Canakinumab Treatment Research Articles

AB0847 Efficacy and Safety of Canakinumab Pre-Filled Syringe in Acute Gouty Arthritis Patients with Chronic Kidney Disease Stage ≥3

BackgroundChronic kidney disease (CKD) limits the treatment options in acute gouty arthritis (GA) patients due to intolerance and contraindications to available therapies. Efficacy and safety of canakinumab (CAN), a selective,...

THU0482 Gene Expression Profiling of Whole Blood Samples of TRAPS Patients Shows Insight into the Molecular Pathogenesis of TRAPS and Response to Canakinumab Treatment

BackgroundTNF receptor-associated periodic syndrome (TRAPS) is an autoinflammatory disease causing unprovoked fevers, myalgia, abdominal pain, rash, headaches, and, in severe cases, AA amyloidosis. It is an autosomal dominant condition resulting...

AB0939 Canakinumab in Clinical Practice. Effectiveness in A Cryopyrin-Associated Periodic Syndrome Single Center Cohort

BackgroundCryopyrin-associated periodic syndrome (CAPS) comprises a group of rare, but severe, autoinflammatory diseases, characterized by urticaria, periodic fever, central nervous system inflammation, arthropathy, and increased risk of amyloidosis. In a...

SAT0537 Long-Term Safety and Efficacy of Canakinumab VS Triamcinolone Acetonide in Patients with Frequent Acute Gouty Arthritis Attacks Who Are Contraindicated, Intolerant or Unresponsive to NSAIDS And/Or Colchicine

BackgroundThere is a medical need for effective alternate treatments for acute gouty arthritis (GA) patients (pts) with frequent GA attacks in whom NSAIDs and/or colchicine are contraindicated, not tolerated or...

CLINICAL CASE: USE OF CANAKINUMAB IN A PATIENT WITH SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS RESISTANT TO IMMUNOSUPPRESSANTS AND GENETICALLY ENGINEERED BIOPHARMACEUTICALS

научный биометрический журнал, который знакомит читателя с клиническими рекомендациями и особенностями применения лекарственных и вакцинных средств у детей, предоставляет исчерпывающую информацию о воздействии лекарственных средств на плод, о проводимых в

A98: Rescue Treatment by Increased Doses of IL‐1 Inhibitors for Macrophage Activation Syndrome in Children With Systemic Juvenile Idiopathic Arthritis

Background/Purpose:macrophage activation syndrome (MAS) is a life‐threatening complication of systemic juvenile idiopathic arthritis (SJIA). More than half cases of MAS are steroid‐resistant and required to use second‐line agents, such as cyclosporine A (CsA), intravenous immunoglobulin (IVIG) and biologic agents. Known interleukin‐1 (IL‐1) is the key cytokine in pathogenesis of MAS and SJIA, so anti‐IL‐1 treatment considered as potential effective treatment. There are several publication about efficacy of increased doses of anakinra during the MAS episodes. Data about efficacy others new IL‐1 blockers (canakinumab and rilonacept) for MAS in SJIA are limited. There are only several cases of MAS during and after canakinumab (CNKB) treatment of SJIA in randomized controlled trials.Methods:a retrospective study of the clinical notes, reports of laboratory investigations and radiological images. We included 3 patients with SJIA who developed MAS. First patient (Pt#1) had the severe form of MAS, resistant to high doses of steroids, IVIG, CsA. After failure of previous treatment anakinra was added, and later changed on CNKB. Second patient (Pt#2) developed SJIA flare with severe MAS after 3rd CNKB injection, resistant to high doses steroids, IVIG, required Fresh Frozen Plasma, third patient (Pt#3) developed only mild MAS after 8th CNKB injection without signs of SJIA flare. Indications for increased doses of CNKB were inefficacy of previous anti IL‐1 treatment in standard and increased doses and severity of MAS (Pt#1, Pt#2) according the manufacture's manual permitted to use the maximum dose of 300 mg per injection. The initial CNKB dose before MAS was 4 mg/kg every 4 weeks in Pt#2 and Pt#3. All patient during the MAS received one single injection of increased dose of CNKB: 15 mg/kg (Pt#1), 12.5 mg/kg (Pt#2) and 7.5 mg/kg (Pt#3). CNKB was injected every 4 weeks with gradually tapering dose up to 4 mg/kg every 4 weeks. All parents signed the inform consent. Institutional Review Board affirmed this kind of treatment.Results:in Pt#1 initial treatment with standard doses of anakinra was insufficient and dose was increased up to 20 mg/kg/day with good response. Later anakinra was changed on CNKB in 1st dose 15 mg/kg every 4 weeks with gradually tapering dose up to 6 mg/kg up to now. The switching from anakinra to CNKB did not loose the efficacy. In Pt#2 after initiation of increased dose of CNKB the flare of JIA and active MAS was dramatically abrupt up to 7th day after 1st injection. Total normalization of lab tests occurred in 2 weeks. After normalization we tapered corticosteroids. In Pt#3 MAS also quickly disappeared, the normalization of lab test also occurred in 10 days. No side and adverse effects were noticed during using of increased anakinra and CNKB doses.Conclusion:SJIA and MAS are both IL‐1‐ dependent conditions. The SJIA flare and MAS usually associated with increased production of pro‐inflammatory cytokines, especially IL‐1β. So we suppose that increased levels of IL‐1β require increased doses of IL‐1 blockers. Our data shows the efficacy and safety of increased doses of IL‐1 blockers. It is necessary to provide future trials to evaluate the efficacy and safety increased doses of IL‐1 blockers for treatment MAS in SJIA.

