Pub Date : 2019-09-01DOI: 10.1358/dot.2019.55.9.3039670
Jake E. Radell, J. Serle
The fixed-dose combination (FDC) of netarsudil 0.02%/ latanoprost 0.005% was approved by the United States Food and Drug Administration (FDA) on March 12, 2019, for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). Netarsudil is a Rho kinase (ROCK) inhibitor and latanoprost is a prostaglandin analogue (PGA). Once-daily administration of this FDC reduces IOP by enhancing aqueous outflow through both the trabecular pathways (ROCK inhibition) and uveoscleral pathways (PGA). Two phase III clinical trials, MERCURY-1 and MERCURY-2, confirmed significantly greater efficacy of the FDC than the individual components, with IOP reductions of 30% or greater observed in 59-65% of subjects treated with FDC compared with 29-37% of subjects treated with latanoprost alone and 21-29% of subjects treated with netarsudil alone. The FDC was well tolerated with mostly mild ocular side effects and limited systemic side effects. This paper will review the work leading to FDA approval and the clinical indications for the use of this combination.
{"title":"Netarsudil/latanoprost fixed-dose combination for the treatment of open-angle glaucoma or ocular hypertension.","authors":"Jake E. Radell, J. Serle","doi":"10.1358/dot.2019.55.9.3039670","DOIUrl":"https://doi.org/10.1358/dot.2019.55.9.3039670","url":null,"abstract":"The fixed-dose combination (FDC) of netarsudil 0.02%/ latanoprost 0.005% was approved by the United States Food and Drug Administration (FDA) on March 12, 2019, for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). Netarsudil is a Rho kinase (ROCK) inhibitor and latanoprost is a prostaglandin analogue (PGA). Once-daily administration of this FDC reduces IOP by enhancing aqueous outflow through both the trabecular pathways (ROCK inhibition) and uveoscleral pathways (PGA). Two phase III clinical trials, MERCURY-1 and MERCURY-2, confirmed significantly greater efficacy of the FDC than the individual components, with IOP reductions of 30% or greater observed in 59-65% of subjects treated with FDC compared with 29-37% of subjects treated with latanoprost alone and 21-29% of subjects treated with netarsudil alone. The FDC was well tolerated with mostly mild ocular side effects and limited systemic side effects. This paper will review the work leading to FDA approval and the clinical indications for the use of this combination.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"55 9 1","pages":"563-574"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47306133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-01DOI: 10.1358/dot.2019.55.9.3039669
K. Fenn, K. Kalinsky
Patients with metastatic triple-negative breast cancer (mTNBC) that has progressed on first-line therapy have a poor prognosis with limited therapeutic options. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate (ADC) that has shown promising efficacy in mTNBC. SG is comprised of SN-38, the active metabolite of irinotecan, conjugated via a hydrolyzable linker to the humanized RS7 antibody targeting trophoblast cell surface antigen 2 (Trop-2), a glycoprotein that is expressed at high levels in many epithelial solid tumors. It has received breakthrough therapy status by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pretreated mTNBC. In this review, we summarize available data regarding the pharmacology, pharmacokinetics, safety and efficacy of SG and describe ongoing and future clinical studies investigating this agent.
