This trial shows that MR prednisone appears to be a safe and effective treatment for GCA with a similar outcome profile to standard IR prednisolone.

Background: Giant cell arteritis (GCA) is a common large vessel vasculitis of the elderly, often associated with sight loss. Glucocorticoids (GC remain the mainstay of treatment, although biologic treatments have been approved. Biomarkers predicting disease severity, relapse rates and damage are lacking in GCA. EULAR recommends ultrasound (US) as the first investigation for suspected GCA. The cardinal US finding, a non-compressible halo, is currently categorised as either negative or positive. However, the extent and severity of this finding may vary. In this study, we hypothesise whether the extent and severity of the halo sign [calculated as a single composite Halo score (HS)] of temporal and axillary arteries may be of diagnostic, prognostic and monitoring importance; whether baseline HS is linked to disease outcomes, relapses and damage; whether HS can stratify GCA patients for individual treatment needs; whether HS can function as an objective monitoring tool during follow up. Methods: This is a prospective, observational study. Suspected GCA Participants will be selected from the GCA FTC at the participating centres in the UK. Informed consent will be obtained, and patients managed as part of standard care. Patients with GCA will have HS (temporal and axillary arteries) measured at baseline and months 1,3,6 and 12 long with routine clinical assessments, blood sampling and patient-reported outcomes (EQ5D). Non-GCA patients will be discharged back to the referral team and will have a telephone interview in 6 months. We aim to recruit 272 suspected GCA referrals which should yield 68 patients (25% of referrals) with confirmed GCA. The recruitment will be completed in 1 year with an estimated total study period of 24 months. Discussion: The identification of prognostic factors in GCA is both timely and needed. A prognostic marker, such as the HS, could help to stratify GCA patients for an appropriate treatment regimen. Tocilizumab, an IL-6R blocking agent, switches off the acute phase response (C-Reactive Protein), making it difficult to measure the disease activity. Therefore, an independent HS, and changes in that score during treatment and follow-up, maybe a more objective measure of response compare to patient-reported symptoms and clinical assessment alone.

Objectives To measure serial interleukin (IL)‐6 levels in newly diagnosed patients with giant cell arteritis (GCA), treated in a randomized controlled trial of modified‐release prednisone (MR) vs immediate‐release prednisolone (IR) used in a tapering regimen conforming to British Society for Rheumatology GCA guidelines. Methods Patients (n = 12) were randomized into 2 treatment arms (7 MR, 5 IR) and followed over 26 weeks. We measured IL‐6 with additional markers. Results A significantly higher overall mean IL‐6 level (P < .05) was seen in IR (mean = 12.15, standard error [SE] = 1.90) compared with MR (mean = 4.39, SE = 1.84). Mean collagen type 1 cross‐linked C‐telopeptide (CTX) concentration was significantly higher (P < .05) in both groups at week 4 (mean = 0.29, SE = 0.04) compared with week 26 (mean = 0.13, SE = 0.02). MR patients had adrenocorticotropic hormone (ACTH) suppression compared with IR (P < .05) throughout without differences in cortisol levels (P = .34). No significant differences were seen between arms in other markers. Conclusion Our study suggests that elevated levels of IL‐6 in new GCA are better suppressed by MR prednisone compared with IR prednisolone. CTX was significantly reduced in both treatment arms indicating early metabolic effect of glucocorticoids on bone. ACTH suppression with MR prednisone may reflect a greater impact on the hypothalamic‐pituitary‐adrenal axis although cortisol was not affected. MR prednisone warrants further investigation in GCA.

Background Lodotra is a modified-release formulation of prednisone taken at 22:00pm, allowing the active drug to be released 4–6 hours later, synchronous with the nocturnal circadian peak of the inflammatory cytokine interleukin-6. Given high relapse rates and adverse events with standard glucocorticoids (GC) in giant cell arteritis (GCA), an exploratory study of efficacy and safety of modified0release prednisone in patients with newly diagnosed GCA was performed. We report here on an interim analysis. Objectives To evaluate the efficacy and safety of delayed-release prednisone in patients with newly diagnosed GCA. Methods This 26 week feasibility study was designed using a randomised open protocol and a blinded evaluator, and compared modified-release (MR) prednisone versus standard of care immediate-release (IR) prednisone in patients with newly diagnosed GCA. Sixteen cases with an unequivocal clinical and laboratory picture of new GCA, either meeting ACR criteria or with typical ischaemic features were recruited. All cases underwent temporal artery biopsy (TAB). All cases were treated with initial high dose IR prednisone (40–60mg) daily for 4 weeks and then randomised to 2 open arms of tapering GC with either standard IR prednisone or MR prednisone. The steroid tapering schedules were identical and the dose was reduced only if disease was controlled by both clinical and laboratory parameters at each visit. Patients were assessed every two weeks for outcome measures, including disease control and flares, GC related and other adverse effects, biomarkers, function (HAQ and patient global VAS), quality of life (EQ5D), and sleep and fatigue scores. Bone density scan was performed at baseline and after 26 weeks. Results 16 patients were recruited (11 female; mean age 79.6). 10 patients had positive TAB, 4 were negative and 2 samples were insufficient for analysis. 10 patients completed the study and are included in this interim analysis; 4 withdrew (1 in MR group, 3 in IR) and 2 patients remain active in the study. At 26 weeks, 5/6 patients taking MR prednisone were in persistent control, compared to 3/4 receiving IR prednisone. There were no statistically significant differences between the groups in terms of reduction in inflammatory markers, and HAQ, VAS, EQ5D and fatigue scores. EQ5D scores were noted to increase in both groups during the study. Cumulative steroid dosages, weight change and DEXA scores were also not statistically different. Patients on MR prednisone, however, reported significantly poorer sleep scores from week 10 to the end of the study. There were 4 SAEs (2 episodes of sepsis requiring admission and 2 osteoporotic fractures), all in the standard IR prednisone group. Conclusions MR prednisone appears to be a safe and effective treatment for GCA with a similar outcome profile to standard GC. Its use may be limited by adverse effects on sleep. Larger studies on MR prednisone are required. Acknowledgements This study was funded by Napp Pharmaceuticals Disclosure of Interest None decla...

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