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Biomarker may predict response to Rituxan in patients with refractory myositis
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Interferon-regulated chemokines and a distinct cytokine response profile may be predictive of the response to Rituxan in patients with refractory myositis, according to this study.
Researchers studied data from the Rituximab in Myositis (RIM) trial of 200 participants, including 76 adult and 48 juvenile patients with refractory dermatomyositis (DM) and 76 patients with adult polymyositis (PM) who were randomized to either an early or late treatment arm. Patients had a mean disease duration of more than 5 years. Patients who responded to Rituxan (rituximab; Biogen Idec and Genentech USA Inc.) had a mean age of 41.3 years, and nonresponders had a mean age of 38.7 years.
Patients were evaluated at baseline, and at 8 weeks and 16 weeks for disease activity, blood markers of disease and serum chemokines and cytokines.
No significant differences in cytokine profiles were seen between the three patient subtypes (juvenile or adult DM, PM), and subsequent analyses were performed with the 177 patients grouped. At baseline, a correlation was seen between muscle VAS and interferon-regulated chemokine, Th1, Th2, Th17 and regulatory cytokine levels.
At 8 weeks, no significant changes were seen in cytokine or chemokine profiles from baseline. At 16 weeks, levels of Th2 and Th17 were increased and regulatory cytokine profiles were reduced. No differences were seen between disease subtypes.
Significant improvement on the physician global assessment and muscle VAS correlated at 16 weeks with higher baseline interferon-regulated chemokine levels following treatment with rituximab. Patients with higher baseline Th1 and regulatory cytokine levels showed more improvement on the muscle VAS following treatment at week 8. Patients with high Th1 levels were less likely to have improvements in the cutaneous VAS, while Th17 levels correlated negatively with the change in the pulmonary VAS at 16 weeks of treatment.
“Our data showed that the major effect of rituximab on cytokine profiles was seen 16 weeks after initiation of therapy, when B-cells were virtually absent in peripheral blood,” the researchers wrote. “Specifically, we found that the scores of serum Th2- and Th17-derived cytokines significantly increased, while the scores of regulatory cytokines (IL-10 and [tumor necrosis factor] TNF-) were decreased compared with baseline levels.” – by Shirley Pulawski
Disclosures: López De Padilla reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.
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