A Randomized Double-Blind Trial of Abatacept and Glucocorticoids for the Treatment of Giant Cell Arteritis

Carol A. Langford¹, David Cuthbertson², Steven R. Ytterberg³, Nader A. Khalidi⁴, Paul A. Monach⁵, Simon Carette⁶, Philip Seo⁷, Larry W. Moreland⁸, Michael Weisman⁹, Curry L. Koening¹⁰, Antoine G. Sreih¹¹, Robert F. Spiera¹², Carol McAlear¹³, Kenneth J. Warrington¹⁴, Christian Pagnoux⁶, Kathleen Maksimowicz-McKinnon¹⁵, Lindsy J. Forbess¹⁶, Gary S. Hoffman¹, Renee Borchin¹⁷, Jeffrey Krischer¹⁷ and Peter A. Merkel¹⁸, ¹Rheumatology, Cleveland Clinic, Cleveland, OH, ²Biostatistics and Informatics, Department of Pediatrics, University of South Florida, Tampa, FL, ³Rheumatology Division, Mayo Clinic, Rochester, MN, ⁴McMaster University, St Joseph's Healthcare Hamilton, Hamilton, ON, Canada, ⁵Rheumatology, Boston University School of Medicine, Boston, MA, ⁶Division of Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, ⁷Division of Rheumatology, Johns Hopkins, Baltimore, MD, ⁸Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, ⁹Cedars-Sinai Medical Center, Los Angeles, CA, ¹⁰Division of rheumatology, George E. Wahlen Department of Veterans Affairs Medical Center Salt Lake City and University of Utah, University of Utah School of Medicine, Salt Lake City, UT, ¹¹Department of Rheumatology, University of Pennsylvania, Philadelphia, PA, ¹²Rheumatology, Hospital for Special Surgery, New York, NY, ¹³Penn Vasculitis Center, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, ¹⁴Rheumatology, Mayo Clinic, Rochester, MN, ¹⁵Rheumatology, University of Pittsburgh, Pittsburgh, PA, ¹⁶Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, ¹⁷University of South Florida, Tampa, FL, ¹⁸Division of Rheumatology, University of Pennsylvania, Philadelphia, PA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: October 27, 2015

Keywords: Abatacept, giant cell arteritis, Late-Breaking 2015, randomized trials, treatment and vasculitis

Session Information

Date: Tuesday, November 10, 2015

Title: ACR Late-breaking Abstract Poster Presentations

Session Type: ACR Late-breaking Abstract Session

Session Time: 9:00AM-11:00AM

Background/Purpose: Giant cell arteritis (GCA) is a large-vessel primary systemic vasculitis. Although glucocorticoids are effective in treating GCA, they are associated with substantial toxicity and relapse of vasculitis occurs in a high percentage of patients. T-cell activation has been implicated in the pathophysiology of GCA. A multi-center, randomized, double-blind, placebo-controlled, withdrawal design trial was conducted to examine the efficacy and safety of treatment with abatacept (CTLA4-Ig) combined with prednisone in patients with GCA.

Methods: Patients with newly diagnosed or relapsing GCA were eligible for the trial. All patients were treated with abatacept 10 mg/kg IV on days 1, 15, 29, and week 8, together with prednisone. At week 12 patients in remission underwent a double-blinded randomization to continue monthly abatacept or be switched to placebo. Patients in both study arms received prednisone according to a standardized taper schedule that reached discontinuation of prednisone at week 28. Patients remained on their randomized assignment until meeting criteria for early termination or until the common closeout date, 12 months after enrollment of the last patient. The primary endpoint was duration of remission (relapse-free survival, RFS). A planned sample size of 30 or more patients was based on detecting a 30% improvement in RFS utilizing a one-sided alpha = 0.1. Kaplan-Meier curves were constructed and differences in treatment arms compared using the log-rank test in an intent-to-treat analysis.

Results: 49 eligible patients with GCA received study drug with 41 reaching the week 12 randomization. Disease characteristics of the 41 randomized patients are outlined in Table 1.

The RFS at 12 months was estimated to be 48% for those receiving abatacept and 31% for those receiving placebo (p=0.049), Figure 1. A longer median duration of remission was seen with abatacept compared to placebo (abatacept 9.9 months, placebo 3.9 months). Covariate analysis examining those variables that differed between study arms did not impact the results.

