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Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: A Head-to-Head Network Meta-Analysis of Mavacamten and Aficamten Imran Saleh; Syamsu Indra; Yenny Dian Andayani; Rukiah Chodilawati; Yuniza
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 8 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i8.1360

Background: Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by myocardial hypercontractility. Mavacamten and aficamten are first-in-class cardiac myosin inhibitors that have demonstrated efficacy in treating obstructive HCM. However, in the absence of direct head-to-head randomized controlled trials (RCTs), their comparative effectiveness and safety remain unquantified. We aimed to indirectly compare the efficacy and safety of mavacamten and aficamten in patients with obstructive HCM. Methods: We conducted a systematic review and Bayesian network meta-analysis of RCTs. We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to December 2024. Eligible studies were RCTs comparing mavacamten or aficamten with placebo in adults with obstructive HCM. The primary efficacy outcomes were the change from baseline in post-exercise left ventricular outflow tract (LVOT) gradient and the change in peak oxygen consumption (pVO₂). The primary safety outcome was the incidence of left ventricular ejection fraction (LVEF) reduction to <50%. Results: Seven RCTs involving 1,025 patients were included. In the network meta-analysis, both aficamten (Mean Difference [MD], -50.8 mmHg; 95% Credible Interval [CrI], -61.2 to -40.4) and mavacamten (MD, -44.9 mmHg; 95% CrI, -53.7 to -36.1) were significantly more effective than placebo in reducing post-exercise LVOT gradient. The indirect comparison between the two agents did not reveal a statistically significant difference (MD, -5.9 mmHg; 95% CrI, -17.8 to 6.0). For pVO₂, both mavacamten and aficamten showed significant improvement over placebo, with no significant difference between them. The odds of LVEF dropping below 50% were numerically higher with mavacamten compared to aficamten, but the difference was not statistically significant (Odds Ratio [OR], 1.52; 95% CrI, 0.65 to 3.54). Conclusion: Mavacamten and aficamten are both highly effective in improving hemodynamic and functional parameters in patients with obstructive HCM. While our indirect comparison did not establish the superiority of one agent over the other, it provides foundational evidence for clinicians. Definitive conclusions await direct head-to-head clinical trials.

Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: A Head-to-Head Network Meta-Analysis of Mavacamten and Aficamten Imran Saleh; Syamsu Indra; Yenny Dian Andayani; Rukiah Chodilawati; Yuniza
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 8 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i8.1360

Background: Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by myocardial hypercontractility. Mavacamten and aficamten are first-in-class cardiac myosin inhibitors that have demonstrated efficacy in treating obstructive HCM. However, in the absence of direct head-to-head randomized controlled trials (RCTs), their comparative effectiveness and safety remain unquantified. We aimed to indirectly compare the efficacy and safety of mavacamten and aficamten in patients with obstructive HCM. Methods: We conducted a systematic review and Bayesian network meta-analysis of RCTs. We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to December 2024. Eligible studies were RCTs comparing mavacamten or aficamten with placebo in adults with obstructive HCM. The primary efficacy outcomes were the change from baseline in post-exercise left ventricular outflow tract (LVOT) gradient and the change in peak oxygen consumption (pVO₂). The primary safety outcome was the incidence of left ventricular ejection fraction (LVEF) reduction to <50%. Results: Seven RCTs involving 1,025 patients were included. In the network meta-analysis, both aficamten (Mean Difference [MD], -50.8 mmHg; 95% Credible Interval [CrI], -61.2 to -40.4) and mavacamten (MD, -44.9 mmHg; 95% CrI, -53.7 to -36.1) were significantly more effective than placebo in reducing post-exercise LVOT gradient. The indirect comparison between the two agents did not reveal a statistically significant difference (MD, -5.9 mmHg; 95% CrI, -17.8 to 6.0). For pVO₂, both mavacamten and aficamten showed significant improvement over placebo, with no significant difference between them. The odds of LVEF dropping below 50% were numerically higher with mavacamten compared to aficamten, but the difference was not statistically significant (Odds Ratio [OR], 1.52; 95% CrI, 0.65 to 3.54). Conclusion: Mavacamten and aficamten are both highly effective in improving hemodynamic and functional parameters in patients with obstructive HCM. While our indirect comparison did not establish the superiority of one agent over the other, it provides foundational evidence for clinicians. Definitive conclusions await direct head-to-head clinical trials.

