Tocilizumab Prevents Progression of Early Systemic Sclerosis-Associated Interstitial Lung Disease

Abstract

Objective: Tocilizumab (TCZ) has demonstrated lung function preservation in 2 randomized controlled trials in early systemic sclerosis (SSc). This effect has yet to be characterized in terms of radiographically evident quantitative lung involvement. We undertook this study to assess the impact of TCZ on lung function preservation in a post hoc analysis, stratifying treatment arms according to the degree of lung involvement.

Methods: The focuSSced trial was a phase III randomized placebo-controlled trial of TCZ in patients with SSc and progressive skin disease. Participants underwent baseline and serial spirometry along with high-resolution chest computed tomography at baseline and at week 48. Quantitative interstitial lung disease (QILD) and fibrosis scores were assessed by computer software. We classified QILD into the following categories of lung involvement: mild (>5-10%), moderate (>10-20%), and severe (>20%).

Results: Of 210 participants recruited for the trial, 136 patients (65%) had ILD. The majority of these patients (77%) had moderate-to-severe involvement (defined as >10% lung involvement). The TCZ arm demonstrated preservation of forced vital capacity percent predicted (FVC%) over 48 weeks (least squares mean change in FVC% = -0.1) compared to placebo (-6.3%). For mild, moderate, and severe QILD, the mean ± SD change in FVC% in the TCZ arm at 48 weeks were -4.1 ± 2.5% (n = 11), 0.7 ± 1.9% (n =19), and 2.1 ± 1.6% (n = 26), respectively, and in the placebo group were -10.0 ± 2.6% (n = 11), -5.7 ± 1.6% (n = 26), and -6.7 ± 2.0% (n = 16), respectively. Similar treatment-related preservation findings were seen independent of fibrosis severity.

Conclusion: TCZ in early SSc-associated ILD with progressive skin disease stabilized FVC% over 48 weeks, independent of the extent of radiographically evident QILD.

Trial registration: ClinicalTrials.gov NCT02453256.

Figure 1:

Relationship between forced vital capacity % predicted and increasing severity of baseline QILD (A ) and increasing severity of baseline QLF (B). FVC= Forced Vital Capacity, QILD= Quantitative Interstitial Lung Disease, QLF= Quantitative Lung Fibrosis

Figure 2:

ILD participants showing a mean trend over time of forced vital capacity change by treatment and quantitative ILD of the whole lung. Note: <5% is removed from this model as there were only 2 evaluable patients in the placebo group and 4 evaluable patients in the treatment group with <5% QILD over 48 weeks. FVC= Forced Vital Capacity; ILD= Interstitial Lung Disease; QILD= quantitative ILD; PBO= Placebo; TCZ= Tocilizumab

Figure 3:

ILD participants showing a mean trend over time of forced vital capacity change by treatment and quantitative lung fibrosis of the whole lung. FVC= Forced Vital Capacity; ILD= Interstitial Lung Disease; PBO= Placebo; TCZ= Tocilizumab