Managing Systemic Sclerosis-Related Interstitial Lung Disease in the Modern Treatment Era

Abstract

REVIEW describes an evidence-based approach for managing SSc-ILD in the current treatment era. This review also highlights emerging SSc-ILD treatment strategies and discusses unresolved issues regarding treatment initiation, treatment response monitoring, and the use and duration of maintenance therapy in SSc-ILD. Current treatment approaches Cyclophosphamide The findings of both RCTs (5, 6) and uncontrolled studies (7, 8) have provided evidence that treatment with CYC is effective for stabilizing SSc-ILD progression. The recently updated EULAR recommendations for the treatment of SSc suggest using CYC as first-line therapy in SSc-ILD (9). In SLS I (n = 158) (6), patients receiving daily oral CYC administered over 12 months experienced an improvement in lung function (forced vital capacity [FVC]%-predicted) relative to patients receiving placebo who had the same extent of radiographic fibrosis, especially when the extent of fibrosis exceeded 50% in the zone of maximal involvement, which roughly corresponded to 25% in the whole lung (10). Moreover, treatment with CYC was associated with an improvement in the extent of both visually assessed and computer-assisted quantitative lung fibrosis compared with placebo (10, 11). A smaller RCT (n = 45) (5) found that 6 months of intravenous (IV) CYC followed by

Treatment modalities and drug survival in a systemic sclerosis real-life patient cohort

“…This results can be explained, as MTX, based on randomized clinical trials (RCTs) and observational studies [12][13][14], is efficient in skin sclerosis and arthritis, the two most frequent manifestations of SSc and currently MTX is included in the EULAR recommendations for skin disease [15], representing the first choice of treatment of most physicians for mild to moderate cases of SSc. On the other hand, CYC and MMF which are considered more potent are recommended for the severe complications of SSc, like progressive PF or cardiac involvement [15][16][17][18][19].…”

Major lung complications of systemic sclerosis

“…In addition to immunosuppression for patients with extensive fibrosis or those predicted to be at risk of lung disease progression, other general measures for the treatment of SSc-associated lung fibrosis include vigorous management of gastro-oesophageal reflux [142]. Combinations of antacids (acid suppressive agents) and prokinetics, as well as simple lifestyle measures, are used in the treatment of gastro-oesophageal reflux.…”

“…Another important treatment approach in SSc-associated lung fibrosis is the management of infection. Prophylactic antibiotics should be considered for preventing community acquired infection in patients reporting frequent lower respiratory tract infections, and for preventing opportunistic infections such as pneumocystis in patients receiving long-term intensive immunosuppression [142].…”

“…The early studies that led to the licensing of various PAH therapies, including bosentan and sildenafil, focused on short term gains in exercise capacity; in these studies, the response of patients with SSc-associated PAH or CTD-associated PAH was often less efficacious than patients with other forms of PAH, although most treatments seem to result in meaningful benefit in the majority of patients with SSc-associated PAH [146,147,148,149]. However, evidence in clinical practice suggests that these therapies have long-term benefits in SSc-associated PAH [142], which is supported by key eventdriven clinical trials published in the past 3 years [150,151,152]: the SERAPHIN trial (which tested the oral endothelin receptor antagonist macitentan), the GRIPHON trial (which tested the prostcyclinreceptor agonist selexipag) and the AMBITION trial (which tested a combination therapy of ambrisentan (endothelin receptor antagonist) and tadalafil (a PDE5 inhibitor)).…”

18F-fluorodeoxyglucose positron-emission tomography/CT and lung involvement in systemic sclerosis

“…Systemic sclerosis (SSc) early lung involvement (interstitial lung disease (ILD)) is characterised by ground glass opacities (GGO) at high-resolution CT (HRCT) 1 2. The literature provides conflicting interpretations of GGO’s clinical significance,3–5 and whether it represents inflammation or early fibrotic changes is a dilemma.…”