Biologic |
Immunologic action |
Evidence to date in SLE |
Number of patients |
Inclusion criteria |
Primary outcome |
Therapeutic regime |
Results |
Future trials in SLE |
Inclusion criteria |
Primary outcome |
Therapeutic regime |
Prospects |
Ofatumumab |
B-cell depletion |
Case reports [3–5] |
1, 1 and a series of four patients |
– |
– |
Variable |
Reduction on disease activityAnti-dsDNA reduction and C3 normalization |
No trials ongoing |
– |
– |
– |
Promising, needs clinical studies |
Obinutuzumab |
B-cell depletion |
Pre-clinical [6] |
– |
– |
– |
– |
B-cell depletion 2-fold the rituximab |
Phase II ongoing on LN |
Class III or IV LN |
Complete Renal Response at week 52 |
1000 mg on days 1, 15, 168 and 182 plus MMF |
Promising, awaiting clinical results |
Ibrutinib |
BTK inhibition |
Pre-clinical [7] |
– |
– |
– |
– |
BTK inhibition on mature B-cell and APC |
No trials ongoing |
– |
– |
– |
Promising, needs clinical studies |
GDC-0853 |
BTK inhibition |
Pre-clinical and phase I [8] |
111 |
– |
– |
20, 60, 150 and 250 mg BID, and 500 mg QD |
BTK inhibition on mature B-cells |
Phase II ongoing |
Moderate to severe SLE |
SRI-4 response |
Low and high dose daily vsplacebo |
Promising, awaits results |
Rigerimod |
T-cell blockade |
Phase IIb [10, 11] |
149 |
ITT SLEDAI≥6 No BILAG A |
SRI-4 |
200 μg every 2 or 4 weeks |
Improvement in subpopulation SLEDAI≥6. Best results 200 μg every 4 weeks |
Phase III ongoing |
SLEDAI-2K ≥6 points |
SRI-4 response |
200 mcg every 4 weeks |
Very promising, awaits results |
Dapirolizumab |
T-cell co-stimulation blockade |
Phase Ib [15] |
24 |
SELENA-SLEDAI≥4 |
SRI-4 and BICLA |
First dose 30 mg/kg then five doses of 15 mg/kg every 2 weeks |
SRI-4 and BICLA response across several endpoints |
Phase II ongoing |
Moderate to severe disease activity |
BICLA response rate at week 24 |
Three different doses vsplacebo |
Promising, awaits results |
Rontalizumab |
IFNα blocker |
Phase II [18, 19] |
159 |
Moderate to severe disease activity |
BILAG |
750 mg every 4 weeks (part 1), 300 mg every 2 weeks (part 2) |
No general superiority; in low IFN signature it had significant superiority |
No trials ongoing |
– |
– |
– |
Dubious results |
Sifalimumab |
IFNα blocker |
Phase IIb [20] |
431 |
SLEDAI-2K≥6 |
SRI-4 |
200, 600, or 1200 mg every 28 days |
Better SRI-4 response in high IFN signature group |
No trials ongoing |
– |
– |
– |
Promising but not pursued |
Anifrolumab |
IFNα blocker |
Phase IIb [21] |
305 |
SLEDAI-2K≥6 |
Composite of SRI-4 and corticosteroids reduction |
300 or 1000 mg every 4 weeks |
Better SRI-4 response in high IFN signature group |
Several phase III including LN and skin lesions |
– |
– |
– |
Very promising, awaits results |
IFN-kinoid |
Induction of anti-IFNα antibodies |
I/II [22] |
28 |
Mild-to-moderate |
– |
30, 60, 120, or 240 μmg |
Dose-related response anti-IFNα.Higher C3 level |
Phase II trial ongoing |
SLEDAI-2K ≥ 6 |
BICLA response at week 36 |
– |
Promising, awaits results |
SM101 |
Autoimmune complexes blockade |
Phase IIa [23] |
51 |
SELENA-SLEDAI≥6 LN was included |
Safety, SRI-4 and BILAG |
6 and 12 mg/kg every week |
Better SRI-4 response |
No trials ongoing |
– |
– |
– |
Promising, needs clinical studies |
SM201 |
Autoimmune complexes blockade |
Pre-clinical [24] |
– |
– |
– |
– |
B-cell inhibition |
No trials ongoing |
– |
– |
– |
Very early to know |
Comments