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Chronic spontaneous urticaria is an idiopathic syndrome defined by recurring itch, hives, or angioedema (or a combination of these symptoms) for more than 6 weeks. Remibrutinib, an oral, highly selective Bruton's tyrosine kinase inhibitor, showed efficacy and favorable safety in phase 2b trials. Data from phase 3 trials are needed. In the identical, multicenter, double-blind, randomized, placebo-controlled REMIX-1 and REMIX-2 trials, we evaluated the efficacy and safety of remibrutinib in patients with symptomatic chronic spontaneous urticaria after treatment with second-generation H -antihistamines. Patients were randomly assigned in a 2:1 ratio to receive oral remibrutinib at a dose of 25 mg twice daily or placebo. The primary end point was the change from baseline to week 12 in the urticaria activity score during a 7-day period (UAS7), which comprises severity scores for itch and hives during 1 week (scores range from 0 to 42, with higher scores indicating greater severity). Key secondary end points included adverse events and a UAS7 of 6 or lower at weeks 2 and 12 and a UAS7 of 0 at week 12. A total of 470 patients in REMIX-1 and 455 in REMIX-2 were randomly assigned to receive either remibrutinib (313 and 300 patients, respectively) or placebo (157 and 155 patients, respectively). The remibrutinib group had a significantly greater decrease in the UAS7 at week 12 than the placebo group (least-squares mean [±SE] change, -20.0±0.7 vs. -13.8±1.0 [P<0.001] in REMIX-1 and -19.4±0.7 vs. -11.7±0.9 [P<0.001] in REMIX-2), which appeared to be sustained through week 24. At week 12, significantly more patients in the remibrutinib group than in the placebo group had a UAS7 of 6 or lower (REMIX-1, 49.8% vs. 24.8% [P<0.001]; REMIX-2, 46.8% vs. 19.6% [P<0.001]) and a UAS7 of 0 (REMIX-1, 31.1% vs. 10.5% [P<0.001]; REMIX-2, 27.9% vs. 6.5% [P<0.001]). The percentages of patients with any adverse event and with serious adverse events were similar in the remibrutinib group and the placebo group, although a higher percentage of patients in the remibrutinib group than in the placebo group had petechiae (3.8% vs. 0.3% in the combined groups). Treatment with oral remibrutinib resulted in a significant improvement in a composite measure of itching and hives at week 12. (Funded by Novartis Pharmaceuticals; REMIX-1 and REMIX-2 ClinicalTrials.gov numbers, NCT05030311 and NCT05032157, respectively.).

Background Systemic juvenile idiopathic arthritis (SJIA) is characterized by recurrent flares of active disease comprising of fever, arthritis and markedly elevated inflammatory markers. Canakinumab (CAN), a fully human, selective, anti-IL-1β monoclonal antibody was approved for SJIA patients (≥2 years old) by over 30 countries including USA, EU, Russia and Canada. CAN treatment in patients with SJIA allows for successful steroid dose reduction/discontinuation and reduces risk to experience a flare.1 Objectives To evaluate the maintenance of efficacy with continued CAN treatment in SJIA patients during the blinded randomized treatment withdrawal part of a large phase III trial. Methods Patients 2–19 yrs of age with active SJIA who had responded to open-label CAN treatment 4mg/kg/4wks sc, maintained a minimum adapted ACR Pediatric criteria [aACR] 30 for up to 32 weeks, and were steroid-free or had successfully reduced systemic steroids to a minimum dose, were randomized to either continue CAN or receive placebo until 37 flare events occurred.1 Patients were considered to have completed the study if they entered clinical remission on medication (CRM), i.e. achieved 24 consecutive weeks of clinical inactive disease (CID).2 A survival analysis of the time to worsening in aACR level, after randomization for the CAN and placebo groups was performed. Time to worsening is the time to fail to maintain at least the same level of ACR response seen at randomization. The