{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:49:49Z","timestamp":1790743789305,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,13]],"date-time":"2023-08-13T00:00:00Z","timestamp":1691884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Interindividual variability in response to rituximab remains unexplored in antineutrophil cytoplasmic antibody (ANCA)\u2013associated vasculitides. Rituximab pharmacokinetics (PK) and pharmacodynamics (PD) as well as genetic polymorphisms could contribute to variability. This ancillary study of the MAINRITSAN 2 trial aimed to explore the relationship between rituximab plasma concentration, genetic polymorphisms in PK\/PD candidate genes, and clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients included in the MAINRITSAN2 trial (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link> identifier: NCT01731561) were randomized to receive a 500\u2010mg fixed\u2010schedule rituximab infusion or an individually tailored regimen. Rituximab plasma concentrations at month 3 (CM3) were assessed. DNA samples (n\u00a0=\u00a053) were genotyped for single\u2010nucleotide polymorphisms within 88 putative PK\/PD candidate genes. The relationship between PK\/PD outcomes and genetic variants was investigated using logistic linear regression in additive and recessive genetic models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One hundred and thirty\u2010five patients were included. The frequency of underexposed patients (&lt;4 \u03bcg\/ml) in the fixed\u2010schedule group was statistically lower compared to that in the tailored\u2010infusion group (2.0% versus 18.0%; <jats:italic>P<\/jats:italic> =\u20090.02, respectively). Low rituximab plasma concentration at 3 months (CM3 &lt;4 \u03bcg\/ml) was an independent risk factor for major relapse (odds ratio 6.56 [95% confidence interval (95% CI) 1.26\u201334.09]; <jats:italic>P<\/jats:italic> =\u20090.025) at month 28 (M28). A sensitivity survival analysis also identified CM3 &lt;4 \u03bcg\/ml as an independent risk factor for major relapse (hazard ratio [HR] 4.81 [95% CI 1.56\u201314.82]; <jats:italic>P<\/jats:italic> =\u20090.006) and relapse (HR 2.70 [95% CI 1.02\u20137.15]; <jats:italic>P<\/jats:italic> =\u20090.046). STAT4 rs2278940 and PRKCA rs8076312 were significantly associated with CM3 but not with major relapse onset at M28.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that drug monitoring could be useful to individualize the schedule of rituximab administration within the maintenance phase.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42556","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T13:44:12Z","timestamp":1683121452000},"page":"2003-2013","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Association Between Plasma Rituximab Concentration and the Risk of Major Relapse in Antineutrophil Cytoplasmic Antibody\u2013Associated Vasculitides During Rituximab Maintenance Therapy"],"prefix":"10.1002","volume":"75","author":[{"given":"Nihel","family":"Khoudour","sequence":"first","affiliation":[{"name":"Department of Pharmacokinetics and Pharmacochemistry Cochin University Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris, CARPEM  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Delestre","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Referral Center for Rare Systemic Autoimmune Diseases, H\u00f4pital Cochin, Assistance Publique\u2010H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Jabot\u2010Hanin","sequence":"additional","affiliation":[{"name":"Bioinformatic Platform, INSERM UMR 1163, Institut Imagine, and Bioinformatics Core Facility, Structure F\u00e9d\u00e9rative de Recherche Necker, INSERM US24\/CNRS UMS 3633 Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Jouinot","sequence":"additional","affiliation":[{"name":"Institut du Cancer Paris CARPEM, AP\u2010HP, APHP Centre, Department of Medical Oncology, ARIANE, Cochin Hospital, and INSERM U\u20101016, CNRS UMR\u20108104 Universit\u00e9 Paris Cit\u00e9, Institut Cochin  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Nectoux","sequence":"additional","affiliation":[{"name":"F\u00e9d\u00e9ration de G\u00e9n\u00e9tique et M\u00e9decine G\u00e9nomique, H\u00f4pital Cochin, AP\u2010HP, Centre\u2010Universit\u00e9 Paris Cit\u00e9, 27 rue du Faubourg\u2010Saint\u2010Jacques, Paris, France, and Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Letouneur","sequence":"additional","affiliation":[{"name":"INSERM U\u20101016, CNRS UMR\u20108104 Universit\u00e9 Paris Cit\u00e9, Institut Cochin  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Izac","sequence":"additional","affiliation":[{"name":"INSERM U\u20101016, CNRS UMR\u20108104 Universit\u00e9 Paris Cit\u00e9, Institut Cochin  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Vidal","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Pharmacochemistry Cochin University Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris, and Universit\u00e9 Paris Cit\u00e9, UMR8038 CNRS, U1268 INSERM, Facult\u00e9 de Pharmacie, PRES Sorbonne Paris Cit\u00e9, CARPEM  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo\u00efc","family":"Guillevin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Referral Center for Rare Systemic Autoimmune Diseases, H\u00f4pital Cochin, Assistance Publique\u2010H\u00f4pitaux de Paris, and Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3573-9203","authenticated-orcid":false,"given":"Xavier","family":"Pu\u00e9chal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Referral Center for Rare Systemic Autoimmune Diseases, H\u00f4pital Cochin, Assistance Publique\u2010H\u00f4pitaux de Paris, and Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Charles","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Institut Mutualiste Montsouris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6612-7336","authenticated-orcid":false,"given":"Benjamin","family":"Terrier","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Referral Center for Rare Systemic Autoimmune Diseases, H\u00f4pital 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