{"entity": "journal", "iuid": "c5e85eda8fbe47aba314395513dcb7a6", "timestamp": "2026-07-20T12:56:13.332Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Clin.%20Pharmacol.%20Ther..json"}, "display": {"href": "https://publications.scilifelab.se/journal/Clin.%20Pharmacol.%20Ther."}}, "title": "Clin. Pharmacol. Ther.", "issn": "1532-6535", "issn-l": "0009-9236", "publications_count": 5, "publications": [{"entity": "publication", "iuid": "a3e0296764c54e03ba99681fee25bca5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a3e0296764c54e03ba99681fee25bca5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a3e0296764c54e03ba99681fee25bca5"}}, "title": "Longitudinal Analysis of Natural History Progression of Rare and Ultra-Rare Cerebellar Ataxias Using Item Response Theory.", "authors": [{"family": "Hamdan", "given": "Alzahra", "initials": "A", "orcid": "0009-0002-3102-2707", "researcher": {"href": "https://publications.scilifelab.se/researcher/b723248aafce4dcd9bce04164bf6e4ec.json"}}, {"family": "Hendrickx", "given": "Niels", "initials": "N", "orcid": "0009-0000-0951-7514", "researcher": {"href": "https://publications.scilifelab.se/researcher/efbad26df28d450da47e241f85d67dd3.json"}}, {"family": "Hooker", "given": "Andrew C", "initials": "AC", "orcid": "0000-0002-2676-5912", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f2a10ae6b38449aa4865cd073be7f24.json"}}, {"family": "Chen", "given": "Xiaomei", "initials": "X", "orcid": "0009-0002-0663-0532", "researcher": {"href": "https://publications.scilifelab.se/researcher/9dfd2d7e0be5469cb564bc373f24311e.json"}}, {"family": "Comets", "given": "Emmanuelle", "initials": "E", "orcid": "0000-0002-9150-9886", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc3f70e414c248c7b04948c3a4e571d8.json"}}, {"family": "Trasch\u00fctz", "given": "Andreas", "initials": "A", "orcid": "0000-0002-8165-5898", "researcher": {"href": "https://publications.scilifelab.se/researcher/20329d73c37449b1b98a20585e096f32.json"}}, {"family": "Sch\u00fcle", "given": "Rebecca", "initials": "R", "orcid": "0000-0002-7781-2766", "researcher": {"href": "https://publications.scilifelab.se/researcher/24310ee59f694c24beb5cabbfb33b0ea.json"}}, {"family": "ARCA Study Group", "given": "", "initials": ""}, {"family": "EVIDENCE\u2010RND Consortium", "given": "", "initials": ""}, {"family": "Mentr\u00e9", "given": "France", "initials": "F", "orcid": "0000-0002-7045-1275", "researcher": {"href": "https://publications.scilifelab.se/researcher/b72e8bb8370c4cc3ab44f0cc01591370.json"}}, {"family": "Synofzik", "given": "Matthis", "initials": "M", "orcid": "0000-0002-2280-7273", "researcher": {"href": "https://publications.scilifelab.se/researcher/7005e3844fd34960a2045bb7febeec57.json"}}, {"family": "Karlsson", "given": "Mats O", "initials": "MO", "orcid": "0000-0003-1258-8297", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b7ca3868f0b431799ea51c4641d1e5a.json"}}], "type": "journal article", "published": "2024-12-00", "journal": {"title": "Clin. Pharmacol. Ther.", "issn": "1532-6535", "volume": "116", "issue": "6", "pages": "1593-1605", "issn-l": "0009-9236"}, "abstract": "Degenerative cerebellar ataxias comprise a heterogeneous group of rare and ultra-rare genetic diseases. While disease-modifying treatments are now on the horizon for many ataxias, robust trial designs and analysis methods are lacking. To better inform trial designs, we applied item response theory (IRT) modeling to evaluate the natural history progression of several ataxias, assessed with the widely used scale for assessment and rating of ataxia (SARA). A longitudinal IRT model was built utilizing real-world data from the large autosomal recessive cerebellar ataxia (ARCA) registry. Disease progression was evaluated for the overall cohort as well as for the 10 most common ARCA genotypes. Sample sizes were calculated for simulated trials with autosomal recessive spastic ataxia Charlevoix-Saguenay (ARSACS) and polymerase gamma (POLG) ataxia, as showcased, across multiple design and analysis scenarios. Longitudinal IRT models were able to describe the changes in the latent variable underlying SARA as a function of time since ataxia onset for both the overall ARCA cohort and the common genotypes. The typical progression rates varied across genotypes between relatively high in POLG (~ 0.98 SARA points/year at SARA = 20) and very low in COQ8A ataxia (~ 0.003 SARA points/year at SARA = 20). Smaller trial sizes were required in case of faster progression, longer trials (~ 75-90% less with 5 years vs. 2 years), and larger drug effects (~ 70-80% less with 100% vs. 50% inhibition). Simulating under the developed IRT model, the longitudinal IRT model had the highest power, with a well-controlled type I error, compared to total score models or end-of-treatment analyses. The established longitudinal IRT framework allows efficient utilization of natural history data and ultimately facilitates the design and analysis of treatment trials in rare and ultra-rare genetic ataxias.", "doi": "10.1002/cpt.3466", "pmid": "39403821", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-25T10:09:52.118Z", "modified": "2025-02-28T14:09:44.213Z"}, {"entity": "publication", "iuid": "9500c75664a34a1c88cb37c1ba8d330a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9500c75664a34a1c88cb37c1ba8d330a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9500c75664a34a1c88cb37c1ba8d330a"}}, "title": "Subcutaneous Marzeptacog Alfa (Activated) for On-Demand Treatment of Bleeding Events in Subjects With Hemophilia A or B With Inhibitors.", "authors": [{"family": "Faraj", "given": "Alan", "initials": "A", "orcid": "0009-0009-0165-363X", "researcher": {"href": "https://publications.scilifelab.se/researcher/34964c6116584659903eb1805dc12f67.json"}}, {"family": "Nyberg", "given": "Joakim", "initials": "J", "orcid": "0000-0002-2839-4940", "researcher": {"href": "https://publications.scilifelab.se/researcher/b6a24e7a2f36420083dad4f082f2eac4.json"}}, {"family": "Blouse", "given": "Grant E", "initials": "GE"}, {"family": "Knudsen", "given": "Tom", "initials": "T"}, {"family": "Simonsson", "given": "Ulrika S H", "initials": "USH", "orcid": "0000-0002-3424-9686", "researcher": {"href": "https://publications.scilifelab.se/researcher/653eb745f8e847d0b4bac44bba7dec4d.json"}}], "type": "journal article", "published": "2024-03-00", "journal": {"title": "Clin. Pharmacol. Ther.", "issn": "1532-6535", "volume": "115", "issue": "3", "pages": "498-505", "issn-l": "0009-9236"}, "abstract": "Marzeptacog alfa (MarzAA) is under development for subcutaneous treatment of episodic bleeds in patients with hemophilia A/B and was studied in a phase III trial evaluating MarzAA compared with standard-of-care (SoC) for on-demand use. The work presented here aimed to evaluate MarzAA and SoC treatment of bleeding events on a standardized four-point efficacy scale (poor, fair, good, and excellent). Two continuous-time Markov modeling approaches were explored; a four-state model analyzing all four categories of bleeding improvement and a two-state model analyzing a binarized outcome (treatment failure (poor/fair), and treatment success (good/excellent)). Different covariates impacting improvement of bleeding episodes as well as a putative relationship between MarzAA exposure and improvement of bleeding episodes were evaluated. In the final four-state model, higher baseline diastolic blood pressure and higher age (> 33 years of age) were found to negatively and positively impact improvement of bleeding condition, respectively. Bleeding events occurring in knees and ankles were found to improve faster than bleeding events at other locations. The covariate effects had most impact on early treatment success (\u2264 3 hours) whereas at later timepoints (> 12 hours), treatment success was similar for all patients indicating that these covariates