The Effects of Daily Prednisone and Tocilizumab on Hemoglobin A_1c During the Treatment of Giant Cell Arteritis.

Abstract

To study the longitudinal effects of both glucocorticoids and tocilizumab, an interleukin-6 receptor inhibitor, on hemoglobin A_1c (HbA_1c ) levels during glucocorticoid tapering. We analyzed patients with complete data from the Giant Cell Arteritis Clinical Research Study (GiACTA) to investigate the impact of both glycemic and nonglycemic factors on changes in HbA_1c levels over the 52-week trial. Giant cell arteritis (GCA) patients were randomized to receive either tocilizumab or placebo in addition to glucocorticoids. We used a multivariable mixed-effects model to evaluate associations of HbA_1c level with daily glucocorticoid dose, randomization to receive tocilizumab, and red blood cell count in patients with and those without diabetes mellitus at baseline, over 52 weeks. In 209 patients, the median HbA_1c level decreased by 0.50% (P < 0.01) in the group that received both tocilizumab and glucocorticoids (tocilizumab/glucocorticoid) and by 0.10% (P < 0.01) in the glucocorticoid-only group. Randomization to tocilizumab/glucocorticoid was associated with lower HbA_1c (β = -0.209% in those without diabetes, P < 0.01; β = -0.290% in those with diabetes, P = 0.23). These changes had a sizable impact on glucose tolerance classification: 42.5% of patients in the tocilizumab/glucocorticoid group improved from prediabetes status to normal, compared to only 12.5% of patients treated with glucocorticoids alone. Daily glucocorticoid dose was associated with HbA_1c level in patients with baseline diabetes (β = 0.018%/mg, P < 0.01) and those without baseline diabetes (β = 0.005%/mg, P < 0.01). Tocilizumab treatment was associated with a substantial reduction in HbA_1c level, independent of glucocorticoid exposure, which may be achieved through a combination of glycemic and nonglycemic effects.