Rheumatology 2021;60:vi21–vi28

Rheumatology doi:10.1093/rheumatology/keab498

New developments in systemic lupus erythematosus

1 1
Michel W. P. Tsang-A-Sjoe and Irene E. M. Bultink

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Abstract
In this review, the results of recent and ongoing clinical trials in patients with SLE are discussed. After many un-
successful trials in the past decade, belimumab was the first biologic specifically designed for SLE that met its pri-
mary end point. At the same time, studies on the pathophysiology of SLE have further elucidated the pathways
involved in the disease, which has led to the identification of new possible therapeutics and has encouraged the
initiation of new trials. These new drugs include biologics that target B cells, T cells and type 1 interferons, and
small molecules that inhibit kinases. Other therapeutics aim to restore immunological balance by restoring toler-
ance. Results from phase II and even phase III trials are promising and it is likely that some of the therapeutics
discussed will receive approval in the following years. Hopefully, this will allow for more tailor-made medicine for
SLE patients in the future.
Key words: biologic therapies, SLE, therapy, targeted therapies

Rheumatology key messages

. Several new therapeutic approaches targeting different molecular pathways show promising results in trials in
SLE.
. Anifrolumab is the second biologic that reached its primary end point in a phase III trial.
. The possibility of targeting different pathways will hopefully allow for more individualized medicine in the future.

Introduction The disease often affects the skin, joints, kidneys and

S U PP L E M E N T
blood, but can virtually affect any organ system resulting
SLE is a chronic systemic auto-immune disease that is in a striking clinical heterogeneity. The 5-year survival of
associated with considerable morbidity and mortality. patients with SLE has improved from 50% in the 1950s
The disease typically affects women of childbearing age to >90% since the 1990s [2, 3], but minimal additional
and follows a relapsing–remitting course. The preva- improvement has occurred over the past decades and
lence varies from 12 to 150 cases per 100 000 people. numerous clinical trials for SLE using biologics targeting
SLE is characterized by the production of autoanti- a specific pathway failed to reach their primary end
bodies against a range of autoantigens including nuclear points [4]. Only one new drug, belimumab, has been
components, formation of immune complexes and de- approved for the treatment of SLE in >60 years [5].
position of immune complexes in a variety of organs, Hydroxychloroquine, glucocorticoids, and the immuno-
leading to inflammation and organ damage. modulatory agents azathioprine, methotrexate and
Environmental and hormonal factors are supposed to in- mycophenolate mofetil are currently the most frequently
fluence the development of SLE in genetically suscep- used drugs. In persistently active or flaring extra-renal
tible individuals by inducing defects in the innate and disease, additional treatment with belimumab is recom-
adaptive immune system [1]. Immune dysregulation in mended, while rituximab or cyclophosphamide may be
patients with SLE can occur at the level of cytokines, T considered in severe, organ-threatening or refractory
cells, B cells and macrophages. disease [6, 7].
The array of clinical phenotypes of SLE reflects the
1
Department of Rheumatology, Amsterdam Rheumatology and complex cellular and molecular mechanisms involved in
immunology Center, Amsterdam University Medical Center, its pathogenesis. Several pathways are involved in each
Amsterdam, The Netherlands patient but the relative contribution of each pathway
Submitted 30 March 2021; accepted 8 June 2021 varies between individuals [8]. The improved insight into
Correspondence to: Michel W. P. Tsang-A-Sjoe, Department of the complex pathogenesis of SLE has inspired the de-
Rheumatology, Amsterdam Rheumatology and immunology Center, velopment of multiple clinical trials using new agents
Amsterdam UMC, location VU University Medical Center, De
Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. directed against recognized targets (Fig. 1). The aim of
E-mail: m.tsang-a-sjoe@amsterdamumc.nl this review is to discuss the results of recent articles on

C The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.
V
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use,
[br]distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Michel W. P. Tsang-A-Sjoe and Irene E. M. Bultink

FIG. 1 Targeted therapies used for the treatment or currently used in clinical trials in SLE

