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Pharmacokinetics and Safety of Ustekinumab in Patients with Juvenile Psoriatic Arthritis: Results of the Real-World Ustekinumab Pediatric Opportunistic Pharmacokinetics Study (U-POPS)
The “Ustekinumab Pediatric Opportunistic Pharmacokinetics Study” (U-POPS) was conducted to evaluate the pharmacokinetics (PK) and safety of ustekinumab, an interleukin-12/23p40 antagonist, in patients with juvenile psoriatic arthritis (jPsA) who were already receiving ustekinumab via an opportunistic study design. U-POPS was based on the clinical hypothesis that PK should be similar in jPsA and pediatric psoriasis (PsO) populations to further strengthen the extrapolation paradigm between the two populations.
Methods
This real-world, open-label study enrolled participants 5 to < 18 years old with jPsA or 6 to < 18 years with PsO (internal control) who were on ustekinumab for ≥ 16 weeks and received ≥ 3 doses to ensure steady-state concentrations. Ustekinumab was prescribed by the treating physician and supplied outside of the study; PK samples were collected at intervals during a maximum of 16 weeks. The primary endpoint was the observed serum ustekinumab concentrations, which were compared to model-predicted values from prior PsO PK data.
Results
The study included 11 patients with jPsA (mean age, 15.1 years) and 20 with pediatric PsO (mean age, 12.6 years), yielding 100 PK samples. The median ustekinumab dose was 45 mg every 12 weeks. Observed serum ustekinumab concentration-time profiles aligned well with model-predicted concentration-time profiles from pediatric PsO patients. Treatment-emergent adverse events (TEAEs) occurred in 25.8% of patients (jPsA, n = 1; PsO, n = 7) and were consistent with those observed in other ustekinumab studies, with no serious TEAEs reported.
Conclusions
The opportunistic U-POPS study confirmed the existing population PK model for ustekinumab and suggests that ustekinumab exposure and time course are similar between jPsA and pediatric PsO populations, with no new safety concerns.
Edwin Lam and Katherine Berezny contributed equally to this project.
Prior presentation: Part of this work was presented at the American College of Rheumatology Convergence 2024; November 14–19, 2024; Washington, DC, USA.
U-POPS Study Group collaborators are listed in acknowledgements section.
Key Summary Points
Why carry out this study?
Juvenile psoriatic arthritis (jPsA) is a complex, chronic, progressive, debilitating musculoskeletal disease that occurs before the age of 16 years
Ustekinumab, an interleukin-12/23p40 antagonist, has been approved for the treatment of psoriatic arthritis in adults and psoriasis (PsO) in adults, adolescents, and children (≥ 6 years of age); however, ustekinumab has yet to be approved globally for the treatment of jPsA
Based on the clinical hypothesis that pharmacokinetics (PK) should be similar in jPsA and pediatric PsO populations, to further strengthen the extrapolation paradigm between the two populations, the real-world, phase 1 U-POPS study investigated the PK and safety of ustekinumab in patients with jPsA who were already receiving ustekinumab in routine clinical care and compared them with a pediatric PsO internal control cohort and previous ustekinumab population PK (popPK) data
What was learned from the study?
The U-POPS opportunistic sampling of real-world patients with jPsA who were already receiving ustekinumab in routine clinical care led to efficient and reliable PK data collection from this difficult-to-recruit patient population
No appreciable PK differences were observed between the jPsA and pediatric PsO populations, and the existing popPK model for ustekinumab was confirmed, further strengthening the extrapolation paradigm between the two populations. No new safety concerns were identified
The results of U-POPS may be useful for supplementing data from the ongoing phase 3 clinical trial of ustekinumab in patients with jPsA
Introduction
Psoriatic arthritis (PsA) is a complex, chronic, progressive, debilitating musculoskeletal disease [1]. Juvenile psoriatic arthritis (jPsA), which occurs before the age of 16 years, comprises between 5 to 8% of children with juvenile idiopathic arthritis (JIA) [2‐5]. jPsA has a calculated annual incidence of approximately three patients per million children [4, 5]. The use of traditional and biologic disease-modifying antirheumatic drugs has improved clinical outcomes in patients with jPsA; however, significant unmet medical need remains [6, 7].
