Drugs[JOURNAL]
Sun
200 papers
Developing CRISPR-Based Therapies for Epidermolysis Bullosa: A Comprehensive Review of Current Strategies.
du Rand A, Buttle B, Sheppard H
Drugs · 2026 Apr · PMID 41731282 · Full text
Currently, there is no permanent treatment for the group of severe monogenic fragile skin conditions epidermolysis bullosa (EB). The recent US Food and Drug Administration (FDA)-approved in vivo gene replacement therapy...
Currently, there is no permanent treatment for the group of severe monogenic fragile skin conditions epidermolysis bullosa (EB). The recent US Food and Drug Administration (FDA)-approved in vivo gene replacement therapy beremagene geperpavec (Vyjuvek) provides a promising solution, but it requires ongoing application and is not applicable to all forms of EB. Targeted gene editing approaches directly addressing pathogenic mutations hold great promise for the development of durable personalized therapies. Here, we comprehensively describe the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) gene editing landscape for EB, critically review the advantages and limitations of emerging therapeutic strategies, and present some future perspectives. We find that the widespread application of Cas9 nuclease is currently hindered by off-target genotoxicity, which can be mitigated using Cas9 nickases. Further, new tools including prime editing have recently emerged and hold significant potential for EB gene therapy. Ongoing developments in gene editing technologies focused on improving safety and editing precision offer significant promise for the future clinical translation of potentially lifelong treatments for people with EB.
Treating Pancreatic Ductal Adenocarcinoma: The Targeted Revolution is Here.
May MS, Park W, O'Reilly EM
Drugs · 2026 Apr · PMID 41731281 · Full text
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies and is a rising cause of morbidity and mortality. An immunosuppressive, hostile tumor microenvironment, and KRAS-driven biology have contribu...
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies and is a rising cause of morbidity and mortality. An immunosuppressive, hostile tumor microenvironment, and KRAS-driven biology have contributed to poor outcomes in PDAC. Recent breakthroughs in targeting tumors with homologous repair deficiency, KRAS mutations, rare gene fusions, and other molecular abnormalities have improved outcomes in subsets of patients. KRAS inhibitors, both allele specific and pan(K)RAS, claudin-targeting biologics, and PRMT5 inhibitors have demonstrated single agent activity in pretreated, biomarker selected PDAC. An improved understanding of the tumor immune microenvironment has facilitated the development of promising cancer vaccines and immunomodulating agents. This review summarizes the current state of PDAC therapeutics and describes drug development targets that will transform outcomes in PDAC in the proximate future.
Autoimmune Bullous Diseases: Therapeutic Update.
Kasperkiewicz M, van Beek N, Schmidt E
Drugs · 2026 Apr · PMID 41729378 · Full text
Autoimmune blistering diseases (AIBDs) are a heterogeneous group of at least a dozen disorders characterized by autoantibodies against structural proteins of desmosomes in the skin and surface-close epithelia in pemphigu...
Autoimmune blistering diseases (AIBDs) are a heterogeneous group of at least a dozen disorders characterized by autoantibodies against structural proteins of desmosomes in the skin and surface-close epithelia in pemphigus and of the dermal-epidermal junction in pemphigoid diseases. Novel disease entities have recently been described. Owing to their relative rarity with annual incidences between below 1 and about 20 new cases per million inhabitants, few randomized controlled trials (RCTs) have been performed. In this review, we summarize the results of recent RCTs and future treatment options for the three most frequent AIBDs, i.e., bullous pemphigoid, pemphigus vulgaris/foliaceus, and mucous membrane pemphigoid. More specifically, RCTs with immunoadsorption, rilzabrutinib, and efgartigimod in pemphigus, as well as dupilumab, benralizumab, mepolizumab, avdoralimab, and efgartigimod in bullous pemphigoid are summarized. The recent US Food and Drug Administration (FDA) approval of the interleukin (IL)-4/IL-13 inhibitor dupilumab for moderate/severe bullous pemphigoid is highlighted. In addition, an overview is given about the current treatment landscape on the basis of national and international guidelines as well the experience of the authors. In all, while licensing of rituximab for pemphigus vulgaris and dupilumab for bullous pemphigoid represents a therapeutic breakthrough, the lack of industry-sponsored RCTs in mucous membrane pemphigoid and the failure of recent RCTs in pemphigus and bullous pemphigoid demonstrate, on the one hand, the high medical need for effective and safe therapies in AIBDs and, on the other hand, the apparent difficulty in finding suitable compounds and appropriate trial designs.