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APC: antigen presenting cell; BAFF: B-cell activating factor; BDCA2: blood dendritic cell antigen 2; BTK: Bruton’s
tyrosine kinase; CD40L: CD40 ligand; IFNR: IFN receptor; JAK: Janus kinase

clinical trials and to summarize ongoing novel clinical tri- patients, trial design and primary outcome parameter.
als in patients with SLE (Table 1). However, data from national registries demonstrated re-
duction in disease activity score and concomitant gluco-
corticoid use in rituximab treated patients [15–17].
Methods
Belimumab
To identify articles relevant to this review, a PubMed
search was conducted using the MeSH terms: (SLE) Belimumab is a monoclonal antibody (mAb) targeting B
with filters: Clinical trial or Randomized Controlled Trial. cell activating factor (BAFF), which is a regulator of B
Papers published between 1 January 2019 and 1 of cell survival. In two landmark phase III trials (BLISS-52
February 2021 were selected. Our search revealed 73 and BLISS-72) [5, 18], patients who received belimumab
original articles. Additionally, a search was conducted on top of standard of care had a higher SLE Responder
on clinicaltrials.gov to identify ongoing trials. Index 4 (SRI4) response rate compared with placebo.
Patients with active lupus nephritis were excluded from
these trials. Extension studies of phase II and III trials
demonstrated long-term safety and tolerability of beli-
B cells
mumab, as well as the suggestion of long-term efficacy
As producers of auto-antibodies, B cells have a key role [19, 20].
in auto-immune diseases. Rituximab (anti-CD20) was A recent phase III randomized, double-blind, placebo-
the first biologic used in SLE that specifically targets the controlled trial (RCT) investigated belimumab in 448
B cell. While successful in many autoimmune diseases lupus nephritis patients [21]. Significantly more patients
including rheumatoid arthritis and ANCA associated vas- who received belimumab achieved the primary efficacy
culitis [9, 10], two major trials in SLE and lupus nephritis renal response compared with placebo at week 104.
failed to achieve their primary end point [11, 12]. The Complete renal response, a major secondary outcome,
reasons for the failure of these two trials are extensively was more frequent in patients who received belimumab
discussed elsewhere [13, 14], but include selection of and their risk of a renal-related event or death was lower

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 New developments in systemic lupus erythematosus

compared with placebo. The safety profile of belimumab seemed promising enough, as a phase III trial in 450
was equal to that of previous trials. The rates of serious patients is currently recruiting (NCT04294667).
adverse events and other adverse events were similar
between standard of care and standard of care plus
belimumab. The results of this trial led to the approval IFNs
of belimumab for treatment of lupus nephritis in March
One of the hallmark features of SLE is the so called IFN
2021.
gene signature [27]. IFNs play a key role in host defence
In an ongoing phase II RCT in 93 childhood SLE
against viruses and belong to an evolutionarily old part
patients, the addition of belimumab to standard of care
of the innate immune system. Increased levels of type 1
did not result in more adverse events at week 52 [22].