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Interleukin (IL)-23 plays a crucial role in the development of PsA and is often elevated in patients with PsA, which indicates its potential as a treatment target [8]. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that binds with high affinity to the p40 subunit common to both IL-12 and IL-23 and has demonstrated effectiveness for the treatment of several inflammatory disorders. Ustekinumab also has been approved for the treatment of moderately to severely active Crohn’s disease and ulcerative colitis in adults using intravenous induction dosing followed by subcutaneous (SC) maintenance dosing. Ustekinumab SC has been approved for the treatment of PsA in adults and psoriasis (PsO) in adults, adolescents, and children (≥ 6 years of age) [9]. However, ustekinumab has been approved for the treatment of jPsA (≥ 6 years of age) only in the USA, Brazil, Russia, Taiwan, and Thailand.
A phase 3, open-label, multicenter study to evaluate the efficacy, pharmacokinetics (PK), safety, and immunogenicity of ustekinumab or guselkumab in patients with active jPsA who had an inadequate response to prior treatment is currently underway (PSUMMIT-Jr; ClinicalTrials.gov: NCT05083182) in support of the European Union Pediatric Investigational Plan for regulatory submission and potential approval of ustekinumab for jPsA in other countries [10]. To potentially decrease the time to conduct the phase 3 PSUMMIT-Jr study, the “Ustekinumab Pediatric Opportunistic PK Study” (U-POPS; ClinicalTrials.gov: NCT05252533), a real-world, open-label study, was conducted as another means to characterize the PK and safety of ustekinumab among patients with jPsA ≥ 5 to < 18 years of age who were already receiving ustekinumab in routine clinical care before enrollment. U-POPS was based on the clinical hypothesis that PK should be similar in jPsA and pediatric PsO populations to further strengthen the extrapolation paradigm between the two populations.
Methods
Patients and Study Design
U-POPS was a real-world, open-label, multicenter, phase 1, opportunistic PK study. To be eligible for the study, patients had to be ≥ 5 to < 18 years of age, inclusive, who had been diagnosed with jPsA (i.e., International League of Associations for Rheumatology or Vancouver criteria [11, 12]) by a qualified healthcare provider (HCP), and/or ≥ 6 to < 18 years of age, inclusive, who had been diagnosed with pediatric PsO by a qualified HCP. The pediatric PsO cohort served as an internal control to validate the jPsA PK data by comparing them to previously obtained PK data in phase 3 pediatric PsO studies [13]. The lower age limit of 6 years for the pediatric PsO cohort was selected to mirror the lower age limit of existing pediatric PsO PK data from the completed CADMUS-Jr study [14].
Patients were not eligible for the study if they had poor tolerability of venipuncture or lack of adequate venous access for required blood sampling, or if they had any condition that, in the opinion of the investigator, meant that participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
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To ensure that patients were at ustekinumab steady state, they were required to have been taking ustekinumab for ≥ 16 weeks prior to enrollment and had received ≥ 3 prior doses of ustekinumab. Ustekinumab was administered SC at a dose and frequency prescribed by the patient’s HCP and obtained by the patient outside of the study as per the HCP’s clinical practice; patients did not have to receive a dose of ustekinumab during the study period. Note that the US labeled dosage in patients with jPsA and pediatric PsO administration is weight-based dosing at the initial, 4-week, and 12-week dose, with patients weighing < 60 kg receiving 0.75 mg/kg, 60–100 kg receiving 45 mg, and > 100 kg receiving 90 mg [9]. The maximum study duration per patient was approximately 16 weeks.
The medical history of each patient was collected as part of the screening visit, using a specific case report form (CRF). The CRF included tick boxes for the presence of common disease-related medical conditions, including axial disease (per investigator assessment).