{"title":"Sacituzumab govitecan: antibody-drug conjugate in triple-negative breast cancer and other solid tumors.","authors":"K. Fenn, K. Kalinsky","doi":"10.1358/dot.2019.55.9.3039669","DOIUrl":"https://doi.org/10.1358/dot.2019.55.9.3039669","url":null,"abstract":"Patients with metastatic triple-negative breast cancer (mTNBC) that has progressed on first-line therapy have a poor prognosis with limited therapeutic options. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate (ADC) that has shown promising efficacy in mTNBC. SG is comprised of SN-38, the active metabolite of irinotecan, conjugated via a hydrolyzable linker to the humanized RS7 antibody targeting trophoblast cell surface antigen 2 (Trop-2), a glycoprotein that is expressed at high levels in many epithelial solid tumors. It has received breakthrough therapy status by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pretreated mTNBC. In this review, we summarize available data regarding the pharmacology, pharmacokinetics, safety and efficacy of SG and describe ongoing and future clinical studies investigating this agent.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"55 9 1","pages":"575-585"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45661711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-01DOI: 10.1358/dot.2019.55.8.3010573
K. Hanna
Erdafitinib is the first Food and Drug Administration (FDA)-approved oral pan-fibroblast growth factor receptor (FGFR) kinase inhibitor that binds to four FGFRs (FGFR-1 to -4), leading to decreased cell signaling and cellular apoptosis. Erdafitinib also binds to RET, colony-stimulating factor 1 receptor (CSF-1R), platelet-derived growth factor receptor α and β (PDGFR-α and PDGFR-β), Fms-related tyrosine kinase 4 (FLT4), KIT and vascular endothelial growth factor receptor 2 (VEGFR-2), exhibiting additional antitumor mechanisms resulting in cell kill. In this article, we provide a comprehensive review of the preclinical and clinical activity of erdafitinib, which has been recently approved in the U.S. for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma with susceptible FGFR3/FGFR2 genetic alterations following progression during or after at least one line of platinum-containing chemotherapy and within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. Erdafitinib is the first oral treatment option for patients with urothelial carcinoma.
{"title":"Erdafitinib to treat urothelial carcinoma.","authors":"K. Hanna","doi":"10.1358/dot.2019.55.8.3010573","DOIUrl":"https://doi.org/10.1358/dot.2019.55.8.3010573","url":null,"abstract":"Erdafitinib is the first Food and Drug Administration (FDA)-approved oral pan-fibroblast growth factor receptor (FGFR) kinase inhibitor that binds to four FGFRs (FGFR-1 to -4), leading to decreased cell signaling and cellular apoptosis. Erdafitinib also binds to RET, colony-stimulating factor 1 receptor (CSF-1R), platelet-derived growth factor receptor α and β (PDGFR-α and PDGFR-β), Fms-related tyrosine kinase 4 (FLT4), KIT and vascular endothelial growth factor receptor 2 (VEGFR-2), exhibiting additional antitumor mechanisms resulting in cell kill. In this article, we provide a comprehensive review of the preclinical and clinical activity of erdafitinib, which has been recently approved in the U.S. for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma with susceptible FGFR3/FGFR2 genetic alterations following progression during or after at least one line of platinum-containing chemotherapy and within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. Erdafitinib is the first oral treatment option for patients with urothelial carcinoma.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"55 8 1","pages":"495-501"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47645687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-01DOI: 10.1358/dot.2019.55.8.3020179
F. Barra, M. Seca, L. Della Corte, P. Giampaolino, S. Ferrero
Uterine leiomyomas represent the most common form of benign gynecological tumors affecting 20-40% of women during their life. Several therapeutic options are available for treating these patients. The use of medical treatment for myomas has largely grown in the last years, in particular for women who would refuse, postpone or are not candidates for surgery. In the last years, the clinical investigation of gonadotropin-releasing hormone (GnRH) antagonists (GnRH-ants) has emerged. This class of drugs exerts pure competitive antagonistic activity on the GnRH receptor at the pituitary gland, producing an immediate stop in the release of gonadotropins and sex steroids. Relugolix is an orally active nonpeptide GnRH-ant, recently licensed for marketing in Japan for the treatment of symptoms related to uterine myomas. Currently, several phase III clinical trials are ongoing to evaluate this molecule in this setting in the U.S. and Europe.
