Background/Purpose: Giant cell arteritis (GCA) requires treatment with high dose corticosteroids with attendant significant adverse events. There is a critical need for alternative therapies. Interleukins 12 (IL-12) and 23 (IL-23) stimulate Th1 and Th17 responses respectively, both hypothesized to be important in GCA pathogenesis. We have recently reported preliminary evidence of efficacy of IL-12/23 blockade with ustekinumab in 14 GCA patients. In this study we report outcomes in a larger cohort of 25 patients.

Methods: We performed a prospective open label study of ustekinumab in patients with refractory GCA. Ustekinumab was administered subcutaneously at a dose of 90mg at week 1 and week 4 followed by every 12 weeks. Patients underwent standardized clinical assessments. Disease activity was based on a combination of clinical assessment, acute phase reactants (ESR, CRP) and available imaging studies. Descriptive statistics were reported as mean and standard deviation (SD), median and interquartile range (IQR) or number (n) and percentages as appropriate, Wilcoxon Signed Rank test was used to compare between group differences. Statistical significance was set at p<0.05. All patients gave written informed consent and ethical approval obtained.

Results: 25 patients commenced ustekinumab having failed to taper corticosteroids and a median of 1 other immunosuppressant, with a median (IQR) of 2 (1, 3) prior relapses of GCA. 84% had experienced significant corticosteroid side effects.  Full demographic and clinical details are shown in Table 1. Median (IQR) duration of ustekinumab treatment at last follow-up was 15 (6, 22) months. Efficacy outcomes are detailed in Table 2. Median (IQR) steroid dose decreased significantly from 15mg (5, 20) to 5mg (3.8, 10) (p=0.002). 7 patients with large vessel vasculitis had follow-up imaging performed with improvement of wall thickening in all and no new stenoses or aneurysms. No patients experienced a relapse of GCA during ustekinumab treatment. 11 adverse events were recorded, 2 respiratory tract infections, and 1 case each of pancreatitis with infected pseudocyst, bell¡¯s palsy, thyroid goitre, alopecia, parasthesia, tinea pedis, urinary tract infection, dental abscess, and cold extremities. 3 patients discontinued ustekinumab due to adverse events or personal preference, 2 subsequently had flares of polymyalgia rheumatica.

Conclusion: Ustekinumab led to significant reductions in steroid dose and acute phase reactants in patients with refractory GCA. The efficacy of ustekinumab in GCA warrants investigation in a randomized controlled trial.    

Table 2

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