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  • 1
    In: Systematic Reviews, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2021-12)
    Abstract: 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
    Type of Medium: Online Resource
    ISSN: 2046-4053
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2662257-9
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  • 2
    In: Arthritis Care & Research, Wiley, Vol. 74, No. 4 ( 2022-04), p. 562-571
    Abstract: To date, the only study that has assessed the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 mRNA) vaccine in systemic lupus erythematosus (SLE) observed a moderate response, but the sample size precluded an accurate analysis of the effect of individual drugs. Therefore, we evaluated the immunogenicity of an inactivated SARS‐CoV‐2 vaccine (Sinovac‐CoronaVac) and the influence of different medications in SLE. Safety was also assessed. Methods We conducted a prospective controlled study of 232 SARS‐CoV‐2–naive SLE patients and 58 SARS‐CoV‐2–naive controls who were vaccinated with 2 doses of Sinovac‐CoronaVac with a 28‐day interval (day 0/day 28 [D0/D28]). Immunogenicity analysis at D0/D28 and D69 included anti‐SARS‐CoV‐2 S1/S2 IgG seroconversion (SC) and neutralizing antibodies (NAb) positivity. The influence of individual drugs on immune response and safety was assessed. Results Patients and controls were well balanced for age ( P  = 0.771). At D69, SLE patients showed a moderate SC (70.2% versus 98.1%; P   〈  0.001) and moderate frequency of NAb positivity (61.5% versus 84.6%; P  = 0.002), although both frequencies were lower than in controls. Factors associated with lower SC in univariate analysis at D69 were prednisone use (odds ratio [OR] 0.215 [95% confidence interval (95% CI) 0.108–0.427] , P   〈  0.001) and mycophenolate mofetil (MMF) use (OR 0.201 [95% CI 0.107–0.378], P   〈  0.001), whereas hydroxychloroquine (HCQ) use led to a 2.5 increase in SC ( P  = 0.011). SLE patients who were receiving HCQ monotherapy had similar SC to controls at D69 (100% versus 98.1%; P  = 1.000). In multivariate analysis, prednisone and MMF use were independently associated with lower SC ( P   〈  0.001) and NAb positivity ( P   〈  0.001). Safety analysis revealed no moderate/severe adverse events. Conclusion Sinovac‐CoronaVac has a moderate immunogenicity in SARS‐CoV‐2–naive SLE patients with an excellent safety profile. We further demonstrate that HCQ may improve SC, whereas prednisone and MMF had a major deleterious effect in vaccine response, reinforcing the need to investigate the role of temporary MMF withdrawal or a vaccine‐booster dose ( ClinicalTrials.gov identifier: NCT04754698).
    Type of Medium: Online Resource
    ISSN: 2151-464X , 2151-4658
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2016713-1
    detail.hit.zdb_id: 645059-3
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  • 3
    In: Lupus, SAGE Publications, Vol. 31, No. 5 ( 2022-04), p. 565-574
    Abstract: The standard of care for thrombotic antiphospholipid syndrome (APS) is anticoagulation with vitamin K antagonists (VKAs). Prothrombin time, and its corresponding international normalized ratio (INR), is the laboratory test routinely performed to assess anticoagulation. Self-management of VKA therapy using point-of-care (POC) devices seems to be an attractive option. Purpose/objective To evaluate the accuracy of a POC device (CoaguChek XS) in APS patients by comparing it with venous laboratory INR. Furthermore, we analyzed whether other clinical and laboratory features could interfere with the CoaguChek XS results. Patients and methods This is a single-center cross-sectional study with 94 APS patients from a tertiary rheumatology clinic performed from August 2014 to March 2015. The comparison between CoaguChek XS and venous laboratory INR results was evaluated using the coefficient of determination (r) followed by the Bland–Altman test. A paired t-test was also applied. A difference of up to ±0.5 INR unit between the two systems was considered clinically acceptable. Results The mean CoaguChek-INR was 2.94 ± 1.41 and venous laboratory INR was 2.43±0.86, with a correlation coefficient (r) of 0.95. Categorizing INR values in ranges (INR 〈 2, INR 2–3, INR 3–4, and INR 〉 4), we found that the INR 〉 4 group presented a lower correlation (r = 0.64) compared to the other ranges ( p 〈 0.05). Although both methods were highly correlated, CoaguChek XS showed higher values than the venous laboratory INR, with an increased average of 0.42 ± 0.54. Therefore, we proposed a simple linear regression model to predict the venous laboratory INR values, using results obtained from CoaguChek XS. A difference ≤0.5 INR unit between the two systems was observed in 57.4% of patients, and the aPL profile did not influence the results. Conclusion Although CoaguChek XS and venous laboratory INR demonstrated a good linear correlation in the group of INR ≤4, extra caution should be taken in APS patients, since a reasonable proportion of patients can present differences in INR results that are not acceptable. We do not recommend routine POC in APS patients.
    Type of Medium: Online Resource
    ISSN: 0961-2033 , 1477-0962
    RVK:
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2008035-9
    detail.hit.zdb_id: 1154407-7
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  • 4
    In: The Lancet, Elsevier BV, Vol. 397, No. 10277 ( 2021-03), p. 881-891
    Type of Medium: Online Resource
    ISSN: 0140-6736
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 3306-6
    SSG: 5,21
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  • 5
    In: Advances in Rheumatology, Springer Science and Business Media LLC, Vol. 62, No. 1 ( 2022-11-22)
    Abstract: To evaluate the disease activity before and after COVID-19 and risk factors associated with outcomes, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV) and death in patients with spondylarthritis (SpA). Methods ReumaCoV Brazil is a multicenter prospective cohort of immune-mediated rheumatic diseases (IMRD) patients with COVID-19 (case group), compared to a control group of IMRD patients without COVID-19. SpA patients enrolled were grouped as axial SpA (axSpA), psoriatic arthritis (PsA) and enteropathic arthritis, according to usual classification criteria. Results 353 SpA patients were included, of whom 229 (64.9%) were axSpA, 118 (33.4%) PsA and 6 enteropathic arthritis (1.7%). No significant difference was observed in disease activity before the study inclusion comparing cases and controls, as well no worsening of disease activity after COVID-19. The risk factors associated with hospitalization were age over 60 years (OR = 3.71; 95% CI 1.62–8.47, p  = 0.001); one or more comorbidities (OR = 2.28; 95% CI 1.02–5.08, p  = 0.001) and leflunomide treatment (OR = 4.46; 95% CI 1.33–24.9, p  = 0.008). Not having comorbidities (OR = 0.11; 95% CI 0.02–0.50, p  = 0.001) played a protective role for hospitalization. In multivariate analysis, leflunomide treatment (OR = 8.69; CI = 95% 1.41–53.64; p  = 0.023) was associated with hospitalization; teleconsultation (OR = 0.14; CI = 95% 0.03–0.71; p  = 0.01) and no comorbidities (OR = 0.14; CI = 95% 0.02–0.76; p  = 0.02) remained at final model as protective factor. Conclusions Our results showed no association between pre-COVID disease activity or that SARS-CoV-2 infection could trigger disease activity in patients with SpA. Teleconsultation and no comorbidities were associated with a lower hospitalization risk. Leflunomide remained significantly associated with higher risk of hospitalization after multiple adjustments.
    Type of Medium: Online Resource
    ISSN: 2523-3106
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2939120-9
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