Tocilizumab in Large Vessel Vasculitis – Different Routes of Administration

Background: Tocilizumab is increasingly used in the treatment of large vessel vasculitis with recent approval for giant cell arteritis. Objective: To determine the efficacy and safety of tocilizumab in large vessel vasculitis in a real-life setting using different routes of administration. Methods: Retrospective analysis of consecutive patients at a tertiary rheumatology department who received tocilizumab for large vessel vasculitis. Results: A total of 11 patients were treated with tocilizumab (8 giant cell arteritis, 2 large vessel vasculitis associated with rheumatoid arthritis, 1 Takayasu arteritis) after a median of 2 other steroid-sparing agents (range 1-4). Of these, 9 received tocilizumab as salvage therapy for active vasculitis and 2 due to the toxicity of their former steroid-sparing medication. After a mean follow-up of 23 months 7 patients were in remission as to vasculitis under a mean prednisolone dose of 1.7 ± 1.5 mg; one patient relapsed after long term remission having discontinued tocilizumab for elective surgery; one patient stopped tocilizumab after attributable infectious complications, and two patients died: one due to complications of vascular surgery, probably not attributable to tocilizumab; and the other due to sepsis secondary to sigmoiditis. Only 3 relapses occurred under continuous tocilizumab treatment. In all these 3 cases, renewed remission could be achieved by switching from subcutaneous (162 mg qw) to intravenous tocilizumab (8mg/kg q4w). Conclusion: Tocilizumab is efficacious in patients with large vessel vasculitis in a real-life situation. Safety appears to be acceptable, but infectious complications have to be considered. Intravenous tocilizumab may be used in patients who relapse under subcutaneous application.

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P191 Real life experience of tocilizumab for the management of giant cell arteritis in Fife, Scotland

Rheumatology ◽

10.1093/rheumatology/keaa111.186 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Paul Allcoat ◽

Stephanie Hart ◽

Sarah J Hailwood ◽

John S McLaren

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Past History ◽

Real Life ◽

Large Vessel Vasculitis ◽

Large Vessel ◽

Service Development ◽

High Dose ◽

Nurse Specialist ◽

Newly Diagnosed

Abstract Background Tocilizumab was accepted by the Scottish Medicines Consortium for use in the management of Giant Cell Arteritis (GCA) on 10.09.18. The Fife Rheumatic Diseases Unit is the first Rheumatology unit in Scotland to introduce a structured process for the management of GCA patients with tocilizumab. We describe here our experience of this new service for NHS Fife. Methods All GCA patients considered for tocilizumab are discussed at our weekly Medication Review Meeting by the Consultant Rheumatologists (JSM & SJH) and Rheumatology Pharmacist (SH). By consensus decision, GCA patients deemed appropriate for tocilizumab treatment are then referred to the Vasculitis Nurse Specialist (VNS; PA) for counselling. We have prospectively recorded data on all GCA patients counselled on tocilizumab from 08.11.18 onwards. Patients are followed up closely in a structured manner by the VNS on a fortnightly basis, with both clinical and laboratory assessment at each visit. The VNS ensures that GCA patients follow a rapid steroid taper in line with that used in the GiACTA Trial. Patients also have laboratory assessments performed between each VNS visit at their GP's surgery (to monitor the ESR) to assist in decision making in view of the rapid steroid taper. The VNS also records the cumulative steroid dose along with drug-related side effects (both from steroids and tocilizumab). Results 14 GCA patients have been counselled and commenced on tocilizumab between 08.11.18 and 18.09.19. We have another 2 GCA patients awaiting counselling and due to start tocilizumab soon. Twelve patients have newly diagnosed GCA (5 with unilateral visual loss), 5 with Large vessel vasculitis and 3 patients have refractory GCA. Of the newly diagnosed patients, the reasons for initiating tocilizumab were as follows: poor control of diabetes mellitus on high dose steroids; large vessel vasculitis confirmed on PET scan; previous long-term steroid exposure due to past history of polymyositis; high osteoporotic risk. Conclusion We have successfully introduced a structured process for the use of tocilizumab in Fife GCA patients via a VNS-led GCA clinic. This ensures robust clinical governance around the issues of safety, efficacy and cost. In addition, by collecting real life prospective data, we will add to the existing information available regarding use of this new therapeutic advance for GCA management in routine clinical practice. This initiative is the first of its kind in Scotland and a new service development for NHS Fife. Disclosures P. Allcoat None. S. Hart None. S.J. Hailwood None. J.S. McLaren Honoraria; J.S.M. has received Speaker fees from Roche.