Mucus as a Treatable Trait in Chronic Airway Diseases.
Cazzola M, Rogliani P, Ora J … +2 more , Calzetta L, Matera MG
Drugs · 2026 Apr · PMID 41712061 · Full text
Chronic airway diseases, including asthma, chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis, are increasingly recognized as heterogeneous disorders characterized by overlapping pathophysiologica...
Chronic airway diseases, including asthma, chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis, are increasingly recognized as heterogeneous disorders characterized by overlapping pathophysiological mechanisms. Among these, abnormalities in mucus production, composition, and clearance have been identified as clinically significant contributors to symptoms, airflow limitation, exacerbations, and disease progression. Within the "treatable traits" framework, mucus-related abnormalities represent a distinct, modifiable phenotype that supports personalized management strategies. This narrative review explores mucus as a treatable trait across chronic airways diseases, integrating mechanistic insights with clinical assessment, biomarkers, and current and emerging therapeutic approaches. We discuss the role of mucus in disease phenotyping, its impact on morbidity, and the potential of targeted interventions to improve outcomes. Recognizing mucus as a treatable trait aligns with the principles of precision medicine and offers a pathway toward individualized therapy beyond traditional diagnostic labels.
More than Glucose Elimination: Additional Benefits of SGLT2 Inhibitors in Glomerular Diseases.
Del Vecchio L, Fernandez-Fernandez B, Fornoni A … +2 more , Kronbichler A, Ortiz A
Drugs · 2026 Apr · PMID 41691570 · Publisher ↗
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have consistent nephroprotective effects across diverse patient populations, including those with glomerular disease without diabetes mellitus. These somehow unexpected b...
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have consistent nephroprotective effects across diverse patient populations, including those with glomerular disease without diabetes mellitus. These somehow unexpected benefits cannot be solely explained by glycosuria and intrarenal hemodynamic effects. Experimental evidence largely supports the effects of SGLT2 inhibitors on several pathways, many of them outside the kidneys. This review explores the mechanisms underlying these benefits, focusing on those of importance in primary and secondary glomerulonephritis. In addition to glucose homeostasis, SGLT2 inhibitors exert local and systemic effects that mimic nutrient deprivation, impacting inflammation, immunity, autophagy, hypoxia responses, ferroptosis, lipotoxicity, and energy metabolism. Sodium-glucose cotransporter 2 inhibitors modulate inflammatory pathways through suppression of cytokines and NLR family pyrin domain containing 3 inflammasome activity, mechanisms relevant to immunoglobulin A glomerulonephritis, lupus nephritis, and anti-neutrophil cytoplasmic antibody-associated vasculitis. They also influence immune cell metabolism, inhibit T-cell activation, and potentially modulate B-cell and macrophage polarization. There is evidence that autophagy may show a dual role in glomerular disease. It could activate innate and adaptive immunity, so triggering the disease, or may protect podocytes, so reducing proteinuria and the risk of progression. Sodium-glucose cotransporter 2 inhibition also modulates the hypoxia inducible factor axis and reduces ferroptosis, possibly contributing to attenuate hypoxia-induced kidney damage. The upregulation of ketogenesis and activation of nutrient-sensing pathways (adenosine monophosphate-activated protein kinase-activated protein kinase, sirtuins, and mammalian target of rapamycin) further supports their role in metabolic reprogramming. Finally, they contribute to preserve gerosuppressor functions by increasing kidney Klotho, a protein with anti-aging, and-inflammatory, and antifibrotic effects, and liver betaine. Although direct clinical evidence on the specific molecular pathways targeted by SGLT2 inhibitors in glomerulonephritis remains limited, preclinical data and emerging human observations suggest SGLT2 inhibitors may offer therapeutic advantages beyond non-specific kidney-cardiovascular protection.
Current and Future Pharmacological Interventions for Acquired Hypothalamic Obesity.
Roth CL, Doelman-Oldenburger NJ, van Santen HM
Drugs · 2026 Apr · PMID 41678022 · Publisher ↗
Hypothalamic obesity (HO) is a rare, complex disorder characterized by disruption of brain pathways regulating energy intake, expenditure, autonomic function, and hormonal signaling. It occurs in rare monogenic obesity s...
