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HemaSphere Nov 2023The oral activin A receptor type I, Janus kinase 1 (JAK1), and JAK2 inhibitor momelotinib demonstrated symptom, spleen, and anemia benefits in intermediate- and...
The oral activin A receptor type I, Janus kinase 1 (JAK1), and JAK2 inhibitor momelotinib demonstrated symptom, spleen, and anemia benefits in intermediate- and high-risk myelofibrosis (MF). Post hoc analyses herein evaluated the efficacy and safety of momelotinib in patients with MF and thrombocytopenia (platelet counts <100 × 10/L) from randomized phase 3 studies: MOMENTUM (momelotinib versus danazol; JAK inhibitor experienced); SIMPLIFY-1 (momelotinib versus ruxolitinib; JAK inhibitor naïve); and SIMPLIFY-2 (momelotinib versus best available therapy; JAK inhibitor experienced); these studies were not statistically powered to assess differences in thrombocytopenic subgroups, and these analyses are descriptive. The treatment effect of momelotinib versus ruxolitinib on week 24 response rates (spleen volume reduction ≥35%/Total Symptom Score reduction ≥50%/transfusion independence) was numerically comparable or better in thrombocytopenic patients versus the overall JAK inhibitor naive population; rates were preserved with momelotinib in thrombocytopenic patients but attenuated with ruxolitinib (momelotinib: 27%/28%/67% overall versus 39%/35%/61% in thrombocytopenic group; ruxolitinib: 29%/42%/49% overall versus 0%/22%/39% in thrombocytopenic group, respectively). In contrast to ruxolitinib, momelotinib maintained high dose intensity throughout the treatment. In the JAK inhibitor experienced population, thrombocytopenic patients had the following: (1) numerically higher symptom and transfusion independence response rates with momelotinib than in control arms; and (2) preserved spleen, symptom, and transfusion independence response rates with momelotinib relative to the overall study populations. The safety profile of momelotinib in thrombocytopenic patients was also consistent with the overall study population. In summary, momelotinib represents a safe and effective treatment option for patients with MF and moderate-to-severe thrombocytopenia.
PubMed: 37908862
DOI: 10.1097/HS9.0000000000000963 -
HemaSphere Nov 2023Myelofibrosis (MF) is a chronic myeloproliferative neoplasm that typically manifests with debilitating symptoms that progressively worsen, negatively impacting patients'...
Myelofibrosis (MF) is a chronic myeloproliferative neoplasm that typically manifests with debilitating symptoms that progressively worsen, negatively impacting patients' quality of life. Fatigue is a multifactorial and burdensome MF-related symptom due to its severity, persistence, and prevalence, with anemia a contributing factor and major unmet need. Clinical trials of the Janus kinase (JAK)1/JAK2/activin A receptor type 1 inhibitor momelotinib have shown consistent anemia benefits, in addition to improvements in MF-related symptoms. The phase 3 MOMENTUM trial in symptomatic and anemic patients met its primary end point, with a greater proportion having a Myelofibrosis Symptom Assessment Form (MFSAF) Total Symptom Score (TSS) reduction ≥50% at week 24 with momelotinib versus danazol. To support the positive primary end point result, we conducted longitudinal, responder, and time-to-event analyses of patient-reported outcomes from MOMENTUM, as measured by the MFSAF, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Patient-Reported Outcomes Measurement Information System (PROMIS) assessments. These analyses demonstrated rapid and durable response benefits with momelotinib, with achievement of first TSS response by day 29 and continued improvement over time. Improvements favored momelotinib versus danazol for each MFSAF individual item, and greater improvements were observed for disease- and cancer-related fatigue and physical functioning at week 24, with significant results for multiple items/domains across the 3 assessments. These findings are consistent in demonstrating that momelotinib provides substantial symptom benefit.