PReS-FINAL-2330: Canakinumab treatment in patients with HIDS

Hyper-IgD and periodic-fever syndrome (HIDS) is a recessively inherited-autoinflammatory condition caused by mevalonate-kinase mutations. It is characterized by early-onset (<1 year of age), 4-6 days-long acute inflammatory episodes that typically recur every 4-6 weeks. The main features during episodes include fever, lymphadenopathies, rash, headache, abdominal pain, diarrhea, and a marked acute phase reaction[1,2]. Previous case reports suggested IL-blockade as a potential therapy. Canakinumab (CAN) is a fully-human, selective anti-IL-1β monoclonal-antibody (MoAb). Preliminary clinical and pharmacokinetics (PK) data of CAN-therapy in active HIDS patients is presented.

PReS-FINAL-2158: Effect of canakinumab on functional ability and health-related quality of life in systemic juvenile idiopathic arthritis (SJIA) patients

Canakinumab (CAN), a selective, fully human, anti-interleukin-1β monoclonal antibody, has been shown to be efficacious in SJIA patients (pts) in 2 phase 3 trials: Trial 1 (4-wk, randomized placebo [PBO]-controlled) and Trial 2 (open-label CAN treatment [Part 1] followed by a randomized PBO-controlled withdrawal phase [Part 2]). In Trial 1, statistically significantly more CAN than PBO group pts achieved an adapted pediatric ACR 30 response and in Trial 2, CAN allowed successful reduction/discontinuation of steroids and significantly reduced risk of flare. Safety profile of CAN was in line with expectations for a biologic agent in active SJIA. The persistent disabling features of SJIA and chronic pain can have a negative impact on health-related quality of life (hrqol). These outcomes were evaluated in the CAN phase 3 program.

PReS13-SPK-1182: Six years of eu paediatric regulation - what was achieved for paediatric rheumatology