change in the proportion in each group of those with CID was also evaluated. Results 100 pts were randomized to a CAN (n=50) or a placebo (n=50) group, of whom 26 (53%) and 27 (54%), respectively, had CID at the start of the randomization part. In the first 2 months, probability of maintaining aACR response was similar for both treatment groups. Thereafter, the probability of maintaining aACR response was greater in the CAN vs. placebo groups. The median time to worsening in aACR level for patients in the placebo group was 141 days (95% CI: 85, 281), and could not be calculated for CAN as <50% of CAN group had a worsening in their aACR level by the end of this phase. The median duration of exposure for the CAN group was 221.5 days (range: 8-617 days). There was a statistically significant relative risk reduction of 51% for the CAN vs. placebo group to experience a worsening in aACR level (HR=0.49; 95% CI: 0.27, 0.90; p=0.0131). CID was achieved by 31 (62.0%) vs. 17 (34.0%) patients in CAN vs placebo group at their last visit (OR=3.4; 95% CI: 1.5, 8.0; p=0.0020) and CRM was reached by 20 (40%) CAN and 2 (4%) placebo pts by the end of the study. Conclusions A greater proportion of SJIA pts who continued CAN treatment maintained/improved their aACR response, achieved CID and CRM than pts who discontinued CAN by being switched to placebo, demonstrating maintenance of efficacy with continued CAN treatment over time. References Ruperto N, et al. N Engl J Med 2012;367(25):2396–406. Wallace CA, J Rheumatol 2004;31(11):2290-4 Disclosure of Interest N. Wulffraat Grant/research support: Abbvie, Roche, Consultant for: Novartis, Pfizer, Roche, N. Ruperto Grant/research support: To Gaslini hospital from Abott, Astrazeneca, BMS, Centocor reserach& development, Eli lilly & company, “Francesco Angelini”, Glaxo Smith & Kline, Italfarmaco, Novartis, Pfizer Inc., Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals Inc., Speakers bureau: Astrazeneca, Bristol Myers and Squibb, Janssen Biologics B.V., Roche, Wyeth, Pfizer, H. Brunner Consultant for: Roche, Janssen, Novartis, Astrazeneca; UCB, Celegene, Pfizer, GSK, Speakers bureau: Novartis, S. Oliveira Grant/research support: Novartis, Roche, Y. Uziel Speakers bureau: Fee for few talks at medical meeting from Novartis, Neopharm, Roche, K. Nistala: None declared, R. Cimaz: None declared, M. Ferrandiz Grant/research support: Principal investigator fees by Novartis, B. Flato Grant/research support: Coinvestigator in the initial study on efficacy by canakinumab treatment in systemic juvenile idiopathic arthritis patients. Expenses for personnel covered by Novartis, M. Gamir: None declared, I. Koné-Paut Grant/research support: SOBI, LFB, Consultant for: Novartis, SOBI, Pfizer, Chugai, C. Gaillez Employee of: Novartis Pharma AG, K. Lheritier Shareholder of: Novartis, Employee of: Novartis Pharma AG, K. Abrams Shareholder of: Novartis, Employee of: Novartis Pharmaceutical corporation, A. Martini Grant/research support: From Bristol Myers and Squibb, Centocor Research & Development,Glaxo Smith to Gaslini hospital for PRINTO research activities, Consultant for: From Bristol Myers and Squibb, Centocor Research & Development,Glaxo Smith & Kline,Novartis,Pfizer Inc,Roche,Sanofi Aventis, Schwarz Biosciences GmbH to Gaslini hospital for PRINTO research activities, Employee of: Gaslini hospital, Speakers bureau: Abbott, Bristol MyersSquibb, Astellas,Boehringer,Italfarmaco,MedImmune,Novartis,NovoNordisk, Pfizer,Sanofi, Roche, Servier, D. Lovell Grant/research support: National Institutes of Health- NIAMS, Consultant for: Astra-Zeneca, Centocor, Amgen, Bristol Meyers Squibb, Abbott, Pfizer, Regeneron, Roche, Novartis, UCB, Forest Research Institute, Horizon, Johnson & Johnson, Speakers bureau: Novartis, Roche DOI 10.1136/annrheumdis-2014-eular.1215