might be clinically relevant for early treatment response. A statistically significant relationship between MarzAA zero-order absorption and improvement of bleedings (P < 0.05) were identified albeit with low precision. No statistically significant difference in treatment response between MarzAA and intravenous SoC was identified, indicating the potential of MarzAA for treatment of episodic bleeding events with a favorable subcutaneous administration route.", "doi": "10.1002/cpt.3172", "pmid": "38173172", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-25T10:09:46.624Z", "modified": "2025-02-28T14:09:39.021Z"}, {"entity": "publication", "iuid": "d52fe9ba559d4dbcb12811ce80a182df", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d52fe9ba559d4dbcb12811ce80a182df.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d52fe9ba559d4dbcb12811ce80a182df"}}, "title": "Exome Sequencing Reveals Common and Rare Variants in F5 Associated With ACE Inhibitor and Angiotensin Receptor Blocker-Induced Angioedema.", "authors": [{"family": "Maroteau", "given": "Cyrielle", "initials": "C", "orcid": "0000-0001-7816-5508", "researcher": {"href": "https://publications.scilifelab.se/researcher/ebfc9425cb394843ac30847955e53ebe.json"}}, {"family": "Siddiqui", "given": "Moneeza Kalhan", "initials": "MK"}, {"family": "Veluchamy", "given": "Abirami", "initials": "A"}, {"family": "Carr", "given": "Fiona", "initials": "F"}, {"family": "White", "given": "Myra", "initials": "M"}, {"family": "Cassidy", "given": "Andrew J", "initials": "AJ"}, {"family": "Baranova", "given": "Ekaterina V", "initials": "EV"}, {"family": "Rasmussen", "given": "Eva R", "initials": "ER"}, {"family": "Eriksson", "given": "Niclas", "initials": "N", "orcid": "0000-0002-2152-4343", "researcher": {"href": "https://publications.scilifelab.se/researcher/64611a83caba46d597f45371b77de26b.json"}}, {"family": "Bloch", "given": "Katarzyna M", "initials": "KM"}, {"family": "Brown", "given": "Nancy J", "initials": "NJ"}, {"family": "Bygum", "given": "Anette", "initials": "A"}, {"family": "Hallberg", "given": "Par", "initials": "P", "orcid": "0000-0003-3465-3280", "researcher": {"href": "https://publications.scilifelab.se/researcher/968cb3fe072d4ed09739e8be6668d168.json"}}, {"family": "Karawajczyk", "given": "Malgorzata", "initials": "M"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PKE"}, {"family": "Yue", "given": "Qun-Ying", "initials": "QY"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC"}, {"family": "von Buchwald", "given": "Christian", "initials": "C"}, {"family": "Alfirevic", "given": "Ana", "initials": "A"}, {"family": "Maitland-van der Zee", "given": "Anke H", "initials": "AH"}, {"family": "Wadelius", "given": "Mia", "initials": "M", "orcid": "0000-0002-6368-2622", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec07b9869a1f4b77b734c5dc567dc630.json"}}, {"family": "Palmer", "given": "Colin N A", "initials": "CNA"}, {"family": "PREDICTION-ADR", "given": "", "initials": ""}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Clin. Pharmacol. Ther.", "issn": "1532-6535", "volume": "108", "issue": "6", "pages": "1195-1202", "issn-l": "0009-9236"}, "abstract": "Angioedema occurring in the head and neck region is a rare and sometimes life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Few studies have investigated the association of common variants with this extreme reaction, but none have explored the combined influence of rare variants yet. Adjudicated cases of ACEI-induced angioedema (ACEI-AE) or ARB-induced angioedema (ARB-AE) and controls were recruited at five different centers. Sequencing of 1,066 samples (408 ACEI-AE, ARB-AE, and 658 controls) was performed using exome-enriched sequence data. A common variant of the F5 gene that causes an increase in blood clotting (rs6025, p.Arg506Gln, also called factor V Leiden), was significantly associated with both ACEI-AE and ARB-AE (odds ratio: 2.85, 