Objective. To assess the efficacy and tolerability of canakinumab, a fully human anti-interleukin-1␤ monoclonal antibody, for the treatment of acute gouty arthritis.Methods. In this 8-week, single-blind, doubledummy, dose-ranging study, patients with acute gouty arthritis whose disease was refractory to or who had contraindications to nonsteroidal antiinflammatory 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 100-mm visual analog scale.Results. Seventy-two hours after treatment, a statistically significant dose response was observed for canakinumab. All canakinumab doses were associated with numerically less pain than triamcinolone acetonide; thus, a dose with equivalent efficacy to triamcinolone acetonide 72 hours after treatment could not be determined. The reduction from baseline in pain intensity with canakinumab 150 mg was greater than with triamcinolone acetonide 24, 48, and 72 hours after treatment (differences of ؊11.5 mm [P ‫؍‬ 0.04], ؊18.2 mm [P ‫؍‬ 0.002], and ؊19.2 mm [P < 0.001], respectively), and 4, 5, and 7 days after treatment (all P < 0.05). Canakinumab significantly reduced the risk of recurrent flares versus triamcinolone acetonide (P < 0.01 for all doses) (relative risk reduction 94% for canakinumab 150 mg versus triamcinolone acetonide). The overall incidence of adverse events was similar for canakinumab (41%) and triamcinolone acetonide (42%); most were mild or moderate in severity.Conclusion. Our findings indicate that canakinumab 150 mg provides rapid and sustained pain relief in patients with acute gouty arthritis, and significantly reduces the risk of recurrent flares compared with triamcinolone acetonide.Gout is a metabolic disease caused by monosodium urate monohydrate (MSU) crystal deposition and is one of the most common forms of inflammatory arthritis in adults (1,2). Its prevalence increases with age and is especially high in older men (2). Gouty arthritis commonly occurs in the lower extremities (3,4), and flares are characterized by rapid onset and build-up of pain, warmth, swelling, decreased range of motion, and redness of the involved joints (3,4). Initial flares last hours to weeks, whereas subsequent flares may be more prolonged. The frequency of flares often increases over time in patients who are inadequately treated (3,4).The goal of therapy in an acute gout flare is prompt and safe termination of pain and inflammation. Acute gouty arthritis is usually treated with nonsteroidal ClinicalTrials.gov identifier: NCT00798369.

ObjectiveThis 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.MethodsIn 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.ResultsA 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.ConclusionsSingle canakinumab doses ≥50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg.

IntroductionWe report the impact of canakinumab, a fully human anti-interleukin-1β monoclonal antibody, on inflammation and health-related quality of life (HRQoL) in patients with difficult-to-treat Gouty Arthritis.MethodsIn 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).ResultsAt 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.ConclusionsCanakinumab 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.Trial registrationclinicaltrials.gov: NCT00798369.

Background. Elderly persons often experience a reduced immune response to influenza vaccination. We evaluated the usual dose of AS03A-adjuvanted H5N1 pandemic vaccine (3.75 μg hemagglutinin of A/Vietnam/1194/2004-like strain) compared with a double dose in an elderly population.Methods. This phase 2, open-label study (NCT00397215; http://www.clinicaltrials.gov) randomized participants (age, ≥61 years) to receive, on days 0 and 21: (1) a single dose of AS03A-adjuvanted vaccine (n = 152), (2) a single dose of nonadjuvanted vaccine (n = 54), (3) a double dose of AS03A-adjuvanted vaccine (n = 145), or (4) a double dose of nonadjuvanted vaccine (n = 44). The primary end point was hemagglutination inhibition (HI) and neutralizing antibody response against vaccine antigen (according-to-protocol cohort).Results. Day 42 geometric mean titers for HI antibodies were 126.8 and 237.3 for single and double doses of the AS03A-adjuvanted vaccine, respectively. Corresponding values for neutralizing antibodies were 447.3 and 595.8. Although the immune response was higher with the double dose, European Committee for Human Medicinal Products criteria for seroconversion and seroprotection rates were achieved in both AS03A-adjuvanted groups. Antigen-specific CD4 T cell responses were elicited. Immune response persistence at 6 months was high. Immune response in the non-adjuvanted groups was considerably less.Conclusions. The AS03A-adjuvanted H5N1 vaccine can be administered elderly persons at the same dose and schedule as in younger adults.

