Evaluation of measurement reliability for selected indices of postural stability based on data from the GYKO Inertial Sensor System.

The main aim of this study is to use comprehensive statistical analyses to evaluate measurement reliability of selected variables that characterize postural stability. The study examined twenty-nine healthy non-athlete students. The examinations were performed twice, with a one-week interval. The Microgate GYKO inertial sensor system was used to evaluate the reliability of variables that characterize postural stability. The relative reliability of the repeated test was evaluated using the intraclass correlation coefficient (ICC) with 95% confidence interval (95% CI). Next, the standard error of measurement (SEM) and minimal detectable change (MDC) were computed. Relative reliability of the repeated test for all analysed variables of ICC ranged from 0.31 to 0.75. For four variables, ICC values were ca. 0.7, i.e., they can be considered as good. For four other variables, ICC ranged from 0.41 to 0.54, with these values considered fair. Satisfactory reproducibility of postural stability measurements using the GYKO inertial sensor system demonstrates that it can offer an inexpensive and efficient alternative to measurements that use force balance platforms.

Efficacy and safety of switching from reference adalimumab to CT-P17 (100 mg/ml): 52-week randomized, double-blind study in rheumatoid arthritis.

OBJECTIVE: To compare the safety and efficacy of switching from reference adalimumab to adalimumab biosimilar CT-P17 with continuing reference adalimumab/CT-P17 in active RA. METHODS: This double-blind, phase III study randomized (1:1) subjects with active RA to receive 40 mg (100 mg/ml) CT-P17 or European Union-sourced reference adalimumab subcutaneously every 2 weeks (Q2W) until week (W) 24 [treatment period (TP) 1]. Thereafter, subjects receiving reference adalimumab were randomized (1:1) to continue reference adalimumab or switch to CT-P17 from W26 (both Q2W until W48; TP2). Subjects receiving CT-P17 in TP1 continued CT-P17. W0-W24 results were previously reported; we present W26-W52 findings. End points were efficacy (including joint damage progression), pharmacokinetics, safety and immunogenicity. RESULTS: Of 607 subjects who initiated TP2 treatment, 303 continued CT-P17, 153 continued reference adalimumab and 151 switched to CT-P17. Efficacy improvements up to W24 were maintained during TP2; efficacy was comparable among groups. At W52, 20% improvement in ACR response rates were 80.5% (continued CT-P17), 77.8% (continued reference adalimumab) and 82.2% (switched to CT-P17). Joint damage progression was minimal. Mean trough serum adalimumab concentrations were similar among groups. CT-P17 and reference adalimumab safety profiles were numerically similar and switching did not affect immunogenicity. At W52, 28.4% (continued CT-P17), 27.0% (continued reference adalimumab) and 28.3% (switched to CT-P17) of subjects were anti-drug antibody-positive. CONCLUSION: Efficacy, pharmacokinetics, safety and immunogenicity of CT-P17 and reference adalimumab were comparable after 1 year of treatment, including after switching from reference adalimumab to CT-P17. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03789292.

Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial.

OBJECTIVE: To assess non-inferiority of s.c. to i.v. CT-P13 in RA. METHODS: Patients with active RA and inadequate response to MTX participated in this phase I/III double-blind study at 76 sites. Patients received CT-P13 i.v. 3 mg/kg [week (W) 0 and W2] before randomization (1:1) at W6 to CT-P13 s.c. via pre-filled syringe (PFS) 120 mg biweekly until W28, or CT-P13 i.v. 3 mg/kg every 8 weeks until W22. Randomization was stratified by country, W2 serum CRP and W6 body weight. From W30, all patients received CT-P13 s.c. In a usability sub-study, patients received CT-P13 s.c. via auto-injector (W46-54) then PFS (W56-64). The primary endpoint was change (decrease) from baseline in disease activity score in 28 joints (DAS28)-CRP at W22 (non-inferiority margin: -0.6). RESULTS: Of 357 patients enrolled, 343 were randomized to CT-P13 s.c. (n = 167) or CT-P13 i.v. (n = 176) at W6. The least-squares mean change (decrease) from baseline (standard error) in DAS28-CRP at W22 was 2.21 (0.22) for CT-P13 s.c. (n = 162) and 1.94 (0.21) for CT-P13 i.v. [n = 168; difference 0.27 (95% CI: 0.02, 0.52)], establishing non-inferiority. Efficacy findings were similar between arms at W54. Safety was similar between arms throughout: 92 (54.8%; CT-P13 s.c.) and 117 (66.9%; CT-P13 i.v.) patients experienced treatment-emergent adverse events (from W6). There were no treatment-related deaths or new safety findings. Usability was similar for CT-P13 s.c. via auto-injector or PFS. CONCLUSION: CT-P13 s.c. was non-inferior to CT-P13 i.v. in active RA. The convenience of s.c. administration could benefit patients. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT03147248.

Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study.

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.

Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3).

OBJECTIVE: To evaluate apremilast treatment in patients with active psoriatic arthritis, including current skin involvement, despite prior therapy with conventional disease-modifying antirheumatic drugs and/or biologic agents. METHODS: Patients (N=505) were randomised (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily. Rescue therapy with apremilast was designated at week 16 for placebo patients not achieving 20% improvement in swollen and tender joint counts. At week 24, the remaining placebo patients were then randomised to apremilast 20 mg twice daily or 30 mg twice daily. The efficacy and safety of apremilast were assessed over 52 weeks. RESULTS: At week 16, significantly more patients receiving apremilast 20 mg twice daily (28%) and 30 mg twice daily (41%) achieved 20% improvement in American College of Rheumatology response criteria versus placebo (18%; p=0.0295 and p<0.0001, respectively), and mean decrease in the Health Assessment Questionnaire-Disability Index score was significantly greater with apremilast 30 mg twice daily (-0.20) versus placebo (-0.07; p=0.0073). In patients with baseline psoriasis body surface area involvement ≥3%, significantly more apremilast 30 mg twice daily patients achieved 50% reduction from baseline Psoriasis Area and Severity Index score (41%) versus placebo (24%; p=0.0098) at week 16. At week 52, observed improvements in these measures demonstrated sustained response with continued apremilast treatment. Most adverse events were mild to moderate in severity; the most common were diarrhoea, nausea, headache and upper respiratory tract infection. CONCLUSIONS: Apremilast demonstrated clinically meaningful improvements in psoriatic arthritis and psoriasis at week 16; sustained improvements were seen with continued treatment through 52 weeks. Apremilast was generally well tolerated and demonstrated an acceptable safety profile. TRIAL REGISTRATION NUMBER: NCT01212770.

Cadaveric comparison of two techniques for intraoperative placement of tibial plateau levelling osteotomies in dogs.

BACKGROUND: Both tibial tuberosity fractures and deviation from the planned postoperative tibial plateau angle have been associated with poor centring of tibial plateau levelling osteotomies (TPLOs). The aim of this cadaveric study was to compare two techniques for centring the osteotomy and preserving the tibial tuberosity width (TTW). METHODS: Stifle radiographs were obtained from 20 limbs of 10 dogs. TPLO was planned on each stifle, and a two-wire technique (TWT) and a technique using the medial collateral ligament (MCL) as an intraoperative landmark were planned. The techniques were executed and marked with radiopaque pins. Further radiographs were obtained and analysed. RESULTS: On average, TWT resulted in a 20.4% increase in TTW and medial collateral ligament technique (MCLT) resulted in a 13.4% decrease. Expressed as a percentage of the radial saw size, the average error in the centring of the osteotomy arising from the TWT was 13.4% and that from the MCLT was 14.2%. LIMITATIONS: This study had a small sample size and involved a single surgeon. CONCLUSION: Neither technique reliably identified the desired centre of the osteotomy, and both had a similar magnitude of error. MCLT resulted in reduced TTW, while TWT resulted in increased TTW. A reduced TTW has been associated with an increased risk of tibial tuberosity fracture, so MCLT is not recommended for clinical use.

Efficacy and Safety of Candidate Biosimilar CT-P43 Versus Originator Ustekinumab in Moderate to Severe Plaque Psoriasis: 28-Week Results of a Randomised, Active-Controlled, Double-Blind, Phase III Study.

