Artikel
Safety and Efficacy of ABT-494, a Novel Selective JAK1 Inhibitor, in Patients With Active Rheumatoid Arthritis: Results From 2 Phase 2b Studies
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Autoren
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Gerd-Rüdiger Burmester
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Josef Smolen
- Dept. of Internal Medicine III, Medical University Vienna, Wien, Österreich
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Michael E. Weinblatt
- Brigham and Women’s Hospital, Division of Rheumatology, Immunology and Allergy, Boston, United States of America
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Joel M. Kremer
- Albany Medical College, The Center for Rheumatology, Albany, United States of America
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Edward C. Keystone
- Mount Sinai Hospital, Rheumatology, Toronto, Canada
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Paul Emery
- University of Leeds, Leeds Institute of Molecular Medicine and LMBRU, Leeds, UK
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Mark C. Genovese
- Stanford University School of Medicine, Palo Alto, United States of America
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Sebastian Meerwein
- AbbVie Inc., North Chicago, USA
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Heidi S. Camp
- AbbVie Inc., North Chicago, USA
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Alan Friedman
- AbbVie Inc., North Chicago, USA
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Li Wang
- AbbVie Inc., North Chicago, USA
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Ahmed A. Othman
- AbbVie Inc., North Chicago, USA
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Nasser Khan
- AbbVie Inc., North Chicago, USA
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Aileen Pangan
- AbbVie Inc., North Chicago, USA
| Veröffentlicht: | 29. August 2016 |
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Gliederung
Text
Background: Two 12-week, randomized, phase 2b double blind studies characterized the safety and efficacy of ABT-494, a selective JAK1 inhibitor, in patients with moderate to severe RA and an inadequate response to methotrexate (MTX-IR; BALANCE-II; n=299) or TNF-α inhibitors (TNF-IR; BALANCE-I; n=276).
Methods: Patients were randomized equally to ABT-494 3, 6, 12, and 18 mg twice daily (BID), 24 mg once daily (QD; BALANCE-II only), or matching placebo. The primary efficacy endpoint in both studies was ACR20 response at Week 12.
Results: Baseline demographics were similar across groups. ACR20 and ACR50 response rates were significantly higher (P<0.05; non-responder imputation) with ABT-494 in studies BALANCE-II and BALANCE-I, respectively, at 6 and 12 mg BID, versus placebo (Table 1 [Tab. 1]). ACR70 response rates were significantly greater for all ABT-494 doses ≥6 mg BID (except 12 mg BID in BALANCE-II). Onset of action was rapid, with significant differences for ACR20 at Week 2 (P≤0.027) at all doses of ABT-494 in BALANCE-II and at doses ≥6 mg BID in BALANCE-I.
The proportion of patients with any adverse event (AE) was numerically higher with ABT-494 vs placebo in both studies (Table 2 [Tab. 2]). Most patients experienced only AEs considered mild by the investigator. Six cases of herpes zoster were observed across ABT-494 dose groups (1.3%) vs 2 cases in placebo (1.9%). There was 1 serious infection in one of the ABT-494 groups (BALANCE-II).
Dose-dependent increases in LDL- and HDL-cholesterol were observed with ABT-494; however, the LDL/HDL ratio remained constant. Liver function test elevations were sporadic, without clear dose dependence. Dose-dependent decreases in hemoglobin were seen but the mean hemoglobin levels were all within the normal range. Mean hemoglobin values remained stable or increased at lower doses (BALANCE-II), most notably in patients with elevated CRP at baseline.
No deaths occurred during the study periods. At post-treatment day 11 of BALANCE-II, a 79-year-old patient (40-year smoking history) in the 6-mg BID dose group was diagnosed with lung cancer and died 3 months later.
Conclusion: These phase 2b studies demonstrated the efficacy of ABT-494 versus placebo in MTX-IR or TNF-IR patients with active RA. ABT-494 had an acceptable safety and tolerability profile.
