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Acute Whole-Body Vibration Exercise Promotes Favorable Handgrip Neuromuscular Modifications in Rheumatoid Arthritis: A Cross-Over Randomized Clinical.
Coelho-Oliveira, AC, Lacerda, ACR, de Souza, ALC, Santos, LMM, da Fonseca, SF, Dos Santos, JM, Ribeiro, VGC, Leite, HR, Figueiredo, PHS, Fernandes, JSC, et al
BioMed research international. 2021;:9774980
Abstract
OBJECTIVE Rheumatoid arthritis (RA) causes progressive changes in the musculoskeletal system compromising neuromuscular control especially in the hands. Whole-body vibration (WBV) could be an alternative for the rehabilitation in this population. This study investigated the immediate effect of WBV while in the modified push-up position on neural ratio (NR) in a single session during handgrip strength (HS) in women with stable RA. METHODS Twenty-one women with RA (diagnosis of disease: ±8 years, erythrocyte sedimentation rate: ±24.8, age: 54± 11 years, BMI: 28 ± 4 kg·m-2) received three experimental interventions for five minutes in a randomized and balanced cross-over order: (1) control-seated with hands at rest, (2) sham-push-up position with hands on the vibration platform that remained disconnected, and (3) vibration-push-up position with hands on the vibration platform turned on (45 Hz, 2 mm, 159.73 m·s-2). At the baseline and immediately after the three experimental interventions, the HS, the electromyographic records (EMGrms), and range of motion (ROM) of the dominant hand were measured. The NR, i.e., the ratio between EMGrms of the flexor digitorum superficialis (FDS) muscle and HS, was also determined. The lower NR represented the greater neuromuscular efficiency (NE). RESULTS The NR was similar at baseline in the three experimental interventions. Despite the nonsignificance of within-interventions (p = 0.0611) and interaction effect (p = 0.1907), WBV exercise reduced the NR compared with the sham and control (p = 0.0003, F = 8.86, η 2 = 0.85, power = 1.00). CONCLUSION Acute WBV exercise under the hands promotes neuromuscular modifications during the handgrip of women with stable RA. Thus, acute WBV exercise may be used as a preparatory exercise for the rehabilitation of the hands in this population. This trial is registered with trial registration 2.544.850 (ReBEC-RBR-2n932c).
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The Bioequivalence of Two Peficitinib Formulations, and the Effect of Food on the Pharmacokinetics of Peficitinib: Two-Way Crossover Studies of a Single Dose of 150 mg Peficitinib in Healthy Volunteers.
Shibata, M, Toyoshima, J, Kaneko, Y, Oda, K, Kiyota, T, Kambayashi, A, Nishimura, T
Clinical pharmacology in drug development. 2021;(3):283-290
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Abstract
The marketed tablet formulation of peficitinib differs from the tablet used during the clinical trials. The bioequivalence of the marketed formulation and developmental tablet, and the food effect on the marketed formulation, were analyzed in 2 Japanese open-label, randomized, 2-way crossover studies in healthy male volunteers. Volunteers received a single oral dose of the marketed 150-mg peficitinib tablet under fasted conditions (bioequivalence), and under fed or fasted conditions (food effect). Bioequivalence was compared with the developmental 150-mg tablet. Samples for pharmacokinetic analysis were collected before dose and ≤72 hours after dose. Safety assessments included adverse events, vital signs, and laboratory variables. In total, 40 and 18 subjects were randomized to the bioequivalence and food effect studies, respectively. The 2 peficitinib formulations were bioequivalent (90% confidence intervals of the geometric mean ratios for Cmax and AUCt of peficitinib were within predefined limits of 0.8 to 1.25). The AUClast and the Cmax of the marketed tablet were 36.8% and 56.4% higher, respectively, under fed versus fasted conditions. Peficitinib was well tolerated. The marketed 150-mg tablet formulation of peficitinib was bioequivalent to the developmental 150-mg formulation, with no discernible safety differences. Bioavailability increased under fed conditions with the marketed tablet formulation.
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The effect of black barberry hydroalcoholic extract on immune mediators in patients with active rheumatoid arthritis: A randomized, double-blind, controlled clinical trial.
