Session Information
Session Type: ACR Plenary Session
Session Time: 11:00AM-12:30PM
Background/Purpose: Both the IL-12 and IL-23 pathways have been linked to SLE pathogenesis. The anti-IL-12/23 p40 monoclonal antibody ustekinumab (UST), which is approved for psoriasis, PsA, and Crohn’s disease, was evaluated in patients with active SLE. We previously reported greater improvement with UST vs PBO in several SLE disease measures through wk24.1 Results through 1 year are reported here.
Methods: We conducted a phase 2, PBO-controlled study in 102 patients with seropositive SLE, defined by SLICC criteria and active disease (SLEDAI score ≥6 and ≥1 BILAG A and/or ≥2 BILAG B scores). Patients were randomized (3:2) to UST (6 mg/kg single IV loading dose, then 90 mg SC q8w beginning at wk8) or PBO, added to standard care. At wk24, PBO patients crossed over to UST (90 mg SC q8w). The primary endpoint was the proportion of patients achieving SLE response index (SRI)-4 response at wk24. Modified intention-to-treat (mITT) analyses across SLE disease activity measures were performed to evaluate for maintenance of response with UST between wk24 and wk48. Safety was assessed through wk56.
Results: SRI-4 response rate was significantly greater (p=0.0057) in the UST group (61.7%) vs PBO group (33.3%) in the wk24 primary endpoint analysis and was sustained at 1 year (63.3%) in the UST group (Table 1). Rates of SLEDAI-2K (65% at wk24 vs 66.7% at 1 year), PGA (67.9% at wk24 vs 75% at 1 year), and active joint (86.5% at wk24 vs 86.5% at 1 year) responses were also sustained from wk24 to 1 year in the UST group (Table 1). CLASI response rate plateaued by wk28 (53.1% at wk24 vs 67.7% at wk28) and was maintained through 1 year in the UST group (68.6%) (Table 1). Among PBO patients who crossed over to UST at wk24 (n=33), 54.5% achieved an SRI-4 response at 1 year. Of UST-exposed patients, 81.7% had ≥1 TEAE, 15.1% had ≥1 SAE, and 7.5% had ≥1 serious infection through 1 year (Table 2). No deaths, malignancies, opportunistic infections, or tuberculosis cases were observed. Safety events were consistent with the known UST safety profile.
Conclusion: UST provided sustained clinical benefit in global and organ-specific SLE activity measures through 1 year, with a safety profile consistent with other indications. Thus, UST may be an effective therapy for SLE.
Reference: van Vollenhoven R, Hahn BH, Tsokos GC, et al. Efficacy and safety of ustekinumab, an interleukin 12/23 inhibitor, in patients with active systemic lupus erythematosus: results of a phase 2, randomized, placebo-controlled study [abstract]. Arthritis Rheumatol. 2017 ; 69 (Suppl 10).
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Table 1. Efficacy results at 24 weeks and 1 year in patients initially randomized to UST |
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UST |
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Week 24 |
Week 48 |
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Randomized patients (mITT) |
60 |
60 |
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SRI-4 responsea, n/randomized (%) |
37/60 (61.7) |
38/60 (63.3) |
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Improvement from baseline in SLEDAI-2K scoreb, n/randomized (%) |
39/60 (65.0) |
40/60 (66.7) |
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≥30% improvement from baseline in PGA, n/evaluablec (%) |
38/56 (67.9) |
39/52 (75.0) |
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≥50% improvement from baseline in the number of joints with pain and signs of inflammation, n/evaluablec,d (%) |
32/37 (86.5) |
32/37 (86.5) |
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≥50% improvement from baseline CLASI activity score, n/evaluablec,e (%) |
17/32 (53.1) |
24/35 (68.6) |
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aSRI-4 response was defined as a ≥4-point reduction in SLEDAI-2K total score, no new BILAG A and no more than 1 new BILAG B domain score, and no worsening (<10% increase) from baseline in the PGA of disease activity score bSLEDAI-2K response defined as ≥4-point improvement from baseline score cValues for patients meeting treatment failure criteria are set to missing from the point of treatment failure forward dPatient subpopulation (67% of total population) with ≥4 joints with pain and signs of inflammation at baseline ePatient subpopulation (60% of total population) with CLASI activity score of ≥4 at baseline CLASI, Cutaneous Lupus Erythematosus Disease Area and Severity Index; mITT, modified intention‑to‑treat; PBO, placebo; PGA, Physician Global Assessment; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000; SRI-4, SLE Responder Index-4; UST, ustekinumab; wk, week. |
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Table 2. Safety results at 24 weeks and 1 year |
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Placebo-controlled period through Week 24 |
Exposed to UST through 1 year |
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PBO |
UST |
Randomized to UST |
All UST |
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Treated patients |
42 |
60 |
60 |
93 |
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Patients with ≥1 TEAE |
29 (69.0) |
47 (78.3) |
54 (90.0) |
76 (81.7) |
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Patients with ≥1 SAE |
4 (9.5) |
5 (8.3) |
10 (16.7) |
14 (15.1) |
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Patients with ≥1 infectiona |
21 (50.0) |
29 (48.3) |
40 (66.7) |
56 (60.2) |
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Patients with ≥1 serious infectiona |
0 (0) |
2 (3.3) |
6 (10.0) |
7 (7.5) |
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Patients with ≥1 DCAE |
4 (9.5) |
4 (6.7) |
5 (8.3) |
6 (6.5) |
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All data are presented as n (%). aBased on infection system organ class DCAE, adverse event leading to discontinuation; PBO, placebo; PBO-UST, patients who crossed over from PBO to UST at wk24; SAE, serious adverse event; TEAE, treatment-emergent adverse event; UST, ustekinumab; wk, week. |
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To cite this abstract in AMA style:
van Vollenhoven R, Hahn BH, Tsokos GC, Wagner C, Lipsky P, Hsu B, Chevrier M, Gordon R, Lo KH, Triebel M, Fei K, Rose S. Efficacy and Safety of Ustekinumab, an Interleukin-12/23 Inhibitor, in Patients with Active Systemic Lupus Erythematosus: 1-Year Results of a Phase 2, Randomized Placebo-Controlled, Crossover Study [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/efficacy-and-safety-of-ustekinumab-an-interleukin-12-23-inhibitor-in-patients-with-active-systemic-lupus-erythematosus-1-year-results-of-a-phase-2-randomized-placebo-controlled-crossover-study/. Accessed .« Back to ACR/ARHP Annual Meeting 2018
ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-ustekinumab-an-interleukin-12-23-inhibitor-in-patients-with-active-systemic-lupus-erythematosus-1-year-results-of-a-phase-2-randomized-placebo-controlled-crossover-study/