Hypothalamic obesity (HO) is a rare, complex disorder characterized by disruption of brain pathways regulating energy intake, expenditure, autonomic function, and hormonal signaling. It occurs in rare monogenic obesity syndromes affecting central leptin-melanocortin pathways or can be acquired (aHO) as a consequence of hypothalamic injury due to a tumor (e.g., craniopharyngioma), its treatment, or trauma. In this narrative review, we focus on aHO. Damage to specific hypothalamic nuclei leads to hyperphagia, central insulin and leptin resistance, decreased sympathetic activity, reduced energy expenditure, and rapid weight gain. Traditional obesity treatments, including lifestyle interventions, often fail to achieve sustained weight loss in patients with aHO. Recent advances in pharmacotherapy show promise by targeting the distinct pathophysiology of aHO. Effective treatment requires personalized approaches due to the heterogeneity of hypothalamic dysfunction and associated comorbidities. Early intervention may improve outcomes, as rapid postoperative weight gain frequently occurs. Emerging therapies target mechanisms of disturbed energy homeostasis pathways. These agents include stimulants, incretin-based therapies (e.g., glucagon-like peptide-1 receptor agonists), insulin modulators, and melanocortin receptor agonists such as setmelanotide. While monotherapies often fail in long-term treatment, combination therapies hold potential to restore energy balance and reduce or eliminate the need for bariatric surgery. Future research should focus on identifying clinical and biomarker profiles of aHO subtypes and evaluating combination therapies. Although challenging, aHO is no longer untreatable. Patients should be referred and managed at specialized centers, with pharmacological treatment preferably conducted within research settings to optimize and personalize care, and to develop evidence-based protocols for this debilitating condition.
Bevifibatide: First Approval.
Fung S
Drugs · 2026 Apr · PMID 41678021 · Publisher ↗
Bevifibatide (; BETAGRIN; batifiban) is a cyclic heptapeptide antagonist of glycoprotein IIb/IIIa (GP IIb/IIa; αIIbβ3 integrin receptor) and the αvβ3 integrin receptor. It was developed by Bio-Thera Solutions for the tre...
Bevifibatide (; BETAGRIN; batifiban) is a cyclic heptapeptide antagonist of glycoprotein IIb/IIIa (GP IIb/IIa; αIIbβ3 integrin receptor) and the αvβ3 integrin receptor. It was developed by Bio-Thera Solutions for the treatment of patients with acute coronary syndrome (ACS) that require percutaneous coronary intervention (PCI). On 25 June 2024, bevifibatide received approval in China for the treatment of patients with a clear diagnosis of ACS who need PCI (including coronary stenting) to reduce the risk of acute occlusion, stent thrombosis, no reflow and slow blood flow. Its first approval is as an add-on to treatment with PCI, antiplatelet and anticoagulant therapies. This article summarizes the milestones in the development of bevifibatide leading to its first approval for reducing the risk of acute occlusion, stent thrombosis, no reflow and slow blood flow in patients with ACS that requires PCI (including coronary stenting).
Ziftomenib: First Approval.
McGuigan A
Drugs · 2026 Apr · PMID 41653248 · Publisher ↗
Ziftomenib (KOMZIFTI) is an oral, selective, once-daily menin inhibitor in development by Kura Oncology for the treatment of NPM1-mutated (NPM1-m) or KMT2A-rearranged (KMT2A-r) acute myeloid leukaemia (AML), KMT2A-r acut...
Ziftomenib (KOMZIFTI) is an oral, selective, once-daily menin inhibitor in development by Kura Oncology for the treatment of NPM1-mutated (NPM1-m) or KMT2A-rearranged (KMT2A-r) acute myeloid leukaemia (AML), KMT2A-r acute lymphoblastic leukaemia and gastrointestinal stromal tumours (GIST). The menin-KMT2A complex and mutated NPM1 proteins co-occupy specific gene promoter sites and increase transcription of leukaemogenic genes. By blocking the interaction between menin and KMT2A, ziftomenib downregulates transcription of key leukaemogenic factors and restores differentiation pathways to exert anti-leukaemic effects in NPM1-m and KMT2A-r AML. Ziftomenib received its first approval on 13 Nov 2025 in the USA for the treatment of adults with relapsed or refractory AML with a susceptible NPM1 mutation who have no satisfactory alternative treatment options. This article summarises the milestones in the development of ziftomenib leading to this first approval for relapsed or refractory AML associated with an NPM1 mutation.