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POS0338 STEROID-SPARING EFFECT OF ANAKINRA IN GIANT-CELL ARTERITIS: A CASE SERIES WITH CLINICAL, BIOLOGICAL AND ICONOGRAPHIC LONG-TERM ASSESSMENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1623 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 397.1-397

Author(s):

S. Deshayes ◽

K. Ly ◽

V. Rieu ◽

G. Maigné ◽

N. M. Silva ◽

...

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Interleukin 1 ◽

Oral Prednisone ◽

Large Vessel ◽

Daily Dose ◽

Sparing Effect ◽

Steroid Sparing

Background:The treatment of giant cell arteritis (GCA) relies on corticosteroids but is burdened by a high rate of relapses and adverse effects. Anti-interleukin-6 treatments show a clear benefit with a significant steroid-sparing effect, but late relapses occur after treatment discontinuation. In addition to interleukin-6, interleukin-1 also appears to play a significant role in GCA pathophysiology.Objectives:We report herein the efficacy of anakinra, an interleukin-1 receptor antagonist, in 6 GCA patients exhibiting corticosteroid dependence or resistance, specifically analyzing the outcome of aortitis in 4 of them, and including the long-term follow-up of 2 previously described patients (1).Methods:This retrospective study analyzed the cases of all GCA patients treated with anakinra from the French Study Group for Large Vessel Vasculitis.Patients had to satisfy the following two criteria to be enrolled in this retrospective study. First, their diagnosis of GCA should be based on the fulfillment of at least 3 criteria of the American College of Rheumatology (ACR) for GCA or on the satisfaction of 2 of these criteria along with the demonstration of LVI on imaging. Second, patients should have received anakinra because of corticosteroid dependence or resistance.Corticosteroid dependence was defined as ≥2 relapses or the combination of 2 of the following criteria: a daily dose of oral prednisone >20 mg/day (or 0.3 mg/kg) at 6 months; a daily dose of oral prednisone >10 mg/day (or 0.2 mg/kg) at 12 months; and/or a treatment maintained >24 months because of a relapsing disease course. Corticosteroid resistance was defined as persistent increased inflammatory parameters at month 3 despite a steroid dosage over 0.5 mg/kg.Results:After a median duration of anakinra therapy of 19 [18–32] months, all 6 patients exhibited complete clinical and biological remission. Among the 4 patients with large-vessel involvement, 2 had a disappearance of aortitis under anakinra, and 2 showed a decrease in vascular uptake. After a median follow-up of 56 [48–63] months, corticosteroids were discontinued in 4 patients, and corticosteroid dosage could be decreased to 5 mg/day in 2 patients. One patient relapsed 13 months after anakinra introduction in the context of increasing the daily anakinra injection interval to every 48 hours. Three patients experienced transient injection-site reactions, and 1 patient had pneumonia.Figure 1.Steroid dosages before and after the introduction of anakinra in 6 patients with giant-cell arteritis and corticosteroid dependence or resistance. The black arrow indicates the time of anakinra introduction.Conclusion:In this short series, anakinra appears to be an efficient and safe steroid-sparing agent in refractory GCA, with a possible beneficial effect on large-vessel involvement.References:[1]Ly K-H, Stirnemann J, Liozon E, Michel M, Fain O, Fauchais A-L. Interleukin-1 blockade in refractory giant cell arteritis. Joint Bone Spine 2014;81:76–8.Disclosure of Interests:Samuel Deshayes: None declared, Kim LY: None declared, Virginie Rieu: None declared, Gwénola Maigné: None declared, Nicolas Martin Silva: None declared, Alain Manrique: None declared, Jacques Monteil: None declared, Hubert de Boysson Speakers bureau: Roche-Chugai, Grant/research support from: Roche-Chugai, Achille Aouba Grant/research support from: SOBI

