scholarly journals SARS-CoV-2 mass vaccination: Urgent questions on vaccine safety that demand answers from international health agencies, regulatory authorities, governments and vaccine developers                  

2021 ◽  
Author(s):  
Roxana Bruno ◽  
Peter A Mccullough ◽  
Teresa Forcades I Vila ◽  
Alexandra Henrion-Caude ◽  
Teresa García-Gasca ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Risk Mitigation ◽  
Safety Data ◽  
Vaccine Safety ◽  
Endothelial Damage ◽  
Mass Vaccination ◽  
High Rate ◽  
Public Confidence ◽  
World Population

Since the start of the COVID-19 outbreak, the race for testing new platforms designed to confer immunity against SARS-CoV-2, has been rampant and unprecedented, leading to conditional emergency authorization of various vaccines. Despite progress on early multidrug therapy for COVID-19 patients, the current mandate is to immunize the world population as quickly as possible. The lack of thorough testing in animals prior to clinical trials, and authorization based on safety data generated during trials that lasted less than 3.5 months, raise questions regarding vaccine safety. The recently identified role of SARS-CoV-2 Spike glycoprotein for inducing endothelial damage characteristic of COVID-19, even in absence of infection, is extremely relevant given that most of the authorized vaccines induce endogenous production of Spike. Given the high rate of occurrence of adverse effects that have been reported to date, as well as the potential for vaccine-driven disease enhancement, Th2-immunopathology, autoimmunity, and immune evasion, there is a need for a better understanding of the benefits and risks of mass vaccination, particularly in groups excluded from clinical trials. Despite calls for caution, the risks of SARS-CoV-2 vaccination have been minimized or ignored by health organizations and government authorities. As for any investigational biomedical program, data safety monitoring boards (DSMB) and event adjudication committees (EAC), should be enacting risk mitigation. If DSMBs and EACs do not do so, we will call for a pause in mass vaccination. If DSMBs and EACs do not exist, then vaccination should be halted immediately, in particular for demographic groups at highest risk of vaccine-associated death or serious adverse effects, during such time as it takes to assemble these boards and commence critical and independent assessments. We urge for pluralistic dialogue in the context of health policies, emphasizing critical questions that require urgent answers, particularly if we wish to avoid a global erosion of public confidence in science and public health.

scholarly journals SARS-CoV-2 mass vaccination: Urgent questions on vaccine safety that demand answers from international health agencies, regulatory authorities, governments and vaccine developers

2021 ◽  
Author(s):  
Karina Acevedo-Whitehouse ◽  
Roxana Bruno ◽  
Peter A Mccullough ◽  
Teresa Forcades I Vila ◽  
Alexandra Henrion-Caude ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Risk Mitigation ◽  
Safety Data ◽  
Vaccine Safety ◽  
Endothelial Damage ◽  
Mass Vaccination ◽  
High Rate ◽  
Public Confidence ◽  
World Population

Since the start of the COVID-19 outbreak, the race for testing new platforms designed to confer immunity against SARS-CoV-2, has been rampant and unprecedented, leading to conditional emergency authorization of various vaccines. Despite progress on early multidrug therapy for COVID-19 patients, the current mandate is to immunize the world population as quickly as possible. The lack of thorough testing in animals prior to clinical trials, and authorization based on safety data generated during trials that lasted less than 3.5 months, raise questions regarding vaccine safety. The recently identified role of SARS-CoV-2 Spike glycoprotein for inducing endothelial damage characteristic of COVID-19, even in absence of infection, is extremely relevant given that most of the authorized vaccines induce endogenous production of Spike. Given the high rate of occurrence of adverse effects that have been reported to date, as well as the potential for vaccine-driven disease enhancement, Th2-immunopathology, autoimmunity, and immune evasion, there is a need for a better understanding of the benefits and risks of mass vaccination, particularly in groups excluded from clinical trials. Despite calls for caution, the risks of SARS-CoV-2 vaccination have been minimized or ignored by health organizations and government authorities. As for any investigational biomedical program, data safety monitoring boards (DSMB) and event adjudication committees (EAC), should be enacting risk mitigation. If DSMBs and EACs do not do so, we will call for a pause in mass vaccination. If DSMBs and EACs do not exist, then vaccination should be halted immediately, in particular for demographic groups at highest risk of vaccine-associated death or serious adverse effects, during such time as it takes to assemble these boards and commence critical and independent assessments. We urge for pluralistic dialogue in the context of health policies, emphasizing critical questions that require urgent answers, particularly if we wish to avoid a global erosion of public confidence in science and public health.

