Background GCA may be an interleukin-6 (IL-6) driven disease and IL-6 blockade is emerging as an exciting therapy of IL-6.¹ We measured serial IL-6 levels in new patients with GCA treated in an RCT of modified-release prednisone (MR) versus immediate-release prednisolone (IR) used in a tapering regimen conforming to BSR guidelines.^2,3

Methods Patients (n=12) were randomised into two treatment arms (7 MR, 5 IR) and followed up over 26 weeks. IL-6 samples were collected at 9am at weeks 4, 10, 18 and 26 and were measured using Beckman Coulter IL-6 immunoassay, validated in a controlled study according to ACB criteria. We also measured bone markers (CTX, P1NP, vitamin D), HbA1c, cortisol, ACTH and PTH.

Results Significantly higher overall mean IL-6 levels were seen in the IR arm (n=5) compared to MR (n=7) [unpaired two-tailed Student's t test]. IL-6 levels in both arms were lowest between weeks 4–10 and continued to decrease in the IR arm to week 26, whereas lower but constant levels were seen in the MR arm (Figure)

Mean CTX concentration was significantly higher at week 4 (M =0.29, SE =0.04) compared to Week 26 (M =0.13, SE =0.02) p=0.002. No significant difference was seen between treatment arms.

Patients on MR had complete suppression of ACTH compared to IR (p<0.05) without a significant difference between groups in 9 am cortisol levels (p=0.3412). No significant differences were seen in levels of vitamin D, calcium, PTH, ESR, CRP, or HbA1c.

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Conclusions Our study suggests that elevated levels of Il-6 are better suppressed by MR prednisone therapy compared to IR prednisolone in new GCA. Bone resorption marker CTX was significantly reduced in both treatment arms. ACTH suppression with MR prednisone may reflect a greater impact on the HPA axis although cortisol levels were not affected.

Our findings suggest that MR prednisone may warrant further clinical trial investigation in GCA.

References

1. Dasgupta, B. and Panayi, G.S., 1990. Interleukin-6 in serum of patients with polymyalgia rheumatica and giant cell arteritis. British journal of rheumatology, 29(6), pp. 456–458.

2. Spies, C.M., Straub, R.H., Cutolo, M. and Buttgereit, F., 2014. Circadian rhythms in rheumatology–a glucocorticoid perspective. Arthritis research & therapy, 16 Suppl 2, pp. S3.

3. Dasgupta, B., Borg, F.A., Hassan, N., Alexander, L., Barraclough, K., Bourke, B., Fulcher, J., Hollywood, J., Hutchings, A., James, P., Kyle, V., Nott, J., Power, M., Samanta, A. and BSR and BHPR Standards, Guidelines and Audit Working Group, 2010. BSR and BHPR guidelines for the management of giant cell arteritis. Rheumatology (Oxford, England), 49(8), pp. 1594–1597.

References

Acknowledgements Napp Pharmaceuticals Limited, Beckman Coulter, Gabriel Labinjo for technical support.

Disclosure of Interest E. Miler: None declared, S. Mapplebeck: None declared, C. Mackerness: None declared, L. Wilson: None declared, T. Aung: None declared, D. Gayford: None declared, J. P. Schofield Grant/research support from: Napp Pharmaceuticals Limited and Napp distributes prednisone MR in U.K. (Lodotra), B. Dasgupta: None declared