Background/Purpose: Recent Phase II (faSScinate) and Phase III (focuSSced) clinical trials of tocilizumab versus placebo in early dcSSc highlighted the potential impact of tocilizumab on lung function with preservation of forced vital capacity (FVC) in those treated with tocilizumab, despite only a trend of benefit for skin fibrosis. Tocilizumab is approved for SSc patients with inflammatory arthritis overlap and has been used in this context at our centre. We report here our experience of tocilizumab in SSc and the impact on lung function.

Methods: In our retrospective study, all SSc patients attending our centre who had ever been on tocilizumab were identified. Most of these patients had overlap inflammatory arthritis. Patients who had participated in the faSScinate trial were excluded, whilst those receiving tocilizumab on a compassionate basis following the phase 3 focuSSced trial were included. Statistical analysis was carried out using the Mann-Whitney-U test.

Results: Of the 32 patients identified, 68.8% (n = 22) were classified as diffuse SSc and 75% (n = 24) patients were female. The most common autoantibodies were ATA (anti-topoisomerase antibody) (34.3%) and ARA (anti-RNA polymerase-III antibody) (18.8%). 46.9% (n = 17) patients had known interstitial lung disease. 6 patients received tocilizumab on a compassionate basis following completion of the open label phase of the focuSSced clinical trial, the remainder had overlap inflammatory arthritis. Mean age of disease onset was 38.6 years, and the median disease duration to tocilizumab initiation was 7.9 years. 11 patients discontinued tocilizumab: 6 due to cessation of the compassionate use access, 2 due to side effects, 3 due to lack of benefit.

75% (n = 24) patients had serial lung function data to compare FVC and DLCO before and after initiation of treatment. Baseline FVC prior to tocilizumab was 3.09L (sd = 0.98) or 91% predicted (sd = 19.7). Baseline DLCO prior to tocilizumab was 5.55ml/min/mmHg (sd = 2.21) or 61.1% predicted (sd = 17). Median duration on tocilizumab was 7 months (IQR =9.5). To standardise results, the yearly change rate in FVC and DLCO was calculated. Median change in % predicted FVC was -1.5% (IQR=10.7) and median change in % predicted DLCO was -0.5% (IQR=6.1). Subgroup analysis revealed a significant difference between autoantibody groups and change in FVC while on tocilizumab. It was notable that there was an increase in median change in FVC in patients with ATA antibody (3.27%, IQR=13.55) whereas there was a decrease in median change in FVC in all other autoantibody groups (-4.7%, IQR=11.1, p = 0.0019). There was a near significant difference in change in DLCO between these antibodies at 12 months (-2.6%, IQR = 4.7, p = 0.056) in favour of improvement in ATA subgroup.

Conclusion: Our findings support potential benefit for lung function in SSc patients on tocilizumab compared to placebo particularly in those with the ATA, and this is consistent with previous trial results. Presence of ATA confers a higher risk of extensive lung fibrosis in SSc, regardless of extent of skin involvement, and so early identification of these cases and use of tocilizumab may prevent development of clinically meaningful lung fibrosis and improve long-term outcome.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/tocilizumab-shows-potential-in-preserving-lung-function-in-systemic-sclerosis-with-positive-anti-topoisomerase-1-scl-70-a-single-centre-cohort-study/