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Results for “off-label use”

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PubMed2026

Study of prescription-indication of antivirals for herpesviruses in a Colombian population: a cross-sectional study.

BACKGROUND: To describe the utilization patterns and therapeutic indications of antivirals used for herpesvirus infections in Colombian patients. RESEARCH DESIGN/METHODS: A cross-sectional study on the use of antivirals for treating outpatients with herpesviruses between November 2023 and January 2024 in a Colombian population database. The Micromedex® database was used to identify Food and Drug Administration (FDA)-approved indications, off-label uses, and potentially inappropriate indications. RESULTS: A total of 14,816 individuals were included (median age:53.0 years [IQR:35.0-65.0]; 60.5% women). Acyclovir was the most frequently prescribed antiviral (oral:77.3%; topical:43.4%). Overall, 56.1% received oral therapy only, 25.2% combined oral and topical therapy, and 18.7% topical therapy only. FDA-approved indications accounted for 29.1% of use (herpes zoster), off-label use for 26.9% (mainly prophylaxis in immunocompromised patients), and potentially inappropriate use for 25.3% (primarily topical treatment of herpes zoster). Acyclovir use (OR:5.93; 95%CI:4.60-7.64) and specialist care (OR:2.17; 95%CI:1.73-2.71) were associated with off-label use. CONCLUSIONS: Antiviral prescribing for herpesvirus infections in a group of patients in Colombia is largely driven by acyclovir, with a substantial proportion of off-label and potentially inappropriate use, particularly involving topical therapies for herpes zoster. These findings highlight significant gaps in adherence to evidence-based recommendations and underscore the need for targeted interventions to optimize prescribing practices.

Humans↗

PubMed2026

The emerging applications of JAK inhibitors in dermatology - a systematic review.

BACKGROUND: Janus kinase (JAK) inhibitors are established treatments for selected dermatologic conditions, but their off-label use has expanded across refractory skin diseases. METHODS: We systematically searched MEDLINE, Embase, and Web of Science from inception to October 1, 2025, for studies reporting off-label JAK inhibitor use in dermatologic disorders beyond approved or late-phase trial indications. RESULTS: Of 9,182 records screened, 277 studies met the inclusion criteria, comprising 210 case reports, 55 case series, and 12 retrospective studies involving 764 patients. Owing to substantial clinical heterogeneity, findings were narratively synthesized using a structured disease-family framework. Off-label use most commonly involved lichenoid, neutrophilic, and granulomatous dermatoses. Overall, 725/764 (94.88%) patients experienced clinical benefit, including complete or near-complete response in 209/764 (27.35%) and significant or partial improvement in 516/764 (67.53%). Thirty-five patients (4.58%) showed no clinical change, and four (0.52%) experienced disease worsening. A total of 154 adverse events were reported, most commonly with tofacitinib; most were mild to moderate, although six were serious and 25 resulted in treatment discontinuation. CONCLUSION: JAK inhibitors demonstrate promising therapeutic potential across a broad spectrum of refractory dermatological diseases. The predominance of uncontrolled case-based evidence, heterogeneous dosing, and frequent combination therapy limits attribution of efficacy and safety to JAK inhibitor monotherapy. Prospective controlled studies are needed to better define their therapeutic role.

Humans↗

PubMed1992

Adverse drug reactions: report of the Australian Veterinary Association Adverse Drug Reaction Subcommittee, 1992.

Fifty-nine reports of suspected adverse drug reactions (ADRs) were received by the Adverse Drug Reaction Subcommittee of the Australian Veterinary Association from February 1991-March 1992 inclusive. The number of reports received/number of animals involved per species was: dogs (23/24); cats (20/30); horses (4/4); cattle (7/10); sheep (3/745); poultry (1/580); pigs (1/8). Of these, 38 (64%) were classified as definite ADRs and 9 (15%) as probable ADRs. In 10 (17%) reports an ADR could not be substantiated or there was insufficient information available to make a decision. Two reports involved veterinarians inadvertently overdosing animals. Eighteen reports involved apparent hypersensitivity reactions and 6 reports involved probable drug interactions. Four reports involved the use of drugs at appropriate doses but in inappropriate clinical situations, and 3 reports were associated with 'off-label' use.

Animals↗

PubMed2026

Mice with the mono-allelic p.R37H Dhdds variant show aberrant glycosylation and interneuron deficits.

