HHE Rheumatology and musculoskeletal supplement 2018 | Page 17

response and 15% with no response respectively. 13
GCA patients typically exceed a cumulative dose
of 5000mg prednisolone over several years. 14
In a large UK retrospective study the average
cumulative prednisolone use over the first two
years from diagnosis was 8600mg; however, 33.4%
received over 10,000mg and 3.3% more than
25,000mg. 2 It is estimated that for every 1000mg
cumulative increase in GC dose, the adverse event
hazard ratio increases by 3%. 14 Unfortunately, this
does not treat the underlying inflammation and
contributes to a higher incidence of steroid
related side effects, estimated to affect 85% of
patients with LV-GCA. 15 These side effects include
diabetes, glaucoma, cataracts, hypertension, heart
failure, osteoporosis, mood disturbance and
increased susceptibility to infection, but this is
Vascular US is a promising
and rapidly developing area
in GCA diagnosis, potentially
avoiding the need for further
invasive investigations such as
temporal artery biopsy
not by any means an exhaustive list. 2 GCA cohorts
are particularly vulnerable due to their older age
and higher prevalence of comorbidities. 16 EULAR
taskforce recommendations suggest the risk of
harm is low for the patients at long-term dosages
of ≤5mg prednisone equivalent per day, whereas
at dosages of >10mg/day, the risk of harm is
elevated. 17 Between 5 and 10mg, the risk of harm
is dependent on additional patient-specific
factors. Not only are patients with relapsing and
refractory GCA at higher risk of adverse effects
secondary to toxic levels of glucocorticoids, but
by definition the disease is sub-optimally
controlled. This can lead directly to vascular
damage such as aneurysms, dissection, rupture
and stenotic disease. As such, the clinical and
economic burden of these sub-groups is amplified.
There remains a large unmet need for effective
glucocorticoid-sparing agents. Currently there is no
good evid ence for cDMARDs in GCA. One meta-
analysis based on three small randomised-controlled
trials (RCTs) suggested a role for methotrexate. 18
References
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3 Dejaco C et al. The spectrum
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However its addition did not help to significantly
reduce cumulative glucocorticoid dose or morbidity
and mortality. 15 There are case series recommending
the use of leflunomide and mycofenolate mofetil,
but these are yet to be tested in an RCT setting. 15
Trials of biologic agents in GCA have had varying
success. To date, no role has been found for use of
anti-TNF agents, with infliximab, etanercept and
adalimumab showing inefficacy. 15 Tocilizumab, an
IL-6 receptor blocker, now has a good evidence base.
IL-6-driven inflammation has been implicated in
GCA since first described by Dasgupta and Panayi
in 1990; however, it was not until recently that an
agent utilising this pathway was available in GCA. 19
In the Phase III trial, GiACTA, 119 newly diagnosed
and 132 relapsing patients were randomised to
receive either weekly or fortnightly subcutaneous
tocilizumab with a 26-week prednisone GC taper,
versus the placebo arms with a 26- and 52-week
prednisone taper alone. 20 Sustained prednisone-free
remission was achieved in 56% and 53% of the
weekly and fortnightly tocilizumab groups,
respectively, compared with only 14% and 18%
in the 26-week and 52-week placebo arms,
respectively. Importantly, the cumulative
prednisone dose was significantly lower in the
treatment arm. Based on these results, tocilizumab
has now been licensed for use by the US FDA and
NICE in the UK. However, even in GiACTA, there
were patients who did not achieve remission on
tocilizumab, and it is not certain about its long-term
impact on vascular damage. Other trials using
biologics such as abatacept are currently ongoing,
and we await the results. Ultimately there is still
more work to be done in finding alternative
treatments.
Conclusions
Introduction of ‘Fast Track Pathways’ can offer
a prompt and secure diagnosis, reducing morbidity
in patients with GCA and minimising inappropriate
glucocorticoid use in those who do not.
Vascular US is a promising and rapidly
developing area in GCA and LV-GCA diagnosis,
potentially avoiding the need for further invasive
investigations such as TAB.
There is a large unmet need beyond
glucocorticoids in GCA and LV-GCA. There are
some new promising treatments, including
biologic therapies such as tocilizumab, but this
will not be suitable for every patient. Further
robust RCTs of other glucocorticoid-sparing
agents are required.
9 Schmidt WA. Ultrasound in the
diagnosis and management of
giant cell arteritis. Rheumatology
(Oxford) 2018;57:ii22–ii31.
10 Pipitone N, Versari A, Salvarani
C. Role of imaging studies in
the diagnosis and follow-up
of large-vessel vasculitis: an
update. Rheumatology (Oxford)
2008;47(4):403–8.
11 Blockmans D, Thorsten
B, Schmidt W. Imaging for
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12 Tuckwell K et al. Newly
diagnosed versus relapsing giant
cell arteritis: Baseline data from
the GiACTA trial. Semin Arthritis
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13 Dasgupta B et al. 2012
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for polymyalgia rheumatica:
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HHE 2018 | hospitalhealthcare.com
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14 Broder MS et al.
Corticosteroid-related adverse
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cell arteritis: A claims-based
analysis. Semin Arthritis Rheum
2016;46(2):246–52.
15 Dejaco C et al. Giant cell
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16 Proven A et al. Glucocorticoid
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17 Strehl C et al. Defining
conditions where long-term
glucocorticoid treatment has
an acceptably low level of harm
to facilitate implementation
of existing recommendations:
viewpoints from an EULAR
task force. Ann Rheum Dis
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18 Mahr AD et al. Adjunctive
methotrexate for treatment
of giant cell arteritis: an
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19 Dasgupta B, Panayi GS.
Interlukin-6 in serum of patient
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20 Stone JH et al. Trial of
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N Engl J Med 2017;377(4):
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