Effects of acalabrutinib: A Synthesis of Findings from 17 Studies

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Original Abstract of the Article

Main Research Findings

Acalabrutinib is a second-generation Bruton's tyrosine kinase (BTK) inhibitor that has shown promise in the treatment of chronic lymphocytic leukemia (CLL). 12 , a meta-analysis of 20 studies, found that new-generation BTKi-based regimens, including acalabrutinib, had a pooled overall response rate (ORR) of 92% and a pooled complete response (CR) rate of 10% in patients with CLL/SLL. Additionally, 16 , a network meta-analysis of nine clinical trials, suggests that a combination of obinutuzumab with acalabrutinib might be the most effective option for first-line treatment of CLL. 14 highlights the improved safety profile and efficacy of acalabrutinib compared to the first-generation BTKi, ibrutinib. 17 presents a new covalent inhibitor, JS25, which exhibits greater selectivity and potency against BTK than clinically used inhibitors like ibrutinib and acalabrutinib, demonstrating its significant therapeutic potential in blood cancers.

Benefits and Risks

Benefit Summary

Acalabrutinib demonstrates effectiveness in treating blood cancers, specifically CLL. 12 suggests that second-generation BTKi, including acalabrutinib, are associated with high response rates and improved long-term survival in CLL/SLL patients. 16 implies that the combination of acalabrutinib and obinutuzumab might outperform other therapies in first-line CLL treatment. 15 mentions that acalabrutinib holds significant potential in treating relapsed/refractory CLL. 17 showcases the effectiveness of a novel BTK inhibitor (JS25) with greater potency than acalabrutinib in various B-cell cancer cell lines.

Risk Summary

Acalabrutinib, like other medications, carries potential side effects. 12 , a meta-analysis, reports common side effects associated with second-generation BTKi, including cytopenia and hypertension. 14 emphasizes that while acalabrutinib shows improved tolerability compared to ibrutinib, it still carries the risk of adverse effects. 15 lists potential side effects of acalabrutinib, such as thrombocytopenia, rash, and gastrointestinal issues. 17 implies that the new BTK inhibitor, JS25, also presents the risk of side effects.

Comparison of Studies

Commonalities

These studies consistently demonstrate the effectiveness of BTKi, including acalabrutinib, in treating blood cancers, particularly CLL. They also suggest that acalabrutinib might exhibit better tolerability than other BTKi. Additionally, these studies highlight the significant advancements achieved in blood cancer treatment due to the development of BTKi.

Differences

The studies differ in their scope, design, and outcome measures. 12 is a meta-analysis, combining data from multiple studies, while 16 employs network meta-analysis. 17 focuses on a new BTK inhibitor. Direct comparison of results from these studies might not be possible due to these variations.

Consistency and Contradictions in Findings

These studies consistently point towards the effectiveness of acalabrutinib in treating blood cancers like CLL. However, the studies often compare the effectiveness and safety of acalabrutinib to other BTKi, making direct comparisons challenging. Further research is needed to explore the long-term effects of acalabrutinib and its effectiveness across diverse patient groups.

Practical Implications and Considerations

Acalabrutinib should be used under the guidance of a healthcare professional with proper diagnosis and treatment. It is essential to follow the doctor's instructions regarding dosage and administration due to the potential for side effects. It's crucial to consult with a physician to determine the most suitable treatment plan based on individual factors and specific needs.

Limitations of Current Research

The current research on acalabrutinib is still limited. Further research is necessary to investigate the long-term effects of acalabrutinib and its effectiveness across different patient populations. While many studies compare acalabrutinib to other BTKi, direct comparisons can be challenging.

Future Research Directions

Future research should focus on evaluating the long-term effects of acalabrutinib and its effectiveness across diverse patient populations. More precise comparisons with other BTKi, using similar study designs and outcome measures, are crucial. Furthermore, thorough investigations into the side effects of acalabrutinib are needed.

Conclusion

Acalabrutinib shows promise as a treatment option for blood cancers like CLL, offering potential benefits compared to other BTKi. While acalabrutinib demonstrates good tolerability, it is essential to acknowledge the possibility of side effects and to use this medication under the supervision of a healthcare professional. Continued research is vital to further understand the long-term effects, optimize treatment strategies, and address remaining uncertainties regarding this promising drug.

Literature analysis of 17 papers
Positive Content
17
Neutral Content
0
Negative Content
0
Article Type
6
6
1
4
17
1.

Apixaban versus enoxaparin in patients with total knee arthroplasty. A meta-analysis of randomised trials.

