Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Effect of IL-1 Inhibition with Canakinumab Compared to Triamcinolone Acetonide on Pain Intensity and New Flares in Gouty Arthritis Patients with Chronic Kidney Disease Stage 25.

Sunkureddi1,  P., Bardin2,  T., Alten3,  R., Schlesinger4,  N., Bloch5,  M., Kiechle6,  T., Krammer6,  G.

Clear Lake Rheumatology Center, Nassau Bay, TX
Hôpital Lariboisière, Paris, France
Charité Teaching Hospital–Schlosspark-Klinik, Berlin, Germany
UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ
Holdsworth House Medical Practice, Sydney, Australia
Novartis Pharma AG, Basel, Switzerland
Novartis Pharmaceutical Corporation, East Hanover, NJ
CHUV, Lausanne, Switzerland

Background/Purpose:

Most gouty arthritis (GA) patients have pre-existing comorbidities. Chronic kidney disease (CKD) is common and can limit treatment options due to intolerance and contraindications to available therapies. Canakinumab, a fully human monoclonal anti-IL-1b antibody, is a potential new therapeutic option for treating acute GA pain and delaying new flares in this difficult to treat GA patient population. Here, we report a post-hoc efficacy and safety analysis of pooled 24-week data from two pivotal Phase III studies (b-RELIEVED and b-RELIEVED-II) for a subgroup of GA patients with renal impairment.

Methods:

In two 12-week multicenter, double-blind, double-dummy, active controlled studies (b-RELIEVED, N=228; b-RELIEVED-II, N=226), patients aged >=18-<=85 yrs meeting ACR 1977 criteria for acute GA and contraindicated, intolerant or unresponsive to NSAIDs and/or colchicine received one single dose of canakinumab 150 mg sc or triamcinolone acetonide (TA) 40 mg im and were re-dosed "on demand" on each new flare, followed by a 12-week extension where study completers received canakinumab 150 mg sc or TA 40 mg im only "on demand" upon a new flare. Here, we report 24-week data in this renal impaired cohort for time to first new flare, pain intensity on visual analog scale (VAS) in most affected joint and safety.

Results:

A total of 380 (83.7%) patients had renal impairment (baseline estimated Glomerular Filtration Rate (eGFR) <90mL/min/1.73m2; corresponding to CKD stages 2–5): 188 (83.6%) in the canakinumab group and 192 (83.8%) in the TA group. At 24 weeks, significantly fewer patients on canakinumab experienced new flares vs those on TA (25.5% vs 47.4%, OR 0.38, 95% CI 0.25–0.59, p<0.0001). Mean VAS scores for the canakinumab group and TA group were 73.9mm vs 73.8mm at baseline, and 38.5mm vs 49.9mm 72 hours post dose (Diff: -10.9 mm; 95% CI: -16.1, -5.8, p<0.0001). This significant difference in pain relief was sustained up to 7 days (Table). 66.5% of patients had adverse events (AEs) with canakinumab vs 52.6% with TA. The most frequent canakinumab AEs were back pain and hypertension (n=10, 5.3% each), headache (n=9, 4.8%); whereas for TA they were hypertension (n=11, 5.7%), arthralgia (n=9, 4.7%), pain in the extremity and worsening of gout (n=8, 4.2 % each). Incidence of infections and infestations were comparable between canakinumab group (14, 7.4%) and TA group (14, 7.3%). There were no opportunistic infections. Serious AEs (canakinumab: n=15, 8%; TA: n=6, 3.1%) were not considered to be related to treatment by the investigator.

Table. Pooled analysis of pain intensity over 7 days post-dose in the CKD stages 2–5 patients

Time *BL6 hours12 hours24 hours48 hours72 hours4 days5 days6 days7 days
Pain intensity (0–100 mm VAS)Canakinumab 150mg sc73.9 (12.73)57.4 (1.40)50.1 (1.58)39.5 (1.78)30.6 (1.86)24.4 (1.84)21.9 (1.78)19.1 (1.76)17.2 (1.79)15.6 (1.72)
LS Mean (SE)TA 40mg im73.8 (12.64)61.3 (1.41)54.9 (1.60)48.1 (1.80)41.7 (1.88)35.3 (1.86)31.1 (1.80)28.4 (1.78)26.3 (1.81)21.8 (1.73)
LS Mean difference canakinumab vs TA, (mm)  -4*-4.7*-8.7*-11.1*-10.9*-9.2*-9.3*-9.1*-6.2*
95% confidence intervals  -7.9, -0.0-9.2, -0.3-13.6, -3.7-16.3, -5.9-16.1, -5.8-14.2, -4.2-14.3, -4.4-14.1, -4.1-11.0, -1.4
* Baseline pain scores are presented as mean±SD; TA, triamcinolone acetonide; *p value<=0.05, LS Mean difference, least square mean. difference; SE, standard error

Conclusion:

Renal impairment is a common comorbidity in GA patients. This post-hoc analysis of these two large clinical trials demonstrated that renal impairment (CKD stages 2–5) did not compromise the therapeutic efficacy and safety of canakinumab in this difficult to treat population.

To cite this abstract, please use the following information:
Sunkureddi, P., Bardin, T., Alten, R., Schlesinger, N., Bloch, M., Kiechle, T., et al; Effect of IL-1 Inhibition with Canakinumab Compared to Triamcinolone Acetonide on Pain Intensity and New Flares in Gouty Arthritis Patients with Chronic Kidney Disease Stage 25. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1020
DOI:

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