Article
Safety of long-term (up to 6 years) canakinumab therapy (<2, 2–<4 and 4–<8mg/Kg) in patients aged <4 to 65 years from Beta-Confident Registry
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Authors
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Jasmin Kümmerle-Deschner
- Universitätskinderklinik Tübingen, Rheumatologie, Tübingen
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Ulrich A. Walker
- Universitäts-Poliklinik, Felix-Platter Spital, Basel, Schweiz
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Hugh Tilson
- University of North Carolina, School of Public Health, Chapel Hill, United States of America
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Philip N. Hawkins
- University College London, Medical School, London, England
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Tom van der Poll
- Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, Amstedam
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Kristina Franke
- Quintiles, IQVIA, Boston University School of Medicine, Boston, USA
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Antonio Speziale
- Novartis Pharma AG, Immunologie & Dermatologie, Basel, Switzerland
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Eleni Vritzali
- Novartis Pharma AG, Basel, Schweiz
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Harold M. Hoffman
- University of California, San Diego, United States of America
| Published: | October 8, 2019 |
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Outline
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Background: The β-confident registry (NCT01213641), a multicenter, long-term (6 years; yrs), prospective, observational study has demonstrated the safety and effectiveness of canakinumab (CAN) in real life CAPS patients (pts) according to their phenotypes. Here we report long-term safety of CAN in pts with CAPS and other autoinflammatory syndromes, enrolled in the β-confident registry, according to their age and dose administered. Objectives were to monitor the long-term safety of different CAN doses (<2, 2−<4 and 4−<8mg/kg) across different age groups (<4 to 65 years) in pts with CAPS and other autoinflammatory syndromes.
Methods: Cumulative safety data were reported as exposure adjusted incidence rate per 100 pt-years (IR/pyr) from the enrollment of the first pt (November 2009) until end of study (December 2015). Pts were followed up for at least 1 yr. The protocol did not mandate any visits or procedures. All observed and reported AEs and SAEs were recorded for the following age groups: <4-, 4−<12-, 12−<18-, 18−<65- and ≥65 yrs.
Results: Of the 285 pts enrolled, 21% (n=60) discontinued the study mainly due to loss of follow-up (35%, n=21) followed by AEs (10%, n=6), poor efficacy (8%, n=5) and pt preference (3%, n=2). In total, 1114 AEs and 155 SAEs were reported in 223 pts (110.7 IR/100 pyr) and 83 pts (15.4 IR/100 pyr), respectively. Exposure adjusted incidence rate of AEs (IR/100 pyr) among pts in the <4 and 4 -<12 yr age group, were lowest in the pts who received <2 mg/kg dose (130.3 and 59.7, respectively) compared to pts who received 2 -<4 mg/kg (450.8 and 169.6, respectively) and 4 -<8 mg/kg (121.5 and 90.0, respectively) CAN dose. In pts aged 12 -<18 yrs, IR/100 pyr were lowest in pts who received 2-<4 mg/kg dose (118.2) compared to pts who received <2 mg/kg (169.6) and 4 -<8 mg/kg (139.4) CAN dose. Similarly, in the 18 -<65 yr age group, IR/100 pyr were lowest in pts who received <2 mg/kg dose (93.1) compared to pts who received 2-<4 mg/kg (100.7) and 4 -<8 mg/kg (154.4) CAN dose. In the ≥65 yr age group, IR/100 pyr decreased with increase in dose (<2 mg/kg: 26, 2−<4 mg/kg: 17). Overall, 5, 13, 19, 84 and 7 SAEs were reported in <4-, 4−<12-, 12−<8-, 18−<65- and ≥65 yr age groups, respectively. One death (metastatic rectal adenocarcinoma in a 76-yr-old MWS patient) was reported.
Conclusion: The β-confident registry is the largest CAPS cohort documented in a registry. In general, incidence of adverse events in each dose group increased with age (<4−<65 yrs). However, no meaningful pattern of AEs was observed with increased dose for each age group. Long-term treatment with canakinumab demonstrated favorable safety profile which was similar to that reported earlier and is well tolerated in CAPS patients aged <4 to 65 years.