Aryaeian, N, Hadidi, M, Mahmoudi, M, Asgari, M, Hezaveh, ZS, Sadehi, SK
Phytotherapy research : PTR. 2021;(2):1062-1068
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease associated with inflammation. In this trial, we aimed to investigate the Immunomodulatory effect of hydroalcoholic extract of black barberry on immune mediators in patients with active rheumatoid arthritis. In this randomized, double-blind, placebo-controlled clinical trial, 80 women with active RA were randomly assigned into two groups of two capsules, each containing 1,000 mg black barberry extract (n = 40) or maltodextrin placebo (n = 40) daily for 12 weeks. Demographic indices, physical activity, dietary intake, and disease activity were investigated using suitable questionnaires. Concentration of cytokines IL-2, IL-4, IL-10, and IL-17 in blood sample were measured using PBMC method. Statistical analysis was performed using SPSS (version 22). At baseline, there were no differences between the two groups in terms of demographic indices, physical activity, and dietary intake (p > .05). Black barberry supplementation reduced the severity of RA. It showed no significant effect on IL-2 and IL-4 cytokines (p > .05). IL-17 levels decreased significantly after the intervention within the black barberry group, while IL-10 had a significant increase in this group (p < .05). Barberry extract may reduce inflammatory and increase anti-inflammatory cytokines in RA, and stimulates the immune response by increasing Th2 production.
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Comparative study evaluating antihistamine versus leukotriene receptor antagonist as adjuvant therapy for rheumatoid arthritis.
Mostafa, TM, Hegazy, SK, El-Ghany, SEA, Kotkata, FAE
European journal of clinical pharmacology. 2021;(12):1825-1834
Abstract
PURPOSE Investigating the efficacy and safety of rupatadine (RUP) versus montelukast (MON) as adjuvant therapy for patients with rheumatoid arthritis (RA). METHODS From December 2018 to December 2019, 75 patients with active RA were enrolled in this randomized double-blind placebo-controlled study. The patients were randomized into three groups (n = 25 in each group); methotrexate (MTX) group which received MTX 15-25 mg/week plus placebo tablet once daily; MTX/RUP group which received MTX plus RUP 10 mg once daily; and MTX/MON group which received MTX plus MON 10 mg once daily. The treatment duration was 3 months. At baseline and 3 months after treatment, blood samples were collected for the biochemical analysis of high-sensitivity C-reactive protein (hs-CRP), interleukins 8 and 17 (IL-8, IL-17), E-selectin, and clusterin (CLU) levels. Clinical and functional assessments using Disease Activity Score-CRP (DAS28-CRP) and Multidimensional Health Assessment Questionnaire (MDHAQ) were performed. RESULTS Both RUP and MON produced clinical and functional improvements which were translated by significant improvements in DAS28-CRP score and MDHAQ. Rupatadine significantly reduced all measured parameters (P < 0.05) except for IL-17 and CLU. Montelukast significantly decreased all measured variables (P < 0.05) except for E-selectin. Interleukin-8 was positively correlated with IL-17 and CLU, while hs-CRP was positively correlated with E-selectin and body mass index (BMI). Both drugs were well tolerated; somnolence was the common side effect for RUP. No neuropsychiatric events were reported with MON. CONCLUSION Rupatadine or montelukast may serve as a potential adjuvant therapy for patients with rheumatoid arthritis secondary to the preliminary evidence of efficacy and safety. ClinicalTrials.gov identifier NCT03770923, December 10, 2018.
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Effects on health-related quality of life in the randomized, controlled crossover trial ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis).
Turesson Wadell, A, Bärebring, L, Hulander, E, Gjertsson, I, Hagberg, L, Lindqvist, HM, Winkvist, A
PloS one. 2021;(10):e0258716
Abstract
BACKGROUND Patients with Rheumatoid Arthritis (RA) often report impaired health-related quality of life (HrQoL) such as difficulties in daily life, pain, fatigue and an affected social life. Even when lowering disease activity, pharmacological treatment does not always resolve these factors. OBJECTIVE To investigate if a proposed anti-inflammatory diet improves HrQoL in patients with RA. DESIGN In this controlled crossover trial, 50 patients were randomized to start with either an intervention diet (anti-inflammatory) or a control diet (usual Swedish intake) for ten weeks followed by a wash out period before switching to the other diet. Participants received food equivalent to ~1100 kcal/day, five days/week, and instructions to consume similarly for the remaining meals. HrQoL was evaluated using Health Assessment Questionnaire (HAQ), 36-item Short Form Survey (SF-36), Visual Analogue Scales (VAS) for pain, fatigue and morning stiffness, and a time scale for morning stiffness. RESULTS Forty-seven participants completed ≥1 diet period and were included in the main analyses. No significant difference between intervention and control diet at end of diet periods was observed for any outcome. However, significant improvements were obtained for SF-36 Physical Functioning (mean:5.79, SE: 2.12, 95% CI: 1.58, 10.01) during the intervention diet period. When excluding participants with anti-rheumatic medication changes, the differences between diet periods increased for most outcomes, favoring the intervention diet period, and the difference for SF-36 Physical Functioning became significant (n = 25, mean:7.90, 95% CI:0.56, 15.24, p = 0.036). CONCLUSIONS In main analyses, the proposed anti-inflammatory diet did not significantly improve HrQoL for patients with RA compared to control diet. In sub-analyses, significant improvements in physical functioning were detected. Larger studies with consistent medication use and in populations more affected by the disease may be needed to obtain conclusive evidence.
