Table 2 Medications available for SLE treatment approved or under clinical investigations

Enpatoran

TLR7/8 inhibitor

NCT05162586 (II, ongoing),

NCT05540327 (II, ongoing)

Attenuating immune response

Suppressing TLR signaling

⁴⁵³

E6742

TLR7/8 inhibitor

NCT05278663 (I/II, completed)

Attenuating immune response

Suppressing TLR signaling

⁴⁵⁴

Hydroxychloroquine

Anti-malaril TLR7/3/9 atagonist

In clinics

Attenuating immune response

Suppressing TLR signaling

⁵⁰⁶

Chloroquine

Anti-malarial TLR7/8/9 atagonist

In clinics

Attenuating immune response

Suppressing TLR signaling

⁴⁵⁹

Quinacrine

Anti-malaril TLR7/9 atagonist

In clinics

Attenuating immune response

Suppressing TLR signaling

⁴⁶¹

Artemisinin

Anti-malaril TLR4 atagonist

In clinics

Attenuating immune response

Suppressing TLR signaling

⁴⁶⁰

Litifilimab

Anti-CD303 antibody

NCT05352919 (III, ongoing),

NCT04961567 (III, ongoing),

NCT04895241 (III, ongoing),

NCT06044337 (III, ongoing),

NCT05531565 (II/III, ongoing),

NCT02847598 (II, completed),

NCT02106897 (I, completed)

Attenuating immune response

Suppressing TLR signaling

^467,468

Anifrolumab

IFNα receptor antibody

In clinics

Attenuating immune response

Suppressing TLR signaling

⁴⁷²

IFNα kinoid

IFNα vaccine

NCT02665364 (I/II, completed),

NCT01058343 (I/II, completed)

Attenuating immune response

Suppressing TLR signaling

^108,475

Rontalizumab

IFNα antibody

NCT00962832 (II, completed)

Attenuating immune response

Suppressing TLR signaling

⁴⁷⁷

Sifalimumab

IFNα antibody

NCT00979654 (II, completed),

NCT01283139 (IIb, completed),

NCT00657189 (II, completed),

NCT00299819 (I, completed),

NCT01031836 (II, completed),

NCT00482989 (I, completed)

Attenuating immune response

Suppressing TLR signaling

^476,477

Upadacitinib

JAK1 inhibitor

NCT05843643 (III, ongoing)

Attenuating immune response

Suppressing JAK/STAT signaling

¹¹⁰

Filgotinib

JAK1 inhibitor

NCT03978520 (II, completed),

NCT03134222 (II, completed),

Attenuating immune response

Suppressing JAK/STAT signaling

^478,479

Fludarabine

STAT1 inhibitor

NCT00001676 (I, completed)

Attenuating immune response

Suppressing JAK/STAT signaling

⁴⁸¹

Artesunate

STAT3 inhibitor

NCT03214731 (IV, NA)

Attenuating immune response

Suppressing JAK/STAT signaling

⁴⁸²

Azathioprine

Purine antagonist

In clinics

Attenuating immune response

Immunosuppressor

^492,499

Cyclophosphamide

Alkylating agent

In clinics

Attenuating immune response

Immunosuppressor

^481,494,497

Mycophenolate mofetil

IMPDH inhibitor

In clinics

Attenuating immune response

Immunosuppressor

^{499,500,501,507,510,511}

Mizoribine

IMPDH inhibitor

NCT02256150 (III, completed)

Attenuating immune response

Immunosuppressor

^490,502

Leflunomide

DHOH inhibitor

In clinics

Attenuating immune response

Immunosuppressor

^492,494,504

Cyclosporine A

Calcineurin inhibitor

In clinics

Attenuating immune response

Immunosuppressor

^493,496

Tacrolimus

Calcineurin inhibitor

In clinics

Attenuating immune response

Immunosuppressor

^509,510,511

Voclosporin

Calcineurin inhibitor

NCT02949973 (II, completed),

NCT05288855 (III, ongoing),

NCT03021499 (III, completed),

NCT02141672 (II, completed),

NCT03597464 (III, completed),

NCT06406205 (III, ongoing),

NCT05306873 (II, ongoing)

Attenuating immune response

Immunosuppressor

^{512,513,515,516}

Autoreactive T cell vaccine

Autoreactive T cell vaccine

Clinical case study

Restoring cytokine microenvironment homeostasis

Targeting T cells

⁵⁹⁹

Rozibafusp alfa

ICOSL and BLyS inhibitotr

NCT02618967 (II, completed),

NCT04058028 (II, completed)

