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Objectives: This ongoing Phase-2, randomised, placebo-controlled, double-blind study evaluated the efficacy, safety and pharmacokinetics of intravenous belimumab in childhood-onset systemic lupus erythematosus (cSLE)., Methods: Patients (5 to 17 years) were randomised to belimumab 10 mg/kg intravenous or placebo every 4 weeks, plus standard SLE therapy. Primary endpoint: SLE Responder Index (SRI4) response rate (Week 52). Key major secondary endpoints: proportion of patients achieving the Paediatric Rheumatology International Trials Organisation/American College of Rheumatology (PRINTO/ACR) response using 50 and '30 alternative' definitions (Week 52), and sustained response (Weeks 44 to 52) by SRI4 and Parent Global Assessment of well-being (Parent-global). Safety and pharmacokinetics were assessed. Study not powered for statistical testing., Results: Ninety-three patients were randomised (belimumab, n=53; placebo, n=40). At Week 52, there were numerically more SRI4 responders with belimumab versus placebo (52.8% vs 43.6%; OR 1.49 (95% CI 0.64 to 3.46)). PRINTO/ACR 30 alternative (52.8% vs 27.5%; OR 2.92 (95% CI 1.19 to 7.17)) and PRINTO/ACR 50 (60.4% vs 35.0%; OR 2.74 (95% CI 1.15 to 6.54)) responses were more frequent with belimumab than placebo, as were sustained responses for SRI4 (belimumab, 43.4%; placebo, 41.0%; OR 1.08 (95% CI 0.46 to 2.52)) and Parent-global (belimumab, 59.1%; placebo, 33.3%; OR 3.49 (95% CI 1.23 to 9.91)). Serious adverse events were reported in 17.0% of belimumab patients and 35.0% of placebo patients; one death occurred (placebo). Week-52, geometric mean (95% CI) belimumab trough concentration was 56.2 (45.2 to 69.8) µg/mL., Conclusion: The belimumab intravenous pharmacokinetics and benefit-risk profile in cSLE are consistent with adult belimumab studies and the 10 mg/kg every 4 weeks dose is appropriate., Trial Registration Number: NCT01649765., Competing Interests: Competing interests: DB, KC, AH, AN, DAR, BJ and HS are employees of GSK and hold shares/options in the company; M-LW is a former employee of GSK; HIB has served the speakers bureau of GSK, Roche and Novartis, has been a consultant to Hoffman-La Roche, Novartis, Pfizer, Sanofi Aventis, Merck Serono, AbbVie, Amgen, Alter, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, BMS, Celgene, EMD Serono, Janssen, MedImmune, Novartis, Pfizer and UCB Biosciences GmbH. Payments are made to CCHMC, the employer of HIB; AM has received honoraria for consultancies (<10 000 US$ each) from Eli-Lilly, EMD Serono, Janssen, Novartis, Pfizer and AbbVie; DML has received honoraria and/or consulting fees (<10 000 US$ each) from AbbVie, Janssen and Sobi; NR has received speaker’s bureau and reimbursement of travel expenses from GSK, honoraria for consultancies (<10 000 US$ each) from Ablynx, AbbVie, AstraZeneca-MedImmune, Biogen, Boehringer, Bristol Myers Squibb, Eli-Lilly, EMD Serono, GSK, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi and Takeda. The IRCCS Istituto Giannina Gaslini (IGG), where NR works as full-time public employee has received contributions (>10 000 US$ each) from BMS, Eli-Lilly, GSK, Hoffmann-La Roche, Janssen, Novartis, Pfizer and Sobi. This funding has been reinvested for research activities of the hospital in a fully independent manner, without any commitment with third parties.; JA has received consulting fees and/or honoraria from AbbVie, BMS, Gebro, Novartis, Pfizer, Roche and Sobi; CA-M has received honoraria for consultancies or speaker bureaus from Pfizer, Eli Lilly and Takeda; ICP has received consulting fees from AbbVie, BMS, Novartis, Pfizer, Roche and Sobi; MS has received honoraria for consultancies or speaker bureaus (<10 000 USD each) from AbbVie, Medac Pharm and Novartis., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: This report aims to determine the safety, pharmacokinetics (PK) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis (polyJIA)., Methods: In this three-part randomised double-blinded placebo-controlled withdrawal trial, all patients received open-label golimumab (30 mg/m 2 of body surface area; maximum: 50 mg/dose) every 4 weeks together with weekly methotrexate during Part 1 (weeks 0-16). Patients with at least 30% improvement per American College of Rheumatology Criteria for JIA (JIA ACR30) in Part 1 entered the double-blinded Part 2 (weeks 16-48) after 1:1 randomisation to continue golimumab or start placebo. In Part 3, golimumab was continued or could be restarted as in Part 1. The primary outcome was JIA flares in Part 2; secondary outcomes included JIA ACR50/70/90 responses, clinical remission, PK and safety., Results: Among 173 patients with polyJIA enrolled, 89.0% (154/173) had a JIA ACR30 response and 79.2%/65.9%/36.4% demonstrated JIA ACR50/70/90 responses in Part 1. At week 48, the primary endpoint was not met as treatment groups had comparable