Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


AIN457 Shows a Good Safety Profile and Clinical Benefit in Patients with Active Rheumatoid Arthritis (RA) Despite Methotrexate Therapy: 16-Weeks Results From a Randomized Proof-of-Concept Trial

Tak1,  Paul P., Durez2,  P., Gomez-Reino3,  JJ., Wittmer4,  B., Chindalore5,  V., Di Padova6,  F., Wright6,  AM.

Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands
University of Louvain, Brussels, Belgium
University Clinical Hospital, Santiago de Compostela, Spain
Commonwealth Biomedical Research, Madisonville, KY
Pinnacle Research Group, Anniston, AL
Novartis Pharma AG, Basel, Switzerland

Purpose:

AIN457 is a fully human IgG1k monoclonal anti-IL17 antibody that selectively neutralizes IL-17A. IL-17 is overexpressed in synovial tissues in RA and preclinical studies support that IL-17A is a key driver of synovial inflammation and degradation of cartilage and bone. This study explores IL-17A blockade with AIN457 as a novel therapeutic approach to RA. The objective is to determine the safety, tolerability and initial evidence of clinical efficacy of AIN457 in patients with active RA despite methotrexate (MTX) therapy up to 16 weeks.

Method:

This was a multicenter, randomized, double blind, parallel-group study. A total of 52 patients with active RA received either, 2 doses of 10 mg/kg AIN457 (N=26) three weeks apart or placebo (N=26). All patients were followed up to 16 weeks. This abstract expands on the previously reported 6-week results to include secondary endpoints and response rates up to 16 weeks.

Results:

Patients characteristics at baseline were comparable between AIN457 and placebo groups (mean age 49.9 vs 49.8 yrs, median disease duration 3.9 vs. 2.9 yrs; median weekly MTX dose 15 mg vs. 12.5 mg, mean DAS28 score 5.88 vs. 5.84, mean tender joint count 17.6 vs. 17.1, mean swollen joint count 11.6 vs. 11.1, median C-reactive protein (CRP) 7.6 vs. 9.8 mg/L). AIN457 was well tolerated and has a favorable consistent PK profile with a long elimination half life of 23 days. Adverse event types and incidence rates were comparable between the groups, with a slightly higher frequency in the AIN457 group (81%vs. 65%). The overall rate of infections was identical in the AIN457 and placebo group (9 events [35%] in each). No cases of neutropenia or immunogenicity were reported. Exploratory analysis showed that a greater percentage of patients treated with AIN457 2×10mg/kg achieved an ACR20 response over 16 weeks compared to placebo [P=0.08] (Table 1). Both ACR50 and ACR70 rates showed numerical improvements with AIN457 compared to placebo. DAS28 assessment showed greater reductions with AIN457 2×10mg/kg compared to placebo over the16-weeks period (EULAR response rates are shown in Table 1). AIN457 induced fast onset of response and sustained reductions in CRP levels through week 16 (Figure 1). This was paralleled by improvements in the patient global assessment (PGA) (Figure 2) and HAQ scores.

Table 1. Rates of ACR and DAS28-based EULAR response in the treatment groups

 AIN457 10mg/kg (N=26)Placebo (N=26)
Weeks since dosingACR20ACR50ACR70ACR20ACR50ACR70
1614 (54%)7 (27%)2 (8%)8 (31%)4 (15%)0 (0%)
 AIN457 10mg/kg (N=26)Placebo (N=26)
Weeks since dosingNoneModerateGoodNoneModerateGood
1610 (38%)8 (31%)8 (31%)16 (62%)5 (19%)5 (19%)

Figure 1. Geometric mean (+/-SE) CRP concentrations over time in the treatment groups.

Figure 2. The mean (+/-SE) patient global assessment score over time in the treatment groups

Conclusion:

The good safety, rapid onset and encouraging efficacy of AIN457 suggest a novel therapeutic concept with the potential for improved patient outcomes. These positive results support development of AIN457 in RA and potentially other immune-mediated disorders.

To cite this abstract, please use the following information:
Tak, Paul P., Durez, P., Gomez-Reino, JJ., Wittmer, B., Chindalore, V., Di Padova, F., et al; AIN457 Shows a Good Safety Profile and Clinical Benefit in Patients with Active Rheumatoid Arthritis (RA) Despite Methotrexate Therapy: 16-Weeks Results From a Randomized Proof-of-Concept Trial [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1922
DOI: 10.1002/art.26995

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