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In vitro glucocorticoid sensitivity associated with glucocorticoid therapy results
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Improved in vivo Disease Activity Scores for patients with rheumatoid arthritis who underwent 2 weeks of glucocorticoid therapy were positively correlated with the quantity and affinity of glucocorticoid receptors, according to study results.
Thirty-six patients with recent-onset rheumatoid arthritis (RA) derived from the treatment in the Rotterdam early arthritis cohort (tREACH) and 35 patients with established RA (FLARE) were evaluated in a prospective study that investigated an association between in vivo and in vitro glucocorticoid (GC) sensitivity. Inclusion criteria for the tREACH group included RA observed in at least one joint and complaints of pain to a rheumatologist for less than 1 year.
tREACH patients were randomly assigned oral GC (15 mg prednisone daily, two treatment arms; n=22) or, as was the FLARE cohort, one intramuscular injection of either 120 mg methylprednisolone or 80 mg triamcinolone acetonide (n=14). Disease Activity Score 44 (DAS) and health assessment questionnaire disability index (HAQ-DI) scores were measured before and after 2 weeks of GC therapy to determine in vivo sensitivity. Researchers calculated in vitro GC sensitivity by the bioassaying effects dexamethasone had on interleukin-2 (IL-2) and GC-induced leucine zipper (GILZ) messenger RNA expression. They used a whole cell dexamethasone binding assay to measure number and affinity (1/KD) of glucocorticoid receptors (GR).
The GR number correlated positively with improved DAS (P=.070), while IL-2-EC50 (P=.029) and GILZ-EC50 (P=.054) showed only near-significant correlations in patients treated with intramuscular GC therapy. Patients who saw improved HAQ scores had higher GR number and KD, but lower GILZ-EC50 values.
“Baseline cellular in vitro glucocorticoid sensitivity is modestly associated with in vivo improvement in DAS and HAQ-DI score following GC bridging therapy in RA,” the researchers concluded. “Further studies are needed to evaluate whether in vitro GC sensitivity may support the development of tailor-made GC therapy in RA.”
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