Developmental delay and seizures with or without movement abnormalities (OMIM 617836) caused by heterozygous pathogenic variants in the DHDDS gene (DHDDS-CDG) is a rare genetic disease that belongs to the progressive encephalopathy spectrum. It results in cognitive delay in affected children, accompanied by myoclonus, seizures, ataxia and tremor, which worsens over time. DHDDS encodes a subunit of a DHDDS/NUS1 cis-prenyltransferase (cis-PTase), a branch point enzyme of the mevalonate pathway essential for N-linked glycosylation. We describe the first mouse model of this disease, DhddsR37H+/- strain, heterozygous for the human recurrent de novo c.110G>A:p.R37H pathogenic variant. DhddsR37H+/- mice present with seizures, myoclonus and memory deficits associated with reduced density or/and maturity of inhibitory interneurons in the cortex. Multiomics analyses of mouse CNS tissues, together with the enzymatic/structural characterization of the R37H DHDDS mutant protein, reveal that the variant produces a catalytically inactive enzyme and results in a brain dolichol deficit, aberrant glycosylation of brain glycoproteins, including those involved in synaptic transmission and major perturbations in the CNS proteome and lipidome. Acetazolamide, a carbonic anhydrase inhibitor clinically approved for treatment of glaucoma, epilepsy, and intracranial hypertension, and successfully used "off-label" to treat genetic movement disorders, reduces seizure susceptibility to pentylenetetrazol in DhddsR37H+/- mice, suggesting potential therapeutic value of using this drug in human DHDDS-CDG patients. Together, our results define cis-PTase as a master regulator of CNS development and function and establish that its monoallelic debilitating variants cause a novel congenital disorder of glycosylation associated with aberrant levels of neuronal proteins and lipids.

DHDDS↗

PubMed2026

UGT1A1 genotype testing for irinotecan: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI-PGx).

Irinotecan, a topoisomerase I inhibitor, is available as both non-pegylated and pegylated formulations. The non-pegylated formulation is licensed for use in advanced colorectal cancer either in combination with other agents or as monotherapy. However, it is also used off-label across a range of gastrointestinal malignancies and in rare malignancies such as glioblastoma and sarcomas. The pegylated formulation is licensed for use as combination therapy in adult patients with metastatic pancreatic adenocarcinoma. Irinotecan is hydrolysed to its active metabolite, SN-38, which is predominantly inactivated by the enzyme uridine diphosphate glucuronosyltransferase UGT1A1. UGT1A1 is encoded by the gene UGT1A1, which is polymorphically expressed, with allele frequencies varying across populations. Poor metabolizers carry two variants that reduce UGT1A1 enzyme expression or activity, leading to increased risk of irinotecan toxicity. Any patient who is about to be prescribed irinotecan for an epithelial malignancy should have pharmacogenetic testing, to identify clinically relevant UGT1A1 variants, where testing is available. Irinotecan dose should be reduced by 30% at Cycle 1 treatment in poor metabolizers for all indications, with doses titrated thereafter based on tolerability and neutrophil counts. The lack of evidence precludes us from making any recommendation for rare malignancies such as sarcomas. Our guideline is consistent with other international pharmacogenetics prescribing guidelines. This guideline is grounded in the latest evidence but cannot account for all individual factors relevant to patient care. Therefore, prescribers must conduct a thorough assessment of each patient's risk-benefit profile, ensuring that therapy is optimized to maximize benefits while minimizing potential harms.

Humans↗

PubMed2025

Potential of MRNA vaccines for mpox prevention: current evidence and future directions.