Nanoencapsulated Sirolimus Plus Pegadricase (NASP) in Uncontrolled Gout: Current Status and Future Directions.
Baraf HSB, Schlesinger N, Strand V
Drugs · 2026 Mar · PMID 41629465 · Full text
Uncontrolled gout (UG) is a progressive arthropathy that develops as a consequence of sustained hyperuricemia. Recombinant uricases can profoundly lower serum urate (SU) and reverse the clinical manifestations of uncontr...
Uncontrolled gout (UG) is a progressive arthropathy that develops as a consequence of sustained hyperuricemia. Recombinant uricases can profoundly lower serum urate (SU) and reverse the clinical manifestations of uncontrolled gout. However, therapeutic uricases are highly immunogenic and can provoke the development of anti-drug antibodies (ADAs), resulting in a loss of effect and potentially severe allergic reactions. Pegloticase is currently the only US Food and Drug Administration-approved uricase indicated for the treatment of UG. The Food and Drug Administration recently approved the co-administration of methotrexate with pegloticase to inhibit ADA formation and enhance the efficacy and tolerability of pegloticase. Nanoencapsulated sirolimus plus pegadricase (NASP) is a novel every-4-week treatment delivered as a sequential two-component infusion consisting of nanoencapsulated sirolimus immediately followed by pegadricase, a novel PEGylated uricase. NASP mitigates ADA formation by promoting uricase-specific immunotolerance, thereby obviating the need for systemic immunomodulatory drugs. Phase I trials demonstrated that NASP inhibited ADA development, allowing sustained pegadricase control and SU lowering for up to 30 days. The dose-finding (phase II) study showed NASP (nanoencapsulated sirolimus 0.1-0.15 mg/kg and pegadricase 0.2 mg/kg) reduced ADA development and supported durable SU lowering. The phase II COMPARE trial demonstrated that monthly NASP was as effective as twice-monthly pegloticase in achieving SU targets at 6 months. Combined phase III DISSOLVE trial data confirmed that NASP significantly lowered SU and increased SU responses in participants with UG. All phase I-III trials demonstrated that NASP was generally well tolerated with no specific safety signals. Overall, NASP has demonstrated robust and durable SU lowering, which ultimately reduced disease burden, supporting positive health-related quality-of-life outcomes. This review summarizes the clinical development of NASP with particular reference to the targeted immunotolerizing strategy that diminishes its immunogenicity. Video abstract available online. Video Abstract.
The Potential of Authorised Drugs to be Repurposed for the Treatment of Osteoarthritis: A Scoping Review of Clinical Studies.
Heijman MWJ, Hartog M, van den Ende CHM … +2 more , Popa CD, van den Bemt BJF
Drugs · 2026 Mar · PMID 41619152 · Full text
UNLABELLED: BACKGROUND AND OBJECTIVES: Drug repurposing offers a low-cost and time-efficient approach to discover an effective and safe disease-modifying treatment for osteoarthritis. Although numerous studies have inves...
UNLABELLED: BACKGROUND AND OBJECTIVES: Drug repurposing offers a low-cost and time-efficient approach to discover an effective and safe disease-modifying treatment for osteoarthritis. Although numerous studies have investigated candidate drugs for repurposing, existing narrative reviews are restricted in scope. This scoping review aims to provide an exhaustive overview of the extent and characteristics of clinical research on authorised drugs investigated for treating osteoarthritis. METHODS: Electronic database searches were performed from inception until July 2025 in MEDLINE, Embase and Cochrane. Authorised drugs approved by the US Food and Drug Administration, European Medicines Agency or Dutch Medicines Evaluation Board, investigated in clinical studies for treating osteoarthritis, were included. Dextrose and drugs indicated for pain (irrespective of aetiology) or osteoarthritis were excluded. Titles and abstracts were screened using ASReview, full texts were assessed accordingly and results were classified per drug. RESULTS: From 26,638 deduplicated records, 201 articles reporting on 220 studies were included in this review: 104 randomised controlled trials (RCTs), including 9 post-hoc analyses, 75 cohort studies, 13 case-control studies, 12 cross-sectional studies, 12 pre-post studies and 4 non-randomised CTs. In total, 52 drugs were identified, with drugs originally indicated for osteoporosis being most frequently investigated. Short-term follow-up studies (< 1 year) were mostly RCTs focussing on symptom-modifying effects, whilst long-term follow-up studies (≥ 1 year) more often used existing data and assessed both symptom- and structure-modifying effects. The most frequently used outcomes were pain (118/220) and function (74/220) for symptoms and grading systems (28/220) for structural changes. Significant effects were observed in 40% of the primary outcomes related to symptoms and structure and in 78% of outcomes related to osteoarthritis incidence or joint replacement. For GLP agonists, antihistamines, coumarins, N-acetylcysteine, sex hormones and statins, however, a mix of disease-modifying and disease-aggravating effects was found. CONCLUSIONS: Many authorised drugs have been investigated in clinical studies to be repurposed for treating osteoarthritis, with short-term studies primarily examining symptom-modifying effects, and most long-term studies also assessing structure-modifying effects. However, the broad and heterogeneous nature of clinical research in this field complicates the accurate evaluation of disease-modifying osteoarthritis drug candidates. This review, therefore, highlights the need for a more strategic research landscape on drug repurposing for osteoarthritis.