BackgroundEfficacy and safety of canakinumab (CAN) in frequently flaring difficult-to-treat gouty arthritis (GA) patients (pts) in whom NSAIDs and/or colchicine are contraindicated, not tolerated or ineffective has been published previously. Here, we present the cumulative results from a single long term extension of two phase III studies.ObjectivesTo evaluate the long-term safety and tolerability of CAN. Frequency of new flares, mean number of doses/pt, pts' assessments of GA pain intensity and global assessment (PGA) of response (both on Likert scale) and hsCRP were measured. The efficacy of CAN to maintain urate lowering therapy (ULT) was explored by assessing serum uric acid (SUA) level in pts' initiating or modifying their ULT while exposed to CAN.MethodsAn 18-month, multi-center, open-label, clinical extension study, where all pts upon completing earlier two extension studies continued to be treated with CAN 150 mg for any new GA flare. The treatment groups were analyzed as “CAN Group” [CG] and “TA Group” [TG], i.e. all patients who were initially randomized to receive CAN or TA, respectively, and received at least one dose of study drug. Safety was assessed in terms of exposure-adjusted incidence of adverse events (AEs) per 100 patient-years (pyr). Maximum total cumulative duration was 3 years.ResultsOf the 456 pts randomized in core studies, 136 pts entered and 122 completed E3. Mean flare rate/yr was lower for the CG (1.1) vs TG (2.5). CG pts maintained clinical efficacy (pain intensity and PGA of response to treatment) upon “on demand” retreatment over 3 years. Median hsCRP levels remained below the upper limit normal in pts re-treated with CAN upon demand for new GA flares from 7 days post initial dose over 3 years until end of study. Thirty% (n=12) of pts initiating or modifying ULT during the E3 (n=40) reached target SUA level (<6mg/mL). Overall, the exposure adjusted incidence of AEs in CG was lower (264.6/100 pyr) than in TG (308.8/100 pyr). Re-treatment with CAN did not result in increased incidence of AEs. Overall, the incidence of exposure adjusted SAEs in CG and TG was 17.3 and 17.7 per100 pyr, respectively. The overall incidence of SAEs did not change in pts re-treated with CAN in CG (15.2 vs 15.1 per 100 pyr). Overall 4 deaths, none study drug-related, (2 in CG, 2 in TG), were reported: 1 intracranial hemorrhage [pt not re-treated with CAN]; 1 pneumonia [pt re-treated with CAN], 1 sudden cardiovascular death and 1 pneumococcal sepsis [TG pt who never received CAN]).ConclusionsOver 3 years, CAN mean dose with “on demand” dosing of 2.68 per pt, maintained pain intensity and PGA response scores in difficult to treat GA pts. These results support the long-term safety of CAN treatment in pts' with frequent GA flares. The safety profile was consistent with that observed in previous studies.Disclosure of InterestR. Alten Grant/research support from: Novartis, Speakers bureau: Novartis, T. Bardin Consultant for: Novartis, Astrazeneca, Menarini, Ipsen Pharma, Sobi, M. Bloch Grant/research support from: support to my institution for research: Novartis, Gilead Sciences, ViiV Healthcare, Bristol Myers-Squibb, Merck, Romark, Abbvie, Consultant for: Advisory Board Gilead Sciences, ViiV Healthcare, Bristol Myers-Squibb, Merck, Eli Lilly, Speakers bureau: Eli Lilly, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, U. Machein Employee of: Novartis, G. Junge Employee of: Novartis, A. So Shareholder of: Novartis (<10,000US$), N. Schlesinger Grant/research support from: Novartis, Consultant for: Novartis, Sobi, Speakers bureau: Novartis, Takeda

