HHE Rheumatology and musculoskeletal supplement 2018 | Page 18

rheumatology and
musculoskeletal
Optimising management of
systemic lupus erythematosus
There is now a better understanding of autoimmunity in systemic lupus erythematosus, which has
led to improved therapeutic strategies, but revolutionary treatments have yet to be discovered
Ioannis Parodis
MD PhD
Division of Rheumatology,
Department of Medicine,
Karolinska Institutet;
Rheumatology Unit,
Karolinska University
Hospital, Stockholm,
Sweden
Systemic lupus erythematosus (SLE) is a chronic
inflammatory autoimmune disorder that
predominantly affects women of child-bearing
age with a ~9:1 female-to-male ratio. Patients
with SLE suffer an impaired health-related quality
of life (HRQoL), and experience fatigue and pain
as major problems.
The pathogenesis of SLE is multifactorial
and its aetiology is largely unknown. 1 Genes,
hormones and environmental factors have been
implicated among the causes of the disease.
Multiple organs may be involved, including
the skin, joints, kidneys and the central nervous
system, with renal and neuropsychiatric SLE
probably constituting the most severe
manifestations. Considerable variations in
severity can be observed during the course of
the disease, with periods of remission and flares,
the intensity of the latter ranging from mild to
severe, to sometimes organ- or life-threatening.
Mortality during the early course of the disease is
associated with activity grade and infections, but
comorbidities, especially cardiovascular disease,
are considerable causes of death at later stages. 2
In SLE, both the innate and the adaptive
immunity may be aberrant, and defective
apoptotic cell clearance is hypothesised to be
a central phenomenon underlying the initiation
of autoreactive responses. The type I interferon
pathway has a central role in the pathogenesis
of SLE, 3 and the hyperactivity of the B cell lineage
also has pivotal significance. The disease is
characterised by a prominent production of
autoantibodies to nuclear components and
immune complex depositions, resulting in
inflammation and damage in organs and/or
tissues. There is now a better understanding of
autoimmunity in SLE, which has led to improved
therapeutic strategies, but revolutionary
treatments have yet to be discovered.
Management of SLE
The management of SLE and the development
of new therapies have been challenging because
of the prominent heterogeneity of the disease
in clinical presentation and underlying
immunopathology, as well as its unpredictable
course. For these reasons, the treatment of SLE
varies and is highly individualised. Commonly
used therapies include corticosteroids,
antimalarial agents, immunosuppressive agents
and non-steroidal anti-inflammatory drugs
(NSAIDs). 4,5 Several immune components have
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HHE 2018 | hospitalhealthcare.com
been identified as potential targets of novel
treatments. Unfortunately, the majority of trials
have failed. In 2011, drug agencies in several
countries approved belimumab, an anti-BAFF (B
cell-activating factor belonging to the TNF family)
monoclonal antibody, for the treatment of SLE. 6,7
The introduction of belimumab has contributed
to improved management; however, it is still
unclear which patient groups are expected to
benefit most from this drug. Considering the cost
and potential toxicity of biologic therapies,
further survey towards identification of predictors
of treatment response is of utmost importance.
Therapeutic strategies in SLE
The management of SLE has traditionally been
non-specific, with symptomatic therapeutic
approaches. As mentioned above, the reasons for
this can be traced to: (i) the lack of therapies
targeting specific immune components, with the
possible exceptions of belimumab, rituximab and
cyclosporine; and (ii), the wide spectrum of
clinical manifestations. The treatment strategies
are therefore individual, depending on the organ
involvement, the severity of the disease and the
complications. Non-major organ involvement may
be treated with for example, glucocorticoids,
antimalarial agents, and NSAIDs. In more severe
or non-responsive cases, azathioprine,
mycophenolate mofetil and methotrexate are
commonly used. Despite their widespread use,
not all of these drugs have been approved for SLE.
The use of antimalarial agents in SLE is
coupled to a wide variety of beneficial effects,
making this drug class the cornerstone of SLE
therapy. 8,9 The modulatory effects of antimalarial
agents on immune responses are mediated by
several mechanisms, for example, through
interference with antigen processing. The use of
antimalarial agents in SLE has been associated
with remission maintenance effects, 8 as well as
prevention of flares and decreased corticosteroid
use during pregnancy. 10 Hydroxychloroquine
has been shown to improve renal prognosis in
patients with lupus nephritis. 11 Based on their
atheroprotective effects, antimalarial agents are
expected to be beneficial in SLE patients at high
risk for thrombotic events; for example, patients
with the antiphospholipid syndrome or high
titres of antiphospholipid antibodies. It is
recommended that all SLE patients receive
adequate doses of antimalarial agents unless it is
contraindicated due to, for example, retinopathy.