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Ustekinumab for the treatment of refractory giant cell arteritis
  1. Richard Conway1,2,
  2. Lorraine O'Neill1,
  3. Eileen O'Flynn1,
  4. Phil Gallagher1,
  5. Geraldine M McCarthy3,
  6. Conor C Murphy4,
  7. Douglas J Veale1,
  8. Ursula Fearon1,
  9. Eamonn S Molloy1
  1. 1 Department of Rheumatology, Centre for Arthritis and Rheumatic Diseases, St Vincent's University Hospital, Dublin Academic Medical Centre, Dublin 4, Ireland
  2. 2 CARD Newman Research Fellow, University College Dublin, Dublin 4, Ireland
  3. 3 Mater Misericordiae University Hospital, Dublin Academic Medical Centre, Dublin 7, Ireland
  4. 4 RCSI Department of Ophthalmology, Royal College of Surgeons of Ireland, Royal Victoria Eye and Ear Hospital, Dublin 2, Ireland
  1. Correspondence to Dr Richard Conway, Department of Rheumatology, Centre for Arthritis and Rheumatic Diseases, St Vincent's University Hospital, Dublin Academic Medical Centre, Elm Park, Dublin 4, D04 T6F4, Ireland; drrichardconway{at}gmail.com

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Giant cell arteritis (GCA) is the most common form of systemic vasculitis.1 Glucocorticoids are the mainstay of therapy, required in high doses for prolonged periods, with consequent serious complications in 86% of patients.2 There is a critical unmet need for a proven safe and effective immunosuppressive therapy in GCA, as agents such as methotrexate and infliximab have shown disappointing results in GCA.3 ,4 Interleukins 12 (IL-12) and 23 (IL-23) are implicated in Th1 and Th17 responses, respectively, both inflammatory pathways relevant to GCA pathogenesis.5 ,6 A recent case series reported the use of ustekinumab in three patients with Takayasu arteritis.7 The aim of this study was to evaluate the glucocorticoid-sparing efficacy of ustekinumab, an IL-12/IL-23-blocking monoclonal antibody, in patients with refractory GCA.

Patients with GCA attending our centre are enrolled in a prospective registry and managed according to standardised protocols in accordance with the British Society for Rheumatology (BSR) guidelines.8 ,9 Patients were eligible to participate in the current study if they met the American College of Rheumatology (ACR) 1990 Classification Criteria for GCA, and had refractory disease (defined as an inability to taper glucocorticoids to <10 mg/day due to symptoms of active GCA with a minimum of two relapses).10 Ustekinumab was prescribed at a dose of 90 mg subcutaneously at week 0, week 4 and then 12 weekly.

The primary outcome was the comparison of the median glucocorticoid dose required to control the disease prior to ustekinumab and at last follow-up. Patients with active disease at study entry could be treated by a temporary increase in glucocorticoids if appropriate. However, for the evaluation of the primary outcome, the dose prior to any such increase was used. Secondary outcomes were physician-assessed GCA relapse (defined as the presence of symptoms of active GCA with or without elevated acute phase reactants) and change in acute phase reactants (erythrocyte sedimentation rate, ESR; C reactive protein, CRP), prior to ustekinumab and at last follow-up. CT angiography was performed for evaluation of large vessel vasculitis where clinically indicated.

Descriptive statistics were reported as mean and SD, median and IQR or number and percentages as appropriate, Wilcoxon signed-rank test was used to compare between group differences. Statistical significance was set at p<0.05. Analyses were performed using SPSS.

Fourteen patients were enrolled in the current study. Patient characteristics are shown in table 1. No patient had a relapse of GCA while receiving ustekinumab. Full details of outcomes are shown in table 2.

Table 1

Characteristics and prior treatment of 14 patients with Giant Cell Arteritis (GCA), treated with ustekinumab

Table 2

Outcome measures pre-ustekinumab and at last follow-up (median follow-up of 13.5 months (range 7–26) after initiation of ustekinumab)

In five patients, ustekinumab frequency was reduced to eight weekly due to persistent constitutional symptoms and elevated acute phase reactants felt to be possibly related to persistently active GCA. Prednisolone dose was not altered. In three patients, symptoms resolved and acute phase reactants normalised. In the remaining two, these features were ultimately attributed to an alternative cause.

Seven patients had large vessel vasculitis on CT Angiogram prior to ustekinumab. Repeat imaging performed in five of these seven, after a median duration of 13 months, showed no new stenoses or aneurysms. Improvement of wall thickening was noted in all five, with full resolution in two.

Six adverse events occurred, one case each of urinary tract infection, tinea pedis, dental abscess, lower respiratory tract infection, alopecia and non-dermatomal limb paraesthesias. A definite relationship to ustekinumab could not be confirmed in any case. Three patients stopped ustekinumab due to adverse events, two of whom subsequently had flares of polymyalgia rheumatica.

In this proof of concept study, ustekinumab permitted a significant reduction in glucocorticoid dose and cessation of other immunosuppressants in patients with refractory GCA. This single centre study was uncontrolled and unblinded. The efficacy and safety of ustekinumab in GCA warrant further evaluation in a randomised controlled trial.

References

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Footnotes

  • Contributors RC, LO and ESM conceived the study. RC performed the data analysis. All authors critically appraised the manuscript and approved the final version.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval St. Vincent's University Hospital Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data used in this study are held in Bone and Joint Unit, St. Vincent's University Hospital, Dublin, Ireland under the custody of EM and can be made available on request.