PubMed: 37901848
DOI: 10.1097/HS9.0000000000000966 -
Drugs Nov 2023Adenomyosis, characterized by the growth of endometrial tissue within the uterine wall, poses significant challenges in treatment. The literature primarily focuses on... (Review)
Review
Adenomyosis, characterized by the growth of endometrial tissue within the uterine wall, poses significant challenges in treatment. The literature primarily focuses on managing abnormal uterine bleeding (AUB) and dysmenorrhea, the main symptoms of adenomyosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) and tranexamic acid provide limited support for mild symptoms or symptom re-exacerbation during hormone therapy. The levonorgestrel-releasing intrauterine system (LNG-IUS) is commonly employed in adenomyosis management, showing promise in symptom improvement and reducing uterine size, despite the lack of standardized guidelines. Dienogest (DNG) also exhibits potential benefits, but limited evidence hinders treatment recommendations. Danazol, while effective, is limited by androgenic side effects. Combined oral contraceptives (COCs) may be less effective than progestins but can be considered for contraception in young patients. Gonadotropin-releasing hormone (GnRH) agonists effectively manage symptoms but induce menopausal symptoms with prolonged use. GnRH antagonists are a recent option requiring further investigation. Aromatase inhibitors (AIs) show promise in alleviating AUB and pelvic pain, but their safety necessitates exploration and limited use within trials for refractory patients. This review highlights the complexity of diagnosing adenomyosis, its coexistence with endometriosis and uterine leiomyomas, and its impact on fertility and quality of life, complicating treatment decisions. It emphasizes the need for research on guidelines for medical management, fertility outcomes, long-term effects of therapies, and exploration of new investigational targets. Future research should optimize therapeutic strategies, expand our understanding of adenomyosis and its management, and establish evidence-based guidelines to improve patient outcomes and quality of life.
Topics: Female; Humans; Adenomyosis; Quality of Life; Uterus; Progestins; Gonadotropin-Releasing Hormone; Levonorgestrel
PubMed: 37837497
DOI: 10.1007/s40265-023-01957-7 -
Journal of Clinical Medicine Sep 2023Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments... (Review)
Review
Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments have been proposed, but still, no guidelines directing the management of adenomyosis are available. While a hysterectomy is typically regarded as the definitive treatment for adenomyosis, the scarcity of high-quality data leaves patients desiring fertility with limited conservative options. Based on the available data, the levonorgestrel-IUD appears to offer the most favorable outcomes. Other treatments, including GnRH antagonists, dienogest, prolactin, and oxytocin modulators, show promise; however, further data are required to establish their efficacy definitively. Furthermore, there are many emerging therapies that have been developed that seem worthy of consideration in the near future. The aim of this narrative review was to explore the current medical treatments available for adenomyosis and to provide a glimpse of future therapies under assessment. For this scope, we performed a literature search on PubMed and Medline from incept to September 2022 using the keywords: "medical treatment", "non-steroidal anti-inflammatory", "progesterone intrauterine device", "dienogest", "combined oral contraceptives", "gonadotropin releasing hormone agonist", "gonadotropin releasing hormone antagonist", "danazol", "aromatase inhibitors", "ulipristal acetate", "anti-platelet therapy", "dopamine", "oxytocin antagonists", "STAT3", "KRAS", "MAPK", "micro-RNA", "mifepristone", "valproic acid", "levo-tetrahydropalamatine", and "andrographolide". The search was limited to articles in English, with subsequent screening of abstracts. Abstracts were screened to select relevant studies.
PubMed: 37834773
DOI: 10.3390/jcm12196130 -
Journal of Personalized Medicine Aug 2023Uterine arteriovenous malformation (AVM) is associated with a risk of massive uterine bleeding. Although uterine artery embolization remains the first-line treatment for...
Uterine arteriovenous malformation (AVM) is associated with a risk of massive uterine bleeding. Although uterine artery embolization remains the first-line treatment for AVM, there has been a recent exploration of pharmacological options. Danazol is known to reduce blood flow to the uterus; however, our understanding of its therapeutic efficacy for AVM remains limited. Herein, we present the results of danazol use in patients with uterine AVM. We retrospectively reviewed the medical records of patients who received danazol for the treatment of AVM between January 2013 and November 2022. The cohort comprised 10 patients who developed AVM after dilatation and curettage (D&C), abortion, or cesarean section. Danazol was administered twice daily at a total dose of 400 mg/day, and was employed for AVM treatment in hemodynamically stable patients who provided consent and were devoid of massive bleeding. Outpatient follow-ups (ultrasound measurements of AVM size and symptom assessment) were performed every 2 weeks. AVM was successfully treated with danazol in most patients with no adverse event. Eight postabortal patients had complete resolution of AVM after an average of 45 days (range 14-70 days). Of two patients who developed AVM after a cesarean section, one experienced AVM reduction, and the other developed massive bleeding, requiring emergency uterine artery embolization. In light of these outcomes, danazol can be potentially prioritized over uterine artery embolization in the treatment of AVM after abortion in hemodynamically stable patients.
