Table 1.
Pharmaceuticals with direct or indirect impact on B cells currently used or trialed for systemic lupus erythematosus.
| Drug name | Mechanism of action | Phase | Main results | References |
|---|---|---|---|---|
| B cell depleting agents | ||||
| Epratuzumab | Humanized anti-CD22 | III | Primary endpoint not met | Clowse et al. (55) |
| Obinutuzumab | Humanized anti-CD20 | II | Primary and secondary endpoints met | Furie et al. (56) |
| Ocrelizumab | Humanized anti-CD20 | III | Primary endpoint not met | Mysler et al. (53) |
| Ofatumumab | Fully human anti-CD20 | R-L | Well-tolerated; reduced proteinuria | Haarhaus et al. (58) |
| R-L | Well-tolerated; safe; efficacy implied | Masoud et al. (59) | ||
| Rituximab | Chimeric anti-CD20 | II/III | Primary and secondary endpoints not met | Merrill et al. (30) |
| III | Primary endpoint not met | Rovin et al. (31) | ||
| B cell survival factor inhibitors | ||||
| Atacicept | Blocks BAFF and APRIL | II/III | Serious infections; terminated | Ginzler et al. (89) |
| Belimumab | Fully human anti-BAFF | III | Superiority over placebo | Navarra et al. (10) |
| III | Superiority over placebo | Furie et al. (11) | ||
| III | Superiority over placebo | Stohl et al. (73) | ||
| III | Superiority over placebo | Zhang et al. (72) | ||
| III/IV | Primary endpoint not met | D'Cruz et al. (77) | ||
| Blisibimod | Inhibits soluble and membrane-bound BAFF | IIb | 200 mg weekly superior over placebo | Furie et al. (90) |
| III | Primary endpoint not met | Merrill et al. (91) | ||
| Tabalumab | Human monoclonal antibody binding soluble and membrane-bound BAFF | III | Primary endpoint not met | Isenberg et al. (92) |
| III | 120 mg every 2 weeks superior over placebo | Merrill et al. (93) | ||
| Terminal stage B cell immunomodulators | ||||
| Bortezomib | Proteasome inhibitor | II | Frequent adverse reactions | Ishii et al. (109) |
| R-L | Efficacy implied | Alexander et al. (107) | ||
| R-L | Efficacy implied | Sjöwall et al. (108) | ||
| B cell depletion and survival factor inhibition combined | ||||
| Rituximab and belimumab | Chimeric anti-CD20 and fully human anti-BAFF | II | Recruitment completed | Jones et al. (115) |
| III | Recruitment completed | Teng et al. (116) | ||
| II | No benefit of add-on belimumab to rituximab and | Aranow et al. (117) | ||
| cyclophosphamide; LN | ||||
| IIa | NET formation reduced; LN | Kraaij et al. (118) | ||
| II | Recruiting; LN | NCT03747159 | ||
| Agents with indirect impact on B cells | ||||
| Anifrolumab | Fully human anti-IFNAR | III | Primary endpoint not met | Furie et al. (126) |
| III | Superiority over placebo | Morand et al. (127) | ||
| Rontalizumab | Humanized anti-IFN-α | II | Primary endpoint not met | Kalunian et al. (124) |
| Sifalimumab | Fully human anti-IFN-α | IIb | Superiority over placebo | Khamashta et al. (123) |
This table summarizes key clinical trials and observational studies of pharmaceuticals used or trialed for systemic lupus erythematosus, which directly or indirectly impact on B cells. Observational real-life studies are provided when clinical trial data are not available or scarce.
APRIL, a proliferation-inducing ligand; BAFF, B cell activating factor belonging to the tumor necrosis factor family; IFN, interferon; IFNAR, type I IFN receptor; LN, lupus nephritis; NET, neutrophil extracellular trap; R-L, real-life.