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IFNs in serum is a typical feature of SLE. Targeting type
Although the study was not powered to determine su-
1 IFNs, therefore, has garnered much interest as a pos-
periority, numerically more patients on belimumab
sible new therapeutic pathway.
achieved the primary end point SRI4 compared with pla-
cebo, but statistical significance was not reached.
However, this study did result in the approval of belimu- Anifrolumab
mab for SLE treatment in children of 5 years or older. Anifrolumab, a human mAb targeting the type I IFN re-
Currently, two ongoing trials are investigating the ceptor subunit 1, surprisingly did not achieve its primary
combination of rituximab and belimumab [23, 24]. In the end point SRI4 in the first phase III trial in SLE (TULIP-1)
BLISS-BELIEVE trial, belimumab is administered sub- [28], after promising results in a phase II trial. However,
cutaneously. Rituximab is then added 4–8 weeks after BICLA, another composite index for response was
the initiation of belimumab, while in the BEAT Lupus achieved significantly more frequently in patients allotted
trial, belimumab is administered intravenously 4–8 weeks to anifrolumab than to placebo. In the second phase III
after two infusions of rituximab. Results of these trials trial in 362 patients, monthly infusions of 300 mg anifrolu-
are expected this year. mab resulted in a higher percentage of patients with a
BICLA response at week 52 than did placebo (48% vs
XmAb5871 32%, respectively) [29]. The success of the second phase
XmAb5871 (obexelimab) is a humanized anti-CD19 anti- III trial of anifrolumab might in part be attributable to the
body Fc-engineered for increased affinity to FcgRIIb. selection of a different primary outcome parameter.
XmAb5871 therefore targets B cells. One hundred and Interestingly, the presence of an IFN gene signature at
four patients with moderate to severe, non-organ threat- baseline was not a predictor for response to anifrolu-
ening disease were enrolled in a RCT [25]. Only hydrox- mab. A possible explanation might be that the majority
ychloroquine and 10 mg prednisolone per day were of patients (83%) had a high IFN gene signature at
allowed as immunosuppressive co-medication. Patients baseline. No significant differences in the number of ad-
were given 2  80 mg Depo-Medrol at the start followed verse and serious adverse events between the anifrolu-
by XmAb5871 or placebo every 14 days. The primary mab and placebo groups were observed, except for
end point (no loss of improvement) did not reach statis- herpes zoster (7.2% for anifrolumab and 1.1% for pla-
tical difference, but a trend favouring XmAb5871 was cebo). US Food and Drug Administration and European
observed. Because of the unique primary end point Medicines Agency approval for anifrolumab are pending.
used in this trial, the results are difficult to interpret.
Sifalimumab
Dapirolizumab In a small phase II open label trial in 66 Japanese
CD40L, which is primarily expressed on T cells but also patients, sifalimumab, an anti-IFN-a mAb, was shown to
on other cells such as B cells and pDCs, plays an im- be safe and well tolerated [30]. Serious adverse events
portant role in the regulation of the immune response occurred in 30% of patients in the first 52 weeks and
through T cell activation, B cell activitation and differenti- were mainly instances of SLE flares. A concern with the
ation, and the release of pro-inflammory cytokines by use of Abs directed against IFN in the current COVID-19
pDCs. Dapirolizumab is a PEGylated mAb with specificity pandemic is that ‘endogenic’ auto-antibodies against
for CD40L. This drug is particularly interesting, because IFN-a, induced by SARS-CoV-2 infection, are associated
PEGylated Abs barely pass the placental membrane and with severe COVID-19 [31].
it is potentially safe to use during pregnancy, which is a
major issue. In a phase IIb, dose-ranging RCT in 182 BIIB059
SLE patients, dapirolizumab or placebo was given on top BIIB059 indirectly targets type I IFN production by tar-
of standard of care [26]. While numerically higher re- geting a receptor of the plasmacytoid dendritic cell
sponse rates were observed in all three dosages of (blood dendritic cell antigen 2, BDCA2) [32]. In a double-
dapirolizumab compared with placebo, a statistically sig- blind RCT, BIIB059 was first given to 54 healthy volun-
nificant difference in BILAG based Composite Lupus teers. In the second part of the trial, BIIB059 administra-
Assessment (BICLA) response as the primary end point tion in 12 patients with SLE decreased expression of
at week 24 was not achieved. The results from this trial IFN response genes in blood, reduced immune infiltrates

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Michel W. P. Tsang-A-Sjoe and Irene E. M. Bultink

in skin lesion biopsies, and clinically decreased skin dis- treated with IL-2 than placebo (7/13, 53.85% vs 2/12,
ease activity. BIIB059 was generally well tolerated al- 16.67%, respectively). A second phase II trial in 500
though one SLE patient experienced nine serious SLE patients is currently recruiting. This study will inves-
adverse events, which were interpreted as unrelated to tigate three different dosages of IL-2 compared with pla-
the BIIB059. A phase II study in cutaneous lupus with or cebo (NCT04077684).
without SLE has recently completed and results of this
trial are awaited (NCT02847598). Ustekinumab
Ustekinumab, an effective biologic for psoriasis, psoriat-
IFN-a kinoid ic arthritis and inflammatory bowel disease, targets the
The IFN-a kinoid (IFN-K) is an immunotherapeutic vac- p40 subunit of IL-12 and IL-23. A phase II trial in 102

