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Allergy, Asthma, and Clinical... May 2023Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, recurring subcutaneous or submucosal swelling. Without effective therapy, HAE can...
BACKGROUND
Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, recurring subcutaneous or submucosal swelling. Without effective therapy, HAE can negatively impact patients' quality of life. Management of HAE includes on-demand treatment of attacks and short- and long-term prophylaxis (LTP) to prevent attacks. Newer therapies may be more tolerable and effective in managing HAE; however, therapies such as androgens are still widely used in some countries owing to their relative ease of access and adequate disease control for some patients. This study evaluated the characteristics, treatment patterns, clinical outcomes, and healthcare resource utilization of a multinational cohort of patients with HAE, with a focus on understanding reasons for recommending or discontinuing available therapies.
METHODS
A retrospective chart review was conducted at 12 centers in six countries and included data from patients with HAE type 1 or 2 who were ≥ 12 years of age at their first clinical visit. The relationship between LTP use and attack rates was evaluated using a multivariable Poisson regression model. Data were collected between March 2018 and July 2019.
RESULTS
Data from 225 patients were collected (62.7% female, 86.2% White, 90.2% type 1); 64.4% of patients had their first HAE-related visit to the center prior to or during 2014. Treatment patterns varied between countries. Overall, 85.8% of patients were prescribed on-demand treatment and 53.8% were prescribed LTP, most commonly the androgen danazol (53.7% of patients who used LTP). Plasma-derived C1 inhibitor (Cinryze) was used by 29.8% of patients for LTP. Patients who received LTP had a significantly lower rate of HAE attacks than patients who did not receive any LTP (incidence rate ratio (95% confidence interval) 0.90 (0.84-0.96)). Androgens were the most commonly discontinued therapy (51.3%), with low tolerability cited as the most frequent reason for discontinuation (50.0%).
CONCLUSIONS
Overall, findings from this study support the use of LTP in the prevention of HAE attacks; a lower rate of attacks was observed with LTP compared with no LTP. However, the type of LTP used varied between countries, with tolerability and accessibility to specific treatments playing important roles in management decision-making.
PubMed: 37248521
DOI: 10.1186/s13223-023-00795-2 -
F&S Reports Jun 2023The development of highly potent gonadotropin-releasing hormone agonists (GnRHa) allowed for a significant addition to options for the medical management of symptomatic...
The development of highly potent gonadotropin-releasing hormone agonists (GnRHa) allowed for a significant addition to options for the medical management of symptomatic endometriosis. Pituitary GnRH receptor down-regulation leads to a hypogonadotropic and secondary hypoestrogenic state resulting in lesion regression and symptom improvement. There may be an additional effect of these agents on the inflammatory processes associated with endometriosis as well. This is a review of critical milestones in the clinical application of these agents. Most initial trials of various GnRHa employed danazol as a control and demonstrated general equivalence in reducing symptoms and extent of lesions but without hyperandrogenic side effects and adverse metabolic changes induced by the latter. Short-acting GnRHa is administered intranasally or subcutaneously. Longer-acting preparations are administered intramuscularly or as subcutaneous implants. GnRHa also decrease symptom recurrence rates after surgical management. The hypoestrogenic side effects, including bone mineral density loss and vasomotor symptoms, have limited the duration of use of these agents alone to six months. The use of an appropriate add-back allows for the mitigation of side effects while maintaining efficacy and allowing extension of use for up to 12 months. There is a limited amount of data regarding the use of GnRHa in adolescents out of concern for the effect on developing bone. These agents should be used with caution in this group. The lack of dose flexibility, need for parental administration, and side effect profiles represent drawbacks to GnRHa use. The development of oral GnRH antagonists with short half-lives, variable dosing, and decreased side effects represents an exciting alternative.
PubMed: 37223763
DOI: 10.1016/j.xfre.2022.11.009 -
The Journal of Allergy and Clinical... Aug 2023Detailed demographic data on people with hereditary angioedema (HAE) and acquired C1 inhibitor deficiency in the United Kingdom are relatively limited. Better...
BACKGROUND
Detailed demographic data on people with hereditary angioedema (HAE) and acquired C1 inhibitor deficiency in the United Kingdom are relatively limited. Better demographic data would be beneficial in planning service provision, identifying areas of improvement, and improving care.
