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ObjectivesTo assess the effect of a temporary interruption in subcutaneous (SC) abatacept on immunogenicity, safety and efficacy in patients with active rheumatoid arthritis despite methotrexate in a phase III trial.MethodsFollowing a 12-week open-label introduction (period I; intravenous abatacept loading dose and weekly fixed-dose SC abatacept 125 mg), patients were randomised 2:1 to double-blind SC placebo or SC abatacept for 12 weeks (period II). At the end of period II, patients receiving SC abatacept continued treatment and patients on placebo were reintroduced to SC abatacept (12-week open-label period III). The co-primary end points were ELISA-detected immunogenicity rate and safety at the end of period II. Efficacy was also monitored.ResultsOf 167 patients entering period I, 72% qualified for period II; during periods II and III, three patients discontinued treatment. Mean (SD) disease duration was 6.6 (6.5) years and Disease Activity Score 28 was 4.8 (0.8). The primary end point was met, with a non-significant increase in immunogenicity upon withdrawal (7/73 placebo vs 0/38 abatacept in period II; p=0.119) which was reversed upon reintroduction of SC abatacept (2/73 vs 1/38, end period III). Safety was comparable regardless of withdrawal, with no unexpected events upon reintroduction. Two patients experienced reactions at the SC injection site. On withdrawal, patients experienced slight worsening in efficacy which improved following reintroduction.ConclusionsOverall immunogenicity to SC abatacept is low, consistent with intravenous abatacept, and is not significantly affected by a 3-month interruption and reintroduction. This stop–start schedule was well tolerated, with little impact on safety and efficacy. These are important considerations for the clinical use of SC abatacept.ClinicalTrials govIdentifier NCT00533897

ObjectiveTo investigate the pharmacokinetics, effectiveness, and safety of subcutaneous (SC) abatacept treatment over 24 months in patients with polyarticular‐course juvenile idiopathic arthritis (JIA).MethodsIn this phase III, open‐label, international, multicenter, single‐arm study, patients with polyarticular JIA (cohort 1, ages 6–17 years and cohort 2, ages 2–5 years) in whom treatment with ≥1 disease‐modifying antirheumatic drug was unsuccessful received weight‐tiered SC abatacept weekly: 10 to <25 kg (50 mg), 25 to <50 kg (87.5 mg), ≥50 kg (125 mg). Patients who had met the JIA–American College of Rheumatology 30% improvement criteria (achieved a JIA‐ACR 30 response) at month 4 were given the option to continue SC abatacept to month 24. The primary end point was the abatacept steady‐state serum trough concentration (Cminss) in cohort 1 at month 4. Other outcome measures included JIA‐ACR 30, 50, 70, 90, 100, and inactive disease status, the median Juvenile Arthritis Disease Activity Score in 71 joints using the C‐reactive protein level (JADAS‐71–CRP) over time, safety, and immunogenicity.ResultsThe median abatacept Cminss at month 4 (primary end point) and at month 24 was above the target therapeutic exposure (10 μg/ml) in both cohorts. The percentage of patients who had achieved JIA‐ACR 30, 50, 70, 90, or 100 responses or had inactive disease responses at month 4 (intent‐to‐treat population) was 83.2%, 72.8%, 52.6%, 28.3%, 14.5%, and 30.1%, respectively, in cohort 1 (n = 173) and 89.1%, 84.8%, 73.9%, 58.7%, 41.3%, and 50.0%, respectively, in cohort 2 (n = 46); the responses were maintained to month 24. The median (interquartile range) JADAS‐71–CRP improved from baseline to month 4: cohort 1, from 21.0 (13.5, 30.3) to 4.6 (2.1, 9.4); cohort 2, from 18.1 (14.0, 23.1) to 2.1 (0.3, 4.4). Improvements were sustained to month 24, at which time 27 of 173 patients (cohort 1) and 11 of 22 patients (cohort 2) had achieved JADAS‐71–CRP remission. No unexpected adverse events were reported; 4 of 172 patients (2.3%) in cohort 1 and 4 of 46 (8.7%) in cohort 2 developed anti‐abatacept antibodies, with no clinical effects.ConclusionWeight‐stratified SC abatacept yielded target therapeutic exposures across age and weight groups, was well tolerated, and improved polyarticular JIA symptoms over 24 months.

