scholarly journals Background Glucocorticoid Therapy Has No Impact on Efficacy and Safety of Abatacept or Adalimumab in Patients with Rheumatoid Arthritis

2020 ◽  
Vol 9 (6) ◽  
pp. 2017
Author(s):  
Yannick Degboé ◽  
Michael Schiff ◽  
Michael Weinblatt ◽  
Roy Fleischmann ◽  
Harris A. Ahmad ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Health Assessment ◽  
Similar Proportion ◽  
Efficacy And Safety ◽  
Reactive Protein ◽  
Radiographic Outcomes ◽  
Score Improvement ◽  
Additional Value ◽  
The Impact

To date, the impact of background glucocorticoids (GC) on the efficacy and safety of abatacept or adalimumab in patients with active rheumatoid arthritis (RA) is not clearly established. This post hoc analysis of (AMPLE) trial (NCT00929864) compared efficacy and safety outcomes over 2 years in patients treated with abatacept or adalimumab plus background methotrexate (MTX), who continued GC (≤10 mg/day) versus those who were not receiving GC (no-GC). Of 646 randomized patients, 317 received abatacept + MTX (161 GC, 156 no-GC) and 326 received adalimumab + MTX (162 GC, 164 no-GC). At Year 2, the adjusted mean changes from baseline in Disease Activity Score (DAS28 C-reactive protein (CRP)) and Health Assessment Questionnaire-Disability Index (HAQ-DI) were not significantly different in the GC versus no-GC subgroups receiving abatacept or adalimumab. A similar proportion of patients achieved remission, HAQ-DI score improvement ≥0.3 and radiographic progression rates. No clinically meaningful safety differences were observed between GC versus no-GC subgroups either with abatacept or adalimumab. In patients with active RA of similar baseline disease activity treated with abatacept or adalimumab plus background MTX, there was no additional value of background GC on clinical, functional or radiographic outcomes over two years.

scholarly journals Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study

2019 ◽  
Vol 78 (8) ◽  
pp. 1033-1040 ◽  
Author(s):  
Sophie Glatt ◽  
Peter C Taylor ◽  
Iain B McInnes ◽  
Georg Schett ◽  
Robert Landewé ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Certolizumab Pegol ◽  
Inadequate Response ◽  
Proof Of Concept ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Reactive Protein ◽  
Dual Inhibition

ObjectiveEvaluate the efficacy and safety of dual neutralisation of interleukin (IL)-17A and IL-17F with bimekizumab, a monoclonal IgG1 antibody, in addition to certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) and inadequate response (IR) to certolizumab pegol.MethodsDuring this phase 2a, double-blind, proof-of-concept (PoC) study (NCT02430909), patients with moderate-to-severe RA received open-label CZP 400 mg at Weeks 0, 2 and 4, and 200 mg at Week 6. Patients with IR at Week 8 (Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP))>3.2) were randomised 2:1 to CZP (200 mg every 2 weeks (Q2W)) plus bimekizumab (240 mg loading dose then 120 mg Q2W) or CZP plus placebo. The primary efficacy and safety variables were change in DAS28(CRP) between Weeks 8 and 20 and incidence of treatment-emergent adverse events (TEAEs).ResultsOf 159 patients enrolled, 79 had IR at Week 8 and were randomised to CZP plus bimekizumab (n=52) or CZP plus placebo (n=27). At Week 20, there was a greater reduction in DAS28(CRP) in the CZP-IR plus bimekizumab group compared with the CZP-IR plus placebo group (99.4% posterior probability). The most frequent TEAEs were infections and infestations (CZP plus bimekizumab, 50.0% (26/52); CZP plus placebo, 22.2% (6/27)).ConclusionsPoC was confirmed based on the rapid decrease in disease activity achieved with 12 weeks of CZP plus bimekizumab. No unexpected or new safety signals were identified when neutralising IL-17A and IL-17F in patients with RA concomitantly treated with CZP, but the rate of TEAEs was higher with dual inhibition.

