Baseline Body Surface Area Research Articles

51214 Deucravacitinib efficacy in palmoplantar and fingernail psoriasis by baseline Psoriasis Area and Severity Index (PASI) and baseline body surface area (BSA) in the phase 3 POETYK PSO-1 and PSO-2 trials

51214 Deucravacitinib efficacy in palmoplantar and fingernail psoriasis by baseline Psoriasis Area and Severity Index (PASI) and baseline body surface area (BSA) in the phase 3 POETYK PSO-1 and PSO-2 trials

51109 Efficacy of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in scalp psoriasis by baseline Psoriasis Area and Severity Index (PASI) and baseline body surface area (BSA): A subanalysis of the phase 3 clinical trial data

51109 Efficacy of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in scalp psoriasis by baseline Psoriasis Area and Severity Index (PASI) and baseline body surface area (BSA): A subanalysis of the phase 3 clinical trial data

Efficacy of Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 (TYK2) Inhibitor, in Scalp Psoriasis by Baseline Psoriasis Area and Severity Index (PASI) and Baseline Body Surface Area (BSA): A Subanalysis of the Phase 3 Clinical Trial Data

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was effective and well tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) trials. Here, efficacy of deucravacitinib in scalp psoriasis was evaluated by baseline severity of psoriasis in the trial patients with scalp involvement. Methods: Patients with moderate to severe scalp involvement (scalp-specific Physician Global Assessment [ss-PGA] ≥3) at baseline were included in this analysis. Efficacy outcomes (ss-PGA 0/1 and Psoriasis Scalp Severity Index [PSSI] 90) were reported through Week 24 (pooled PSO-1/PSO-2, before PSO-2 rerandomization, n=514) and Week 52 (PSO-1, continuous deucravacitinib treatment, n=192). Outcomes were stratified by baseline PASI score 12-<15 (low) or ≥15 (high) and baseline BSA involvement 10%-≤15% (low) or >15% (high). Results: ss-PGA 0/1 response rates were high and slightly greater in the high versus low PASI subgroup at Week 24 (65.8% and 58.3%, respectively) and Week 52 (73.5% and 60.0%). Similarly, PSSI 90 response rates were high and also somewhat greater in the high versus low PASI subgroup at Week 24 (55.3% and 45.8%) and Week 52 (66.0% and 53.3%). Across the 2 baseline BSA subgroups, ss-PGA 0/1 and PSSI 90 response rates were comparable at Weeks 24 and 52. Conclusion: Deucravacitinib treatment was effective in patients with scalp involvement in psoriasis regardless of overall baseline disease severity.

Baricitinib Improvement Across Regions in Atopic Dermatitis Patients with Baseline Body Surface Area up to 40% and Severe Itch.

Patients with moderate-to-severe atopic dermatitis (AD) who are most likely to respond to the Janus kinase (JAK) 1/2 inhibitor baricitinib (BARI) are known to have an impacted body surface area (BSA) ≤ 40% and severe itch (numerical rating scale [NRS] ≥ 7], collectively termed 'BARI itch-dominant' patients. Our objective is to build on our previous work by providing a body region-specific, clinical characterization of the BARI itch-dominant patient at baseline and their response to BARI 4 mg. BREEZE-AD7 was a phase 3 trial in adults with moderate-to-severe AD receiving placebo or 2 mg or 4 mg BARI in combination with topical corticosteroids. Assessing only data from BARI itch-dominant patients, we summarized the baseline characteristics and conducted body region-specific analyses on Eczema Area and Severity Index (EASI) data in order to report the response to placebo versus BARI 4 mg within this patient subtype. BARI 4 mg was highly effective across all body regions; at week 16, 75% improvement was seen in EASI scores (EASI75), and response rates with BARI 4 mg (head/neck, 58.3%; trunk, 69.2%; upper extremities, 61.5%; lower extremities, 87.5%) all exceeded those with placebo (head/neck: 37.5%; trunk, 40.6%; upper extremities, 18.8%; lower extremities, 40.6%) as well as the overall EASI75 rates of the intent-to-treat (ITT) population (BARI, 48.0%; placebo, 23.0%). At baseline, most BARI itch-dominant patients presented with involvement of all regions (mean regional BSA 22.7%-40.3%), highest in the head and neck, mean EASI region scores of 15.7-24.0, and considerably severe sign ratings (mean EASI sub-scores: 1.4-2.3, out of 3), especially for erythema. BARI itch-dominant patients exhibit AD involvement across all body regions and considerable sign severity, especially erythema. In response to BARI 4 mg, EASI quickly improved across regions, substantially more so in this subtype than in the ITT population.

