Tocilizumab in Patients with Systemic Sclerosis-associated Interstitial Lung Disease A Systematic Review and Meta-Analysis

Background: The American Thoracic Society (ATS) convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). Objective: To conduct a systematic review and evaluate the literature to determine the impact of treating patients with SSc-ILD with tocilizumab on prespecified critical and important outcomes determined by the ATS guideline panel. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through June 2022 for studies using tocilizumab to treat patients with SSc-ILD. Data Extraction: Mortality and disease progression were determined to be critical outcomes of focus, with quality of life and adverse events important outcomes. Data on these outcomes were extracted and meta-analyses performed using the generic inverse variance method when possible. The Grading of Recommendations, Assessment, Development, and Evaluation Working Group method was used to assess the quality of evidence. Synthesis: The literature review resulted in five studies for inclusion. The absolute decrease from baseline in forced vital capacity (FVC) for the tocilizumab arm was 118ml, 241ml, and 129ml less than the placebo arm at 24, 48, and 96weeks, respectively, favoring tocilizumab. The mean decrease in FVC% predicted at 48weeks was 6.50% less and the risk of decrease >10% was 66% less in the tocilizumab arm, whereas patients were 1.97 times more likely to have any increase in FVC% predicted if they received tocilizumab in place of placebo. When the placebo arm was given tocilizumab from 48 to 96weeks, the mean change in absolute FVC was 54.90ml less and the mean change in FVC% predicted was 1.30% less. For diffusing capacity of the lung for carbon monoxide (DLCO)% predicted, at 48weeks there was 1.50% less change and from 48 to 96weeks there was 5.40% less change in the tocilizumab arm. Quantitative Interstitial Lung Disease scores and Quantitative Lung Fibrosis scores at 48weeks and modified Rodnan skin scores at 72weeks all favored the tocilizumab arm, as did several adverse event parameters, including serious adverse events (mean difference, -27.40; 95% confidence interval, -30.10 to -24.70). The quality of evidence was very low grade. Conclusions: Tocilizumab use in patients with SSc-ILD is associated with less disease progression and a better toxicity profile than placebo. However, the quality of evidence is very low, and large prospective studies dedicated to assessing tocilizumab specifically for SSc-ILD are needed.