Attenuating immune response

Targeting B cells

⁵³⁵

Dapirolizumab Pegol

CD40L antibody

NCT04976322 (III, ongoing),

NCT02804763 (II, completed),

NCT04294667 (III, completed)

Attenuating immune response

Targeting B cells

⁵¹⁹

Rigerimod

small nuclear U1RNP-70K derived peptide

NCT02504645 (II, completed)

Attenuating immune response

Targeting B cells

⁴⁸⁶

Belimumab

BLyS inhibitor

In clinics

Attenuating immune response

Targeting B cells

^522,523

Blisibimod

BLyS inhibitor

NCT01395745 (III, completed),

NCT02514967 (III, terminated),

NCT02074020 (III, withdrawn),

NCT01305746 (II, completed),

NCT01162681 (II, completed)

Attenuating immune response

Targeting B cells

^525,526

Tabalumab

BLyS inhibitor

NCT02041091 (III, terminated),

NCT01488708 (III, terminated),

NCT01205438 (III, completed),

NCT01196091 (III, completed)

Attenuating immune response

Targeting B cells

^527,528

Ianalumab

BLyS-R inhibitor

NCT06411639 (I, ongoing),

NCT06133972 (III, ongoing),

NCT06293365 (II, ongoing),

NCT05126277 (III, ongoing),

NCT05639114 (III, ongoing),

NCT05624749 (III, ongoing),

NCT03656562 (II, ongoing)

Attenuating immune response

Targeting B cells

⁵²⁹

Telitacicept

BLyS and APRIL inhibitor

In clinics

Attenuating immune response

Targeting B cells

⁵³³

Atacicept

BLyS and APRIL inhibitor

NCT02070978 (II, terminated),

NCT01972568 (II, completed),

NCT00624338 (II/III, completed),

NCT00573157 (II/III, terminated)

Attenuating immune response

Targeting B cells

^531,532

Elsubrutinib+Upadacitinib

BTK inhibitor+JAK1 inhibitor

NCT03978520 (II, completed),

NCT04451772 (II, completed)

Attenuating immune response

Targeting B cells

¹¹⁰

Elsubrutinib

BTK inhibitor

NCT04451772 (II, completed),

NCT03978520 (II, completed)

Attenuating immune response

Targeting B cells

¹¹⁰

Branebrutinib

BTK inhibitor

NCT04186871 (II, completed)

Attenuating immune response

Targeting B cells

⁵³⁹

Fenebrutinib

BTK inhibitor

NCT02908100 (II, completed)

Attenuating immune response

Targeting B cells

⁵⁴⁰

Evobrutinib

BTK inhibitor

NCT02975336 (II, terminated),

NCT02537028 (I, completed)

Attenuating immune response

Targeting B cells

⁵⁴¹

Orelabrutinib

BTK inhibitor

NCT04305197 (I/II, completed),

NCT05688696 (II, ongoing)

Attenuating immune response

Targeting B cells

^542,543

Zanubrutinib

BTK inhibitor

NCT04643470 (II, ongoing)

Attenuating immune response

Targeting B cells

⁵⁴⁴

AC0058TA

BTK inhibitor

NCT03878303 (I, NA)

Attenuating immune response

Targeting B cells

⁵⁴⁵

Obexelimab

CD19 and FcγRIIb antibody

NCT02725515 (II, completed)

NCT06559163(II, ongoing)

Attenuating immune response

Targeting B cells

⁵⁴⁸

autologous CD19 CAR-T cells

CD19 CAR-T cells

NCT06150651 (I, ongoing),

NCT06316791 (I, ongoing),

NCT06333483 (I, ongoing),

NCT06342960 (I/II, ongoing),

NCT05869955 (I, ongoing),

NCT06316076 (I, ongoing)

NCT06121297 (I/II, ongoing),

NCT06189157 (I/II, ongoing),

NCT06316791 (I, ongoing),

NCT06347718 (I/II, ongoing),

NCT05938725 (I/II, ongoing),

NCT03030976 (I, NA)

Attenuating immune response

Targeting B cells

^551,552

autologous CD19/BCMA CAR-T cells

CD19/BCMA CAR-T cells

NCT06428188 (I/II, ongoing),

NCT05846347 (I, ongoing),

NCT06503224 (NA, ongoing),

NCT06530849 (I/II, ongoing),

NCT06285279 (I, ongoing)

Attenuating immune response

Targeting B cells

⁵⁵⁵

autologous BCMA CAR-T cells

BCMA CAR-T cells

NCT06038474 (II, ongoing)