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BackgroundAlthough commonly diagnosed, gout often remains a poorly managed disease. This is partially due to a lack of awareness of the long-term effect of gout among patients and healthcare professionals.AimTo understand unmet needs for patients and provide insight into achieving better treatment.Design & settingA quantitative online questionnaire collected from 1100 people with gout from 14 countries within Europe.MethodPatients were recruited to complete an online survey via healthcare professional (HCP) referral, patient associations, or market research panels. Patients were included if they had been diagnosed with gout by a physician. Prior to commencement, patients were made aware that this study was sponsored by Grünenthal. The responses collected were collated and analyses were performed.ResultsPatients had an average of 2.9 gout flares within a 12-month period. Although 79% of patients were satisfied with treatment, inadequate gout control was also reported by 71% of patients. Furthermore, 84% experienced moderate-to-severe pain with their most recent flare. Of those who acknowledged treatment dissatisfaction, only 24% discussed other options with their GP. Most patients reported irregular follow-up and serum uric acid (sUA) monitoring. In addition, loss of belief that more can be done was a key barrier for patients.ConclusionPatients reported severe pain and social burden, coupled with low treatment expectation and lack of awareness of target sUA. Education around knowing and reaching sUA target is needed so that patients can receive and GPs can deliver higher quality management.

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Background: Rituximab (RTX) in combination with methotrexate (MTX) has been licensed since 2006 for the management of severe active rheumatoid arthritis (RA) in patients who have failed at least one anti-tumour necrosis factor (anti-TNF) therapy. Published clinical trials have demonstrated the efficacy of RTX in improving both clinical symptoms and patients' physical function. This study aimed to assess the effectiveness of RTX in RA patients treated in routine clinical practice by examining clinical and patient reported outcomes six months after receiving a first course of RTX. Methods: The analysis involved 550 RA patients registered with the BSRBR, who were starting RTX and were followed up for at least 6 months. Change in Disease Activity Score (DAS28) and European League Against Rheumatism (EULAR) response were used to assess the clinical response while change in Health Assessment Questionnaire (HAQ) score was used to assess the physical function of the patients 6 months after starting RTX. The change in DAS28 and HAQ was compared between seronegative and seropositive patients and anti-TNF naïve patients versus anti-TNF failures. The response was also compared between patients receiving RTX in combination with MTX, other non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) or no nbDMARDs. Results: The mean (S.D.) age of the cohort was 59 (12) years and 78% of the patients were females. The patients had a mean (S.D.) of 15 (10) years of disease duration. 16% were biologic naïve while 84% were anti-TNF failures. 32% of the patients were seronegative and 68% were seropositive. The mean (95% CI) DAS28 at baseline was 6.2 (6.1, 6.3) which decreased to 4.8 (4.7, 4.9) at 6 months of follow up. 16% were EULAR good responders, 43% were moderate responders and 41% were non responders. The mean (95% CI) change in HAQ was À0.1 (À0.2, À0.1) (Table 1). The mean change in DAS28 was similar in seropositive and seronegative patients (p ¼ 0.18) while the anti-TNF naïve patients showed a greater reduction in DAS28 scores than anti-TNF failures (p ¼ 0.05). Patients receiving RTX in combination with MTX showed similar changes in DAS28 and HAQ compared to patients receiving RTX alone or with other nbDMARDs. Conclusions: RTX has proven to be effective in the routine clinical practice. Anti-TNF naïve patients seem to benefit more from RTX treatment than anti-TNF failures.