AB0619 Connective tissue disease-associated interstitial lung disease treated with cyclophosphamide or rituximab: a unicentre, open-label and comparative study

Background

To date, rheumatologists do not have curative treatments for connective tissue disease-associated interstitial lung disease (CTD-ILD) (1), therefore an stabilization of the disease is considered as a therapeutic success. One of the most frequent drugs used for achieving this goal is Cyclophosphamide (CYC); however, in the last years there has been an increasing interest in the use of Rituximab (RTX) as a treatment for CTD-ILD.

Objectives

To compare long-term effectiveness of CYC vs. RTX as a treatment in patients with CTD-ILD.

Methods

Unicentre and retrospective study in which it was analyzed clinical and image data of 26 CTD-ILD patients treated with CYC or RTX between June 2004 and December 2016. Previously, we checked that baseline characteristics and baseline levels of Pulmonary Function Tests (PFTs) in both groups were similar by using Fisher and T-student tests. The primary outcome of the study was the stabilization of PFTs or HRTC (High Resolution Tomography Computed Tomography) considering as relapse: a) a deterioration ≥10% in FVC (Forced Vital Capacity), or b) a decrement ≥15% in DLCO (diffusing capacity of carbon monoxide), or c) a worsening in HRCT. The prognostic effect of each treatment on stabilization was evaluated using the Kaplan-Meier method and Long Rank test. Subsequently, values of FEV1 (forced expiratory volume in one second), FVC, DLCO and DLCO/VA were compared 12 months after the beginning of the treatment with their corresponding baseline levels in both groups, using paired T-test. Finally, direct comparison between the CYC and the RTX groups was performed at the 12-months time point using T-test.

Results

The study includes 20 women and 6 men with an average age of 58.9±14.2 years. 14 patients had a diagnosis of Systemic Sclerosis whereas 12 had other types of CTD. From the 26 patients, 15 received CYC and 11 RTX, according to the physician9s decision. Both groups presented similar baseline characteristics and levels in PFTs. The Kaplan-Meier method showed that the treatment had an influence on the stabilization of CTD-ILD, although long Rank test was non-significative. The average of months without relapse in CYC and RTX group was 59.79±9.50 and 79.27±7.81 respectively. Patients in the CYC group did not present any changes in FEV1, FVC, DLCO and DLCO/VA levels during the first year of treatment. In contrast, patients in RTX group showed an increase of all PFTs levels during the first year of monitoring, although these differences were non-significatives. A direct comparison between both treatment groups after 12 months showed lower levels of all PFTs in CYC vs RTX, been DLCO/VA (67.30±10.69 and 86.25±4.59, respectively) statistically significative.

Conclusions

This study suggests, in patients with ILD-CTD, that CYC treatment stabilizes the lung function, whereas RTX shows a tendency to improve it. Also, patients with RTX treatment shows a larger mean time of stabilization than CYC group. However, large scale randomized controlled trials are needed to confirm these results.

References

Fischer A, du Bois A. Interstitial lung disease in connective tissue disorders. Lancet 2012;380:689–98.

Disclosure of Interest

None declared