Clinical and Molecular Findings After Autologous Stem Cell Transplantation or Cyclophosphamide for Scleroderma: Handling Missing Longitudinal Data

Objective Among individuals with systemic sclerosis (SSc) randomized to cyclophosphamide (CYC) (n = 34) or hematopoietic stem cell transplantation (HSCT) (n = 33), we examined longitudinal trends of clinical, pulmonary function, and quality of life measures while accounting for the influence of earl...

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Published in:Arthritis care & research (2010) 2023-02, Vol.75 (2), p.307-316
Main Authors: Keyes‐Elstein, Lynette, Pinckney, Ashley, Goldmuntz, Ellen, Welch, Beverly, Franks, Jennifer M., Martyanov, Viktor, Wood, Tammara A., Crofford, Leslie, Mayes, Maureen, McSweeney, Peter, Nash, Richard, Georges, George, Csuka, M. E., Simms, Robert, Furst, Daniel, Khanna, Dinesh, Clair, E. William St, Whitfield, Michael L., Sullivan, Keith M.
Format: Article
Language:English
Subjects:
Autografts
Carbon monoxide
Cyclophosphamide
Cyclophosphamide - therapeutic use
Gene expression
Hematopoietic Stem Cell Transplantation - adverse effects
Hematopoietic Stem Cell Transplantation - methods
Hematopoietic stem cells
Humans
Immunosuppressive Agents - therapeutic use
Inflammation
Mathematical models
Quality of Life
Regression analysis
Respiratory function
Scleroderma
Scleroderma, Localized - drug therapy
Scleroderma, Systemic - diagnosis
Scleroderma, Systemic - drug therapy
Statistical analysis
Stem cell transplantation
Systemic sclerosis
Transplantation, Autologous
Treatment Outcome
Trends
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Summary:Objective Among individuals with systemic sclerosis (SSc) randomized to cyclophosphamide (CYC) (n = 34) or hematopoietic stem cell transplantation (HSCT) (n = 33), we examined longitudinal trends of clinical, pulmonary function, and quality of life measures while accounting for the influence of early failures on treatment comparisons. Methods Assuming that data were missing at random, mixed‐effects regression models were used to estimate longitudinal trends for clinical measures when comparing treatment groups. Results were compared to observed means and to longitudinal trends estimated from shared parameter models, assuming that data were missing not at random. Longitudinal trends for SSc intrinsic molecular subsets defined by baseline gene expression signatures (normal‐like, inflammatory, and fibroproliferative signatures) were also studied. Results Available observed means for pulmonary function tests appeared to improve over time in both arms. However, after accounting for participant loss, forced vital capacity in HSCT recipients increased by 0.77 percentage points/year but worsened by –3.70/year for CYC (P = 0.004). Similar results were found for diffusing capacity for carbon monoxide and quality of life indicators. Results for both analytic models were consistent. HSCT recipients in the inflammatory (n = 20) and fibroproliferative (n = 20) subsets had superior long‐term trends compared to CYC for pulmonary and quality of life measures. HSCT was also superior for modified Rodnan skin thickness scores in the fibroproliferative subset. For the normal‐like subset (n = 22), superiority of HSCT was less apparent. Conclusion Longitudinal trends estimated from 2 statistical models affirm the efficacy of HSCT over CYC in severe SSc. Failure to account for early loss of participants may distort estimated clinical trends over the long term.
ISSN:2151-464X
2151-4658
2151-4658
DOI:10.1002/acr.24785