Predictive Models of Clinical Improvement in Rituximab-Treated Myositis Patients Using Clinical Features, Autoantibodies, and Biomarkers


Background: Response to rituximab so far is unpredictable in patients with refractory myositis. Predictive models of clinical improvement are developed using clinical, laboratory, and gene expression/cytokine/chemokine variables in rituximab-treated refractory myositis patients. Methods: We analyzed data for 200 myositis patients (76 with adult polymyositis (PM), 76 with adult dermatomyositis (DM), and 48 with juvenile (DM)) in the rituximab in myositis trial. Clinical improvement is defined as the change from baseline to 24 weeks in Physician Global Visual Analog Scale (VAS). We analyze the association of baseline variables with improvements: demographics, myositis subtype, clinical and laboratory parameters, autoantibody status, and interferon (IFN)- regulated chemokines. Multivariable linear regression models are developed by using stepwise variable selection methods. Results: A “base” multivariable model to predict improvement with clinical and laboratory variablesonly is built with modest predictive ability (adjusted R2 = 0.21). This model includes two significant factors at baseline: Physician Global VAS and Muscle Disease Activity VAS. A “final” multivariable model to predict improvement including non-standard laboratory measures is developed and demonstrated better predictive ability (adjusted R2 = 0.32). This model includes Physician Global VAS, IFN chemokine score and IL-2 levels. The “final” model explained 11% more variability than the “base” model. Conclusions: Changes in disease activity over time following treatment with rituximab in refractory myositis can be predicted. These models can be clinically useful to optimize treatment selection in myositis.

