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.

Coupled Field Analysis of Phenomena in Hybrid Excited Magnetorheological Fluid Brake.

The paper presents a field model of coupled phenomena occurring in an axisymmetric magnetorheological brake. The coupling between transient fluid dynamics and electromagnetic and thermal fields as well as mechanical equilibrium equations is taken into account. The magnetic field in the studied brake is of an excited hybrid manner, i.e., by the permanent magnets (PMs) and current Is in the excitation winding. The finite element method and a step-by-step algorithm have been implemented in the proposed field model of coupled phenomena in the considered brake. The nonlinearity of the magnetic circuit and rheological properties of a magnetorheological fluid (MR fluid) as well as the influence of temperature on the properties of materials have been taken into account. To solve equations of the obtained field model, the Newton-Raphson method and the coupled block over-relaxation method have been implemented. The elaborated algorithm has been successfully used in the analysis of the phenomena in the considered magnetorheological brake. The accuracy of the developed model and its usefulness have been verified by a comparative analysis of the results of simulation and laboratory tests carried out for the developed prototype of the studied brake.

Application of Multi-Branch Cauer Circuits in the Analysis of Electromagnetic Transducers Used in Wireless Transfer Power Systems.

In this paper, the feasibility of applying a multi-branch equivalent model employing first- and second-order Cauer circuits for the analysis of electromagnetic transducers used in systems of wireless power transfer is discussed. A method of formulating an equivalent model (EqM) is presented, and an example is shown for a wireless power transfer system (WPTS) consisting of an air transformer with field concentrators. A method is proposed to synthesize the EqM of the considered transducer based on the time-harmonic field model, an optimization algorithm employing the evolution strategy (ES) and the equivalent Cauer circuits. A comparative analysis of the performance of the considered WPTS under high-frequency voltage supply calculated using the proposed EqM and a 3D field model in the time domain using the finite element method (FEM) was carried out. The selected results of the conducted analysis are presented and discussed.

Optimal Digital Implementation of Fractional-Order Models in a Microcontroller.

The growing number of operations in implementations of the non-local fractional differentiation operator is cumbersome for real applications with strict performance and memory storage requirements. This demands use of one of the available approximation methods. In this paper, the analysis of the classic integer- (IO) and fractional-order (FO) models of the brushless DC (BLDC) micromotor mounted on a steel rotating arms, and next, the discretization and efficient implementation of the models in a microcontroller (MCU) is performed. Two different methods for the FO model are examined, including the approximation of the fractional-order operator s ν ( ν ∈ R ) using the Oustaloup Recursive filter and the numerical evaluation of the fractional differintegral operator based on the Grünwald-Letnikov definition and Short Memory Principle. The models are verified against the results of several experiments conducted on an ARM Cortex-M7-based STM32F746ZG unit. Additionally, some software optimization techniques for the Cortex-M microcontroller family are discussed. The described steps are universal and can also be easily adapted to any other microcontroller. The values for integral absolute error (IAE) and integral square error (ISE) performance indices, calculated on the basis of simulations performed in MATLAB, are used to evaluate accuracy.

Effect of zirconia surface treatment on its wettability by liquid ceramics.

STATEMENT OF PROBLEM: The wettability of the framework by liquid ceramics is important in ensuring a suitable bond between veneering ceramics and zirconia. PURPOSE: The purpose of this in vitro study was to examine the dependence of the wetting angle on temperature to determine the transition temperature from nonwettable to wettable states and to calculate the values of the relative wetting forces of the milled surfaces. MATERIAL AND METHODS: Fifty zirconia cylinders were divided into 5 groups (n=10) and subjected to the following treatments: milling, grinding, polishing, and airborne-particle abrasion with Al2O3 or SiC. After treatment, the specimens were rinsed, dried, and examined with respect to their wettability by liquid ceramics by using the automated Thermo-Wet test bench. The results were statistically analyzed by an ANOVA (α=.05). RESULTS: The most rapid wettability was obtained through airborne-particle abrasion with Al2O3 at 930 °C. Additionally, the highest relative bond strength (with respect to the machined surface) was obtained with Al2O3 abrasion. CONCLUSIONS: Because of variations in the wettability of the zirconia surface after different treatment methods, the firing temperature of the ceramic should also vary depending on the type of surface treatment applied. Thus, it is determined individually according to the chosen method.

