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Assessment of romiplostim immunogenicity in adult patients in clinical trials and in a global postmarketing registry.

ABSTRACT: Antibodies to first-generation recombinant thrombopoietin (TPO) neutralized endogenous TPO and caused thrombocytopenia in some healthy subjects and chemotherapy patients. The second-generation TPO receptor agonist romiplostim, having no sequence homology to TPO, was developed to avoid immunogenicity. This analysis examined development of binding and neutralising antibodies to romiplostim or TPO among adults with immune thrombocytopenia (ITP) in 13 clinical trials and a global postmarketing registry. 60/961 (6·2%) patients from clinical trials developed anti-romiplostim-binding antibodies post-baseline. The first positive binding antibody was detected 14 weeks (median) after starting romiplostim, at median romiplostim dose of 2 µg/kg and median platelet count of 29.5 × 109 /l; most subjects had ?98·5% of platelet assessments showing response. Neutralising antibodies to romiplostim developed in 0·4% of patients, but were unrelated to romiplostim dose and did not affect platelet count. Thirty-three patients (3·4%) developed anti-TPO-binding antibodies; none developed anti-TPO-neutralising antibodies. In the global postmarketing registry, 9/184 (4·9%) patients with spontaneously submitted samples had binding antibodies. One patient with loss of response had anti-romiplostim-neutralising antibodies (negative at follow-up). Collectively, anti-romiplostim-binding antibodies developed infrequently. In the few patients who developed neutralising antibodies to romiplostim, there was no cross-reactivity with TPO and no associated loss of platelet response.

SUBMITTER: Mytych DT

PROVIDER: S-EPMC7540503 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Assessment of romiplostim immunogenicity in adult patients in clinical trials and in a global postmarketing registry.

Mytych Daniel T DT Park Joseph K JK Kim June J Barger Troy E TE Boshier Andy A Jawa Vibha V Kuter David J DJ

British journal of haematology 20200420 6

Antibodies to first-generation recombinant thrombopoietin (TPO) neutralized endogenous TPO and caused thrombocytopenia in some healthy subjects and chemotherapy patients. The second-generation TPO receptor agonist romiplostim, having no sequence homology to TPO, was developed to avoid immunogenicity. This analysis examined development of binding and neutralising antibodies to romiplostim or TPO among adults with immune thrombocytopenia (ITP) in 13 clinical trials and a global postmarketing regis ...[more]

PMID: 32311075

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Project description:Background and objectiveUpadacitinib is indicated for diseases affecting persons of childbearing potential including rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis; however, teratogenicity was observed in animal studies. Given the potential for human fetal risk, pregnancy avoidance measures were required during clinical trials. This analysis describes pregnancy outcomes in patients exposed to upadacitinib during pregnancy.MethodsClinical trial and postmarketing cases of in utero exposure to upadacitinib were identified in AbbVie's safety database through 25 April, 2023. Analysis of clinical trial cases and postmarketing reports are presented separately; prospective and retrospectively reported pregnancy outcomes are integrated for each. Descriptive rates are presented to summarize outcomes.ResultsThere were 128 maternal upadacitinib-exposed pregnancies with known outcomes identified; 80 and 48 pregnancies were reported in clinical trials and the postmarketing setting, respectively. In clinical trials (mean in utero exposure of 5 weeks, 3 days), live births (54%), spontaneous abortions (24%), elective terminations (21%), and ectopic pregnancy (1%) were reported. There was one report of a congenital malformation: a 35-week infant with an atrial septal defect. In postmarketing cases, live births (46%), spontaneous abortions (38%), elective terminations (15%), and ectopic pregnancy (2%) were reported.ConclusionsAs the data are limited for in utero exposure to upadacitinib, definitive conclusions cannot be drawn regarding the effect of upadacitinib on pregnancy outcomes. Rates of adverse pregnancy outcomes with upadacitinib exposure were comparable to rates observed in the general population or patients with autoimmune inflammatory diseases. To date, no apparent evidence of teratogenicity exists in the analyses of human pregnancies exposed to upadacitinib during the first trimester.

Project description:BackgroundPain is a frequent reason for contacting the Emergency Medical Services (EMS), and effective pain management constitutes one of its cornerstones. The aims of this study have been: (a) to describe the prevalence of pain intensity ratings in EMS care of patients with pain-related conditions; (b) to describe pain treatment in the EMS setting in terms of drugs administered and the proportion of patients receiving analgesics and (c) to investigate the relationship between patients' self-reported pain intensity and vital signs.MethodsThis is a retrospective observational cohort study using data from 394,700 EMS missions conducted 2021 and 2022, as recorded in the Swedish Ambulance Registry. The study focused on patients who contacted the EMS due to pain, trauma, or injury. Pain intensity was recorded using the Numeric Rating Scale (NRS). NRS scores of 5-10 were considered as high-level pain and NRS ≤ 4 as low-level. Descriptive statistics were used to present categorical and continuous variables. Chi-square tests were applied for dichotomous variables, while Kruskal-Wallis tests were used for ordinal data. Logistic regression analysis was carried out to identify factors associated with pain intensity and analgesic treatment. p value < 0.001 was considered statistically significant.ResultsPain intensity was recorded in 23.6% of cases. Most patients rated their pain as high-level (NRS 5-10, 57.4% of those assessed). Analgesics were administered in 27.5% of cases, with higher administration rates observed when pain intensity was documented. Female sex, higher breathing rates, and higher systolic blood pressure were associated with higher pain intensity, while increasing age was associated with lower odds of reporting high-level pain intensity. No significant association was found between heart rate and pain intensity.ConclusionThis 2-year cohort study highlights significant deficiencies in recorded pain assessment and management in the Swedish EMS. Only 22.5% of the patients had their pain assessed with a validated scale, while 27.5% received analgesics, although pain-related conditions were a common reason for contacting the EMS. The findings indicate a lack of systematic pain assessment which puts many patients at risk of insufficient pain relief.

Dataset Information

Assessment of romiplostim immunogenicity in adult patients in clinical trials and in a global postmarketing registry.

Publications

Assessment of romiplostim immunogenicity in adult patients in clinical trials and in a global postmarketing registry.

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