Differences in Predictive Factors for Sustained Clinical Remission with Abatacept Between Younger and Elderly Patients with Biologic-naive Rheumatoid Arthritis: Results from the ABROAD Study

2016 ◽  
Vol 43 (11) ◽  
pp. 1974-1983 ◽  
Author(s):  
Masahiro Sekiguchi ◽  
Takao Fujii ◽  
Kiyoshi Matsui ◽  
Kosaku Murakami ◽  
Satoshi Morita ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Elderly Patients ◽  
Disease Activity ◽  
Predictive Factors ◽  
Clinical Remission ◽  
Health Assessment ◽  
The Elderly ◽  
Joint Disease ◽  
Younger Patients ◽  
Reactive Protein

Objective.To differentiate predictive factors for sustained clinical remission between elderly and younger patients with rheumatoid arthritis (RA) receiving abatacept (ABA) as an initial biological disease-modifying antirheumatic drug.Methods.The study involved 277 biologic-naive patients with RA with high or moderate disease activity, who were treated with intravenous ABA and evaluated for 48 weeks in 43 Japanese hospitals and rheumatology clinics (the ABatacept Research Outcomes as a First-line Biological Agent in the Real WorlD study: UMIN000004651). Predictive factors associated with sustained clinical remission defined by the 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) during the 24–48–week or 36–48–week periods were determined in elderly (≥ 65 yrs, n = 148) and younger patient groups (< 65 yrs, n = 129) using logistic regression analysis.Results.Clinical remission was achieved at 24 and 48 weeks in 35.1% and 36.5% of patients in the elderly group and 34.9% and 43.4% in the younger group, respectively. In elderly patients, anticitrullinated protein antibody (ACPA) positivity and a lower DAS28-CRP score were significantly associated with sustained clinical remission; however, a lower Health Assessment Questionnaire-Disability Index (HAQ-DI) score was not related to sustained clinical remission. In younger patients, lower DAS28-CRP and HAQ-DI scores were predictive factors for sustained clinical remission, whereas ACPA positivity was not a useful predictive factor for sustained clinical remission.Conclusion.Although the effectiveness of ABA in biologic-naive patients with RA was equally recognized in elderly and younger patients, the baseline clinical characteristics associated with sustained clinical remission were substantially different.

scholarly journals The Impact of Time Length to Boolean Remission for Tight Disease Activity Control After Acquisition in Rheumatoid Arthritis Patients

2021 ◽  
Author(s):  
Ichiro Yoshii ◽  
Tatsumi Chijiwa ◽  
Naoya Sawada
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Remission Rate ◽  
Health Assessment ◽  
Time Length ◽  
First Remission ◽  
The Impact ◽  
Questionnaire Disability

Abstract Importance of time length to achieving clinical remission on disease activity control, daily activities (ADL) and quality of life (QOL) maintenance after the remission was investigated for patients with rheumatoid arthritis (RA).In patients who achieved remission once or more, relationship between time length from initiation to achieve remission (TL) and patients’ background data at baseline, and relationship between TL and mean simplified disease activity score (SDAI), modified Health Assessment Questionnaire Disability Index (HAQ-DI) score, pain score with visual analog scale (PS-VAS), Sharp/van der Heijde Score (SHS) and quality of life score (QOLS) at the first remission and thereafter were evaluated statistically. Patients were divided into two groups whether TL was within 6 months or longer (G≤6 and G>6). Change of the parameters and Boolean remission rate (BRR) after the first remission between the two groups were compared statistically.In 465 patients, TL correlated significantly with the SDAI score, the HAQ score, PS-VAS, SHS, and the QOLS after the remission. The SDAI score and the BRR after the first remission were significantly better in the G≤6 than in the G>6.TL is an important key to guarantee good disease activity control, ADL and QOL.

scholarly journals Clinical aspects of the use of etanercept in treatment of rheumatoid arthritis.