The role of ultrasonography in monitoring long-standing rheumatoid arthritis: a pilot study.

OBJECTIVE: Rheumatoid arthritis (RA) is a condition that poses many diagnostic problems. As a result, it is often diagnosed too late, which makes effective treatment more difficult. The course of the disease is chronic, and it causes irreversible changes in the musculoskeletal system, as well as bone destruction, and this in turn impairs the proper monitoring of the treatment. Therefore, in order to assess the treatment's efficacy, as well as a clinical examination of the patient and laboratory tests, diagnostic imaging is being used more frequently in routine practice. The aim of this paper is to assess the usefulness of power Doppler ultrasonography in the assessment of MCP joints in patients with chronic RA (LSRA), in comparison with DAS28, X-ray, and MRI. MATERIAL AND METHODS: The study involved 26 patients with LSRA, treated with biologics. It lasted for a year. At the moment of enrolment, the condition had lasted for a minimum of 5 years, and DAS28 was > 5.1. The patients had visits every three months. During every visit, a PDUS test was performed and the DAS28 was determined. In the first and last month of the study the patients underwent X-ray and MRI tests. RESULTS: At the end of the study, the DAS28 of 26 (100%) patients was lower or equal to 3.2. Based on PDUS and MRI tests, no synovitis was found in 21 (81%) and 18 (69%) patients, respectively. According to the MRI results, radiological changes progressed in 5 (19%) of them. All patients who showed progress of radiological changes also had visible synovitis during their PDUS test. CONCLUSIONS: PDUS in patients with LSRA can be helpful in selecting patients, who are likely to develop a progression of radiological changes.

Assessment of the usefulness of skin autofluorescence as an indicator of disease activity and of the risk of developing diabetes in patients suffering from rheumatoid arthritis.

OBJECTIVES: Diabetes develops much more often in patients suffering from rheumatoid arthritis (RA) than in healthy population. One of the parameters which allow to evaluate the risk of developing diabetes and cardiovascular diseases (CVD) is the level of advanced glycation end products (AGE) in the skin. In patients suffering from RA, an increase in AGE level may be also linked with the course of the underlying disease. The aim of the study was to evaluate the correlation between the AGE level and the course of RA as well as other risk factors for the development of diabetes and CVD. MATERIAL AND METHODS: The study included 148 patients divided into three groups: group I - patients with RA (n = 102, 79 F/23 M), group II - patients with RA and diabetes (n = 21, 14 F/7 M), group III - healthy individuals (n = 25, 16 F/9 M). Each patient underwent a skin autofluorescence signal (SAF) examination with an AGE Reader, which allows the assessment of AGE level, as well as being subjected to the laboratory tests panel. Additionally, patients from group I and II have had their DAS28 (ESR) indicator calculated. RESULTS: In groups I, II, and III, the respective mean SAF values, expressed in arbitrary units [au], were to 2.54, 2.74, and 1.96 au. Between-group differences in terms of mean SAF values were statistically significant (p < 0.05). CONCLUSIONS: Significantly higher mean SAF values in groups I and II as compared to group III suggest that the increase in the AGE level in patients with RA is linked with the underlying disease and does not have to correspond with the real risk of diabetes and CVD. In conclusion, despite the known limitations of the technique, measuring AGE levels allows for closer monitoring of RA patients who are at a higher risk of developing diabetes.

CT-Based Evaluation of Volumetric Posterior Pelvic Bone Density with Implications for the Percutaneous Screw Fixation of the Sacroiliac Joint.

