Dataset Information

ACCLAIM: A randomized trial of abatacept (CTLA4-Ig) for relapsing-remitting multiple sclerosis.

ABSTRACT:

Background

Costimulatory blockade of T lymphocytes with the CTLA4-Ig fusion protein abatacept could be an effective treatment for the immune-mediated neuroinflammatory disease relapsing-remitting multiple sclerosis (RRMS).

Objective

To evaluate efficacy and safety of abatacept in RRMS.

Methods

ACCLAIM (A Cooperative Clinical Study of Abatacept in Multiple Sclerosis) was a Phase II, randomized, double-blind, placebo-controlled, multi-center trial. In all, 65 of 123 planned participants with RRMS were randomized to monthly intravenous infusions of abatacept or placebo for 24 weeks in a 2:1 ratio, switched to the opposite treatment at 28 weeks, and received their final dose of study medication at 52 weeks. Enrollment was closed early due to slow accrual. The primary endpoint was the mean number of new gadolinium-enhancing (Gd+) lesions obtained on magnetic resonance imaging (MRI) scans performed every 4 weeks.

Results

No statistically significant differences were observed in mean number of new Gd+ MRI lesions between the abatacept and placebo groups. No statistically significant differences were observed in other MRI and clinical parameters of RRMS disease activity. Abatacept was well tolerated.

Conclusion

The ACCLAIM study did not demonstrate efficacy of abatacept in reducing the number of new Gd+ MRI lesions, or clinical measures of disease activity in RRMS.

SUBMITTER: Khoury SJ

PROVIDER: S-EPMC5288398 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

ACCLAIM: A randomized trial of abatacept (CTLA4-Ig) for relapsing-remitting multiple sclerosis.

Khoury Samia J SJ Rochon James J Ding Linna L Byron Margie M Ryker Kristin K Tosta Patti P Gao Wendy W Freedman Mark S MS Arnold Douglas L DL Sayre Peter H PH Smilek Dawn E DE

Multiple sclerosis (Houndmills, Basingstoke, England) 20160805 5

<h4>Background</h4>Costimulatory blockade of T lymphocytes with the CTLA4-Ig fusion protein abatacept could be an effective treatment for the immune-mediated neuroinflammatory disease relapsing-remitting multiple sclerosis (RRMS).<h4>Objective</h4>To evaluate efficacy and safety of abatacept in RRMS.<h4>Methods</h4>ACCLAIM (A Cooperative Clinical Study of Abatacept in Multiple Sclerosis) was a Phase II, randomized, double-blind, placebo-controlled, multi-center trial. In all, 65 of 123 planned p ...[more]

PMID: 27481207

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Project description:For almost three decades in many countries azathioprine has been used to treat relapsing-remitting multiple sclerosis. However its efficacy was usually considered marginal and following approval of ? interferons for this indication it was no longer recommended as first line treatment, even if presently no conclusive direct ? interferon-azathioprine comparison exists. To compare azathioprine efficacy versus the currently available ? interferons in relapsing-remitting multiple sclerosis, a multicenter, randomized, controlled, single-blinded, non-inferiority trial was conducted in 30 Italian multiple sclerosis centers. Eligible patients (relapsing-remitting course; ? 2 relapses in the last 2 years) were randomly assigned to azathioprine or ? interferons. The primary outcome was annualized relapse rate ratio (RR) over 2 years. Key secondary outcome was number of new brain MRI lesions. Patients (n = 150) were randomized in 2 groups (77 azathioprine, 73 ? interferons). At 2 years, clinical evaluation was completed in 127 patients (62 azathioprine, 65 ? interferons). Annualized relapse rate was 0.26 (95% Confidence Interval, CI, 0.19-0.37) in the azathioprine and 0.39 (95% CI 0.30-0.51) in the interferon group. Non-inferiority analysis showed that azathioprine was at least as effective as ? interferons (relapse RRAZA/IFN 0.67, one-sided 95% CI 0.96; p<0.01). MRI outcomes were analyzed in 97 patients (50 azathioprine and 47 ? interferons). Annualized new T2 lesion rate was 0.76 (95% CI 0.61-0.95) in the azathioprine and 0.69 (95% CI 0.54-0.88) in the interferon group. Treatment discontinuations due to adverse events were higher (20.3% vs. 7.8%, p = 0.03) in the azathioprine than in the interferon group, and concentrated within the first months of treatment, whereas in the interferon group discontinuations occurred mainly during the second year. The results of this study indicate that efficacy of azathioprine is not inferior to that of ? interferons for patients with relapsing-remitting multiple sclerosis. Considering also the convenience of the oral administration, and the low cost for health service providers, azathioprine may represent an alternative to interferon treatment, while the different side effect profiles of both medications have to be taken into account.EudraCT 2006-004937-13.

Dataset Information

ACCLAIM: A randomized trial of abatacept (CTLA4-Ig) for relapsing-remitting multiple sclerosis.

Background

Objective

Methods

Results

Conclusion

Publications

ACCLAIM: A randomized trial of abatacept (CTLA4-Ig) for relapsing-remitting multiple sclerosis.

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