BACKGROUND: CT-P43 is a candidate ustekinumab biosimilar in clinical development. OBJECTIVES: This paper aims to demonstrate equivalent efficacy of CT-P43 to originator ustekinumab in adults with moderate to severe plaque psoriasis. METHODS: This double-blind, phase III trial randomised patients (1:1) to receive subcutaneous CT-P43 or originator ustekinumab (45/90 mg for patients with baseline body weight ≤ 100 kg/> 100 kg) at week 0 and week 4 in Treatment Period I. Prior to week 16 dosing in Treatment Period II, patients receiving originator ustekinumab were re-randomised (1:1) to continue originator ustekinumab or switch to CT-P43; patients initially randomised to CT-P43 continued receiving CT-P43 (at weeks 16, 28 and 40). The primary endpoint of the trial was mean per cent improvement from baseline in Psoriasis Area Severity Index (PASI) score at week 12. Equivalence was concluded if confidence intervals (CIs) for the estimate of treatment difference were within pre-defined equivalence margins: ± 10% [90% CI; modified intent-to-treat set; Food and Drug Administration (FDA) approach] or ± 15% [95% CI; full analysis set for patients only receiving 45 mg doses in Treatment Period I; European Medicines Agency (EMA) approach]. Additional efficacy, pharmacokinetic, safety and immunogenicity endpoints were evaluated through week 52. Results to week 28 are reported here. RESULTS: In Treatment Period I, 509 patients were randomised (CT-P43: N = 256; originator ustekinumab: N = 253). The mean per cent improvement in PASI score at week12 was 77.93% and 75.89% for CT-P43 and originator ustekinumab, respectively (FDA approach); per the EMA approach, corresponding values were 78.26% and 77.33%. Estimated treatment differences were 2.05 (90% CI -0.23, 4.32) and 0.94 (95% CI -2.29, 4.16); equivalence was achieved for both sets of assumptions. Further efficacy parameters and pharmacokinetic, safety and immunogenicity outcomes were comparable between treatment groups, including after switching from originator ustekinumab to CT-P43. CONCLUSIONS: CT-P43 demonstrated equivalent efficacy to originator ustekinumab in patients with moderate to severe plaque psoriasis, with comparable pharmacokinetic, safety and immunogenicity profiles. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04673786; date of registration: 17 December, 2020.

Efficacy and safety of CT-P47 versus reference tocilizumab: 32-week results of a randomised, active-controlled, double-blind, phase III study in patients with rheumatoid arthritis, including 8 weeks of switching data from reference tocilizumab to CT-P47.

OBJECTIVES: To demonstrate efficacy equivalence of CT-P47 and EU-approved reference tocilizumab (r-TCZ) in patients with rheumatoid arthritis (RA). METHODS: This double-blind, phase III study randomised (1:1) patients to receive CT-P47 or r-TCZ (8 mg/kg) every 4 weeks until week 20 during treatment period (TP) 1. Prior to week 24 dosing, patients receiving r-TCZ were randomised (1:1) to continue r-TCZ or switch to CT-P47; patients receiving CT-P47 continued CT-P47 (TP2, 8 mg/kg every 4 weeks until week 48). The dual primary endpoints (for different regulatory requirements) were mean changes from baseline in Disease Activity Score in 28 joints (DAS28; erythrocyte sedimentation rate (ESR)) at week 12 and week 24. Efficacy equivalence was determined if CIs for the treatment difference were within predefined equivalence margins: (95% CI -0.6, 0.6 (analysis of covariance (ANCOVA)) at week 12 or 90% CI -0.6, 0.5 (ANCOVA with multiple imputation) at week 24). Additional efficacy, pharmacokinetic (PK) and safety endpoints, including immunogenicity, were investigated. Findings up to week 32 are presented. RESULTS: In TP1, 471 patients were randomised (234 CT-P47; 237 r-TCZ). The 95% and 90% CIs for the estimated treatment differences were contained within the predefined equivalence margins; the estimated difference in DAS28-ESR at week 12 was -0.01 (95% CI -0.26, 0.24) and at week 24 was -0.10 (90% CI -0.30, 0.10). Secondary efficacy endpoints, PKs and overall safety were comparable between groups up to week 32. CONCLUSIONS: Efficacy equivalence, alongside comparable PK, safety and immunogenicity profiles, was determined between CT-P47 and r-TCZ in adults with RA, including after switching from r-TCZ to CT-P47.