95% confidence interval (CI), 1.89-4.25). A burden test analysis of five rare missense variants in F5 was also found to be associated with ACEI-AE or ARB-AE, P = 2.09 \u00d7 10-3 . A combined gene risk score of these variants, and the common variants rs6025 and rs6020, showed that individuals carrying at least one variant had 2.21 (95% CI, 1.49-3.27, P = 6.30 \u00d7 10-9 ) times the odds of having ACEI-AE or ARB-AE. The increased risk due to the common Leiden allele was confirmed in a genome-wide association study from the United States. A high risk of angioedema was also observed for the rs6020 variant that is the main coagulation defect-causing variant in black African and Asian populations. We found that deleterious missense variants in F5 are associated with an increased risk of ACEI-AE or ARB-AE.", "doi": "10.1002/cpt.1927", "pmid": "32496628", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-11-16T09:14:47.719Z", "modified": "2021-11-10T12:44:38.679Z"}, {"entity": "publication", "iuid": "d7571e14d8e34260a48b322d331e382e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d7571e14d8e34260a48b322d331e382e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d7571e14d8e34260a48b322d331e382e"}}, "title": "Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions.", "authors": [{"family": "Nicoletti", "given": "Paola", "initials": "P"}, {"family": "Barrett", "given": "Sarah", "initials": "S"}, {"family": "McEvoy", "given": "Laurence", "initials": "L"}, {"family": "Daly", "given": "Ann K", "initials": "AK"}, {"family": "Aithal", "given": "Guruprasad", "initials": "G"}, {"family": "Lucena", "given": "M Isabel", "initials": "MI"}, {"family": "Andrade", "given": "Raul J", "initials": "RJ"}, {"family": "Wadelius", "given": "Mia", "initials": "M"}, {"family": "Hallberg", "given": "P\u00e4r", "initials": "P"}, {"family": "Stephens", "given": "Camilla", "initials": "C"}, {"family": "Bjornsson", "given": "Einar S", "initials": "ES"}, {"family": "Friedmann", "given": "Peter", "initials": "P"}, {"family": "Kainu", "given": "Kati", "initials": "K"}, {"family": "Laitinen", "given": "Tarja", "initials": "T"}, {"family": "Marson", "given": "Anthony", "initials": "A"}, {"family": "Molokhia", "given": "Mariam", "initials": "M"}, {"family": "Phillips", "given": "Elizabeth", "initials": "E"}, {"family": "Pichler", "given": "Werner", "initials": "W"}, {"family": "Romano", "given": "Antonino", "initials": "A"}, {"family": "Shear", "given": "Neil", "initials": "N"}, {"family": "Sills", "given": "Graeme", "initials": "G"}, {"family": "Tanno", "given": "Luciana K", "initials": "LK"}, {"family": "Swale", "given": "Ashley", "initials": "A"}, {"family": "Floratos", "given": "Aris", "initials": "A"}, {"family": "Shen", "given": "Yufeng", "initials": "Y"}, {"family": "Nelson", "given": "Matthew R", "initials": "MR"}, {"family": "Watkins", "given": "Paul B", "initials": "PB"}, {"family": "Daly", "given": "Mark J", "initials": "MJ"}, {"family": "Morris", "given": "Andrew P", "initials": "AP"}, {"family": "Alfirevic", "given": "Ana", "initials": "A"}, {"family": "Pirmohamed", "given": "Munir", "initials": "M"}], "type": "journal article", "published": "2019-05-07", "journal": {"volume": null, "issn": "1532-6535", "issue": null, "title": "Clin. Pharmacol. Ther.", "issn-l": "0009-9236"}, "abstract": "Carbamazepine (CBZ) causes life-threating T-cell-mediated hypersensitivity reactions, including serious cutaneous adverse reactions (SCARs) and drug-induced liver injury (CBZ-DILI). In order to evaluate shared or phenotype-specific genetic predisposing factors for CBZ hypersensitivity reactions, we performed a meta-analysis of two genomewide association studies (GWAS) on a total of 43 well-phenotyped Northern and Southern European CBZ-SCAR cases and 10,701 population controls and a GWAS on 12 CBZ-DILI cases and 8,438 ethnically matched population controls. HLA-A*31:01 was identified as the strongest genetic