Exposure-efficacy and exposure-safety analyses of ropeginterferon alfa-2b treatment in patients with polycythaemia vera.

To investigate the exposure-response (E-R) relationship, including exposure-efficacy and exposure-safety, of ropeginterferon alfa-2b treatment in patients with polycythaemia vera (PV). Based on the results of the phase II trial A20-202 regarding ropeginterferon alfa-2b in patients with PV, E-R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E-R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa-2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment-related adverse events (TRAEs). A clear relationship between the exposure to ropeginterferon alfa-2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure-JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa-2b and baseline body surface area. Exposure-safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance. Our analyses have shown that patients with PV treated with ropeginterferon alfa-2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250-350-500 μg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa-2b for PV treatment in China.

Impact of Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, Deucravacitinib, on Psoriasis in Patients with Active Psoriatic Arthritis: Results from a Phase 2 Trial

Introduction: Deucravacitinib (DEUC), an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy. DEUC was superior to apremilast and placebo (PBO) in two phase 3 trials in patients with moderate to severe PsO. DEUC was efficacious on multiple measures of arthritis severity vs PBO in a phase 2 trial in patients with active psoriatic arthritis (PsA) who had ≥1 PsO lesion (≥2 cm). In patients with body surface area (BSA) involvement ≥3% at baseline (80% of patients in this trial), a greater proportion achieved PASI 75 with DEUC (6 mg QD: 42.4%, P=0.01; 12 mg QD: 59.6%, P<0.0001) vs PBO (20.4%) at Week 16. This analysis evaluated the impact of DEUC on PsO in patients with PsA in the phase 2 trial (NCT03881059).
 Methods: The phase 2 double-blind PsA trial randomized patients (N=203) 1:1:1 to PBO, DEUC 6 mg once daily (QD), or DEUC 12 mg QD. After Week 16, patients could enroll in an optional, double-blind period until Week 52. DEUC-treated patients achieving minimal disease activity at Week 16 continued DEUC to Week 52. PsO disease activity measurements were assessed.
 Results: Baseline PsO characteristics were comparable across groups. At Week 16, significant decreases from baseline in mean PASI were observed with DEUC vs PBO in patients with baseline BSA ≥3%-<10% or PASI ≤12 even with very low baseline PASI scores, and also in those with baseline BSA ≥10% and PASI >12. Significant decreases in PASI from baseline were observed with DEUC vs PBO in patients with background csDMARD use (DEUC 6 mg, -4.0 and 12 mg, -4.9 vs PBO, -2.3; both P<0.05) and those without csDMARD use (-3.7 and -4.0 vs -2.5, respectively; both P<0.001). At Week 16, greater proportions of DEUC vs PBO patients achieved PASI ≤1 with baseline BSA ≥3% (DEUC 6 mg: 32.2%; DEUC 12 mg: 44.2%; PBO: 18.5%) and in patients with baseline BSA ≥10% and PASI >12 (23.1%; 28.6%; 0.0%). In patients with baseline BSA ≥3%, decreases in mean PASI at Week 16 were maintained through Week 52 in patients continuing DEUC 6 mg (absolute PASI score, Week 16: 2.39, Week 52: 1.22) and 12 mg (Week 16: 0.64, Week 52: 0.24).
 Conclusion: DEUC significantly improved PsO in patients with PsA, regardless of baseline PsO severity and background csDMARD use. Improvement was comparable to that observed in the phase 3 POETYK PSO-1 trial.
 
 
 
 
 
 
 
 
 

Population pharmacokinetics of methotrexate and 7-hydroxymethotrexate and delayed excretion in infants and young children with brain tumors