Efficacy and Safety of IL-5 Pathway-Targeting Biologics (Mepolizumab, Reslizumab, Benralizumab) in the Management of Hypereosinophilic Syndromes: A Systematic Review and Meta-Analysis Yuniza; Melani; Ratna Maila Dewi Anggraini; Yenny Dian Andayani
Open Access Indonesian Journal of Medical Reviews Vol. 5 No. 5 (2025): Open Access Indonesian Journal of Medical Reviews
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/oaijmr.v5i5.780

Hypereosinophilic syndromes (HES) are rare disorders defined by persistent eosinophilia and eosinophil-driven organ damage. Interleukin-5 (IL-5) is the central cytokine governing eosinophil maturation and survival, establishing its pathway as a critical therapeutic target. While individual trials of biologics targeting the IL-5 pathway—mepolizumab, reslizumab, and benralizumab—have shown promise, a quantitative synthesis of their class-wide efficacy and safety in HES is needed. This study aimed to meta-analyze the evidence for these agents in managing HES. Following PRISMA guidelines, we systematically searched PubMed, Embase, and Cochrane Library through December 2024 for randomized controlled trials (RCTs) and prospective observational studies of IL-5 pathway biologics in patients with HES. Primary outcomes were the proportion of patients achieving hematologic response and the annualized rate of clinical exacerbations. Key secondary outcomes included oral corticosteroid (OCS) dose reduction and adverse events (AEs). Data were pooled using a random-effects model, with extensive, pre-planned subgroup and sensitivity analyses to explore heterogeneity. Seven studies (3 RCTs, 4 observational) involving 388 patients were included. Patients receiving IL-5 pathway biologics had significantly higher odds of achieving hematologic response (Odds Ratio [OR] 9.85; 95% Confidence Interval [CI] 5.12-18.96; p<0.0001), a finding robust to sensitivity analyses of different response definitions. The annualized exacerbation rate was reduced by 64% (Rate Ratio 0.36; 95% CI 0.25-0.52; p<0.0001). The intervention led to a mean daily OCS reduction of 12.5 mg (95% CI -15.8 to -9.2 mg; p<0.0001). Subgroup analysis revealed this effect was more pronounced in observational studies than in RCTs. The overall risk of AEs was not significantly increased. This meta-analysis provides robust evidence that biologics targeting the IL-5 pathway are highly effective and generally safe for managing PDGFRA-negative HES. They induce high rates of hematologic remission, substantially reduce clinical exacerbations, and facilitate a significant corticosteroid-sparing effect. These findings strongly support their role as a foundational component of modern HES therapy, though long-term safety and efficacy within distinct HES subtypes warrant further investigation.

Targeting the TGF-β Pathway to Overcome Resistance to Immune Checkpoint Inhibitors in Microsatellite Stable Metastatic Colorectal Cancer: A Systematic Review and Pooled Analysis of Efficacy and Tumor Microenvironment Modulation Aprizal Satria; Norman Djamaludin; Yenny Dian Andayani; Mediarty Syahrir
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 9 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i9.1395