BackgroundGouty arthritis (GA) patients who experience frequent flares and have comorbidities have limited treatment options and need effective alternative treatments. Canakinumab (CAN), a selective, human, anti-interleukin-1β monoclonal antibody, has been approved in the European Union for the treatment of difficult-to-treat GA patients.ObjectivesA liquid formulation of CAN, presented as pre-filled syringe (CAN-PFS) has been developed to improve upon the lyophilized form (CAN-LYO) that requires reconstitution. A cumulative safety and efficacy results covering a total of 48 weeks are presented.MethodsGA patients completing the 12 week core study1 were enrolled in a 36 week open label extension (E1) study. All patients entering E1 received CAN-PFS 150 mg sc on demand upon new GA flare irrespective of assigned treatment during randomization [CAN-PFS, CAN-LYO or triamcinolone acetonide 40 mg (TA)]. The primary objective was to confirm the long-term safety of CAN-PFS vs TA. Secondary objectives included evaluation of CAN-PFS vs TA and CAN-LYO vs PFS for the time to first new flare over 48 weeks. Long-term safety outcomes and safety upon re-treatment were assessed as exposure-adjusted incidence rate of adverse events (AEs) and serious AEs (SAEs).ResultsOf 397 patients randomized in the core study, 232 (58.4%) entered E1, of which 198 (50%) completed E1. Baseline characteristics were comparable between the treatment groups. The exposure-adjusted incidence of AEs was lower for both CAN-PFS (254.9/100 pyr) and CAN-LYO (224.8/100 pyr) groups when compared with TA (362.7/100 pyr) over the 48 weeks. The exposure-adjusted incidence of SAEs was 14.7/100, 16.1/100, 15.5/100 pyr in patients randomized to CAN-PFS, CAN-LYO and TA groups, respectively. Infections and infestations were the most frequently reported SAE in the CAN-PFS (3.4/100 pyr), CAN-LYO (3.2/100 pyr), TA (0/100 pyr) groups. Over 48 weeks, one death (cardiac failure), not suspected to be related to study drug, was reported in a patient randomized to CAN-PFS who was not re-treated over 48 weeks. Overall, no new safety signals were observed in this extension study. CAN-PFS treatment significantly delayed time to first new flare vs TA patients with a relative risk reduction of 55% (HR, 0.45; 95% CI, 0.32 to 0.64; p<0.0001) over 48 weeks. The mean number of new GA flares per patient was lower for both CAN-LYO (0.50) and CAN-PFS (0.76) groups when compared with the TA group (0.96). Patients in the CAN-PFS group had a 56% reduction in the number of new flares compared to the TA group (rate ratio of 0.44, 95% CI 0.32 to 0.61, p<0.0001). However, both CAN treatments showed a similar mean flare rate per year (CAN-PFS, 0.95; CAN-LYO, 1.13).ConclusionsThese results further corroborate the long-term safety and efficacy of canakinumab liquid formulation in patients with frequent GA flares. The safety profile of canakinumab was consistent with the one observed in the core study and the efficacy of canakinumab pre-filled syringe was maintained upon re-treatment.ReferencesSunkureddi P, et al. Arthritis & Rheumatism 2013;65(10):S498.Disclosure of InterestR. Möricke: None declared, P. Sunkureddi Grant/research support from: Novartis, E. Toth: None declared, J. Brown Grant/research support from: Abvie, Amgen, Eli Lilly, Novartis, Pfizer, Roche, Takeda, Consultant for: Amgen, Eli Lilly, Speakers bureau: Amgen, Eli Lilly, U. Machein Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, G. Junge Employee of: Novartis, A. Kivitz: None declared

BackgroundPeriodic fever syndromes (PFS) are a group of rare auto-inflammatory conditions, which includes, among others, cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), hyper-IgD syndrome/mevalonate kinase deficiency (HIDS/MKD), TNF-receptor associated periodic syndrome (TRAPS). Canakinumab (CAN), a fully human, highly specific anti-IL-1β neutralising monoclonal antibody, is effective in CAPS.1 IL-1β has been shown to be involved in the pathogenesis of FMF, HIDS/MKD and TRAPS, for whom no approved treatment exists. A series of small open label studies suggested efficacy of CAN in colchicine resistant/intolerant FMF (crFMF), HIDS/MKD and TRAPS.2,3 We report the efficacy and safety of CAN from the randomised treatment epoch of a phase III trial in patients (pts) with crFMF, HIDS/MKD or TRAPS.ObjectivesPrimary objective of this phase III pivotal trial was