PurposeThe objectives of this study were to develop a population pharmacokinetic model of methotrexate (MTX) and its primary metabolite 7-hydroxymethotrexate (7OHMTX) in children with brain tumors, to identify the sources of pharmacokinetic variability, and to assess whether MTX and 7OHMTX systemic exposures were related to toxicity. MethodsPatients received 2.5 or 5 g/m2 MTX as a 24-hour infusion and serial samples were analyzed for MTX and 7OHMTX by an LC-MS/MS method. Pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling. Demographics, laboratory values, and genetic polymorphisms were considered as potential covariates to explain the pharmacokinetic variability. Association between MTX and 7OHMTX systemic exposures and MTX-related toxicities were explored using random intercept logistic regression models. ResultsThe population pharmacokinetics of MTX and 7OHMTX were adequately characterized using two-compartment models in 142 patients (median 1.91 y; age range 0.09 to 4.94 y) in 513 courses. The MTX and 7OHMTX population clearance values were 4.6 and 3.0 l/h/m2, respectively. Baseline body surface area and estimated glomerular filtration rate were significant covariates on both MTX and 7OHMTX plasma disposition. Pharmacogenetic genotypes were associated with MTX pharmacokinetic parameters but had only modest influence. No significant association was observed between MTX or 7OHMTX exposure and MTX-related toxicity. ConclusionsMTX and 7OHMTX plasma disposition were characterized for the first time in young children with brain tumors. No exposure-toxicity relationship was identified in this study, presumably due to aggressive clinical management which led to a low MTX-related toxicity rate.

Effect of empagliflozin on cardiac remodelling in South Asian and non-South Asian individuals: insights from the EMPA-HEART CardioLink-6 randomised clinical trial

BackgroundThis exploratory sub-analysis of the EMPA-HEART CardioLink-6 trial examined whether the previously reported benefit of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin on left ventricular (LV) mass (LVM) regression differs between individuals of South Asian and non-South Asian ethnicity.MethodsEMPA-HEART CardioLink-6 was a double-blind, placebo-controlled clinical trial that randomised 97 individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) to either empagliflozin 10 mg daily or placebo for 6 months. LV parameters and function were assessed using cardiac magnetic resonance imaging. The 6-month changes in LVM and LV volumes, all indexed to baseline body surface area, for South Asian participants were compared to those for non-South Asian individuals.ResultsCompared to the non-South Asian group, the South Asian sub-cohort comprised more males, was younger and had a lower median body mass index. The adjusted difference for LVMi change over 6 months was -4.3 g/m2 (95% confidence interval [CI], -7.5, -1.0; P = 0.042) for the South Asian group and -2.3 g/m2 (95% CI, -6.4, 1.9; P = 0.28) for the non-South Asian group (Pinteraction = 0.45). There was no between-group difference for the adjusted differences in baseline body surface area-indexed LV volumes and LV ejection fraction.ConclusionsThere was no meaningful difference in empagliflozin-associated LVM regression between South Asian and non-South Asian individuals living with T2DM and CAD in the EMPA-HEART CardioLink-6 trial.Trial registrationClinicalTrials.gov Identifier: NCT02998970 (First posted on 21/12/ 2016).

Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, in Moderate to Severe Plaque Psoriasis: Efficacy by Baseline Body Surface Area (BSA) Involvement and Baseline Psoriasis Area and Severity Index (PASI)

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. In the phase 3 POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials, deucravacitinib was significantly more efficacious than placebo and apremilast. This analysis evaluated deucravacitinib efficacy by two measures of baseline disease severity, BSA involvement and PASI scores.
 Methods: Patients were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily in both trials, which included 16-week placebo-controlled and 24-week apremilast-controlled periods from Day 1. Of patients randomized to deucravacitinib, those in PSO-1 were treated continuously for 52 weeks; in PSO-2, Week 24 PASI 75 responders were rerandomized to continued deucravacitinib or placebo. Patients randomized to placebo crossed over to deucravacitinib at Week 16 and were treated through Week 52. Efficacy outcomes, including ≥75%/≥90%/100% reductions from baseline in PASI (PASI 75/90/100) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1), were evaluated using nonresponder imputation in disease severity subgroups defined by baseline BSA involvement (10%-<15%, 15%-<20%, 20%-<30%, ≥30%) and PASI score (12-<15, ≥15). Results are reported through Week 24 in the pooled PSO-1/PSO-2 population (apremilast-controlled) and through Week 52 in the PSO-1 population (continuous deucravacitinib treatment).
 Results: In the pooled PSO-1/PSO-2 population (N=1686), 391 (23.2%) had baseline BSA involvement of 10%-<15% (deucravacitinib, n=194), 371 (22.0%) had 15%-<20% (deucravacitinib, n=183), 391 (23.2%) had 20%-<30% (deucravacitinib, n=198), and 533 (31.6%) had ≥30% (deucravacitinib, n=268). For baseline PASI scores, 387 (23.0%) had a score of 12-<15 (deucravacitinib, n=183) and 1298 (77.0%) had a score of ≥15 (deucravacitinib, n=660). Deucravacitinib-treated patients had comparable PASI 75 response rates across all subgroups at Week 16 (BSA subgroups, 50.5%-58.2%; PASI subgroups, 48.6%-57.0%) and at Week 24 (BSA subgroups, 62.0%-64.1%; PASI subgroups, 59.9%-63.8%), with superior responses versus those in patients receiving placebo or apremilast evaluated in each subgroup. Similar findings were observed for all other efficacy measures. In PSO-1, efficacy was maintained through Week 52 with continuous deucravacitinib treatment across BSA (PASI 75, 67.1%-75.7%; sPGA 0/1, 52.1%-61.2%) and PASI subgroups (PASI 75, 65.6%-73.1%; sPGA 0/1, 54.7%-58.8%).
 Conclusion: Deucravacitinib was efficacious in patients with moderate or severe plaque psoriasis regardless of extent of baseline BSA involvement or PASI scores.

