Reliability and Minimal Clinically Important Differences (MCID) of Forced Vital Capacity: Post-Hoc Analyses from the Scleroderma Lung Studies (SLS-I and II)

Suzanne Kafaja¹, Philip J. Clements², Holly Wilhalme³, Daniel E. Furst⁴, Chi-hong Tseng², Kim Hyun⁵, Jonathan Goldin³, Elizabeth R. Volkmann³, Michael Roth², Donald P. Tashkin⁶ and Dinesh Khanna⁷, ¹Medicine/Rheumatology, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA, ²Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, ³University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, ⁴David Geffen School of Medicine at UCLA, Los Angeles, CA, ⁵Radiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, ⁶David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, ⁷University of Michigan, Ann Arbor, MI

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: interstitial lung disease, Lung, Lung Disease, scleroderma and systemic sclerosis

Session Information

Date: Sunday, November 13, 2016

Title: Systemic Sclerosis, Fibrosing Syndromes, and Raynaud's – Clinical Aspects and Therapeutics I

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Forced vital capacity (FVC) is used as a primary outcome measure in clinical trials of systemic sclerosis-related interstitial lung disease (SSc-ILD). Minimally Clinically Important Difference (MCID) can help interpret whether changes in outcomes are meaningful and can potentially lead to management changes. Our objective was to define inter-rater reliability and MCID of FVC using SLS-I and II data.

Methods: SLS-I and II patients (pts) were adults with SSc with disease duration of ≤7 years, FVC between 45-85 %-predicted and symptomatic ILD. In SLS-1, pts were randomized to daily oral cyclophosphamide (CYC) or matching placebo for 1 year. SLS-II pts were randomized to either mycophenolate mofetil (MMF) for 2 years or daily oral CYC for 1 year followed by 1 yr of placebo. Spirometry was assessed at 3-month intervals. We evaluated the test-retest reliability for FVC between the screening and baseline visits using intra-class correlation (ICC). An ICC of ≥0.90 was considered acceptable. MCID estimates were calculated in the pooled SLS I and II data using SF-36 health transition question: “Compared to one year ago, how would you rate your health in general now?” Pts answering “a little better” or “a little worse)” were defined as the MCID changed subgroup. We also assessed the association of MCID for improvement and worsening of FVC (absolute change in % predicted from baseline) with the patient reported outcomes (PROs): HAQ-DI, Mahler’s Transition Dyspnea Index (TDI), Saint George’s Respiratory Questionnaire (SLS II only), computer-assisted quantitation of extent of fibrosis (QLF) and of total ILD (QILD) on HRCT (12-0 month in SLS-1 and 24-0 month in SLSII). Student’s t-test compared the mean difference in outcomes between the MCID improvement/ worsening and “no change” group. P-values < 0.05 were considered statistically significant.

Results: FVC reliability was 0.90 for SLS I, 0.97 for SLS II pts and 0.93 for the combined database. The MCID estimate for improvement in FVC% predicted, after adjusting for “no change” group, was a mean change of 2.97% and -3.32% (p<0.05) for worsening. For easy interpretation, FVC% change of >3% was used as the MCID estimate for improvement and >3.3% for worsening. When FVC improved by ≥3%, trends toward significant improvement were noted for SGRQ, SF-36 MCS and QLF, while statistically significant improvement was noted for SF-36 PCS, TDI, HAQ-DI and QILD (Table 1). For negative FVC changes ≥3.3%, worsening was noted in all PROs with statistically significant worsening in SGRQ, TDI, QILD and QLF scores.

Conclusion: Reliability of FVC measurement was acceptable. Our analysis supports an absolute change of +3% for improvement and -3.3% for worsening in FVC% predicted as the MCID estimates for improvement and worsening in SSc-ILD. Estimates correspond to changes in the PROs as well as HRCT quantification of ILD. This needs to be validated in future SSc-ILD trials. Table 1. Change in PROs, HRCT-QILD and QLF based on MCID estimates of FVC %

§ Positive score denotes improvement in health; ¶ Negative score denotes improvement in health; Ref refers to reference level.

Disclosure: S. Kafaja, None; P. J. Clements, None; H. Wilhalme, None; D. E. Furst, None; C. H. Tseng, None; K. Hyun, None; J. Goldin, None; E. R. Volkmann, None; M. Roth, None; D. P. Tashkin, None; D. Khanna, Bristol-Myers Squibb, 2,Pfizer Inc, 2,Roche Pharmaceuticals, 5,Sanofi-Aventis Pharmaceutical, 5,BAYER, 5,CYTORI, 5,EMD Serono, 5,Roche Pharmaceuticals, 2,Actelion Pharmaceuticals US, 5.

To cite this abstract in AMA style:

Kafaja S, Clements PJ, Wilhalme H, Furst DE, Tseng CH, Hyun K, Goldin J, Volkmann ER, Roth M, Tashkin DP, Khanna D. Reliability and Minimal Clinically Important Differences (MCID) of Forced Vital Capacity: Post-Hoc Analyses from the Scleroderma Lung Studies (SLS-I and II) [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/reliability-and-minimal-clinically-important-differences-mcid-of-forced-vital-capacity-post-hoc-analyses-from-the-scleroderma-lung-studies-sls-i-and-ii/. Accessed .

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