OBJECTIVE
To obtain more accurate data on the demographics of HAE and acquired C1 inhibitor deficiency in the United Kingdom, including treatment modalities and services available to patients.
METHODS
A survey was distributed to all centers in the United Kingdom that look after patients with HAE and acquired C1 inhibitor deficiency to collect these data.
RESULTS
The survey identified 1152 patients with HAE-1/2 (58% female and 92% type 1), 22 patients with HAE with normal C1 inhibitor, and 91 patients with acquired C1 inhibitor deficiency. Data were provided by 37 centers across the United Kingdom. This gives a minimum prevalence of 1:59,000 for HAE-1/2 and 1:734,000 for acquired C1 inhibitor deficiency in the United Kingdom. A total of 45% of patients with HAE were on long-term prophylaxis (LTP) with the most used medication being danazol (55% of all patients on LTP). Eighty-two percent of patients with HAE had a home supply of acute treatment with C1 inhibitor or icatibant. A total of 45% of patients had a supply of icatibant and 56% had a supply of C1 inhibitor at home.
CONCLUSIONS
Data obtained from the survey provide useful information about the demographics and treatment modalities used in HAE and acquired C1 inhibitor deficiency in the United Kingdom. These data are useful for planning service provision and improving services for these patients.
Topics: Humans; Female; Male; Angioedemas, Hereditary; Complement C1 Inhibitor Protein; Danazol; United Kingdom; Surveys and Questionnaires
PubMed: 37146882
DOI: 10.1016/j.jaip.2023.04.035 -
Cureus Apr 2023Endometriosis, defined as the development of endometrial tissue outside of the uterine cavity, is a common gynecological disorder. The prevalence of pelvic endometriosis... (Review)
Review
Endometriosis, defined as the development of endometrial tissue outside of the uterine cavity, is a common gynecological disorder. The prevalence of pelvic endometriosis approaches 6%-10% in the general female population, and in women with pain, infertility, or both, the frequency is 35%-50%. The gold standard recommended process for diagnosing endometriosis is laparoscopy, an invasive surgical procedure, with or without histologic verification. The currently available nonsurgical treatments include oral contraceptives (estrogen-progestogen preparations), progestogen preparations (containing progesterone derivatives), androgenic hormones (danazol), and gonadotropin-releasing hormone (GnRH) agonists and antagonists. Two GnRH types have been discovered in mammals, GnRH I and GnRH II. In particular, GnRH I is released by the hypothalamus; however, it can be present in various tissues and organs of the body, including neural tissue, where it exerts neuroendocrine, autocrine, and paracrine actions in the peripheral and central nervous system (CNS). Interestingly, another GnRH isoform, GnRH III, has been identified, which has 60% similarity with GnRH I from which it varies by four amino acids. This peptide has been shown to have a significant role in reproduction, specifically in gametogenesis and steroidogenesis. Further research is needed to identify innovative treatment options for endometriosis, such as the therapeutic exogenous administration of GnRH II or antagonists of the GnRH I receptor. In this review, we examined the role of GnRH in endometriosis, outlining the specific actions of GnRH and GnRH receptors (GnRHRs). The innovative use of GnRH analogs and antagonists in the treatment of endometriosis is also discussed.
PubMed: 37122983
DOI: 10.7759/cureus.38136 -
Blood Advances Jul 2023Momelotinib is the first inhibitor of Janus kinase 1 (JAK1) and JAK2 shown to also inhibit activin A receptor type 1 (ACVR1), a key regulator of iron homeostasis, and...
