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

Arthritis Rheumatol. 2021 Jul;73(7):1301-1310. doi: 10.1002/art.41668. Epub 2021 May 25.

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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Disease Progression
  • Female
  • Fibrosis
  • Humans
  • Image Processing, Computer-Assisted
  • Lung / diagnostic imaging*
  • Lung / pathology
  • Lung / physiopathology
  • Lung Diseases, Interstitial / diagnostic imaging
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / physiopathology
  • Male
  • Middle Aged
  • Scleroderma, Systemic / drug therapy*
  • Severity of Illness Index
  • Spirometry
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Vital Capacity

Substances

  • Antibodies, Monoclonal, Humanized
  • tocilizumab

Associated data

  • ClinicalTrials.gov/NCT02453256