Primary retropharyngeal leiomyosarcoma in a young cat.

Case summary: An Oriental Shorthair cat, aged 1 year and 6 months, developed progressive stridor and a palpable right ventral cervical mass. Fine-needle aspiration of the mass was inconclusive, while thoracic radiography and CT showed no evidence of metastasis. There was initial improvement in stridor with oral doxycycline and prednisolone treatment, but it recurred 4 weeks later and excisional biopsy was performed. Histopathology with immunohistochemistry diagnosed leiomyosarcoma with incomplete surgical margins. Adjunctive radiation therapy was declined. Repeated physical examination and CT 7 months postoperatively documented no evidence of mass recurrence. Relevance and novel information: This is the first reported case of retropharyngeal leiomyosarcoma in a young cat with no evidence of local reoccurrence 7 months following an excisional biopsy.

Relationships between selected indices of postural stability and sports performance in elite badminton players: Pilot study.

The main aim of this study was to determine the relationships between postural stability and the place in the ranking of badminton players. The study examined 10 elite players from Polish national badminton team. The scope of the study included basic somatic characteristics, such as body height, body weight, BMI, and training experience. A Microgate GYKO inertial sensor system was used to assess the postural stability of athletes. Using Spearman's rank correlation, cause-and-effect relationships between the place in the sports ranking and the analyzed variables characterizing postural stability were recognized. Depending on the distribution and homogeneity of variance, the significance of differences in variables that characterize postural stability between players of different sports skill levels (two groups) was calculated. The Student's t-test or Mann-Whitney's U-test was used for this purpose. In general, the athletes with higher positions on the ranking list presented a higher level of postural stability in both tests, which is also confirmed by the normalized values. However, for all variables of postural stability, no statistically significant correlations with sports ranking were observed. Higher values of Spearman's rank correlation coefficients were found for the test performed in the one-foot standing test compared to the two-foot test. The results obtained indicate that particular attention in badminton training should be paid to the development of the level of postural stability in order to improve sports performance.

Influence of training and selection on postural stability and its relationship with sport level in judo practitioners aged 11-14 years.

The aim of this study is to determine the influence of training and selection on postural stability and its relationship with the sports level of judo practitioners aged 11-14 years. The study group consisted of 21 children judokas, aged 11-12, and 80 of their non-training peers, as well as 19 adolescent judokas, aged 13-14, and 76 of their non-training peers. The judokas were surveyed during regional championships. The level of achievement was determined by the place taken in the tournament. The balance was assessed with the use of a CQ Stab 2P stabilographic platform (CQ Elektronik System, Poland). The device recorded the position of the foot center of pressure (COP) from 6 sensors; 3 of them being located in each platform plate. The following parameters describing the movement of the foot COP were analyzed: total path length calculated in both axes (SP); mean COP inclination (MA), size of the surface area delineated by COP (SA); mean COP frequency (MF). Significantly higher values of SP, MA, and SA were noted in non-training children (aged 11-12), while MF values were significantly higher in young judokas. The same regularity was found in the older age group. Upon comparing the means between children judokas and adolescent judokas, significant differences were noted in the case of SP and MF. In both cases, higher mean values were found in the younger judoka group. A similar comparison in the non-training group indicates statistically significant better values of all analyzed indicators in the 13-14 year-old group, except for MF. Upon examining the relationship between the values of the parameters characterizing the balance level and the sports level, both in the group of training children and adolescents, insignificant values of correlation coefficients were obtained.

Efficacy and safety of biosimilar CT-P17 versus reference adalimumab in subjects with rheumatoid arthritis: 24-week results from a randomized study.