First Line and Treatment Sequencing in EGFR-Mutated Metastatic NSCLC: What is Right for Which Patient?
Abdayem P, Parisi C, Planchard D
Drugs · 2026 Mar · PMID 41619151 · Full text
The therapeutic landscape for non-small-cell lung cancer (NSCLC) harbouring epidermal growth factor (EGFR) gene mutations is undergoing significant transformation. For classical EGFR mutations such as exon 19 deletion an...
The therapeutic landscape for non-small-cell lung cancer (NSCLC) harbouring epidermal growth factor (EGFR) gene mutations is undergoing significant transformation. For classical EGFR mutations such as exon 19 deletion and exon 21 L858R mutation, combination strategies in the first-line setting, based on the results of the MARIPOSA (lazertinib and amivantamab) and FLAURA 2 (platinum-based doublet chemotherapy and osimertinib) trials, provide promising outcomes. Compared to osimertinib monotherapy, they potentially delay both the onset of molecular resistance to treatment and the intracranial progression of the disease. Selecting the best first-line option should take into consideration patient and genome-related factors as well as the burden of the disease including the presence of central nervous system metastases. Beyond first-line therapy, novel agents-including antibody-drug conjugates, bispecific antibodies, and T-cell engagers-have emerged as innovative options for pretreated patients with EGFR-mutated disease. Optimising the treatment sequence in advanced EGFR-mutated NSCLC is crucial to ensure the best survival outcomes along with the best treatment tolerance and quality of life. Predictive biomarkers are strongly needed as well as biomarker-based escalation and de-escalation clinical trials.
Pharmacological Management of Obesity in Pregnancy: A Review of Current and Emerging Therapies.
Fotheringham P, McGee RG, Chang R … +2 more , Kennedy D, Simmons D
Drugs · 2026 Mar · PMID 41619150 · Full text
The escalating prevalence of maternal obesity and excess gestational weight gain poses significant risks to both maternal and child health. Current management strategies, primarily focused on lifestyle interventions, oft...
The escalating prevalence of maternal obesity and excess gestational weight gain poses significant risks to both maternal and child health. Current management strategies, primarily focused on lifestyle interventions, often have limited efficacy, creating an urgent unmet clinical need. This review summarises the evidence for pharmacological management of obesity in pregnancy. We systematically searched the literature to evaluate historical and emerging weight management therapies for use in pregnancy. Existing medications such as metformin, orlistat, and naltrexone-bupropion have limited application due to modest efficacy or inconsistent safety data. Newer agents like glucagon-like peptide-1 (GLP-1) receptor agonists are transforming obesity care but are not currently recommended during pregnancy due to insufficient safety information. While animal studies have raised concerns regarding foetal growth, large human observational studies have not yet demonstrated a significant independent risk of major congenital malformations after accounting for confounding maternal comorbidities. Future progress depends on robust, collaborative research, including pregnancy registries, to determine if these agents could have a role in carefully selected, high-risk cases. Clinical guidance continues to support adherence to National Academy of Medicine gestational weight-gain targets, particularly the modest recommended gain for women with obesity.
Metabolic Checkpoints in IgA Nephropathy: From Pathogenesis to Precision Medicine.
Liu H, Yao Y, Zhang C … +1 more , Xiong J
Drugs · 2026 Mar · PMID 41618071 · Publisher ↗
Immunoglobulin A nephropathy (IgAN), the most prevalent primary glomerulopathy globally, exhibits intricate pathomechanisms and significant clinical heterogeneity, with up to 50% of patients progressing to kidney failure...