JIA flare rates (golimumab vs placebo: 32/78=41% vs 36/76=47%; p=0.41), and rates of clinical remission were comparable (golimumab vs placebo: 10/78=12.8% vs 9/76=11.8%). Adverse event and serious adverse event rates were similar in the treatment groups during Part 2. Injection site reactions occurred with <1% of all injections. PK analysis confirmed adequate golimumab dosing for polyJIA., Conclusion: Although the primary endpoint was not met, golimumab resulted in rapid, clinically meaningful, improvement in children with active polyJIA. Golimumab was well tolerated, and no unexpected safety events occurred., Clinical Trial Registration: NCT01230827; Results., Competing Interests: Competing interests: HIB has served as a consultant and steering committee member for Janssen Research & Development, a consultant for AstraZeneca, Pfizer and Takeda and received research support from Novartis, Roche and UCB. NR served on the speaker’s bureau and as a consultant for AbbVie, Amgen, Alter, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, BMS, Celgene, CrescendoBio, EMD Serono, F. Hoffmann-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda and UCB Biosciences GmbH. DJL has served as a consultant for Boehringer Ingelheim, Celgene, Janssen Research & Development and Novartis, as a trial investigator for AbbVie, Bristol-Myers Squibb, Janssen Research & Development, Roche, Pfizer and UBC and received research support from the National Institutes of Health. NRP received fees from AbbVie and Roche. FS received research support from Janssen. KM received research support from Pfizer, AbbVie, Roche and Deutsche Kinder-Rheumastiftung and fees from AbbVie, Genzyme, Medac, Pfizer and Pharm-Allergan. IN received fees from AbbVie, Bristol-Myers Squibb, Novartis, Pfizer and Roche and grants from Pfizer and Roche. EA received research support from AbbVie, Bristol-Myers Squibb, Janssen, Novartis, Pfizer and Roche and fees from AbbVie, Bristol-Myers Squibb, Medac, Merck Sharp & Dohme, Novartis, Pfizer and Roche. KEG, ZX, JHL, LK, SLL and MJL are employees of Janssen Research & Development, LLC and own stock in Johnson & Johnson. AM received speaking and consulting fees from AbbVie, Boehringer, Celgene, CrescendoBio, Janssen, MedImmune, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Vertex and Servier. Nothing to disclose: NT, GH, VGC, CAM, AR, DJK, EDS, VP, MRMV, ES, MB, ARK, VK, RJ, WE, IF, BRL., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To assess the efficacy and safety of switching from the infliximab reference product (RP; Remicade) to its biosimilar CT-P13 (Remsima, Inflectra) or continuing CT-P13 in patients with rheumatoid arthritis (RA) for an additional six infusions., Methods: This open-label extension study recruited patients with RA who had completed the 54-week, randomised, parallel-group study comparing CT-P13 with RP (PLANETRA; NCT01217086). CT-P13 (3 mg/kg) was administered intravenously every 8 weeks from weeks 62 to 102. All patients received concomitant methotrexate. Endpoints included American College of Rheumatology 20% (ACR20) response, ACR50, ACR70, immunogenicity and safety. Data were analysed for patients who received CT-P13 for 102 weeks (maintenance group) and for those who received RP for 54 weeks and then switched to CT-P13 (switch group)., Results: Overall, 302 of 455 patients who completed the PLANETRA study enrolled into the extension. Of these, 158 had received CT-P13 (maintenance group) and 144 RP (switch group). Response rates at week 102 for maintenance versus switch groups, respectively, were 71.7% vs 71.8% for ACR20, 48.0% vs 51.4% for ACR50 and 24.3% vs 26.1% for ACR70. The proportion of patients with antidrug antibodies was comparable between groups (week 102: 40.3% vs 44.8%, respectively). Treatment-emergent adverse events occurred in similar proportions of patients in the two groups during the extension study (53.5% and 53.8%, respectively)., Conclusions: Comparable efficacy and tolerability were observed in patients who switched from RP to its biosimilar CT-P13 for an additional year and in those who had long-term CT-P13 treatment for 2 years., Trial Registration Number: NCT01571219; Results., Competing Interests: DHY and WP: consultation for CELLTRION. AB reports personal fees from Abbvie and grants from Samsung Bioepis and Abbvie, outside the submitted work; HUK, SJL and SYK are full-time employees of CELLTRION., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: To investigate the efficacy and safety of switching from infliximab reference product (RP) to its biosimilar or maintaining biosimilar treatment in patients with ankylosing spondylitis (AS)., Methods: This open-label extension study recruited patients with AS who completed a 54-week, randomised controlled study comparing CT-P13 with RP (PLANETAS). CT-P13 (5 mg/kg) was administered intravenously every 8 weeks from week 62 to week 102. Efficacy