This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and are consistent with Good Clinical Practices and applicable regulatory requirements. The study protocol, protocol amendments, and other relevant documents were reviewed and approved by the institutional review board (IRB) of the participating site (Lurie Children’s Hospital of Chicago IRB, University of Cincinnati Medical IRB, Columbia University Medical Center IRB, Akron Children’s Hospital IRB) or the central IRB (Sterling IRB; IRB ID: 9300-*MASTER) before the study was initiated. Participants or their legally designated representatives provided their written consent to participate in the study after having been informed about the nature and purpose of the study, participation/termination conditions, and risks and benefits.
PK Analysis
The primary endpoint was the observed serum ustekinumab concentrations (μg/ml), which were measured in collected samples using a validated, specific, and sensitive electrochemiluminescence immunoassay on the Meso Scale Discovery platform (Gaithersburg, MD, USA) by or under the supervision of the sponsor [15, 16]. The lowest quantifiable concentration of the assay was 0.1688 μg/ml. Each patient had approximately three study visits, with one PK draw per visit (≥ 7 days apart); a fourth PK sample was collected if the patient agreed. Per the study protocol, it was recommended to collect a trough concentration for each patient during the study (i.e., drawn within 7 days before the next ustekinumab administration and no longer than 12 weeks after the last dose of ustekinumab administration).
Serum ustekinumab concentrations were plotted against the time since last dose. The time course of observed serum ustekinumab concentrations over an every-12-week (q12w) dosing interval was plotted against model-predicted median concentrations, generated using a previously developed adult and pediatric PsO population PK (popPK) model [13]. Briefly, a popPK model was developed to evaluate the consistency in PK of ustekinumab, which combined data from patients with available serum ustekinumab concentrations collected from four phase 3 adult and pediatric PsO studies (LOTUS, PEARL, CADMUS, and CADMUS-Jr). LOTUS (ClinicalTrials.gov ID: NCT01008995) included 317 adult Chinese patients, and PEARL (ClinicalTrials.gov ID: NCT00747344) included 116 Taiwanese and Korean adult patients with moderate-to-severe plaque PsO [13, 17, 18]. CADMUS (ClinicalTrials.gov ID: NCT01090427) included 110 patients with PsO who were ≥ 12 to < 18 years old treated with ustekinumab (standard or half-standard dosing regimens SC at weeks 0, 4, and then q12w) [13, 19]. CADMUS-Jr (ClinicalTrials.gov ID: NCT02698475) included 42 patients with PsO who were ≥ 6 to < 12 years old treated with ustekinumab (standard dosing regimen SC at weeks 0, 4, and then q12w) [13, 14].
A one-compartment model with first-order absorption and elimination was used to model the combined data. The simulations were based on 1000 subjects, and body weight values were sampled with replacement from the National Health and Nutrition Examination Survey (NHANES) III growth database [20]. Given the mixture of pediatric and adult data and the knowledge that body weight is a significant covariate affecting the PK of ustekinumab, body weight was accounted for in the structural PK model. The typical apparent clearance (CL/F) and apparent volume of distribution (V/F) values in patients with pediatric PsO using the primary popPK model were estimated to be 0.20 l/day and 6.77 l, respectively. Taken together, the PK behavior of ustekinumab is similar between adult and pediatric patients after considering body weight. Details of the popPK analysis model were previously published [13].
Safety
Safety data were collected throughout the study, including treatment-emergent adverse events (TEAEs), related TEAEs, as assessed by the investigator, and serious TEAEs, which included TEAEs leading to death or to termination of study participation. TEAEs of special interest included malignancy, active tuberculosis, and opportunistic infections. TEAEs of clinical interest included infections, injection site reactions, and hypersensitivity reactions.
Statistical Analysis
No formal statistical hypothesis was tested in this study, and no comparative statistical analyses were performed. Data were summarized using simple descriptive summary statistics, such as number of observations, mean, standard deviation (SD), median, range, and interquartile range, as appropriate. The sample size determination was not based on statistical considerations; rather, it was based on empirical considerations and is appropriate for the study design, the availability and ongoing generation of safety and PK data of ustekinumab in other pediatric studies, and the low prevalence of jPsA.