Background: The clinical utility of immune checkpoint inhibitors (ICIs) in metastatic colorectal cancer (mCRC) is restricted to a minority of tumors with mismatch repair deficiency. The vast majority, classified as microsatellite stable (MSS), display profound resistance driven by an immunosuppressive tumor microenvironment (TME) orchestrated by transforming growth factor-β (TGF-β). This study aimed to synthesize the evidence for combining TGF-β pathway inhibitors with ICIs to reverse this resistance. Methods: A systematic search of PubMed, Embase, Cochrane Library, and major oncology conference abstracts was conducted through December 2024 for preclinical and clinical studies evaluating TGF-β inhibition combined with ICIs in CRC. Due to the non-randomized nature of the clinical evidence, a pooled analysis of the single-arm objective response rate (ORR) was performed using a random-effects model. Progression-free survival (PFS), duration of response (DoR), and TME modulation were synthesized narratively. Results: Seven studies (four preclinical, three early-phase clinical) met the inclusion criteria. In the pooled analysis of 218 patients with predominantly MSS-mCRC from three clinical trials, the combination therapy yielded a pooled ORR of 14.2% (95% Confidence Interval [CI]: 9.1% – 20.2%), with moderate heterogeneity (I² = 38%). This represents a clinically meaningful improvement over the expected <1% response rate to ICI monotherapy in this population. Narrative synthesis of survival data indicated a median PFS ranging from 2.5 to 3.7 months and a promising median DoR exceeding 10 months in responders. Preclinical data consistently demonstrated that combination therapy synergistically inhibited tumor growth by remodeling the TME, marked by increased CD8+ T-cell infiltration and reduced stromal fibrosis. Conclusion: This systematic review and pooled analysis provide the most current synthesis of evidence for targeting the TGF-β pathway in MSS-mCRC. While preliminary and based on early-phase trials, the data show that this combination strategy can induce durable responses in a subset of patients by promoting an inflamed TME. These findings strongly support the continued investigation of this approach in biomarker-driven, randomized controlled trials.

Targeting the TGF-β Pathway to Overcome Resistance to Immune Checkpoint Inhibitors in Microsatellite Stable Metastatic Colorectal Cancer: A Systematic Review and Pooled Analysis of Efficacy and Tumor Microenvironment Modulation Aprizal Satria; Norman Djamaludin; Yenny Dian Andayani; Mediarty Syahrir
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 9 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i9.1395

Background: The clinical utility of immune checkpoint inhibitors (ICIs) in metastatic colorectal cancer (mCRC) is restricted to a minority of tumors with mismatch repair deficiency. The vast majority, classified as microsatellite stable (MSS), display profound resistance driven by an immunosuppressive tumor microenvironment (TME) orchestrated by transforming growth factor-β (TGF-β). This study aimed to synthesize the evidence for combining TGF-β pathway inhibitors with ICIs to reverse this resistance. Methods: A systematic search of PubMed, Embase, Cochrane Library, and major oncology conference abstracts was conducted through December 2024 for preclinical and clinical studies evaluating TGF-β inhibition combined with ICIs in CRC. Due to the non-randomized nature of the clinical evidence, a pooled analysis of the single-arm objective response rate (ORR) was performed using a random-effects model. Progression-free survival (PFS), duration of response (DoR), and TME modulation were synthesized narratively. Results: Seven studies (four preclinical, three early-phase clinical) met the inclusion criteria. In the pooled analysis of 218 patients with predominantly MSS-mCRC from three clinical trials, the combination therapy yielded a pooled ORR of 14.2% (95% Confidence Interval [CI]: 9.1% – 20.2%), with moderate heterogeneity (I² = 38%). This represents a clinically meaningful improvement over the expected <1% response rate to ICI monotherapy in this population. Narrative synthesis of survival data indicated a median PFS ranging from 2.5 to 3.7 months and a promising median DoR exceeding 10 months in responders. Preclinical data consistently demonstrated that combination therapy synergistically inhibited tumor growth by remodeling the TME, marked by increased CD8+ T-cell infiltration and reduced stromal fibrosis. Conclusion: This systematic review and pooled analysis provide the most current synthesis of evidence for targeting the TGF-β pathway in MSS-mCRC. While preliminary and based on early-phase trials, the data show that this combination strategy can induce durable responses in a subset of patients by promoting an inflamed TME. These findings strongly support the continued investigation of this approach in biomarker-driven, randomized controlled trials.