Momelotinib is the first inhibitor of Janus kinase 1 (JAK1) and JAK2 shown to also inhibit activin A receptor type 1 (ACVR1), a key regulator of iron homeostasis, and has demonstrated improvements in splenomegaly, constitutional symptoms, and anemia in myelofibrosis (MF). This long-term analysis pooled data from 3 randomized phase 3 studies of momelotinib (MOMENTUM, SIMPLIFY-1, and SIMPLIFY-2), representing MF disease from early (JAK inhibitor-naive) to late (JAK inhibitor-experienced) stages. Patients in the control arms (danazol in MOMENTUM, ruxolitinib in SIMPLIFY-1, and best available therapy in SIMPLIFY-2) could cross over to receive momelotinib at the end of the 24-week randomized period, and all patients could continue momelotinib treatment after the completion of these studies via an extended access protocol (XAP). Across these studies, 725 patients with MF received momelotinib; 12% remained on therapy for ≥5 years, with a median treatment exposure of 11.3 months (range, 0.1-90.4 months). The most common nonhematologic treatment-emergent adverse event (AE) occurring in ≥20% of patients was diarrhea (any grade, 27% and grade ≥3, 3%). Any-grade thrombocytopenia, anemia, and neutropenia occurred in 25%, 23%, and 7% of patients, respectively. The most common reason for momelotinib discontinuation was thrombocytopenia (4% discontinuation rate). The incidence of AEs of clinical importance (eg, infections, malignant transformation, peripheral neuropathy, and hemorrhage) did not increase over time. This analysis of one of the largest randomized trial databases for a JAK inhibitor to date in MF demonstrated a consistent safety profile of momelotinib without long-term or cumulative toxicity. These trials were registered at www.clinicaltrials.gov as: MOMENTUM (#NCT04173494), SIMPLIFY-1 (#NCT01969838), SIMPLIFY-2 (#NCT02101268), and XAP (#NCT03441113).
Topics: Humans; Primary Myelofibrosis; Janus Kinase Inhibitors; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Anemia; Thrombocytopenia
PubMed: 37042865
DOI: 10.1182/bloodadvances.2022009311 -
HemaSphere Apr 2023
PubMed: 36999006
DOI: 10.1097/HS9.0000000000000867 -
Therapeutic Advances in Reproductive... 2023The newly released specify that adolescents should be offered menstrual suppression as part of their treatment plans to suppress menses and alleviate dysphoria, provide... (Review)
Review
UNLABELLED
The newly released specify that adolescents should be offered menstrual suppression as part of their treatment plans to suppress menses and alleviate dysphoria, provide contraception, or improve irregular bleeding on testosterone therapy. This is a review of current evidence-based options for reversible interventions for menstrual suppression in adolescents with gender dysphoria or incongruence. Shared decision-making should be used by the clinician at all times, and the clinician should be intentional in prioritizing the patient's stated needs and desires when offering interventions. No method should be withheld due to the experience of gender incongruence alone. Contraceptive options offering menstrual suppression include depot-medroxyprogesterone acetate, levonorgestrel intrauterine systems, progestin-only contraceptive pills, and combined hormonal contraceptives. Non-contraceptive options include norethindrone acetate, oral medroxyprogesterone acetate, gonadotropin-releasing hormone analogues/agonists, and danazol. Certain patients may also benefit from non-pharmacologic interventions, such as specialty menstrual underwear.
PLAIN LANGUAGE SUMMARY
Newly released recommendations for the care of teens and young adults with gender dysphoria or incongruence specifically recommend using medications to get rid of menstrual periods if desired or medically necessary. Patients may ask for this to help improve dysphoria, as a feature they want in birth control, or simply because they do not want to have periods. Because temporarily getting rid of periods is something that doctors can do for any patient old enough to have periods, patients with gender dysphoria should also be able to have their periods temporarily stopped using medications if requested. Doctors should ensure that they always help the patient make a decision that is right for them instead of prescribing what they think is right without considering the patient's input. Options for temporarily getting rid of periods can include birth control, such as oral contraceptive pills, patches, or rings; intrauterine devices; or shots, and it can also be done with things that are not birth control, such a progesterone pills or puberty blockers. Finally, some patients may only need improved period hygiene with period underwear to feel better in their bodies.
