BackgroundCanakinumab (CAN) has been shown not to impair antibody production following vaccination in children in an open-label phase 3 study (NCT01302860).1 Here we present the results from the extension of this study.ObjectivesTo evaluate the presence of protective antibody levels following immunisation with inactivated vaccines in CAPS patients during extension study.MethodsPatients who completed the core study were allowed to continue into the extension study on the standard dosing regimen of 2 mg/kg subcutaneous CAN every 8 weeks or on last dose/dosing regimen received in the core study. Vaccination response was evaluated using post-vaccination antibody titres at 4 and 8 weeks after immunisation. Patients were considered assessable for an antibody response to a specific vaccination if they had a measurement of antibody titre 0–14 days post-vaccination (pre-vaccination assessment) and at least 1 subsequent measurement of antibody titre at 4 weeks and/or 8 weeks post-vaccination. However, for patients with adequate pre-dose antibody titres and maintained during the trial, the specific patient vaccination was deemed non-assessable.ResultsDuring the extension phase, of 17 patients (≤6 years), 4 received 8 types of vaccinations against Corynebacterium diphtheriae, Bordetella pertussis, Neisseria meningitidis, Clostridium tetani, influenza type A and type B, Haemophilus influenzae B, Streptococcus pneumoniae, or hepatitis B. Of 20 unique patient-vaccination cases, 17 were assessable for a vaccination response, whereas for the remaining 3, pre-dose antibody titre was not available. For 16 (94.1%) assessable cases, post-vaccination antibody titres increased above protective levels. For one patient who received Tetravec formulation (diphtheria, tetanus and acellular pertussis combination), the response observed for 1 (vaccination against Clostridium tetani) of the 3 vaccines included in Tetravac represented optical density rather than antibody concentrations and hence considered non-evaluable. For 19/20 patient-vaccinations, including those without pre-dose antibody titres, protective levels were observed during the study, which were maintained throughout the extension study.ConclusionsCanakinumab appeared to have no effect on post-vaccination antibody production following the administration of non-live vaccines in CAPS patients.References Brogan P, et al. Arthritis Rheumatol. 2015;67:(S10). Disclosure of InterestP. Brogan Grant/research support from: Novartis, Roche and SOBI, Consultant for: Novartis, M. Hofer Consultant for: Novartis, J. Kuemmerle-Deschner Grant/research support from: Novartis, SOBI, Baxalta, Consultant for: Novartis, B. Lauwerys: None declared, A. Speziale Employee of: Novartis, X. Wei Employee of: Novartis, R. Laxer Grant/research support from: Novartis for Database funding
BackgroundSJIA is a distinct and debilitating form of arthritis associated with elevated cytokine (interleukin [IL]-1 and IL-6) levels.1 Studies have shown that biologics (IL-1 and IL-6 inhibitors), including canakinumab (CAN), a selective, human anti-IL-1β monoclonal antibody, are more effective than conventional medications (NSAIDs, corticosteroids, methotrexate) in the treatment of SJIA patients (pts).1,2 However, little is known about long-term efficacy and safety of biologics in SJIA.ObjectivesTo assess long-term efficacy and safety of CAN treatment in a 5-year (yr) follow-up of SJIA pts.MethodsThis was an open-label extension study of SJIA patients participating in the clinical trials of CAN, with details reported earlier.3 Pts (age, 2–20 yrs) received subcutaneous (sc) CAN (4 mg/kg) every 4 wks. Baseline is defined as the starting point of the extension trial. Efficacy measurements were done every 3 months including adapted paediatric response criteria (aACR), clinical inactive disease, clinical remission on medication (12 months of continuous clinical inactive disease) and juvenile arthritis disease activity score (JADAS). Safety was assessed monthly.ResultsOverall, 147 pts had a median treatment duration of 3.2 yrs, and 82 (56%) were exposed to CAN for >3 yrs (total treatment exposure of ∼365 pt-yrs). At 3 month of CAN therapy, 50% of pts had inactive disease, increasing to 49% at last assessment. Of the 107 pts with an aACR 30 at entry to the extension, 61.7% had aACR 100, with 86.0%, 87.9% and 91.6% having aACR 70/50/30 responses, respectively at last assessment. Clinical remission on medication was achieved in 43.0% of pts. Median JADAS10-CRP at baseline was 8.2 (indicating moderate disease activity), and at last assessment, median change from baseline was −0.2, with a median score of 1.8, indicating low disease activity, with similar results noted for JADAS27-CRP. Most common adverse event (AE) was infection (2.0 infections/100 pyr) typically involving the upper respiratory tract. Overall, 47 (32.0%) pts had >1 serious AE (SAE; mostly infections, macrophage activation syndrome [MAS] or SJIA flare), 10 cases of MAS (43.8 events/100 pyr) were reported, and 18 (12.2%) pts discontinued due to an AE. No deaths were reported.ConclusionsIn patients previously treated with CAN in pivotal trials, response to treatment was sustained or improved during long-term treatment in the extension study. Safety profile of CAN was consistent with safety findings from previous studies.ReferencesRuperto N, et al. N Engl J Med. 2012;367:2396–406.Ringold S, et al. Arthhritis & Rheum. 2013;65(10):2499–512.Ruperto N, et al. Ann Rheum Dis. 2015;74(2):608.Disclosure of InterestN. Ruperto Grant/research support from: Abbott, BMS, “Francesco Angelini”, GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma, Wyeth, Speakers bureau: Abbott, AbbVie, Amgen, Biogenidec, Astellas, Alter, AstraZeneca, Boehringer, BMS, CD-Pharma,Celgene, CrescendoBio, EMD Serono,Hoff...