Efficacy of Secukinumab in Patients With Mild to Moderate Psoriasis: A Pooled Analysis of 6 Phase 3 Studies

Introduction: Secukinumab has demonstrated sustained long-term efficacy for the treatment of patients with moderate to severe plaque psoriasis, but efficacy in mild to moderate psoriasis has not been rigorously evaluated. The secukinumab phase 3 clinical trial program included patients with mild to moderate psoriasis among populations with active psoriatic arthritis (EXCEED and FUTURE 2-5; NCT02745080, NCT01752634, NCT01989468, NCT02294227, and NCT02404350), and among patients with moderate to severe palmoplantar psoriasis (GESTURE; NCT01806597). Here, we report efficacy and safety of secukinumab in a pooled population of patients with mild to moderate psoriasis.
 Methods: This post hoc analysis included patients from the phase 3 EXCEED, FUTURE 2-5, and GESTURE trials, with mild to moderate psoriasis defined as either a baseline affected body surface area (BSA) of 3%-10% or a baseline Investigator’s Global Assessment modified 2011 score (IGA) of 2 or 3. Patients were pooled by treatment received through Week 16 (treatment period 1) and from Weeks 16 to 52 (treatment period 2), according to the following groups: treatment period 1 (secukinumab 300 mg, secukinumab 150 mg, or placebo) and treatment period 2 (secukinumab 300 mg or secukinumab 150 mg). Efficacy was assessed by the proportion of patients achieving 75% improvement in the Psoriasis Area and Severity Index (PASI75), PASI90, and PASI100 among patients with a BSA 3%-10%; and by IGA 0/1 response with ≥2-point improvement among patients with baseline IGA score of 2 or 3. Descriptive statistics were reported for each outcome. Missing data were imputed using non-responder imputation.
 Results: Overall, 654 patients and 971 patients had mild to moderate psoriasis at baseline as defined by a BSA of 3%-10% or IGA score of 2 or 3, respectively. Demographics and baseline disease characteristics were similar between populations defined by BSA and by IGA. Among patients with a baseline BSA of 3%-10%, secukinumab resulted in greater achievement of PASI75/90/100 vs placebo at Week 12 (secukinumab 300 mg: 62.8%/44.4%/33.1%; secukinumab 150 mg: 48.0%/29.1%/19.4%; placebo: 11.7%/9.0%/8.0%), with increased responses at Week 52 (secukinumab 300 mg: 65.7%/56.5%/47.3%; secukinumab 150 mg: 58.1%/40.5%/31.3%). The proportion of patients with baseline IGA=2 or 3 achieving IGA 0/1 response with ≥2-point improvement was greater among patients receiving secukinumab 300 mg (46.6%) or 150 mg (37.2%) than placebo (8.6%) at Week 12, with increased responses at Week 52 (secukinumab 300 mg: 52.5%; secukinumab 150 mg: 44.4%).
 Conclusions: Secukinumab led to improvements in measures of disease severity among patients with mild to moderate psoriasis after 12 weeks of treatment vs placebo in a pooled analysis of patients with psoriatic arthritis or palmoplantar psoriasis. Both doses of secukinumab showed increased efficacy from Week 12 to Week 52.