{"title":"Relugolix for the treatment of uterine fibroids.","authors":"F. Barra, M. Seca, L. Della Corte, P. Giampaolino, S. Ferrero","doi":"10.1358/dot.2019.55.8.3020179","DOIUrl":"https://doi.org/10.1358/dot.2019.55.8.3020179","url":null,"abstract":"Uterine leiomyomas represent the most common form of benign gynecological tumors affecting 20-40% of women during their life. Several therapeutic options are available for treating these patients. The use of medical treatment for myomas has largely grown in the last years, in particular for women who would refuse, postpone or are not candidates for surgery. In the last years, the clinical investigation of gonadotropin-releasing hormone (GnRH) antagonists (GnRH-ants) has emerged. This class of drugs exerts pure competitive antagonistic activity on the GnRH receptor at the pituitary gland, producing an immediate stop in the release of gonadotropins and sex steroids. Relugolix is an orally active nonpeptide GnRH-ant, recently licensed for marketing in Japan for the treatment of symptoms related to uterine myomas. Currently, several phase III clinical trials are ongoing to evaluate this molecule in this setting in the U.S. and Europe.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"55 8 1","pages":"503-512"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45614705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-01DOI: 10.1358/dot.2019.55.8.2999891
R. Gupta, L. Bhatt, K. Prabhavalkar
Despite incessant advancement in the therapeutic regimens against colorectal cancer (CRC), treatment failure, metastasis and serious side effects associated with the available therapeutic options demand specific targeted therapies that could help in improving the survival rate with significantly less toxicity, fewer untoward effects and improved efficacy. In-depth studies highlighted the potential of CRC to be immune-responsive, thereby opening a new door in the development of strategies to combat CRC. Immunotherapy has attracted a myriad of researchers with a hope that it could potentially increase the efficacy of the treatment regimens in parallel to the reduction of toxicity. Colorectal tumors undergo immune evasion, suppressing patients' immunity and making them susceptible to infections. Therefore, a viable option could be stimulating a patient's own immune system with the help of immune modulators to fight against CRC. This review briefly discusses the immune responsiveness of CRC as well as tumor-associated antigens in CRC, and highlights the current endeavors of the scientific community in the field of immune modulators against CRC that are under development including varied types of vaccines, checkpoint inhibitors and adoptive T-cell therapy.
{"title":"Combating colorectal cancer with immunotherapy: Where are we?","authors":"R. Gupta, L. Bhatt, K. Prabhavalkar","doi":"10.1358/dot.2019.55.8.2999891","DOIUrl":"https://doi.org/10.1358/dot.2019.55.8.2999891","url":null,"abstract":"Despite incessant advancement in the therapeutic regimens against colorectal cancer (CRC), treatment failure, metastasis and serious side effects associated with the available therapeutic options demand specific targeted therapies that could help in improving the survival rate with significantly less toxicity, fewer untoward effects and improved efficacy. In-depth studies highlighted the potential of CRC to be immune-responsive, thereby opening a new door in the development of strategies to combat CRC. Immunotherapy has attracted a myriad of researchers with a hope that it could potentially increase the efficacy of the treatment regimens in parallel to the reduction of toxicity. Colorectal tumors undergo immune evasion, suppressing patients' immunity and making them susceptible to infections. Therefore, a viable option could be stimulating a patient's own immune system with the help of immune modulators to fight against CRC. This review briefly discusses the immune responsiveness of CRC as well as tumor-associated antigens in CRC, and highlights the current endeavors of the scientific community in the field of immune modulators against CRC that are under development including varied types of vaccines, checkpoint inhibitors and adoptive T-cell therapy.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"55 8 1","pages":"513-528"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45719688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-01DOI: 10.1358/dot.2019.55.8.3005176
T. Hernández-Guerrero, B. Doger, V. Moreno
Cutaneous squamous cell carcinoma (cSCC) is the second most frequent type of malignancy in Caucasians worldwide. Several factors have been correlated with aggressiveness and likelihood of recurrence and distant metastases, which are challenging to control. Metastatic disease has a dismal prognosis, and standard chemotherapy has failed to significantly improve outcomes. Recently, it has been recognized that cSCCs are highly mutated tumors with a denoting potential likelihood of response to immune checkpoint blockade. Cemiplimab is an anti-programmed cell death protein 1 (PD-1) antibody recently approved for the treatment of unresectable locally advanced or metastatic cSCC by the U.S. Food and Drug Administration (FDA) and the European Commission with a compelling response rate and an acceptable safety profile.
