ObjectivesTo 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.MethodsThis 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).ResultsOverall, 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).ConclusionsComparable 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 numberNCT01571219; Results.

ObjectivesTo 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).MethodsThis 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).ResultsOverall, 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.ConclusionsThis 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 numberNCT01571206; Results.

Objective To evaluate fenebrutinib, an oral and highly selective noncovalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthritis (RA). Methods Patients with RA and an inadequate response to methotrexate (MTX) (cohort 1; n = 480) were randomized to receive fenebrutinib (50 mg once daily, 150 mg once daily, or 200 mg twice daily), adalimumab (40 mg every other week), or placebo. Patients with RA and an inadequate response to tumor necrosis factor inhibitors (cohort 2; n = 98) received fenebrutinib (200 mg twice daily) or placebo. Both cohorts continued MTX therapy. Results In cohort 1, the percentages of patients in whom American College of Rheumatology 50% improvement criteria (ACR50) was achieved at week 12 were similar in the fenebrutinib 50 mg once daily and placebo groups, and were higher in the fenebrutinib 150 mg once daily group (28%) and 200 mg twice daily group (35%) than in the placebo group (15%) (P = 0.016 and P = 0.0003, respectively). Fenebrutinib 200 mg twice daily and adalimumab (36%) were comparable (P = 0.81). In cohort 2, ACR50 was achieved in more patients receiving fenebrutinib 200 mg twice daily (25%) than placebo (12%) (P = 0.072). The most common adverse events in the fenebrutinib groups included nausea, headache, anemia, and upper respiratory tract infections. Fenebrutinib had significant effects on myeloid and B cell biomarkers (CCL4 and rheumatoid factor). Fenebrutinib and adalimumab caused overlapping as well as distinct changes in B cell and myeloid biomarkers. Conclusion Fenebrutinib demonstrates efficacy comparable to adalimumab in patients with an inadequate response to MTX, and safety consistent with existing immunomodulatory therapies for RA. These data support targeting both B and myeloid cells via this novel mechanism for potential efficacy in the treatment of RA.

BackgroundEfficacy and safety of a new subcutaneous (SC) formulation (CT-P13 SC) up to Week 30 were comparable with intravenous (IV) formulation (CT-P13 IV) in both patients with rheumatoid arthritis (RA) [1] and Crohn's disease [2].ObjectivesThis report is to further investigate pharmacokinetics, efficacy and overall safety of CT-P13 SC in patients with RA throughout the 1-year treatment period.MethodsPatients with active RA (presence of 6 or more swollen and tender joints [of 28 assessed], and serum C-reactive protein [CRP] concentration >0.6 mg/dL) were treated with CT-P13 IV at Weeks 0 and 2, and were randomized for continuation with CT-P13 IV or SC administration at Week 6. The IV cohort received CT-P13 IV 3 mg/kg every 8 weeks and the SC cohorts received CT-P13 SC 90 mg, 120 mg or 180 mg, respectively, every 2 weeks up to Week 54. Pharmacokinetics blood samples were collected before study drug administration at each visit and drug levels were determined by electrochemiluminescent assay. Efficacy parameters including DAS28 and ACR criteria and overall safety were evaluated.ResultsA total of 50 patients were enrolled, of whom 48 patients were randomly assigned at Week 6 into 4 cohorts (1:1:1:1 ratio). The mean Ctrough (pre-dose serum concentration of CT-P13 before next dose injection) of SC cohorts throughout the study visits were higher than those of IV cohort after randomization at Week 6. Ctrough levels increased with SC dose and were sufficiently higher than the target therapeutic concentration (1 μg/mL) throughout the study period (Figure 1). Overall, the efficacy results of CT-P13 SC up to Week 54 were comparable to those of CT-P13 IV. Disease improvement by DAS28 (CRP) and ACR20 were comparable across all 4 cohorts, regardless of the route of administration or dosage of CT-P13 (Table 1). The safety profiles which occurred after study drug administration at Week 6 in SC cohorts were generally comparable to those of IV cohort and appeared similar to those previously reported for IV infliximab [3]. All injection site reactions were grade 1 or 2. No malignancy or death was reported (Table 1).ConclusionThe results from 1-year treatment suggest similar efficacy and safety of CT-P13 SC to CT-P13 IV in RA. The mean serum concentration in all SC cohorts consistently exceeded the threshold of target therapeutic concentration. These results show that the novel SC formulation of CT-P13 may enhance treatment options for use of infliximab biosimilar by providing high consistency in drug exposure.Reference1Westhovens et al., Annals of the Rheumatic Disease 2018;77:315.2Schreiber et al., Gastroenterology 2018;154(6):S-1371.3Yoo et al., Arthritis Research & Therapy 2016;18:82. Disclosure of InterestsDaeHyun Yoo Grant/research support from: Celltrion, Inc., Consultant for: Celltrion, Inc., Janusz Jaworski Grant/research support from: Celltrion, Inc., Ewa Matyska-Piekarska Grant/research support from: Celltrion, Inc., Svitlana Smiyan Grant/research support from: Celltrion, Inc., Delina Ivanova Grant/research support from:...