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cine aimed to induce antibodies against IFN-a. A phase patients reported significantly greater SRI4 response
II RCT in 185 SLE patients was recently conducted [33]. rates in the ustekinumab group (62%) vs the placebo
Neutralizing anti-IFN-a2b serum antibodies were group (33%) at the primary end point analysis at week
detected in 91% of treated patients at week 36. While 24 [37]. This response rate was maintained at week 48
the first co-primary end point of neutralization of the IFN in the ustekinumab group [38]. However, the subsequent
signature was achieved, the clinical end point of a modi- phase III trial was terminated prematurely after a pre-
fied BICLA was not. A secondary clinical outcome par- planned interim efficacy analysis failed to show efficacy.
ameter, Lupus Low Disease Activity State, reached its No new safety issues were reported. Current analyses
end point (53% of patients assigned to IFN-K compared focus on elucidating the differences in outcome between
with 30% of patients assigned to placebo). While ad- the phase II and III trials. It seems unlikely that ustekinu-
verse events and serious adverse events were compar- mab will be further developed for SLE treatment.
able in both groups, significantly more patients in the
IFN-K group had upper respiratory tract infections com-
pared with placebo (17.6% vs 5.4%). The increased rate Kinase inhibitors
of upper respiratory tract infections underlines the safety Baricitinib
concern for severe COVID-19, as previously mentioned.
In a 24-week double-blind phase II RCT of 314 SLE
Omalizumab patients with cutaneous lupus and/or arthritis, 2 or 4 mg
daily baricitinib, an oral Janus kinase (JAK)1/2 inhibitor,
Omalizumab, a mAb targeting IgE, is currently used in
demonstrated significantly better reduction in skin dis-
IgE mediated asthma, among others. Its presumed
ease and/or arthritis compared with placebo in the 4 mg
method of action in SLE is by hampering plasmacytoid
baricitinib subgroup. Serious infections and SAEs were
dendritic cells and basophil activation and thereby
more frequent in the 4 mg subgroup while AEs were
reducing type I IFN production [34]. A small RCT in 16
similar between the groups [39]. The results of two
patients demonstrated an improvement in SLEDAI 2000
phase III RCTs on the efficacy and safety of 2 or 4 mg
(SLEDAI-2K) scores in the omalizumab group compared
daily baricitinib compared with placebo are currently
with the placebo group at week 16. Subjects receiving
expected.
omalizumab showed a trend toward improvement in IFN
gene signature.
Tofacitinib
In a single centre open-label case series of 10 SLE
Cytokines patients, treatment with the oral JAK1/3 inhibitor tofaciti-
nib, 5 mg twice daily, resulted in complete resolution of
IL-2 arthritis in four out of four patients, complete resolution
Deficiency of regulatory T cells (Tregs) has been impli- of mucocutaneous manifestations in six out of nine
cated in many autoimmune diseases, including SLE. patients and partial or no response in the remaining
Tregs have an important role in tolerance and control of three patients with rash. SLEDAI-2K and physician glo-
inflammation. A previous open clinical trial, in which IL-2 bal assessment scores improved significantly [40].
was administered to patients with varying autoimmune
diseases, demonstrated specific Treg expansion and ac- Voclosporin
tivation without effector T cell activation [35]. Six out of Voclosporin, a novel high potency calcineurin inhibitor,
46 patients in this trial had SLE. A subsequent RCT in combination with mycophenolate mofetil and rapidly
treated 60 SLE patients in a 1:1 ratio with IL-2 or pla- tapered oral glucocorticoids (vs placebo) demonstrated
cebo [36]. At the primary end point at week 12, the SRI4 superior efficacy compared with standard therapy in a
response rates were 55% for IL-2 and 30% for placebo, phase III RCT in 357 patients with active lupus nephritis
which did not reach statistical significance. However, at (AURORA) after 52 weeks [41]. The incidence of SAEs
week 24, SRI4 response rates did significantly differ was similar between the groups. Based on this success-
(66% and 37%, respectively). Furthermore, complete re- ful trial, approval of voclosporin for the treatment of
mission of lupus nephritis was more frequent in patients lupus nephritis is expected in the near future.

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 New developments in systemic lupus erythematosus

Sirolimus after cessation of iguratimod. A phase II trial in 120

Sirolimus, a mammalian target of rapamycin inhibitor of lupus nephritis patients is currently recruiting
antigen-induced T cell proliferation, was investigated in (NCT02936375).
a single-arm, open-label phase I/II trial in patients with
active, therapy-resistant SLE [42]. In the 29 patients who Umbilical cord derived mesenchymal stem cells
completed treatment during 12 months, significant A study in Chinese patients aimed to investigate the role
reductions in disease activity (assessed using SLEDAI of peripheral tolerogenic CD1cþ dendritic cells and the
and BILAG) and glucocorticoid use were reported. A levels of serum FLT3L, a marker for common dendritic
single-arm, open-label phase II study in 20 patients with cells in SLE [49]. A decrease in CD1cþ dendritic cells
connective tissue disease-related refractory thrombo- and serum levels of FLT3L was observed in SLE

