State of the Art REVIEW
Table 2 | Continued
No of patients Primary outcome measure
Agent (target)
Inclusion criteria
Result*
Reference
136
Evobrutinib (B TK)
SLEDAI >6 and seropositive
469
SRI(4)
PBO, 45.6%; evobrutinib 25 mg 55.7% (difference 10.0, odds ratio 1.55 (0.91-2.64), P=0.052); 75 mg 51.7% (difference 6.1, odds ratio 1.29 (0.76-2.18), P=0.1741; 100 mg 48.2%, difference 2.6, odds ratio 1.13 (0.67-1.93), P=0. 329) PBO 44%, fenebrutinib 51%, (P=0.37 )
13 7
Fenebrutinib (BTK)
SLEDAI >8 plus PGA >1 and seropositive
260
SRI(4)
BICLA dose-response association P= 0.07
Dapirolizumab (CD40 )
138
SLEDAI >6 plus BILAG >1A or >2B and seropositive
182
139
Filgotinib (JAK1) and lanraplenib (SYK)§
CLASI A score >10
47
Least squares mean change in CLASI A score
PBO −5.5 (standard error 2.56), filgotinib −8.7 (1.85), lanraplenib 4.5 (1.91)
14 0
Ustekinumab (interleukin 12/23)
SLEDAI >6 and seropositive
102
SRI(4)
PBO 33%, ustekinumab 62%, difference 28% (10–47), P=0.00 6
PBO 56%, ustekinumab 4 4%
1 41 142
SLEDAI >6 and seropositive SLEDAI >6 and seropositive
516 760
SRI(4) SRI(4)
Baricitinib (JAK1/2)
PBO 46%, baricitinib 4 mg 57% odds ratio 1.57 (1.09-2.27), P=0.016 PBO 46%, baricitinib 4 mg 47% odds ratio 1.07 (0.75-1.53), P=0.7 1 Least-squares mean (± standard error) change from baseline PBO 11.6±1.3, litifilimab 15.0±1.2, difference −3.4 joints (–6.7 to –0.2) P=0.0 4) Least squares mean (± standard error) per cent changes in CLASI A PBO –14.5±6.4, litifilimab 50 mg –38.8±7.5 150mg –47.9±7.5, 450 mg –42.5±5.5 PBO 35%, iberdomide 0.45mg 54%, adjusted difference, 19.4 (4.1 to 33.4); P=0.01) PBO 34.4%; deucravicitinib 3 mg BD 58.2% (odds ratio 2.8 (1.5-5.1, P<0.001); 6 mg BID 49.5% (odds ratio 1.9 (1.0-3.4, P=0.02); 12 mg daily 44.9%.
14 3
SLEDAI >6 and seropositive
775
SRI(4)
144
Litifilimab (BDCA2 )
>4 tender joints and >4 swollen joints and SLEDAI skin domain positive and seropositive
132
Change from baseline in the sum of the swollen and tender joint counts
145
132
Per cent change in CLASI A
146
Iberdomide (Cereblon-Ailois/ Ikaros)
SLEDAI >6 and seropositive
289
SRI(4)
147
Deucravicitinib (TYK2)
SLEDAI >6 plus BILAG >1A or >2B and seropositive
363
SRI(4)
PBO 89 months, abetimus 124 months 148
Abetimus (anti-dsDNA)
Renal flare within the past 4 years Active lupus nephritis on biopsy within 12 months, and UPCR >1.0
298 144
Renal flare
PBO 30.6%, rituximab 26.4 %
14 9
Rituximab (CD20)
Complete renal response (inactive urinary sediment and UPCR <0.5, normal or improved serum creatinine) Confirmed complete response (UPCR <0.26, inactive sediment, no loss of eGFR) Primary efficacy renal response (UPCR <0.7, eGFR within 20% of baseline, or >60 mL/min/1.7 3 m2) Complete renal response (UPCR <0.5, eGFR >60 mL/min/1.73 m 2 or <20% reduced from baseline Complete renal response (UPCR <0.5, eGFR >60 mL/min/1. 7 3m2 or <20% reduced from baseline Difference in mean change from baseline to week 52 in 24 hour UPCR Complete renal response (UPCR <0.5, normal renal function, inactive sediment)
150
Abatacept (CD28, via CTLA4 ) Active lupus nephritis class III or IV on biopsy within 12 months; if >3 months, also UPCR >0.44 and active sediment
298
PBO 20.0%, abatacept high dose 22.2%, abatacept lower dose 27.3%, PBO 32%, belimumab 43%, odds ratio 1.6 (1.0 to 2.3), P=0.0 3 PBO 19.3%, voclosporin low dose 32.6% (odds ratio 2.03 (1.01- 4.05); P=0.046), high dose 27.3% (odds ratio 1.59 (0.78-3.27); P=0.2024. PBO 23%, voclosporin 41.4%, OR 2·65; (1.64-4.27), P<0.0001 PBO 70%, anifrolumab 69%, geometric mean ratio 1.03 (0.62-1.71), P=0.905
15 1
Belimumab (BAFF)
Active lupus nephritis class III, IV, or V on biopsy within 6 months, UPCR >1.0, and eGFR >30 mL/min/1.7 3 m2 Active lupus nephritis class III, IV, +/- V on biopsy within 6 months, UPCR >1.5, eGFR >45 mL/min/1.73 m 2 Active lupus nephritis class III, IV, +/- V on biopsy within 24 months, UPCR >1.5, eGFR >45 mL/min/1. 7 3m2 Active lupus nephritis class III, IV +/- V on biopsy within 3 months, UPCR >1.0, and eGFR >35 mL/min/1.7 3 m2 Active lupus nephritis class III or IV on biopsy within 6 months, UPCR >1.0, and eGFR >30 mL/min/1. 7 3m2
448
152
Voclosporin (Calcineurin )
265
153
357
154
Anifrolumab (IFNAR)
147
15 5
Obinutuzumab (CD20)
125
PBO 23%, Obinutuzumab 35%, difference 12% (−3.4% to 28%), P=0.11 5
BAFF=anti-B cell activating factor; BICLA=BILAG-based composite lupus assessment; BILAG=British Isles lupus assessment group; CI=confidence interval; CLASI=cutaneous lupus area and severity index; DHEA=dehydroepiandrosterone; eGFR=estimated glomerular filtration rate; PBO=placebo, PGA=physician global assessment; PtGA=patient global assessment; SLAM=systemic lupus activity measure; SLEDAI=systemic lupus erythematosus disease activity index; SRI= systemic lupus erythematosus responder index; TYK2=tyrosine kinase 2; UPCR=urine protein creatinine ratio. *Results for primary outcome measure are shown as reported in the cited publication. Differences, odds ratios, and 95% confidence intervals are shown if reported. †Variations in SLEDAI versions used exist between studies; all are simply termed SLEDAI in this table. ‡Driven by a >4 point reduction in SLEDAI. §Studied in patients with active cutaneous lupus, with or without a diagnosis of systemic lupus erythematosus.
the bmj | BMJ 2023;383:073980 | doi: 10.1136/bmj-2022-073980
7
Powered by FlippingBook