to demonstrate that CAN 150 mg (or 2 mg/kg for pts ≤40 kg) sc q4w is superior to placebo (PBO) in achieving a clinically meaningful response defined as resolution of the index flare at Day 15 and no new disease flares over 16 wks of treatment. Secondary objectives were: % pts who achieved a physician global assessment of disease activity (PGA) <2 (minimal/none); % pts with C-reactive protein (CRP) ≤10 mg/L; serum amyloid A level (SAA) ≤10 mg/L at Wk 16.MethodsThe trial (NCT02059291) consists of 3 disease cohorts (crFMF, HIDS/MKD and TRAPS) and 4 study epochs (E1–4): a screening epoch (E1) of up to 12 wks, a randomised treatment epoch (E2) of 16 wks, a randomised withdrawal epoch (E3) of 24 wks and an open-label treatment epoch (E4) of 72 wks. Pts (age ≥2 years) with crFMF, HIDS/MKD or TRAPS with a flare during E1 were randomised (1:1) in E2 to receive CAN or PBO. Safety assessments included adverse events (AEs).ResultsOf 181 pts (crFMF, n=63; HIDS/MKD, n=72; TRAPS, n=46) randomised in E2, 6 pts discontinued (5 PBO; 1 CAN). In all 3 disease cohorts, the proportion of pts who were responders for the primary outcome at Wk 16 was significantly higher with CAN vs PBO (Table). At Wk 16, a significantly higher proportion of pts achieved PGA score <2, CRP ≤10 mg/L and SAA ≤10 mg/L in the CAN group vs PBO in all 3 cohorts (Table). No new safety findings were reported in the CAN-treated pts through E2 (Table).ConclusionsThese results demonstrated superior efficacy of canakinumab at dose level of 150 mg q4w after a 16 weeks treatment period compared to placebo. The overall safety profile was not distinct from previous controlled studies and expectations in an auto-inflammatory patient population.Disclosure of InterestF. De Benedetti Grant/research support from: Pfizer, Abbvie, Roche, Novartis, Novimmune, BMS, J. Anton Grant/research support from: Novartis, Pfizer, Abbvie, Roche, SOBI, Consultant for: Novartis, M. Gattorno Grant/research support from: Novartis, SOBI, Consultant for: Novartis, SOBI, Speakers bureau: Novartis, SOBI, H. Lachmann Consultant for: Novartis, SOBI, Takeda, GSK, Speakers bureau: Novartis, SOBI, I. Kone-Paut Grant/research support from: SOBI, Roche, Novartis, Consultant for: Novartis, SOBI, Pfizer, Abbvie, Chugai, S. Ozen Consultant for: Novartis, Speakers bureau: SOBI, J. Frenkel Grant/research support from: Novartis, SOBI, A. Simon Grant/research support from: CSL Behring, Novartis, Xoma/Servier, A. Zeft: None declared, E. Ben-Chetrit Consultant for: Novartis, H. Hoffman Grant/research support from: BMS, Consultant for: Novartis, SOBI, Regeneron, Speakers bureau: Novartis, Y. Joubert Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, A. Speziale Employee of: Novartis, G. Junge Employee of: Novartis

BackgroundPeriodic fever syndromes are a group of rare autoinflammatory conditions that includes, among others, cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), hyper-IgD syndrome/mevalonate kinase deficiency (HIDS/MKD) and TNF receptor-associated periodic syndrome (TRAPS). The pharmacokinetics (PK) of canakinumab (CAN) and total interleukin (IL)-1β kinetics have been well characterised in CAPS patients (pts).1 Here we present the PK and pharmacodynamics (PD) of CAN in colchicine resistant/intolerant (crFMF), HIDS/MKD and TRAPS pts.ObjectivesTo evaluate the PK and PD of CAN (solution for injection-liquid in vial [LIVI]) from the phase III study in crFMF, HIDS/MKD and TRAPS pts at Week 16.MethodsThe study (NCT02059291) comprised of 3 disease cohorts (crFMF, HIDS/MKD and TRAPS). Each cohort followed the same study design across 4 epochs (screening epoch [up to 12 weeks], randomised treatment epoch [16 weeks], randomised withdrawal epoch [24 weeks] and open-label treatment epoch [72 weeks]). Pts (age, ≥2 years) with crFMF, HIDS/MKD or TRAPS who had a flare during Epoch 1 were randomised (1:1) in Epoch 2 to receive subcutaneous (sc) CAN 150 mg (or 2 mg/kg for pts