Author: HuangJiahao, CaoYunfei, LiaoCun, WuLiucheng, GaoFeng

Lower bleeding
VTE prevention
Bleeding
Mortality

The study found that apixaban is non-inferior to subcutaneous enoxaparin for the prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA). Apixaban was associated with a lower major bleeding rate than enoxaparin.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

2.

Apixaban and rivaroxaban safety after hip and knee arthroplasty: a meta-analysis.

Author: AlvesCarlos, Batel-MarquesFrancisco, MacedoAna Filipa

Reduced bleeding

A meta-analysis compared the safety of apixaban and rivaroxaban, two direct Xa coagulation factor inhibitors, in patients undergoing knee and hip arthroplasty. Apixaban was associated with fewer major and total bleeding events after knee arthroplasty compared to rivaroxaban, with no significant differences observed after hip arthroplasty.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation.

Author: WallentinLars, LopesRenato D, HannaMichael, ThomasLaine, HellkampAnne, NepalSunil, HylekElaine M, Al-KhatibSana M, AlexanderJohn H, AlingsMarco, AmerenaJohn, AnsellJack, AylwardPhilip, BartunekJozef, CommerfordPatrick, De CaterinaRaffaele, ErolCetin, HarjolaVeli-Pekka, HeldClaes, HorowitzJohn D, HuberKurt, HustedSteen, KeltaiMatyas, LanasFernando, LishengLiu, McMurrayJohn J V, OhByung-Hee, RosenqvistMårten, RuzylloWitold, StegPhilippe Gabriel, VinereanuDragos, XavierDenis, GrangerChristopher B,

Stroke reduction
Bleeding risk

This analysis of the ARISTOTLE trial, which compared apixaban to warfarin for stroke prevention in atrial fibrillation, examined treatment effects in relation to time in therapeutic range (TTR). The findings indicate that apixaban may provide benefits regardless of TTR, while warfarin's effectiveness is more dependent on TTR.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

The effects of apixaban on hospitalizations in patients with different types of atrial fibrillation: insights from the AVERROES trial.

Author: HohnloserStefan H, ShestakovskaOlga, EikelboomJohn, FranzosiMaria Grazia, TanRu San, ZhuJun, YusufSalim, ConnollyStuart J

Cardiovascular hospitalization reduction

Apixaban therapy was associated with a lower risk of cardiovascular hospitalization in patients with atrial fibrillation (AF), particularly for stroke and other cardiovascular causes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

Evaluating the efficacy and safety of apixaban, a new oral anticoagulant, using Bayesian meta-analysis.

Author: VillaLorenzo A, MaloneDaniel C, RossDaniel

Thromboembolism treatment
Bleeding events

Apixaban, a direct factor Xa inhibitor, showed similar efficacy and safety to enoxaparin for the treatment of acute venous thromboembolism. While both agents demonstrated effectiveness in preventing venous thromboembolism, there was no clear superiority of apixaban over enoxaparin.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

6.

Apixaban and risk of myocardial infarction: meta-analysis of randomized controlled trials.

Author: TornyosAdrienn, VorobcsukAndrás, KupóPéter, AradiDániel, KehlDániel, KomócsiAndrás

MI prevention
Bleeding risk

This systematic review evaluated the risk of myocardial infarction (MI) and mortality in patients receiving apixaban, a new-generation oral anti-Xa agent. Pooled results showed no increase in the risk of MI or mortality in apixaban-treated patients compared to control groups.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial.

Author: HeldClaes, HylekElaine M, AlexanderJohn H, HannaMichael, LopesRenato D, WojdylaDaniel M, ThomasLaine, Al-KhalidiHussein, AlingsMarco, XavierDennis, AnsellJack, GotoShinya, RuzylloWitold, RosenqvistMårten, VerheugtFreek W A, ZhuJun, GrangerChristopher B, WallentinLars

Atrial fibrillation treatment
Stroke prevention
Major bleed

This ancillary study evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

A meta-analysis of randomized controlled trials of the risk of bleeding with apixaban versus vitamin K antagonists.

Author: ToumaLahoud, FilionKristian B, AtallahRenée, EbergMaria, EisenbergMark J

All-cause mortality reduction
Apixaban effectiveness
Bleeding risk reduction

This meta-analysis compared the risks of bleeding and all-cause mortality between apixaban and vitamin K antagonists (VKAs) for stroke prevention, knee replacement surgery, and venous thromboembolism. Apixaban was associated with a lower risk of bleeding and all-cause mortality.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

9.

Apixaban Reduces Hospitalizations in Patients With Venous Thromboembolism: An Analysis of the Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy (AMPLIFY) Trial.

