Australian Doctor Australian Doctor 15th December 2017 | Page 21

adlaimumab (Humira), golimumab
(Simponi), infliximab (Remicade)
and certolizumab pegol (Cimzia).
Each agent targets the same mol-
ecule (tumour necrosis factor) but
each has subtle differences in struc-
ture that translate to differences
in dose frequency and mode of
administration, half-life and effect
on extra-articular features.
These agents are particularly
effective for joint symptoms, skin
disease, dactylitis, enthesitis and
axial disease. 29
Adverse effects associated with
TNF inhibitors are uncommon
but well documented. It must be
emphasized that the benefits to
patients who respond to treatment
are immense and the risks of ther-
apy must be put into this context.
The most common adverse
effects are injection site reaction
(SC agents), which manifests as
an erythematous area at the site of
injection. The area is generally pru-
ritic, raised and warm and may per-
sist for 48-72 hours. The reaction
can be managed with conventional
antihistamines and topical corticos-
teroids. Most local reactions will
subside with ongoing therapy but
occasionally, if reactions remain
troublesome, a switch to an alter-
nate anti-TNF is recommended.
Community-acquired
infec-
tions do not occur with increased
frequency in patients treated with
anti-TNF agents but if infections
do occur, usual treatment is rea-
sonable. Often patients will not
develop the usual early signals of
infection (for example, dysuria and
fever with a UTI) but will complain
of lassitude or non-specific symp-
toms.
If bacterial infections occur, it
is reasonable to cease the anti-
TNF agent until the patient has
recovered and consider a more
prolonged course of antibiotics if
recovery is slow.
All patients are screened for TB
prior to administration of anti-
TNF therapies (QuantiFERON TB
GOLD or Mantoux, chest X-ray)
as well as for Hepatitis B and C
and HIV. The risk of reactivation
of TB in particular is a concern in
patients with previous exposure
and latent disease. If latent disease
is diagnosed, patients are treated
with isoniazid before beginning
anti-TNF therapy.
Drug-induced lupus and demy-
elination are two rare complica-
tions of TNF inhibitors. A lupus
reaction to TNF inhibitors usually
presents in a patient who has been
stable for some time but develops increasing fatigue, joint pain, low-
grade fever and, occasionally, a
skin rash or pruritus. 30 Demyeli-
nation most commonly manifests
as optic neuritis and is a very rare
complication.
Janus kinase inhibitors in patients with active psoriatic
arthritis who are unresponsive to
anti-TNF therapy. 41
Anti-IL17 therapy
Secukinumab
(Cosentyx)
has
recently become available for
patients with conventional, syn-
thetic DMARD refractory dis-
ease. 31 Secukinumab is a fully
human IgG1 monoclonal antibody
that selectively binds to the inter-
leukin-17A (IL-17A) cytokine and
inhibits its interaction with the
IL-17 receptor.
Secukinumab is administered
subcutaneously once a week for
four weeks and then subcutane-
ously once a month thereafter.
Adverse effects are similar to the
anti-TNF agents with the caveat
that the agent does not appear to
result in demyelinating illness, and
the risk of oropharyngeal candidi-
asis is increased in patients tak-
ing the medication. Importantly,
there is no data supporting the use
of secukinumab in patients with
suspected associated inflamma-
tory bowel disease or documented
uveitis.
Anti-IL23 therapy D
Ustekinumab (Stelara) is a fully
human monoclonal IgG antibody
directed against the common p40
chain of both IL-12 and IL-23 and
administered subcutaneously. The
medication is administered by sub-
cutaneous injection at baseline and
six weeks, and then every three
months. Although the drug has
excellent data for psoriasis control,
the results in psoriatic arthritis have
been less impressive, but it remains
an option for patients with anti-
TNF unresponsive disease. 32
Phosphodiesterase inhibitors
Apremilast
Apremilast (Otezla) is an orally
administered inhibitor of phos-
phodiesterase 4 (PDE4), which has
downstream effects on inflamma-
tory cytokine expression through
increased levels of intracellular
cAMP resulting in reduced levels of
TNF-alpha, IL-12 and IL-23. 33
Otezla is licensed in Australia as
an oral twice-daily formulation for
active psoriatic arthritis. The medi-
cation does not have PBS approval
and is therefore not subsidised,
limiting treatment opportunities.
Otezla appears to have a moderate
effect on disease activity with joint
responses lower than those observed
with TNF inhibitors. 34 Although it
provides a favourable safety profile
and efficacy data is acceptable, it
is not widely available in Australia
because of cost limitations.
T-cell inhibition
Abatacept
Abatacept is licensed for use in
rheumatoid arthritis and has been
investigated for the treatment of
psoriatic arthritis. T-cells have a
central role in the pathogenesis of
this condition.