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Objective: To evaluate the long-term efficacy and safety of canakinumab and explore prediction of response in patients with systemic juvenile idiopathic arthritis (JIA) with or without fever at treatment initiation., Methods: At enrollment, patients with active systemic JIA (ages 2 to <20 years) started open-label canakinumab (4 mg/kg every 4 weeks subcutaneously). Efficacy measures included the adapted American College of Rheumatology (ACR) Pediatric 50/70/90 criteria, the Juvenile Arthritis Disease Activity Score (JADAS), and clinically inactive disease and clinical remission on medication, evaluated by either the JADAS or ACR criteria., Results: Of the 123 patients (70 with fever and 52 without fever [fever status was not reported for 1 patient]), 84 (68.3%) completed the study (median duration 1.8 years). Comparable efficacy (adapted ACR Pediatric 50/70/90/100) was observed by day 15 in both subgroups (60.0%/48.6%/37.1%/24.3% in those with fever and 67.3%/48.1%/34.6%/19.2% in those without fever), and further increased thereafter. By month 6, clinical remission according to the JADAS or the ACR criteria was achieved in 17 (24.3%) and 26 (37.1%), respectively, of patients with fever and 9 (17.3%) and 12 (23.1%), respectively, of patients without fever. Median time to onset of clinical remission according to the JADAS or ACR criteria was 57 and 30 days, respectively, in those with fever, and 58 and 142 days, respectively, in those without fever. An adapted ACR Pediatric 50 response by day 15 was the strongest predictor of achieving clinical remission according to the JADAS (odds ratio [OR] 13 [95% confidence interval (95% CI) 4, 42]; P < 0.0001) or glucocorticoid discontinuation (OR 19 [95% CI 3, 114]; P = 0.002). Of the 71 of 123 patients (57.7%) who received glucocorticoids at study entry, 27 (38.0%) discontinued glucocorticoids and 21 (29.6%) reached a dose of <0.2 mg/kg/day, with no difference between those with and those without fever; 13 patients (10.6%) tolerated a sustained canakinumab dose reduction to 2 mg/kg every 4 weeks. No new safety findings were observed., Conclusion: Canakinumab provided rapid and sustained improvement of active systemic JIA irrespective of the presence of fever at treatment initiation., (© 2020, American College of Rheumatology.)

Objectives: To evaluate the long-term efficacy and safety of canakinumab in patients with active systemic juvenile idiopathic arthritis (JIA)., Methods: Patients (2-19 years) entered two phase III studies and continued in the long-term extension (LTE) study. Efficacy assessments were performed every 3 months, including adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and ACR clinical remission on medication criteria (CR ACR ). Efficacy analyses are reported as per the intent-to-treat population., Results: 144 of the 177 patients (81%) enrolled in the core study entered the LTE. Overall, 75 patients (42%) completed and 102 (58%) discontinued mainly for inefficacy (63/102, 62%), with higher discontinuation rates noted in the late responders group (n=25/31, 81%) versus early responders (n=11/38, 29%). At 2 years, aJIA-ACR 50/70/90 response rates were 62%, 61% and 54%, respectively. CR ACR was achieved by 20% of patients at month 6; 32% at 2 years. A JADAS low disease activity score was achieved by 49% of patients at 2 years. Efficacy results were maintained up to 5 years. Of the 128/177 (72.3%) patients on glucocorticoids, 20 (15.6%) discontinued and 28 (22%) tapered to 0.150 mg/kg/day. Seven patients discontinued canakinumab due to CR. There were 13 macrophage activation syndrome (three previously reported) and no additional deaths (three previously reported). No new safety findings were observed., Conclusion: Response to canakinumab treatment was sustained and associated with substantial glucocorticoid dose reduction or discontinuation and a relatively low retention-on-treatment rate. No new safety findings were observed on long-term use of canakinumab., Trial Registration Numbers: NCT00886769, NCT00889863, NCT00426218 and NCT00891046., Competing Interests: Competing interests: NR: consultant and speaker’s bureaus from AbbVie, Ablynx, Amgen, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, MedImmune, Novartis, Pfizer, R-Pharm, Roche, Sanofi, Servier, Takeda; NR works as a full-time public employee of the public hospital Istituto Giannina Gaslini, which has received contributions from Bristol-Myers Squibb, Hoffman-La Roche, Janssen, Novartis, Pfizer, Sobi