Immunoglobulin A nephropathy (IgAN), the most prevalent primary glomerulopathy globally, exhibits intricate pathomechanisms and significant clinical heterogeneity, with up to 50% of patients progressing to kidney failure within 20 years. Contemporary management of IgAN combines causal therapy against pathogenic galactose-deficient immunoglobulin A1, including enteric budesonide with symptom-oriented interventions via renin-angiotensin system inhibitors to mitigate hypertension, glomerular hyperfiltration, proteinuria, and cardiovascular sequelae. Nevertheless, suboptimal treatment efficacy observed in 20-30% of patients with IgAN implies the existence of additional pathogenic mechanisms beyond current therapeutic targeting. Emerging evidence underscores the pivotal role of metabolic checkpoints-central regulatory hubs governing glucose, lipid, amino acid, and mitochondrial networks-in driving a self-perpetuating pathogenic loop linking metabolic reprogramming and immune dysregulation in IgAN. Mechanistically, hypoxia-driven stabilization of hypoxia-inducible factor 1-alpha hyperactivates aerobic glycolysis, fueling T helper 17 cell/T regulatory cell imbalance and mesangial proliferative injury. Peroxisome proliferator-activated receptor dysfunction exacerbates lipotoxic damage and fibrosis. Indoleamine 2,3-dioxygenase 1- and arginase 1-mediated amino acid metabolic disturbances disrupt immune homeostasis. Meanwhile, mitochondrial oxidative stress, coupled with maladaptive unfolded protein response, propagates tubular injury through reactive oxygen species-mediated NOD-like receptor family pyrin domain containing 3 inflammasome activation and epigenetic dysregulation. Interventions targeting metabolic checkpoints, including sodium-glucose cotransporter 2 inhibitors, mechanistic target of rapamycin inhibitors and peroxisome proliferator-activated receptor-γ agonists demonstrate promising renoprotective effects in IgAN preclinical models and early-phase trials, heralding the era of dual metabolic-immune precision therapeutics. However, it is critical to emphasize that these emerging strategies currently constitute a hypothesis-generating framework and must be validated in future large-scale, randomized controlled trials with adequate power and follow-up before clinical application. Future research should integrate multi-omics and single-cell analysis to delineate metabolic heterogeneity and develop renal-targeted nanodelivery systems for endotype-based precision medicine. This paradigm shift will guide IgAN mechanism exploration and management, transitioning from conventional immunosuppression to metabolic-immune synergy regulation.
Developments and Challenges in Treating Rheumatoid Arthritis-Related Interstitial Lung Disease: From Pathogenesis to Treatment Opportunities.
Sebastiani M, Luppi F, Bendstrup E
Drugs · 2026 Mar · PMID 41609952 · Full text
Interstitial lung disease (ILD) is the most severe extra-articular manifestation of rheumatoid arthritis (RA), representing one the most frequent causes of death for patients with RA. The treatment of RA-ILD is still deb...
Interstitial lung disease (ILD) is the most severe extra-articular manifestation of rheumatoid arthritis (RA), representing one the most frequent causes of death for patients with RA. The treatment of RA-ILD is still debated and challenging for both rheumatologist and pulmonologist. Ideally, it should aim to control the underlying joint disease activity, to prevent ILD, or to reduce the progression of lung damage, in particular fibrotic changes. Disease-modifying antirheumatic drugs (DMARDS) are used in daily practice for the treatment of joint involvement but are not demonstrated to be effective in ILD, although good control of the systemic disease might improve patients' prognosis. However, immunosuppressants, usually suggested for the treatment of ILD related to autoimmune rheumatic diseases, often have low efficacy in regard to inflammatory joint manifestations of RA. Finally, the awareness of potential pulmonary toxicity related to disease-modifying antirheumatic drugs further complicates this scenario. Therefore, a multidisciplinary discussion, including at least a rheumatologist, pulmonologist, pathologist, and thoracic radiologist is generally requested to decide the best therapeutic strategy for an individual patient. In this paper, we will review the current available options for the treatment of RA-ILD, focusing on their possible use according to the current knowledge on pathogenesis and clinical evolution of RA-ILD.
Remibrutinib: First Approval.
