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Migraine is a common disabling neurological condition for which head pain is the most common bothersome symptom. People with migraine also experience other associated symptoms, such as nausea, photophobia, phonophobia, fatigue, and neck pain, though these symptoms can start and end at different times during the attack. Associated symptoms can be as disabling as head pain, and-as they continue-can interfere with activities of daily living. Treating earlier in an attack before central sensitization may be more effective in preventing the development of other associated symptoms during a migraine attack. To understand how to discuss early treatment with patients with migraine, it is important to understand the phases of migraine and how to consider treatment during prodrome. Several studies have evaluated the treatment of migraine as early as prodrome. A study of ubrogepant used during prodrome showed improved prodrome symptoms and reduced the chances of proceeding to the headache phase of migraine compared with placebo. Another time to treat early is during situations known to cause migraine, such as menses. Data have shown that certain acute treatments taken regularly during the menstrual cycle and starting before the onset of migraine can be effective in reducing migraine attacks related to menses. In this article, we discuss the data available on treating migraine attacks early, both during prodrome phase and for the situational prevention of migraine during predictable triggers. Further clinical and real-world data are needed to continue to explore this concept and provide better management options for patients.

Nipocalimab (nipocalimab-aahu; IMAAVY™) is a fully human monoclonal antibody that binds to and blocks the neonatal fragment crystallizable (Fc) receptor (FcRn) resulting in the reduction of circulating IgG levels. It is being developed by Johnson & Johnson for the treatment of a number of autoimmune disorders. On 29 April 2025, nipocalimab received its first approval in the USA for the treatment of generalized myasthenia gravis in adult and pediatric patients ≥ 12 years of age who are anti-acetylcholine receptor or anti-muscle specific tyrosine kinase antibody positive. Regulatory review of nipocalimab is underway for generalized myasthenia gravis in Japan and the European Union. This article summarizes the milestones in the development of nipocalimab leading to this first approval for generalized myasthenia gravis.

The use of methadone has been associated with corrected QT (QTc) prolongation. However, conclusions about the dangers of methadone are limited by its dual use for narcotic abuse deterrence. All these observations can deter physicians from prescribing methadone in patients with chronic pain, particularly those with cancer pain. The aim of this review was to evaluate the existing data regarding the relevance of QT changes, the risk factors for QTc prolongation, as well as the risk for cardiac events and mortality, in patients receiving methadone for chronic pain. In total, 15 studies were evaluated. They differed greatly in design (prospective, retrospective), levels of QTc ranges, number of patients included, and methadone doses. Data suggest that the relevance of QTc prolongation induced by methadone seems to be minimal, also considering the range of dosages commonly used in both noncancer and cancer pain. Some risk factors for QTc prolongation have been identified. Information regarding a prior history or prolonged QTc interval, a family history of a prolonged QTc interval, or a family history of sudden, unexplained death is crucial. In this population and at clinical methadone dosages, serious cardiac events have not been described. Low doses of methadone commonly used in most chronic patients may not require QTc monitoring. When a patient is receiving various medications that could potentially prolong QTc, clinicians may consider obtaining a manually measured QTc. Early discussions with patients regarding goals of care, risks, and benefits will help avoid QTc measurements at regular intervals.

Sipavibart (KAVIGALE^®), a recombinant human immunoglobulin (Ig)G1-based antibody, is being developed by AstraZeneca for the pre-exposure prophylaxis of COVID-19 in immunocompromised individuals. Sipavibart was approved in December 2024 in Japan to prevent the onset of infection caused by SARS-CoV-2 in adults and adolescents aged ≥ 12 years weighing ≥ 40 kg where vaccination against infection caused by SARS-CoV-2 is not recommended or may not achieve a sufficient immune response. Sipavibart was also approved in the EU for the pre-exposure prophylaxis of COVID-19 in adults and adolescents aged ≥ 12 years weighing ≥ 40 kg who are immunocompromised due to a medical condition or receipt of immunosuppressive treatments in January 2025 and in Canada in March 2025. This article summarizes the milestones in the development of sipavibart leading to this first approval for the pre-exposure prophylaxis of COVID-19 in immunocompromised adults and adolescents.