weighing ≤40 kg) every 4 weeks (q4w) or placebo. Blinded uptitration (up to 300 mg) was allowed for pts not resolving the index flare by day15. Samples for CAN concentrations and total IL-1β were collected at baseline (Day 1), and trough samples at weeks 2, 4, 8, 12 and 16.ResultsIn crFMF, HIDS/MKD and TRAPS pts, the serum clearance and steady-state volume of distribution of CAN varied according to body weight and were estimated to be 0.14±0.04 L/day and 4.96±1.35 L, respectively. The estimated half-life of CAN was 25.6±6.4 days. CAN minimal concentration at Week 16 following 150 mg sc q4w dosing was estimated to be 15.3±6.6 μg/mL. The estimated steady state area under the serum concentration-time curve from time zero to the end of the dosing interval tau (AUCtau) was 648±202 μg.day/mL. Similar results were obtained in 3 diseases. CAN binding to circulating IL-1β was demonstrated by increase in total IL-1β following CAN dosing in all 3 diseases. In pts requiring up titration to 300 mg, levels of total IL-1β were higher suggesting higher production of IL-1β.ConclusionsThis was first study to evaluate the PK characteristics of canakinumab given in the LIVI form. The results observed in crFMF, HIDS/MKD and TRAPS patients were similar to those observed in other indications (CAPS and SJIA) using the lyophilisate form. These data suggested that new formulation did not affect PK/PD of the drug and similarly to CAPS, patients with higher levels of IL-1β may require canakinumab up-titration to have an optimal disease control.ReferencesChakraborty A, et al. Clin Pharmacokinet. 2012;51:e1–18.Disclosure of InterestF. De Benedetti Grant/research support from: Pfizer, Abbvie, Roche, Novartis, Novimmune, BMS, J. Anton Grant/research support from: Novartis, Pfizer, Abbvie, Roche, SOBI, Consultant for: Novartis, M. Gattorno Grant/research support from: Novartis, SOBI, Consultant for: Novartis, SOBI, Speakers bureau: Novartis, SOBI, H. Lachmann Consultant for: Novartis, SOBI, Takeda, GSK, Speakers bureau: Novartis, SOBI, I. Kone-Paut Grant/research support from: SOBI, Roche, Novartis, Consultant for: Novartis, SOBI, Pfizer, Abbvie, Chugai, S. Ozen Consultant for: Novartis, Speakers bureau: SOBI, J. Frenkel Grant/research support from: Novartis, SOBI, A. Simon Grant/research support from: CSL Behring, Novartis, Xoma/Servier, A. Zeft: None declared, E. Ben-Chetrit Consultant for: Novartis, H. Hoffman Grant/research support from: BMS, Consultant for: Novartis, SOBI, Regeneron, Speakers bureau: Novartis, Y. Joubert Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, A. Speziale Employee of: Novartis, G. Junge Employee of: Novartis, X. Xu Employee of: Novartis

BackgroundPeriodic Fever Syndromes (PFS) are rare autoinflammatory conditions including Familial Mediterranean Fever (FMF), Hyper-IgD Syndrome/ Mevalonate Kinase Deficiency (HIDS/MKD), and TNF-Receptor Associated Periodic Syndrome (TRAPS).1 It has been shown that colchicine-resistant FMF (crFMF), HIDS/MKD and TRAPS considerably impact physical and emotional aspects of patients' lives.2–4 Open label studies suggested that canakinumab (CAN), a fully human and highly specific anti-IL-1β monoclonal antibody, is efficacious in crFMF, HIDS/MKD and TRAPS.5–7 To date, there is no data showing the effect of CAN on Health-Related Quality of Life (HRQoL) in PFS patients.ObjectivesTo evaluate the effect of CAN on HRQoL using Child Health Questionnaire – Parent Form 50 (CHQ-PF50) and SF-12 Health Survey (SF-12) in PFS patients.MethodsIn a Phase 3 randomised placebo controlled study of CAN in PFS (NCT02059291), SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS) were assessed in adults. For children (>5–<18 years), CHQ-PF50 Physical (PhS) and Psychosocial (PsS) Summary scores were assessed.Results181 patients were randomised to CAN or placebo in 3 cohorts (63 crFMF, 72 MKD/HIDS, 46 TRAPS). 