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

• Published in: Annals of the rheumatic diseases Vol. 77; no. Suppl 2; p. 93
• Main Authors: Kuemmerle-Deschner, J.B., Walker, U.A., Tilson, H.H., Hawkins, P.N., van der Poll, T., Franke, K., Speziale, A., Vritzali, E., Hoffman, H.H.
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2018
• Subjects: Adenocarcinoma; Age; Age groups; Arthritis; Metastases; Monoclonal antibodies; Patients; Pharmaceuticals; Phenotypes; Rectum; Safety
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2018-eular.2569

BackgroundThe 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.1 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.ObjectivesTo monitor the long-term safety of different CAN doses (<2, 2−<4 and 4−<8 mg/kg) across different age groups (<4 to 65 years) in pts with CAPS and other autoinflammatory syndromes.MethodsCumulative 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:<4-, 4−<12-, 12−<18-, 18−<65 and≥65 years.ResultsOf 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 year 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 years, 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 year 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 year 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 year age groups, respectively. One death (metastatic rectal adenocarcinoma in a 76-yr-old MWS patient) was reported.ConclusionsThe 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 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 earlier2 and is well tolerated in CAPS patients aged <4 to 65 years.Reference[1] Kuemmerle-Deschner JB, et al. Ann Rheum Dis2015;74(S2):850.[2] Hoffman HM, et al. Arthritis Rheumatol2016;68(suppl 10).AcknowledgementsThe study was sponsored by Novartis Pharma AGDisclosure of InterestJ. 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