Author: LiuXianchen, JohnsonMargot, MardekianJack, PhatakHemant, ThompsonJohn, CohenAlexander T

Reduced bleeding
Reduced hospitalization

Apixaban, a direct oral anticoagulant, was noninferior to enoxaparin/warfarin in preventing recurrent venous thromboembolism (VTE) or VTE-related death in the AMPLIFY trial. Apixaban was also associated with significantly less bleeding. This analysis found that apixaban led to fewer all-cause hospitalizations than enoxaparin/warfarin.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial.

Author: Jaspers FocksJeroen, BrouwerMarc A, WojdylaDaniel M, ThomasLaine, LopesRenato D, WashamJeffrey B, LanasFernando, XavierDenis, HustedSteen, WallentinLars, AlexanderJohn H, GrangerChristopher B, VerheugtFreek W A

Apixaban effective
Apixaban safe
Increased bleeding
Increased mortality
Increased thromboembolic

Apixaban is more effective than warfarin in reducing the risk of stroke and systemic embolism in patients with atrial fibrillation and polypharmacy. Apixaban is as safe as warfarin in this patient population.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

11.

Interacting medication use and the treatment effects of apixaban versus warfarin: results from the ARISTOTLE Trial.

Author: WashamJeffrey B, HohnloserStefan H, LopesRenato D, WojdylaDaniel M, VinereanuDragos, AlexanderJohn H, GershBernard J, HannaMichael, HorowitzJohn, HylekElaine M, XavierDenis, VerheugtFreek W A, WallentinLars, GrangerChristopher B,

Stroke prevention
Systemic embolism prevention
Major bleeding

Interacting medications did not significantly affect the efficacy or safety of apixaban compared to warfarin in patients with atrial fibrillation.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

12.

Efficacy and safety of new-generation Bruton tyrosine kinase inhibitors in chronic lymphocytic leukemia/small lymphocytic lymphoma: a systematic review and meta-analysis.

Author: YinShuo, ZhengXiaohong, ZhangWeichunbai, ZhaoHanyun, ZhangRong, LiWenbin, ChenFeng

CLL/SLL treatment
Good tolerance
Improved efficacy
BTKi combination AEs
Cytopenia
Hypertension

Bruton tyrosine kinase inhibitors (BTKi) are a class of drugs used to treat chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). This systematic review evaluated the efficacy and safety of new-generation BTKi-based regimens for the treatment of CLL/SLL.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

13.

Structure of BTK kinase domain with the second-generation inhibitors acalabrutinib and tirabrutinib.

Author: LinDavid Y, AndreottiAmy H

Improved drug selectivity
Reduced off-target effects
Autoimmune disorders
Cancer

This study reports the first crystal structures of the BTK kinase domain in complex with acalabrutinib and tirabrutinib, providing insight into the superior selectivity of acalabrutinib and guiding future BTK inhibitor development.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

14.

SOHO State of the Art Updates and Next Questions: Updates on BTK Inhibitors for the Treatment of Chronic Lymphocytic Leukemia.

Author: EasawSaumya, EzzatiShawyon, CoombsCatherine C

Improved CLL outcomes
Intolerance
Resistance

This review discusses the evolution of Bruton's tyrosine kinase (BTK) inhibitors (BTKi) in the management of chronic lymphocytic leukemia (CLL). The article explores the development of newer BTKi, including the third generation of noncovalent or reversible BTKi, and BTK degraders, which hold promise for overcoming resistance and intolerance to cBTKi.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

15.

Current Treatment Options in Relapsed and Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: a Review.

Author: IslamPrioty

CLL treatment

This review discusses the current treatment landscape for relapsed and refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL), outlining different therapeutic approaches based on prior therapies and highlighting the importance of clinical trial enrollment for patients with complex disease.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

16.

Molecular-Biology-Driven Frontline Treatment for Chronic Lymphocytic Leukemia: A Network Meta-Analysis of Randomized Clinical Trials.

Author: RizzutoAndrea, PirreraAngelo, GigliottaEmilia, MancusoSalvatrice, VulloCandida, CamardaGiulia Maria, RotoloCristina, RoppoloArianna, SpotoCorinne, GentileMassimo, BottaCirino, SiragusaSergio

CLL remission
Chemotherapy-free treatment

This systematic review and network meta-analysis assessed the efficacy and safety of different treatment regimens for first-line chronic lymphocytic leukemia. The combination of obinutuzumab with acalabrutinib showed the best overall results, including progression-free survival and overall response rate.

Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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