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cytopenia, of whom 14 were diagnosed with SLE, patients compared with healthy controls. Next, 21 SLE
reported an overall response rate of 71.4% and com- patients with refractory disease received infusions with
plete remission rate of 64.3% in this subgroup [43]. No umbilical cord derived mesenchymal stem cells. After
severe side effects were reported. transplantation, the frequency and absolute number of
CD1cþ DCs were significantly increased after 24 and
Leflunomide 72 h. Serum FLT3L levels also increased. Clinically, the
Leflunomide, an inhibitor of dihydroorotate dehydrogen- SLEDAI score significantly declined in the first 11
ase leading to a decrease in B and T cells, given orally patients with 6 months of follow-up, during which two
with a loading dose of 40 mg/day for 3 days and fol- patients achieved complete remission and two patients
lowed by 20 mg/day, was demonstrated as effective as flared. No adverse events were reported.
intravenously cyclophosphamide (0.8–1.0 g monthly) in Mechanistically, it was shown that FLT3L promotes the
combination with prednisone in the induction treatment proliferation and inhibits the apoptosis of tolerogenic
of proliferative lupus nephritis in an RCT of 24 weeks in CD1cþ dendritic cells, which might be the mode of ac-
100 Chinese patients [44]. Rates of complete and partial tion to suppress inflammation in SLE. A new phase II
clinical remission and rates of adverse events were simi- trial further explores the potential of umbilical cord
lar between the groups. derived mesenchymal stem cells in lupus nephritis
(NCT03673748).
Bruton’s tyrosine kinase inhibitors
Bruton’s tyrosine kinase (BTK) inhibitors have multiple
effects on B cells and macrophages. A phase II RCT of
Ongoing registered clinical trials in SLE
fenebrutinib 150 or 200 mg/day vs placebo in 260 Currently, several clinical trials investigating novel mo-
patients with non-renal SLE reported an SRI4 response lecular pathways in patients with SLE are ongoing. An
of 51% in the fenebrutinib 150 mg/day group, 52% in overview of selected studies and their molecular target
the 200 mg/day group, and 44% in the placebo group, is summarized in Table 1.
which differences were not significant [45]. A phase II
RCT with another oral BTK inhibitor, evobrutinib (in three
different dosages), vs placebo in 469 patients with ac- Conclusion
tive SLE reported no treatment effect of evobrutinib vs
placebo at any dose [46]. A phase II trial studying elsu- The need for new therapies in SLE is high as persistent
brutinib (BTK inhibitor) alone or in combination with upa- disease activity despite currently approved therapies is
dacitinib (JAK inhibitor) compared with placebo is common and toxicity of drugs such as glucocorticoids
ongoing (NCT03978520). and cyclophosphamide majorly impacts quality of life.
Treatment of SLE is still challenging due to the wide
clinical and pathophysiological heterogeneity of the dis-
Immunomodulators ease, which also poses a challenge to clinical trial de-
sign. Targeting an identified pathogenic pathway in SLE
Iguratimod
will only benefit the subgroup of patients in whom that
Iguratimod is a synthetic small molecule that can inhibit pathway is relevant, which underlines the need for tail-
nuclear factor-jB (NF-jB) activation and consequently ored therapy.
reduces immunoglobulin production [47]. Its modulatory In the past two years, several new therapies targeting
effect is through B cell differentiation. In an open-label different molecular pathways have demonstrated
study [48], 14 refractory lupus nephritis patients, 10 of encouraging results in clinical trials in SLE. After the ap-
whom had recent treatment failure and four had proval of belimumab, trials using fully humanized mono-
repeated relapses with inadequate initial responses, clonals targeting B cells or combinations of biologics
were enrolled. Out of 12 patients, five had a complete have been initiated. A second group of drugs target
and seven a partial renal response, of whom three had a interferon, be it directly, such as anifrolumab and sarilu-
relapse within 144 weeks of follow-up. There was one mab, or more indirectly, such as BIIB059 or omalizu-
serious adverse event (anaemia), which fully recovered mab. We are eagerly awaiting the results of phase III

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Michel W. P. Tsang-A-Sjoe and Irene E. M. Bultink

TABLE 1 Ongoing registered clinical trials in SLE

Therapy Target Trial phase Participants (target) Trial registration

B cells
Belimumab/rituximab BAFF/CD20 III 292 NCT03312907
Belimumab/rituximab BAFF/CD20 II (LN) 70 NCT03312907
Ianalumab/iscalimab BAFF/CD40 II 120 NCT03656562
Dapirolizumab CD40L III 450 NCT04294667
Rozibafusp alpha ICOSL/BAFF II 320 NCT04058028
RC-18 TACI-Fc fusion protein II (completed) 249 NCT02885610

