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Indian Journal of Dermatology Sep 2014The advent of biologics in dermatologic treatment armentarium has added refreshing dimensions, for it is a major breakthrough. Several agents are now available for use.... (Review)
Review
The advent of biologics in dermatologic treatment armentarium has added refreshing dimensions, for it is a major breakthrough. Several agents are now available for use. It is therefore imperative to succinctly comprehend their pharmacokinetics for their apt use. A concerted endeavor has been made to delve on this subject. The major groups of biologics have been covered and include: Drugs acting against TNF-α, Alefacept, Ustekinumab, Rituximab, IVIG and Omalizumab. The relevant pharmacokinetic characteristics have been detailed. Their respective label (approved) and off-label (unapproved) indications have been defined, highlighting their dosage protocol, availability and mode of administration. The evidence level of each indication has also been discussed to apprise the clinician of their current and prospective uses. Individual anti-TNF drugs are not identical in their actions and often one is superior to the other in a particular disease. Hence, the section on anti-TNF agents mentions the literature on each drug separately, and not as a group. The limitations for their use have also been clearly brought out.
PubMed: 25284845
DOI: 10.4103/0019-5154.139859 -
Inflammopharmacology Jun 2023Psoriasis represents an immune-mediated disease with an unclear cause that's marked by inflammation triggered by dysfunction in the immune system, which results in... (Review)
Review
Psoriasis represents an immune-mediated disease with an unclear cause that's marked by inflammation triggered by dysfunction in the immune system, which results in inflammation in various parts of the skin. There could be obvious symptoms, such as elevated plaques; these plaques may appear differently depending on the type of skin. This disease can cause inflammation in the elbows, lower back, scalp, knees, or other regions of the body. It can begin at any age, although it most commonly affects individuals between the ages of 50 and 60. Specific cells (such as T cells) have been observed to play an obvious role in the pathogenesis of psoriasis, in addition to specific immunological molecules such as TNF-, IL-12, IL-23, IL-17, and other molecules that can aid in the pathogenesis of psoriasis. So, during the past two decades, biologists have created chemical drugs that target these cells or molecules and therefore prevent the disease from occurring. Alefacept, efalizumab, Adalimumab, Ustekinumab, and Secukinumab are a few examples of chemical drugs. It was discovered that these chemical drugs have long-term side effects that can cause defects in the patient's body, such as the development of the rare but life-threatening disorder progressive multifocal leukoencephalopathy (PCL). Its rapidly progressive infection of the central nervous system caused by the JC virus and other drugs may cause increased production of neutralising anti-drug antibodies (ADA) and the risk of infusion reactions like pruritus, flushing, hypertension, headache, and rash. So, our context intends to talk in our review about natural products or plants that may have therapeutic characteristics for this disease and may have few or no side effects on the patient's body.
Topics: Humans; Middle Aged; Antibodies, Monoclonal; Psoriasis; Adalimumab; Interleukin-12; Inflammation
PubMed: 36995575
DOI: 10.1007/s10787-023-01178-0 -
International Journal of Molecular... Nov 2017Biological therapy became available for psoriasis with the introduction of alefacept at the beginning of this century. Up to then, systemic treatment options comprised... (Review)
Review
Biological therapy became available for psoriasis with the introduction of alefacept at the beginning of this century. Up to then, systemic treatment options comprised small molecule drugs, targeting the immune system in a non-specific manner. The first biologics targeted T-cell activation and migration and served as an alternative to small molecules. However, significant improvement in outcome was first accomplished with the introduction of tumor necrosis factor-α inhibitors that were already approved for other inflammatory disorders, including rheumatic diseases. Along with the progress in understanding psoriasis pathogenesis, highly targeted and effective therapies have since developed with the perspective not only to improve but to clear psoriasis. These accomplishments enable future achievement of advanced goals to individualize treatment best suited for each patient. Mechanistic studies with patients treated with the new highly targeted biologics may guide us towards these goals. This review offers an overview of biologics developed for psoriasis and illustrate a historical progress in the treatment of this common chronic inflammatory skin condition.
Topics: Animals; Biological Products; Biological Therapy; Biosimilar Pharmaceuticals; Humans; Psoriasis
PubMed: 29104241
DOI: 10.3390/ijms18112297 -
Dermatologic Therapy 2009The treatment of psoriasis has undergone a revolution with the advent of biologic therapies, including infliximab, etanercept, adalimumab, efalizumab, and alefacept.... (Review)
Review
The treatment of psoriasis has undergone a revolution with the advent of biologic therapies, including infliximab, etanercept, adalimumab, efalizumab, and alefacept. Biologics are generally safe and well tolerated. However, there has been concern over the risk of lymphoma with use of these agents because of their immunosuppressive properties. This review summarizes the current evidence in regards to lymphoma risk with biologic therapy obtained from case reports and case series, observational studies, clinical trials, and meta-analyses. The majority of data for T-cell inhibitors comes from case reports and relatively small, short-term clinical trials. In addition to published case reports and case series, TNF-alpha inhibitors have also been studied extensively in large cohort studies and meta-analyses of clinical trials derived primarily from the rheumatoid arthritis population. Current data are neither sufficient to completely rule out an increased risk of lymphoma associated with biologics, nor to firmly establish a causal relationship between biologics and lymphoma. Short- to intermediate-term treatment with biologics (e.g., up to 4 years) appears to be very safe with respect to lymphoma risk, especially with TNF-alpha inhibitors in which their potential risks appear to be well defined. Continued vigilance is warranted; however, in the appropriate patient, the risk-to-benefit profile of psoriasis treatment with respect to lymphoma risk appears highly favorable.
