Session Information
Session Type: ACR Late-breaking Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: The IL-12/23 pathway has been implicated in the pathogenesis of SLE. The anti-IL12/23 monoclonal antibody ustekinumab (UST) is efficacious in the treatment of psoriasis, psoriatic arthritis, and Crohn’s disease. Here, we evaluated the safety and efficacy of UST in patients (pts) with active SLE.
Methods: We conducted a phase 2, placebo (PBO)-controlled study in 102 adults with seropositive (ANA, anti-dsDNA, and/or anti-Smith antibodies) SLE by SLICC criteria and active disease (SLEDAI score ≥6 and ≥1 BILAG A and/or ≥2 BILAG B scores) despite standard-of-care therapy. Pts (n=102) were randomized (3:2) to receive UST IV ~6 mg/kg or PBO at wk0, followed by SC injections of UST 90mg q8w or PBO, both added to standard care; stratification factors were consent for skin biopsy (y/n), disease features, (eg, presence of lupus nephritis, baseline concomitant SLE medications, SLEDAI score), site/region, and race. The primary endpoint was the proportion of patients achieving SLE response index (SRI)-4 response at wk24. Major secondary endpoints at wk24 included change from baseline in SLEDAI-2K, change from baseline in Physician’s Global Assessment (PGA), and proportion of pts with BICLA response. Endpoint analyses included all pts who received ≥1 dose of study agent, had ≥1 measurement prior to administration, and had ≥1 post-baseline measurement. Patients with missing data and treatment failures were imputed as nonresponders.
Results: Baseline pt demographic and disease characteristics were well-balanced between treatment groups (female=91%; mean age=41 (18-66) years; mean SLEDAI-2K= 10.9). At wk24, 60% of pts in the UST group had an SRI-4 response vs 31% in the PBO group (p=0.0046), with a treatment effect favoring UST beginning at wk12. Pts in the UST group had greater median change from wk0 to wk24 in SLEDAI-2K and PGA vs PBO (Table). No difference was observed in the proportion of pts achieving a BICLA composite response at wk24, although among BICLA nonresponders, a greater proportion of UST pts had no BILAG worsening vs PBO. The risk of a new BILAG flare (≥1 new BILAG A or ≥2 new BILAG B) was significantly lower in the UST group vs. PBO (HR 0.11 [95% CI 0.01-0.94]; p=0.0078). UST demonstrated improvement in musculoskeletal and mucocutaneous disease features vs PBO. Improvements in anti-dsDNA and C3 levels were also noted through wk24 with UST. Through wk24, 78% of UST pts and 67% of PBO pts had ≥1 adverse event; 8.3% and 9.5%, respectively, had ≥1 serious adverse event (Table). There were no deaths in the study. Safety events were consistent with the UST safety profile in other studied indications.
Conclusion: UST showed significantly better efficacy in clinical and laboratory parameters in the treatment of active SLE compared with placebo, while demonstrating a comparable safety profile. UST may be an effective therapy with a novel mechanism of action in the treatment of SLE.
