Effects of cyclophosphamide and rituximab in patients with connective tissue diseases with severe interstitial lung disease

Abstract

ObjectiveWe aimed to analyse the effects of real-life immunomodulatory therapy with cyclophosphamide and rituximab for interstitial lung disease (ILD) in patients with systemic sclerosis (SSc-ILD), anti-synthetase syndrome (ASS-ILD), or Sjögren's syndrome (SjS-ILD), in a single academic centre. Methods All inpatients with connective tissue diseases treated with intravenous bolus cyclophosphamide or rituximab were identified from the Medical Centre records. Information on patient characteristics, chest CT results, pulmonary functiontests, therapies, and severe adverse events, were extracted from inpatient and outpatient records. ResultsIntravenous cyclophosphamide bolus therapy was used in 27 patients with SSc. Cyclophosphamide improved forced vital capacity (FVC) by more than 10% in 4 patients and stabilised it at -0.4% to +3.25% in 8. Rituximab constituted a rescue therapy in 14 SSc patients, and was used for treating 4 patients with ASS-ILD, 2 patients with SjS-ILD and one additional SSc-ILD patient. Rituximab led to FVC improvements of at least 5% in 8 patients and to stabilisation in another 6. 6 patients under cyclophosphamide and 8 patients under rituximab experienced severe adverse events. 8 of the 34 patients died, half of them from causes potentially related to therapy. ConclusionIn this subset of severely sick patients with connective tissue diseases, cyclophosphamide and/or rituximab led to improvement in 12 patients, and stabilisation was seen in 14. Despite the new options with nintedanib, immunomodulation remains a relevant therapeutic modality for ILD associated with connective tissue disease.

Long-term evaluation of pulmonary function and survival of patients with interstitial pneumonia with autoimmune features

“…Huapaya et al (38) showed no difference in FVC% and DLCO% between patients treated and those not treated with mycophenolate mofetil (MMF). Benad et al (39) showed that cyclophosphamide and/or rituximab led to improvement of FVC% in 12 patients, and stabilisation in 14 out of 27 severely sick patients with ILD associated with systemic sclerosis, antisynthetase syndrome and Sjögren's syndrome. In our survival and mixed model analysis of FVC% and DLCO%, there was no difference over time, even after adjusting the models for the prior use of treatment.…”

Systemic sclerosis: one year in review 2023

“…Alongside data on the proven efficacy of "classic" immunosuppressants such as cyclophosphamide and rituximab, which consolidate their use in the treatment of SSc-ILD (48), in the last year the focus has been mainly on tocilizumab (TCZ). After two randomised controlled trials (RCTs), namely faSScinate and focuSSced, showed a trend in improvement of skin fibrosis and in prevention of lung function worsening in a highly enriched population of patients with early, inflammatory, diffuse and progressive SSc, the most suitable field of application for this anti-IL-6 receptor antibody has been investigated.…”

Perspective Chapter: Pulmonary System and Sjogren’s Syndrome

“…Among the therapy, azathioprine [79,216] and mycophenolate mofetil [217,218] have been reported. Biologic therapy, such as rituximab, a humanized monoclonal antibody targeting mature B-cells (CD20+), was tried in case series and reports with promising results [219], in reparatory cases [220] and also associated with lymphoproliferative diseases [221][222][223], in special cases, such as in shrinking lung syndrome associated with SS [224]. Off-the-label cases reported other biologicals, such as tocilizumab [225] and abatacept [226].…”