2018 ◽  
Vol 95 (11) ◽  
pp. 1007-1012
Author(s):  
Pavel A. Shesternya ◽  
M. M. Petrova ◽  
O. D. Gritsenko
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Health Assessment ◽  
Stable Condition ◽  
Treatment Interruption ◽  
Treat To Target ◽  
Clinical Aspects ◽  
Reactive Protein ◽  
Effective Combination ◽  
Number Of Patients

Background. Maintaining of a favourable response of tumour necrosis factor inhibitors is one of the most challenging to rheumatologist. Only limited data have been published addressing this field. The aim of our study was investigate efficacy of etanercept (ETN) and evaluate maintaining response after ETN discontinuation in patients who have achieved remission or low disease activity (REM/LDA) of rheumatoid arthritis (RA). Methods. Patients with high disease activity (n = 29) received ETN 50 mg injection and methotrexate 10-20 mg once weekly were included in analysis. Frequency of REM/LDA scoring by DAS 28-joint counts and C-reactive protein level (DAS28-CRP), changes from baseline in DAS28-CRP, Health Assessment Questionnaire (HAQ), global assessment of disease activity by patient and provider (PtGA and PrGA) were evaluated. We assessed persistent of achieved REM/LDA after the ETN discontinued. Results. We saw fast decreasing of active flare already after first month: HAQ (1.4 ± 0.6 vs 2.0 ± 0.6, p = 0.048), PtGA (49.5 ± 17.9 vs 75.6 ± 14.9, p = 0.016) and PrGA (46.6 ± 14.7 vs 77.0 ± 12.3, p = 0.014). DAS28-CRP changes from baseline become significant after second month (3.9 ± 1.1 vs 6.2 ± 0.6, р = 0.005). After 6 months 82.6% patients had DAS28-CRP < 3.2 and 41.4% patients had HAQ < 0.5. Maintenance of REM/LDA lasted 3 month after ETN discontinuation. Conclusion. ETN+MTX is very effective combination in treat to target strategy of RA treatment. In patients who have achieved REM/LDA maintained stable condition during three months after ETN withdrawn. It might be consider in a number of patients in case of accidental or necessary treatment interruption.

scholarly journals Neuropathic pain in a sample of Egyptian patients with rheumatoid arthritis

2020 ◽  
Vol 47 (1) ◽  
Author(s):  
Abdullah Radwan ◽  
Ahmed Borai
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Neuropathic Pain ◽  
Disease Activity ◽  
Functional Disability ◽  
Disease Duration ◽  
Univariate Analysis ◽  
Health Assessment ◽  
Reactive Protein ◽  
Important Symptom

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by polyarthritis that may cause irreversible joint disability. Pain is the most important symptom in RA patients that requires more attention and careful evaluation. Despite the improvement in medications used to control inflammation in RA patients, a relevant number of them still experience neuropathic pain even with disease remission. This study was conducted to estimate the frequency of neuropathic pain (NP) in RA patients and to assess its relationship with disease activity, functional status, and overweight. Results NP was detected in 12.5% (14 patients) of RA patients. Highly significant differences were found between RA patients with NP and those without NP as regards disease duration, visual analog scale (VAS) of pain, disease activity score 28 (DAS28-ESR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), body mass index (BMI), health assessment questionnaire (HAQ) score, and Douleur Neuropathique in 4 (DN4) questionnaire for NP assessment (p < 0.001). The correlation between the DN4 questionnaire and the parameters of disease activity in RA patients with NP was not significant. By univariate analysis, the possible risk factors for NP in RA patients were disease duration, VAS, DAS28-ESR, HAQ, and BMI; however, by multivariate analysis, no possible risk factors for NP in RA patients were detected. Conclusion Although pain in patients with RA was classified as nociceptive in nature, a relevant proportion of patients might also have NP. NP in RA patients was related to functional disability, high disease activity, and overweight.

scholarly journals Effectiveness and safety of certolizumab pegol in rheumatoid arthritis patients in Canadian practice: 2-year results from the observational FαsT-CAN study