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Table. Efficacy and safety results at Week 24. |
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Placebo |
Ustekinumab |
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Patients randomized, n |
42 |
60 |
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Efficacy |
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Patients with SRI-4 response, n (%) |
13 (31.0) |
36 (60.0) |
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P value |
0.0046a |
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Change from baseline in SLEDAI-2K, median (range) |
-2.0 (-20; 10) |
-6.0 (-10; 3) |
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P value |
0.0265a,b |
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Change from baseline in PGA, median (range) |
-1.6 (-5.6; 2.7) |
-2.5 (-6.6; 2.8) |
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P value |
0.2110a,b |
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Patients with BICLA response, n (%) |
14 (33.3) |
21 (35.0) |
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P value |
0.9939a |
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Proportion of BICLA nonresponders with no BILAG worsening, n/N (%) |
11/28 (39.2) |
29/39 (74.4) |
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P value |
0.0043 |
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Patients with 50% improvement from baseline joint disease activityc, % (95% CI) |
63.2 (61.7-64.6) |
87.7 (86.8-88.6) |
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P value |
0.0208d |
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Patients with 50% improvement from baseline CLASI activity scored, % (95% CI) |
25.2 (23.1-27.4) |
58.7 (57.4-60.1) |
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P value |
0.0429e |
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Change from baseline in anti-dsDNA (kIU/L)f, median (range) |
-12.6 (-168.8; 233.1) |
-30.7 (-2919.6; 132.9) |
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P value |
0.1073h |
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Change from baseline in Complement C3 (mg/dL)g, median (range) |
0.15 (-12.4; 21.8) |
6.60 (-17; 50.8) |
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P value |
0.0636h |
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Adverse events |
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Patients with ≥1 TEAE, n (%) |
28 (66.7) |
47 (78.3) |
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Most Common TEAEs, n (%) |
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Upper respiratory tract infection |
9 (21.4) |
5 (8.3) |
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Urinary tract infection |
5 (11.9) |
6 (10.0) |
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Nasopharyngitis |
3 (7.1) |
6 (10.0) |
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Headache |
5 (11.9) |
4 (6.7) |
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Patients with ≥1 SAE, n (%) |
4 (9.5) |
5 (8.3) |
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aPrespecified analyses; all other analyses shown here were post-hoc. bOne-sided test for no difference between two treatment groups based upon a Wilcoxon non-parametric median test for difference of location cPatient subpopulation (67% of total population) with at least 4 joints with pain and signs of inflammation at baseline dPatient subpopulation (58% of total population) with CLASI activity score of at least 4 at baseline eProportions of responders and p values based on a modified intention to treat analysis using a multiple imputation model for missing data from weeks 16 to 24 fPatient subpopulation (42% of total population) with anti-dsDNA autoantibodies present at baseline gPatient subpopulation (41% of total population) with low Complement C3 levels present at baseline hOne-sided test for no difference between two treatment groups based upon a Wilcoxon non-parametric median test for difference of location BICLA, BILAG-based Combined Lupus Assessment; BILAG, British Isles Lupus Assessment Group; CLASI, Cutaneous Lupus Erythematosus Disease Area and Severity Index; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000; ; PGA, physician’s global assessment; SRI-4, SLE Response Index TEAE, treatment emergent adverse event |
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Disclosure: R. van Vollenhoven, Janssen Research & Development, LLC, 5; B. H. Hahn, BMS, Squibb, Janssen, 5; G. C. Tsokos, Janssen Research & Development, LLC, 5; C. Wagner, Janssen Research & Development, LLC, 3,Johnson & Johnson, 1; P. Lipsky, Janssen Research & Development, LLC, 5; B. Hsu, Johnson & Johnson, 1,Johnson & Johnson, 3; M. Chevrier, Johnson & Johnson, 1,Janssen Research Development LLC, 3; R. Gordon, Janssen Research & Development, LLC, 3,Johnson & Johnson, 1; M. Triebel, Janssen Biologics Europe, 3; S. Rose, Janssen Research & Development, LLC, 3,Johnson & Johnson, 1.
To cite this abstract in AMA style:
van Vollenhoven R, Hahn BH, Tsokos GC, Wagner C, Lipsky P, Hsu B, Chevrier M, Gordon R, Triebel M, Rose S. 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). https://acrabstracts.org/abstract/efficacy-and-safety-of-ustekinumab-an-interleukin-1223-inhibitor-in-patients-with-active-systemic-lupus-erythematosus-results-of-a-phase-2-randomized-placebo-controlled-study/. Accessed .« Back to ACR/ARHP Annual Meeting 2017
ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-ustekinumab-an-interleukin-1223-inhibitor-in-patients-with-active-systemic-lupus-erythematosus-results-of-a-phase-2-randomized-placebo-controlled-study/