In 2022, the presumption of monkeypox (mpox) to be of limited epidemiology shifted when a global outbreak was announced. Being a member of the Orthopoxvirus genus in the Poxviridae family, it'd been reported in over 82 countries with over 17 000 confirmed cases by July 2022, thus showing its capability for spreading rapidly. As the smallpox vaccine offers 85% cross-immunity against mpox, the outbreak highlighted the attenuation of global immunity against orthopoxviruses after the cessation of vaccination campaigns against smallpox. The mortality of this virus is higher in vulnerable populations such as children, pregnant women, the elderly, and immunosuppressed individuals. With treatment methods being limited to off-label use of antivirals, the need for urgent and efficient preventative measures is emphasized. At present, JYNNEOS (Modified Vaccinia Ankara-Bavarian Nordic), showing favorable safety, and ACAM2000, a live attenuated virus with a high risk of side effects, are two vaccines that are indicated for mpox immunization. However, neither of them has proven full safety, efficacy, and widespread accessibility against mpox. Hence, the use of mRNA vaccines has emerged as a better alternative to traditional vaccinations, as they leverage synthetic messenger RNA to instruct host cells to produce antigens, eliciting both humoral and cellular immune responses. Though they provided rapid scalability, adaptability to emerging viral variants, and an established safety profile after the COVID-19 pandemic, their usage in preventing mpox remains an area of research. This paper elucidates the potential of mRNA technology to address the unmet needs in mpox prevention. It also highlights the need for genomic surveillance, immunological insights, and innovative delivery systems.

COVID-19↗

PubMed2026

Treatment of localized rectal cancer in the Nordic countries-comparison of Nordic to Dutch, ESMO, and NCCN guidelines.

BACKGROUND: Rectal cancer treatment in Nordic countries has traditionally differed, especially regarding neoadjuvant treatment. The aim of this review is to give an overview of the current rectal cancer guidelines in the Nordics and compare these to international guidelines. METHODS: Oncologists and colorectal surgeons from the Nordic countries (Denmark, Finland, Norway, and Sweden) and the Netherlands were invited to participate in this narrative review. Two consensus meetings were held to agree on the content. All authors provided recommendations from their national guidelines. In addition, recommendations from the European Society of Medical Oncology (ESMO) and from the US National Comprehensive Cancer Network (NCCN) guidelines were extracted. RESULTS: Several differences between the included guidelines were identified. The radiological "sigmoid take-off" definition for the upper margin of the rectum has been adapted in Denmark and the Netherlands, whereas the other guidelines rely on distance from the anal verge on rigid sigmoidoscopy. Indications for direct surgery vary considerably, where the NCCN guidelines recommend more aggressive neoadjuvant treatment, primarily total neoadjuvant therapy (TNT), the Nordic and European guidelines open for direct surgery more often, and reserve especially TNT for high-risk cases. European countries more often recommend short-course radiotherapy, whereas NCCN maintains chemoradiotherapy as the mainstay. Whereas intentional and opportunistic organ preservation is an established part of the Dutch, NCCN, and ESMO guidelines, its use is mostly restricted to clinical trials in the Nordics. The Nordics and the Netherlands are restrictive in terms of adjuvant treatment, which is frequently recommended in ESMO and NCCN. Whereas neoadjuvant immunotherapy is recommended for mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) rectal cancer in NCCN, this use is off-label in Europe and not routinely recommended. CONCLUSION: Although all guidelines rely on the same evidence, there are considerable differences, especially in the indications and type of oncologic treatment, both in the neoadjuvant and in the adjuvant setting.

Rectal Neoplasms↗

PubMed2026

Matched targeted therapy use after broad genomic profiling in advanced Non-Small cell lung cancer.

INTRODUCTION: While broad genomic profiling is increasingly used in advanced NSCLC (aNSCLC), the impact of test results on subsequent guideline-concordant targeted therapy selection remains incompletely understood. METHODS: Using a merged dataset of two large, nationwide, patient-level databases, we identified patients who were diagnosed with aNSCLC 2017-2023, had potentially actionable genomic profiling findings, and initiated systemic therapy. Patients were categorized into actionability subgroups based on contemporaneous regulatory approvals and NCCN guideline recommendations. Within each subgroup, we assessed receipt of guideline-concordant targeted therapy within 24 months, including potential underuse (non-receipt of recommended treatment) and overuse (receipt of non-recommended treatment). RESULTS: Among 6620 patients (67.4% ≥65 years, 54.6% female, 68.9% White), guideline-concordant targeted therapy use varied substantially by actionability category: 2313 (89.6%) of 2582 patients with available 1st-line on-label options received them (10.4% underuse), while 212 (67.3%) of 315 patients with available later-line on-label options received them after 1st-line (32.7% underuse). Among 441 patients with available guideline-concordant off-label options, only 122 (27.7%) received them (72.3% underuse). Conversely, 238 (8.6%) of 3282 patients received matched but guideline-discordant off-label options, representing overuse of ineffective or unestablished therapies. Smoking history, squamous histology, and high PD-L1 expression were associated with lower targeted therapy receipt. CONCLUSIONS: In this cohort study of aNSCLC care, the guideline concordance of targeted therapy use varied by clinical actionability of molecular testing results. Underuse was more common in patients with later-line and off-label targeted therapy options. Patients with classical smoking-related risk profiles were substantially less likely to receive targeted therapy even when actionable alterations were identified.

