Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Gouty arthritis (GA) is a chronic inflammatory disease. Targeting the inflammatory pathway through IL-1β inhibition with canakinumab (CAN) may provide significant long-term benefits. CAN safety versus triamcinolone acetonide (TA) over initial 24 weeks (blinded study) for patients (pts) with history of frequent attacks (≥3 in year before baseline) was reported earlier from core (β-RELIEVED [β-REL] and β-REL-II) and first extension (E1) studies1. Herein we present full 18-month long-term CAN safety data, including open-label second extension (E2) studies.
Methods:
GA pts completing β-REL E1 and β-REL-II E1 studies1 were enrolled in these 1-year, open-label, E2 studies. All pts entering E2, whether randomized to CAN or TA, received CAN 150 mg sc on demand upon new attack. Data are presented only for pts randomized to CAN, and are reported cumulatively, i.e. including corresponding data from previously reported core and E1 studies. Long-term safety outcomes and safety upon re-treatment are presented as incidence rate per 100 patient-years (pyr) of study participation for AEs and SAEs. Deaths are reported for all pts (randomized to CAN or TA). Selected predefined notable laboratory abnormalities are shown (neutrophils, platelets, liver and renal function tests). Long-term attack rate per year is also provided.
Results:
In total, 69/115 (60%) and 72/112 (64.3%) of the pts randomized to CAN in the two core studies entered the two E2 studies, of which 68 and 64 pts, respectively completed the E2 studies. The 2 study populations had differing baseline comorbidity and geographic origin. Lab data (not time adjusted) for neutropenia appears worse after retreatment in β-REL E2, and deterioration of creatinine clearance appears worse after retreatment (Table 1). The time-adjusted incidence rates for AEs were 302.4/100 pyr and 360/100 pyr, and for SAEs were 27.9/100 pyr and 13.9/100 pyr in β-REL E2 and β-REL-II E2 respectively (Table 1). The time-adjusted incidence rates of any AEs, infection AEs, any SAEs, and selected SAEs before and after re-treatment are presented in Table 1. Incidence rates for AEs and SAEs declined after re-treatment, with the exception of SAEs in β-REL-II E2, which increased from 2.9/100 pyr to 10.9/100 pyr (no infection SAEs after retreatment in β-REL-II E2, and other SAEs fit no special pattern). In the total safety population (N=454, core and all extensions), there were 4 deaths, 2 in the core studies previously reported1 and 2 during the β-REL E2 study (one patient in the CAN group died from pneumonia; one patient in the TA group who never received CAN died of pneumococcal sepsis). None of the deaths was suspected by investigators to be study drug related. The mean rates of new attacks per year on CAN were 1.21 and 1.18 in β-REL E2 and in β-REL-II E2.
Conclusion:
The clinical safety profile of CAN upon re-treatment was maintained long-term with no new infection concerns.
