ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2161

Ustekinumab for the Treatment of Refractory Giant Cell Arteritis

Richard Conway1,2, Lorraine O'Neill3,4, Eileen O'Flynn3, Geraldine M. McCarthy5,6, Conor Murphy7, Douglas J. Veale8, Ursula Fearon9 and Eamonn S. Molloy10, 1CARD Newman Research Fellow, University College Dublin, Dublin, Ireland, 2Centre for Arthritis and Rheumatic Diseases, Dublin Academic Medical Centre, University College Dublin, Dublin, Ireland, 3Rheumatology, Dublin Academic Medical Centre, St. Vincent's University Hospital, Dublin, Ireland, 4Rheumatology, St. Vincent's University Hospital, Dublin 4, Ireland, 5Rheumatology, Mater Misericordiae University Hospital, Dublin 7, Ireland, 6University College Dublin, Dublin, Ireland, 7Department of Ophthalmology, Royal Victoria Eye and Ear Hospital, Dublin, Ireland, 8St Vincent's University Hospital, Centre for Arthritis and Rheumatic Diseases, Dublin Academic Medical Centre, Dublin 4, Ireland, 9St. Vincent's University Hospital, Centre for Arthritis and Rheumatic Diseases, Dublin Academic Medical Centre, Dublin 4, Ireland, 10St Vincent's University Hospital, Centre for Arthritis and Rheumatic Diseases, Dublin Academic Medical Centre, St Vincent's University Hospital, Dublin 4, Dublin 4, Ireland

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords:

Session Information

Date: Monday, November 9, 2015

Title: Vasculitis II

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose:

Giant cell arteritis (GCA) requires treatment with high dose corticosteroids. Many patients require chronic steroid therapy with associated significant side effects. 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. The aim of this study was to evaluate the efficacy and safety of ustekinumab, an IL12/IL23 inhibitor in GCA.

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. 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. All patients gave written informed consent and the study was approved by the ethics committee of St. Vincent’s University Hospital.

Results:

12 patients commenced ustekinumab having failed to taper corticosteroid monotherapy and a median of 1 other immunosuppressive agent, 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 treatment at last follow-up was 8 (5, 11) months, 3 patients required an increase in dosing interval to 8-weekly. Median (IQR) steroid dose decreased significantly from 23mg (15, 33) to 5mg (3, 8) (p=0.003). No patient experienced a relapse of GCA during ustekinumab treatment. Efficacy outcomes are detailed in Table 2. 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.

Conclusion:

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

Table 1: Baseline demographic and clinical details of included patients

Age, years, median (IQR)

68 (61, 73)

Female, n (%)

 10 (83)

ACR criteria, n (%)

12 (100)

Biopsy positive, n (%)

7 (58)

Temporal artery ultrasound positive, n (%)

2 (17)

CT Angiogram positive, n (%)

3 (25)

Cranial-ischaemic complications, n (%)

2 (17%)

Vasculitis Damage Index, median (IQR)

2 (0, 2)

Disease duration, months, median (IQR)

30 (15, 39)

Failed steroid monotherapy, n (%)

12 (100)

Failed immunosuppressant, n (%)

11 (92)

Immunosuppressants failed, median (range)

1 (0, 3)

Failed methotrexate, n (%)

10 (83)

Duration methotrexate, months, median (IQR)

10 (5, 36)

Dose methotrexate, mg/week, median (IQR)

20 (15, 21)

Relapses, median (IQR)

3 (2, 5)

Clinical features at last relapse

Cranial, n (%)

PMR, n (%)

Constitutional, n (%)

Large vessel vasculitis, n (%)

7 (58)

5 (42)

6 (50)

4 (33)

Corticosteroid adverse events, n (%)

10 (83)

Table 2: Efficacy and safety outcomes

 

Outcome

At ustekinumab initiation

At last follow-up on ustekinumab

p-value

BVAS (median, IQR)

1 (0, 2)

0 (0, 0)

0.018

Prednisolone dose, mg, median (IQR)

23 (15, 33)

5 (3, 8)

0.003

ESR, mm/hr, median (IQR)

12 (2, 20)

18 (7, 30)

0.744

CRP mg/dL, median (IQR)

5 (2, 25)

16 (9, 36)

0.843

Physician assessed active GCA

12

1

–

Stopped corticosteroids, n (%)

–

3 (25)

–

Stopped other immunosuppressant, n (%)

–

8 (67)

–

Disclosure: R. Conway, None; L. O'Neill, None; E. O'Flynn, None; G. M. McCarthy, None; C. Murphy, None; D. J. Veale, None; U. Fearon, None; E. S. Molloy, None.

To cite this abstract in AMA style:

Conway R, O'Neill L, O'Flynn E, McCarthy GM, Murphy C, Veale DJ, Fearon U, Molloy ES. Ustekinumab for the Treatment of Refractory Giant Cell Arteritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/ustekinumab-for-the-treatment-of-refractory-giant-cell-arteritis/. Accessed .

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