Background/Purpose: Interstitial lung disease (ILD) is a common and life-threatening organ manifestation of patients with various connective tissue diseases (CTDs), and with systemic sclerosis and anti-synthetase syndromes, in particular. B cell depletion with rituximab (RTX) is used as an off-label rescue therapy in patients with CTD-ILD progressing despite conventional immunosuppression. The purpose of this study was to systematically evaluate the outcome of such RTX rescue therapy in our center.     

Methods: For the years 2009 through 2018, a monocentric historical prospective chart review was performed on all patients with RTX treatment for interstitial lung disease and a connective tissue disease. Patients were identified by systematically screening documentation of all CTD patients treated for ILD on the Rheumatology ward and of all patients with systemic sclerosis (SSc), poly- or dermatomyositis, mixed connective tissue disease (MCTD) and Sjögren’s syndrome for patients with ILD and treated with rituximab. All patients were followed until the end of 2018, death, or loss of follow-up (n=1). ILD was confirmed by both high resolution CT imaging and pulmonary function tests (PFT) with forced vital capacity (FVC) and/or total lung capacity (TLC) and/or corrected diffusion capacity for carbon monoxide (DLCOc) < 80% of predicted value. Mean changes in %FVC (n=18), %TLC (n=20) and %DLCOc (n=17) to baseline were compared between 2-12 months before (pre-RTX) and 2-12 months after (post-RTX) the initial RTX administration. Paired t-test and Wilcoxon matched pairs signed rank test were used as appropriate.

Results: A total 21 patients were identified, of whom 15 and 2 patients met the ACR/EULAR criteria for SSc and primary Sjögren’s syndrome (SjS), respectively, and 4 patients the EULAR/ACR criteria for polymyositis (PM). Patients received RTX at a median of 13 [IQR 5-49] months after the ILD diagnosis. The median follow-up after initial RTX treatment was 2.1 (0.1-9.8) years. The baseline median FVC was 63.2% [IQR 52.9-78.2%], mean±SD TLC 72.1±17.3% and mean±SD DLCOc 38.4±18.3%. Before RTX administration, patients had received a median of 2 (1-4) other immunosuppressive therapies, including cyclophosphamide in n=14 patients. In contrast to a mean decline of -6.4±11.8% in FVC and  -3.2±8.5% in TLC in the pre-RTX interval, paired analysis of PFT data showed a mean improvement of +5.2±9% in FVC (p< 0.01) and of +2.6±8.1% in TLC (p=0.04) post-RTX. No significant improvement in DLCOc was seen (pre-RTX -2.8% [IQR -12.2-0.8%], post-RTX -1.8% [IQR -3.3-11.1%]). A total of five of the 21 RTX-treated patients died. One SSc patient died of non-small-cell-lung cancer with brain metastases, diagnosed 1.5 years after last RTX treatment. One patient with SSc developed pneumonia after the first RTX administration and died in septic shock. Two other SSc patients (one with sigmoid cancer) died of right heart failure due to pulmonary embolism 1 and 7 months after last RTX administration. The death of one patient with PM was reported due to an unspecified malignancy.

Conclusion: Our monocentric experience is in line with stabilization of lung function in CTD patients undergoing RTX rescue therapy for severe, refractory ILD, and in SSc, in particular.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rituximab-rescue-therapy-in-patients-with-systemic-sclerosis-or-other-connective-tissue-diseases-and-refractory-interstitial-lung-disease/