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Olazagasti, J. , Crowson, C. , Hein, M. , de Padilla, C. , Aggarwal, R. , Oddis, C. and Reed, A. (2015) Predictive Models of Clinical Improvement in Rituximab-Treated Myositis Patients Using Clinical Features, Autoantibodies, and Biomarkers. Open Journal of Rheumatology and Autoimmune Diseases, 5, 68-80. doi: 10.4236/ojra.2015.53012.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Mastaglia, F.L., Garlepp, M.J., Phillips, B.A. and Zilko, P.J. (2003) Inflammatory Myopathies: Clinical, Diagnostic and Therapeutic Aspects. Muscle Nerve, 27, 407-425.
[2] Hoogendijk, J.E., Amato, A.A., Lecky, B.R., Choy, E.H., Lundberg, I.E., Rose, M.R., et al. (2004) Trial Design in Adult Idiopathic Inflammatory Myopathies, with the Exception of Inclusion Body Myositis. 119th ENMC International Workshop, Naarden, 10-12 October 2003, 337-345.
[3] Rider, L.G. and Miller, F.W. (1997) Classification and Treatment of the Juvenile Idiopathic Inflammatory Myopathies. Rheumatic Disease Clinics of North America, 23, 619-655.
[4] Nalotto, L., Iaccarino, L., Zen, M., Gatto, M., Borella, E., Domenighetti, M., et al. (2013) Rituximab in Refractory Idiopathic Inflammatory Myopathies and Antisynthetase Syndrome: Personal Experience and Review of the Literature. Immunologic Research, 56, 362-370.
[5] Oddis, C.V., Reed, A.M., Aggarwal, R., Rider, L.G., Ascherman, D.P., Levesque, M.C., et al. (2013) Rituximab in the Treatment of Refractory Adult and Juvenile Dermatomyositis and Adult Polymyositis: A Randomized, Placebo-Phase Trial. Arthritis and Rheumatism, 65, 314-324.
[6] Stone, J.H., Merkel, P.A., Spiera, R., Seo, P., Langford, C.A., Hoffman, G.S., et al. (2010) Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis. New England Journal of Medicine, 363, 221-232.
[7] Aggarwal, R., Reed, A.M., Ascherman, D., Barohn, R., Feldman, B., et al. (2013) Clinical and Serologic Predictors of Response in Rituximab-Treated Refractory Adult and Juvenile Dermatomyositis and Adult Polymyositis.
[8] Lundberg, I., Ulfgren, A.K., Nyberg, P., Andersson, U. and Klareskog, L. (1997) Cytokine Production in Muscle Tissue of Patients with Idiopathic Inflammatory Myopathies. Arthritis and Rheumatism, 40, 865-874.
[9] Aleksza, M., Szegedi, A., Antal-Szalmas, P., Irinyi, B., Gergely, L., Ponyi, A., et al. (2005) Altered Cytokine Expression of Peripheral Blood Lymphocytes in Polymyositis and Dermatomyositis. Annals of the Rheumatic Diseases, 64, 1485-1489.
[10] Bilgic, H., Ytterberg, S.R., Amin, S., McNallan, K.T., Wilson, J.C., Koeuth, T., et al. (2009) Interleukin-6 and Type I Interferon-Regulated Genes and Chemokines Mark Disease Activity in Dermatomyositis. Arthritis and Rheumatism, 60, 3436-3446.
[11] Szodoray, P., Alex, P., Knowlton, N., Centola, M., Dozmorov, I., Csipo, I., et al. (2010) Idiopathic Inflammatory Myo- pathies, Signified by Distinctive Peripheral Cytokines, Chemokines and the TNF Family Members B-Cell Activating Factor and a Proliferation Inducing Ligand. Rheumatology, 49, 1867-1877.
[12] de Padilla, C.L., Crowson, C.S., Hein, M.S., Khun, H., Aggarwal, R., Levesque, M.C., et al. (2013) Interferon-Regu- lated Chemokine and Innate Cytokine Scores Identify Refractory Myositis Patients That Respond Better to Rtuximab Therapy. Arthritis and Rheumatism, 65, S887-S888.
[13] Reed, A.M., Peterson, E., Bilgic, H., Ytterberg, S.R., Amin, S., Hein, M.S., et al. (2012) Changes in Novel Biomarkers of Disease Activity in Juvenile and Adult Dermatomyositis Are Sensitive Biomarkers of Disease Course. Arthritis and Rheumatism, 64, 4078-4086.
[14] Bauer, J.W., Batliwalla, F.M., Wilson, J.C., Koeuth, T., Singh, S., et al. (2008) Baseline IFN-Regulated Chemokine Levels Are Strong Predictors of Systemic Lupus Erythematosus Flare (Abstract). Arthritis Rheumatology, 58, S805.
[15] Lundberg, I., Ulfgren, A.K., Nyberg, P., Andersson, U. and Klareskog, L. (1997) Cytokine Production in Muscle Tissue of Patients with Idiopathic Inflammatory Myopathies. Arthritis Rheumatology, 40, 865-874.
[16] Chinoy, H., Salway, F., John, S., Fertig, N., Tait, B.D., Oddis, C.V., et al. (2007) Interferon-Gamma and Interleukin-4 Gene Polymorphisms in Caucasian Idiopathic Inflammatory Myopathy Patients in UK. Annals of the Rheumatic Diseases, 66, 970-973.
[17] Tournadre, A., Lenief, V. and Miossec, P. (2010) Expression of Toll-Like Receptor 3 and Toll-Like Receptor 7 in Muscle Is Characteristic of Inflammatory Myopathy and Is Differentially Regulated by Th1 and Th17 Cytokines. Arthritis and Rheumatism, 62, 2144-2151.
[18] Shen, H., Xia, L., Lu, J. and Xiao, W. (2011) Interleukin-17 and Interleukin-23 in Patients with Polymyositis and Dermatomyositis. Scandinavian Journal of Rheumatology, 40, 217-220.
[19] Tibshirani, R. (1996) Regression Shrinkage and Selection via the Lasso. Journal of the Royal Statistical Society, 58, 267-288.
[20] Lundberg, I.E., Barbasso, S., Ulfgren, A.K., Gracie, J.A. and McInnes, I.B. (2005) Expression of IL-18 in Muscle Tissue of Patients with Treatment-Resistant Idiopathic Inflammatory Myopathies. Arthritis Research Therapy, 7, 57.
[21] Kurasawa, K., Nawata, Y., Takabayashi, K., Kumano, K., Kita, Y., Takiguchi, Y., et al. (2002) Activation of Pulmonary T Cells in Corticosteroid-Resistant and -Sensitive Interstitial Pneumonitis in Dermatomyositis/Polymyositis. Cli- nical Experimental Immunology, 129, 541-548.

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