Expert Opinion on Pharmacotherapy最新文献

Introduction: Palovarotene is a retinoic acid receptor gamma agonist that was studied in phase-2 and phase-3 clinical trials for the inhibition of new heterotopic ossification (HO) in fibrodysplasia ossificans progressiva (FOP). Despite numerous setbacks and regulatory delays, palovarotene is now the first approved FOP treatment in the U.S.A. Canada and Australia but remains unapproved in Europe where concerns surrounding the drug and its path to regional market authorization persist.

Areas covered: The developmental history of palovarotene and an overview of the clinical trials and the regulatory approval journey are discussed by global FOP experts.

Expert opinion: While post hoc analyses indicate that palovarotene may have modest benefits for the inhibition of new HO formation in FOP, a number of limitations and concerns remain about its generalized use. Although the long-term risks and benefits of treatment with palovarotene remain unknown, the regional approval of palovarotene marks a milestone for the FOP community at the very beginning of a new era of clinical trials.

Introduction: Dysmenorrhea is a painful symptom associated with uterine contractions and menstrual bleeding and is treated by administering analgesic drugs. Since progesterone receptors (PRs) have a major role in regulating uterine tissues (myometrium and endometrium) physiology, oral contraceptives are used off-label for treating primary or secondary dysmenorrhea. The development of selective progesterone receptor modulators (SPRMs), a class of synthetic steroids with agonistic, antagonistic, or mixed effects in targeting PRs in different tissues, stimulated their possible clinical use for treating secondary dysmenorrhea related to uterine diseases (endometriosis, adenomyosis, uterine fibroids).

Areas covered: The present review examines the development of the clinical trials and observational studies done with the different SPRMs for the treatment of dysmenorrhea in patients with uterine diseases.

Expert opinion: Mifepristone, telapristone acetate and vilaprisan have antagonistic activity on PRs, whereas ulipristal acetate and asoprisnil have both potent antagonist and partial agonist effects.Since no studies have been done on primary dysmenorrhea, the different SPRMs have been evaluated in the treatment of endometriosis, adenomyosis and uterine fibroid-related dysmenorrhea.

Introduction: Osteoporosis is a metabolic skeletal disease characterized by low bone mass and strength, and increased risk for fragility fractures. It is a major health issue in aging populations, due to fracture-associated increased disability and mortality. Antiresorptive treatments are first line choices in most of the cases.

Areas covered: Bone homeostasis is complicated, and multiple factors can compromise skeletal health. Bone turnover is a continuous process regulated by the coupled activities of bone cells that preserves skeletal strength and integrity. Imbalance between bone resorption and formation leads to bone loss and increased susceptibility to fractures. Antiresorptives prevent bone loss and reduce fracture risk, by targeting osteoclastogenesis and osteoclast function and survival. Their major drawback is the coupling of osteoclast and osteoblast activity, due to which any reduction in bone resorption is followed by suppression of bone formation.

Expert opinion: During the last couple of decades significant progress has been made in understanding of the genetic and molecular basis of osteoporosis. Critical pathways and key molecules that mediate regulation of bone resorption have been identified. These factors may underpin novel therapeutic avenues for osteoporosis, but their potential for translation into clinical applications is yet to be tested.

Introduction: BPH/male LUTS is a prevalent condition in the aging male population with multifactorial pathophysiology. Pharmacotherapy remains the cornerstone of treatment in patients who fail conservative treatment. 5-α-Reductase inhibitors (5-ARIs) are the only class of medication shown to reduce the risk of acute retention and BPH-related surgery and, thus, are commonly used along with other "short acting" medications in combination treatments.

Areas covered: Combination treatments with α-blockers and 5-ARIs have been investigated extensively in high quality trials that prove the long-term efficacy of such treatments with acceptable rates of side effects. Combination treatments involving 5-ARIs and other classes of medications (anticholinergics, b3 agonists, PDEI) have been shown to be beneficial in the short term and but studies with longer follow-up periods are required to fully establish their role.

Expert opinion: A-blocker/5-ARI combination treatment is a reasonable approach for patients with male LUTS/BPH who are at increased risk of disease progression or have incomplete response to monotherapies. Other combination treatments with 5-ARIs and PDEI or anticholinergics/β-3 agonists can be tried based on predominant symptoms or side effect profile, but patients should be informed about the lack of long-term data.

Introduction: Atherogenic dyslipidaemia with increased triglycerides, low high-density lipoprotein cholesterol levels and increased small dense low-density lipoprotein (LDL) particles is a major risk factor contributing to the increased cardiovascular (CV) risk in patients with type 2 diabetes (T2D). This is regarded as a residual risk after achieving target levels of LDL cholesterol.

Areas covered: This article reviews the novel therapies to reduce triglycerides in patients with T2D. These were identified by a PubMed search and mainly focus on pemafibrate and the drugs targeting apolipoprotein C3 (apoC3) and angiopoietin-like 3 (ANGPTL3).

Expert opinion: Current therapies to reduce triglycerides in patients with T2D include fibrates and omega-3 fatty acids but these are often not sufficient and the evidence for CV benefits is limited. Pemafibrate was effective in reducing triglycerides in patients with T2D but did not reduce CV events in the PROMINENT study. Inhibitors of apoC3 are effective in reducing triglycerides even in familial chylomicronaemia syndrome and olezarsen and plozasiran in this group are being studied in patients with combined hyperlipidemia. The ANGPTL3 inhibitor evinacumab has been approved for homozygous familial hypercholesterolemia and other ANGPTL3 inhibitors may prove be useful to reduce triglycerides in T2D.