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Cytokines/chemokines
Secukinumab Anti-IL17 mAb III (LN) 460 NCT04181762
BOS161721 Anti-IL21 mAb I/II (completed) 143 NCT03371251
Guselkumab Anti-IL23 mAb II (LN) 60 NCT04376827
BT063 Anti-IL10 mAb II (completed) 36 NCT02554019
Aldesleukin IL2 II (completed) 16 NCT03312335
IL2 II 500 NCT04077684
ILT-101 IL2 II (completed) 100 NCT02955617
LY3471851 (NKTR-358) IL2 II 280 NCT04433585
AMG592 IL2 I 29 NCT03451422
AMG592 IL2 II 320 NCT04058028
PF-06835375 Anti-CXCR5 antagonist I 112 NCT03334851
Kinases
AC0058TA BTK I 32 NCT03878303
Orelabrutinib (ICP-022) BTK I/II (completed) 60 NCT04305197
Branebrutinib BTK II 185 NCT04186871
Elsubrutinib/upadacitinib BTK/JAK1 II 325 NCT03978520
Elsubrutinib/upadacitinib BTK/JAK1 II 260 NCT04451772
Baricitinib JAK1/2 III 1100 NCT03843125
Baricitinib JAK1/2 III 750 NCT03616964
Baricitinib JAK1/2 III 809 NCT03616912
PF-06700841 JAK1/TYK2 II 448 NCT03845517
BMS986165 TYK2 II 360 NCT03920267
BMS986165 TYK2 II 360 NCT03252587
BMS986165 TYK2 II (LN) 78 NCT03943147
Cenerimod S1P II 500 NCT03742037
Other
Itolizumab Anti-CD6 mAb I 60 NCT04128579
Iberdomide (CC-220) Cereblon E3 ligase modulator II (completed) 42 NCT02185040
Curcumin II 68 NCT03953261
SM934 Artesimin analogue II 48 NCT03951259
Mesenchymal stem cells II 81 NCT02633163
Lenabasum (JBT-101) CB2 agonist II 100 NCT03093402
KZR-616 Immunoproteasome II 68 NCT03393013

BAFF: B cell activating factor; BTK: Bruton’s tyrosine kinase; CD40L: CD40 ligand; JAK: Janus kinase; mAb: monoclonal
antibody; TYK: tyrosine kinase.

trials using small molecules such as the JAK inhibitor are interesting because their mode of action is to restore
baricitinib, which has shown potent effects in other tolerance. Future studies should elucidate whether their
rheumatic diseases and the calcineurin inhibitor voclo- safety profile is also more favourable compared with
sporin. The oral route of administration is preferred by immunosuppressants.
most patients and the short half-life provides a favour- The road is long, but we are confident that several
able safety aspect. new targeted therapies will receive approval in the next
Because most SLE patients are females of childbear- decade, which will hopefully allow for more tailor-made
ing potential, dapirolizumab pegol deserves special at- medicine for SLE patients in the future.
tention. PEGylated mAbs do not or only minimally
Funding: This paper is published as part of a supple-
transfer across the blood–placental barrier, thus poten-
ment supported by a grant from UCB Pharma.
tially allowing safe continuation during pregnancy [50].
A fourth group of potential new treatments covered in Disclosure statement: I.E.M.B reports personal fees from
our review contains immunomodulators. These drugs Eli Lilly, MSD, Amgen, UCB Pharma, GSK, Roche and

vi26 https://academic.oup.com/rheumatology
 New developments in systemic lupus erythematosus

Sanofi Genzyme outside the submitted work. M.W.P.T 13 Ramos L, Isenberg D. Rituximab: the lupus journey. Curr
has declared no conflicts of interest. Treatment Options Rheumatol 2015;1:30–41.
14 Dorner T, Lipsky PE. Beyond pan-B-cell-directed ther-
apy—new avenues and insights into the pathogenesis of
SLE. Nat Rev Rheumatol 2016;12:645–57.
Data availability statement 15 Terrier B, Amoura Z, Ravaud P et al.; Club Rhumatismes
The authors declare that all data supporting the findings et Inflammation. Safety and efficacy of rituximab in
systemic lupus erythematosus: results from 136 patients
of this study are available within the article.
from the French AutoImmunity and Rituximab registry.
Arthritis Rheum 2010;62:2458–66.
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