A Randomized, Double‐Blind Trial of Abatacept (CTLA‐4Ig) for the Treatment of Takayasu Arteritis

Abstract

Objective To compare the efficacy of abatacept to placebo for the treatment of Takayasu’s arteritis (TAK). Methods In this multicenter trial, patients with newly-diagnosed or relapsing TAK were treated with abatacept 10 mg/kg IV on days 1, 15, 29, week 8, together with prednisone. At week 12, patients in remission underwent a double-blinded randomization to continue monthly abatacept or switch to placebo. Patients in both study arms received a standardized prednisone taper, reaching 20 mg daily at week 12 with discontinuation of prednisone at week 28 and remained on their randomized assignment until meeting criteria for early termination or until 12 months after enrollment of the last patient. The primary endpoint was duration of remission (relapse-free survival). Results Thirty-four eligible patients with TAK were enrolled and treated with prednisone and abatacept; 26 reached the week 12 randomization and underwent a blinded randomization to abatacept or placebo. The relapse-free survival at 12 months was 22% for those receiving abatacept and 40% for those receiving placebo (p= 0.853). Treatment with abatacept in patients with TAK enrolled in this study was not associated with a longer median duration of remission (abatacept 5.5 months, placebo 5.7 months). There was no difference in the frequency or severity of adverse events between treatment arms, including infection. Conclusions In patients with TAK the addition of abatacept to a treatment regimen with prednisone did not reduce the risk of relapse.

Takayasu arteritis: challenges in diagnosis and management

“…This was a negative trial which did not show any difference in relapse-free survival among patients randomised to abatacept or placebo after having achieved remission with prednisone and abatacept 43. Despite the negative results, this trial highlights important elements necessary to run a successful trial of a rare vasculitis: a multicentre, collaborative approach, a predetermined definition of disease activity, blinded assessment of relapse, protocol-driven imaging schedule to assess for asymptomatic progression of arterial disease 43.…”

“…This was a negative trial which did not show any difference in relapse-free survival among patients randomised to abatacept or placebo after having achieved remission with prednisone and abatacept 43. Despite the negative results, this trial highlights important elements necessary to run a successful trial of a rare vasculitis: a multicentre, collaborative approach, a predetermined definition of disease activity, blinded assessment of relapse, protocol-driven imaging schedule to assess for asymptomatic progression of arterial disease 43. In 2009, the European League Against Rheumatism34 developed recommendations for the management of large-vessel vasculitis to include the following: early initiation of corticosteroid therapy for induction of remission, use of immunosuppressive agents as adjunctive therapy, clinical monitoring of therapy with inflammatory markers as supportive data and revascularisation to be performed in expert centres during the quiescent phase of disease 34…”

Review: What Is the Current Evidence for Disease Subsets in Giant Cell Arteritis?

“…However, side effects are frequently encountered with long‐term glucocorticoid treatment in elderly patients with GCA . Recently, novel targeted treatments have emerged as potent alternatives for maintenance of glucocorticoid‐free disease remission in patients with GCA .…”

“…Various clinical and immunologic factors have been linked to the risk of cranial ischemic symptoms, relapse rates, and overall glucocorticoid requirements in patients with GCA. Immunologic heterogeneity in GCA is further suggested by outcomes of recent trials with anti–interleukin‐6 receptor (anti–IL‐6R) and CTLA‐4Ig therapy, because these targeted treatments are not effective in all GCA patients . Taken together, these findings indicate that there may be distinct categories of GCA patients.…”

Development of a Core Set of Outcome Measures for Large-vessel Vasculitis: Report from OMERACT 2016

“…In particular, four major clinical trials examining the role of various biologic medicines are of interest: A randomized trial of abatacept for the treatment of LVV (36, 37), a phase 2 randomized trial of tocilizumab in GCA (18) and TAK (38), a phase III randomized trial of tocilizumab in GCA (GiACTA) (39), and a phase III randomized trial of sirukumab in GCA (SIRRESTA; ClinicalTrials.gov Identifier: NCT02531633). Other investigational drugs are being explored for the treatment of LVV such as uztekinumab (NCT02955147), baricitinib (NCT03026504), and anakinra (NCT02902731).…”