BACKGROUND: To demonstrate equivalent efficacy of the proposed high-concentration (100 mg/ml), citrate-free adalimumab biosimilar CT-P17 to European Union-approved adalimumab (EU-adalimumab) in subjects with active rheumatoid arthritis (RA). METHODS: This randomized, double-blind phase III study ( ClinicalTrials.gov , NCT03789292) randomized (1:1) subjects with active RA at 52 centers to receive CT-P17 or EU-adalimumab 40 mg subcutaneously every 2 weeks until week 52. Results to week 24 are reported here. The primary endpoint was 20% improvement by American College of Rheumatology criteria (ACR20) response rate at week 24. Equivalence was concluded if the corresponding confidence intervals (CIs) for the estimate of treatment difference were within predefined equivalence margins: - 15 to 15% (95% CI; European Medicines Agency assumption); - 12 to 15% (90% CI; Food and Drug Administration assumption). Additional efficacy, pharmacokinetic, usability, safety, and immunogenicity endpoints were evaluated. RESULTS: 648 subjects were randomized (324 CT-P17; 324 EU-adalimumab). The ACR20 response rate at week 24 was 82.7% (n = 268/324) in both groups (intention-to-treat population). The 95% CI (- 5.94 to 5.94) and 90% CI (- 4.98 to 4.98) were within predefined equivalence margins for both assumptions and equivalent efficacy was concluded. Additional endpoints and overall safety were comparable between groups. Mean trough serum concentrations of CT-P17 were slightly higher than those of EU-adalimumab. Immunogenicity was slightly lower numerically for the CT-P17 group than for the EU-adalimumab group. CONCLUSIONS: CT-P17 and EU-adalimumab have equivalent efficacy and comparable safety and immunogenicity in subjects with active RA. Overall safety of CT-P17 is consistent with the known safety profile of reference adalimumab. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03789292 . Registered 28 December 2018-retrospectively registered.

Absolute and relative reliability of several measures of static postural stability calculated using a GYKO inertial sensor system.

PURPOSE: The aim of this study was to analyse absolute and relative reliability of a number of postural static stability measures obtained from a GYKO inertial sensor system in young adults. METHODS: The study examined 29 healthy non-athlete young adults. A test was performed for 30 s while standing on one foot, without moving, with eyes open and arms relaxed along the sides of the body. The examinations were performed twice, with a one-week interval. Relative reliability was measured using the intraclass correlation coefficient (ICC) and the 95% confidence interval (95% CI), whereas the absolute reliability was evaluated based on the standard error of measurement (SEM) and the minimal detectable change (MDC). RESULTS: The results of this study showed moderate to good relative reliability scores for all the postural stability measures, with ICC values ranging from 0.62 to 0.70. For most of the analysed variables, SEM% ranged from ca. 10 to 14%. Relatively high SEM% values were obtained only for two variables (Area, Convex Hull Area). CONCLUSIONS: The low costs of GYKO inertial sensor systems, the fast and easy installation, the mobility and high reliability of the measurement of postural stability show that it can be effective alternative to stabilographic platforms.

The Effects of Intermittent Hypoxic Training on Anaerobic and Aerobic Power in Boxers.

BACKGROUND: The aim of the study was to evaluate the effects of intermittent hypoxic training (IHT) on anaerobic and aerobic fitness in elite, national boxers. METHODS: The study was conducted over a period of 6 weeks. It comprised 30 national championship boxers, divided into 2 groups: the experimental and control. Both groups performed the same boxing training twice a day (morning and afternoon training). In the afternoon, the experimental group performed training under normobaric conditions in a hypoxic chamber (IHT), while the control group undertook exercise in standard normoxic conditions. In both groups, before and after the 6-week programme, basic anthropometric indices as well as anaerobic (Wingate Test) and aerobic (graded test) fitness were assessed. RESULTS: There was a significant increase in anaerobic peak power (988.2 vs. 1011.8 W), mean anaerobic power (741.1 vs. 764.8 W), total work (22.84 vs. 22.39 kJ), and a decrease in fatigue index (20.33 vs. 18.6 W·s-1) as well as time to peak power (5.01 vs. 4.72 s). Such changes were not observed in the control group. In both groups, no significant changes in endurance performance were noted after the training session - peak oxygen uptake did not significantly vary after IHT. CONCLUSIONS: Our results have practical application for coaches, as the IHT seems to be effective in improving anaerobic performance among boxers.

Switch from reference etanercept to SDZ ETN, an etanercept biosimilar, does not impact efficacy, safety, and immunogenicity of etanercept in patients with moderate-to-severe rheumatoid arthritis: 48-week results from the phase III, randomized, double-blind EQUIRA study.

