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Abstract
Background ABT-494 is a novel selective JAK1 inhibitor.
Objectives The safety, efficacy, and dose response of ABT-494 were characterized vs placebo (PBO) in patients (pts) with moderately to severely active RA and an inadequate response to ≥1 anti-TNF biologic therapy (TNF-IR).
Methods This was a phase 2b, 12-week, double-blind PBO-controlled study; TNF-IR pts receiving stable background methotrexate (MTX) were randomized 1:1:1:1:1 to ABT-494 3, 6, 12, and 18 mg twice daily (BID) or matching PBO. The primary efficacy endpoint was the proportion of pts who achieved an ACR20 response at week 12.
Results All 276 pts had failed ≥1 anti-TNF therapy prior to enrollment; 28% had received ≥2 anti-TNF biologics and 20% had also received non–anti-TNF biologics. Baseline (BL) characteristics were similar in all treatment groups. The proportion of pts achieving ACR20 at week 12 was significantly higher for all ABT-494 groups vs PBO (Table 1). There was a significant (P<0.01) dose response between PBO and all ABT-494 treatment groups for ACR20 response rates (non-responder imputation) at week 12. ACR50 and ACR70 responses were statistically significantly higher at doses of ≥6 mg BID. Changes in DAS28(CRP) from BL were significantly greater for all doses of ABT-494 vs PBO. Onset of action was rapid, with significant differences in ACR20 and change in DAS28(CRP) from BL at week 2 (P≤0.007) for 6, 12, and 18 mg BID vs PBO. Low disease activity and clinical remission per DAS28(CRP) criteria were achieved statistically significantly more often in the 12-mg BID dose group vs PBO. The incidences of AEs were numerically higher in ABT-494 dose groups, with some trend towards dose dependency (Table 2). The majority of infections were mild. There was one serious infection (“bronchiectasis”) in the PBO group and none in the ABT-494 treatment groups were reported. Five pts had non-serious events of herpes zoster: 1 pt each in the ABT-494 3 mg, 12 mg, and 18 mg BID treatment groups, and 2 pts in the PBO group. One pt in the 6-mg BID dose group reported 2 events of non-melanoma skin cancer (basal cell and squamous cell carcinomas). There was 1 report of anemia in the 18-mg BID dose group. No deaths were reported during the study.
Conclusions This phase 2b study demonstrated the clinical efficacy of ABT-494 vs PBO when dosed in combination with MTX in TNF-IR pts with active RA. ABT-494 had an acceptable safety and tolerability profile.
Acknowledgement The design, study conduct, analysis, and financial support of the clinical trial (NCT01960855) were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the content. All authors had access to all relevant data. Mariana Ovnic and Michael J. Theisen of Complete Publication Solutions, LLC, provided medical writing support paid for by AbbVie. This presentation contains information on the investigational product ABT-494.
Disclosure of Interest J. M. Kremer Shareholder of: Corrona, Grant/research support from: AbbVie, Lilly, Novartis, and Pfizer, Consultant for: AbbVie, Lilly, Pfizer, Medimmune, Sanofi, and Regeron, Employee of: Corrona, E. C. Keystone Grant/research support from: AbbVie and Lilly, Consultant for: AbbVie and Lilly, Speakers bureau: AbbVie and Lilly, P. Emery Grant/research support from: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Lilly, and Takeda, Consultant for: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Lilly, and Takeda, H. S. Camp Shareholder of: AbbVie, Employee of: AbbVie, A. Friedman Shareholder of: AbbVie, Employee of: AbbVie, L. Wang Shareholder of: AbbVie, Employee of: AbbVie, A. A. Othman Shareholder of: AbbVie, Employee of: AbbVie, N. Khan Shareholder of: AbbVie, Employee of: AbbVie, S. Jungerwirth Shareholder of: AbbVie, Employee of: AbbVie