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Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study.

ABSTRACT: This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1? monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment.In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4×4-weekly doses of canakinumab (50+50+25+25 mg subcutaneously); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks.A dose-response for canakinumab was not apparent with any of the four predefined dose-response models. The estimated canakinumab dose with equivalent efficacy to colchicine was below the range of doses tested. At 16 weeks, there was a 62% to 72% reduction in the mean number of flares per patient for canakinumab doses ?50 mg versus colchicine based on a negative binomial model (rate ratio: 0.28-0.38, p?0.0083), and the percentage of patients experiencing ?1 flare was significantly lower for all canakinumab doses (15% to 27%) versus colchicine (44%, p<0.05). There was a 64% to 72% reduction in the risk of experiencing ?1 flare for canakinumab doses ?50 mg versus colchicine at 16 weeks (hazard ratio (HR): 0.28-0.36, p?0.05). The incidence of adverse events was similar across treatment groups.Single canakinumab doses ?50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg.

SUBMITTER: Schlesinger N

PROVIDER: S-EPMC3103669 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study.

Schlesinger Naomi N Mysler Eduardo E Lin Hsiao-Yi HY De Meulemeester Marc M Rovensky Jozef J Arulmani Udayasankar U Balfour Alison A Krammer Gerhard G Sallstig Peter P So Alexander A

Annals of the rheumatic diseases 20110503 7

<h4>Objective</h4>This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1β monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment.<h4>Methods</h4>In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4×4-weekly ...[more]

PMID: 21540198

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Project description:OBJECTIVE:To assess the safety and efficacy of etoricoxib, a selective cyclo-oxygenase-2 inhibitor, in comparison with indometacin in the treatment of acute gouty arthritis. DESIGN:Randomised, double blind, active comparator controlled trial. SETTING:43 outpatient study centres in 11 countries. PARTICIPANTS:142 men and eight women (75 patients per treatment group) aged 18 years or over presenting with clinically diagnosed acute gout within 48 hours of onset. INTERVENTIONS:Etoricoxib 120 mg administered orally once daily versus indometacin 50 mg administered orally three times daily, both for 8 days. MAIN OUTCOME MEASURES:Patients' assessment of pain in the study joint over days 2 to 5 (primary end point); investigators' and patients' global assessments of response to treatment and tenderness of the study joint (key secondary end points). RESULTS:Etoricoxib showed efficacy comparable to indometacin. Patients' assessment of pain in the study joint (0-4 point Likert scale, "no pain" to "extreme pain") over days 2 to 5 showed a least squares mean change from baseline of -1.72 (95% confidence interval -1.90 to -1.55) for etoricoxib and -1.83 (-2.01 to -1.65) for indometacin. The difference between treatment groups met prespecified comparability criteria. All other efficacy end points, including those reflecting reduction in inflammation and analgesia, provided corroborative evidence of comparable efficacy. Significant pain relief was evident at the first measurement, 4 hours after the first dose of treatment. Prespecified safety analyses revealed that drug related adverse experiences occurred significantly less frequently with etoricoxib (22.7%) than with indometacin (46.7%) (P=0.003), although overall adverse experience rates were similar between the two treatment groups. CONCLUSION:Etoricoxib 120 mg once daily provides rapid and effective treatment for acute gouty arthritis comparable to indometacin 50 mg three times daily. Etoricoxib was generally safe and well tolerated in this study.

Project description:We report the impact of canakinumab, a fully human anti-interleukin-1? monoclonal antibody, on inflammation and health-related quality of life (HRQoL) in patients with difficult-to-treat Gouty Arthritis.In this eight-week, single-blind, double-dummy, dose-ranging study, patients with acute Gouty Arthritis flares who were unresponsive or intolerant to--or had contraindications for--non-steroidal anti-inflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg) (N = 143) or an intramuscular dose of triamcinolone acetonide 40 mg (N = 57). Patients assessed pain using a Likert scale, physicians assessed clinical signs of joint inflammation, and HRQoL was measured using the 36-item Short-Form Health Survey (SF-36) (acute version).At baseline, 98% of patients were suffering from moderate-to-extreme pain. The percentage of patients with no or mild pain was numerically greater in most canakinumab groups compared with triamcinolone acetonide from 24 to 72 hours post-dose; the difference was statistically significant for canakinumab 150 mg at these time points (P < 0.05). Treatment with canakinumab 150 mg was associated with statistically significant lower Likert scores for tenderness (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.27 to 7.89; P = 0.014) and swelling (OR, 2.7; 95% CI, 1.09 to 6.50, P = 0.032) at 72 hours compared with triamcinolone acetonide. Median C-reactive protein and serum amyloid A levels were normalized by seven days post-dose in most canakinumab groups, but remained elevated in the triamcinolone acetonide group. Improvements in physical health were observed at seven days post-dose in all treatment groups; increases in scores were highest for canakinumab 150 mg. In this group, the mean SF-36 physical component summary score increased by 12.0 points from baseline to 48.3 at seven days post-dose. SF-36 scores for physical functioning and bodily pain for the canakinumab 150 mg group approached those for the US general population by seven days post-dose and reached norm values by eight weeks post-dose.Canakinumab 150 mg provided significantly greater and more rapid reduction in pain and signs and symptoms of inflammation compared with triamcinolone acetonide 40 mg. Improvements in HRQoL were seen in both treatment groups with a faster onset with canakinumab 150 mg compared with triamcinolone acetonide 40 mg.clinicaltrials.gov: NCT00798369.

