Treatment of rheumatoid arthritis patients with interleukin-1 receptor antagonists: Radiologic assessment

Objectives: The radiologic findings of a placebo-controlled, dose-ranging, multicenter, multinational trial have been reported previously. Radiographs were evaluated using the Larsen scoring method and Erosion Joint Count. Af ter completion of the study, a subset of the films was read again using a m odified Sharp score. This article will focus on the methodologies, scoring indices, and outcomes of the Larsen and Erosion Joint Count evaluations. Mo dified Sharp scores are presented in a separate article. Methods: A 6-month, phase II, randomized, double-blind, placebo-controlled trial was conducted involving 472 patients with active rheumatoid arthritis . Patients from 41 centers in 11 countries were randomly selected to receiv e 30 mg/d, 75 mg/d, or 150 mg/d of recombinant: human interleukin-1 recepto r antagonist (IL-1ra) subcutaneously daily or placebo. Radiographic criteri a were circulated to all centers, and the same 2 radiologists used the Lars en score and the Erosion Joint Count to score what was essentially a homoge neous film collection. At the completion of the study, a subset of radiogra phs also was read using the Genant-modified Sharp score. Patients in any of the treatment arms had the option of continuing in an extension trial for an additional 6 months, and those in the placebo arm had the option of bein g randomly placed into one of the treatment arms. Results: The Larsen and Erosion Joint Count data from these patients confir m that at 24 weeks, patients receiving placebo worsened by an average of 6. 49 Larsen units, whereas those receiving 30, 75, or 150 mg/d of IL-1ra wors ened by 3.53, 4.19, and 3.90 Larsen units, respectively. Overall, patients receiving therapy worsened by an average of 3.86 units, achieving statistic al significance versus placebo (P = .034). These data are not significantly different from those of the main trial. Mean values were ANOVA-adjusted fo r country and treatment-group interactions. Similarly, the Erosion Joint Co unt in placebo patients worsened by an average of 2.64, whereas those recei ving 30, 75, or 150 mg/d of IL-1ra worsened by 1.46, 1.05, and 1.70, respec tively. The overall therapy and 75 mg/d arm achieved significance versus pl acebo (P = .002 and P less than or equal to .001, respectively). Preliminar y data from the extension study indicate continuing benefit. Conclusions: Treatment with IL-1ra reduced the rate of joint deterioration and development of new bone erosions. Semin Arthritis Rheum 30:21-25 (Suppl 2). Copyright (C) 2001 by W.B. Saunde rs Company.