Oral (15A169)

Ustekinumab for the Treatment of Refractory Giant Cell Arteritis

Author(s)

R Conway, L O’Neill, E O’Flynn, GM McCarthy, CC Murphy, DJ Veale, U Fearon, ES Molloy

Department(s)/Institutions

CARD Newman Research Fellow, University College Dublin, Ireland, Centre for Arthritis and Rheumatic Diseases, Dublin Academic Medical Centre, University College Dublin, Ireland, Department of Rheumatology, St. Vincent’s University Hospital, Dublin 4, Ireland, Mater Misericordiae University Hospital, Dublin Academic Medical Centre, Eccles St. Dublin 7, Ireland, Department of Ophthalmology, Royal College of Surgeons of Ireland, Royal Victoria Eye and Ear Hospital, Adelaide Road, Dublin 2, Ireland

Introduction

Giant cell arteritis (GCA) requires treatment with high dose corticosteroids. Many patients require chronic steroid therapy with associated significant side effects.

Aims/Background

There is a lack of proven alternative therapies. Interleukin 12 (IL12) and interleukin 23 (IL23) drive Th1 and Th17 responses respectively which are central to the pathogenesis of GCA. Our aim was to evaluate the efficacy and safety of ustekinumab, an IL12/IL23 inhibitor in GCA.

Method

We performed a prospective open label study of ustekinumab in patients with refractory GCA. All patients met the 1990 ACR classification criteria for GCA. 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 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.

Results

12 patients commenced ustekinumab having failed to taper corticosteroid monotherapy and a median of 1 other immunosuppressant, with a median (IQR) of 3 (2, 5) prior relapses of GCA. 83% had experienced significant corticosteroid side effects. Full demographic and clinical details are shown in Table 1. Median (IQR) duration of ustekinumab at last follow-up was 8 (5, 11) months. Patients with clinician assessed active GCA decreased from 12 to 1. Median BVAS (IQR) decreased from 1 (0, 2) to 0 (0, 0) (p=0.018). Median (IQR) steroid dose decreased from 23mg (15, 33) to 5mg (3, 8) (p=0.003). 8 patients were able to stop other immunosuppressants and 3 were able to stop corticosteroids. There was no significant change in ESR or CRP and no patient experienced a relapse of GCA during ustekinumab treatment. 5 adverse events were recorded, 1 UTI, 1 LRTI, 1 hair loss, 1 parasthesia, and 1 dental abscess. 3 patients discontinued ustekinumab due to adverse events or personal preference, 2 subsequently had a relapse of GCA.

Conclusions

Ustekinumab permitted a significant reduction in steroid dose and other immunosuppressants in patients with refractory GCA. The efficacy of ustekinumab in GCA warrants further investigation in a randomized controlled trial.