2019 ◽  
Vol 11 ◽  
pp. 1759720X1983115
Author(s):  
Louis Bessette ◽  
Boulos Haraoui ◽  
Andrew Chow ◽  
Isabelle Fortin ◽  
Sanjay Dixit ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Real World ◽  
Certolizumab Pegol ◽  
Health Assessment ◽  
Work Productivity ◽  
Primary Objective ◽  
Joint Disease ◽  
Specific Work ◽  
The Impact

Background: The aim of this study was to assess the real-world effectiveness and safety of certolizumab pegol (CZP) in rheumatoid arthritis (RA) patients, and the impact on patients’ productivity, pain, and fatigue, in Canadian practice. Methods: FαsT-CAN, a 2-year prospective, observational study, evaluated CZP use in Canadian adults with moderate to severe, active RA. The primary objective was to assess the proportion of patients achieving 28-joint Disease Activity Scores (DAS28) <2.6 at Week 104. Secondary and additional endpoints assessed the improvements in Patients’ Assessment of Arthritis Pain (PtAAP), fatigue, Health Assessment Questionnaire-Disability Index (HAQ-DI), and the proportion of patients achieving minimal clinically important differences (MCID) in HAQ-DI. Validated arthritis-specific Work Productivity Surveys (WPS-RA) assessed the RA-associated impact on productivity. Incidence of CZP-related treatment-emergent adverse events (TEAEs) was reported for patients receiving ⩾1 dose of CZP (safety set). Results: The full analysis set (baseline DAS28 ⩾ 2.6, ⩾1 dose of CZP and ⩾1 valid post-baseline DAS28 measurement) included 451 of the 546 patients recruited into the study; a total of 229/451 (50.8%) patients completed Week 104. At Week 104, 90/451 (20.0%) patients achieved DAS28 < 2.6. Rapid improvements in disease activity, pain, and fatigue were observed. At Week 104, 66.2% of patients achieved HAQ-DI MCID. Patients employed at Week 104, reported reduced absenteeism, and improved productivity. CZP-related TEAEs were consistent with the known CZP safety profile. Conclusions: CZP was an effective RA treatment in Canadian practice, and no new CZP-related safety signals were identified. The improvements in household and workplace productivity are the first observations in a real-world Canadian setting.

scholarly journals Influence of disease activity on functional capacity in patients with rheumatoid arthritis

2015 ◽  
Vol 72 (1) ◽  
pp. 21-25 ◽  
Author(s):  
Jelena Jovanovic ◽  
Miodrag Stojanovic ◽  
Vladimir Jovanovic ◽  
Aleksandar Dimic ◽  
Sladjana Bozilov ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Functional Status ◽  
Functional Disability ◽  
Health Assessment ◽  
Group Iii ◽  
Group I ◽  
Group Ii ◽  
The Impact ◽  
Significant Factors

Background/Aim. Progressive erosive changes in cartilage and bone in rheumatoid arthritis (RA) ultimately lead to joint deformities and disability which may be early, severe and permanent. Consequently, there is the reduction of functional ability and changes in the quality of life. The aim of this study was to estimate the impact of disease activity on functional status of patients with RA. Methods. A prospective investigation included 74 patients with RA who were treated in the Rheumatology Clinic of the ?Niska Banja? Institute. Assessment of functional status (capacity) was measured by the Health Assessment Questionnaire (HAQ) with the values from 0 to 3 that patients fill out on their own. The patients were then divided into three groups: the group I with the HAQ values from 0.125 to 1.000, the group II with the values from 1.125 to 2.000 and the group III with the values from 2.125 to 3.000. Disease activity was measured by Disease Activity Score (DAS28). The assessment also included sedimentation rate (SE) influence, IgM rheumatoid factor (RF) and C-reactive protein (CRP) positivity, age, and disease duration. Results. The patients with the most severe functional damage estimated by the HAQ - the group III, had the highest values of DAS28 SE (7.4 ? 0.8) compared to the group II (6.5 ? 1.2) and the group I (3.4 ? 1.2). The group III also showed the highest values of DAS28 CRP (7.1 ? 0.8) compared to the group II (6.7 ? 0.8) and the group I (3.6 ? 0.4). Compared with the patients with small and moderate functional damage, the patients in the group III had positive IgM RF and CRP as well as higher SE values more frequently and the difference was statistically significant. In the univariate logistic model, the tested parameters of DAS28 SE, DAS 28 CRP, SE, RF and CRP represent significant predictors of functional disability. The most significant factors that increase the odds of patient having the most severe functional damage include DAS28 SE which increases the odds by 5.5 times (OR = 5.450, 95% CI = 3.211-7.690, p = 0.001), DAS28 CRP by 5.1 times (OR = 5.111, 95% CI = 2.123-10.636, p < 0.01), and the presence of increased CRP (OR = 5.219, 95% CI = 1.305-18.231, p = 0.019) by 5.2 times. Conclusion. Functional status evaluated by the HAQ is a standard for assessment of RA due to its convenience and good correlation with parameters of disease activity. The most significant factors that increase the odds that the patient has the greatest functional damage are DAS28 SE, DAS28 CRP and the presence of CRP.

