OP0085 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
Authors: J.B. Kuemmerle-Deschner, U.A. Walker, H.H. Tilson, P.N. Hawkins, T. van der Poll, K. Franke, A. Speziale, E. Vritzali, H.H. Hoffman
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> 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.<sup>1</sup> 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. <h3>Objectives</h3> To monitor the long-term safety of different CAN doses (&lt;2, 2−&lt;4 and 4−&lt;8 mg/kg) across different age groups (&lt;4 to 65 years) in pts with CAPS and other autoinflammatory syndromes. <h3>Methods</h3> 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 year. The protocol did not mandate any visits or procedures. All observed and reported AEs and SAEs were recorded for the following age groups:&lt;4-, 4−&lt;12-, 12−&lt;18-, 18−&lt;65 and≥65 years. <h3>Results</h3> 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 &lt;4 and 4 -&lt;12 year age group, were lowest in the pts who received &lt;2 mg/kg dose (130.3 and 59.7, respectively) compared to pts who received 2 -&lt;4 mg/kg (450.8 and 169.6, respectively) and 4 -&lt;8 mg/kg (121.5 and 90.0, respectively) CAN dose. In pts aged 12 -&lt;18 years, IR/100 pyr were lowest in pts who received 2-&lt;4 mg/kg dose (118.2) compared to pts who received &lt;2 mg/kg (169.6) and 4 -&lt;8 mg/kg (139.4) CAN dose. Similarly, in the 18 -&lt;65 year age group, IR/100 pyr were lowest in pts who received &lt;2 mg/kg dose (93.1) compared to pts who received 2-&lt;4 mg/kg (100.7) and 4 -&lt;8 mg/kg (154.4) CAN dose. In the ≥65 year age group, IR/100 pyr decreased with increase in dose (&lt;2 mg/kg: 26, 2−&lt;4 mg/kg: 17). Overall, 5, 13, 19, 84 and 7 SAEs were reported in &lt;4-, 4−&lt;12-, 12−&lt;8-, 18−&lt;65 and≥65 year age groups, respectively. One death (metastatic rectal adenocarcinoma in a 76-yr-old MWS patient) was reported. <h3>Conclusions</h3> 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 (&lt;4−&lt;65 years). However, no meaningful pattern of AEs was observed with increased dose for each age group. Long-term treatment with canakinumab demonstrated favourable safety profile which was similar to that reported earlier<sup>2</sup> and is well tolerated in CAPS patients aged &lt;4 to 65 years. <h3>Reference</h3> [1] Kuemmerle-Deschner JB, et al. Ann Rheum Dis2015;74(S2):850. [2] Hoffman HM, et al. <i>Arthritis Rheumatol</i>2016;68(suppl 10). <h3>Acknowledgements</h3> The study was sponsored by Novartis Pharma AG <h3>Disclosure of Interest</h3> J. Kuemmerle-Deschner Consultant for: Novartis Pharmaceutical Corporation, SOBI, and Baxalta, U. A. Walker Consultant for: Novartis Pharmaceutical Corporation, H. Tilson Consultant for: Novartis Pharmaceutical Corporation, P. N. Hawkins: None declared, T. van der Poll: None declared, K. Franke Consultant for: Novartis, A. Speziale Employee of: Novartis, E. Vritzali Employee of: Novartis, H. Hoffman Grant/research support from: Burroughs-Wellcome, Consultant for: Novartis Pharmaceutical Corporation, Sobi, Speakers bureau: Novartis Pharmaceutical Corporation