129 adverse events occurred in 35 patients, including 23 serious adverse events in 15 patients. There was no difference in the frequency or severity of adverse events between treatment arms, including the rate of infection.

Conclusion: In patients with GCA the addition of abatacept to a standard treatment regimen with prednisone reduced the risk of relapse of vasculitis and was not associated with a higher rate of toxicity compared to prednisone alone. This study provides the first trial-level evidence of a targeted immunomodulatory therapy that has demonstrated efficacy for the treatment of GCA.

Disclosure: C. A. Langford, Bristol-Myers Squibb, 2,Genentech and Biogen IDEC Inc., 2,GlaxoSmithKline, 2; D. Cuthbertson, None; S. R. Ytterberg, Bristol-Myers Squibb, 2; N. A. Khalidi, Bristol-Myers Squibb, 2,GlaxoSmithKline, 2,Roche Pharmaceuticals, 2,Roche Pharmaceuticals, 9,Bayer, 2; P. A. Monach, Bristol-Myers Squibb, 2,Genentech and Biogen IDEC Inc., 2; S. Carette, Bristol-Myers Squibb, 2; P. Seo, Bristol-Myers Squibb, 2; L. W. Moreland, Bristol-Myers Squibb, 2; M. Weisman, Bristol-Myers Squibb, 2; C. L. Koening, Bristol-Myers Squibb, 2,Roche Pharmaceuticals, 2; A. G. Sreih, Bristol-Myers Squibb, 2,Genentech and Biogen IDEC Inc., 2,GlaxoSmithKline, 2,Chemocentryx, 2,Celgene, 2; R. F. Spiera, Bristol-Myers Squibb, 2,Genentech and Biogen IDEC Inc., 2,Roche Pharmaceuticals, 2; C. McAlear, Bristol-Myers Squibb, 2; K. J. Warrington, Bristol-Myers Squibb, 2,Roche Pharmaceuticals, 2; C. Pagnoux, Bristol-Myers Squibb, 2,Roche Pharmaceuticals, 5,Genzyme Corporation, 5,GlaxoSmithKline, 5,Roche Pharmaceuticals, 2,Roche Pharmaceuticals, 8,Bristol-Myers Squibb, 8,EuroImmune, 2,EuroImmune, 8,Terumo-BCT, 2,Terumo-BCT, 8; K. Maksimowicz-McKinnon, None; L. J. Forbess, Bristol-Myers Squibb, 2,Roche Pharmaceuticals, 2,Chemocentryx, 2,Genentech and Biogen IDEC Inc., 2; G. S. Hoffman, Roche Pharmaceuticals, 5,Sanofi-Aventis Pharmaceutical, 5,Regeneron, 5,Ardea Biosciences, 5,Prothena, 5; R. Borchin, None; J. Krischer, Bristol-Myers Squibb, 2; P. A. Merkel, Bristol-Myers Squibb, 2,Actelion Pharmaceuticals US, 2,Celgene, 2,Chemocentryx, 2,Genentech and Biogen IDEC Inc., 2,GlaxoSmithKline, 2,Actelion Pharmaceuticals US, 5,Alexion Pharmaceuticals, Inc., 5,Chemocentryx, 5,Genentech and Biogen IDEC Inc., 5,Genzyme Corporation, 5,GlaxoSmithKline, 5,Sanofi-Aventis Pharmaceutical, 5.

To cite this abstract in AMA style:

Langford CA, Cuthbertson D, Ytterberg SR, Khalidi NA, Monach PA, Carette S, Seo P, Moreland LW, Weisman M, Koening CL, Sreih AG, Spiera RF, McAlear C, Warrington KJ, Pagnoux C, Maksimowicz-McKinnon K, Forbess LJ, Hoffman GS, Borchin R, Krischer J, Merkel PA. A Randomized Double-Blind Trial of Abatacept and Glucocorticoids for the Treatment of Giant Cell Arteritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/a-randomized-double-blind-trial-of-abatacept-and-glucocorticoids-for-the-treatment-of-giant-cell-arteritis/. Accessed .

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