Combination Therapy With Guselkumab and Golimumab in Patients With Moderately to Severely Active Ulcerative Colitis: Pharmacokinetics, Immunogenicity and Drug-Drug Interactions
Clin Pharmacol Ther. 2024 Mar 15. doi: 10.1002/cpt.3235. Online ahead of print.ABSTRACTA proof-of-concept study with the combination of guselkumab and golimumab in patients with ulcerative colitis (UC) has shown that the combination therapy resulted in greater efficacy than the individual monotherapies. The current analysis evaluated the pharmacokinetics (PK) and immunogenicity of guselkumab and golimumab in both the combination therapy and individual monotherapies. Blood samples were collected to evaluate serum concentrations and immunogenicity of guselkumab and golimumab. Population PK (PopPK) models were developed to as...
Source: Clinical Pharmacology and Therapeutics - March 15, 2024 Category: Drugs & Pharmacology Authors: Jie Shao Marion Vetter An Vermeulen Brian G Feagan Bruce E Sands Julian Pan és Zhenhua Xu Source Type: research

Comparative Risk of Injury with Concurrent Use of Opioids and Skeletal Muscle Relaxants
In conclusion, the relative injury rate associated with different SMRs used concurrently with the three most dispensed opioids appears to vary depending on the specific opioid and the order of combination initiation. If confirmed by future studies, clinicians should consider the varying injury rates when prescribing SMRs to individuals using hydrocodone, oxycodone, and tramadol.PMID:38482733 | DOI:10.1002/cpt.3248 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - March 14, 2024 Category: Drugs & Pharmacology Authors: Cheng Chen Sean Hennessy Colleen M Brensinger Todd A Miano Warren B Bilker Sascha Dublin Sophie P Chung John R Horn Anika Tiwari Charles E Leonard Source Type: research

Gene Polymorphisms of NLRP3 Associated With Plasma Levels of 4 β-Hydroxycholesterol, an Endogenous Marker of CYP3A Activity, in Patients With Asthma
Clin Pharmacol Ther. 2024 Mar 14. doi: 10.1002/cpt.3254. Online ahead of print.ABSTRACTInflammation decreases the activity of cytochrome P450 3A (CYP3A). Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) is responsible for regulating the inflammatory response, and its genetic polymorphisms have been linked to inflammatory diseases such as asthma. However, there have been few studies on the effect of NLRP3 on CYP3A activity. We aimed to investigate the association between polymorphisms in the NLRP3 gene and plasma 4β-hydroxycholesterol (4βOHC), an endogenous marker of C...
Source: Clinical Pharmacology and Therapeutics - March 14, 2024 Category: Drugs & Pharmacology Authors: Keita Hirai Tomoki Kimura Yuya Suzuki Takayuki Shimoshikiryo Toshihiro Shirai Kunihiko Itoh Source Type: research

A Clinical Practice Perspective on the Evaluation of OATP1B1-associated Drug Interactions
Clin Pharmacol Ther. 2024 Mar 14. doi: 10.1002/cpt.3247. Online ahead of print.NO ABSTRACTPMID:38483031 | DOI:10.1002/cpt.3247 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - March 14, 2024 Category: Drugs & Pharmacology Authors: C éline K Stäuble Markus L Lampert Samuel S Allemann Henriette E Meyer Zu Schwabedissen Source Type: research

Comparative Risk of Injury with Concurrent Use of Opioids and Skeletal Muscle Relaxants
In conclusion, the relative injury rate associated with different SMRs used concurrently with the three most dispensed opioids appears to vary depending on the specific opioid and the order of combination initiation. If confirmed by future studies, clinicians should consider the varying injury rates when prescribing SMRs to individuals using hydrocodone, oxycodone, and tramadol.PMID:38482733 | DOI:10.1002/cpt.3248 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - March 14, 2024 Category: Drugs & Pharmacology Authors: Cheng Chen Sean Hennessy Colleen M Brensinger Todd A Miano Warren B Bilker Sascha Dublin Sophie P Chung John R Horn Anika Tiwari Charles E Leonard Source Type: research

