Table 1. Cytokine-targeted therapies for treatment of autoimmune diseases.
| Target cytokine | Structure | Drug | Clinical application | Under investigation (phase IIb or III) |
|---|---|---|---|---|
| TNF-ɑ | sTNFR2-IgG1 Fc | Etanercept | RA, pJIA, AS, Psoriasis, PsA | |
| Anti-TNF mAb | Infliximab | RA, AS, Psoriasis, PsA, UC, CD | ||
| Off-label use: BD, sarcoidosis | ||||
| Adalimumab | RA, pJIA, AS, psoriasis, PsA, UC, CD, hiradenitis suppurativa, uveitis | |||
| Off-label use: BD | ||||
| Golimumab | RA, AS, PsA, UC | |||
| Certolizumab | RA, AS, psoriasis, PsA, CD | |||
| IL-1 | IL-1R antagonist | Anakinra | RA, CAPS | Kawasaki disease (NCT04656184) |
| Off-label use: AOSD, sJIA, gout, recurrent pericarditis, and many others | ||||
| IL-1R1-IgG Fc | Rilonacept | CAPS, DIRA, recurrent pericarditis | ||
| Off-label use: AOSD, gout, and many others | ||||
| Anti-IL-1β mAb | Canakinumab | AOSD, sJIA, CAPS, TRAPS, HIDS/MKD, FMF | COVID19-associated CRS (12) | |
| Off-label use: gout and many others | ||||
| IL-6 | Anti-IL-6 mAb | Sirukumab | RA (13,14)* | |
| Olokizumab | RA (15) (NCT02760407, NCT02760433, NCT03120949) | |||
| Clazakizumab | RA (NCT02015520) | |||
| PsA (16) | ||||
| COVID19-associated CRS (NCT04343989) | ||||
| Siltuximab | CAR-T-associated CRS (NCT04975555) | |||
| Anti-IL-6R mAb | Tocilizumab | RA, sJIA, pJIA, SSc-associated ILD, Giant cell arteritis, CRS | PMR (NCT02908217) | |
| Off-label use: AOSD, Takayasu arteritis | NMOSD (17) | |||
| COVID19 pneumonia (18,19) (NCT04409262) | ||||
| Sarilumab | RA | COVID19-associated CRS (20) (NCT04315298) | ||
| Vobarilizumab | RA (NCT02518620) | |||
| IL-17 | Anti-IL-17 mAb | Ixekizumab | Psoriasis, PsA, axial SpA | |
| Secukinumab | AS, Psoriasis, PsA | SLE (NCT04181762) | ||
| Axial SpA (21) (NCT04156620, NCT04732117) | ||||
| Hiradenitis supprativa (NCT03713619, NCT03713632, NCT04179175) | ||||
| Giant cell arteritis (NCT04930094) | ||||
| Grave’s ophthalmopathy (NCT03713619) | ||||
| Anti-IL-17R mAb | Brodalumab | Psoriasis | Axial SpA (22) | |
| PsA (23) | ||||
| SSc (NCT03957681) | ||||
| Anti-IL17A/F mAb | Bimekizumab | AS (NCT03928743) | ||
| Axial SpA (NCT03928704, NCT04436640) | ||||
| Psoriasis (24,25) (NCT03598790, NCT03766685) | ||||
| PsA (NCT03895203, NCT03896581, NCT04009499, NCT04109976) | ||||
| Hiradenitis suppruativa (NCT04242446, NCT04242498, NCT04901195) | ||||
| IL-23 | Anti-p40 mAb | Ustekinumab | Psoriasis, PsA, UC, CD | Idiopathic inflammatory myositis (NCT03981744) |
| Takayasu arteritis (NCT04882072) | ||||
| Anti-p19 mAb | Guselkumab | Psoriasis, PsA | UC (NCT04033445) | |
| CD (NCT03466411, NCT04397263) | ||||
| Risankizumab | Psoriasis | PsA (26,27) | ||
| UC (NCT03398135, NCT03398148) | ||||
| CD (NCT03104413, NCT03105102, NCT03105128, NCT04524611) | ||||
| Tildrakizumab | Psoriasis | PsA (NCT03552276, NCT04314544, NCT04314531, NCT04991116) | ||
| Mirikizumab | Psoriasis (NCT03482011, NCT03535194, NCT03556202) | |||
| UC (NCT03518086, NCT03519945, NCT03524092) | ||||
| CD (NCT03926130, NCT04232553) | ||||
| Type 1 IFN | Anti-IFNR1 mAb | Anifrolumab | SLE |
This table includes drugs with one or more approved indications for autoimmune diseases. The indication covers only the area of autoimmune diseases.
pJIA, polyarticular juvenile idiopathic arthritis; UC, ulcerative colitis; CD, Crohn’s disease; BD, Behcet’s disease; sJIA, systemic juvenile idiopathic arthritis; DIRA, deficiency of IL-1 receptor antagonist; TRAPS, TNF receptor associated periodic syndrome; HIDS/MKD, hyperimmunoglobulin D syndrome/Mevalonate kinase deficiency; FMF, familial Mediterranean fever; CRS, cytokine release syndrome; CAR-T, chimeric Ag receptor-T cell; SSc-associated ILD, systemic sclerosis-associated interstitial lung disease, PMR, polymyalgia rheumatica, NMOSD, neuromyelitis optica spectrum disorder; axial SpA, axial spondyloarthritis.
*Despite positive results in phase III clinical trials, FDA did not recommend sirukumab for treatment of RA due to safety issues.