PubMed: 37763057
DOI: 10.3390/jpm13091289 -
Healthcare (Basel, Switzerland) Sep 2023This real-world analysis investigated the characteristics and treatment patterns of patients with hereditary angioedema (HAE) in Italy using the administrative data of...
This real-world analysis investigated the characteristics and treatment patterns of patients with hereditary angioedema (HAE) in Italy using the administrative data of health units across Italy. Patients were identified via exemption code or HAE-specific treatments (thus, all known forms, type I, II and, III, were included). The index date was that of first prescription of HAE treatments within the inclusion period (01/2010-06/2021) or of the date of exemption. The number of HAE patients included was 148 (43.2% male, mean age 43.3 years). Gastrointestinal disorders affected 36.5% patients, hypertension affected 28.4%, hypercholesterolemia affected 11.5%, and depression affected 9.5%. The frequent gastrointestinal involvement was further confirmed by the use of antiemetics and systemic antihistamines that doubled after the index date. Among patients enrolled by treatment ( = 125), = 105 (84%) were receiving a treatment for acute attacks. This analysis provided insights into the characterization of patients with HAE and their management in Italian clinical practice, suggesting that an unmet therapeutic need could be present for such patients in terms of the clinical burden.
PubMed: 37761706
DOI: 10.3390/healthcare11182509 -
ERJ Open Research Sep 2023Telomere dysfunction can underly the development of idiopathic pulmonary fibrosis (IPF), and recent work suggests that patients with telomere syndromes might benefit...
BACKGROUND
Telomere dysfunction can underly the development of idiopathic pulmonary fibrosis (IPF), and recent work suggests that patients with telomere syndromes might benefit from treatment with androgens, such as danazol.
METHODS
This was a prospective observational cohort study. 50 patients with IPF received off-label treatment with danazol after they showed progressive disease under treatment with pirfenidone or nintedanib. The primary outcome was the difference in yearly decline in forced vital capacity (FVC) prior to (pre) and after (post) start of treatment with danazol.
RESULTS
There was no significant difference in FVC-decline between 1 year pre and 1 year post start of danazol treatment (mean decline pre 395 mL (95% confidence interval (CI) 290-500) compared to post 461 mL (95% CI 259-712); p=0.46; paired t-test). 11 patients (22%) were still on danazol after 1 year, and 39 patients had stopped danazol, mainly because of side-effects (56%) or death (33%). In patients who were still using danazol after 1 year, FVC-decline significantly slowed down under danazol treatment (mean pre 512 mL (95% CI 308-716) post 198 mL (95% CI 16-380); p=0.04). Median survival post danazol was 14.9 months (95% CI 11.0-18.8).
CONCLUSION
Danazol as a treatment of last resort in patients with IPF did not lead to slowing of lung function decline and was associated with significant side-effects. It remains to be determined if earlier treatment or treatment of specific patient subgroups is beneficial.
PubMed: 37753281
DOI: 10.1183/23120541.00131-2023 -
The World Allergy Organization Journal Sep 2023Due to the lack of structured and systematic information available, the aim of this study was to describe the epidemiology, diagnosis, healthcare processes, and...
INTRODUCTION AND OBJECTIVES
Due to the lack of structured and systematic information available, the aim of this study was to describe the epidemiology, diagnosis, healthcare processes, and treatment patterns of hereditary angioedema (HAE) in Mexico. To achieve this, different data sources were consulted regarding medical literature, structured health system databases, and angioedema-specialized physicians (AEP) opinion regarding HAE.
MATERIAL AND METHODS
A mixed methods approach was conducted in 4 phases: I) systematic literature review (SLR) and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines; II) review of national health system (NHS) databases and systematic reports; III) physician survey; and IV) an epidemiologic model. ICD 10 D84.1 encoded records from the NHS were used to estimate the number of patients with HAE attended and treated during 2019. A survey was implemented to increase understanding of the clinical profile and treatments used.