BACKGROUND: Sandoz etanercept (SDZ ETN; GP2015) is an etanercept biosimilar with equivalent efficacy and comparable safety and immunogenicity to reference etanercept (ETN) in patients with moderate-to-severe chronic plaque-type psoriasis. METHODS: EQUIRA was a phase III, double-blind study conducted in patients with moderate-to-severe rheumatoid arthritis and inadequate response to disease-modifying anti-rheumatic drugs. Eligible patients were randomized 1:1 to receive subcutaneous 50 mg SDZ ETN or ETN, once-weekly, for 24 weeks. At week 24, patients with at least moderate EULAR response in the SDZ ETN group continued SDZ ETN treatment, and those in the ETN group were switched to receive 50 mg SDZ ETN, for up to 48 weeks. Patients received concomitant methotrexate at a stable dose (10-25 mg/week) and folic acid (≥ 5 mg/week). Equivalence between SDZ ETN and ETN for change from baseline in disease activity score including 28 joint count C-reactive protein (DAS28-CRP) at week 24 (primary endpoint) and comparable safety and immunogenicity profile of SDZ ETN and ETN have previously been demonstrated at week 24. Herein, we present the 48-week results of the study after a single switch from ETN to its biosimilar at week 24. RESULTS: The least squares mean (standard error) change in DAS28-CRP from baseline up to week 48 was comparable between "continued SDZ ETN" (- 2.90 [0.12], n = 148) and "switched to SDZ ETN" (- 2.78 [0.13], n = 131) groups. The proportion of patients achieving EULAR good/moderate responses based on DAS28-erythrocyte sedimentation rate and ACR20/50/70 response rates were comparable between the two groups. The proportion of patients with at least one treatment-emergent adverse event was 42.9% in the "continued SDZ ETN" and 38.0% in the "switched to SDZ ETN" groups. Serious adverse events occurred in 4 patients in each of the two groups. After week 24, none of the patients in the switched group developed anti-drug antibodies (ADAs), while 4 patients in the continued SDZ ETN group had single-event, very low titer, non-neutralizing ADAs detected. CONCLUSIONS: The 48-week results from the EQUIRA study demonstrate that switch from ETN to SDZ ETN in patients with moderate-to-severe rheumatoid arthritis does not impact the efficacy, safety, or immunogenicity of etanercept. TRIAL REGISTRATION: EudraCT number 2012-002009-23 , Registered 19 April 2012-prospectively registered.

Long-Term Efficacy and Safety of Biosimilar CT-P10 Versus Innovator Rituximab in Rheumatoid Arthritis: 48-Week Results from a Randomized Phase III Trial.

OBJECTIVE: The aim of this study was to investigate long-term clinical outcomes of extended treatment with CT-P10, a rituximab biosimilar, compared with rituximab reference products sourced from the USA and the EU (US-RTX and EU-RTX) in rheumatoid arthritis (RA) for up to 48 weeks. METHODS: In this multinational, randomized, double-blind trial, adults with active RA received up to two courses of CT-P10, US-RTX, or EU-RTX alongside methotrexate. Efficacy endpoints included Disease Activity Score 28-joint count (DAS28) and American College of Rheumatology (ACR) response rates. Pharmacokinetics, pharmacodynamics, immunogenicity, and safety were also assessed. RESULTS: Of 372 patients randomized to the study drug, 330 (88.7%) completed the second treatment course. Mean change from baseline to week 48 in DAS28-C-reactive protein was comparable in the CT-P10 and combined rituximab (US-RTX and EU-RTX) groups (- 2.7 and - 2.6, respectively). ACR20, ACR50, and ACR70 response rates at week 48 indicated no differences between groups (80.6%, 55.4%, and 31.7% vs. 79.8%, 53.9%, and 33.7% in the CT-P10 and combined rituximab groups, respectively). Similar improvements in the Health Assessment Questionnaire Disability Index and all medical outcomes in the Short Form 36-Item Health Survey, including physical and mental health, were seen in all groups. At week 48, antidrug antibodies were detected in 4.9%, 9.4%, and 8.6% of patients in the CT-P10, US-RTX, and EU-RTX groups, respectively. CT-P10 and rituximab displayed similar pharmacokinetic, pharmacodynamic, and safety profiles. CONCLUSION: CT-P10 was similar to EU-RTX and US-RTX in terms of efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, and safety up to week 48. CLINICALTRIALS. GOV IDENTIFIER: NCT02149121.