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Results
The study was conducted from 2022 to 2023 at eight sites in the US. A total of 31 patients were enrolled, 11 patients in the jPsA cohort and 20 in the pediatric PsO cohort. Baseline demographic characteristics were generally similar between cohorts (Table 1). At enrollment, the mean patient age was 13.5 (SD, 3.0) years, with 9 (29.0%) of the patients between 5 to < 12 years old and 22 (71.0%) of the patients between ages 12 to < 18 years old. Most patients were white (64.5%) and female (74.2%). Approximately half (51.6%) of the patients weighed < 60 kg. At baseline, nearly all patients (90.3%) had PsO, and one-quarter (25.8%) had a family history of PsO. The most common prior jPsA and/or PsO medication was methotrexate (35.5%).
Table 1
Baseline characteristics and medication history
jPsA (N = 11)
Pediatric PsO (N = 20)
Total (N = 31)
Demographics
Age, years
Mean (SD)
15.1 (1.5)
12.6 (3.3)
13.5 (3.0)
Median (IQR)
15.0 (14.0;17.0)
12.5 (10.0;16.0)
14.0 (11.0;16.0)
Age category, n (%)
5 to < 12
0
9 (45.0)
9 (29.0)
12 to < 18
11 (100.0)
11 (55.0)
22 (71.0)
Female, n (%)
8 (72.7)
15 (75.0)
23 (74.2)
Race, n (%)
White
8 (72.7)
12 (60.0)
20 (64.5)
Black or African American
1 (9.1)
3 (15.0)
4 (12.9)
Asian
0
1 (5.0)
1 (3.2)
Multiple
0
1 (5.0)
1 (3.2)
Not reported
1 (9.1)
1 (5.0)
2 (6.5)
Unknown
1 (9.1)
2 (10.0)
3 (9.7)
Weight, kg
Mean (SD)
62.7 (17.4)
59.7 (26.6)
60.8 (23.5)
Median (IQR)
61.50 (50.0; 65.2)
56.60 (36.5; 73.3)
57.20 (48.5; 71.8)
Weight category, n (%)
< 60 kg
5 (45.5)
11 (55.0)
16 (51.6)
≥ 60 kg
6 (54.5)
9 (45.0)
15 (48.4)
BMI, mean (SD), kg/m2
22.5 (6.2)
24.5 (8.2)
23.8 (7.5)
Baseline disease-related medical history (≥ 5% total)a, n (%)
PsO
9 (81.8)
19 (95.0)
28 (90.3)
Family history of PsO
6 (54.5)
2 (10.0)
8 (25.8)
Polyarthritis
5 (45.5)
0
5 (16.1)
Axial disease
4 (36.4)
0
4 (12.9)
Antinuclear antibody positive
3 (27.3)
0
3 (9.7)
Chronic pain/juvenile fibromyalgia
3 (27.3)
0
3 (9.7)
Enthesitis
3 (27.3)
0
3 (9.7)
Common prior jPsA and/or PsO medications (≥ 10% total), n (%)
Methotrexate
8 (72.7)
3 (15.0)
11 (35.5)
Triamcinolone
3 (27.3)
4 (20.0)
7 (22.6)
Adalimumab
5 (45.5)
1 (5.0)
6 (19.4)
Etanercept
3 (27.3)
2 (10.0)
5 (16.1)
Secukinumab
4 (36.4)
1 (5.0)
5 (16.1)
BMI body mass index, IQR interquartile range, jPsA juvenile psoriatic arthritis, PsO psoriasis, SD standard deviation
aPatients may appear in more than one category
The most commonly used concomitant medications during the study were propionic acid derivatives (19.4%), including ibuprofen and naproxen sodium, COVID-19 vaccines (16.1%), paracetamol (6.5%), glucocorticoids (6.5%), and other topical medications for PsO (6.5%).