Peripheral nerve block (PNB) is now a commonly used analgesic treatment in clinical anesthesia owing to ongoing advancements in ultrasound imaging technology, which provides clear images of the nerves. Multimodal analgesia based on peripheral nerve blocks is replacing the conventional opioid-based analgesic strategy. However, after the nerve block effect is removed, some patients experience rebound pain (RP), which exacerbates suffering. The benefits of PNB as a perioperative analgesic may be completely negated if RP is discovered and treated too late, even if it can be promptly managed with analgesics. The definitions, clinical signs, risk factors, pathophysiology, and prevention of RP after PNBs are reviewed in this article. At present, the mechanism of RP after PNB is still unclear, but different types of RP may share similar mechanisms in the pain transmission pathway. In this review, we have determined the characteristics of RP and tried to identify the high-risk factors. Among the many means of preventing and reducing the incidence of RP identified, a single block with adjuvant dexamethasone is a reliable regimen, but for the time being, the application of a catheter would be a more reliable method of reducing RP. This review also provides recommendations for the proper use of nerve blocks as supplemental analgesics under clinical anesthesia.

Tiratricol (Emcitate^®) is an orally bioavailable small molecule being developed by Egetis Therapeutics for the treatment of monocarboxylate transporter 8 (MCT8) deficiency. Tiratricol, an analogue and metabolite of the thyroid hormone triiodothyronine (T3), has thyromimetic effects but differs from T3 in that it can enter cells independent of MCT8. Tiratricol received its first approval on 12 February 2025 in the European Union, for the treatment of peripheral thyrotoxicosis in patients with MCT8 deficiency (Allan-Herndon-Dudley Syndrome), from birth. Tiratricol will be available as 350 µg dispersible tablets. Tiratricol is currently undergoing clinical development for MCT8 deficiency in several other countries including the USA. This article summarizes the milestones in the development of tiratricol leading to this first approval for MCT8 deficiency.

Background: Plecanatide is a novel guanylate cyclase-C agonist for the treatment of functional constipation (FC). Its efficacy may vary across different racial populations.

Objective: This study aimed to comprehensively evaluate the efficacy, safety, and pharmacokinetics of plecanatide in Chinese patients with FC.

Methods: This phase III, randomized, double-blind, placebo-controlled trial was conducted across 40 hospitals in China. A total of 648 patients with FC were randomly assigned in a ratio of 1:1 to receive either plecanatide 3 mg or placebo for 12 weeks, followed by a 2-week follow-up. The primary efficacy endpoint was the durable overall complete spontaneous bowel movement (CSBM) response rate. Data on adverse events were collected. A post hoc logistic regression analysis was performed to identify predictors of durable overall CSBM response.

Results: After 12 weeks of continuous treatment, the durable overall CSBM response rates were 23.5% in the plecanatide group and 10.2% in the placebo group (p  <  0.001). Plecanatide significantly increased the mean weekly frequency of CSBM (1.89 vs 0.9) and SBM (2.33 vs 1.03) compared with placebo throughout the treatment period. In addition, all other secondary efficacy endpoints showed statistically significant improvements with plecanatide compared with placebo. The most common treatment-related emergent adverse event was diarrhea, which occurred in 4.3% of plecanatide-treated patients and 0.6% of placebo-treated patients (p = 0.002). Plasma concentrations of plecanatide and its metabolite SP-338 remained below the lower limit of quantification (0.500 ng/ml) at all assessed time points. Weekly CSBM response at week 2 (odds ratio 43.476; 95% confidence interval 18.274-103.432) and baseline stool consistency (odds ratio 0.550; 95% confidence interval 0.366-0.827) were identified as effective predictors of durable overall CSBM response. Even among plecanatide non-responders, a significant improvement in SBM frequency compared with placebo was observed over the 12-week treatment period.