Phase III Randomized Study of SB5, an Adalimumab Biosimilar, Versus Reference Adalimumab in Patients With Moderate-to-Severe Rheumatoid Arthritis.

OBJECTIVE: SB5 is a biosimilar agent for adalimumab (ADA). The aim of this study was to evaluate the efficacy, pharmacokinetics (PK), safety, and immunogenicity of SB5 in comparison with reference ADA in patients with rheumatoid arthritis (RA). METHODS: In this phase III, randomized, double-blind, parallel-group study, patients with moderately to severely active RA despite treatment with methotrexate were randomized 1:1 to receive SB5 or reference ADA at a dosage of 40 mg subcutaneously every other week. The primary efficacy end point was the response rate based on the American College of Rheumatology 20% improvement criteria (ACR20) at week 24 in the per-protocol set (completer analysis). Additional end points included efficacy, PK, safety, and immunogenicity assessments. RESULTS: Of the 544 patients randomized to receive a study drug, the full analysis set comprised 542 patients (269 in the SB5 group, 273 in the reference ADA group) and the per-protocol set comprised 476 patients (239 receiving SB5, 237 receiving reference ADA). The ACR20 response rate at week 24 in the per-protocol set was equivalent between those receiving SB5 and those receiving reference ADA (72.4% and 72.2%, respectively); the difference in the ACR20 response rate (0.1%, [95% confidence interval -7.83%, 8.13%]) was within the predefined equivalence margin (±15%). Similar results were seen in the full analysis set (missing data being considered a nonresponse). The SB5 and reference ADA treatment groups were comparable across other end points, including the ACR 50% and ACR 70% improvement response rates, Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate, PK data, incidence of treatment-emergent adverse events, and the antidrug antibody response. Subgroup analyses showed that the efficacy and safety of SB5 and reference ADA were comparable regardless of antidrug antibody status. CONCLUSION: The ACR20 response rate at week 24 was equivalent between patients treated with the biosimilar agent SB5 and those treated with reference ADA. SB5 and reference ADA were both well tolerated, with comparable safety profiles, in patients with RA.

Switching From Reference Adalimumab to SB5 (Adalimumab Biosimilar) in Patients With Rheumatoid Arthritis: Fifty-Two-Week Phase III Randomized Study Results.

OBJECTIVE: The 24-week equivalent efficacy and comparable safety results of the biosimilar SB5 and reference adalimumab (ADA) from the phase III randomized study in patients with moderate-to-severe rheumatoid arthritis (RA) have been reported previously. We undertook this transition study to evaluate patients who switched from ADA to SB5 or who continued to receive SB5 or ADA up to 52 weeks. METHODS: In this phase III study, patients were initially randomized 1:1 to receive SB5 or ADA (40 mg subcutaneously every other week). At 24 weeks, patients receiving ADA were rerandomized 1:1 to continue with ADA (ADA/ADA group) or to switch to SB5 (ADA/SB5 group) up to week 52; patients receiving SB5 continued with SB5 for 52 weeks (SB5 group). Efficacy, safety, and immunogenicity were evaluated up to 52 weeks. RESULTS: The full analysis set population consisted of 542 patients (269 in the SB5 group, 273 in the ADA overall group [patients who were randomized to receive ADA at week 0], 125 in the ADA/SB5 group, and 129 in the ADA/ADA group). The percentages of patients meeting the American College of Rheumatology 20%, 50%, or 70% improvement criteria (achieving an ACR20, ACR50, or ACR70 response) at week 24 were maintained after the transition from ADA to SB5, and these response rates were comparable across treatment groups throughout the study. ACR20 response rates ranged from 73.4% to 78.8% at week 52. Radiographic progression was minimal and comparable across treatment groups. The safety profile and the incidence of antidrug antibodies were comparable across treatment groups after transition. CONCLUSION: SB5 was well tolerated over 1 year in patients with RA, with efficacy, safety, and immunogenicity comparable to those of ADA. Switching from ADA to SB5 had no treatment-emergent issues such as increased adverse events, increased immunogenicity, or loss of efficacy.