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Similar lipid level changes in early rheumatoid arthritis patients following 1-year treat-to-target strategy with adalimumab plus methotrexate versus placebo plus methotrexate: secondary analyses from the randomised controlled OPERA trial.
Mašić, D, Stengaard-Pedersen, K, Løgstrup, BB, Hørslev-Petersen, K, Hetland, ML, Junker, P, Østergaard, M, Ammitzbøll, C, Möller, S, Christensen, R, et al
Rheumatology international. 2021;(3):543-549
Abstract
To compare changes in low-density lipoprotein cholesterol and other lipids in patients with rheumatoid arthritis (RA) randomised to a 1-year treat-to-target strategy with either adalimumab plus methotrexate or placebo plus methotrexate. Prespecified secondary analyses from the OPERA trial, where 180 early and treatment-naïve RA patients received methotrexate 20 mg once weekly in combination with either placebo or subcutaneous adalimumab 40 mg every other week. Serum lipid levels were measured at baseline and after 1 year. Changes in lipid levels were analysed using mixed linear models based on the intention-to-treat (ITT) population. Overall, 174 patients were included in the ITT population (adalimumab plus methotrexate n = 86; placebo plus methotrexate n = 88). Differences between changes in lipid levels were low-density lipoprotein cholesterol 0.18 mmol/l [95% CI - 0.05 to 0.42], total cholesterol 0.27 mmol/l [- 0.002 to 0.54], high-density lipoprotein cholesterol 0.05 mmol/l [- 0.06 to 0.15], triglycerides 0.11 mmol/l [- 0.08 to 0.29], very-low-density lipoprotein cholesterol 0.03 mmol/l [- 0.05 to 0.12], and non-high-density lipoprotein cholesterol 0.22 mmol/l [- 0.02 to 0.46]. In early RA patients treated to tight control of inflammation over a period of 1 year with either adalimumab plus methotrexate or placebo plus methotrexate, changes in lipid levels were similar. Trial registration number: NCT00660647.
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Effects of hydroalcoholic extract of Berberis Integerrima on the anthropometric indices and metabolic profile in active rheumatoid arthritis patients.
Aryaeian, N, Sedehi, SK, Khorshidi, M, Zarezadeh, M, Hosseini, A, Shahram, F
Complementary therapies in medicine. 2020;:102331
Abstract
OBJECTIVES Since, the main cause of death in Rheumatoid arthritis (RA) patients is the presence of type 2 diabetes, abnormal increase in blood lipids, blood pressure and obesity, the aim of this study was to assess the effects of Barberry on the anthropometric indices and metabolic profile in patients with RA. DESIGN present study was a double-blinded, placebo-controlled randomized clinical trial. SETTING 70 active RA patients were randomly allocated into intervention or placebo group INTERVENTION Participants received 6 capsules of 500 mg barberry extract or placebo for 3 months. MAIN OUTCOME MEASURES Serum levels of fasting blood sugar (FBS), triglyceride (TG), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C), systolic and diastolic blood pressure and anthropometric factors were assessed at baseline and at the end of the trial. RESULTS The results of intervention on 62 patients showed that weight, BMI, and conicity index increased in both groups, but this was significant only in the placebo group (p < 0.001). Waist and hip circumference were decreased in the intervention group and increased significantly in the placebo group (p < 0.001). Body fat percent (p = 0.04), LDL-C (p = 0.05) and SBP (p = 0.02) significantly were decreased in the intervention group. The results showed a significant decrease in body fat percent (p = 0.05), hip circumference (p < 0.001), FBS (p = 0.03) and HDL-C (p = 0.03) in the intervention group compared to the placebo. CONCLUSIONS Overall, the results of this study demonstrated that the extract of Berberis Integerrima had beneficial effects on metabolic profile and anthropometric indices in RA patients.
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Cardiovascular Safety of Tocilizumab Versus Etanercept in Rheumatoid Arthritis: A Randomized Controlled Trial.
