Patterns and predictors of change in outcome measures in clinical trials in scleroderma: an individual patient meta-analysis of 629 subjects with diffuse cutaneous systemic sclerosis.
Patterns and predictors of change in outcome measures in clinical trials in scleroderma: an individual patient meta-analysis of 629 subjects with diffuse cutaneous systemic sclerosis.
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DOI：
10.1002/art.34427
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发表时间：
2012-10
影响因子：
--
通讯作者：
Seibold, J. R.
中科院分区：
文献类型：
--
作者：
Merkel, P. A.;Silliman, N. P.;Clements, P. J.;Denton, C. P.;Furst, D. E.;Mayes, M. D.;Pope, J. E.;Polisson, R. P.;Streisand, J. B.;Seibold, J. R.
To examine the range and responsiveness to change of clinical outcome measures and study the predictors of clinical response for patients with diffuse cutaneous systemic sclerosis (dcSSc) in the context of clinical trials. Data from 629 patients with dcSSc who participated in 7 multicenter clinical therapeutic trials were combined. Trials used common outcome measures: modified Rodnan skin score (MRSS), the Health Assessment Questionnaire (HAQ), Patient Global Assessment (PtGA), pulmonary function tests (FVC, DLCO), and oral aperture (OAp). The combined database included 629 patients: 82% women; mean age = 46.5 ± 11.8 years (range 15–82) with disease duration (months): mean: 19.4 ± 15.9, median = 47.0, range 1.0–144.0. Outcomes tended to improve during trials for patients with more severe disease at study entry and worsen for patients with less severe disease at entry. There were weak negative correlations between baseline values and change over 6 months for MRSS (r = −0.17; p<.0001), HAQ (r = −0.15; p= .002), and PtGA (r = −0.44; p<.0001). Baseline FVC and OAp did not predict change in 6 months. Baseline DLCO values were positively correlated with change in DLCO at 6 months (r= −0.32; p<.0001). Disease duration was mildly negatively predictive of change in MRSS at 6 months (r = −0.27; p<.0001) and substantial bidirectional variation in change in MRSS and HAQ was seen over the spectrum of disease duration. 63% of patients with “early” disease (<18 months) had a decline in MRSS and 37% had an increase in MRSS. 81% of patients with late disease (≥ 18 months) had a decline in MRSS and 19% had an increase in MRSS. 53% of patients with early disease had a decline in HAQ and 47% had an increase in HAQ. 51% of patients with late disease had a decline in HAQ and 49% had an increase in HAQ. Multivariate mixed models did not demonstrate that any baseline variables were strongly predictive of subsequent outcome. These results did not differ when comparing trials of early vs. late disease or trial “completers” vs. “non-completers”. Among patients with dcSSc enrolled in clinical trials, standard outcome measures tend to improve for patients with more severe disease at study entry and worsen for patients with less severe disease at entry. Overall, MRSS scores improve during observation periods while HAQ and lung function are mostly static, although there are wide variations in individual changes in these measures. None of these variables, including disease duration, reliably identify groups of subjects whose MRSS will predictably increase or decrease in the course of a clinical trial. These findings have important implications for clinical trial design in scleroderma.
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影响因子：
158.5
作者：
Tashkin, Donald P.;Elashoff, Robert;Metersky, Mark
通讯作者：
Metersky, Mark
影响因子：
27.4
作者：
FURST, DE;CLEMENTS, PJ;PAULUS, HE
通讯作者：
PAULUS, HE
影响因子：
--
作者：
Khanna, Dinesh;Clements, Philip J.;Seibold, James R.
通讯作者：
Seibold, James R.
影响因子：
27.4
作者：
Khanna, D.;Lovell, D. J.;Furst, D. E.
通讯作者：
Furst, D. E.
DOI：
10.1002/art.1790040106
发表时间：
1991-03-01
期刊：
Arthritis care and research : the official journal of the Arthritis Health Professions Association
影响因子：
--
作者：
Poole, J L;Steen, V D
通讯作者：
Steen, V D