{"title":"Cemiplimab for the treatment of advanced cutaneous squamous cell carcinoma.","authors":"T. Hernández-Guerrero, B. Doger, V. Moreno","doi":"10.1358/dot.2019.55.8.3005176","DOIUrl":"https://doi.org/10.1358/dot.2019.55.8.3005176","url":null,"abstract":"Cutaneous squamous cell carcinoma (cSCC) is the second most frequent type of malignancy in Caucasians worldwide. Several factors have been correlated with aggressiveness and likelihood of recurrence and distant metastases, which are challenging to control. Metastatic disease has a dismal prognosis, and standard chemotherapy has failed to significantly improve outcomes. Recently, it has been recognized that cSCCs are highly mutated tumors with a denoting potential likelihood of response to immune checkpoint blockade. Cemiplimab is an anti-programmed cell death protein 1 (PD-1) antibody recently approved for the treatment of unresectable locally advanced or metastatic cSCC by the U.S. Food and Drug Administration (FDA) and the European Commission with a compelling response rate and an acceptable safety profile.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"55 8 1","pages":"485-494"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46842000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-01DOI: 10.1358/dot.2019.55.7.2965363
D. Paton
The Food and Drug Administration (FDA) approved on August 10, 2018, a soft, reusable, flexible silicone ring (56 mm diameter) containing segesterone acetate and ethinyl estradiol as the first contraceptive vaginal ring (CVR) that can be used for a year and that is totally under the control of the woman using it. The vaginal ring releases segesterone and ethinyl estradiol at estimated rates of 150 mcg/day and 13 mcg/day, respectively. The CVR is inserted into the upper two-thirds of the vagina and left in place for 21 days, then removed for 7 days. The same ring can be used for 13 cycles for a total of a year's contraception. The CVR was found to be 97.5% effective in preventing pregnancy with a Pearl Index of 2.98. The adverse effects in women using the ring were similar in nature and frequency to those reported during the use of other hormonal contraceptives. The one exception was the occurrence of venous thromboembolism, which was reported more often than expected. Because of this, the FDA has required a postmarketing study to determine the true incidence of this adverse effect. The CVR was developed by the Population Council, is known as Annovera, and will be marketed by TherapeuticsMD in the U.S.
{"title":"Contraceptive vaginal ring containing segesterone acetate and ethinyl estradiol: long-acting, patient-controlled, procedure-free, reversible prescription birth control.","authors":"D. Paton","doi":"10.1358/dot.2019.55.7.2965363","DOIUrl":"https://doi.org/10.1358/dot.2019.55.7.2965363","url":null,"abstract":"The Food and Drug Administration (FDA) approved on August 10, 2018, a soft, reusable, flexible silicone ring (56 mm diameter) containing segesterone acetate and ethinyl estradiol as the first contraceptive vaginal ring (CVR) that can be used for a year and that is totally under the control of the woman using it. The vaginal ring releases segesterone and ethinyl estradiol at estimated rates of 150 mcg/day and 13 mcg/day, respectively. The CVR is inserted into the upper two-thirds of the vagina and left in place for 21 days, then removed for 7 days. The same ring can be used for 13 cycles for a total of a year's contraception. The CVR was found to be 97.5% effective in preventing pregnancy with a Pearl Index of 2.98. The adverse effects in women using the ring were similar in nature and frequency to those reported during the use of other hormonal contraceptives. The one exception was the occurrence of venous thromboembolism, which was reported more often than expected. Because of this, the FDA has required a postmarketing study to determine the true incidence of this adverse effect. The CVR was developed by the Population Council, is known as Annovera, and will be marketed by TherapeuticsMD in the U.S.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"55 7 1","pages":"449-457"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49005857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-01DOI: 10.1358/dot.2019.55.7.2958474
A. Kaur Gill, Y. Bansal, R. Bhandari, S. Kaur, J. Kaur, R. Singh, A. Kuhad, A. Kuhad