COVID-19 vaccine hesitancy among individuals with cancer, autoimmune diseases, and other serious comorbid conditions: A cross-sectional internet-based survey (Preprint)

2021 ◽  
Author(s):  
Richard Tsai ◽  
John Hervey ◽  
Kathleen Hoffman ◽  
Jessica Wood ◽  
John Novack ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Native American ◽  
Autoimmune Diseases ◽  
Media Coverage ◽  
Safety Data ◽  
Vaccine Safety ◽  
Vaccine Hesitancy ◽  
Comorbid Conditions ◽  
Cross Sectional ◽  
Chronic Lung Diseases

BACKGROUND Individuals with comorbid conditions have been disproportionately affected by COVID-19. Since regulatory clinical trials with COVID-19 vaccines excluded those with immunocompromising conditions, few patients with cancer and autoimmune diseases were enrolled. With limited vaccine safety data available, vulnerable populations may have conflicted vaccine attitudes. OBJECTIVE To assess the incidence and reasons for COVID-19 vaccine hesitancy and to assess early vaccine safety. METHODS We conducted a cross-sectional internet-based survey, fielded January 15, 2021 through February 22, 2021, with international participation (74% USA). A random sample of members of Inspire, an online health community of over 2.2 million individuals with comorbid conditions, completed a 55-item online survey. RESULTS 21,943 individuals completed the survey (100% with comorbidities including 27% cancer, 23% autoimmune diseases, 38% chronic lung diseases). 10% declared they would not, 4% stated they probably would not, and 5% were not sure they would agree to vaccination (hesitancy rate 19%). Factors associated with hesitancy included younger age, female gender, black-Pacific-Island-Native American heritage, less formal education, conservative political tendencies, resistance to masks or routine influenza vaccinations, and distrust of media coverage. 5501 (25%) had received at least one COVID-19 vaccine injection, including 29% of US participants. Following the first injection, 69% self-reported local and 40% systemic reactions, which increased following the second injection to 76% and 67%, respectively, with patterns mimicking clinical trials. CONCLUSIONS Nearly one in five individuals with serious comorbid conditions harbor COVID-19 hesitancy. Early safety experiences among those who have been vaccinated should be reassuring.

scholarly journals COVID-19 vaccine hesitancy among individuals with cancer, autoimmune diseases, and other serious comorbid conditions

2021 ◽  
Author(s):  
Richard Tsai ◽  
John Hervey ◽  
Kathleen D Hoffman ◽  
Jessica Wood ◽  
John Novack ◽  
...  
Keyword(s):  
Clinical Trials ◽  
General Population ◽  
Autoimmune Diseases ◽  
Online Survey ◽  
Safety Data ◽  
Vaccine Safety ◽  
Vaccine Hesitancy ◽  
List Type ◽  
Comorbid Conditions ◽  
Chronic Lung Diseases

AbstractBackgroundIndividuals with comorbid conditions have been disproportionately affected by COVID-19. Since regulatory clinical trials with COVID-19 vaccines excluded those with immunocompromising conditions, few patients with cancer and autoimmune diseases were enrolled. With limited vaccine safety data available, vulnerable populations may have conflicted vaccine attitudes.MethodsTo assess the incidence and reasons for COVID-19 vaccine hesitancy and to assess early vaccine safety, we conducted a cross-sectional online survey, fielded January 15, 2021 through February 22, 2021, with international participation (74% USA). A random sample of members of Inspire, an⍰online health⍰community⍰of over 2.2⍰million individuals⍰with comorbid conditions, completed a 55-item online survey.Results21,943 individuals completed the survey (100% with comorbidities including 27% cancer, 23% autoimmune diseases, 38% chronic lung diseases). 10% declared they would not, 4% stated they probably would not, and 5% were not sure they would agree to vaccination (hesitancy rate 19%). Factors associated with hesitancy included younger age, female gender, black-Pacific-Island-Native American heritage, less formal education, conservative political tendencies, resistance to masks or routine influenza vaccinations, and distrust of media coverage. 5501 (25%) had received at least one COVID-19 vaccine injection, including 29% of US participants. Following the first injection, 69% self-reported local and 40% systemic reactions, which increased following the second injection to 76% and 67%, respectively, with patterns mimicking clinical trials.ConclusionNearly one in five individuals with serious comorbid conditions harbor COVID-19 hesitancy. Early safety experiences among those who have been vaccinated should be reassuring.HighlightsIndividuals with serious comorbid conditions, including cancer, have been disproportionately affected by COVID-19 and therefore have been prioritized for vaccinationAn online survey of nearly 22,000 individuals with comorbid conditions revealed that nearly one in 5 expressed vaccine hesitancy.Reasons for hesitancy in this comorbid population mimicked surveys of the general population.Self-reported safety profiles among individuals with comorbid conditions were acceptable, and generally milder than reports in clinical trials among the general population.

