PMID- 34001647 OWN - NLM STAT- MEDLINE DCOM- 20210831 LR - 20210831 IS - 2056-5933 (Electronic) IS - 2056-5933 (Linking) VI - 7 IP - 2 DP - 2021 May TI - Long-term safety and effectiveness of canakinumab therapy in patients with cryopyrin-associated periodic syndrome: results from the beta-Confident Registry. LID - 10.1136/rmdopen-2021-001663 [doi] LID - e001663 AB - OBJECTIVE: To report the long-term safety and effectiveness of canakinumab, a fully human anti-interleukin 1beta monoclonal antibody, in patients with cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID), in a real-world setting. METHODS: From December 2009 to December 2015, the beta-Confident Registry prospectively enrolled patients with CAPS and non-CAPS conditions who received canakinumab per routine care and were prospectively followed for up to 6 years. The registry protocol did not mandate specific visits or procedures; however, all observed adverse events (AEs) and serious adverse events (SAEs) had to be recorded. Canakinumab effectiveness was evaluated by Physician's Global Assessment (PGA). RESULTS: Of 288 patients enrolled, 3 were excluded due to missing informed consent. Among the remaining 285 patients, 243 (85.3%) were patients with CAPS and 42 (14.7%) had atypical CAPS (6.3%) or other conditions (8.4%). The median age was 26.6 years. Based on PGA, 58 of 123 (47.2%) patients with CAPS had no disease activity at 48 months, and 65 of 123 (52.8%) experienced mild/moderate disease activity at 48 months. Among CAPS phenotypes, AE incidence rates per 100 patient-years were lowest for FCAS (73.1; 95% CI 60.3 to 87.8) compared with those with MWS (105.0; 95% CI 97.2 to 113.2) or NOMID (104.6; 95% CI 86.6 to 125.2). One hundred twenty-eight SAEs were reported in 68 patients with CAPS (incidence rate/100 patient-years, 14.0; 95% CI 11.6 to 16.6). One death (metastatic rectal adenocarcinoma in a patient with MWS) was reported. CONCLUSIONS: The response to canakinumab was sustained for up to 6 years. Canakinumab demonstrated a favourable safety profile over long-term treatment in patients with CAPS. TRIAL REGISTRATION NUMBER: NCT01213641. CI - (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ. FAU - Walker, Ulrich A AU - Walker UA AUID- ORCID: 0000-0002-9183-550X AD - Department of Rheumatology, University Hospital Basel, Basel, Switzerland ulrich.walker@usb.ch. FAU - Tilson, Hugh H AU - Tilson HH AD - Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA. FAU - Hawkins, Philip N AU - Hawkins PN AD - University College London, London, UK. FAU - Poll, Tom van der AU - Poll TV AD - Amsterdam Medical Center, University of Amsterdam, Amsterdam, The Netherlands. FAU - Noviello, Stephanie AU - Noviello S AD - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. FAU - Levy, Jeremy AU - Levy J AD - Novartis Pharma AG, Basel, Switzerland. FAU - Vritzali, Eleni AU - Vritzali E AD - Novartis Pharma AG, Basel, Switzerland. FAU - Hoffman, Hal M AU - Hoffman HM AD - University of California San Diego, San Diego, California, USA. AD - Rady Children's Hospital San Diego, San Diego, California, USA. FAU - Kuemmerle-Deschner, Jasmin B AU - Kuemmerle-Deschner JB AUID- ORCID: 0000-0002-6365-6598 AD - Division of Pediatric Rheumatology, Department of Paediatrics and Autoinflammation Reference Center Tuebingen, University Hospital Tuebingen, Tubingen, Germany. CN - CACZ885D2401 Study Investigators LA - eng SI - ClinicalTrials.gov/NCT01213641 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - RMD Open JT - RMD open JID - 101662038 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 37CQ2C7X93 (canakinumab) SB - IM MH - Adult MH - Antibodies, Monoclonal/adverse effects MH - Antibodies, Monoclonal, Humanized MH - *Cryopyrin-Associated Periodic Syndromes/drug therapy/genetics MH - Humans MH - Registries PMC - PMC8130749 OTO - NOTNLM OT - biological therapy OT - cryopyrin-associated periodic syndromes OT - inflammation COIS- Competing interests: UAW reports personal fees from Novartis, during the conduct of the study. HHT reports honorarium and travel expenses from Novartis, during the conduct of the study; serving on Scientific Advisory Boards for Pharmacoepidemiology Studies for GSK, Novartis, Seqirus, Jazz and Allergan. For all of these HHT receives only honoraria and expenses. PNH, TvdP and EV have nothing to declare. SN is an employee and shareholder of Novartis; shareholder of Bristol-Myers Squibb, Merck and Johnson & Johnson. JL reports personal fees from Novartis, during the conduct of the study; personal fees from Novartis, outside the submitted work. HH reports personal fees from IFM, Novartis, Regeneron and Sobi; grants from Jecure, Takeda and Zomagen, outside the submitted work. JBK-D reports grant support and speaker fees from Novartis and Sobi, during the conduct of the study. EDAT- 2021/05/19 06:00 MHDA- 2021/09/01 06:00 PMCR- 2021/05/17 CRDT- 2021/05/18 06:28 PHST- 2021/03/10 00:00 [received] PHST- 2021/04/24 00:00 [revised] PHST- 2021/05/04 00:00 [accepted] PHST- 2021/05/18 06:28 [entrez] PHST- 2021/05/19 06:00 [pubmed] PHST- 2021/09/01 06:00 [medline] PHST- 2021/05/17 00:00 [pmc-release] AID - rmdopen-2021-001663 [pii] AID - 10.1136/rmdopen-2021-001663 [doi] PST - ppublish SO - RMD Open. 2021 May;7(2):e001663. doi: 10.1136/rmdopen-2021-001663.