Depression is a neuropsychiatric disorder that affects more than 350 million people all over the world. There are psychological and pharmacological treatments for depression which mainly focus on monoaminergic neurotransmission theory. The main concern regarding available antidepressants is the lag period and other side effects, such as sexual dysfunction. Gepirone is a drug of the azapirone group which is a 5-HT1A receptor agonist belonging to the buspirone family. Gepirone is under clinical development and has been shown to be more effective than selective serotonin reuptake inhibitors (SSRIs), as this drug treats the psychiatric disorders without causing sexual dysfunction, which limits the use of SSRIs. It possesses greater selectivity for the 5-HT1A receptor than SSRIs. Clinical studies have shown that gepirone has differential action at pre- and postsynaptic 5-HT1A receptors. Gepirone extended-release tablets (gepirone ER, Travivo) showed promising effects in adult outpatients for the treatment of major depressive disorder (MDD) in a double-blind, randomized, placebo-controlled clinical study. Gepirone also showed an antianxiety effect in a placebo-controlled trial in generalized anxiety disorder. Absorption of gepirone is increased when administered with food as there is no substantial change in Cmax and half-life but it significantly increases AUC and mean residence time. Gepirone undergoes first-pass metabolism and its major metabolites are 1- (2-pyrimidinyl)-piperazine (1-PP) and 3-OH-gepirone, both of which are pharmacologically active. In addition to its better efficacy, gepirone is well tolerated and the major adverse effects observed have been nausea, dizziness and lightheadedness. Evidence from preclinical and clinical studies revealed that gepirone could be a breakthrough therapeutic agent in the treatment of anxiety and MDD.
{"title":"Gepirone hydrochloride: a novel antidepressant with 5-HT1A agonistic properties.","authors":"A. Kaur Gill, Y. Bansal, R. Bhandari, S. Kaur, J. Kaur, R. Singh, A. Kuhad, A. Kuhad","doi":"10.1358/dot.2019.55.7.2958474","DOIUrl":"https://doi.org/10.1358/dot.2019.55.7.2958474","url":null,"abstract":"Depression is a neuropsychiatric disorder that affects more than 350 million people all over the world. There are psychological and pharmacological treatments for depression which mainly focus on monoaminergic neurotransmission theory. The main concern regarding available antidepressants is the lag period and other side effects, such as sexual dysfunction. Gepirone is a drug of the azapirone group which is a 5-HT1A receptor agonist belonging to the buspirone family. Gepirone is under clinical development and has been shown to be more effective than selective serotonin reuptake inhibitors (SSRIs), as this drug treats the psychiatric disorders without causing sexual dysfunction, which limits the use of SSRIs. It possesses greater selectivity for the 5-HT1A receptor than SSRIs. Clinical studies have shown that gepirone has differential action at pre- and postsynaptic 5-HT1A receptors. Gepirone extended-release tablets (gepirone ER, Travivo) showed promising effects in adult outpatients for the treatment of major depressive disorder (MDD) in a double-blind, randomized, placebo-controlled clinical study. Gepirone also showed an antianxiety effect in a placebo-controlled trial in generalized anxiety disorder. Absorption of gepirone is increased when administered with food as there is no substantial change in Cmax and half-life but it significantly increases AUC and mean residence time. Gepirone undergoes first-pass metabolism and its major metabolites are 1- (2-pyrimidinyl)-piperazine (1-PP) and 3-OH-gepirone, both of which are pharmacologically active. In addition to its better efficacy, gepirone is well tolerated and the major adverse effects observed have been nausea, dizziness and lightheadedness. Evidence from preclinical and clinical studies revealed that gepirone could be a breakthrough therapeutic agent in the treatment of anxiety and MDD.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"55 7 1","pages":"423-437"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46130303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-01DOI: 10.1358/dot.2019.55.7.2985293
B. Wedi
Lanadelumab is a human monoclonal antibody against plasma kallikrein indicated for prevention of attacks of hereditary angioedema (HAE). HAE is caused by SERPING1 gene mutations resulting in decreased or dysfunctional plasma protease C1 inhibitor (C1-INH) leading to a loss of inhibition of plasma kallikrein activity with subsequent cleavage of high-molecular weight kininogen and release of bradykinin. There is a clear need for a non-plasma-derived, safe, effective and convenient prophylaxis of HAE attacks to reduce patients' daily burden of disease and disability. The percentage of patients who were attack-free for the last 16 weeks of a controlled study was 77% in the group receiving 300 mg lanadelumab every 2 weeks, compared with 3% with placebo. The most common side effects were mild injection-site reactions. Lanadelumab has the potential to change the approach from on-demand treatment to prophylaxis in HAE. Future studies will have to confirm long-term safety and efficacy of prophylactic long-term inhibition of plasma kallikrein.