Conclusions: Plecanatide 3 mg was effective and well tolerated in the treatment of Chinese patients with FC. A weekly CSBM response at week 2 may serve as a predictor of 12-week durable overall efficacy. Patients who did not achieve the primary endpoint may still benefit from plecanatide treatment.

Clinicaltrials: GOV: NCT0515132.

Recaticimab (^®), a humanized monoclonal immunoglobulin G1 antibody that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), is being developed by Suzhou Suncadia Biopharmaceutical for the treatment of hypercholesteremia and mixed dyslipidemia. Recaticimab received its first approval on 8 January 2025 in China, as an adjunct to diet, in combination with statins (with or without other lipid-lowering therapies) in adults with primary hypercholesterolemia (including heterozygous familial and non-familial hypercholesterolemia) and mixed dyslipidemia who have not achieved their low-density lipoprotein cholesterol (LDL-C) target despite receiving moderate or higher doses of statins, and for use as monotherapy in adults with non-familial hypercholesterolemia and mixed dyslipidemia to reduce LDL-C, total cholesterol, and apolipoprotein B levels. This article summarizes the milestones in the development of recaticimab leading to this first approval for hypercholesterolemia and mixed dyslipidemia.

Background: Renin-angiotensin-aldosterone system inhibitors (RAASi) and its combination therapy are essential supportive treatments for patients with chronic kidney disease (CKD) and heart failure (HF). Hyperkalemia (HK) is the major safety concern associated with the treatments, which often leads to RAASi dose reduction or discontinuation, thereby compromising cardiovascular protective effects. Although novel potassium binders (NPBs) are recommended by current guidelines for the treatment of HK, systematic evidence is needed to guide their use in RAASi optimization and HK management. A systematic review and meta-analysis was conducted to evaluate the incidence of HK in patients with CKD or HF who received RAASi and the efficacy of NPBs in RAASi optimization.

Methods: PubMed, Medline, Embase, and the Cochrane Library were searched from January 1, 2011 to December 31, 2023. Any studies of adult patients with CKD or HF who received RAASi were included in systematic review of HK incidence and risk factors (part 1). Randomized controlled trials (RCTs) of NPBs in patients with CKD or HF were included in meta-analysis on the efficacy of novel potassium binders (NPBs) (part 2). The primary outcome was optimization of RAASi therapy with NPBs. A pooled analysis was conducted in part 1. Network meta-analyses using a random-effects model were performed in part 2.

Results: A total of 83 studies (24 with CKD, 54 with HF, and 5 with CKD and HF) were included in part 1 and 8 RCTs (2 with CKD, 4 with HF, and 2 with CKD and HF) were included in part 2. The pooled HK incidence was 10.7% overall at any criteria and in all patients who received RAASi. The highest incidence of HK was observed with the combination of angiotensin converting enzyme inhibitor (ACEi)/angiotensin ii receptor blockers (ARBs)/angiotensin receptor-neprilysin inhibitor (ARNi)+ mineralocorticoid receptor antagonists (MRAs) (24.4%), followed by the triple therapy ACEi/ARB/ARNi+ sodium glucose cotransporter-2 inhibitor (SGLT2i)+MRA (10.9%), and ACEi/ARB/ARNi + SGLT2i (2.2%). Novel potassium binders improved RAASi optimization by 38% compared with placebo (risk ratio, 1.38; 95% CI, 1.16-1.65). Additionally, NPBs decreased the incidence of HK by 28% and reduced the level of potassium by 0.71 mEq/L. The CKD population showed a higher optimization rate than the HF population (84% vs 29%).

Conclusion: The RAASi treatment was associated with high prevalence of HK, especially in bigeminal and triple therapy. The NPBs were effective in RAASi optimization and HK management, especially among the CKD population.