ObjectivesTo evaluate the efficacy and safety of subcutaneous golimumab as add-on therapy in patients with active rheumatoid arthritis (RA) despite disease-modifying antirheumatic drug (DMARD) treatment. To evaluate an intravenous plus subcutaneous (IV+SC) golimumab strategy in patients who had not attained remission.MethodsGO-MORE was an open-label, multinational, prospective study in patients with active RA in typical clinical practice settings. In part 1, patients received add-on monthly 50-mg subcutaneous golimumab for 6 months. The percentage of patients with good/moderate European League Against Rheumatism (EULAR) 28-joint disease activity score (DAS28)–erythrocyte sedimentation rate (ESR) response was compared in patient subgroups with various concurrent or previous DMARD treatments. In part 2, patients with EULAR responses but not remission were randomly assigned to receive IV+SC or subcutaneous golimumab to month 12; DAS28–ESR remission was measured.Results3366 patients were enrolled. At baseline of part 1, 3280 efficacy-evaluable patients had mean disease duration of 7.6 years and mean DAS28–ESR of 5.97 (SD=1.095). At month 6, 82.1% achieved good/moderate EULAR responses and 23.9% attained remission. When EULAR responses were analysed by the number of previously failed DMARD or the concomitant methotrexate dose, DMARD type, or corticosteroid use, no statistically significant differences were observed. Part 2 patients (N=490) who received IV+SC or subcutaneous golimumab achieved similar remission rates (∼25%). Adverse events were consistent with previous reports of golimumab and other tumour necrosis antagonists in this population.ConclusionsAdd-on monthly subcutaneous golimumab resulted in good/moderate EULAR response in most patients; 25% achieved remission after 6 more months of golimumab, but an IV+SC regimen provided no additional efficacy over the subcutaneous regimen.

BackgroundCHS-0214 is a proposed biosimilar of etanercept, a fusion protein inhibiting tumor necrosis factor that is approved for several inflammatory autoimmune diseases.ObjectivesThis Phase III multi-center study compared the efficacy, safety, and immunogenicity of CHS-0214 with etanercept for 24 weeks (Part 1) in patients with moderate/severe RA who had an inadequate response to MTX; then all patients received open-label CHS-0214 for 24 weeks with a final evaluation at Week 52 (Part 2).MethodsPatients were randomized to 50 mg of CHS-0214 or etanercept subcutaneously QWx24 weeks (Part 1). The primary endpoint was the ACR20 response rate at Week 24. To establish the equivalence of CHS-0214 to etanercept, the 95% confidence interval (CI) of the treatment difference between groups had to be within [–15%, 15%]. Secondary efficacy endpoints (ACR50, ACR 70, and change in DAS28-CRP), safety, and immunogenicity were also evaluated.ResultsIn 13 countries, 644 patients on MTX were randomized and received treatment. Baseline characteristics were comparable between treatment groups. Part 1 results are reported here. At 24 weeks, 512 patients were evaluable for efficacy. The ACR20 response rate was 91.0% (233/256) in the CHS-0214 group and 90.6% (232/256) in the etanercept group. The 95% CI of the treatment difference was [- 4.55, 5.37], which was within the pre-defined equivalence range. The response rates at 24 weeks were 67.6% vs. 63.7% for ACR50 and 38.3% vs. 37.9% for ACR70 in the CHS-0214 and etanercept groups, respectively. Mean (±SD) DAS28-CRP scores were 5.45 (± 1.00) and 5.42 (±1.00) at baseline and decreased to 2.67 (± 1.18) and 2.73 (±1.14) at 24 weeks in the CHS-0214 and etanercept groups, respectively (See Figure).Among the 644 patients, adverse events (AEs) occurred in 60.8% and 65.0% of patients in the CHS-0214 and etanercept groups, respectively, including all infections combined in 34.3% and 32.2%, respectively. Investigator-designated treatment-related AEs occurred in 16.4% and 21.9% of patients, respectively, and most commonly included: injection site reactions (2.2% and 13.4%) and all infections combined (7.7% and 5.3%). Treatment-related serious AEs occurred in 3 (0.9%) patients treated with CHS-0214 (cholecystitis, increased blood creatinine phosphokinase, and bronchospasm) and 1 (0.3%) patient treated with etanercept (sepsis). Binding anti-drug antibodies occurred in 1.3% and 4.7% of patients in the CHS-0214 and etanercept groups.ConclusionsThese results demonstrated equivalence of CHS-0214 to etanercept with respect to efficacy as measured by the primary endpoint (ACR20 at Week 24) and other measures (ACR50, ACR70, and DAS28-CRP). CHS-0214 was well tolerated with no clinically meaningful differences to etanercept with regard to safety and immunogenicity.Disclosure of InterestJ. O'Dell: None declared, T. Takeuchi: None declared, Y. Tanaka: None declared, I. Louw: None declared, T. Tiabut: None declared, M. Kai: None declared, M. Oribe: None declared, S. Nakashima Employee of: Daiichi Sankyo Co., Ltd.,...