Project description:BackgroundThere is a paucity of community-based data regarding the prevalence and impact of gout flares as these may often be self-managed. The aim of this study was to determine the prevalence of self-reported gout and gout flares, the use of urate-lowering therapy (ULT), and the association of gout flares with health-related quality of life (HRQoL) in a large community sample. Covariate associations with flare frequency and allopurinol use were also examined.MethodsThe South Australian Health Omnibus Survey is an annual, face-to-face population-based survey. Data collected in the 2017 survey included self-reported medically diagnosed gout, allopurinol use (first-line ULT in Australia), and gout attacks (flares) in the last 12 months, in addition to sociodemographic variables and health-related quality of life (HRQoL, SF-12). Data were weighted to the Australian Bureau of Statistics 2016 census data to reflect the South Australian population. Participants 25 years and over (n = 2778) were included in the analysis.ResultsThe prevalence of gout was 6.5% (95%CI 5.5, 7.5). Amongst participants with gout, 37.1% (95%CI 29.6, 45.3) reported currently using allopurinol, while 23.2% (95%CI 16.9, 21.0) reported prior use (38% discontinuation rate). Frequent flares (≥ 2 in the last year) were reported by 25% of participants with gout and were more likely with younger age, higher body mass index, and current allopurinol use (p < 0.05). The frequency of gout flares was associated with a lower physical HRQoL (p = 0.012). Current allopurinol use was reported by 51% of participants with frequent gout flares.ConclusionFlares were frequently reported by people with gout in the community. Gout flares were associated with reduced physical HRQoL. Almost one half of people with frequent gout flares were not receiving allopurinol, and current allopurinol use was associated with frequent gout flares, suggesting undertreated disease and suboptimal use of ULT. Determining covariate associations with flares and ineffective allopurinol use may identify means of improving treatment and reducing flares.

Project description:BackgroundWe aimed to assess the safety and tolerability of different doses of canakinumab versus placebo in patients with type 2 diabetes mellitus (T2DM).MethodsData were pooled from three studies in 1026 T2DM patients with different routes of administration, treatment regimens and follow-up duration. Canakinumab groups were categorised as low (0.03 mg/kg i.v. once; N = 20), intermediate (0.1 and 0.3 mg/kg i.v. once, 5 and 15 mg s.c. monthly; N = 247), medium (1.5 mg/kg i.v. once, 50 mg s.c. monthly and 150 mg s.c. once; N = 268), and high doses (10 mg/kg i.v. once and 150 mg s.c. monthly; N = 137) and compared with placebo (N = 354). Incidences of adverse events (AEs), serious AEs (SAEs), discontinuations due to AEs, deaths, AEs of special interest related to interleukin-1β inhibition and T2DM disease, and laboratory abnormalities related to haematology and biochemistry parameters were reported. Safety was also analysed by age (<65, ≥65) and gender.ResultsAverage exposure across all groups was ≈ 6 months (maximum ~17 months). No dose response in AEs was observed but a trend towards more patients having at least one AE across canakinumab groups relative to placebo (P = 0.0152) was observed. SAEs were few and the incidence rate for most canakinumab groups was lower than that of placebo group except for the high-dose group (0.94% versus 0.58% per month in placebo). A total of five patients discontinued treatment due to AEs across treatment groups. No death was reported in any of the three studies. A small, non-significant increase in the incidence rate of infection AEs was observed on canakinumab groups relative to placebo. Canakinumab was associated with mostly mild decreases in WBC, neutrophils and platelet counts. Additionally, mild increases in SGPT, SGOT and bilirubin were reported. Overall, despite small differences, no clinically relevant findings were observed with respect to laboratory values and vital signs.ConclusionsThis pooled analysis demonstrated that canakinumab was safe and well tolerated over a treatment period up to 1.4 years at the four pooled doses evaluated, in agreement with safety findings reported in the individual studies.

Project description:BackgroundAspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation.MethodsThis was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight individual who has self reported sensitivity to aspartame were compared to 48 age and gender matched aspartame non-sensitive individuals. They were given aspartame (100mg)-containing or control snack bars randomly at least 7 days apart. The main outcome measures were acute effects of aspartame measured using repeated ratings of 14 symptoms, biochemistry and metabonomics.ResultsAspartame sensitive and non-sensitive participants differed psychologically at baseline in handling feelings and perceived stress. Sensitive participants had higher triglycerides (2.05 ± 1.44 vs. 1.26 ± 0.84mmol/L; p value 0.008) and lower HDL-C (1.16 ± 0.34 vs. 1.35 ± 0.54 mmol/L; p value 0.04), reflected in 1H NMR serum analysis that showed differences in the baseline lipid content between the two groups. Urine metabonomic studies showed no significant differences. None of the rated symptoms differed between aspartame and control bars, or between sensitive and control participants. However, aspartame sensitive participants rated more symptoms particularly in the first test session, whether this was placebo or control. Aspartame and control bars affected GLP-1, GIP, tyrosine and phenylalanine levels equally in both aspartame sensitive and non-sensitive subjects.ConclusionUsing a comprehensive battery of psychological tests, biochemistry and state of the art metabonomics there was no evidence of any acute adverse responses to aspartame. This independent study gives reassurance to both regulatory bodies and the public that acute ingestion of aspartame does not have any detectable psychological or metabolic effects in humans.Trial registrationISRCTN Registry ISRCTN39650237.

Dataset Information

Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study.

Publications

Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study.

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