Three (9.7%) patients discontinued the study early (prior to having three blood samples drawn) for the following reasons: one patient in the jPsA cohort was lost to follow-up, one patient in the jPsA cohort was withdrawn from the study by a parent or guardian, and one patient in the pediatric PsO cohort did not meet the prior dosing requirement for enrollment.
PK Samples and Ustekinumab Exposure
In total, 100 ustekinumab PK samples were collected, 34 from patients with jPsA and 66 from patients with pediatric PsO. Each patient had at least one scheduled PK sample drawn, 29 (93.5%) patients had at least two, 27 (87.1%) had at least three, and 12 (38.7%) had four. The median (range) total ustekinumab dose received in the study for all patients was 45 (18 to 180) mg and was generally administered q12w for both cohorts.
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Serum Ustekinumab Concentrations over Time
Observed serum ustekinumab concentration-time course profiles from patients with jPsA and pediatric PsO were adequately captured when overlaid against model-predicted concentration-time profiles produced using the previously developed popPK model (Fig. 1a). When grouped by body-weight-adjusted dosing regimen (i.e., < 45 mg, 45 mg, or 90 mg), the observed serum ustekinumab concentration-time course was adequately captured when overlaid with model-predicted profiles (Fig. 1b).
Fig. 1
Serum ustekinumab concentration (µg/ml) versus time since last dose (weeks) for a all patients and b by weight-based doses. Includes patients with missing pretreatment dosing information. Shaded bands represent the 90% prediction intervals (N = 3000 for panel a; N = 1000 for each dose group in panel b). One sample from a patient with jPsA in the 45-mg dose group was excluded from this figure. The patient had a serum ustekinumab concentration of 14.55 μg/ml at visit 4. By visit 4, the dose and dosing interval for this patient were switched by the healthcare provider from 45 mg every 12 weeks to 90 mg every 8 weeks, and the visit 4 sample was taken approximately 10.5 days after the last dose. jPsA juvenile psoriatic arthritis
Two patients with jPsA in the 45-mg dose group (i.e., body weights 60 to 100 kg) had a higher than median observed serum ustekinumab concentrations (> 7.00 μg/ml) (Fig. 1b). One patient had serum ustekinumab concentrations of 9.48 μg/ml at visit 1, 5.20 μg/ml at visit 2, 9.29 μg/ml at visit 3, and 14.55 μg/ml at visit 4. By visit 4, the dose and dosing interval for this patient were switched by the HCP from 45 mg q12w to 90 mg every 8 weeks, and the visit 4 sample was taken approximately 10.5 days after the last dose, which likely explains the observed serum ustekinumab concentration of 14.55 μg/ml. This sample value was excluded from Fig. 1. Another patient had serum ustekinumab concentrations of 4.57 μg/ml at visit 1, 3.12 μg/ml at visit 2, 1.42 μg/ml at visit 3, and 7.98 μg/ml at visit 4 (received 45 mg q12w throughout), with the highest value observed approximately 21.8 days following the last dose.
Effect of Body Weight on Serum Ustekinumab Concentration
At visit 1, steady-state serum ustekinumab concentrations by body weight category (< 60 kg and ≥ 60 kg) were similar in both jPsA and pediatric PsO cohorts. For patients weighing < 60 kg, serum ustekinumab concentrations were 0.25–9.48 μg/ml in the jPsA cohort and 0–3.44 μg/ml in the pediatric PsO cohort. For patients weighing ≥ 60 kg, serum ustekinumab concentrations were 0–5.56 μg/ml in the jPsA cohort and 0–4.25 μg/ml in the pediatric PsO cohort.
Safety
Through the end of the study, TEAEs were reported for eight patients (n = 1 jPsA; n = 7 pediatric PsO) (Table 2). Two patients in the pediatric PsO cohort reported non-serious TEAEs that the investigator considered to be related to ustekinumab treatment (gastrointestinal disorders and PsO). One patient who was initially enrolled in the PsO cohort was subsequently diagnosed with jPsA during the course of the trial with the reporting of two TEAEs (arthritis and a human leukocyte antigen B27 [HLA-B*27] positive laboratory result), both of which were considered by the investigator to be unrelated to ustekinumab treatment; this patient was analyzed as part of the jPsA cohort. No serious TEAEs, serious infections, malignancies, injection site and/or hypersensitivity reactions, deaths, or TEAEs leading to termination of study participation were reported. TEAEs of clinical interest included two infections (ear infection and influenza), both in the pediatric PsO cohort.