Introduction: Vulvovaginal atrophy (VVA) predominantly affects postmenopausal women due to hormonal decline but can also occur in premenopausal women with conditions such as primary ovarian insufficiency or exposure to anti-estrogen medications. Contributing factors include smoking and certain medical treatments. Symptoms like dyspareunia and loss of sexual function affect many women but are underreported due to stigma and lack of awareness. Current treatments range from over-the-counter lubricants to hormonal therapies like estrogen receptor agonists, which improve vaginal elasticity and moisture with minimal systemic absorption.

Areas covered: This review evaluates current and emerging estrogen receptor agonists for VVA treatment. A comprehensive search was conducted using PubMed between August and September 2024, supplemented by snowball sampling from key references.

Expert opinion: Despite its prevalence, VVA remains underdiagnosed, with increasing recognition due to longer lifespans and focus on quality of life. Diagnosis involves comprehensive symptom assessment, including sexual history, urinary tract infection frequency, and clinical exams, with vaginal pH measurements and smear microscopy to determine the condition's severity. Treatment usually involves estrogen, but not all women can safely use it, and preferences toward estrogen must be respected. Alternatives like selective estrogen receptor modulators (SERMs) such as prasterone and ospemifene show promise but need more long-term safety data. Emerging options like E3 and E4 demonstrate efficacy and safety in low doses. Future treatments will emphasize convenience and adherence, making timely diagnosis and management of VVA routine in women's health care.

Introduction: Candida species produce a wide array of infections ranging from mucocutaneous to systemic infections. Candida albicans remains the most common species identified; however, the non-albicans Candida species have continued to increase as the diagnosis and therapeutic regimens have progressed.

Areas covered: This review with discussion of the various Candida species, especially the non-albicans species, some of the important mechanisms of resistance, and newer in vitro and clinical studies describing the recent and novel antifungal options such as rezafungin, ibrexafungerp, and oteseconazole, along with a novel antifungal, fosmanogepix.

Expert opinion: Initial antifungal therapy is frequently obsolete due to the expansion of antifungal resistance. This is especially true with C. glabrata, C. krusei, and most recently with C. auris. The newer and novel antifungals discussed here will add valuable tools to our antifungal armamentarium to be able to appropriately and adequately treat and manage these difficult infections. Each of the antifungals has unique and novel properties that will expand the arsenal useful to treat these fungal infections in the years to come.

Introduction: Pulmonary fibrosis (PF) post-COVID-19 has been identified as an important complication of Long-COVID, especially in patients with severe respiratory symptoms. High-resolution computed tomography (HRCT) is the main tool for detecting fibrotic lesions in patients with PF post-COVID-19.

Areas covered: We conducted a systematic review with the following objectives: (1) to summarize the incidence and disease burden of post‑COVID‑19 pulmonary fibrosis, (2) to provide information on available therapies and drugs for its management, (3) to comprehensively evaluate the initial treatment efficacy of these drugs, and (4) to identify the limitations and challenges associated with current treatment approaches.

Expert opinion: Cutting-edge treatments for PF post-COVID-19 are focused on the complex and multifactorial nature of the disease progreession during Long COVID, which involves chronic inflammation, fibroblast activation, and excessive extracellular matrix deposition leading to stiffening and fibrosis of lung tissue. While traditional antifibrotic drugs with nintedanid and pirfenidone are being used, novel therapies with anti-interleukines, mesenchymal stem cells, and Rho-kinase inhibitors promise the new treatment approaches for patients with PF post-COVID-19. Further research and clinical trials are needed to determine the most effective strategies for managing this complex condition, with the goal of improving patient outcomes and quality of life.

Introduction: Hyperphosphatemia in advanced CKD often accompanies high PTH and FGF23 levels, impaired bone mineralization, ectopic calcifications, and increased cardiovascular risks. Novel treatments are now available to lower serum phosphorus effectively. However, safety, tolerability, and patient adherence must be evaluated to determine the best therapeutic option for hyperphosphatemia.

Areas covered: This review examines available treatment strategies for hyperphosphatemia in CKD patients and new emerging treatments, emphasizing the latest inhibitors of active phosphate absorption.

Expert opinion: Despite the numerous compounds available, managing hyperphosphatemia in CKD remains challenging. While many phosphate binders exist, they often have limitations and side effects. Aluminum carries significant toxicity risks. Calcium-based binders are effective but can cause hypercalcemia and vascular calcification. Lanthanum is absorbed in the gut, but its long-term tissue deposition appears clinically irrelevant. Sevelamer reduces vascular calcification but has inconclusive data and gastrointestinal side effects. Iron-based binders are effective but may cause gastrointestinal discomfort and lack long-term outcome data. New inhibitors of intestinal phosphate absorption show promise with low pill burden but need more clinical validation. Although these newer compounds might eventually improve phosphate management in CKD patients, enhancing adherence and reducing pill burden, future studies are required to elucidate the best treatment for hyperphosphatemia.