Table 2.
A selection of clinical trials modifying cellular signalling and their endpoints of B cell-signalling targeted therapies for SLE.
| Targets | Biologicals | Trial/Phase | Country | Number Enrolled |
Primary Outcome |
Result |
|---|---|---|---|---|---|---|
| CD40/CD40L | Dapirolizumab | Phase IIb (NCT02804763) | Europe, Latin America, and North America. | 182 | Dose–response based on BICLA responder rates at week 24 | Did not meet the primary outcome but reduction in disease activity and severe flares was observed [98]. |
| IFNAR | Anifrolumab | TULIP–2, Phase III (NCT02446899) | 119 sites in 16 countries. | 362 | BICLA response at week 52 | Met the primary outcome [99]. |
| JAK1/3 | Tofacitinib | Phase I (NCT02535689) | USA. | 30 | Safety of tofacitinib in SLE subjects (time frame: 5 years) | A dose of tofacitinib (5 mg twice daily) is safe and well tolerated in SLE patients [100]. |
| JAK1/2 | Baricitinib | BRAVE I, Phase II (NCT02708095) | 78 centres in 11 countries in Asia, Europe, North America, and South America. | 314 | SLEDAI-2K arthritis or rash resolution at week 24 |
Met the primary outcome [101]. |
| TYK2 | Deucravacitinib | Phase II (NCT03252587) | 162 sites in 17 countries in Asia, Europe, North America, and South America. | 363 | SRI-4 response at week 32 | Met the primary outcome [102]. |
| BTK | Fenebrutinib | Phase II (NCT02908100) | 44 sites in 12 countries mainly in Latin America, the US, and Western Europe. | 260 | SRI-4 response at week 48 | Did not meet the primary outcome, but significantly reduced levels of CD19-positive B cells, including plasmablasts [103]. |
BICLA: BILAG-based Composite Lupus Assessment; BTK: protein tyrosine kinase BTK; IFNAR: type I interferon receptor; SLEDAI-2K: Systemic Lupus Erythematosus Disease Activity Index 2000; SRI-4: SLE Responder Index 4; TYK2: Tyrosine Kinase 2.