EU Paediatric Regulation was adopted by the European Parliament and the Council in December 2006. First meeting of the Paediatric Committee took place in July 2007. 1. Paediatric investigation Plans (PIPs) In 2007-2013 The European Medicines Agency (EMA) and its Paediatric Committee have agreed more than 600 Paediatric Investigation Plans (PIPs) with pharmaceutical companies, to provide data on the efficacy and safety of medicines for diseases of children. · For treatment of JIA PIP was agreed for the following substances: abatacept, adalimumab, anakinra, anti-BAFF antibody, anti-IL-6 antibody, anti-IL17 antibody, anti-IL-17A antibody, apremilast, baricitinib, canakinumab, certolizumab, denosumab, etanercept, givinostat, golimumab, olokizumab, sarilumab, tocilizumab, tofacitinib and ustekinumab. · For treatment of SLE in children PIP was agreed for anti-BAFF, belimumab and epratuzumab. · For treatment of CAPS PIP was agreed for anakinra, anti-IL-1beta antibody and canakinumab. 2. Clinical trials More paediatric clinical trials were done (data from EudraCT, accessible at the European Clinical Trials Register): 3. New authorised indications for children · 12/11/2009: canakinumab for treatment of CAPS. · 25/08/2008: adalimumab - treatment of active polyarticular juvenile idiopathic arthritis in adolescents from 13 to 17 years of age. · 20/01/2010 abatacept - treatment of moderate to severe active polyarticular juvenile idiopathic arthritis in paediatric patients 6 years of age and older. · 18/03/2011 adalimumab - treatment of active polyarticular juvenile idiopathic arthritis in the paediatric population aged from 4 to 12 years. · 01/08/2011: tocilizumab - treatment of active systemic juvenile idiopathic arthritis (sJIA) in patients 2 years of age and older. · 24/08/2011: etanercept - polyarticular juvenile idiopathic arthritis (JIA) from the age of 2 years. · 24/08/2012: etanercept - treatment of RF+ and RF- polyarthritis, extended oligoarthritis from 2 years of age, psoriatic arthritis and ERA from 12 years of age. · 17/01/2013 - adalimumab - treatment of active polyarticular juvenile idiopathic arthritis in the paediatric population aged from 2 to 4 years old. · 25/04/2013 - tocilizumab - treatment of polyarthritis (RF+, RF- and extended oligoarthritis) from 2 years old (EC decision pending at the time of abstract submission). 4. A network of paediatric research networks Enpr-EMA works by fostering collaboration from within and outside the European Union (EU), including between members, patients associations, academia and the pharmaceutical industry.) PRINTO and JSWG of PRES are members of Enpr-EMA. 5. Expert meetings at EMA: Paediatric rheumatology (2009, 2010), Gastroenterology and rheumatology (2010). 6. Development of scientific guidelines (JIA, SLE, GIOP). 7. Pharmacovigilance ENCEPP - (PharmaChild protocol agreed).

PReS-FINAL-2224: Canakinumab treatment regimens in CAPS-patients

Canakinumab is a recombinant monoclonal fully human antibody against Interleukin-1β and approved for the treatment of CAPS in many countries including Europe and the US. Current dose recommendations are 150 mg (body weight >40 kg) respectively 2 mg/kg body weight (15 to 40 kg) every 8 weeks but yield insufficient response in some individuals, especially in children and patients with severe phenotypes [1].

OR10-006 - Canakinumab in patients with TRAPS

TNF-receptor associated periodic syndrome (TRAPS) is a rare, dominantly inherited periodic fever syndrome due to mutations of the TNFRSF1A gene. The IL-1 receptor antagonist anakinra has been reported to be an efficacious daily treatment. Canakinumab (CAN) is a fully human monoclonal selective anti-IL-1β antibody with a T1/2 of ~4 wks. Interim clinical and PK data of CAN treatment in patients with active TRAPS are presented.

PW03-020 – A decade of ANTI-IL-1 therpay for CAPS in the UK

In October 2002, the first patient with CAPS was treated successfully with the anti-IL-1 agent anakinra at our Centre in the UK, and in 2009 a nationally funded canakinumab treatment service initiated for CAPS in England. By the end of 2012, 82 symptomatic individuals have been assessed at our Centre.

PW02-041 - Canakinumab treatment regimens in CAPS-patients

Canakinumab is a recombinant monoclonal fully human antibody against Interleukin-1β and currently the only drug approved for the treatment of CAPS in Europe. Current dose recommendations are 150mg (body weight >40kg) respectively 2mg/kg bodyweight (15 to 40kg) every 8 weeks but yield insufficient response in some individuals, especially in children and patients with severe phenotypes [1].

CLINICAL CASE OF CANAKINUMAB USE IN A PATIENT WITH SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS

The article presents a case of successful use of therapeutic monoclonal antibodies to interleukin 1 (canakinumab) at severe systemic juvenile idiopathic arthritis. Canakinumab treatment promptly provided reduction in clinical and laboratory disease activity indicators, increase in life quality, development of inactive disease stage and allowed avoiding prescription of glucocorticoids.