Review of in Vitro Activity, Pharmacokinetic Characteristics, Safety, and Clinical Efficacy of Cefprozil, a New Oral Cephalosporin

1993 ◽  
Vol 27 (9) ◽  
pp. 1082-1089 ◽  
Author(s):  
Steven L. Barriere
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Clinical Efficacy ◽  
Broad Spectrum ◽  
Safety Data ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Oral Cephalosporin ◽  
Gram Negative

OBJECTIVE: To review the pharmacokinetics, microbiology, clinical efficacy, safety, and tolerance of cefprozil, a new, broad-spectrum oral cephalosporin. DATA SOURCES: Published clinical trials and microbiologic, pharmacokinetic, and safety data were identified by MEDLINE; additional references were derived from bibliographies of these articles; microbiologic data on file were provided by Bristol-Myers Squibb. STUDY SELECTION: Only published comparative clinical trial reports are included in the review of clinical efficacy. Noncomparative clinical data pertaining to uses of cefprozil not approved by the Food and Drug Administration are not included. DATA SYNTHESIS: Data are presented on the in vitro microbiologic activity of cefprozil against 10 152 bacterial isolates, including most of the clinically important streptococci (e.g., Streptococcus pyogenes, Streptococcus pneumoniae), beta-lactamase-positive and -negative Staphylococcus aureus and Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Proteus mirabilis, Clostridium difficile, and numerous other gram-negative aerobes and anaerobes. In clinical trials, cefprozil appears to be at least as effective as commonly used comparison agents such as cefaclor, cefixime, and amoxicillin/clavulanic acid. Additionally, cefprozil is better tolerated than the latter two agents, especially with regard to gastrointestinal adverse effects. CONCLUSIONS: Cefprozil is a broad-spectrum cephalosporin that provides coverage against both gram-negative and -positive bacteria that may cause otitis media, pharyngitis/tonsillitis, skin and skin-structure infections, secondary bacterial infection of acute bronchitis, and acute bacterial exacerbations of chronic bronchitis. The beta-lactamase stability of cefprozil appears to exceed that of other oral cephalosporins for some important pathogens. Cefprozil is used primarily for second-line treatment as less-expensive, first-line generic alternatives generally are available. Cefprozil demonstrates clinical advantages over many other orally administered beta-lactam antibiotics in terms of antimicrobial spectrum, a once- or twice-daily dosing regimen, and/or reduced incidence of adverse effects.

COVID-19 and antiphospholipid antibodies: A position statement and management guidance from AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION)

Lupus ◽  
2021 ◽  
pp. 096120332110625
Author(s):  
Xin Wang ◽  
Elena Gkrouzman ◽  
Danieli Castro Oliveira Andrade ◽  
Laura Andreoli ◽  
Medha Barbhaiya ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Neutrophil Extracellular Traps ◽  
Position Statement ◽  
Endothelial Damage ◽  
High Rate ◽  
Research Network ◽  
Extracellular Traps ◽  
Management Guidance

Coronavirus disease 2019 (COVID-19) is associated with a high rate of thrombosis. Prolonged activated partial thromboplastin times (aPTT) and antiphospholipid antibodies (aPL) are reported in COVID-19 patients. The majority of publications have not reported whether patients develop clinically relevant persistent aPL, and the clinical significance of new aPL-positivity in COVID-19 is currently unknown. However, the reports of aPL-positivity in COVID-19 raised the question whether common mechanisms exist in the pathogenesis of COVID-19 and antiphospholipid syndrome (APS). In both conditions, thrombotic microangiopathy resulting in microvascular injury and thrombosis is hypothesized to occur through multiple pathways, including endothelial damage, complement activation, and release of neutrophil extracellular traps (NETosis). APS-ACTION, an international APS research network, created a COVID-19 working group that reviewed common mechanisms, positive aPL tests in COVID-19 patients, and implications of COVID-19 infection for patients with known aPL positivity or APS, with the goals of proposing guidance for clinical management and monitoring of aPL-positive COVID-19 patients. This guidance also serves as a call and focus for clinical and basic scientific research.