Effect of Acute Effort on Isometric Strength and Body Balance: Trained vs. Untrained Paradigm.

Years of training in competitive sports leads to human body adaptation to a specific type of exercise. In judo bouts, maintaining hand grip on an opponent's clothes and postural balance is essential for the effective technical and tactical actions. This study compares changes after maximal anaerobic exercise among judo athletes and untrained subjects regarding 1) maximum isometric handgrip strength (HGSmax) and accuracy at the perceived 50% maximum handgrip force (1/2HGSmax) and 2) the balance of 13 judo athletes at national (n = 8) and international (n = 5) competitive levels and 19 untrained university students. The groups did not differ in age, body height, and weight. Body mass index (BMI) and body composition (JAWON) were evaluated. The Wingate Anaerobic Test (WAnT, Monark 875E) measured recommended anaerobic capacity indices. Hand grip strength (Takei dynamometer) and balance (biplate balance platform) were measured before warm-up (T1), before the WAnT test (T2), and after (T3). Parametric or non-parametric tests were performed after verifying the variable distribution assumption. Judoists had higher BMI and fat-free mass index (FFMI) than the students. The athletes also showed higher relative total work and relative peak power and lower levels of lactic acid. The difference in judoists between HGSmax at T1 and HGSmax at T3 was statistically significant. Before warm-up (T1), athletes showed higher strength (more divergent from the calculated ½HGSmax value) compared to students. Substantial fatigue after the WAnT test significantly deteriorated the body stability indices, which were significantly better in judo athletes at all time points. The findings suggest specific body adaptations in judoists, especially for body composition, anaerobic energy system efficiency, and postural balance. These characteristics could be trained for specifically by judo athletes to meet the time-motion and anaerobic demands of contemporary bouts.

Comparable long-term efficacy, as assessed by patient-reported outcomes, safety and pharmacokinetics, of CT-P13 and reference infliximab in patients with ankylosing spondylitis: 54-week results from the randomized, parallel-group PLANETAS study.

BACKGROUND: CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®) and is approved in Europe and elsewhere, mostly for the same indications as RP. The aim of this study was to compare the 54-week efficacy, immunogenicity, pharmacokinetics (PK) and safety of CT-P13 with RP in patients with ankylosing spondylitis (AS), with a focus on patient-reported outcomes (PROs). METHODS: This was a multinational, double-blind, parallel-group study in patients with active AS. Participants were randomized (1:1) to receive CT-P13 (5 mg/kg) or RP (5 mg/kg) at weeks 0, 2, 6 and then every 8 weeks up to week 54. To assess responses, standardized assessment tools were used with an intention-to-treat analysis of observed data. Anti-drug antibodies (ADAs), PK parameters, and safety outcomes were also assessed. RESULTS: Of 250 randomized patients (n = 125 per group), 210 (84.0 %) completed 54 weeks of treatment, with similar completion rates between groups. At week 54, Assessment of Spondylo Arthritis international Society (ASAS)20 response, ASAS40 response and ASAS partial remission were comparable between treatment groups. Changes from baseline in PROs such as mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; CT-P13 -3.1 versus RP -2.8), Bath Ankylosing Spondylitis Functional Index (BASFI; -2.9 versus -2.7), and Short Form Health Survey (SF-36) scores (9.26 versus 10.13 for physical component summary; 7.30 versus 6.54 for mental component summary) were similar between treatment groups. At 54 weeks, 19.5 % and 23.0 % of patients receiving CT-P13 and RP, respectively, had ADAs. All observed PK parameters of CT-P13 and RP, including maximum and minimum serum concentrations, were similar through 54 weeks. The influence of ADAs on PK was similar in the two treatment groups. Most adverse events were mild or moderate in severity. There was no notable difference between treatment groups in the incidence of adverse events, serious adverse events, infections and infusion-related reactions. CONCLUSIONS: CT-P13 and RP have highly comparable efficacy (including PROs) and PK up to week 54. Over a 1-year period, CT-P13 was well tolerated and displayed a safety profile comparable to RP; no differences in immunogenicity were observed. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01220518 . Registered 4 October 2010.