Pharmacokinetic and pharmacodynamic properties of canakinumab in patients with gouty arthritis

Pharmacokinetics and pharmacodynamics of the anti-interleukin (IL)-1β monoclonal antibody, canakinumab, in gouty arthritis patients from three studies are reported. Canakinumab has low serum clearance (0.214 L/day), low steady-state volume of distribution (7.44 L), a 25.8-day half-life, and approximately 60% subcutaneous absolute bioavailability in a typical 93-kg patient. Creatinine clearance had a small positive impact on serum canakinumab clearance that is not likely to be clinically relevant. Binding to circulating IL-1β was demonstrated by increases in total serum IL-1β following canakinumab dosing. Total IL-1β kinetics and canakinumab pharmacokinetics were characterized by a population-based pharmacokinetic-binding model, where the estimated apparent in vivo dissociation constant (signifying binding affinity of canakinumab to circulating IL-1β) was 0.99 nmol/L in gouty arthritis patients. Canakinumab treatment provided rapid, sustained decreases in C-reactive protein and serum amyloid A, provided superior pain relief to triamcinolone acetonide, and increased time to first recurrent attack (P ≤ 0.01 favoring all canakinumab doses vs. triamcinolone acetonide).

Impact of interleukin-1β antibody (canakinumab) on glycaemic indicators in patients with type 2 diabetes mellitus: Results of secondary endpoints from a randomized, placebo-controlled trial

Aims/hypothesisThis study was conducted to determine the optimal monthly subcutaneous dose of canakinumab (a human monoclonal anti-human IL-1β antibody) needed to improve glucose control in metformin-treated patients with type 2 diabetes mellitus (T2DM). MethodsThis was a parallel-group, randomized, double-blind, multicentre, placebo-controlled study designed to assess the effect on HbA1c and the safety/tolerability of four monthly doses of canakinumab (5, 15, 50, or 150mg) as an add-on to metformin over 4 months. ResultsPatients (n=551; mean age 54.1 years; mean baseline HbA1c 7.4%) were randomized and treated in a double-blind fashion to canakinumab 5mg (n=93), 15mg (n=95), 50mg (n=92), 150mg (n=92) or placebo (n=179) monthly. There was no dose response detected between active canakinumab doses, but all doses numerically lowered HbA1c (primary endpoint) from baseline between 0.19% and 0.31% (placebo-unadjusted), with maximal effect noted in the 50mg dose of canakinumab (−0.18% difference vs placebo; multiplicity-adjusted, P=0.13902) as reported earlier (Ridker et al., 2012). No other glycaemic control parameters (FPG, fasting insulin, plasma glucose AUC0–4h, 2-h PPG, peak glucose, C-peptide AUC0–4h, peak C-peptide, insulin AUC0–4h, peak insulin, ISR0–2h, HOMA-β and HOMA-IR) showed any meaningful changes by canakinumab therapy. Canakinumab treatment was safe and well tolerated. There were no relevant differences in adverse events between the canakinumab and placebo groups. Conclusions/interpretationA 4-month course of monthly canakinumab (50mg) produced a numerical reduction of HbA1c in T2DM patients on metformin, potentially by improving beta-cell function. The safety and tolerability profile of canakinumab was consistent with prior trials. Trial registrationRegistry: http://www.ClinicalTrials.gov, Registration No.: NCT00900146

THU0490 Canakinumab Treatment of Patients with Hyper-IgD Syndrome: An Open-Label, Multicenter, Pilot Study

BackgroundHyper-IgD and periodic fever syndrome (HIDS) is a recessively inherited autoinflammatory disease caused by melavonate kinase (MVK) gene mutations. It is characterized by recurrent, early-onset, 4-6 days-long acute episodes with...

AB1191 Within-patient analysis during anakinra and canakinumab treatment in cryopyrin associated periodic syndrome

BackgroundAnti-IL1 drugs have been shown to be an effective treatment for the control of disease activity in patients with CAPS. Anakinra has been used for several years and his long-term...

THU0396 Efficacy and safety of canakinumab in patients with TNF receptor associated periodic syndrome (TRAPS)

BackgroundTNF-receptor associated periodic syndrome (TRAPS) is a rare dominantly inherited periodic fever syndrome involving a genetic mutation of the TNF Super Family Receptor 1A gene. Usually presenting in childhood, it...

AB1172 Safety and efficacy of a 12-MO canakinumab administration in patients with systemic juvenile idiopathic arthritis: Data from the greek national registry

BackgroundTargeted treatments are becoming the mainstay for many autoinflammatory diseases, including the systemic juvenile idiopathic arthritis (sJIA). Canakinumab (CAB), a fully human anti-interleukin-1β (IL-1β) antibody, has recently been shown to...