HHE Rheumatology and musculoskeletal supplement 2018 | Page 25

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safety and efficacy of Octagam 10% in patients
with DM (NCT02728752); and an open label study
of subcutaneous immunoglobulin in patients with
DM (NCT02271165).
Tocilizumab, an interleukin-6 (pro-
inflammatory cytokine) receptor antagonist,
is approved for the treatment of rheumatoid
arthritis and systemic juvenile idiopathic
arthritis. 12 The ongoing tocilizumab study is
a multicentre, randomised, placebo-controlled
trial to determine effectiveness of tocilizumab in
the treatment of patients with refractory adult
PM and DM (NCT02043548).
Abatacept, a modulator of T-cell activation by
binding to CD80 and CD86 molecules on antigen-
presenting cells, thereby blocking interaction
with CD28 on T cells, 13 is approved for the
treatment of adult rheumatoid arthritis,
polyarticular juvenile idiopathic arthritis and
psoriatic arthritis. Recently, results of a
randomised, open-label, ‘delayed-start’ treatment
trial in DM/PM were published (ARTEMIS;
NCT01315938). In this pilot study, treatment with
abatacept resulted in lower disease activity in
nearly half of the patients (42%). In patients with
repeat muscle biopsies, an increased frequency of
Foxp3+ Tregs at six months suggested a positive
effect of treatment in muscle tissue. 14 Abatacept is
currently being studied in a randomised, double-
blinded, controlled pilot trial to evaluate the
efficacy and safety of subcutaneous abatacept in
treating interstitial lung disease associated with
anti-synthetase syndrome (NCT03215927); in an
open label study of abatacept for the treatment of
refractory juvenile DM (NCT02594735) and Phase
III, randomised, double blind clinical trial to
evaluate efficacy and safety of abatacept in adults
with active IIM (NCT02971683). The later study is
unique in that it includes not only DM and PM
but also IMNM cases and adult JDM patients as
well.
Siponimod is a selective modulator of
sphingosine 1-phosphate receptor (S1P1,5) that
inhibits the movement of ly mphocytes out of
lymph nodes. 15 A double-blind, randomised,
placebo-controlled study of siponimod in patients
with active DM (NCT02029274) completed
recruitment in 2016 and a previous multicentre
double-blind, placebo controlled study of
siponimod in PM (NCT01801917) was prematurely
stopped in 2016 due to slow recruitment and
small sample size.
Ajulemic acid (JBT-101) is a synthetic
compound that selectively binds to the
cannabinoid receptor type 2 (CB2) 16 promoting
anti-inflammatory and anti-fibrotic effects by
increasing production of PGJ2 (an endogenous
anti-inflammatory ligand) and decreasing
collagen neosynthesis by fibroblasts. 17
Ajulemic acid is currently being studied in
a Phase II, double-blinded, randomised,
placebo-controlled study to investigate the
safety, tolerability and efficacy in patients
with DM (NCT02466243).
Interferon (IFN)-Kinoid is an inactivated form
of IFNα2b that has been studied as a therapeutic
vaccine in patients with systemic lupus
erythematosus. It has been shown to induce
a polyclonal response against most of the IFNα
subtypes, decreasing IFN and B cell-associated
transcripts. 18 It is currently being studied in a
single-blind, randomised, proof of concept study
to evaluate the production of anti-IFNα antibodies
(immune response) in adults with DM
(NCT02980198).
Anakinra is a recombinant IL‑1 receptor
antagonist. It was studied in a small open-label
study that included 15 patients with refractory
PM, DM and IBM (NCT01165008).
Seven patients showed a response in this
non-randomised study. 19 There are no ongoing
studies of anakinra in the IIMs.
IBM
Bimagrumab is an antibody against the activin
type II B receptor (ActRIIB) that results in
inhibition of the activity of myostatin and activins
(negative regulators of muscle mass). Bimagrumab
has been shown to induce skeletal muscle
hypertrophy in mice, 20 to result in expedited
recovery of skeletal muscle volume in acute
disuse atrophy 21 and to increase muscle mass and
function in a small open-label study of patients
with IBM. 22 A randomised, multicentre, double-
blinded, placebo-controlled study of safety and
efficacy of bimagrumab in patients with IBM
(NCT01925209) showed that bimagrumab was
well tolerated; however, it did not reach the
primary endpoint of improving the 6-minute walk
distance (6MWD) test or showed improvement in
muscle strength. 23
Follistatin is a glycoprotein expressed in all
tissues in variable concentrations. 24 It promotes
muscle growth by binding to ActRIIB and
neutralising the effect of various members of
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HHE 2018 | hospitalhealthcare.com
Steroid-sparing
immuno-
suppressive
or immuno-
modulating
therapy is
usually used in
patients with
moderate to
severe diseases
or those
with medical
comorbidities
making long-
term prednisone
use undesirable