• Rheumatological Autoimmune Disorders
• Lower Respiratory Infections
• Rheumatology Clinical Trials

• Rheumatological Autoimmune Disorders
• Lower Respiratory Infections
• Rheumatology
• Rheumatology Clinical Trials

Interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) frequently results in ventilatory restriction, a major cause of death in these individuals. Clinical trials in patients with SSc-related ILD have traditionally used forced vital capacity percentage (FVC%) predicted as a primary outcome measure [Hoyles RK et al. Arthritis Rheum 2006; Tashkin DP et al. N Engl J Med 2006]. Cyclophosphamide treatment of patients with SSc has been associated with improvements in clinically meaningful outcome measures other than FVC%. Elizabeth Volkmann, MD, University of California at Los Angeles, Los Angeles, California, USA, discussed the development of a composite outcome measure that included the FVC%, the computer-based quantitative lung fibrosis in the zone of maximum fibrosis (QLF-ZM) score from thoracic high-resolution computed tomography (CT) lung scans, the scleroderma modified Health Assessment Questionnaire Disability Index (HAQ-DI), and the Transition Dyspnea Index (TDI) for SSc-related ILD.

The objective of the analysis reported by Dr. Volkmann was to develop a composite outcome measure to assess treatment response in patients with SSc–ILD in clinical studies, and to create a more comprehensive measure than FVC% alone. The Scleroderma Lung Study I [SLSI; Tashkin DP et al. N Engl J Med 2006] compared oral cyclophosphamide with placebo in patients with active SSc and ILD. Of the 158 patients enrolled in the SLSI trial, 83 (41 treated with cyclophosphamide and 42 treated with placebo) had baseline and 12-month follow-up CT available and were analyzed for this presentation. There was no significant difference in baseline characteristics between the two treatment groups.

A univariate analysis that tested for treatment effects for individual outcomes, including FVC% predicted, total lung capacity predicted (TLC), QLF-ZM and whole-lung (WL) scores, quantitative interstitial lung disease (QILD)–ZM and –WL scores, HAQ-DI, TDI, and the visual analogue scale for breathing (VAS-B), was conducted to determine which variables had a significant treatment effect at 12 months. The results are shown in Table 1.

Principal component analyses were then conducted that combined those variables with significant treatment effect to assess the difference between treatment groups. The composite outcome composed of FVC% predicted, QLF, HAQ-DI, and TDI demonstrated a strong treatment effect favoring cyclophosphamide (p=0.0005). Another analysis was performed that eliminated FVC% from the composite outcome, combining TDI, HAQ-DI, and QLF-ZM; this did not change the overall treatment effect (p=0.0004). Both composite outcome measures demonstrated a more robust treatment effect than FVC% predicted alone.

Limitations to this analysis include a possible bias arising from selecting only patients with complete outcome data, although Dr. Volkmann commented that there were no differences in baseline characteristics between patients included in this analysis and all patients in SLSI. The quantitative imaging analysis used in this study is a novel approach and is currently not widely available for clinical use.

A composite outcome with structural (QLF), physiologic (FVC% and TDI), and patient-oriented (HAQ-DI) outcomes may serve as a more comprehensive measure of treatment response in SSc–ILD than the current standard of FVC%. The most robust treatment effect was observed in the composite outcome that included QLF, TDI, and HAQ-DI but did not include FVC%. Analysis of additional data sets is needed to validate this model.

• © 2014 MD Conference Express®