Topics: Biological Products; Biological Therapy; Dermatologic Agents; Humans; Lymphoma; Psoriasis; Risk; T-Lymphocytes; Tumor Necrosis Factor-alpha
PubMed: 19845719
DOI: 10.1111/j.1529-8019.2009.01258.x -
Clinical Immunology (Orlando, Fla.) May 2007The pathogenesis of various inflammatory cutaneous diseases such as psoriasis, atopic dermatitis and mycosis fungoides relies greatly on the abnormal function of T... (Review)
Review
The pathogenesis of various inflammatory cutaneous diseases such as psoriasis, atopic dermatitis and mycosis fungoides relies greatly on the abnormal function of T cells. Fundamental knowledge of the role of T cells in the cutaneous immune response has led to the development and production of biologic molecules designed to block T cell function at various steps, specifically activation (i.e. alefacept, efalizumab), trafficking into inflamed skin (i.e. efalizumab) and effector function under cytokine control (i.e. etanercept, infliximab, adalimumab, and anti-IL-12 antibody). We review the immune abnormalities and the role of T cells in psoriasis, and the recent biologic therapies, which share the common mission to hinder T cell activity in inflammatory diseases. An advantage from the preciseness of these biologic therapies is the potential limit of non-specific and potentially devastating organ toxicity, which commonly plagues other systemic therapies.
Topics: Alefacept; Antibodies, Monoclonal; Cell Movement; Dermatologic Agents; Etanercept; Humans; Immunoglobulin G; Immunotherapy; Lymphocyte Activation; Psoriasis; Receptors, Tumor Necrosis Factor; Recombinant Fusion Proteins; T-Lymphocytes
PubMed: 17317321
DOI: 10.1016/j.clim.2007.01.006 -
The Journal of Clinical Investigation Aug 2015Type 1 diabetes (T1D) results from destruction of pancreatic β cells by autoreactive effector T cells. We hypothesized that the immunomodulatory drug alefacept would... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Type 1 diabetes (T1D) results from destruction of pancreatic β cells by autoreactive effector T cells. We hypothesized that the immunomodulatory drug alefacept would result in targeted quantitative and qualitative changes in effector T cells and prolonged preservation of endogenous insulin secretion by the remaining β cells in patients with newly diagnosed T1D.
METHODS
In a multicenter, randomized, double-blind, placebo-controlled trial, we compared alefacept (two 12-week courses of 15 mg/wk i.m., separated by a 12-week pause) with placebo in patients with recent onset of T1D. Endpoints were assessed at 24 months and included meal-stimulated C-peptide AUC, insulin use, hypoglycemic events, and immunologic responses.
RESULTS
A total of 49 patients were enrolled. At 24 months, or 15 months after the last dose of alefacept, both the 4-hour and the 2-hour C-peptide AUCs were significantly greater in the treatment group than in the control group (P = 0.002 and 0.015, respectively). Exogenous insulin requirements were lower (P = 0.002) and rates of major hypoglycemic events were about 50% reduced (P < 0.001) in the alefacept group compared with placebo at 24 months. There was no apparent between-group difference in glycemic control or adverse events. Alefacept treatment depleted CD4+ and CD8+ central memory T cells (Tcm) and effector memory T cells (Tem) (P < 0.01), preserved Tregs, increased the ratios of Treg to Tem and Tcm (P < 0.01), and increased the percentage of PD-1+CD4+ Tem and Tcm (P < 0.01).
CONCLUSIONS
In patients with newly diagnosed T1D, two 12-week courses of alefacept preserved C-peptide secretion, reduced insulin use and hypoglycemic events, and induced favorable immunologic profiles at 24 months, well over 1 year after cessation of therapy.
TRIAL REGISTRATION
https://clinicaltrials.gov/ NCT00965458.
FUNDING
NIH and Astellas.
Topics: Adolescent; Adult; Alefacept; C-Peptide; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Child; Dermatologic Agents; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Humans; Immunologic Memory; Male; Recombinant Fusion Proteins; Time Factors
PubMed: 26193635
DOI: 10.1172/JCI81722 -
Psoriasis (Auckland, N.Z.) 2022The quality of life in psoriatic patients is significantly impaired. Since this century, there have been biologics as a treatment for psoriasis. These biologics reduce... (Review)
Review
BACKGROUND
The quality of life in psoriatic patients is significantly impaired. Since this century, there have been biologics as a treatment for psoriasis. These biologics reduce symptoms, but more knowledge is needed about potential improvements in quality of life. As a result, biological therapy may be more valuable for patients who experience a lot of burden from their chronic skin condition in daily life. The aim of this systematic review was to investigate the possible improvement of the Dermatology Life Quality Index (DLQI) in psoriatic patients using biologics.
