The Efficacy and Safety of Pirfenidone Combined With Immunosuppressant Therapy in Connective Tissue Disease-Associated Interstitial Lung Disease: A 24-Week Prospective Controlled Cohort Study

Abstract

ObjectiveInterstitial lung disease (ILD) is a common manifestation of connective tissue disease (CTD) that manifests as several subtypes with significant differences in prognosis. It is necessary to evaluate the efficacy and safety of pirfenidone (PFD) combined with immunosuppressant (IS) in the treatment of CTD-ILD.MethodsA total of 111 patients with CTD-ILD were enrolled, including those with systemic sclerosis (SSc), inflammatory myopathy (IIM), rheumatoid arthritis (RA), and other CTDs (such as systemic lupus erythematosus, primary Sjogren's syndrome, and undifferentiated CTD). After evaluation of the high-resolution computed tomography (HRCT), pulmonary function (PF), and basic disease activity, patients either were or were not prescribed PFD and were followed up regularly for 24 weeks.ResultsAfter 24 weeks of treatment, predicted forced vital capacity (FVC%) in the SSc-PFD group had improved by 6.60%, whereas this value was 0.55% in patients with SSc-no-PFD. The elevation in FVC% was also significant in IIM-PFD over the IIM-no-PFD controls (7.50 vs. 1.00%). The predicted diffusing capacity for carbon monoxide (DLCo%) of RA-PFD was enhanced by 7.40%, whereas that of RA-no-PFD decreased by 5.50%. When performing a subtype analysis of HRCT images, the change in FVC% among patients with SSc with a tendency toward usual interstitial pneumonia (UIP) was higher in those given PFD (SSc-PFD-UIP) than the no-PFD group (8.05 vs. −3.20%). However, in IIM patients with a non-UIP tendency, PFD displayed better therapeutic effects than the control (10.50 vs. 1.00%). DLCo% improved significantly in patients with the PFD-treated RA-non-UIP subtype compared with the patients with no-PFD (10.40 vs. −4.45%). Dichotomizing the patients around a baseline FVC% or DLCo% value of 70%, the PFD arm had a more improved FVC% than the no-PFD arm within the high-baseline-FVC% subgroups of patients with SSc and IIM (6.60 vs. 0.10%, 6.30 vs. 1.10%). In patients with RA-PFD, DLCo% showed a significant increase in the subgroup with low baseline DLCo% compared to that in patients with RA-no-PFD (7.40 vs. −6.60%).ConclusionThe response of PF to PFD varied between CTD-ILD subsets. Patients with SSc and IIM showed obvious improvements in FVC%, especially patients with SSc-UIP and IIM-non-UIP. In RA, the subsets of patients with non-UIP and a lower baseline DLCo% most benefited from PFD.

Efficacy of Pirfenidone and Nintedanib in Interstitial Lung Diseases Other than Idiopathic Pulmonary Fibrosis: A Systematic Review

“…The majority of the studies were rejected because they either included IPF patients (n = 71), had multiple publications for the same study (n = 8), had study designs, comments, or case series (n = 5), or were pharmacokinetic or safety profile studies (n = 4). A final pool of 10 studies was included in the systematic review, with a total of 1990 patients enrolled (Table 1) [9,10,[13][14][15][16][17][18][19][20]. Eight studies reported data on patients treated with pirfenidone, while two studies reported data on patients treated with nintedanib.…”

“…Eight studies reported data on patients treated with pirfenidone, while two studies reported data on patients treated with nintedanib. Selected papers were published from 2002 to 2022, with a high frequency in the period 2019-2022 (8/10, 80%) [9,10,[13][14][15][16][17][18]. The majority had a randomized, double-blind, placebo-controlled design (8/10, 80%) [9,10,13,[15][16][17]19,20].…”

Dysregulated B cell function and disease pathogenesis in systemic sclerosis

“…Both the SENSCIS trial and the ongoing Scleroderma lung study III are assessing the effect of combination therapy with oral anti-fibrotics and MMF. It is therefore likely that future treatment approaches will include a combination of immune modulatory and anti-fibrotic therapy with B cells appearing to play a crucial role in the interaction of these pathways ( 164 , 165 ).…”

Recent advances in the treatment of systemic sclerosis associated interstitial lung disease

“…Aside from using immunomodulatory therapies on their own, future directions for combined antifibrotic and immunomodulatory therapies in CTD-ILD will hopefully come from the Scleroderma Lung Study-3 (SLS-3) trial, which will compare the effect of the combination of pirfenidone and mycophenolate with mycophenolate and placebo on FVC at 18 months 55 . There is already promising data for pirfenidone from a recent randomized control trial conducted by Wang et al who demonstrated that patients with SSc-ILD who receive both pirfenidone and immunosuppressants have a statistically significant improvement in FVC at 24 weeks compared to patients receiving only immunosuppressants (56). Furthermore, the LOTUSS study in which patients with SSc-ILD received pirfenidone for either 2 weeks or for 4 weeks demonstrated that pirfenidone has an acceptable side effect and safety profile, so pirfenidone is a promising antifibrotic therapy to continue exploring for patients with CTD-ILD (81).…”