Fung S
Drugs · 2026 Mar · PMID 41559488 · Publisher ↗
Remibrutinib (Rhapsido) is an orally administered, selective Bruton's tyrosine kinase (BTK) inhibitor being developed by Novartis for the treatment of chronic spontaneous urticaria (CSU) as well as other immune-mediated...
Remibrutinib (Rhapsido) is an orally administered, selective Bruton's tyrosine kinase (BTK) inhibitor being developed by Novartis for the treatment of chronic spontaneous urticaria (CSU) as well as other immune-mediated disorders. On 30 September 2025 remibrutinib received its first approval in the USA for treatment of CSU in adult patients who remain symptomatic despite H-antihistamine treatment. It has subsequently been approved for use in the same indication in China and is under regulatory review in the EU and Japan. This article summarises the milestones in the development of remibrutinib leading to this first approval for CSU in adult patients who remain symptomatic despite H-antihistamine treatment.
Correction: Ifupinostat: First Approval.
Fung S
Drugs · 2026 Feb · PMID 41553621 · Publisher ↗
Abstract loading — click title to view on PubMed.
Treatment Sequencing in Advanced Urothelial Cancer.
Riaz IB, Humayun MA, Khaki AR … +1 more , Hussain SA
Drugs · 2026 Feb · PMID 41549173 · Publisher ↗
Treatment paradigms for advanced urothelial carcinoma have evolved rapidly with the introduction of antibody-drug conjugates and novel immunotherapy combinations. Enfortumab vedotin plus pembrolizumab has redefined first...
Treatment paradigms for advanced urothelial carcinoma have evolved rapidly with the introduction of antibody-drug conjugates and novel immunotherapy combinations. Enfortumab vedotin plus pembrolizumab has redefined first-line therapy, demonstrating unprecedented survival benefits compared with platinum-based chemotherapy. However, high cost and limited availability remain major barriers to its global implementation. Accordingly, gemcitabine-cisplatin with nivolumab and platinum-based chemotherapy followed by maintenance avelumab remain validated evidence-based alternatives, particularly for cisplatin-eligible patients or in regions where enfortumab vedotin plus pembrolizumab is not readily accessible. These advances have created new challenges in treatment sequencing, particularly for patients who progress after enfortumab vedotin plus pembrolizumab, where prospective evidence remains limited. Enfortumab vedotin monotherapy retains activity post-platinum and immune checkpoint inhibition, erdafitinib provides a targeted benefit in fibroblast growth factor receptor 3-altered tumors, and trastuzumab deruxtecan has emerged as a later-line option for HER2-positive disease. In parallel, circulating tumor DNA is an emerging biomarker with potential to individualize sequencing strategies, although its clinical application remains investigational. This review synthesizes current evidence and highlights practical considerations, emphasizing the need to balance therapeutic innovation with cost effectiveness, equitable access, and global applicability, while identifying critical research priorities in the post-enfortumab vedotin plus pembrolizumab era.
Zongertinib: First Approval.
Lee A
Drugs · 2026 Mar · PMID 41549172 · Publisher ↗
Zongertinib (HERNEXEOS) is a small molecule, irreversible, HER2-specific tyrosine kinase inhibitor being developed by Boehringer Ingelheim for the treatment of advanced solid tumours with HER2 aberrations. Zongertinib se...
Zongertinib (HERNEXEOS) is a small molecule, irreversible, HER2-specific tyrosine kinase inhibitor being developed by Boehringer Ingelheim for the treatment of advanced solid tumours with HER2 aberrations. Zongertinib selectively inhibits HER2-expressing cells, including those with HER2 mutations, while sparing cells expressing wild-type EGFR. It received its first approval under accelerated approval in August 2025 in the USA following positive results from the Beamion LUNG-1 phase Ia/Ib trial in patients with previously treated HER2-mutant non-small cell lung cancer (NSCLC). This article summarizes the milestones in the development of zongertinib leading to this first approval for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours have HER2 tyrosine kinase domain activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy.
Effect of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors on Lipoprotein(a) Levels: An Umbrella Review of Meta-analyses of Randomized Controlled Trials.
Qiao W, Feng Y, Wen Z … +2 more , Dou L, Li Y
Drugs · 2026 Feb · PMID 41549171 · Publisher ↗
BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is a genetically determined, causal risk factor for atherosclerotic cardiovascular disease, but effective therapies remain limited. Proprotein convertase subtilisin/kexin type...
BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is a genetically determined, causal risk factor for atherosclerotic cardiovascular disease, but effective therapies remain limited. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are primarily used to lower low-density lipoprotein cholesterol (LDL-C), yet their effects on Lp(a) have been inconsistently reported. This umbrella review synthesizes meta-analytic evidence on PCSK9 inhibitors and Lp(a). METHODS: We systematically searched PubMed, Embase, Web of Science, and Cochrane Library through April 2025 for meta-analyses of randomized controlled trials (RCTs) comparing PCSK9 inhibitors (alirocumab, evolocumab, inclisiran) with placebo or standard therapy. The primary outcome was mean percentage change in Lp(a). Methodological quality was assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), and evidence certainty was graded with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Overlap of primary trials was quantified using the Corrected Covered Area (CCA), and sensitivity analyses were performed to account for overlapping evidence. RESULTS: Twenty-one meta-analyses (116 RCTs; 231,796 participants) were included. The PCSK9 inhibitors consistently reduced Lp(a): evolocumab (29.68-46.68%; high certainty), alirocumab (18.55-26.46%; high certainty), and inclisiran (18.00%; high certainty). Higher biweekly doses yielded larger decreases (e.g., alirocumab 150 mg: 24.6%; evolocumab 140 mg: 26.8%, high certainty). Reductions were dose-dependent and broadly consistent across populations, comparators, follow-up durations, and baseline Lp(a). The Lp(a) reductions correlated modestly with LDL-C (β = 0.28; 95% CI 0.07-0.49) and apolipoprotein B (apoB) (β = 0.33; 95% CI 0.03-0.63). Concomitant reductions in LDL-C, apoB, and major adverse cardiovascular events were supported by high and moderate certainty evidence. Safety was favorable, with injection-site reactions being the most common adverse event. Sensitivity analyses confirmed robustness of findings after accounting for overlapping trials. CONCLUSIONS: The PCSK9 inhibitors, particularly evolocumab 140 mg every 2 weeks, significantly lower Lp(a) alongside LDL-C and apoB. These findings highlight the consistent Lp(a)-lowering effect of PCSK9 inhibitors. However, the observed cardiovascular benefits are largely attributable to concomitant LDL-C reduction, and the incremental contribution of Lp(a) lowering remains uncertain. Confirmation from outcome trials specifically designed to target Lp(a) is required. REGISTRATION: PROSPERO CRD420251048597.
Lipid-Lowering Therapies in Patients with Chronic Kidney Disease: A Perspective on High-Density Lipoprotein Cholesterol.
Naim MAAZ, Sumida K, Streja E … +4 more , Thomas F, Davis RL, Kalantar-Zadeh K, Kovesdy CP
Drugs · 2026 Feb · PMID 41528633 · Publisher ↗
Chronic kidney disease (CKD) increases the risk of cardiovascular disease (CVD), with dyslipidemia being a contributing risk factor. In patients with CKD, diminished antioxidant, anti-inflammatory, and cholesterol transp...
Chronic kidney disease (CKD) increases the risk of cardiovascular disease (CVD), with dyslipidemia being a contributing risk factor. In patients with CKD, diminished antioxidant, anti-inflammatory, and cholesterol transport capacities of high-density lipoprotein cholesterol (HDL-C) may contribute to atherosclerosis and poor CVD outcomes. Different lipid-lowering therapies (LLTs) have demonstrated efficacy in correcting dyslipidemia in patients without kidney disease, including substantial elevations in HDL-C levels with triglyceride-lowering therapies, such as fibrates and niacin, as well as novel HDL-targeted therapies, including cholesterol-ester transfer protein inhibitors. However, the effects of HDL-elevating therapies in populations without kidney disease may not readily be extrapolated to patients with CKD, given the distinct dyslipidemia patterns and the lack of high-quality clinical trials in this population. Despite plausible mechanisms of HDL-elevation to improve clinical outcomes, current clinical guidelines only recommend statin use for the treatment of hyperlipidemia in patients with non-dialysis-dependent CKD. In this narrative review, we discuss how HDL-C functionality is affected in patients with CKD and explore evidence investigating different LLTs for HDL elevation and improved clinical outcomes in this population. In patients with CKD, we recommend further investigation of HDL-targeted therapies, comparative effectiveness evaluation of HDL-elevating LLTs versus statins across various clinical endpoints, and whether HDL-C elevation mediates these outcomes.
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