EFFICACY OF MODIFIED BISMUTH QUADRUPLE THERAPY (RBMA) AS FIRST-LINE THERAPY FOR ERADICATION OF HELICOBACTER PYLORI IN PATIENTS WITH CHRONIC GASTRITIS

2019 ◽  
pp. 28-32
Author(s):  
Van Huy Tran
Keyword(s):  
Helicobacter Pylori ◽  
Adverse Effects ◽  
Chronic Gastritis ◽  
Eradication Rate ◽  
High Rate ◽  
First Line ◽  
Helicobacter Pylori Eradication ◽  
Quadruple Therapy ◽  
First Line Therapy ◽  
Line Therapy

Background and aims: Efficacy with substitution of tetracycline with amoxicillin, an antibiotics having a very low resistance rate and a high tolerability, in bismuth quadruple therapy (BQT) have not been studied in Vietnam. Our study aimed to evaluate the efficacy and tolerability of modified BQT vs. standard BQT for first-line Helicobacter pylori eradication. Patients and methods: This is a randomized, prospective study. 120 patients with H.pylori positive-chronic gastritis were randomly divided into two groups. The RBMA group containing rabeprazole 20 mg, bismuth subsalicylic 524mg, metronidazole 500mg, amoxicillin 1000mg, all 2 times a day, for 14 days. The RBMT group received rabeprazole, bismuth subsalicylic, metronidazole and tetracycline. Evaluation for compliance and drug-related side effects were evaluated at the end of two weeks. 4-6 weeks after the end of treatment, the H.pylori eradication rate was determined by the C13urease breath test. Results: Eradication rate was not statistically significative different between the RBMA and the RBMT: 91.2%; 95% confidence interval, 78.2% - 96.7%) vs. 90%; 95% CI, 81.6% - 96.3%) by per-protocol analysis (p = 0.42) and 86.7% (95%CI, 75.84% - 93.09%) vs. 75% (95%CI, 62.1% - 85.3%) by intention-to-treat analysis (ITT, p = 0.06). Adverse effects were significant higher in the RBMT group than in the RBMA group (48.3% vs. 26.7%; p = 0.071) and rate of good compliance was significantly higher in RBMA group than in RBMT group (p < 0.05). Conclusion: The modified BQT including rabeprazole, bismuth, metronidazole and amoxicillin achieved a fairly high rate of H.pylori infection eradication with a higher compliance and lower rate of adverse effects compared to the BQT in patients with chronic gastritis. Further studies need to conduct to confirm this new regimens as a first-line therapy in our country. Key words: Modified bismuth quadruple therapy, BQT, Helicobacter pylori eradication

Potential of Mirabegron and its Extended-release Formulations for the Treatment of Overactive Bladder Syndrome

2020 ◽  
Vol 21 (2) ◽  
pp. 79-88 ◽  
Author(s):  
Pankaj Mandpe ◽  
Bala Prabhakar ◽  
Pravin Shende
Keyword(s):  
Clinical Trials ◽  
Overactive Bladder ◽  
Adverse Effects ◽  
Symptomatic Relief ◽  
Phase Iii ◽  
Overactive Bladder Syndrome ◽  
Modified Release ◽  
Blurred Vision ◽  
Antimuscarinic Drugs ◽  
Tablet Dosage

Background: Overactive bladder syndrome is a broadly occurring urological disorder with a distressing impact on the quality of life. The commonly used antimuscarinic drugs show poor patient compliance because of unsatisfactory potency, tolerability and high occurrence of adverse effects such as dry mouth, blurred vision, constipation, dizziness etc. Mirabegron is the first approved β3-adrenoreceptor agonist, used as mono or in combination therapies for overactive bladder syndrome. Objective: The present review provides an insight into the mechanism, pharmacokinetics, toxicokinetics, clinical trials and the development of various conventional and modified-release dosage forms of mirabegron for the treatment of overactive bladder syndrome. Results: The clinical trials of phase II and phase III of mirabegron demonstrated symptomatic relief from the overactive bladder without disturbing the micturition cycle. To date, mirabegron showed promising results for safety, tolerability and efficacy in patients with overactive bladder syndrome. The modified-release tablet dosage form of mirabegron appear to be a proficient and suitable replacement for antimuscarinics and revealed the tremendous potential to overcome the adverse effects of conventional antimuscarinic drugs like Oxybutyline chloride ER, Detrol LA, VESIcare, etc. Conclusion: Mirabegron shows a distinct mode of action, i.e., targeting β3-adrenoreceptors and improving bladder storage without altering void contractions. The limited side effects, high safety, efficacy and tolerability of mirabegron present an adequate substitute to antimuscarinics. However, long-term analysis and clinical studies are prerequisites for assessing the safety, tolerability and efficacy profile of mirabegron.

Prebiotics and Probiotics in Inflammatory Bowel Disease: Where are we now and where are we going?