Gene Polymorphisms of NLRP3 Associated With Plasma Levels of 4 β-Hydroxycholesterol, an Endogenous Marker of CYP3A Activity, in Patients With Asthma
Clin Pharmacol Ther. 2024 Mar 14. doi: 10.1002/cpt.3254. Online ahead of print.ABSTRACTInflammation decreases the activity of cytochrome P450 3A (CYP3A). Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) is responsible for regulating the inflammatory response, and its genetic polymorphisms have been linked to inflammatory diseases such as asthma. However, there have been few studies on the effect of NLRP3 on CYP3A activity. We aimed to investigate the association between polymorphisms in the NLRP3 gene and plasma 4β-hydroxycholesterol (4βOHC), an endogenous marker of C...
Source: Clinical Pharmacology and Therapeutics - March 14, 2024 Category: Drugs & Pharmacology Authors: Keita Hirai Tomoki Kimura Yuya Suzuki Takayuki Shimoshikiryo Toshihiro Shirai Kunihiko Itoh Source Type: research

A Clinical Practice Perspective on the Evaluation of OATP1B1-associated Drug Interactions
Clin Pharmacol Ther. 2024 Mar 14. doi: 10.1002/cpt.3247. Online ahead of print.NO ABSTRACTPMID:38483031 | DOI:10.1002/cpt.3247 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - March 14, 2024 Category: Drugs & Pharmacology Authors: C éline K Stäuble Markus L Lampert Samuel S Allemann Henriette E Meyer Zu Schwabedissen Source Type: research

Artificial Intelligence and Disease Modeling: Focus on Neurological Disorders
Clin Pharmacol Ther. 2024 Mar 13. doi: 10.1002/cpt.3253. Online ahead of print.NO ABSTRACTPMID:38480479 | DOI:10.1002/cpt.3253 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - March 13, 2024 Category: Drugs & Pharmacology Authors: Benjamin Ribba Gennaro Pagano Niklas Korsbo Vijay Ivaturi Antoine Soubret Source Type: research

Efficacy and safety of antiplatelet therapy in COVID-19: Insights from a  meta-analysis of randomized controlled trials
CONCLUSION: Antiplatelet therapy does not confer mortality benefit in COVID-19 patients but lowers major thrombotic events while increasing major bleeding risks. Ongoing large RCTs will provide more information on the therapeutic value of this therapy.PMID:38469705 | DOI:10.5414/CP204497 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - March 12, 2024 Category: Drugs & Pharmacology Authors: Guoying Kao Yunlin Chen Jinqi Fan Source Type: research

Efficacy and safety of antiplatelet therapy in COVID-19: Insights from a  meta-analysis of randomized controlled trials
CONCLUSION: Antiplatelet therapy does not confer mortality benefit in COVID-19 patients but lowers major thrombotic events while increasing major bleeding risks. Ongoing large RCTs will provide more information on the therapeutic value of this therapy.PMID:38469705 | DOI:10.5414/CP204497 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - March 12, 2024 Category: Drugs & Pharmacology Authors: Guoying Kao Yunlin Chen Jinqi Fan Source Type: research

Efficacy and safety of antiplatelet therapy in COVID-19: Insights from a  meta-analysis of randomized controlled trials
CONCLUSION: Antiplatelet therapy does not confer mortality benefit in COVID-19 patients but lowers major thrombotic events while increasing major bleeding risks. Ongoing large RCTs will provide more information on the therapeutic value of this therapy.PMID:38469705 | DOI:10.5414/CP204497 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - March 12, 2024 Category: Drugs & Pharmacology Authors: Guoying Kao Yunlin Chen Jinqi Fan Source Type: research

Impact of Treatment Modality and Route of Administration on Cytokine Release Syndrome in Relapsed or Refractory Multiple Myeloma: A Meta-Analysis
This study utilized a meta-analysis approach to compare the CRS profile in BCMA-targeting CAR-T vs. BsAb immunotherapies administered either i.v. or s.c. in patients with RRMM. A total of 36 studies including 1,560 patients with RRMM treated with BCMA-targeting CAR-T and BsAb therapies were included in the analysis. The current analysis suggests that compared with BsAbs, CAR-T therapies were associated with higher CRS incidences (88% vs. 59%), higher rates of grade ≥ 3 CRS (7% vs. 2%), longer CRS duration (5 vs. 2 days), and more prevalent tocilizumab use (44% vs. 25%). The proportion of CRS grade ≥ 3 may also be lower...
Source: Clinical Pharmacology and Therapeutics - March 9, 2024 Category: Drugs & Pharmacology Authors: Pooneh Soltantabar Sheena Sharma Diane Wang Hoi-Kei Lon Akos Czibere Anne Hickmann Mohamed Elmeliegy Source Type: research