end points included the proportion of patients achieving Assessment of SpondyloArthritis international Society (ASAS)20. Antidrug antibodies (ADAs) were measured using an electrochemiluminescent method. Data were analysed for patients treated with CT-P13 in the main PLANETAS study and the extension (maintenance group) and those who were switched to CT-P13 during the extension study (switch group)., Results: Overall, 174 (82.9%) of 210 patients who completed the first 54 weeks of PLANETAS and agreed to participate in the extension were enrolled. Among these, 88 were maintained on CT-P13 and 86 were switched to CT-P13 from RP. In these maintenance and switch groups, respectively, ASAS20 response rates at week 102 were 80.7% and 76.9%. ASAS40 and ASAS partial remission were also similar between groups. ADA positivity rates were comparable (week 102: 23.3% vs 27.4%). Adverse events led to treatment discontinuation during the extension study in 3 (3.3%) and 4 (4.8%) patients, respectively., Conclusions: This is the first study to show that switching from RP to its biosimilar CT-P13 is possible without negative effects on safety or efficacy in patients with AS. In the maintenance group, CT-P13 was effective and well tolerated over 2 years of treatment., Trial Registration Number: NCT01571206; Results., Competing Interests: DHY and WP: Consultation for Celltrion. MB has received research grants from Celltrion, personal fees from lectures for Roche, Abbvie, MSD, Pfizer, Egis, UCB outside the submitted work; JB has received honoraria for talks, advisory boards, paid consultancies or grants for studies from Abbvie (Abbott), Amgen, Boehringer Ingelheim, Bristol-Myers-Squibb, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Janssen, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB. HUK, SJL, YJB and SYK are full-time employees of Celltrion. Otherwise, none declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: To assess safety, immunogenicity and efficacy in rheumatoid arthritis (RA) patients switched from long-term intravenous to subcutaneous (SC) abatacept., Methods: In this phase IIIb, open-label, single-arm trial, patients who completed ≥4 years of intravenous abatacept (in long-term extensions of two phase III studies) were enrolled to receive SC abatacept (125 mg/week). The primary objective was safety during the first 3 months after switching from intravenous therapy., Results: 123 patients entered the study (mean Disease Activity Score 28 (based on C reactive protein) and HAQ-DI of 3.4 and 0.94, respectively). At month 3, 120 (97.6%) patients were continuing to receive SC abatacept; no patients discontinued due to lack of efficacy. Adverse events (AEs) were reported in 49 (39.8%) patients through month 3. One patient (0.8%) discontinued due to an AE and one patient (0.8%) experienced a serious AE. Two (1.6%) patients had SC injection site reactions (erythema, pain), both with mild intensity. Clinical efficacy was maintained throughout. Limited impact on immunogenicity was observed when switching routes of administration., Conclusion: These data demonstrate that patients can switch from long-term monthly intravenous abatacept to a weekly fixed dose of 125 mg SC abatacept with no increased safety concerns. This study further supports SC abatacept as an alternative treatment option for patients with RA.

Objective: To evaluate abatacept treatment over 3 years in patients with rheumatoid arthritis (RA) refractory to methotrexate (MTX)., Methods: Patients randomised to abatacept or placebo (+MTX) during the 1-year double-blind period of the Abatacept in Inadequate responders to Methotrexate (AIM) trial received open-label abatacept (+MTX) in the long-term extension (LTE). Safety was assessed for patients who received ≥ 1 dose of abatacept, regardless of randomisation group. Efficacy was assessed for patients randomised to abatacept who entered the LTE., Results: 433 and 219 patients were randomised and treated with abatacept or placebo, respectively; 378 and 161 entered the LTE. At year 3, 440/539 patients were ongoing. No unexpected safety events were observed in the LTE. By year 3, incidence rates of adverse event and serious adverse events were 249.8/100 and 15.1/100 patient-years, respectively. Incidence rates were generally stable over time. At year 3, 84.8%, 63.4% and 37.5% of patients achieved American College of Rheumatology (ACR) criteria of 20, 50 and 70, respectively, compared with 82.3%, 54.3% and 32.4% of patients at year 1. Mean changes in Genant-modified Sharp scores were reduced progressively over 3 years, with significantly greater inhibition during year 3 compared with year 2 (p=0.022 for total score)., Conclusion: In MTX-inadequate responders with RA, abatacept provided consistent safety and sustained efficacy over 3 years. The data suggest an increasing inhibitory disease-modifying effect on radiographic progression.