2020 ◽  
Vol 15 (3) ◽  
pp. 216-233 ◽  
Author(s):  
Maliha Naseer ◽  
Shiva Poola ◽  
Syed Ali ◽  
Sami Samiullah ◽  
Veysel Tahan
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Effects ◽  
Bowel Disease ◽  
Relapse Prevention ◽  
Remission Induction ◽  
Inflammatory Bowel

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn’s disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms “prebiotics AND ulcerative colitis”, “probiotics AND ulcerative colitis”, “prebiotics AND Crohn's disease”, “probiotics AND Crohn's disease”, “probiotics AND acute pouchitis”, “probiotics AND chronic pouchitis” and “prebiotics AND pouchitis”. Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.

scholarly journals Tuberculosis and viral hepatitis in patients treated with certolizumab pegol in Asia-Pacific countries and worldwide: real-world and clinical trial data

2020 ◽  
Author(s):  
Chak Sing Lau ◽  
Yi-Hsing Chen ◽  
Keith Lim ◽  
Marc de Longueville ◽  
Catherine Arendt ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Viral Hepatitis ◽  
Central Europe ◽  
Real World ◽  
Certolizumab Pegol ◽  
Safety Data ◽  
Asia Pacific ◽  
Hbv Reactivation ◽  
Post Marketing

Abstract Introduction/objectives To evaluate the incidence rate (IR) of tuberculosis (TB) and viral hepatitis B and C (HBV/HCV) during certolizumab pegol (CZP) treatment, worldwide and in Asia-Pacific countries, across clinical trials and post-marketing reports (non-interventional studies and real-world practice). Method CZP safety data were pooled across 49 clinical trials from 1998 to June 2017. Post-marketing reports were from initial commercialization until March 2015 (TB)/February 2017 (HBV/HCV). All suspected TB and HBV/HCV cases underwent centralized retrospective review by external experts. Incidence rates (IRs) were calculated per 100 patient-years (PY) of CZP exposure. Results Among 11,317 clinical trial patients (21,695 PY), 62 TB cases were confirmed (IR 0.29/100 PY) including 2 in Japan (0.10/100 PY) and 3 in other Asia-Pacific countries (0.58/100 PY). From > 238,000 PY estimated post-marketing CZP exposure, there were 31 confirmed TB cases (0.01/100 PY): 5 in Japan (0.05/100 PY), 1 in other Asia-Pacific countries (0.03/100 PY). Reported regional TB IRs were highest in eastern Europe (0.17/100 PY), central Europe (0.09/100 PY), and Mexico (0.16/100 PY). Across clinical trials, there was 1 confirmed HBV reactivation and no HCV cases. From > 420,000 PY estimated post-marketing CZP exposure, 5 HBV/HCV cases were confirmed (0.001/100 PY): 2 HCV reactivations; 1 new HCV; plus 2 HBV reactivations in Japan (0.008/100 PY). Conclusions CZP TB risk is aligned with nationwide TB rates, being slightly higher in Asia-Pacific countries excluding Japan. Overall, TB and HBV/HCV risk with CZP treatment is currently relatively low, as risk can be minimized with patient/physician education, screening, and vigilant treatment, according to international guidelines. Key Points:• TB rates were highest in eastern/central Europe, Mexico, and Asia-Pacific regions.• With the implementation of stricter TB screening and risk evaluations in 2007, especially in high TB incidence countries, there was a notable reduction TB occurrence.• Safety profile of biologics in real-world settings complements controlled studies.• TB and hepatitis (HBV/HCV) risk with certolizumab pegol (CZP) treatment is low.

The Use of Methotrexate in Rheumatoid Arthritis

1985 ◽  
Vol 19 (5) ◽  
pp. 349-358 ◽  
Author(s):  
Peter W. Letendre ◽  
Douglas J. DeJong ◽  
Donald R. Miller
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Folic Acid ◽  
Side Effects ◽  
Adverse Effects ◽  
Systemic Administration ◽  
Refractory Disease ◽  
Controlled Clinical Trials ◽  
Folic Acid Antagonist ◽  
Acid Antagonist

The use of methotrexate in rheumatoid arthritis is reviewed. Methotrexate, a folic acid antagonist, is sometimes employed in an attempt to symptomatically control patients whose disease does not respond adequately to conventional therapies. Systemic administration of 7.5–15 mg/wk in a “pulse” fashion appears to be effective without precipitating severe adverse effects. However, concern over potentially serious side effects and a lack of well-controlled clinical trials have limited its use to severe, refractory disease. Further studies are needed before its role in rheumatoid arthritis can justifiably be expanded.

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