Algorithmic Identification of Treatment-Emergent Adverse Events From Clinical Notes Using Large Language Models: A Pilot Study in Inflammatory Bowel Disease
Clin Pharmacol Ther. 2024 Mar 8. doi: 10.1002/cpt.3226. Online ahead of print.ABSTRACTOutpatient clinical notes are a rich source of information regarding drug safety. However, data in these notes are currently underutilized for pharmacovigilance due to methodological limitations in text mining. Large language models (LLMs) like Bidirectional Encoder Representations from Transformers (BERT) have shown progress in a range of natural language processing tasks but have not yet been evaluated on adverse event (AE) detection. We adapted a new clinical LLM, University of California - San Francisco (UCSF)-BERT, to identify seriou...
Source: Clinical Pharmacology and Therapeutics - March 9, 2024 Category: Drugs & Pharmacology Authors: Anna L Silverman Madhumita Sushil Balu Bhasuran Dana Ludwig James Buchanan Rebecca Racz Mahalakshmi Parakala Samer El-Kamary Ohenewaa Ahima Artur Belov Lauren Choi Monisha Billings Yan Li Nadia Habal Qi Liu Jawahar Tiwari Atul J Butte Vivek A Rudrapatna Source Type: research

Impact of Treatment Modality and Route of Administration on Cytokine Release Syndrome in Relapsed or Refractory Multiple Myeloma: A Meta-Analysis
This study utilized a meta-analysis approach to compare the CRS profile in BCMA-targeting CAR-T vs. BsAb immunotherapies administered either i.v. or s.c. in patients with RRMM. A total of 36 studies including 1,560 patients with RRMM treated with BCMA-targeting CAR-T and BsAb therapies were included in the analysis. The current analysis suggests that compared with BsAbs, CAR-T therapies were associated with higher CRS incidences (88% vs. 59%), higher rates of grade ≥ 3 CRS (7% vs. 2%), longer CRS duration (5 vs. 2 days), and more prevalent tocilizumab use (44% vs. 25%). The proportion of CRS grade ≥ 3 may also be lower...
Source: Clinical Pharmacology and Therapeutics - March 9, 2024 Category: Drugs & Pharmacology Authors: Pooneh Soltantabar Sheena Sharma Diane Wang Hoi-Kei Lon Akos Czibere Anne Hickmann Mohamed Elmeliegy Source Type: research

Algorithmic Identification of Treatment-Emergent Adverse Events From Clinical Notes Using Large Language Models: A Pilot Study in Inflammatory Bowel Disease
Clin Pharmacol Ther. 2024 Mar 8. doi: 10.1002/cpt.3226. Online ahead of print.ABSTRACTOutpatient clinical notes are a rich source of information regarding drug safety. However, data in these notes are currently underutilized for pharmacovigilance due to methodological limitations in text mining. Large language models (LLMs) like Bidirectional Encoder Representations from Transformers (BERT) have shown progress in a range of natural language processing tasks but have not yet been evaluated on adverse event (AE) detection. We adapted a new clinical LLM, University of California - San Francisco (UCSF)-BERT, to identify seriou...
Source: Clinical Pharmacology and Therapeutics - March 9, 2024 Category: Drugs & Pharmacology Authors: Anna L Silverman Madhumita Sushil Balu Bhasuran Dana Ludwig James Buchanan Rebecca Racz Mahalakshmi Parakala Samer El-Kamary Ohenewaa Ahima Artur Belov Lauren Choi Monisha Billings Yan Li Nadia Habal Qi Liu Jawahar Tiwari Atul J Butte Vivek A Rudrapatna Source Type: research