scholarly journals Equivalence and switching between biosimilars and reference molecules in rheumatoid arthritis: protocol for a systematic review and meta-analysis

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Bruna O. Ascef ◽  
Matheus O. Almeida ◽  
Ana Cristina de Medeiros Ribeiro ◽  
Danieli C. O. Andrade ◽  
Haliton A. de Oliveira Júnior ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Treatment Success ◽  
Health Assessment ◽  
Efficacy And Safety ◽  
Biologic Drugs ◽  
Link Type ◽  
The Impact

Abstract Background Biologic drugs such as adalimumab, etanercept, and infliximab represent major first-line and second-line treatments for rheumatoid arthritis (RA) patients. However, their high cost poses a massive burden on healthcare systems worldwide. The expiration of patents for these biologics has driven the production of biosimilar drugs, which are potentially less costly and remarkably similar, albeit not identical to the reference molecules. This paper aims to outline the protocol of a systematic review that will investigate the efficacy and safety profile of biosimilars compared to biologics (objective 1) and the impact of switching between biosimilar drugs and reference biologics on the management of RA patients (objective 2). Methods We will investigate the effects of any biosimilars of adalimumab, etanercept, and infliximab on RA patients. We will include randomized controlled trials (RCTs) or quasi-RCTs to assess efficacy and safety outcomes and RCTs with two- or multiple-part designs to evaluate the consequences of switching from reference biologics to biosimilar drugs (and vice-versa). Electronic searches will be performed through MEDLINE (via PubMed), EMBASE, LILACS, and CENTRAL (from inception to April 2021). Two independent reviewers will screen studies, extract data, and evaluate the risk of bias. The latter will be carried out considering specific domains from equivalence trials and switching studies. Random-effects models will be fitted to obtain summary estimates using either relative risk or standardized mean difference as a metric. The primary outcome will be the rate of treatment success according to the American College of Rheumatology 20 (ACR20), and the co-primary outcome will be the Health Assessment Questionnaire—Disability Index (HAQ-DI). Conclusions will be based on equivalence hypothesis testing using predefined margins of equivalence elicited from a group of experienced rheumatologists and prior studies. The overall certainty of the evidence will be assessed based on the GRADE system. Discussion The present investigation proposes a comprehensive, clinician-oriented approach to assess the equivalence and the impact of switching between biosimilars and biologics on the management of patients with RA. Our results will elucidate the efficacy, safety, immunogenicity of biosimilars, and the clinical consequences of substituting biologics with biosimilars in the management of RA. Systematic review registration PROSPERO CRD42019137152 and CRD42019137155

scholarly journals Safety, Tolerability, and Efficacy of Tocilizumab in Rheumatoid Arthritis: An Open-Label Phase 4 Study in Patients from the Middle East