Attenuating immune response

Targeting B cells

⁵⁵⁶

autologous CD20/BCMA CAR-T cells

CD20/BCMA CAR-T cells

NCT06249438(I, ongoing)

Attenuating immune response

Targeting B cells

⁵⁵⁷

autologous CD19/CD20 CAR-T cells

CD19/CD20 CAR-T cells

NCT06462144 (I, ongoing),

NCT06153095 (I/II, ongoing),

NCT06567080 (I, ongoing)

Attenuating immune response

Targeting B cells

^558,559,560

allogeneic CD19 CAR-T cells

allogeneic CD19 CAR-T cells

NCT05988216 (NA, ongoing),

NCT06340490 (I, ongoing),

NCT05859997 (NA, ongoing),

NCT06429800 (I, NA),

NCT06294236 (I, ongoing),

NCT06375993 (I, NA)

Attenuating immune response

Targeting B cells

^{561,562,563,564,565,566}

CD19 CAR-NK cells

CD19 CAR-NK cells

NCT06421701 (I, ongoing),

NCT06010472 (I, ongoing),

NCT06557265 (I, ongoing),

NCT06518668 (I, ongoing),

NCT06468683 (I, NA),

NCT06377228 (I, NA),

NCT06255028 (I, ongoing)

Attenuating immune response

Targeting B cells

^567,568

Rituximab

CD20 antibody

NCT00036491 (I/II, completed),

NCT00556192 (II, completed),

NCT03312907 (III, completed),

NCT02284984 (II, completed),

NCT00381810 (III, terminated),

NCT00137969 (II/III, completed),

NCT00282347 (III, completed),

NCT00293072 (II, completed),NCT05207358 (IV, ongoing),

NCT05828147 (IV, ongoing),

NCT04127747 (IV, NA)

Attenuating immune response

Targeting B cells

^495,570,571

Rituximab+AB-101

CD20 antibody+NK cells

NCT06265220 (I, ongoing),

NCT06581562 (I, ongoing)

Attenuating immune response

Targeting B cells

^574,575

Ofatumumab

CD20 antibody

Clinical case study

Attenuating immune response

Targeting B cells

⁵⁷⁶

Ocrelizumab

CD20 antibody

NCT00626197 (III, terminated),

NCT00539838 (III, terminated)

Attenuating immune response

Targeting B cells

⁵⁷⁷

Obinutuzumab

CD20 antibody

NCT05039619 (II, ongoing),

NCT02550652 (II, completed),

NCT04702256 (III, ongoing),

NCT04221477 (III, ongoing),

NCT04963296 (III, ongoing)

Attenuating immune response

Targeting B cells

⁵⁷⁸

Epratuzumab

CD22 antibody

NCT01408576 (III, completed),

NCT01262365 (III, completed),

NCT01261793 (III, completed),

NCT01534403 (II, completed),

NCT01449071 (I/II, completed),

NCT02306629 (I, completed),

NCT00660881 (II, completed),

NCT00383513 (II, completed),

NCT00624351 (II, completed),

NCT00011908 (I, completed),

NCT00383214 (III, terminatied),

NCT00111306 (III, terminatied)

Attenuating immune response

Targeting B cells

^102,106

Abatacept

Fusion protein interrupting CD80/CD86 signaling

NCT00705367 (I, completed),

NCT01714817 (III, terminated),

NCT00119678 (II, completed),

NCT00774852 (II, completed),

NCT02270957 (II, completed),

NCT00430677 (II/III, terminated),

NCT02429934 (II/III, terminated),

NCT04186871 (II, completed)

Attenuating immune response

Targeting B cells

^583,585

Daratumumab

CD38 antibody

NCT04868838 (II, ongoing),

NCT04810754 (II, NA)

Attenuating immune response

Targeting B cells

^588,709]

Bortezomib

Proteasome inhibitor

NCT01169857 (IV, withdrawn),

NCT02102594 (II, terminated)

Attenuating immune response

Targeting B cells

^589,591

Abetimus sodium

Crosslinking dsDNA receptor on B cells

NCT00390091 (II, withdrawn),

NCT00035308 (III, completed),

NCT00089804 (III, terminated)

Attenuating immune response

Targeting B cells

⁶⁰¹

Immunoglobulin

Immunoglobulin

NCT01841619 (I, completed),

NCT00460928 (I, completed)