71 adults ≥18 years and 110 children (age range ≥2–<18 years). Patients reported early clinically meaningful improvement in SF-12 PCS scores reported at Week (Wk) 5 which were sustained and increased to a large effect size by Wk 16 for all indications (Table). Similarly, clinically meaningful improvements in SF-12 MCS, CHQ-PF50 PhS and PsS was observed in all indications, with the exception of PsS in HIDS/MKD and TRAPS patients (Table).Table 1.Patient reported outcomesMean change from baseline (n/N)crFMFHIDS/MKDTRAPSWeek 5Week 16Week 5Week 16Week 5Week 16SF-12 PCS7.9 (29/30)9.55 (30/31)13.81 (15/15)13.81 (14/14)9.63 (16/17)11.64 (13/14)SF-12 MCS4.83 (29/30)4.27 (30/31)6.41 (15/15)8.14 (14/14)5.65 (16/17)5.51 (13/14)CHQ-PF50 PhS13.2 (21/24)20.1 (18/21)5.5 (32/34)9.9 (27/29)7.4 (16/18)14.9 (13/14)CHQ-PF50 PsS4.1 (21/24)7.2 (18/21)1.8* (32/34)5.2 (27/29)0.9* (16/18)1.2* (13/14)N = total number of patients; n = patients who received at least one dose of canakinumab. *Minimal important difference8,9from baseline was not achieved.ConclusionsCanakinumab showed rapid improvement by Week 5 in patient reported outcomes in adults and children with PFS, which was sustained through Week 16.ReferencesSavic S. and Wood P. Clin. Med. 2011;11(4):396–401Dandekar P, et al. Pediatr. Rheumatol. 13(S1):P22Dandekar P, et al. Pediatr. Rheumatol. 13(S1):P23Dandekar P, et al. Pediatr. Rheumatol. 13(S1):P24Brik R, et al. Arthritis Rheumatol. 2014;66(11):3241–3Arostegui, J.I, et al. Arthritis Rheumatol. 2015; 67 (S10)Gattorno M, et al. Arthritis Rheumatol. 2015; 67 (S10)User's manual for the SF-12v2 Health Survey, 3rd ed. 2012Cohen J, et. al. Statistical Power Analysis for the Behavioural Sciences,2nd ed. 1988Disclosure of InterestH. Lachmann Consultant for: Novartis, SOBI, Takeda, GSK, Speakers bureau: Novartis, SOBI, A. Simon Grant/research support from: CSL Behring, Novartis, Xoma/Servier, J. Anton Grant/research support from: Novartis, Pfizer, Abbvie, Roche, SOBI, Consultant for: Novartis, M. Gattorno Grant/research support from: Novartis, SOBI, Consultant for: Novartis, SOBI, Speakers bureau: Novartis, SOBI, I. Kone-Paut Grant/research support from: SOBI, Roche, Novartis, Consultant for: Novartis, SOBI, Pfizer, Abbvie, Chugai, S. Ozen Consultant for: Novartis, Speakers bureau: SOBI, J. Frenkel Grant/research support from: Novartis, SOBI, E. Ben-Chetrit Consultant for: Novartis, H. Hoffman Grant/research support from: Bristol Myers Squibb, Consultant for: Novartis, Sob Biovitrum, Regeneron, Speakers bureau: Novartis, A. Zeft: None declared, Y. Joubert Employee of: Novartis, K. Lheritier Employee of: Novartis, A. Speziale: None declared, G. Junge Employee of: Novartis, J. Gregson Employee of: Novartis, F. De Benedetti Grant/research support from: Pfizer, Abbvie, Roche, Novartis, Novimmune, BMS

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,Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda, Vertex, H. Brunner Consultant for: Novartis, Roche, Pfizer, UCB, Celgene, Regeneron, Amgen, Astrazeneca, GSK, BMS, Speakers bureau: Novartis, Roche, P. Quartier Grant/research support from: Abbvie, BMS, Chugai-Roche, Novartis, Pfizer, SOBI, Consultant for: Abbvie, Novartis, Servier, SOBI, Speakers bureau: Abbvie, BMS, Chugai-Roche, Medimmune, Novartis, Pfizer, SOBI, T. Constantin: None declared, E. Alexeeva Grant/research support from: Roche, Abbott, Novartis, Pfizer, Bristol-Myers Squibb, Centocor, Speakers bureau: Roche, Novartis, Merck Sharp Dohme, Bristol-Myers Squibb, Medac, Pfizer, R. Schneider Consultant for: Novartis, Novimmune, Sobi, Innomar Strategies, I. Kone-Paut Grant/research support from: SOBI, Novartis, Roche, Consultant for: Novartis, SOBI, Pfizer, Abbvie, Roche/Chugai, K. Schikler Consultant for: Novartis, Novimmune, Sobi, Innomar Strategies, K. Marzan Grant/research support from: Novartis, Abbvie, N. Wulffraat Grant/research support from: Novartis, S. Padeh: None declared, V. Chasnyk: None declared, C. Wouters Grant/research support from: GSK, Novartis, Roche, J. Kuemmerle-Deschner Grant/research support from: Novartis, Consultant for: Novartis, SOBI, Baxalta, T. Kallinich: None declared, B. Lauwerys: None declared, E. Haddad: None declared, E. Nasonov: None declared, M. Trachana Grant/research support from: Novartis, Abbvie, Bristol Meyers, Consultant for: Novartis, Roche, Pfizer, O. Vougiouka: None declared, K. Leon Employee of: Novartis, A. Speziale Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, A. Martini 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, Biogenidecm Bristol MyersSquibb, Astellas, Behringer, Italfarmaco, Janssen, MedImmune, Novartis, NovoNordisk, Pfizer, Sanofi, Roche, Servier, Takeda, D. Lovell Grant/research support from: National Institutes of Health, Consultant for: Astra-Zeneca, Bristol Meyers Squibb, AbbVee, Pfizer, Roche, Novartis, UCB, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, Glaxo Smith Kline, Boehringer Ingelheim, Celgene, Jannsen, Speakers bureau: Genentech, Roche, Novartis

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 independent manner besides any commitment with third parties, Consultant for: AbbVie, Amgen, Biogenidec, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer, BMS, Celgene, CrescendoBio, EMD Serono, Hoffman-La Roche, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda, UCB Biosciences GmbH, Speakers bureau: AbbVie, Amgen, Biogenidec, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer, BMS, Celgene, CrescendoBio, EMD Serono, Hoffman-La Roche, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda, UCB Biosciences GmbH, H. Brunner Consultant for: Novartis, Genentech/Roche, BMS, Pfizer, Astrazeneca, Jannsen, Tekada, Biogen, BAXALTA, Speakers bureau: Novartis, Genentech/Roche, P. Quartier Grant/research support from: Abbvie, Novartis, Pfizer, Roche, Consultant for: Abbvie, Novartis, Sobi, Speakers bureau: Abbvie, BMS, Novartis, Pfizer, Roche, Sobi, T. Constantin Consultant for: Pfizer, Abbvie, Roche, Novartis, Bristol-Myers Squibb, Speakers bureau: Pfizer, Abbvie, Roche, Novartis, Bristol-Myers Squibb, E. Alexeeva Grant/research support from: Roche, Abbott, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Pfizer, I. Kone-Paut Grant/research support from: Grant/research support to my institution: SOBI, Roche, Novartis, Consultant for: Novartis, SOBI, Pfizer, CHUGAI, Abbvie, K. Marzan Grant/research support from: Novartis and Abbvie, N. Wulffraat Grant/research support from: Sobi, AbbVie, Consultant for: Novartis, Pfizer, R. Schneider Consultant for: Novartis, Roche, Sobi, S. Padeh: None declared, V. Chasnyk: None declared, C. Wouters Grant/research support from: Unrestricted grant support GSK, Novartis, Roche, J. Kuemmerle-Deschner Grant/research support from: Novartis, Consultant for: Novartis, SOBI, Baxalta, T. Kallinich Speakers bureau: Novartis, B. Lauwerys: None declared, E. Haddad Grant/research support from: Unrestricted Institutional Educational Fund, E. Nasonov: None declared, M. Trachana Grant/research support from: Pfizer, O. Vougiouka Grant/research support from: Novartis, K. Leon Employee of: Novartis, A. Speziale Employee of: Novartis, K. Lheritier Employee of: Novartis, A. Martini Grant/research support from: Abbott, Bristol Myers and Squibb, Francesco Angelini S.P.A., Glaxo Smith &Kline, Janssen Biotech Inc Novartis,Pfizer Inc,Roche,Sanofi Aventis and SchwarzBiosciences GmbH funded Gaslini Institute for the PRINTO research activities, Consultant for: Bristol Myers and Squibb, Janssen Biotech Inc,Glaxo Smith & Kline, Novartis,Pfizer Inc, Roche, Sanofi Aventis and Schwarz Biosciences GmbH Biosciences GmbH funded Gaslini Institute for the PRINTO research activities, D. Lovell Grant/research support from: National Institutes of Health, NIAMS, Consultant for: Astra-Zeneca, Bristol Meyers Squibb, AbbVee, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, Glaxo Smith Kline, Boehringer Ingelheim, Celgene, Jannsen, Speakers bureau: Genentech