Evaluating Response Trends of Chlormethine/Mechlorethamine Gel in Patients With Stage I-IIA Mycosis Fungoides: Analysis of Individual Patient Data From a Randomized Controlled Phase II Study to Facilitate Optimal Treatment Experiences

IntroductionChlormethine (CL) gel was approved for treatment of mycosis fungoides based on the pivotal 201 trial (NCT00168064). Data visualization from individual patients is a powerful tool for discovery of hidden treatment trends. Here, we present a post hoc analysis of individual patient data from the pivotal trial to provide a more granular depiction of treatment and response changes over time, with an emphasis on end of treatment status. Materials and MethodsIndividual patient response data were plotted over a 12-month treatment period to visualize patient experiences while using CL gel. Responder status was assigned according to end-of-treatment Composite Assessment of Index Lesion Severity (CAILS) score, and patients were classified as early (≤4 months) or late responders based on timing of response. Baseline and active treatment characteristics were compared between early and late responders, and baseline body surface area (BSA) was compared between responders and patients with stable or progressive disease. ResultsData from 123 patients with baseline and postbaseline results were included. At the end of treatment, 64.2%/55.3% were responders, 30.9%/34.1% had stable disease, and 4.9%/10.6% had progressive disease by CAILS and mSWAT, respectively. Among patients who responded to treatment, 64.6% and 35.4% were early and late responders, respectively. Response pattern analysis also identified patients with an intermittent response or initial progressive disease. Baseline BSA was not associated with responder status. Late responders had longer treatment duration and higher postbaseline plaque elevation, while early responders had a higher frequency of dermatitis. ConclusionsResults presented here can facilitate optimal treatment experiences for patients starting CL gel.

Baseline Body Surface Area and Itch Severity Define Response to Baricitinib in Patients with Moderate-to-Severe Atopic Dermatitis at Week 16.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by heterogeneous clinical phenotypes and high symptom burden, especially through itch. Baricitinib (BARI), an oral Janus Kinase 1/2 inhibitor, is approved in Europe, Japan, and other countries, for treatment of adults with moderate-to-severe AD who are candidates for systemic therapy. This post hoc analysis of a Phase 3 topical corticosteroid (TCS) combination therapy trial (BREEZE-AD7) aims to characterize patients who might benefit most from BARI. Classification and regression tree (CART) analysis was used to identify baseline predictors for patients treated with BARI 4-mg, who achieved≥75% improvement in Eczema Area and Severity Index (EASI75), or EASI75 or Itch Numerical Rating Scale (NRS)≥4-point improvement at week 16 (responders), versus non-responders. Subgroup efficacy analyses were performed based on identified predictor variables, combined with Itch NRS<7/≥7. Missing data were imputed as non-responder. Baseline body surface area (BSA) was identified by CART as strongest variable predicting response to BARI at week 16, with a cut-off around 40% (BSA≤40%). When combining BSA with itch severity, highest response rates were achieved by BARI patients with BSA≤40%/Itch NRS≥7 at baseline. In this subgroup, 69% and 58% of patients treated with BARI 4-mg achieved EASI75 and Itch NRS≥4-point response at week 16, respectively. While these response rates were 65% and 50% for BARI 4-mg patients with baseline BSA≤40%/Itch NRS<7, they were 33% and 11% in BSA>40%/Itch NRS<7, and 32% and 49% in BSA>40%/Itch NRS≥7 subgroups, respectively. Using a machine learning approach, patients with moderate-to-severe AD and a BSA affecting 10-40% and Itch NRS≥7 were characterized as likely to benefit most from BARI 4-mg TCS combination therapy. This was confirmed by subgroup analyses, which showed that these patients are most likely to show favorable response rates in improving AD signs and symptoms, specifically itch, after 16weeks of treatment.

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: efficacy by baseline body surface area (BSA) involvement and baseline Psoriasis Area and Severity Index (PASI)

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: efficacy by baseline body surface area (BSA) involvement and baseline Psoriasis Area and Severity Index (PASI)

Real-World Outcomes of Adalimumab Treatment for Moderate and Severe Psoriasis in Korean Patients (RAPSODI Study).