MATERIALS AND METHODS
An online search was performed in the PubMed database to identify relevant articles. Inclusion criteria for studies were psoriatic patients, a measurement of DLQI with biologics and without biologics. Exclusion criteria for studies were abstracts not written in English, publications before 2012, full text unavailable, quality of life measurements other than DLQI. Results from the studies with different biologics were combined into the outcome measure: ≥5 points of improvement in the DLQI score. Results of the studies in which biologics were compared with (conventional) systemic therapy were combined in the outcome measure: improvement of the DLQI score is better with biologics than with systemic therapy.
RESULTS
There were nine included articles with a total of 19.926 patients. Adalimumab, alefacept, etanercept, infliximab, ustekinumab and secukinumab were included biologics. Six studies measured the change in DLQI of different biologics in number of points. Of these six studies, 22 sub-analyses were performed and 20 of them showed a DLQI improvement of ≥5 points. The improvement in DLQI was better with biologics than with systemic therapy in two of the three measured studies.
CONCLUSION
Quality of life of psoriatic patients will be improved by the studied biologics. In the future, more research is needed into biologics on patient and quality of life characteristics.
PubMed: 35637943
DOI: 10.2147/PTT.S356568 -
The Journal of Allergy and Clinical... Sep 2012Hypereosinophilic syndromes (HESs) are a diverse group of conditions characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration... (Review)
Review
Hypereosinophilic syndromes (HESs) are a diverse group of conditions characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. HESs are chronic disorders with significant morbidity and mortality. Although the availability of targeted chemotherapeutic agents, including imatinib, has improved quality of life and survival in some patients with HESs, additional agents with increased efficacy and decreased toxicity are sorely needed. The purpose of this review is to provide an overview of eosinophil biology with an emphasis on potential targets of pharmacotherapy and to provide a summary of potential eosinophil-targeting agents, including those in development, in clinical trials, or approved for other disorders.
Topics: Alefacept; Alemtuzumab; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Cell Movement; Clinical Trials as Topic; Eosinophils; Humans; Hypereosinophilic Syndrome; Interleukin-5; Omalizumab; Phosphorothioate Oligonucleotides; Recombinant Fusion Proteins
PubMed: 22935585
DOI: 10.1016/j.jaci.2012.07.027 -
American Journal of Transplantation :... Jul 2013Memory T cells play a central role in mediating allograft rejection and are a rational target for immunosuppressive therapy. Alefacept is a recombinant LFA3/IgG1 fusion... (Randomized Controlled Trial)
Randomized Controlled Trial
Memory T cells play a central role in mediating allograft rejection and are a rational target for immunosuppressive therapy. Alefacept is a recombinant LFA3/IgG1 fusion protein that reduces the number of memory T cells in both psoriatic lesions and the peripheral circulation of psoriasis patients. This study evaluated the efficacy and safety of alefacept compared with placebo when combined with tacrolimus, mycophenolate mofetil and corticosteroids in de novo renal transplant recipients. Between December 2007 and March 2009 patients were randomized in a double-blind fashion to receive alefacept (n = 105) or placebo (n = 107) for 3 months and were then followed for a further 3 months. The primary efficacy endpoint was the incidence of biopsy-confirmed acute T cell mediated rejection (Banff grade ≥ 1) through Month 6. Memory T cell counts were significantly reduced in the alefacept group from Week 3 to study end compared with placebo. However, there was no significant difference between the alefacept and placebo groups for the primary efficacy endpoint (alefacept, 11.0% vs. placebo, 7.0%, p = 0.3). Patient and graft survival as well as renal function was similar between treatment groups. Safety and tolerability were generally similar between the treatment arms. Malignancy was higher in the alefacept treatment arm.
Topics: Adolescent; Adult; Aged; Alefacept; Biopsy; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Routes; Drug Therapy, Combination; Follow-Up Studies; Glucocorticoids; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Methylprednisolone; Middle Aged; Mycophenolic Acid; Recombinant Fusion Proteins; Retrospective Studies; Tacrolimus; Tissue Donors; Treatment Outcome; Young Adult
PubMed: 23730730
DOI: 10.1111/ajt.12303 -
Annals of the Rheumatic Diseases Nov 2005Alefacept is a bioengineered fusion protein of soluble lymphocyte function antigen (LFA-3) with Fc fragments of IgG1. It is marketed in many countries for the treatment... (Review)
Review
Alefacept is a bioengineered fusion protein of soluble lymphocyte function antigen (LFA-3) with Fc fragments of IgG1. It is marketed in many countries for the treatment of moderate to severe psoriasis. This paper reviews the data supporting the use of alefacept in psoriasis and psoriatic arthritis.
Topics: Alefacept; Arthritis, Psoriatic; Combined Modality Therapy; Drug Monitoring; Humans; Immunosuppressive Agents; Psoriasis; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins
PubMed: 16239390
DOI: 10.1136/ard.2005.042655