SSc-ILD (18 votes: 14 strong recommendation for use, 4 conditional recommendations for use).

2. 2)

   Suggests the use of cyclophosphamide to treat patients with SSc-ILD (17 votes: 5 strong recommendation for use, 12 conditional recommendations for use).

3. 3)

   Suggests the use of rituximab to treat patients with SSc-ILD (18 votes: 1 strong recommendation for use, 16 conditional recommendation for use, 1 abstention due to insufficient expertise).

4. 4)

   Suggests the use of tocilizumab to treat patients with SSc-ILD (16 votes: 16 conditional recommendation for use).

5. 5)

   Suggests the use of nintedanib to treat patients with SSc-ILD (14 votes: 1 strong recommendation for use, 11 conditional recommendation for use, 1 conditional recommendation against use, 1 abstention due to insufficient expertise).

6. 6)

   Suggests the use of nintedanib plus mycophenolate to treat patients with SSc-ILD (14 votes: 1 strong recommendation for use, 11 conditional recommendation for use, 2 abstentions due to insufficient expertise).

7. 7)

   Recommends further research into the efficacy, effectiveness, and safety of pirfenidone to treat patients with SSc-ILD (13 votes: 2 conditional recommendation against use, 11 abstentions due to insufficient evidence).

8. 8)

   Recommends further research into the efficacy, effectiveness, and safety of pirfenidone plus mycophenolate to treat patients with SSc-ILD (13 votes: 1 conditional recommendation against use, 12 abstentions due to insufficient evidence).

The above recommendations were not assessed as a stepwise algorithm. Clinicians are encouraged to use these recommendations in conjunction with shared decision-making with patients, incorporating side effects and personal values and preferences before administration.