Canakinumab relieves symptoms of acute flares and improves health-related quality of life in patients with difficult-to-treat Gouty Arthritis by suppressing inflammation: results of a randomized, dose-ranging study

Abstract

Introduction: We report the impact of canakinumab, a fully human anti-interleukin-1β monoclonal antibody, on inflammation and health-related quality of life (HRQoL) in patients with difficult-to-treat Gouty Arthritis.

Methods: In this eight-week, single-blind, double-dummy, dose-ranging study, patients with acute Gouty Arthritis flares who were unresponsive or intolerant to--or had contraindications for--non-steroidal anti-inflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg) (N = 143) or an intramuscular dose of triamcinolone acetonide 40 mg (N = 57). Patients assessed pain using a Likert scale, physicians assessed clinical signs of joint inflammation, and HRQoL was measured using the 36-item Short-Form Health Survey (SF-36) (acute version).

Results: At baseline, 98% of patients were suffering from moderate-to-extreme pain. The percentage of patients with no or mild pain was numerically greater in most canakinumab groups compared with triamcinolone acetonide from 24 to 72 hours post-dose; the difference was statistically significant for canakinumab 150 mg at these time points (P < 0.05). Treatment with canakinumab 150 mg was associated with statistically significant lower Likert scores for tenderness (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.27 to 7.89; P = 0.014) and swelling (OR, 2.7; 95% CI, 1.09 to 6.50, P = 0.032) at 72 hours compared with triamcinolone acetonide. Median C-reactive protein and serum amyloid A levels were normalized by seven days post-dose in most canakinumab groups, but remained elevated in the triamcinolone acetonide group. Improvements in physical health were observed at seven days post-dose in all treatment groups; increases in scores were highest for canakinumab 150 mg. In this group, the mean SF-36 physical component summary score increased by 12.0 points from baseline to 48.3 at seven days post-dose. SF-36 scores for physical functioning and bodily pain for the canakinumab 150 mg group approached those for the US general population by seven days post-dose and reached norm values by eight weeks post-dose.

Conclusions: Canakinumab 150 mg provided significantly greater and more rapid reduction in pain and signs and symptoms of inflammation compared with triamcinolone acetonide 40 mg. Improvements in HRQoL were seen in both treatment groups with a faster onset with canakinumab 150 mg compared with triamcinolone acetonide 40 mg.

Trial registration: clinicaltrials.gov: NCT00798369.

Figure 1

Study disposition. Number of patients who entered and completed the study and reasons for discontinuation.

Figure 2

Percentage of patients experiencing no or mild pain following administration of study medication. Pain assessments made using a 5-point Likert scale. *P < 0.05 for canakinumab 150 mg vs triamcinolone acetonide 40 mg. CI, confidence interval; LS, least-squares.

Figure 3

Reduction in joint inflammation following administration of study medication. Physician's assessment of joint tenderness in patients receiving canakinumab 150 mg (a) or triamcinolone acetonide (TA) 40 mg (b) and physician's assessment of joint swelling in patients receiving canakinumab 150 mg (c) or triamcinolone acetonide 40 mg (d). Physicians assessed inflammation in the target joint using the following tenderness and swelling scales: tenderness rated as none, 'no pain'; mild, 'pain'; moderate, 'pain and winces'; severe, 'pain; winces and withdraws'; and swelling rated as none, 'no swelling'; mild, 'palpable'; moderate, 'visible'; and severe, 'bulging beyond the joint margins'. Percentages are rounded to one unit therefore numbers at each time point do not necessarily add to 100. TA, triamcinolone acetonide.

Figure 4

Physician's and patient's global assessment of response and clinical signs of inflammation (72 hours post-dose).

Figure 5

Spidergrams showing HRQoL improvement (SF-36 scores): canakinumab 150 mg (A); triamcinolone acetonide 40 mg (B). Acute version 2 of SF-36, 36-item Short-Form Health Survey; HRQoL, health-related quality of life.