Abstract:
BACKGROUND:Therapeutic proteins have revolutionized the treatment of many diseases. In the near future, many more therapeutic proteins are likely to become available for an increasingly wide range of indications. OBJECTIVES:This article reviews the incidence, causes, and consequences of formation of antibodies to therapeutic proteins and suggests ways to address issues surrounding immunogenicity. METHODS:Searches of MEDLINE and EMBASE databases were performed, covering the period 1990 to May 2002. Search terms included immunogenicity, antibodies, and the names of specific therapeutic proteins and classes of therapeutic proteins. Bibliographies of retrieved articles were not searched. RESULTS:All exogenous proteins, including therapeutic ones, have the potential to cause antibody formation. The reported incidence of antibody formation with therapeutic proteins varies widely between proteins and between studies (depending on the assay techniques used). The clinical consequences of antibody formation vary with the type of antibody present; for example, neutralizing antibodies are more likely to cause loss of efficacy than nonneutralizing antibodies. The immunogenicity of therapeutic proteins can be influenced by many factors, including the genetic background of the patient, the type of disease, the type of protein (human or nonhuman), the presence of conjugates or fragments, the route of administration, dose frequency, and duration of treatment. Manufacturing, handling, and storage can introduce contaminants, or alter the 3-dimensional structure of the protein via oxidation or aggregate formation. Various means have been suggested by which therapeutic proteins might be modified to reduce their immunogenicity, including PEGylation, site-specific mutagenesis, exon shuffling, and humanization of monoclonal antibodies. In the future, it may even be possible to predict the immunogenicity of new therapeutic proteins more accurately, using specifically designed animal models, including nonhuman primates and transgenic mice. CONCLUSIONS:Scientists and clinicians are becoming increasingly aware of the importance of assessing the immunogenicity of new molecules as they are introduced, and of existing molecules whenever they are modified or their manufacturing process is changed. Immune responses to therapeutic proteins are usually only of clinical significance if they are associated with the development of treatment resistance. Although various means to reduce the immunogenicity of therapeutic proteins have been suggested, monitoring for antibodies during clinical trials and postmarketing surveillance remains an important issue for all therapeutic proteins.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Schellekens Hdoi
10.1016/s0149-2918(02)80075-3subject
Has Abstractpub_date
2002-11-01 00:00:00pages
1720-40; discussion 1719issue
11eissn
0149-2918issn
1879-114Xpii
S0149291802800753journal_volume
24pub_type
杂志文章,评审abstract::Patients with Parkinson's disease experience disabling non-motor symptoms, including autonomic dysfunction, cognitive decline, and sleep disorders. Pharmacologic treatments for these symptoms are often ineffective or have intolerable side effects. Therefore, non-pharmacologic interventions are an attractive alternativ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.11.004
更新日期:2018-01-01 00:00:00
abstract:PURPOSE:Despite the rapid proliferation of hyaluronate (HA) and corticosteroid (CO) injections and clinical guidelines regarding their use in osteoarthritis (OA), information on the characteristics of people receiving these injections is scarce. We describe the use of injections among adults with radiographically confi...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.01.006
更新日期:2017-02-01 00:00:00
abstract:PURPOSE:Few studies have investigated restless legs syndrome (RLS) treatment effects on individual International RLS Study Group Rating Scale (IRLS) items. We assessed the effects of gabapentin enacarbil (GEn) on individual IRLS items and their correlation with sleep disturbances in adults with moderate-to-severe prima...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/j.clinthera.2016.05.008
更新日期:2016-07-01 00:00:00
abstract::This multicenter, randomized, double-blind study compared the efficacy and tolerability of ondansetron 8 mg twice daily for 3 days with placebo in preventing nausea and vomiting in 81 patients receiving cyclophosphamide-doxorubicin-based chemotherapy. The first dose of study drug was administered 30 minutes before the...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/0149-2918(95)80087-5
更新日期:1995-11-01 00:00:00
abstract:BACKGROUND:Imprudent prescribing of antibiotics for patients with colds, upper respiratory tract infections (URIs), and bronchitis may contribute to antibiotic resistance and waste economic resources. OBJECTIVE:The purpose of this study was to determine the antibiotic prescribing rate for adults diagnosed with colds, ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(02)85013-5
更新日期:2002-01-01 00:00:00
