Supplement Article |
PP13. PHASE II STUDY OF THE SAFETY AND EFFICACY OF INFLIXIMAB IN GIANT CELL ARTERITIS (GCA): 22 WEEK INTERIM ANALYSIS
1 Cleveland Clinic Foundation, Cleveland, OH, USA, 2 Hospital Clinic Provincial Internal Medicine, Barcelona, Spain, 3 Emory University, Atlanta, GA, USA, 4 Johns Hopkins Vasculitis Center, Baltimore, MD, USA, 5 Arcispedale Santa Maria Nuova, Reggio Emila, Italy, 6 Boston University School of Medicine, Boston, MA, USA, 7 Centocor, Inc. Malvern, PA, USA
Background: Although GCA is responsive to glucocorticoids (GCS), therapy causes significant toxicity and often fails to induce sustained remission.
Purpose: Assess safety and efficacy of infliximab (IFX) in patients (pts) with new onset GCA in a randomized, double-blind, placebo-controlled, multi-center, Phase II study.
Methods: Eligibility: diagnosis of GCA (ACR criteria); GCA of 
4 weeks (wks) duration; resolution of GCA features and normal ESR following treatment with 40–60 mg prednisone or prednisolone/day; remission for 1 wk prior to randomization. Exclusions: absence of infection, malignancies within 5 years, congestive heart failure and advanced disease of critical organs. Treatment randomization: 1:2 ratio, to receive infusions of placebo or IFX 5 mg/kg, respectively, at wks 0, 2, 6, 14, 22, 30, 38, 46. All pts received GCS on a specified tapering schedule with starting dose between 40–60 mg/day. Visits: every 4 wks, through 54 wks; interim analyses at wk 22. Primary endpoints: proportion of relapse-free patients through wk 22 and safety (frequency and types of adverse events). Relapse definition: rise in ESR, normal to 
40 mm; and one of following (i) 1 or more specified features of GCA; and (ii) any other features of GCA not attributable to any other cause and a concomitant increase in dose of GCS. Secondary endpoints included: (i) proportion of relapse-free patients at week 54; (ii) time to 1st relapse; and (iii) cumulative dose of GCS.
Results: 44 pts were randomized (placebo, n = 16, IFX, n = 28) at 22 centers in 5 countries. Mean age in both groups (gps) was 71.0 years (range: 50–93). Baseline features between gps were comparable except for gender (placebo 31.3% males vs. IFX 14.3% males); fever (placebo 50.0% vs. IFX 17.9%) and visual impairment (placebo 31.3% vs. IFX 7.1%). More IFX-treated pts had positive temporal artery biopsies (66.7 placebo vs. IFX 92.3%). Efficacy was evaluated using cumulative data from 22 wks follow up. There were no differences between gps in regard to: (1) proportion of pts remaining relapse-free (50% placebo vs. 43% IFX, p = 0.651), (2) cumulative doses of GCS therapy (placebo mean±SD = 3117±971 mg vs. IFX = 3051±770 mg, p = NS) and (3) among pts who had 1st relapse, days to 1st relapse (placebo median = 84.5, IFX median = 96.5, p = NS). There was 1 case of heart failure in an IFX-treated pt. Infections were infrequent and limited to upper respiratory tract (12.5% placebo vs. 14.3% IFX).
Conclusions: In this elderly population of pts with newly diagnosed GCA, IFX 5 mg/kg every 8 weeks, was well-tolerated, but during 22 weeks of treatment did not reduce number of 1st relapses or cumulative GCS dosage.