Table 2
Summary of TEAEs
Patients with ≥ 1a, n (%)
jPsA (N = 11)
Pediatric PsO (N = 20)
Total (N = 31)
TEAEs
1 (9.1)b
7 (35.0)
8 (25.8)
Related TEAEsc
0
2 (10.0)
2 (6.5)
Related non-serious TEAEsc
0
2 (10.0)d
2 (6.5)
Serious TEAEs
0
0
0
TEAEs leading to deathe
0
0
0
TEAEs leading to termination of study participation
The U-POPS opportunistic sampling of real-world patients with jPsA who were already receiving ustekinumab in routine clinical care led to efficient and reliable PK data collection from this difficult-to-recruit patient population [21]. We hypothesized that there would be no appreciable PK differences between the jPsA and pediatric PsO populations, given the clinical similarities between jPsA and pediatric PsO and the lack of clinically meaningful effects of age on the disposition of ustekinumab [22, 23]. In fact, the US Food and Drug Administration (FDA) approved SC ustekinumab for jPsA in patients ≥ 6 years of age on the basis of extrapolation analyses between pediatric patients with PsO and adult patients with PsA [9, 22]. The results of U-POPS confirm the existing popPK model for ustekinumab in pediatric patients and suggest that ustekinumab exposure and time course are similar between patients with jPsA and those with pediatric PsO. The overlapping steady-state serum ustekinumab concentrations in the jPsA and pediatric PsO cohorts when evaluated by body weight category substantiated the similarity of PK profiles in these patient populations. No new safety concerns were identified.
The opportunistic study design may augment data from randomized clinical trials and has been used by the Pediatric Trial Network to support pediatric medication label changes by the FDA [21, 24‐27]. The findings from U-POPS supplement data from the ongoing phase 3, open-label ustekinumab study in jPsA (PSUMMIT-Jr). For the primary endpoint, the opportunistic trial design likely provided a more rapid method to collect PK data and show the overlap with existing pediatric PsO PK data than attempting to recruit newly diagnosed patients with jPsA into a clinical trial, which would have required more stringent inclusion and exclusion criteria. Additionally, the analysis of PK samples in U-POPS could be completed more rapidly than in PSUMMIT-Jr because the study duration per patient was only approximately 16 weeks compared to the 52-week duration in PSUMMIT-Jr [10].
The PK concentration-time profiles observed for patients with jPsA in this study were similar to the previous findings observed for pediatric patients with PsO [14, 19]. Observed ustekinumab concentration-time courses from patients with jPsA and pediatric PsO treated with ustekinumab were adequately captured in both populations when overlaid with model-predicted concentration-time profiles using a previously developed popPK model [13]. The model was further validated using PK samples from patients with pediatric PsO receiving ustekinumab from the current study, suggesting that ustekinumab exposures and time courses are similar between patients with jPsA and those with pediatric PsO. Two patients receiving 45 mg ustekinumab had high serum ustekinumab concentrations. The outlier serum ustekinumab concentrations observed for these two patients were likely due to the opportunistic design, where the use of historical dosing records and real-world use by the HCP may limit the interpretation of these results.
Methotrexate is a common first-line therapy for PsA [28] and was the most common prior medication in this study, with 72.7% of the jPsA cohort and 15.0% of the pediatric PsO cohort having a history of methotrexate use. Although studies are lacking on whether prior treatment with methotrexate for PsA affects subsequent ustekinumab therapy, concomitant methotrexate does not appear to impact ustekinumab PK, immunogenicity, efficacy, or safety in PsA [29‐31].
