State of the Art REVIEW
Table 2 | Trials of novel treatments for systemic lupus erythematosus and lupus nephritis. Products highlighted in green have received regulatory approval for use in systemic lupus erythematosus or lupus nephritis
No of patients Primary outcome measure
Agent (target)
Inclusion criteria
Result*
Reference
117
DHEA/prasterone (sex hormones)
SLAM score >7
120
Mean change from baseline in SLAM score Quantitatively specified improvement of the principal severe lupus manifestation no clinical deterioration + improvement or stabilization in two disease activity measures (SLEDAI†, SLAM) and 2 quality of life measures (PtGA and Krupp Fatigue Severity Scale). Major clinical response (BILAG C scores or better in all organs without severe flare) Proportion of patients with a new BILAG defined flare Per cent change in SELENA–SLEDAI score and time to first mild/moderate or severe flare
DHEA -2.6 +/- 3.4; PBO 2.0 +/- 3.8
118
Severe active lupus
21
DHEA 7/9 patients versus PBO 4/10 patients (P< 0.10)
119
SLAM score >7 or SLEDAI >2
381
DHEA 51.3%; PBO 42.2% (P=0.074).
Rituximab 15.9%, PBO 12.4%; P=0.97 5 120
Rituximab (CD20)
>1 BILAG A or >2 BILAG B score
257
121
Abatacept (CD28, via CTLA4) BILAG defined active polyarthritis discoid lesions or pleuritis/pericarditis 118
Abatacept 79.7%, PBO 82.5%; (treatment difference –3.5 (95% CI 15.3 to 8.3) Belimumab −19.5% + 2.7 versus PBO: −17.2% + 5 .1 Belimumab 58%, PBO 44%, odds ratio 1.83 (1.30 to 2.59), P=0·0006. Belimumab 43.2% versus PBO 33.5%; P=0.017 No difference between treatment arms (numerical results not reported) PBO 21% versus epratuzumab 200 mg/mo (30.8%), 800 mg/mo (26.3%), 2400 mg/mo 43.2%; P=0.148. PBO 34.1%, 1200 mg every other week 39.8% (P=0.175 versus placebo), and epratuzumab 600 mg every week 37.5% (P=0.442 ) PBO 33.5%, 1200 mg every other week 34.1% (P=0.899 versus placebo), and epratuzumab 600 mg every week 35.2% (P=0.716) PBO 29.3%, 120 mg Q2W 31.8% and 120 mg Q4W 35.2% (P>0.05) PBO 27.7%, 120 mg Q2W 38.4% (=0.002), 120 mg Q4W 34.8% (p=0.051 ) PBO 44.0%, atacicept 75 mg 57.8% (adjusted odds ratio 1.78; 95% CI 1.01 to 3.12), P=0.045, atacicept 150 mg 53.8% (adjusted PBO 35.3%, blisibimod 37.2%, P=0.635 PBO 42.3%, blisibimod 46.9%, P=0.35 2 PBO 41.8%, rontalizumab 45.5%, P=0.60 PBO 45.4%, sifaljmumab 200 mg 58.3% (P=0.057), 600 mg 56.5% (P=0.094), 1200 mg 59.8% (P=0.0 31) PBO 17.6%, anifrolumab 300 mg 34.3%, odds ratio 2.38 (1.33–4.26), P=0.014; anifrolumab 1000 mg 28.8%, odds ratio 1.94 (1.08–3.49), P=0.0 63 PBO 40%, anifrolumab 300 mg 36%; difference −4.2 (95% CI −14.2 to 5.8), P=0·41 PBO 31.5%, anifrolumab 300 mg 47.8%, adjusted difference 16.3 (6.3 to 26.3); P=0. 001 odds ratio 1.56; 95% CI 0.89 to 2.72), P=0.121
1 22
Belimumab (BAFF)
SLEDAI >4
449
123
SLEDAI >6 and seropositive
867
SRI(4)‡
124
SLEDAI >6 and seropositive
819
SRI(4)
125
Edratide (hCDR1)
SLEDAI 6-12
340
Reduction in SLEDAI 2K and adjusted mean SLEDAI 2K
126
Epratuzumab (CD22)
>1 BILAG A or >2 BILAG B and SLEDAI >6 >1 BILAG A or >2 BILAG B and SLEDAI K >6 and seropositive
227
BICLA
12 7
793
BICLA
127
>1 BILAG A or >2 BILAG B and SLEDAI K >6 and seropositive
791
BICLA
128
Tabalumab (BAFF)
SLEDAI >6 and seropositive
1164 SRI(5)
12 9
SLEDAI >6 and seropositive
1124 SRI(5)
130
Atacicept (BAFF/APRIL )
SLEDAI >6 and seropositive
306
SRI(4)
131
Blisibimod (BAFF)
SLEDAI >6 and seropositive
547
SRI(5)
13 2
SLEDAI >10 and seropositive
442
SRI(6)
133
Rontalizumab (interferon alfa )
>1 BILAG A or >2 BILAG B and seropositive
238
Reduction in all BILAG A to B or less, and/or B to C or less
Sifalimumab (interferon alfa) SLEDAI >6 and >1 BILAG A or >2 BILAG B and PGA >1 and seropositive 432
134
1 35
Anifrolumab (IFN AR)
SLEDAI >6 plus BILAG >1A or >2B plus PGA >1 and seropositive
307
SRI(4) plus glucocorticoid taper
113
SLEDAI >6 plus BILAG >1A or >2B plus PGA >1 and seropositive SLEDAI >6 plus BILAG >1A or >2B plus PGA >1 and seropositive
457
SRI(4)
112
362
BICLA
( Continued )
6
doi: 10.1136/bmj-2022-073980 | BMJ 2023;383:073980 | the bmj
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