Attenuating immune response

Targeting B cells

⁶⁰²

Eculizumab

C5 antibody

Clinical case study

Attenuating immune response

Attenuating over-activated complement system

^604,605,606

Ravulizumab

C5 antibody

NCT04564339 (II, ongoing)

Attenuating immune response

Attenuating over-activated complement system

⁶⁰⁷

Avacopan

C5a receptor inhibitor

NCT05984251 (I, completed)

Attenuating immune response

Attenuating over-activated complement system

⁶⁰⁸

Pegcetacoplan

C3 inhibitor

NCT03453619 (II, completed)

Attenuating immune response

Attenuating over-activated complement system

⁶⁰⁹

Tocilizumab

IL6 receptor antibody

NCT05835986 (I, ongoing),

NCT05155345 (I, ongoing)

Restoring cytokine microenvironment homeostasis

Th1/Th2 balance

⁶¹²

PF-04236921

IL6 antibody

NCT01405196 (II, completed)

Restoring cytokine microenvironment homeostasis

Th1/Th2 balance

¹⁰⁷

Sirukumab

IL6 antibody

NCT01273389 (II, completed),

NCT01702740 (I, completed)

Restoring cytokine microenvironment homeostasis

Th1/Th2 balance

⁶¹⁴

Ustekinumab

IL12 and IL23 antibody

NCT02349061 (II, completed),

NCT04060888 (III, withdrawn),

NCT03517722 (II, terminated)

Restoring cytokine microenvironment homeostasis

Th1/Th2 balance

^616,617

Apremilast

PDE4 inhibitor

NCT00708916 (I/II, completed)

Restoring cytokine microenvironment homeostasis

Th1/Th2 balance, Treg/Th17 balance

⁶¹⁹

Low dose IL2

Low dose IL2

NCT04077684 (II, ongoing),

NCT05339217 (III, ongoing),

NCT05631717 (III, ongoing),

NCT03312335 (II, completed),

NCT01988506 (II, completed),

NCT05262686 (III, NA),

NCT02084238 (NA, completed),

NCT02932137 (NA, completed),

NCT04397107 (NA, completed)

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

^628,629,631

Stem cells

Stem cells

NCT00076752 (II, completed),

NCT03917797 (II, ongoing),

NCT03673748 (II, ongoing),

NCT04318600 (I, completed),

NCT04184258 (I/II, completed),

NCT03171194 (I, completed),

NCT02633163 (II, ongoing),

NCT05018858 (I, ongoing),

NCT00271934 (II, completed),

NCT03828071 (NA, completed)

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

^622,623,624

BT063

IL-10 antibody

NCT02554019 (II, completed)

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

⁶³²

Secukinumab

IL17A antibody

NCT05232864 (III, terminated),

NCT04181762 (III, terminated),

NCT03866317 (II, withdrawn)

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

^635,636,637

Exosomes from MSCs

Exosomes from MSC

Clinical case study

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

⁶³⁸

Betamethasone

Glucocorticoid

In clinics

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

⁶³⁹

Dexamethasone

Glucocorticoid

In clinics

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

⁶⁴⁰

Hydrocortisone

Glucocorticoid

In clinics

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

⁶⁴¹

Prednisone

Glucocorticoid

In clinics

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

⁶⁴²

Prednisolone

Glucocorticoid

In clinics

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

⁶⁴³

Triamcinolone

Glucocorticoid

In clinics

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

^644,645

Methylprednisolone

Glucocorticoid

In clinics

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

⁶⁴⁷

Rapamycin

mTOR inhibitor

NCT00779194 (I/II completed),

NCT04582136 (II, ongoing),

NCT04892212 (I/II, NA),

NCT00392951 (I/II, completed),

NCT0473695 (II, planned)

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

^654,655

Atorvastatin

Statin

NCT00065806 (III, completed)

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

⁶⁵⁷

Pravastatin

Statin

NCT00054938 (II, completed)

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

⁶⁵⁹

Rosuvastatin

Statin

NCT01170585 (II, completed)

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

⁶⁶⁰

Simvastatin

Statin

NCT01953835 (I, completed)

Restoring cytokine microenvironment homeostasis

Treg/Th17 balance

⁶⁶¹

Plasma exchange

Complement

Clinical case study

Rescuing impaired debris clearance machinery

Adding complements

Decrease ICs

^667,668,669

Plasma transfusion

Complement

Clinical case study

Rescuing impaired debris clearance machinery

Adding complements

^665,666

Valziflocept

soluble human FcγRIIb

clinical trial (ACR Meeting Abstracts)

Rescuing impaired debris clearance machinery

Decrease ICs deposition

^663,664