Limitations of this study included the small number of patients, variable dosing schedules, and short study duration. To enroll patients with the rare disease of jPsA already prescribed ustekinumab, patients remained on their ustekinumab dosing scheme as prescribed by their treating HCP during the study. The small sample size and short duration of the trial resulted in the collection of limited safety data. Nonetheless, the overall observed safety profile of ustekinumab in this study was consistent with that observed in other pediatric and adult ustekinumab clinical trials and is consistent with the known safety profile of ustekinumab [14, 17‐19, 32]. Additionally, most patients enrolled in the study were female (74.2%). A female predominance of PsA has been recently reported in the literature [33], which might have been reflected in the U-POPS population; however, the small sample size precludes drawing any conclusions regarding this observation. Interpretation of the PK data was also limited by the opportunistic study design, use of historical dosing records, and real-world dosing of ustekinumab. Only four PK samples were available in the 90-mg dose category (> 100 kg), all of which were from the same patient in the pediatric PsO cohort, which may limit the generalizability of these findings to children weighing ≥ 100 kg. Furthermore, the PK data were limited to the observed concentration-over-time profiles, which may restrict the interpretation of the exposure (i.e., area under the concentration-time curve and maximum concentration) efficacy relationship in the jPsA population.
Conclusion
The opportunistic U-POPS study allowed for efficient PK data collection in this difficult-to-recruit population. No appreciable differences in PK profiles were observed between the jPsA and pediatric PsO populations, further strengthening the extrapolation paradigm between the two populations. These data may be useful for supplementing data from the ongoing phase 3 clinical trial of ustekinumab in patients with jPsA.
Acknowledgements
The authors thank the participants of the U-POPS study. We also thank Yang Chen (formerly of Johnson & Johnson) for participation in the study design, An Vermeulen and Mahesh Samtani of Johnson & Johnson for oversight and review of the population PK overlay, and Richard Strauss of Johnson & Johnson for input throughout the project. Finally, we thank the Pediatric Rheumatology Collaborative Study Group for their constructive input to the study and support of its completion. U-POPS Study Group Collaborators: Iris Reyhan; Children’s Hospital Los Angeles, Los Angeles, CA. Kathryn Cook; Akron Children’s Hospital, Akron, OH
Medical Writing/Editorial Assistance
Medical writing support was provided by Cindy C. Taylor, PhD, of Certara under the direction of the authors in accordance with Good Publication Practice guidelines (Ann Intern Med. 2022;175:1298-1304). This assistance was funded by Johnson & Johnson.
Declarations
Conflict of Interest
Amy S. Paller is an investigator for AbbVie, BioMendics, Dermavant, Eli Lilly, Incyte, Johnson & Johnson, Regeneron, and UCB; is a consultant for Abeona, Arcutis, BioCryst, Boehringer-Ingelheim, Castle Creek, Chiesi, Dermavant, Johnson & Johnson, Krystal, LEO, Lilly, L’Oreal, MoonLake Immunotherapeutics, Pelthos, Quoin, Regeneron, and Sanofi; and serves on the data safety monitoring boards of AbbVie, Abeona, BioCryst, Daiichi Sankyo, and Galderma. Corey J. Bishop, Jocelyn H. Leu, Katherine Berezny, Kathleen G. Lomax, Renping Zhang, Sophia G. Liva, and Valerie Smith are employees of Johnson & Johnson and own company stock/stock options. Edwin Lam was an employee of Johnson & Johnson when this work was conducted, their current affiliation is Biogen. Hermine I. Brunner reports having received contributions in the past 3 years from AbbVie, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, F. Hoffmann-La Roche, Janssen, UCB, Novartis, and Pfizer (this funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment to third parties); reports having received consulting fees from AbbVie, Astra Zeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, F. Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharm, UCB, and Sanofi; and has served on speakers’ bureaus for GlaxoSmithKline, Novartis, and Roche. Lucia Z. Diaz is an investigator for Janssen and Regeneron. Lara Wine Lee has received consulting fees from AbbVie, Chiesi, Kimberly-Clark Corporation, Krystal Biotech, and Nobelpharma; served as an investigator for AbbVie, Amryt Pharma, Arcutis Biotherapeutics, Bristol Myers Squibb, Castle Creek Biosciences, Celgene Corporation, Galderma, Incyte, Janssen, Kiniksa Pharmaceuticals, Eli Lilly, Mayne Pharma, Novartis, Pfizer, Regeneron, Sanofi, Target Pharma, Trevi Therapeutics, and UCB; and has served as an advisory board member for Eli Lilly, Novartis, Pfizer, and Regeneron. Cory Rubin reports being an investigator for AbbVie, Apollo Therapeutics, Bristol Myers Squibb, Bluefin, Cara Therapeutics, Castle Biosciences, CorEvitas, DermTech, Horizon Therapeutics, Incyte, Janssen, LEO Pharma, MoonLake Therapeutics, Pfizer, Regeneron, Sanofi, and Union Therapeutics; a consultant for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Incyte, LEO Pharma, Pfizer, Regeneron, Sanofi, and UCB; and a speaker for AbbVie, Amgen, Boehringer Ingelheim, Castle Biosciences, Dermavant, DermTech, Galderma, Incyte, LEO Pharma, Pfizer, Regeneron, Sanofi, Sun Pharma, UCB, and Verrica. Ruy Carrasco reports being on the board of directors for BEN AI Inc. and owns company stocks. Lisa Imundo and Azadeh Majlessi have no disclosures to report.
Ethical Approval
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. The study protocol, protocol amendments, and other relevant documents were reviewed and approved by the institutional review board (IRB) of the participating site (Lurie Children’s Hospital of Chicago IRB, University of Cincinnati Medical IRB, Columbia University Medical Center IRB, Akron Children’s Hospital IRB) or the central IRB (Sterling IRB; IRB ID: 9300-*MASTER) before the study was initiated. Participants or their legally designated representatives provided their written consent to participate in the study after having been informed about the nature and purpose of the study, participation/termination conditions, and risks and benefits.
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Pharmacokinetics and Safety of Ustekinumab in Patients with Juvenile Psoriatic Arthritis: Results of the Real-World Ustekinumab Pediatric Opportunistic Pharmacokinetics Study (U-POPS)
Verfasst von
Edwin Lam
Katherine Berezny
Corey J. Bishop
Kathleen G. Lomax
Sophia G. Liva
Hermine I. Brunner
Amy S. Paller
Lucia Z. Diaz
Lara Wine Lee
Cory Rubin
Ruy Carrasco
Lisa Imundo
Azadeh Majlessi
Valerie Smith
Renping Zhang
Jocelyn H. Leu
the U-POPS Study Group
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Erwachsene mit Covid-19 erhielten in den Monaten nach einem PCR-Nachweis deutlich häufiger eine neue CRS-Diagnose als Personen mit negativem PCR-Test. Der Risikoanstieg zeigte sich unter allen Varianten, am stärksten in der Omikron-Periode.
In der nicht-interventionellen Real-World-Studie HANNA wurde Nivolumab bei Menschen mit rezidiviertem oder metastasiertem Plattenepithelkarzinom der Kopf-Hals-Region in verschiedenen Therapielinien geprüft. Ein Kollege präsentierte auf dem diesjährigen Krebskongress in Berlin die finalen Daten.
Die Effektivität von Checkpoint-Inhibitoren wird unter anderem durch das Mikrobiom und Komedikationen beeinflusst. Wie Ballaststoffe wirken und welche Medikamente man nicht zusammen mit der Immuntherapie geben sollte, zeigten eine Kollegin und ein Kollege auf dem DKK in Berlin auf.
Neue molekularpathologische Methoden erhöhen die diagnostische Sensitivität bei Tumorerkrankungen. Aber verfeinert ein stetiges Mehr an molekularer Diagnostik auch die therapeutische Präzision? Diese Frage wurde im Rahmen des Deutschen Krebskongresses (DKK) 2026 in Berlin diskutiert.