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P205 The contemporary presentation and management of giant cell arteritis with large vessel vasculitis

Rheumatology ◽

10.1093/rheumatology/keab247.200 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Owen Cronin ◽

Neil D McKay ◽

Hannah Preston ◽

Helen Harris ◽

Barbara Hauser

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Polymyalgia Rheumatica ◽

Large Vessel Vasculitis ◽

Large Vessel ◽

Ct Angiogram ◽

Pet Ct ◽

The Mean ◽

Vessel Involvement

Abstract Background/Aims Giant cell arteritis with large vessel vasculitis (LV-GCA) represents a distinct, less researched sub-category of giant cell arteritis (GCA). In comparison to cranial GCA, the patient’s diagnostic pathway is less well described and it is thought that LV-GCA is underdiagnosed, including in patients with polymyalgia rheumatica and cranial-GCA. Advances in imaging (e.g. PET-CT) and treatment (tocilizumab), have provided additional options in the diagnosis and management of LV-GCA. The aim was to describe the contemporary clinical journey for patients diagnosed with LV-GCA. Methods The electronic patient health record system in NHS Lothian (TrakCare) was used to collect relevant data. Patients with imaging-confirmed large vessel vasculitis, diagnosed with GCA after 1 January 2017 were included. Follow-up was until August 2020. Results Eighteen patients with LV-GCA were included. The mean age was 65 years and 66.7% were female. Two patients had known cranial-GCA but 89% of patients were diagnosed exclusively with large vessel involvement. The most common symptoms were malaise (55%), weight loss (55%), polymyalgia rheumatica (55%) and limb claudication (44%). Pyrexia of unknown origin was a feature in only 17% of patients. Two patients were asymptomatic and were investigated on the basis of raised inflammatory markers. Mean CRP at baseline was 99mg/L and ESR 85mm/hour. The mean time from symptom-onset to diagnosis was 6.8 months (range 1 to 15 months). Sixteen patients (89%) were reviewed by at least one other secondary care specialist. One third of patients were referred from General Medicine followed by Vascular Surgery (16%) and General Practice (16%). 7/18 patients were inpatients at the time of referral. 56% of patients required two modalities of imaging to confirm large vessel involvement. The most commonly used imaging techniques (in descending order) were CT-Chest/Abdomen/Pelvis, CT-angiogram, PET-CT and Vascular Ultrasound. 50% of patients underwent follow-up imaging, most commonly MR- or CT-angiography. Mean follow-up was for 1.6 years. The mean prednisolone dose at 3 months (n = 18) was 24mg daily and 8mg at 12 months (n = 12). 28% of patients relapsed during the follow-up period at 4, 5, 8, 9 and 24 months post-diagnosis. 7/18 patients were commenced on methotrexate for steroid-side effects or for relapse. 8/18 received subcutaneous tocilizumab in combination with methotrexate in two cases. Three patients were started on azathioprine but only one continued. Conclusion In modern-day clinical practice, patients with LV-GCA experience a longer time to diagnosis than those with cranial symptoms. Patients with LV-GCA can experience an array of constitutional symptoms. Frequently, more than one imaging modality is required to confirm LV-GCA and the majority of patients will have seen other hospital specialists or have been admitted to hospital before diagnosis. Methotrexate and tocilizumab are the most frequently-used and effective steroid-adjunct in this single-centre cohort. Disclosure O. Cronin: None. N.D. McKay: Consultancies; Gilead. Other; Has received support for conference attendance from Pfizer and Gilead, Has received educational support from UCB, Gilead, Celgene, Biogen, Sanofi, Abbvie, Novartis, Pfizer. H. Preston: None. H. Harris: None. B. Hauser: None.

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P188 Tocilizumab for giant cell arteritis: real world experience in a single UK centre

Rheumatology ◽

10.1093/rheumatology/keaa111.183 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Gary Reynolds ◽

Bridget Griffiths ◽

Karolyn Houghton ◽

Ben Thompson ◽

Alice R Lorenzi ◽

...

