Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Efficacy and safety of canakinumab (CAN), a selective, fully human, anti-interleukin-1β monoclonal antibody, in systemic juvenile idiopathic arthritis (SJIA) patients has been demonstrated in two phase 3 trials (1 and 2). 1 SJIA is associated with severe functional impairment and chronic pain that markedly affect the health-related quality of life (HRQoL). Here, we present the effects of CAN therapy on patient-reported outcomes (PROs) from the phase 3 studies.
Methods:
In Trial 1, 84 pts were randomized to CAN (43) and PBO (41) and followed for 1 month. In Trial 2, 177 pts (including 71 from Trial 1) received open label CAN in Part 1, of which 100 CAN-responders entered part 2 and were randomized 1:1 to placebo or continued CAN. PROs considered were functional ability by the Childhood Health Assessment Questionnaire [CHAQ©], pain as measured on a visual analog scale [VAS] of 0-100 mm, and HRQoL by the Child Health Questionnaire–Parent Form (CHQ-PF50 for pts age 5-18 yrs) with rating on physical (PhS) and psychosocial (PsS) health status. Between-treatment differences were evaluated using analysis covariance models with repeated measures adjusting for treatment group, time, stratification factors and the treatment group-by-time interaction as explanatory variables.
Results:
At the end of Trial 1, there was significant improvement (p=0.0002) in functional ability with CAN, resulting in an estimated difference (ED) in CHAQ score of -0.69 between the CAN and PBO group at Day 29 from baseline [BL]; this ED constitutes about 3.6x the minimal clinically important difference (-0.19) 2in the CHAQ score. Pain intensity significantly declined (both p <0.0001) in the CAN group vs. PBO both at Day 15 (ED, -46.42) and Day 29 (ED, -41.86). Similarly, HRQoL significantly improved from BL for CAN vs. PBO, with an ED in CHQ-PF50 PhS scores of 12.07 and 7.28 for the CHQ-PsS (both, p<0.005) over 1 month with CAN, respectively. Even more pronounced improvements in functional ability, pain and HRQoL were observed in Trial 2 (Table).
Patient Reported Outcomes in Trial 2
|
Outcome measure, mean (SD) |
Baseline CAN, N=177 |
End of Part 1 CAN, N=177 |
End of Part 2 CAN, N=50 |
End of Part 2 PBO*, N=50 |
|
CHAQ disability score |
1.7 (0.8) |
0.74 (0.9) |
0.5 (0.9) |
0.6 (0.8) |
|
Pain intensity by 0-100 mm VAS |
66.6 (23.3) |
20.2 (25.8) |
13.6 (26.9) |
17.0 (24.2) |
|
CHQ-PF50 PhS score |
16.1 (14.3) |
37.7 (17.2) |
43.6 (17.4) |
39.0 (18.1) |
|
CHQ-PF50 PsS score |
41.6 (11.1) |
50.7 (11.1) |
53.6 (11.3) |
52.7 (9.8) |
Note: Results are based on patients with both baseline and post-baseline values. n
Conclusion:
Treatment with CAN demonstrated rapid, marked and continued improvement in patient-reported outcome of SJIA patients, including a significant increase in functional ability, reduction of pain and HRQoL.
References
- Ruperto N, et al. N Engl J Med 2012;367(25):2396–406.
- Brunner HI, et al. J Clin Rheumatol 2005;32: 150–61.
Disclosure:
R. Schneider,
Hoffmann-La Roche, Inc.,
5,
Novartis Pharmaceutical Corporation,
5,
Innomar Strategies,
5;
H. Brunner,
Novartis, Genentech, Medimmune, EMD Serono, AMS, Pfizer, UCB, Jannsen,
5,
Genentech,
8;
N. Ruperto,
To Gaslini Hospital: Abbott, Astrazeneca, BMS, Centocor Research & Development, Eli Lilly and Company, “Francesco Angelini”, Glaxo Smith & Kline, Italfarmaco, Novartis, Pfizer Inc., Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuti,
2,
Astrazeneca, Bristol Myers and Squibb, Janssen Biologics B.V., Roche, Wyeth, Pfizer,
8;
N. Wulffraat,
Novartis, Pfizer, Roche,
5;
P. Quartier,
Abbvie, Chugai-Roche, Novartis, Pfizer,
2,
Abbvie, BMS, Chugai-Roche, Novartis, Pfizer, Servier, Sweedish Orphan Biovitrum,
5,
Chugai-Roche, Novartis, Pfizer,
8;
R. Brik,
Novartis,
2,
Novartis,
5;
L. McCann,
None;
H. E. Foster,
Pfizer, BioMarin,
2,
Pfizer Inc,
8;
M. Frosch,
None;
V. Gerloni,
None;
L. Harel,
None;
C. Len,
None;
K. Houghton,
None;
R. Joos,
None;
K. Abrams,
Novartis Pharmaceutical Corporation,
3,
Novartis,
1;
K. Lheritier,
Novartis Pharma AG,
3,
Novartis,
1;
S. Kessabi,
Novartis Pharma AG,
3;
A. Martini,
Abbott, Astrazeneca, Bristol Myers and Squibb, Janssen Biologics B.V., Ely Lilly and Company, “Francesco Angelini”, Glaxo Smith & Kline, Italfarmaco, Novartis, Pfizer Inc., Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals Inc.,
2,
Abbott, Astrazeneca, Bristol Myers and Squibb, Janssen Biologics B.V., Ely Lilly and Company, “Francesco Angelini”, Glaxo Smith & Kline, Italfarmaco, Novartis, Pfizer Inc., Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals Inc.,
5,
Astellas, Astrazeneca, Bristol Myers and Squibb, -Glaxo Smith & Kline, Italfarmaco , MedImmune, Novartis ,
8;
D. J. Lovell,
NIH ,
2,
Astra-Zeneca, Centocor, Jansen, Wyeth, Amgen, Bristol-Meyers Squibb, Abbott, Pfizer, Regeneron, Hoffman La-Roche, Novartis, Genentech,
5,
Genentech, Roche,
8.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/marked-improvement-in-patient-reported-outcomes-of-children-with-active-systemic-juvenile-idiopathic-arthritis-with-canakinumab-treatment-results-of-the-phase-iii-program/