Background: Operative treatment of fragility fractures of the pelvis has become a gold standard. Preoperative planning, including the assessment of the pathway for iliosacral screws, is crucial. The anchorage of the screw depends on the bone quality. Some recent studies have concentrated on assessing bone mineral density (BMD) with the use of Hounsfield unit (HU) values obtained from CT scans. The aim of the present study is to determine the best sacral levels of S1-S3 on the pathway of iliosacral screws for sacroiliac joint fixation. Methods: Patients admitted to the Independent Public Healthcare Center in Rypin between 1 of September and 1 of December in 2023, who had CT scans of the pelvis performed on them for different reasons, were included in this study. In total, 103 patients-56 men and 47 women-were enrolled in the study and consecutively separated into two groups of different ages: 18-60 years old (group A) and above 60 years old (group B). The volumetric bone density expressed in HU values was measured with sacral levels of S1, S2 and S3. Apart from the bodies of sacral vertebrae S1-S3, our measurements involved the ala of the ilium in the vicinity of the sacroiliac joint and the wing of the sacrum. All the measurements were performed on the pathway of presumptive iliosacral screws to stabilize the sacroiliac joint. Results: In group A (58 patients) the highest bone density in sacral bodies was found in S1 that gradually decreased to S3, while the opposite tendency was demonstrated in the ala of ilium. The HU values in the wing of the sacrum did not display statistical significance. In group B (45 patients), the highest bone density was also found in the sacral body S1 that decreased toward S3 but in the ala of ilium, the highest bone density was found with level S1 and lowest with level S2. In both groups, the highest bone density referred to the wing of the sacrum. Conclusion: While the perfect construct for posterior pelvic ring fixation remains unclear, our findings may imply that sacroiliac joint screws inserted into the wing of the sacrum of greater bone density could provide much more successful fixation in comparison to those anchored in the body of sacral vertebra of lesser bone density.

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.

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.

Comparative clinical efficacy and safety of the proposed biosimilar ABP 710 with infliximab reference product in patients with rheumatoid arthritis.

BACKGROUND: ABP 710 is being developed as a biosimilar to infliximab reference product (RP). Analytical similarity and pharmacokinetic equivalence between the two have been previously demonstrated. Here we report results from a comparative clinical study that evaluated the efficacy and safety of ABP 710 relative to the RP in patients with rheumatoid arthritis (RA). METHODS: In this multicenter, randomized, double-blind, 50-week equivalence study, patients with moderate to severe active RA despite methotrexate received 3-mg/kg infusions of ABP 710 or RP at predetermined intervals based on initial randomization and then with re-randomization at week 22. The primary endpoint was response difference (RD) of ACR20 at week 22, with clinical equivalence evaluated based on 90% CI of - 15%, 15%. Secondary endpoints included Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP), ACR20, ACR50, and ACR70 across time, as well as safety and immunogenicity assessments. RESULTS: A total of 558 patients were randomized for the initial treatment (ABP 710 n = 279; RP n = 279). The estimated RD of ACR20 at week 22 was 9.37% with 90% CI (2.67%, 15.96%). The lower bound was within the pre-specified criteria, thus confirming non-inferiority; the upper bound exceeded the pre-specified criteria by 0.96% such that superiority could not be ruled out statistically. In a post hoc analysis with adjustment for random imbalance in baseline factors, the CI of RD was narrowed (0.75%, 13.62%). Changes from baseline in DAS28-CRP as well as ACR20, ACR50, and ACR70 response rates across time and hybrid ACR evaluations were similar for the initial and initial/re-randomized treatment groups. Adverse events and incidence of anti-drug antibodies were similar between treatment groups. CONCLUSIONS: These efficacy and safety results support similarity with no clinically meaningful differences between ABP 710 and infliximab RP. Although we were unable to statistically confirm non-superiority, post hoc analysis was supportive of non-superiority. DAS28-CRP, ACR20, ACR50, ACR70, and hybrid ACR evaluations over the entire study were consistently comparable as were safety and immunogenicity. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT02937701. Registered August 30, 2016.