Effectiveness of Nigella sativa Addition against TNF-Alpha in Stage III and IV Breast Cancer Undergoing Doxorubicin and Cyclophosphamide Chemotherapy at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia Friyoga Syahril; Wirdah, Aisyah; Nur Qodir; Irfanuddin; Irsan Saleh; Yenny Dian Andayani; Mediarty; Norman Djamaluddin
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 8 No. 2 (2024): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v8i2.924

Background: Breast cancer is a malignancy caused by the continuous uncontrolled growth of the component cells of the ducts or lobules of the breast gland. Globally, breast cancer is the second leading cause of death in women. Nigella sativa contains substances thymoquinone. Thymoquinone can inhibit the progression of cancer through anti-inflammatory, anti-oxidant mechanisms, inhibit proliferation, trigger apoptosis, and prevent angiogenesis. Chronic inflammation in breast cancer is mediated by one of them is TNF-alpha tumors. Elevated levels of TNF-α have a significant association with poor prognosis and progression of breast cancer. This study aims to determine the effectiveness of the additional Nigella sativa in declining TNF-α levels in breast cancer patients at Dr. Mohammad Hoesin General Hospital Palembang. Methods: This research used a randomized, open clinical trial design, which was carried out at the internal medicine hematology-oncology medical polyclinic and the surgical oncology polyclinic of Dr. Mohammad Hoesin General Hospital Palembang from January 2023 to October 2023. Data processing for data analysis used SPSS version 26 for Windows. Results: There were 36 research subjects followed during the study period and received Doxorubicin chemotherapy and cyclophosphamide (AC), which were divided into treatment groups of 18 people (chemotherapy with the addition of Nigella sativa @600 mg 2x2 capsule/ day and a control group of 18 people. A TNF-alpha examination was carried out before and after to assess the comparison before and after. From the results, it was found that TNF-alpha levels in the treatment group showed a decrease in TNF-alpha with a p-value <0.001. Conclusion: The addition of Nigella sativa has the effect of reducing TNF-alpha in breast cancer patients receiving AC chemotherapy at Dr. Mohammad Hoesin General Hospital, Palembang.

Effectiveness of Nigella sativa Addition against TNF-Alpha in Stage III and IV Breast Cancer Undergoing Doxorubicin and Cyclophosphamide Chemotherapy at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia Friyoga Syahril; Wirdah, Aisyah; Nur Qodir; Irfanuddin; Irsan Saleh; Yenny Dian Andayani; Mediarty; Norman Djamaluddin
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 8 No. 2 (2024): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v8i2.924

Background: Breast cancer is a malignancy caused by the continuous uncontrolled growth of the component cells of the ducts or lobules of the breast gland. Globally, breast cancer is the second leading cause of death in women. Nigella sativa contains substances thymoquinone. Thymoquinone can inhibit the progression of cancer through anti-inflammatory, anti-oxidant mechanisms, inhibit proliferation, trigger apoptosis, and prevent angiogenesis. Chronic inflammation in breast cancer is mediated by one of them is TNF-alpha tumors. Elevated levels of TNF-α have a significant association with poor prognosis and progression of breast cancer. This study aims to determine the effectiveness of the additional Nigella sativa in declining TNF-α levels in breast cancer patients at Dr. Mohammad Hoesin General Hospital Palembang. Methods: This research used a randomized, open clinical trial design, which was carried out at the internal medicine hematology-oncology medical polyclinic and the surgical oncology polyclinic of Dr. Mohammad Hoesin General Hospital Palembang from January 2023 to October 2023. Data processing for data analysis used SPSS version 26 for Windows. Results: There were 36 research subjects followed during the study period and received Doxorubicin chemotherapy and cyclophosphamide (AC), which were divided into treatment groups of 18 people (chemotherapy with the addition of Nigella sativa @600 mg 2x2 capsule/ day and a control group of 18 people. A TNF-alpha examination was carried out before and after to assess the comparison before and after. From the results, it was found that TNF-alpha levels in the treatment group showed a decrease in TNF-alpha with a p-value <0.001. Conclusion: The addition of Nigella sativa has the effect of reducing TNF-alpha in breast cancer patients receiving AC chemotherapy at Dr. Mohammad Hoesin General Hospital, Palembang.

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