predisposing factor for both CBZ-SCAR (odds ratio (OR)\u00a0=\u00a08.0; 95% CI 4.10-15.80; P\u00a0=\u00a01.2\u00a0\u00d7\u00a010\n                -9 ) and CBZ-DILI (OR\u00a0=\u00a07.3; 95% CI 2.47-23.67; P\u00a0=\u00a00.0004) in European populations. The association with HLA-A*31:01 in patients with SCAR was mainly driven by hypersensitivity syndrome (OR\u00a0=\u00a012.9; P\u00a0=\u00a02.1\u00a0\u00d7\u00a010-9 ) rather than by Stevens-Johnson syndrome/toxic epidermal necrolysis cases, which showed an association with HLA-B*57:01. We also identified a novel risk locus mapping to ALK only for CBZ-SCAR cases, which needs replication in additional cohorts and functional evaluation.", "doi": "10.1002/cpt.1493", "pmid": "31066027", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [], "notes": [], "created": "2019-07-05T12:56:58.063Z", "modified": "2020-01-21T13:56:14.304Z"}, {"entity": "publication", "iuid": "3463715dd7664c96bd06baa4e0719f09", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3463715dd7664c96bd06baa4e0719f09.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3463715dd7664c96bd06baa4e0719f09"}}, "title": "Sulfasalazine-Induced Agranulocytosis Is Associated With the Human Leukocyte Antigen Locus.", "authors": [{"family": "Wadelius", "given": "Mia", "initials": "M"}, {"family": "Eriksson", "given": "Niclas", "initials": "N"}, {"family": "Kreutz", "given": "Reinhold", "initials": "R"}, {"family": "Bondon-Guitton", "given": "Emmanuelle", "initials": "E"}, {"family": "Iba\u00f1ez", "given": "Luisa", "initials": "L"}, {"family": "Carvajal", "given": "Alfonso", "initials": "A"}, {"family": "Lucena", "given": "M Isabel", "initials": "MI"}, {"family": "Sancho Ponce", "given": "Esther", "initials": "E"}, {"family": "Molokhia", "given": "Mariam", "initials": "M"}, {"family": "Martin", "given": "Javier", "initials": "J"}, {"family": "Axelsson", "given": "Tomas", "initials": "T"}, {"family": "Kohnke", "given": "Hugo", "initials": "H"}, {"family": "Yue", "given": "Qun-Ying", "initials": "QY"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PKE"}, {"family": "Bengtsson", "given": "Mats", "initials": "M"}, {"family": "Hallberg", "given": "P\u00e4r", "initials": "P"}, {"family": "EuDAC", "given": "", "initials": ""}], "type": "journal article", "published": "2018-05-00", "journal": {"volume": "103", "issn": "1532-6535", "issue": "5", "pages": "843-853", "title": "Clin. Pharmacol. Ther.", "issn-l": "0009-9236"}, "abstract": "Agranulocytosis is a serious, although rare, adverse reaction to sulfasalazine, which is used to treat inflammatory joint and bowel disease. We performed a genome-wide association study comprising 9,380,034 polymorphisms and 180 HLA alleles in 36 cases of sulfasalazine-induced agranulocytosis and 5,170 population controls. Sulfasalazine-induced agranulocytosis was significantly associated with the HLA region on chromosome 6. The top hit (rs9266634) was located close to HLA-B, odds ratio (OR) 5.36 (95% confidence interval (CI) (2.97, 9.69) P = 2.55 \u00d7 10 -8 ). We HLA-sequenced a second cohort consisting of 40 cases and 142 treated controls, and confirmed significant associations with HLA-B*08:01, OR = 2.25 (95% CI (1.02, 4.97) P = 0.0439), in particular the HLA-B*08:01 haplotype HLA-DQB1*02:01-DRB1*03:01-B*08:01-C*07:01, OR = 3.79 (95% CI (1.63, 8.80) P = 0.0019), and with HLA-A*31:01, OR = 4.81 (95% CI (1.52, 15.26) P = 0.0077). The number needed to test for HLA-B*08:01 and HLA-A*31:01 to avoid one case was estimated to be 1,500. We suggest that intensified monitoring or alternative treatment should be considered for known carriers of HLA-B*08:01 or HLA-A*31:01.", "doi": "10.1002/cpt.805", "pmid": "28762467", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC5947520"}], "notes": [], "created": "2019-01-04T09:53:05.174Z", "modified": "2021-06-21T14:28:06.039Z"}], "created": "2017-05-09T09:12:13.385Z", "modified": "2020-11-27T13:14:04.833Z"}