1. Schlesinger N, et al. Ann Rheum Dis (2012).
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TABLE 1
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Time-adjusted AEs*/SAEs*
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β-RELIEVED E2
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β-RELIEVED-II E2
|
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Randomized to CAN* 150 mg sc (N=113)** |
Randomized to CAN* 150 mg sc (N=112) |
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All CAN (N=113) |
Retreated with CAN (N=69)
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All CAN (N=112)
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Retreated with CAN (N=62)
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Before
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After
|
Before
|
After
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AEs and SAEs
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All values: n (IR/100 pyr)
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Any AEs
|
336 (302.4)
|
136 (400.1) |
112 (224.3) |
388 (360.0)
|
127 (370.0) |
163 (354.8) |
|
Infections |
55 (49.5)
|
23 (67.7) |
21 (42.0) |
51 (47.3)
|
17 (49.5) |
21 (45.7) |
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Any SAEs
|
31 (27.9)
|
10 (29.4) |
13 (26.0) |
15 (13.9)
|
1 (2.9) |
5 (10.9) |
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Individual system organ class with IR/100 pyr >2.0 in any column |
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Cardiac disorders |
5 (4.5)
|
1 (2.9) |
2 (4.0) |
2 (1.9)
|
0 |
1 (2.2) |
|
Eye disorders |
2 (1.8)
|
2 (5.9) |
0 |
0
|
0 |
0 |
|
Infections & infestations |
3 (2.7)
|
2 (5.9) |
1 (2.0) |
3 (2.8)
|
1 (2.9) |
0 |
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Metabolism & nutrition dis. |
2 (1.8)
|
1 (2.9) |
1 (2.0) |
1 (0.9)
|
0 |
1 (2.2) |
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Muskuloskeletal & connective tissue disorders
|
2 (1.8)
|
2 (5.9) |
0 |
2 (1.9)
|
0 |
0 |
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Neoplasms benign, malignant & unspecified (incl cysts & polyps)
|
1 (0.9)
|
0 |
1 (2.0) |
1 (0.9)
|
0 |
1 (2.2) |
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Nervous system disorders |
5 (4.5)
|
1 (2.9) |
4 (8.0) |
4 (3.7)
|
0 |
2 (4.4) |
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Renal & urinary disorders |
5 (4.5)
|
1 (2.9) |
3 (6.0) |
0
|
0 |
0 |
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Laboratory results, notable abnormalities (not time-adjusted)
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All values: n (%)
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Neutrophils (<1.0 109/L)†
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5 (4.4)
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2 (2.8) |
2 (2.9) |
5 (4.5)
|
1 (1.6) |
5 (8.1) |
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Platelets (<75.0 109/L)† |
0 |
0 |
0 |
0 |
0 |
0 |
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ALT (≥5xULN) † |
0 |
0 |
0 |
1 (0.9) |
0 |
1 (1.6) |
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AST (≥5xULN) † |
0 |
0 |
0 |
1 (0.9) |
0 |
1 (1.6) |
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Total bilirubin (≥2xULN if ALT and/or AST ≥3 x ULN) † |
0 |
0 |
0 |
0 |
0 |
0 |
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Serum creatinine (≥3xULN)†
|
1 (0.9) |
0 (0) |
0 (0) |
1 (0.9) |
1 (1.6) |
1 (1.6) |
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Creatinine clearance (≥25% decrease from baseline) † |
21 (19.3) |
7 (10.4) |
13 (19.4) |
19 (17.0) |
5 (8.1) |
10 (16.1) |
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* Primary system organ class; CAN: canakinumab; IR/100 pyr: incidence rate per 100 patient-years ** 2/115 pts were misrandomized and thus excluded from analysis (only 113 analyzed) † Newly occurring or worsening notably abnormal values (not time-adjusted) |
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Disclosure:
A. So,
Novartis Pharmaceutical Corporation,
5,
Novartis Pharmaceutical Corporation,
8,
Menarini,
8,
Ardea Biosciences,
5;
R. Alten,
Novartis Pharmaceutical Corporation,
2,
Novartis Pharmaceutical Corporation,
5,
Novartis Pharmaceutical Corporation,
8;
H. R. Schumacher,
Takeda,
5,
Novartis Pharmaceutical Corporation,
5,
Ardea,
5,
Xoma Corporation ,
5,
Regeneron,
5,
Savient,
5,
Pfizer Inc,
5;
M. Bloch,
Novartis Pharmaceutical Corporation,
2;
T. Bardin,
Menarini,
2,
Novartis Pharmaceutical Corporation,
5,
Ipsen,
5,
Menarini,
5,
Ardea,
5,
Biocryst,
5;
M. R. John,
Novartis Pharma AG,
3,
Novartis Pharma AG,
1;
G. Krammer,
Novartis Pharma AG,
3,
Novartis Pharma AG,
1;
J. M. Nebesky,
Novartis Pharma AG,
3;
A. Tao,
Novartis Pharmaceutical Corporation,
3;
N. Schlesinger,
Novartis Pharmaceutical Corporation,
2,
Novartis Pharmaceutical Corporation,
5,
URL Pharma,
5,
Savient,
5,
Takeda,
5,
Rx Enzyme,
5,
Novartis Pharmaceutical Corporation,
8,
Takeda,
8,
Savient,
8.
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