abstract:PURPOSE:We estimated the real-world costs of bleeding-related episodes (BREs) in adults with primary immune thrombocytopenia (ITP). METHODS:This retrospective cohort study used the MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases. We identified adult patients...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.01.023
更新日期:2017-03-01 00:00:00
abstract::Quinfamide, a luminal amebicide, is a dichloroacetyl quinolol used to treat chronic and subacute intestinal amebiasis. Several previous dose-ranging studies have indicated that quinfamide is effective in a total dose of 300, 600, or 1,200 mg. The present study was undertaken to determine the efficacy of 100- and 200-m...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract:BACKGROUND:During the past 5 years, there has been much concern about the safety of and ease of access to drugs that are unavailable without a prescription in the United States but are manufactured and can be purchased over the counter (OTC) in Mexico. However, based on a literature search, studies have not been perfor...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2005.05.007
更新日期:2005-05-01 00:00:00
abstract::Possible changes in the kinin-prekallikrein system after infusion of factor VIII concentrate were studied in seven patients with severe hemophilia. The functional and immunological activities of factors XI and XII, prekallikrein, high molecular weight kininogen, and C-1-esterase inhibitor were measured before and at 0...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::Coexisting diseases may have unforeseen yet clinically significant effects on patients' well-being. Both generic and disease-specific measures are frequently used to assess health-related quality of life (QOL). The present study assessed the effects of comorbidity on the results of QOL measures through an analysis of ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/S0149-2918(00)88295-8
更新日期:1999-02-01 00:00:00
abstract:PURPOSE:This study explored the performance of trigger in detecting adverse drug reactions (ADRs), the confounding variables impairing the causal association of the ADRs, and the underreporting rate by hospital health professionals. METHODS:A 6-month cross-sectional study was conducted in a public general hospital. Da...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2016.11.005
更新日期:2017-04-01 00:00:00
abstract:BACKGROUND:During the past decade, there has been some progress in the pharmacotherapy of schizophrenia and schizoaffective disorder. Current evidence supports the use of various second-generation, or atypical, antipsychotic medications, although few of these agents have been associated with long-term efficacy and tole...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2010.01.021
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:PHX1149 is a dipeptidyl peptidase-4 (DPP4) inhibitor that is currently in clinical development for the treatment of type 2 diabetes mellitus. PHX1149 is a small (molecular weight = 241.16 Da), highly water-soluble (>2 g/mL), orally active molecule with a selectivity index of 15- to 319-fold relative to those...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2007.08.005
更新日期:2007-08-01 00:00:00
abstract:PURPOSE:We applied Multi-Criteria Decision Analysis (MCDA) methods in a structured benefit-risk assessment of cladribine and newer approved disease-modifying drugs (DMDs) for patients with relapsing-remitting multiple sclerosis (RRMS). METHODS:Decision conferencing with clinical neurologists as decision makers was use...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2018.12.015
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND:Meclofenoxate hydrochloride is a psychostimulant in the nootropic agent group available in capsule and tablet formulations approved for traumatic cataphora, alcoholic poisoning, anoxia neonatorum, and children's enuresis in China. Although these 2 generic formulations are marketed in China, information regar...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2008.09.013
更新日期:2008-09-01 00:00:00
abstract:BACKGROUND:Many patients with type 2 diabetes mellitus (T2DM) also have hypertension, which is commonly treated with thiazide diuretics, including hydrochlorothiazide (HCTZ). Canagliflozin, a sodium glucose cotransporter 2 inhibitor developed for the treatment of T2DM, lowers plasma glucose by inhibiting renal glucose ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.02.022
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND:Most patients with hypertension in the United States and Europe fail to achieve the recommended target blood pressure (BP) of <140/90 mm Hg. Combination therapy is required in approximately two thirds of all patients whose BP is >20/10 mm Hg above the goal. Combination therapy with agents having complementar...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clinthera.2007.02.003
更新日期:2007-02-01 00:00:00
abstract:PURPOSE:The International Conference on Harmonisation E14 guideline mandates an intensive cardiac safety evaluation in a clinical thorough QT study, typically in healthy subjects, for all new non-antiarrhythmic drugs with systemic bioavailability. This thorough QT study investigated the effects of therapeutic (2 mg) an...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2015.09.006