Keyword(s):

Urinary Tract ◽

Adverse Events ◽

Giant Cell Arteritis ◽

Giant Cell ◽

Urinary Tract Infections ◽

Visual Loss ◽

Large Vessel Vasculitis ◽

Large Vessel ◽

Tract Infections ◽

Clinical Records

Abstract Background Tocilizumab was approved for the treatment of giant cell arteritis (GCA) by NICE in April 2018. This decision followed the GiACTA (Giant Cell Arteritis Actemra) study, a randomised control trial that demonstrated a beneficial effect of tocilizumab in reducing the frequency of disease flare and overall prednisolone requirements. However, as noted in the NICE appraisal, the extent to which the patient population in the GiACTA study reflects the population it is eventually used for in UK clinical practice is not clear. To address this, we analysed the records of all patients started on tocilizumab treatment for GCA in a single centre since its approval. Methods We performed a retrospective analysis of the clinical records of all patients started on tocilizumab for GCA at the Freeman Hospital in Newcastle. All patients are discussed in a regional connective tissue disease MDT prior to the initiation of therapy to ensure they fulfil NICE guidelines. At each subsequent visit adverse events related to both tocilizumab and corticosteroids and any flares of GCA or ischaemic events are recorded. Results In total 14 patients started tocilizumab since June 2018, with a cumulative exposure of 8 patient-years. The mean age was 74 years, slightly older than the average age in the GiACTA trial (69 years). In contrast to GiACTA where 48% of patients were newly diagnosed, all our patients had established disease. In our cohort 36% of patients had CT PET evidence of large vessel vasculitis, similar to the rate in GiACTA (40%) but higher than the national average of around 5%. Incidence of visual loss in our treated patients was higher at 29% than recorded in the general GCA population in the DC-VAS study (7.9%). In those treated for relapsing disease around half (56%) had recorded previous significant adverse events with steroids, including heart failure, hypertension and mood changes. Five patients had infections requiring antibiotics (cellulitis/ulcer in three, chest infection in one, urinary tract infections in two), with two serious infections requiring hospital admission (both urinary tract infections). No patients had further ischaemic events while on treatment. All patients were on a lower dose of prednisolone following treatment with an average of a 63% reduction in steroid dose. Conclusion The modest number of patients receiving tocilizumab for GCA suggests we are not treating everyone at first relapse. The higher rates of large vessel vasculitis, visual loss and previous steroid-induced complications suggest a preference for saving tocilizumab for a more severely affected subset of patients. In this preliminary data there were reassuringly no recorded ischaemic events following treatment and steroid doses were successfully reduced in all patients. Disclosures G. Reynolds None. B. Griffiths None. K. Houghton None. B. Thompson None. A.R. Lorenzi None. J. Heaney None.

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Tuberculosis Infection in Chinese Patients with Giant Cell Arteritis

Scientific Reports ◽

10.1038/s41598-019-50892-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Yun Zhang ◽

Dongmei Wang ◽

Yue Yin ◽

Yu Wang ◽

Hongwei Fan ◽

...

Keyword(s):

Weight Loss ◽

Giant Cell Arteritis ◽

Giant Cell ◽

White Blood Cells ◽

Large Vessel Vasculitis ◽

Large Vessel ◽

Chinese Patients ◽

Lower Percentage ◽

Onset Age ◽

Obvious Weight Loss

Abstract Giant cell arteritis (GCA) is a medium- and large-vessel vasculitis with an onset age after 50 years. Takayasu arteritis (TA), which is also a large-vessel vasculitis with an onset age earlier than 40 years, was suggested to be associated with tuberculosis (TB). However, the association between GCA and TB was rarely reported. This study was to retrospectively analyze clinical data of GCA patients at Peking Union Medical College Hospital and elucidate the association between GCA and TB. Ninety-one patients diagnosed with GCA were included in the study. A total of 20 patients (22.0%) had a history of active tuberculosis and received anti-tuberculosis therapy. On comparing the clinical features of patients with GCA and concomitant TB and those without TB, obvious weight loss (P = 0.011), lower percentage of dyslipidemia (P = 0.042), higher percentage of anti-phospholipid antibodies (P = 0.010), and lower white blood cells (P = 0.006) were noted in the TB group. In conclusion, this study demonstrated the percentage of TB history in patients with GCA was higher than that in the Chinese general population. Clinicians should recognize the possibility of comorbid TB in patients with obvious weight loss and relatively lower white blood cell count.

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