Giles, JT, Sattar, N, Gabriel, S, Ridker, PM, Gay, S, Warne, C, Musselman, D, Brockwell, L, Shittu, E, Klearman, M, et al
Arthritis & rheumatology (Hoboken, N.J.). 2020;(1):31-40
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Abstract
OBJECTIVE To assess the risk of major adverse cardiovascular events (MACE) in patients with rheumatoid arthritis (RA) treated with tocilizumab compared to those treated with the tumor necrosis factor inhibitor etanercept. METHODS This randomized, open-label, parallel-group trial enrolled patients with active seropositive RA (n = 3,080) who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs and who had at least 1 cardiovascular (CV) risk factor. Patients were randomly assigned 1:1 to receive open-label tocilizumab at 8 mg/kg/month or etanercept at 50 mg/week. All patients were followed up for a mean of 3.2 years. The primary end point was comparison of time to first occurrence of MACE. The trial was powered to exclude a relative hazard ratio for MACE of 1.8 or higher in the tocilizumab group compared to the etanercept group. RESULTS By week 4 of treatment, the serum low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels were a median 11.1%, 5.7%, and 13.6% higher, respectively, in patients receiving tocilizumab compared to those receiving etanercept (each P < 0.001). During follow-up, 83 MACE occurred in the tocilizumab group compared to 78 MACE in the etanercept group. The estimated hazard ratio for occurrence of MACE in the tocilizumab group relative to the etanercept group was 1.05 (95% confidence interval 0.77-1.43). Results were similar in sensitivity analyses and in the on-treatment population analysis. Adverse events occurred more frequently in the tocilizumab group, including serious infection and gastrointestinal perforation. CONCLUSION The results of this trial, which provide insights into the CV safety of tocilizumab as compared to etanercept, ruled out a risk for occurrence of MACE of 1.43 or higher in patients treated with tocilizumab. This result should be interpreted in the context of the clinical efficacy and non-CV safety of tocilizumab.
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A Randomized, Double-Blind Study Comparing Pharmacokinetics and Pharmacodynamics of Proposed Biosimilar ABP 798 With Rituximab Reference Product in Subjects With Moderate to Severe Rheumatoid Arthritis.
Burmester, G, Chien, D, Chow, V, Gessner, M, Pan, J, Cohen, S
Clinical pharmacology in drug development. 2020;(8):1003-1014
Abstract
ABP 798 is a proposed biosimilar to rituximab reference product (RP), an anti-CD20 monoclonal antibody. Pharmacokinetics (PK), pharmacodynamics (PD), and safety results from the comparative clinical study that evaluated the PK, PD, safety, efficacy, and immunogenicity of ABP 798 versus rituximab RP are presented here. Subjects with moderate to severe rheumatoid arthritis (RA) received 2 doses of ABP 798, United States-sourced RP (rituximab US) or European Union-sourced RP (rituximab EU), each consisting of two 1000-mg infusions 2 weeks apart. For the second dose (week 24), ABP 798- and rituximab EU-treated subjects received the same treatment; rituximab US-treated subjects transitioned to ABP 798. End points included area under the serum concentration-time curve from time 0 extrapolated to infinity and maximum observed serum concentration following the second infusion of the first dose (PK) and percentage of subjects with complete CD19+ cell depletion days 1-33 (PD). Primary analysis established PK similarity between ABP 798 and rituximab RP based on 90% confidence intervals of the adjusted geometric mean ratios being within a prespecified equivalence margin of 0.8 and 1.25. Complete CD19+ B-cell depletion on day 3 among groups confirmed PD similarity. These findings demonstrated PK/PD similarity between ABP 798 and rituximab RP in subjects with moderate to severe RA.
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Formulation of Topical Dosage Forms Containing Synthetic and Natural Anti-Inflammatory Agents for the Treatment of Rheumatoid Arthritis.
Jurca, T, Józsa, L, Suciu, R, Pallag, A, Marian, E, Bácskay, I, Mureșan, M, Stan, RL, Cevei, M, Cioară, F, et al
Molecules (Basel, Switzerland). 2020;(1)
Abstract
Topical anti-inflammatory and analgesic effect for the treatment of rheumatoid arthritis is of major interest because of their fewer side effects compared to oral therapy. The purpose of this study was to prepare different types of topical formulations (ointments and gels) containing synthetic and natural anti-inflammatory agents with different excipients (e.g.,: surfactants, gel-forming) for the treatment of rheumatoid arthritis. The combination of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), diclofenac sodium, a topical analgesic agent methyl salicylate, and a lyophilized extract of Calendula officinalis with antioxidant effect were used in our formulations. The aim was to select the appropriate excipients and dosage form for the formulation in order to enhance the diffusion of active substances and to certify the antioxidant, analgesic, and anti-inflammatory effects of these formulations. To characterize the physicochemical properties of the formulations, rheological studies, and texture profile analysis were carried out. Membrane diffusion and permeability studies were performed with Franz-diffusion method. The therapeutic properties of the formulations have been proven by an antioxidant assay and a randomized prospective study that was carried out on 115 patients with rheumatoid arthritis. The results showed that the treatment with the gel containing diclofenac sodium, methyl salicylate, and lyophilized Calendula officinalis as active ingredients, 2-propenoic acid homopolymer (Synthalen K) as gel-forming excipient, distilled water, triethanolamine, and glycerol had a beneficial analgesic and local anti-inflammatory effect.