Journal Article↗

PubMed2026

An Application of Iterative Health Economic Evaluation: An Update on the Early Cost Effectiveness of Whole-Genome Sequencing in Advanced Non-small-Cell Lung Cancer.

OBJECTIVE: Whole genome sequencing (WGS) can identify more druggable targets than the standard of care (SoC) panels, however, its health effects and costs are highly uncertain. Given the rapidly evolving treatment landscape and pricing, an iterative approach is crucial to continuously reassess evidence and adapt economic models. Our objective was to update a previously developed economic model for WGS. METHODS: We used a structured approach to identify and report model elements requiring updates, based on established tools and methodological guidance, and applied it to the probabilistic decision model by Simons et al.(2021), which compared SoC, WGS, and SoC followed by WGS in patients with inoperable stage IIIB, C/IV NSCLC in the Dutch setting. RESULTS: Updates included a new treatment (sotorasib), revised drug and diagnostic costs, and adherence to the latest guidelines. Drug and WGS diagnostics costs fell by 8% and 26%, respectively. SoC diagnostic prices increased by 17%. We explored the impact of the prevalence of druggable targets, effectiveness of off-label treatments, (academic-specific) diagnostic costs, and price negotiations. The ICER of WGS versus SoC decreased from €737,197 to €419,053/QALY. WGS would become cost-effective if diagnostic costs descended from €2,180 to €1,246 or if additional druggable targets were identified in ≥3.3% of patients. CONCLUSION: Our structured approach effectively identified items in the original analysis requiring updates and provides a foundation for further developing a checklist to guide iterative HTA. Continued monitoring and assessment of new treatment options, the dynamic diagnostics and costs throughout the life-cycle remain necessary to determine when WGS can be considered cost-effective.

NSCLC↗

PubMed2026

Tumor Mutational Landscape and Its Correlation With Histopathological Characteristics in Breast Cancer.

BACKGROUND/AIM: In breast cancer, knowledge of the associations between clinicopathologic characteristics, genetic changes, and subtype-specific patterns is expanding. This study investigated how pathological and clinical variables affect the actionability of Next Generation Sequencing (NGS)-based tumor molecular data. MATERIALS AND METHODS: 227 breast cancer patients referred to Genekor's laboratory for tumor molecular profile analysis were included in the study. Pathology records were used to assess critical clinicopathological features, including HER2, ER, PR, Ki67, grade, metastatic site, and age. A 1021-gene NGS-based multigene panel was utilized to assess tumor biology alongside tumor mutational burden (TMB) and microsatellite instability (MSI). RESULTS: Comprehensive genomic profiling revealed that 95.6% of the patients harbored at least one oncogenic or likely oncogenic alteration, highlighting the high diagnostic yield of NGS-based testing. Distinct subtype-specific patterns were observed: HR+/HER2- tumors were enriched for PIK3CA and ESR1 gene alterations, whereas triple-negative breast cancer (TNBC) was dominated by TP53 alterations. Clinically actionable alterations were most common in HR+/HER2- tumors (~60% on-label), whereas TNBC more often harbored off-label or trial-associated targets. The inclusion of tumor-agnostic biomarkers (TMB/MSI) increased on-label actionability up to 64.5% in HR+/HER2- tumors, primarily driven by TMB-high cases. Median TMB values were low, and age was the only independent predictor. Furthermore, the presence of actionable alterations was significantly higher in metastatic tumors, and TP53 alterations were associated with aggressive tumor characteristics. CONCLUSION: Comprehensive NGS-based genomic profiling identifies clinically actionable alterations in over half of breast cancer patients, with substantial variability across molecular subtypes. The HR+/HER2- subtype demonstrates the highest prevalence of on-label actionable biomarkers. These findings support the routine implementation of comprehensive genomic profiling, especially in metastatic HER2-negative breast cancer, to guide precision oncology strategies and enable enrollment in biomarker-driven clinical trials.

Humans↗