Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Treatment of Active Ankylosing Spondylitis with AbataceptAn Open Label 24-Week Study.

Song2,  In-Ho, Heldmann1,  Frank, Rudwaleit3,  Martin, Haibel2,  Hildrun, Weiss4,  Anja, Braun1,  Jurgen, Sieper2,  Joachim

Centre of Rheumatology, Herne, Germany
Charite Campus Benjamin-Franklin, Medical Clinic I, Rheumatology, Berlin, Germany
Charite Campus Benjamin-Franklin, Medical Clinic I, Rheumatology, Berlin, Germany
German Rheumatism Research Center, Berlin, Germany

Background:

An immunotherapy targeting T cells in ankylosing spondylitis (AS) might be of interest, given histological studies have shown T-cell clusters in facette joints and antigen-specific T cell response has been described in AS [1]. There is still an unmet medical need as some patients with AS may even not respond to anti-TNF agents.

Objective:

To explore prospectively the short term efficacy and safety of abatacept in patients either naïve or with an inadequate response (IR) to anti-TNF agents.

Methods:

In this open label (OL) pilot study, abatacept (10mg/kg) was administered intravenously on days 1, 15, 29 and every 28 days thereafter up to week 24 in 15 anti-TNF-naive patients (group 1) and 15 patients with IR to anti-TNF (group 2) with active AS. The primary end point was the proportion of patients with assessment of SpondyloArthritis international Society criteria (ASAS 40) in both groups at week 24 for which the likelihood of targeted minimum true response rates of 30% was investigated by estimating the 95% confidence interval [95% CI] of the observed response rates. Disease activity was assessed using ASAS and BASDAI responses, pain and CRP levels in the intent to treat population using LOCF analysis. Safety was assessed in patients who received at least 1 dose of OL abatacept.

Results:

Of 15 patients enrolled in group 1 and group 2 respectively, each 12 completed 24 weeks (withdrawals for inefficacy each 2 in group 1 and 2) and SAE (each 1 in group1 and 2). In group 1 and 2, baseline characteristics were: 60% and 73% of males, mean disease duration of 14.5 (SD 10.3) and 20.5 (SD 10.8) years; 100% and 93% HLA-B27 positive and mean age of 38.0 (SD 7.2) and 45.3 years (SD 9.8), respectively.

At week 24, 13.3%[2.4%; 38.4%] of patients in group1 and 0%[0%; 21.3%] of group 2 achieved ASAS 40 (Table). The upper limit of the 95% CI in group 1 but not in group 2 exceeded the pre-specified minimum true response rates of 30%. We found no change of T cell function in regards of interferon-gamma (IFN-gamma) (% of IFN-gamma positive cells out of CD4 positive cells after stimulation with phorbol myristate acetate (PMA) ionomycin 14.8% at screening and 13.1% at week 24) or interleukin-17 secretion (% of IL-17 positive cells out of CD4 positive cells after stimulation with PMA ionomycin 1.5% at screening and 0.9% at week 24) supporting that T cell function is not suppressed but only modulated. Overall, abatacept was well-tolerated with 5 serious events (SAEs), including 1 gastroenteritis. Three mild to moderate acute infusion reactions were reported. There was no death, opportunistic infection, malignancy or TB reported.

Conclusions:

In this pilot AS study, Abatacept was well tolerated. A major response was not observed in our study, but an efficacy cannot be excluded based on the limited sample size. Its short term therapeutic potential needs to be further evaluated.

Table: ASAS20/40/partial remission (PR) and BASDAI20/50 response rates in TNF-blocker naive and TNF-blocker failure patients at week 24

 TNF-blocker-naive patients (n=15)TNF-blocker failure patients (n=15)
ASAS2026.7%20.0%
ASAS4013.3%0%
ASAS PR6.7%0%
BASDAI2033.3%20.0%
BASDAI506.7%0%

1.Appel, H, et al. Arthritis Res Ther 2006;8(5)R143.

To cite this abstract, please use the following information:
Song, In-Ho, Heldmann, Frank, Rudwaleit, Martin, Haibel, Hildrun, Weiss, Anja, Braun, Jurgen, et al; Treatment of Active Ankylosing Spondylitis with AbataceptAn Open Label 24-Week Study. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1961
DOI: 10.1002/art.29726

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