更新日期:2015-11-01 00:00:00
abstract:BACKGROUND:Few effective treatment methods are available for subacute sclerosing panencephalitis (SSPE),an infection associated with the measles virus. Interferons have shown some benefit in previous studies and clinical practice. OBJECTIVE:The purpose of this study was to compare the efficacy of 2 different regimens ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2004.11.002
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:Mycophenolate mofetil (MMF) is an immunosuppressant indicated for prophylaxis of acute organ transplant rejection. Generic MMF is less costly than the branded product, but European regulatory authorities require bioequivalence studies for the marketing of generics. OBJECTIVES:The aims of the 2 studies repor...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2011.04.003
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:Cefprozil and erythromycin are acceptable alternatives to penicillin in the treatment of pharyngitis/tonsillitis due to group A beta-hemolytic streptococcus (GABHS). OBJECTIVE:The purpose of this trial was to determine the relative efficacy and tolerability of cefprozil and erythromycin in the treatment of ...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0149-2918(00)89084-0
更新日期:2001-11-01 00:00:00
abstract:PURPOSE:We undertook a preliminary assessment of the efficacy of administering intravenous dexamethasone (DEX) for relieving the nausea and dizziness accompanying vestibular neuritis (VN). METHODS:Between November 2013 and October 2014, 26 patients with VN were prospectively enrolled in this study. The patients were r...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2015.09.010
更新日期:2015-11-01 00:00:00
abstract:BACKGROUND:According to evidence-based guidelines, the combination of inhaled corticosteroids and inhaled long-acting beta(2)-agonists in a single inhaler is recommended for patients with chronic obstructive pulmonary disease (COPD) who are experiencing exacerbations. The relative effectiveness of combination products ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2010.06.022
更新日期:2010-07-01 00:00:00
abstract:BACKGROUND:Alendronate, an oral bisphosphonate, is available for the treatment of osteoporosis in a 70-mg once-weekly and a 10-mg once-daily formulation. OBJECTIVES:This study aimed to determine patient preference for once-weekly versus once-daily dosing with alendronate, and to determine which treatment regimen the p...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0149-2918(02)80085-6
更新日期:2002-11-01 00:00:00
abstract:BACKGROUND:Patients' adherence to antiosteoporotic drug therapy is essential to prevent fracture and complications of osteoporosis over the long term. The guidance given in treating osteoporosis can potentially enhance adherence. OBJECTIVE:This study was conducted to compare adherence to osteoporosis regimens by patie...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2013.05.019
更新日期:2013-07-01 00:00:00
abstract:PURPOSE:Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This analysis compared the efficacy and safety of tofacitinib with biologic disease-modifying antirheumatic drugs in patients with RA and a prior inadequate response (IR) to tumor necrosis factor inhibitors (TNFi). ME...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/j.clinthera.2016.11.004
更新日期:2016-12-01 00:00:00
abstract:PURPOSE:Public discourse regarding the hepatitis C virus (HCV) drug Sovaldi® (sofosbuvir) has become inflamed, generating much heat but little light concerning the clinical, health economic, and quality-of-life merits of Sovaldi®. The purpose of this article is to provide a factual basis for evaluating the claims regar...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2015.02.009
更新日期:2015-05-01 00:00:00
abstract:PURPOSE:This study was designed to evaluate the safety and pharmacokinetic profiles of MRX-I tablet, an oxazolidinone antibacterial agent, in healthy Chinese subjects. METHODS:The study was composed of 3 sequential periods. Period 1 was a randomized, double-blind, placebo-controlled, sequential ascending dose (50 to 1...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2017.12.017
更新日期:2018-02-01 00:00:00
abstract:PURPOSE:Geriatric patients are more sensitive to the anesthetic effects of propofol and its adverse effects, such as hypotension, than is the general population; thus, a reduced dose (1-1.5 mg/kg) is recommended for the induction of anesthesia. The extent to which clinicians follow established dosing guidelines has not...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2015.10.005
更新日期:2015-12-01 00:00:00
abstract::This study evaluated the efficacy, safety, and most suitable dose of omeprazole in short-term acute treatment (4 weeks) and maintenance treatment (6 months) of patients older than 60 years of age with endoscopically diagnosed gastric ulcer (GU) or duodenal ulcer (DU). This randomized, prospective study included 156 pa...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1994-11-01 00:00:00