Systemic sclerosis associated interstitial lung disease - individualized immunosuppressive therapy and course of lung function: results of the EUSTAR group

Abstract

Background: Interstitial lung disease in systemic sclerosis (SSc-ILD) is a major cause of SSc-related death. Imunosuppressive treatment (IS) is used in patients with SSc for various organ manifestations mainly to ameliorate progression of SSc-ILD. Data on everyday IS prescription patterns and clinical courses of lung function during and after therapy are scarce.

Methods: We analysed patients fulfilling American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) 2013 criteria for SSc-ILD and at least one report of IS. Types of IS, pulmonary function tests (PFT) and PFT courses during IS treatment were evaluated.

Results: EUSTAR contains 3778/11,496 patients with SSc-ILD (33%), with IS in 2681/3,778 (71%). Glucocorticoid (GC) monotherapy was prescribed in 30.6% patients with GC combinations plus cyclophosphamide (CYC) (11.9%), azathioprine (AZA) (9.2%), methotrexate (MTX) (8.7%), or mycophenolate mofetil (MMF) (7.3%). Intensive IS (MMF + GC, CYC or CYC + GC) was started in patients with the worst PFTs and ground glass opacifications on imaging. Patients without IS showed slightly less worsening in forced vital capacity (FVC) when starting with FVC 50-75% or >75%. GC showed negative trends when starting with FVC <50%. Regarding diffusing capacity for carbon monoxide (DLCO), negative DLCO trends were found in patients with MMF.

Conclusions: IS is broadly prescribed in SSc-ILD. Clusters of clinical and functional characteristics guide individualised treatment. Data favour distinguished decision-making, pointing to either watchful waiting and close monitoring in the early stages or start of immunosuppressive treatment in moderately impaired lung function. Advantages of specific IS are difficult to depict due to confounding by indication. Data do not support liberal use of GC in SSc-ILD.

Keywords: Follow up; Immunosuppressants; Interstitial lung disease; Lung function; Systemic sclerosis.

Fig. 1

Frequencies of immunosuppressants ever used and highest therapy combination ever used per patient. GC glucocorticoids, CYC cyclophosphamide, AZA azathioprine, MTX methotrexate, MMF mycophenolate mofetil, RTX rituximab, DPA D-penicillamine, a-TNF anti-tumour necrosis factor, IMA imatinib

Fig. 2

Monotherapies (Mono) and combinations of immunosuppressants ever used, percentages are based on the number of patients. Treatment regimens with frequencies <0.5% were omitted. GC glucocorticoids, CYC cyclophosphamide, AZA azathioprine, MTX methotrexate, MMF mycophenolate mofetil, RTX rituximab, DPA D-penicillamine, a-TNF anti-tumour necrosis factor, IMA imatinib

Fig. 3

Patients grouped according to severity of lung function combined with the respective immunosuppression (IS) and clinical parameters. never IS patients who had never taken immunosuppressant drugs, FVC forced vital capacity, DLCO diffusing capacity of the lung for carbon monoxide, SB single breath, MTX methotrexate, GC glucocorticoid, AZA azathioprine, MMF mycophenolate mofetil, CYC cyclophosphamide, PFT pulmonary function test, NYHA New York Heart Association, ACA anti-centromere antibodies, SCL70 anti-topoisomerase I antibody, CRP C-reactive protein

Fig. 4

Change in lung function over all patients distinguished in three categories of values at the start of specific therapy (or at baseline for patients who never took immunosuppressant therapy (never IS)) assessed by forced vital capacity (FVC) (a) and diffusing capacity of the lung for carbon monoxide (DLCO) (b). Effects of different therapies on change in FVC (c) and change in DLCO (d) compared to the overall trend within these three categories, adjusted for differences in sex, age, disease duration, extent of skin involvement and initial FVC or DLCO value, respectively. Additive effects indicate the same slope shifted to a higher (+) or lower (-) level; positive multiplicative effects indicate a steeper rising or less declining slope; negative multiplicative effects indicate a stronger declining slope. CYC cyclophosphamide, MMF mycophenolate mofetil, TNF tumor necrosis factor inhibitor, GC glucocorticoid, MTX methotrexate, AZA azathioprine, IS immunosuppression