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Mohammed Hammoudeh ◽  
Adel Al Awadhi ◽  
Eman Haji Hasan ◽  
Maassoumeh Akhlaghi ◽  
Arman Ahmadzadeh ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Middle Eastern ◽  
Health Assessment ◽  
Open Label ◽  
Meaningful Improvement ◽  
End Points ◽  
Safety And Efficacy ◽  
Reactive Protein ◽  
Open Label Phase

This open-label study investigated the safety and efficacy of tocilizumab in Middle Eastern patients with rheumatoid arthritis (RA). Patients whose Disease Activity Score based on 28 joints (DAS28) was >3.2 received tocilizumab 8 mg/kg intravenously every 4 weeks for 24 weeks. Patients receiving aTNF ± nonbiologic disease-modifying antirheumatic drug(s) (DMARD(s)) switched to tocilizumab; patients receiving nonbiologic DMARD monotherapy added tocilizumab. Primary end points were adverse events (AEs), serious AEs (SAEs), and laboratory parameters; secondary end points were DAS28, Health Assessment Questionnaire-Disability Index, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Eighty-eight of 95 patients completed 24 weeks. Overall, 125 AEs were reported in 43 (45%) patients; the most common were increased hepatic enzymes (16%) and cholesterol (11%). Eight patients experienced SAEs. Significant changes from baseline to week 24 occurred for hemoglobin, neutrophils, platelets, total cholesterol, and liver enzymes (P<0.05). DAS28, CRP, and ESR decreased significantly from baseline at each visit (P<0.0001). At week 24, the proportions of patients reporting DAS28 clinically meaningful improvement (decrease ≥1.2), low disease activity (DAS28 ≥2.6 to ≤3.2), and remission (DAS28 <2.6) were 92%, 23%, and 64%, respectively. Safety and efficacy of tocilizumab were consistent with values reported in Western patients.

scholarly journals Additional impact on muscle function when treating active rheumatoid arthritis patients with high alphacalcidol doses

2017 ◽  
Vol 74 (11) ◽  
pp. 1036-1042
Author(s):  
Katarina Simic-Pasalic ◽  
Katarina Gosic ◽  
Andjela Gavrilovic ◽  
Jelena Vojinovic
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Muscle Function ◽  
Laboratory Tests ◽  
Active Rheumatoid Arthritis ◽  
Disease Activity Score ◽  
Efficacy And Safety ◽  
Timed Up And Go ◽  
The Impact ◽  
Active Disease

Background/Aim. Hormone D (vitamin D) plays an important role in immunoregulation and musculoskeletal metabolism. The aim of this study was to assess the impact of alfacalcidol (ILD3) or prednisone use on muscle function and disease activity in active rheumatoid arthritis (RA). Methods. The study included 67 RA patients with the active disease, disease activity score (DAS28) > 3.2, on the highest tolerable methotrexate (MTX) dose during last 3 months. Data collected were: DAS 28, muscle function tests [chair rising test (CRT) timed up and go (TUG), 6 minutes walk (6MWT), tandem walk (TW)], efficacy and safety laboratory tests. At enrollment, patients were randomly assigned to three-month supplementation with 1 ?g (group A1) or 2 ?g (group A2) or 3 ?g (group A3) of 1?D3 daily or prednisone (group C) 20 mg daily, for the first month and 10 mg afterward, in addition to MTX. Results. After the treatment, we found highly significantly reduced disease activity in all four treatment arms (DAS28 p < 0.01). 1?D3 2 ?g (A2 group, n = 19) treated patients significantly improved muscle function (TUG, 6MWT), while 1?D3 3 ?g treated (A3, n = 16) improved 6MWT (p < 0.05), and CRT (p < 0.01). Serum 25(OH)D3 significantly decreased in the group C (p < 0.01), in contrast to its changes obtained in alfacalcidol treated ones. Conclusion. 1?D3 2 ?g and 3 ?g daily is as effective as prednisone (mean 13.3 mg daily) in RA activity control and also has the additional favorable impact on muscle function.

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