for the coordination activity of the PRINTO network. HIB: consultant: AstraZeneca, Bristol-Myers Squibb, Genentech, Janssen, Novartis, Pfizer, Sanofi, Takeda; speaker’s bureaus: Genentech, Novartis Pierre Quartier; has received consultant fees from Novimmune, Novartis and SOBI; has received speaker’s bureaus from Abbvie, BMS, Chugai-Roche, Lilly, Novartis, Pfizer and Sobi; has acted as coordinator or investigator in clinical trials for Abbvie, BMS, Chugai-Roche, Novartis, Sanofi, Sobi; has acted as member of a data monitoring board committee for Sanofi. NMW has received grant/research support from AbbVie; has received consultant fees from AbbVie, Sobi and Novartis. GH has received speaker’s bureaus from AbbVie, Boehringer Ingelheim, Chugai, MSD, Novartis, Pfizer, Roche and Sobi; has received scientific grants from AbbVie, Chugai, MSD, Novartis, Pfizer and Roche. OK has received speaker’s bureaus from Novartis, Roche, Pfizer and Abbvie. RS has received consultant fees from Novartis, Sobi and Novimmune. JLA has received consultant fees and speaker’s bureaus from AbbVie, Gebro, Novartis, Pfizer, Roche, Sanofi and Sobi. RC has received consultant fees and speaker’s bureaus from Bristol-Myers Squibb, Janssen, Novartis, Pfizer, Sanofi, Roche, Lilly and GlaxoSmithKline. HEF has acted as member of advisory boards for AbbVie, Novartis, Pfizer, Sanofi and Sobi; has received unrestricted educational bursaries from Pfizer, Genzyme, BioMarin and Sobi to develop educational resources for healthcare professionals. DF has received grant/research support from Pfizer and Novartis; has received consultant fees from Novartis, Pfizer, Chugai-Roche and Sobi; has received speaker’s bureaus from Novartis. SCR has received grants for clinical research from Novartis. AVR has received honoraria and participated in Advisory Boards for Novartis. RT has received lecture fees from Pfizer and Bristol-Myers Squibb. JL received fees from Novartis for conducting the statistical analysis. EV is an employee of Novartis Pharma, Basel, Switzerland. AM has no conflicts of interest to declare since March 2016 when he became the Scientific Director of the Istituto Giannina Gaslini, because this role does not allow him to render private consultancy resulting in personal income; consultant on behalf of the Istituto Giannina Gaslini: AbbVie, Boehringer, Novartis, R-Pharm. Istituto Giannina Gaslini has received contributions from Bristol-Myers Squibb, Hoffman-La Roche, Janssen, Novartis, Pfizer, Sobi for the coordination activity of the PRINTO network. DJL has received grant/research support from AbbVie, Bristol-Myers Squibb, NIH, Pfizer, Roche; speaker’s bureaus from Genentech; consultant of AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech, GlaxoSmithKline, Janssen, Johnson & Johnson, Novartis, Takeda, UCB. EU, FC, JB, MF, MF-d, RB and TC have nothing to disclose., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the long-term safety of rituximab (RTX) in rheumatoid arthritis (RA) patients in daily clinical practice., Methods: This was a multicentre (17 Greek Rheumatology sites), prospective, long-term, pharmacovigilance study of patients with moderate to severe RA and an inadequate response or intolerance to ≥1 anti-tumour necrosis factor (TNF) agents. Adverse events (AEs) were recorded and collected prospectively every 2-6 months., Results: 234 patients (mean age: 59±12.5, 79.5% women, mean DAS28: 5.35±1.32) were included and followed for 27.7 months (median). The overall AEs, serious AE (SAEs) and serious infection (SIEs) rate were 48.36, 6.68 and 2.53/100 patient-years, respectively. Three cases of hepatitis B virus (HBV) reactivation were recorded (two in chronic and one in past HBV infection). Withdrawals due to AEs (5.6%) occurred more frequently during the first cycles of RTX therapy while repeated RTX cycles were not associated with an increased risk of AEs. There were 3 deaths with an incidence rate of 0.69/100 patient-years. Age ≥65 years was associated with a higher incidence rate ratio of AEs and SAEs as compared to <65 years (1.53, p=0.002 and 2.88, p=0.005, respectively). Drug retention rate during 434.28 patient-years of follow-up was 57.3%. Factors associated with drug discontinuation by multivariate analysis included age, baseline swollen joint count and no use of concomitant methotrexate therapy., Conclusions: Long-term RTX therapy in a real-life RA cohort, did not reveal any new safety issues. Advanced age was associated with increased risk of AEs and premature drug discontinuation.