{"title":"Lanadelumab to treat hereditary angioedema.","authors":"B. Wedi","doi":"10.1358/dot.2019.55.7.2985293","DOIUrl":"https://doi.org/10.1358/dot.2019.55.7.2985293","url":null,"abstract":"Lanadelumab is a human monoclonal antibody against plasma kallikrein indicated for prevention of attacks of hereditary angioedema (HAE). HAE is caused by SERPING1 gene mutations resulting in decreased or dysfunctional plasma protease C1 inhibitor (C1-INH) leading to a loss of inhibition of plasma kallikrein activity with subsequent cleavage of high-molecular weight kininogen and release of bradykinin. There is a clear need for a non-plasma-derived, safe, effective and convenient prophylaxis of HAE attacks to reduce patients' daily burden of disease and disability. The percentage of patients who were attack-free for the last 16 weeks of a controlled study was 77% in the group receiving 300 mg lanadelumab every 2 weeks, compared with 3% with placebo. The most common side effects were mild injection-site reactions. Lanadelumab has the potential to change the approach from on-demand treatment to prophylaxis in HAE. Future studies will have to confirm long-term safety and efficacy of prophylactic long-term inhibition of plasma kallikrein.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"55 7 1","pages":"439-448"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46161564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-01DOI: 10.1358/dot.2019.55.7.3010575
Ayesha Girach, Abdullah Aamir, Panagiotis Zis
The placebo effect is a phenomenon of great scientific interest that affects the response in both inactive and active treatments. It is broadly understood as the product of a central integration of positive expectations, reward learning and continuous conditioning inducing physiological changes in the brain. The placebo effect is accepted as a phenomenon which can be harnessed in clinical practice. It has emerged that there is not a single neurobiological mechanism involved in placebo responses, but many depending on the underlying disease. Molecular neuroimaging techniques with positron emission tomography and selective radiotracers have been significant in the understanding of the neurobiological systems involved in the placebo effect. The aim of this review was to summarize the key findings relating to the neurobiology behind the placebo effect.
{"title":"The neurobiology under the placebo effect.","authors":"Ayesha Girach, Abdullah Aamir, Panagiotis Zis","doi":"10.1358/dot.2019.55.7.3010575","DOIUrl":"https://doi.org/10.1358/dot.2019.55.7.3010575","url":null,"abstract":"The placebo effect is a phenomenon of great scientific interest that affects the response in both inactive and active treatments. It is broadly understood as the product of a central integration of positive expectations, reward learning and continuous conditioning inducing physiological changes in the brain. The placebo effect is accepted as a phenomenon which can be harnessed in clinical practice. It has emerged that there is not a single neurobiological mechanism involved in placebo responses, but many depending on the underlying disease. Molecular neuroimaging techniques with positron emission tomography and selective radiotracers have been significant in the understanding of the neurobiological systems involved in the placebo effect. The aim of this review was to summarize the key findings relating to the neurobiology behind the placebo effect.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"55 7 1","pages":"469-476"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47655542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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