|
| Agent | Mechanism of action | Molecular target | Clinical phase of completed clinical trials | Clinical phase of ongoing clinical trials | Major outcomes/Safety profile | Future prospects |
|
| Belimumab | BLyS inhibition | BLyS (soluble) | III [19, 20, 27] | III, IV | Significantly higher SRI-4 response at week 52 in three major phase III clinical trials than placebo. Positive impact on immunological parameters. | ++
(approved in EU and US as for the use in non-renal SLE as add-on therapy) |
|
| Tabalumab | BLyS/APRIL inhibition | BLyS (soluble and membrane-bound) | III [38, 39] | - | No significant benefits over placebo (SRI-5). Slightly higher proportion of responders compared to placebo in post hoc analysis using SRI-4. | +/-
(studies were discontinued) |
|
Blisibimod
| BLyS/APRIL inhibition | BLyS (soluble and membrane-bound) | III [43] | - | No significant clinical benefits. Beneficial biological effects. | +/- |
|
| Atacicept | BLyS/APRIL inhibition | BLyS, APRIL | IIb [49] | - | Slightly better SRI-4 response in patients with low-to-moderate disease activity compared to placebo. High risk of infective complications. | +/- |
|
Abetimus sodium
| B cell tolerance induction | Anti-dsDNA antibody-producing B cells/circulating anti-dsDNA antibodies | II/II, III [53, 54] | - | Promising results in phase II/III clinical trials. No efficacy in phase III clinical trials. | +/- |
|
Rituximab
| B cell depletion | CD20 | III [62, 63] | II, III
(including LN) | Primary end points in clinical trials not reached. Large number of reports and recommendations confirming its efficacy in certain subsets of patients. | + |
|
Ocrelizumab
| B cell depletion | CD20 | III [85] | - | Clinical trials prematurely terminated due to increased risk of adverse events. | - |
|
Ofatumumab
| B cell depletion | CD20 | Case series [87, 88] | - | Reduction of disease activity and anti-dsDNA antibody titres. Normalization of C3 complement component. | + |
|
Obinutuzumab
| B cell depletion | CD20 | Preclinical studies [93] | II (LN) | B cell depletion at least 2-fold more efficient than rituximab. | + |
|
Epratuzumab
| B cell signaling modulation | CD22 | III [102] | - | Lack of clinical efficacy. Favorable safety profile. | - |
|
Rontalizumab
| Type I interferon inhibition | IFNα | II [119] | - | No general superiority over placebo. Significant benefit in low IFN signature group. | +/- |
|
| Sifalimumab | Type I interferon inhibition | IFNα | IIb [122] | - | Better SRI-4 response in high IFN signature group. | +
(studies were discontinued) |
|
Anifrolumab
| Type I interferon inhibition | IFNAR1 | IIb [126] | III (several trials including LN) | Better SRI-4 response in high IFN signature group. | + |
|
Tocilizumab
| Cytokine inhibition | IL-6 receptor | I [140] | - | Improvement in clinical parameters. Reduction of anti-dsDNA antibody titers. | + |
|
Sirukumab
| Cytokine inhibition | IL-6 | II (proof-of-concept) [142] | - | Lack of clinical efficacy. Frequent serious adverse events. | - |
|
Eculizumab
| Complement blockade | Monoclonal antibody against complement component C5 | I [149] | - | Short-lasting biological efficacy was noted only for higher doses. | - |
|
Ruplizumab/
Toralizumab | T cell costimulation blockade | CD40L | Open label/
I [151, 152] | - | Clinical trials were terminated due to thromboembolic complications. | - |
|
Dapirolizumab
| T cell costimulation blockade | CD40-CD40L | Ib [153] | III | Disease activity reduction (SRI-4, BICLA). | + |
|
Abatacept
| T cell costimulation blockade | CD28/CTLA4-CD80/CD86 | IIb, II/III [159, 160] | III (including LN) | No significant clinical benefits. Most beneficial in patients who had polyarthritis as the primary manifestation. Safe and well tolerated. | + |
|