RESULTS
A prevalence rate of 0.9/50 000 inhabitants was estimated for 2019. In the same year, an estimated 317 HAE type 1 patients were recorded in the NHS, aged ≥11 years old. The most frequent clinical symptoms were cutaneous edema (67.5%) and abdominal pain (47.9%). A severe episode with laryngeal edema appeared in 27.5% of cases. Acute episodes were mainly moderate to severe (77.0%), with an annual per capita frequency of emergency visits of 7.6 patient-year (range 1-12/patient-year). The main reasons for hospitalization corresponded to laryngeal facial, tongue, and abdominal edemas, representing 73.3% of annual ICD 10 D84.1 reported hospitalizations. The main treatments that patients with HAE received were fresh frozen plasma for acute attacks and danazol for short-term prophylaxis (STP).
CONCLUSIONS
Despite efforts to make HAE visible, according to this study, cases recognized and treated in the NHS represent only 16.6% of the estimated prevalence.
PubMed: 37727628
DOI: 10.1016/j.waojou.2023.100812 -
The World Allergy Organization Journal Aug 2023I have read the article titled "" by Wang et al (2022) with great interest. This study examined the change in throat microbiota and its association with laryngeal edema...
I have read the article titled "" by Wang et al (2022) with great interest. This study examined the change in throat microbiota and its association with laryngeal edema (LE) attacks and attack severity in hereditary angioedema (HAE) patients. This study demonstrated the comparative richness of Bacteroidetes and Prevotellaceae in recent LE attacks and detected positive association between the attack severity scores and Bacteroidetes richness. Nevertheless, I have some questions and concerns about the methodological design of their study. For instance, in the article, the description of HAE and HAE patients is not exactly correct. I do not also agree with the authors on the effect of long-term prophylactic danazol use in HAE patients of this study. It is very important when or how the swab was obtained after the LE attack. The last, not the least, point now is what the authors suggest to improve this dysbiosis in these HAE patients. The discussion to elaborate these points in the study could be helpful and enlightening for readers and future research in this area.
PubMed: 37577027
DOI: 10.1016/j.waojou.2023.100806 -
Medicine Aug 2023Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases, laparoscopic fertility preservation surgery is considered a common treatment for EMT. The present study aimed to evaluate the efficacy and safety of dienogest, leuprolide, danazol, gestrinone, mifepristone and levonorgestrel intrauterine system (LNG-IUS) in relieving symptoms and delaying the recurrence of EMT cysts after fertility protection surgery.
METHODS
We searched PubMed, the Cochrane Library, Web of Science, EMBase, China National Knowledge Infrastructure, VIP Database, China Biology Medicine disc, WanFang Data databases to collect randomized controlled trials (RCT) related to dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS as a follow-up treatment after fertility preserving surgery for EMT. After literature screening, data extraction and quality evaluation, effective rate, recurrence rate, pregnancy rate and adverse reaction rate were used as outcome indicators to evaluate the efficacy and safety of drugs. Evidence networks included in the study were drawn and publication bias was assessed. The drugs most likely to be the best postoperative treatment were explored through mixed comparison of different drugs and efficacy ranking.
RESULT
Effective rate: dienogest, leprerelin, gestrinone and LNG-IUS were better than placebo after EMT fertility preservation surgery; dienogest was superior to mifepristone and danazol. LNG-IUS is superior to danazol. LNG-IUS has the highest potential for improving the effectiveness of EMT symptoms. Recurrence rate: the application of dienogest, leuprolide, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was lower than that of placebo; dienogest and LNG-IUS were lower than danazol. The recurrence rate of dinorgestrel was the last place with the highest performance. Pregnancy rate: in the cases with fertility requirements, dienogest and,leuprolide were better than placebo after EMT fertility preservation surgery; dienogest was superior to danazol, gestrinone and mifepristone. Leuprolide is superior to danazol and gestrinone. The first rank of dienogest pregnancy rate was the highest. Adverse reaction rate: the application of dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was higher than that of placebo. After placebo, LNG-IUS had the highest adverse reaction rate.
CONCLUSION
For patients after fertility preserving surgery for EMT, the recurrence rate of dienogest was the last place with highest preference. The first rank of dienogest pregnancy was the highest.
Topics: Female; Humans; Endometriosis; Danazol; Gestrinone; Leuprolide; Mifepristone; Network Meta-Analysis; Levonorgestrel
PubMed: 37543781
DOI: 10.1097/MD.0000000000034496