BackgroundWhile the treatment with intravenous (IV) CT-P13, an infliximab biosimilar, is effective and well tolerated, a new subcutaneous (SC) CT-P13 formulation (CT-P13 SC) is developed to provide additional, more convenient treatment options and opportunity for self-injection.ObjectivesTo find the optimal dose of CT-P13 SC and to evaluate efficacy, PK and safety over the first 30 weeks in patients with rheumatoid arthritis.MethodsThis study consists of 1 cohort with CT-P13 IV, and 3 cohorts with 3 different doses of CT-P13 SC injected biweekly. All enrolled patients initially received CT-P13 IV at Weeks 0 and 2 and patients who received 2 full doses and displayed no safety concerns were randomly assigned to receive either CT-P13 SC or IV at Week 6. Using part 1 result, PK-PD modelling was conducted for the 3 regimens.ResultsA total of 50 patients were enrolled, of whom 48 patients were randomly assigned into 4 cohorts.Overall, the efficacy results of CT-P13 SC up to Week 30 were comparable to those of CT-P13 IV. Disease improvement by DAS28 and ACR20 were comparable across all 4 cohorts, regardless of the route of administration or dosage of CT-P13 (table 1).The safety profiles in CT-P13 SC cohorts were generally comparable to CT-P13 IV. One of the 2 patients who experienced a hypersensitivity reaction became anti-drug antibody (ADA) positive at Week 6 and experienced hypersensitivity from Week 2 to 8. All injection site reactions were grade 1 or 2. The proportion of ADA (positive) was lower in the SC cohorts.In PK-PD modelling, bioavailability was 59% (95% CI, 52%–67%). The dose linearity in SC regimens was confirmed based on Weeks 22 to 30 Ctrough, AUCτ and Cmax, ss (figure 1). Ctrough were greater (above 4 µg/mL) than the target exposure (1 µg/mL)[1][2] in all SC regimens. There was a trend towards slightly lower DAS28 score in all SC regimens, which was consistent with the higher Ctrough comparing with CT-P13 IV. Based on the exposure-response safety analyses, there was no correlation between PK (AUCτ or Cmax) and safety (IRRs or infections).Abstract THU0191 – Table 1Efficacy and safety up to Week 30Cohort 1IV 3 mg/kg(n=13)Cohort 2SC 90 mg(n=11)Cohort 3SC 120 mg(n=12)Cohort 4SC 180 mg(n=12) DAS28 (CRP), mean±SDWeek 05.4±0.86.3±0.85.7±0.95.5±0.8 Week 63.9±1.54.6±1.13.9±1.23.4±1.2Week 223.9±1.63.7±1.03.3±1.42.8±1.3Week 303.3±1.33.0±1.13.1±1.02.7±1.0ACR20,n (%)Week 68 (61.5)8 (72.7)7 (58.3)7 (58.3)Week 228 (61.5)8 (72.7)9 (75.0)11 (91.7)Week 3011 (84.6)10 (90.9)10 (83.3)12 (100)Safety, n (%)Hypersensitivity/IRR01 (9.1)1 (8.3)0Injection site reactions02 (18.2)02 (16.7)Infections4 (30.8)2 (18.2)04 (33.3)ADA9 (69.2)3 (27.3)4 (33.3)1 (8.3)Abstract THU0191 – Figure 1Mean (± SD) Simulated CT-P13 Serum Concentration vs Time Profiles for the Simulated Fixed Dose SC Maintenance Dosing Regimens with Overlaid IV Maintenance Reference Treatment (Semi-Logarithmic Scale). Solid line=Period 1 (IV reference regimen: IV loading+IV maintenance dose). Dashed line=Period 2 (SC test regimen: IV loading+SC maintenance dose)Abstract ...