BackgroundThe main therapeutic goals that can determine success of biologic treatment in systemic juvenile idiopathic arthritis (SJIA) include achieving and maintaining clinical remission, controlling disease activity and tapering corticosteroids (CS). Canakinumab (CAN) has been shown to improve several of these parameters in previous studies1. However, little is known about SJIA patients (pts) using CAN long-term.ObjectivesTo evaluate the efficacy, safety and long-term treatment response of CAN treatment-naïve pts with active SJIA.MethodsThis was an open-label, non-comparative study (NCT00891046) of CAN-naïve SJIA pts (age ≥2 - <20 yrs) receiving CAN 4 mg/kg by s.c. q4w. Efficacy was assessed by the adapted pediatric ACR (aACR 30/50/70/90/100) responses compared to baseline (BL); inactive disease (ID) or clinical remission (ID for >6 Mo) and changes in JADAS-CRP (Juvenile Arthritis Disease Activity Score- C-reactive protein) scores over time. Safety was assessed by adverse events (AEs) and serious AEs (SAEs) reports.ResultsA total of 123 pts with active SJIA were enrolled of whom 70 (57%) pts had fever and 71 (57.7%) pts used CS at BL. Mean CRP was 117.8 mg/L (normal: 0–10mg/L) and, on average, pts had, 9.9 active joints and 8.9 joints with limited motion. A rapid response was observed at Day 15, 59 (51%) with aACR ≥70 responses and 27 (26%) having aACR 100 responses. These responses increased and were maintained at subsequent time points (Table). Overall, 73.0% of pts had ID on at least 1 visit. At 6th month, clinical remission was achieved in 52 (42.3%) pts and 33 (26.8%) pts had clinical remission for at least 12 consecutive months. At BL, the median JADAS10-CRP score was 22.3 (indicating high disease activity), with median changes from BL of -12.0 at Day 15 and -16.8 at last assessment indicating moderate and low disease activity, respectively. At the last assessment, 59 (48.4%) pts were rated as ID (JADAS <1); 14 (11.5%) with low active disease activity (JADAS >1 and <3.8); while 14 (11.5%) had moderate and 35 (28.7%) with high disease activity. 24 (33.8%) pts were steroid-free at last assessment. A total of 53 (43.4%) pts had at least 1 AE. Overall rate of AEs was 2.25 events/ 100 patient-days and SAEs was 0.15/ 100 patient-days. 40 (32.5%) pts had SAEs and the most commonly reported were disease flares or worsening of SJIA in 13 (10.6%) pts, macrophage activation syndrome in 6 (4.9%) pts, and pyrexia in 4 (3.3%) pts. No deaths were reported in this study.ConclusionsIn this long-term study, CAN treatment was associated with rapid response and sustained therapeutic effect over the long-term in the naïve pts with active SJIA. The safety profile is consistent with other CAN studies.ReferencesRuperto et al. N Engl J Med. 2012;367:2396–406.Disclosure of InterestN. Ruperto Grant/research support from: BMS, GlaxoSmithKline (GSK), Hoffman-La Roche, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi and Merck Serono funded The Gaslini Hospital for the research activities of the hospital in a fully ...
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