PubMed: 36938373
DOI: 10.1177/26334941231158251 -
Blood Research Apr 2023Myelofibrosis (MF) includes primary MF, post-essential thrombocythemia MF, and post-polycythemia vera MF. MF is a progressive myeloid neoplasm characterized by... (Review)
Review
Myelofibrosis (MF) includes primary MF, post-essential thrombocythemia MF, and post-polycythemia vera MF. MF is a progressive myeloid neoplasm characterized by ineffective clonal hematopoiesis, extramedullary hematopoiesis, a reactive bone marrow environment resulting in reticulin deposition and fibrosis, and a propensity for leukemia transformation. The identification of driver mutations in , , and has contributed to a better understanding of disease pathogenesis and has led to the development of MF-specific therapies, such as JAK2 inhibitors. Despite the fact that ruxolitinib and fedratinib have been clinically developed and approved, their use is limited due to adverse effects such as anemia and thrombocytopenia. Recently, pacritinib has been approved for a group of thrombocytopenic patients with significant unmet clinical needs. In symptomatic and anemic patients with prior JAK inhibitor exposure, momelotinib was superior to danazol in preventing exacerbation of anemia and in controlling MF-associated signs and symptoms, such as spleen size. Although the development of JAK inhibitors is remarkable, modifying the natural course of the disease remains a priority. Therefore, many novel treatments are currently under clinical development. Agents targeting bromodomain and extra-terminal protein, anti-apoptotic protein Bcl-xL, and phosphatidylinositol-3-kinase delta have been studied in combination with JAK inhibitors. These combinations have been employed in both the frontline and "add-on" approaches. In addition, several agents are being studied as monotherapies for ruxolitinib-resistant or -ineligible patients. We reviewed several new MF treatments in the advanced stages of clinical development and treatment options for cytopenic patients.
PubMed: 36891574
DOI: 10.5045/br.2023.2023012 -
La Revue de Medecine Interne Jul 2023Hereditary angioedema, with or without deficient C1 inhibitor level or function, is a rare disease characterized by recurrent attacks of noninflammatory subcutaneous... (Review)
Review
Hereditary angioedema, with or without deficient C1 inhibitor level or function, is a rare disease characterized by recurrent attacks of noninflammatory subcutaneous and/or submucosal edema. It may be life-threatening and substantially affects quality of life. Attacks may be spontaneous or induced, in a setting of emotional stress, by infections or physical trauma, in particular. As the key mediator is bradykinin, this angioedema does not respond to the usual treatments of mast cell-mediated angioedema (antihistamines, corticosteroids, adrenaline), which is much more frequent. Therapeutic management of hereditary angioedema first consists in treating severe attacks with a selective B2 bradykinin receptor antagonist or a C1 inhibitor concentrate. The latter or an attenuated androgen (danazol) can be used for short-term prophylaxis. Therapeutic solutions conventionally proposed for long-term prophylaxis (danazol, antifibrinolytics [tranexamic acid], C1 inhibitor concentrate) vary in efficacy and/or pose problems of safety or ease of use. Kallikrein inhibitors (subcutaneous lanadelumab, oral berotralstat) recently made available as disease-modifying treatment constitute an important advance in long-term prophylaxis of hereditary angioedema attacks. The advent of these new drugs is accompanied by a new ambition for patients: optimize control of the disease and thereby minimize its impact on quality of life.
Topics: Humans; Angioedemas, Hereditary; Danazol; Quality of Life; Angioedema; Bradykinin
PubMed: 36872215
DOI: 10.1016/j.revmed.2023.01.020 -
Revista Alergia Mexico (Tecamachalco,... Feb 2023Hereditary angioedema is an autosomal dominant genetic disease, associated with increased levels of bradykinin. It is classified into 3 types according to the C1-INH...
INTRODUCTION
Hereditary angioedema is an autosomal dominant genetic disease, associated with increased levels of bradykinin. It is classified into 3 types according to the C1-INH enzyme. The diagnosis is clinical and laboratory. Its treatment is divided into short- and long-term and crisis prophylaxis.
CASE REPORT
40-year-old female patient who came to the emergency service for labial edema without resolution with corticosteroids. The tests for IgE, C4 and C1 esterase inhibitors had a low result. She currently uses danazol prophylactically and fresh frozen plasma in crises.
CONCLUSIONS
Since it is a disease that considerably affects the quality of life, hereditary angioedema must be diagnosed and an effective treatment plan made to prevent or reduce its complications.
Topics: Female; Humans; Adult; Angioedemas, Hereditary; Bradykinin; Quality of Life; Danazol
PubMed: 36869013
DOI: 10.29262/ram.v69i3.1057