Psoriasis imposes a significant treatment burden on patients, particularly impacting well-being and quality of life (QoL). The psychosocial impact of psoriasis treatments remains unexplored in most patient populations. To assess the impact of adalimumab on health-related QoL (HRQoL) in Korean patients with psoriasis. This 24-week, multicenter, observational study, assessed HRQoL in Korean patients treated with adalimumab in a real-world setting. Patient-reported outcomes (PROs) including European Quality of Life-5 Dimension scale (EQ-5D), EQ-5D VAS, SF-36, and DLQI were evaluated at week 16 and 24, versus baseline. Patient satisfaction was assessed using TSQM. Among 97 enrolled patients, 77 were assessed for treatment effectiveness. Most patients were male (52, 67.5%) and mean age was 45.4 years. Median baseline body surface area and Psoriasis Area and Severity Index (PASI) scores were 15.00 (range 4.00~80.00) and 12.40 (range 2.70~39.40), respectively. Statistically significant improvements in all PROs were observed between baseline and week 24. Mean EQ-5D score improved from 0.88 (standard deviation [SD], 0.14) at baseline to 0.91 (SD, 0.17) at week 24 (p=0.0067). The number of patients with changes in PASI 75, 90, or 100 from baseline to week 16 and 24 were 65 (84.4%), 17 (22.1%), and 1 (1.3%); and 64 (83.1%), 21 (27.3%), and 2 (2.6%), respectively. Overall treatment satisfaction was reported, including effectiveness and convenience. No unexpected safety findings were noted. Adalimumab improved QoL and was well-tolerated in Korean patients with moderate to severe psoriasis, as demonstrated in a real-world setting. Clinical trial registration number (clinicaltrials.gov: NCT03099083).

Population Pharmacokinetics of Inotuzumab Ozogamicin (InO) As Single Agent in Pediatric Relapsed/Refractory Acute Lymphoblastic Leukemia - Results from the ITCC-059 Phase IA and Phase II Trial

INTRODUCTION: This population pharmacokinetics (PopPK) analysis assessed the disposition of InO, a CD22 directed antibody conjugated with calicheamicin, as single agent in pediatric subjects with relapsed/refractory (R/R) B-cell precursor CD22+ acute lymphoblastic leukemia (BCP-ALL). Pooled data from the phase IA and II of the trial ITCC-059 (EudraCT:2016-000227-71) are presented. Clinical results from the Phase IA and Phase II were reported previously (Brivio et al., 2021; Pennesi et al., 2022). The trial was sponsored by Erasmus MC and financed by Pfizer. METHODS: Patients aged 1-18 years, in M2 or M3 marrow status, and either ≥ 2nd relapsed, transplanted after 1st relapse, or with refractory disease were enrolled. In Phase I, InO (fractionated in 3 doses/cycle at day 1, 8 and 15) was initially administered at 1.4 mg/m2/cycle (0.6 + 0.4 + 0.4 mg/m2, dose level 1 (DL1)), then escalated to 1.8 mg/m2 (0.8 + 0.5 + 0.5 mg/m2, DL2). In Phase II, patients received 1.8 mg/m2/cycle of InO, or 1.5 mg/m2/cycle (0.5 + 0.5 + 0.5 mg/m2) once remission was achieved. A maximum of 6 cycles were allowed, except for patients proceeding to transplant, for which maximum 2-3 cycles were recommended. A sparse sampling schedule was applied (on day 1, 8, 15 and 22 (cycle 1) or 28 (cycles 2-3)). The PopPK of InO was developed using nonlinear mixed-effects analysis and combining pediatric data from the trial ITCC-059 with data from 11 trials in 765 adult patients with R/R ALL (n=234) or non-Hodgkin's lymphoma (NHL) (n=531) provided by Pfizer. A prior PopPK model developed for adults (Garrett et al., 2019) was used as a basis for pediatric data. This model had two-compartments with both a linear clearance (CL1) and time-dependent clearance (CLt) that includes a decay coefficient (kdes). Covariates included in that analysis, based on Garret et al., were baseline body surface area (BSA) on CL1, CLt, and volume of distribution in the central compartment; diagnosis (ALL/NHL) and/or bioanalytical assay method on CL1, and the decay coefficient associated with time-dependent clearance (kdes); absence of concomitant rituximab (RITXI) on CL1; and baseline percentage of blasts in the peripheral blood (BLSTPB) as a covariate on kdes of CLt. Simulations were performed to predict InO exposures in both pediatric and adult patients at a fixed dosing regimen of 1.8 mg/m2/cycle. RESULTS: Pharmacokinetic pediatric data were collected from 53 patients (See table 1 for baseline characteristics); 13 treated at DL1, and 40 at DL2; in total 563 serum PK observations were collected. When combined with adult data, the final analysis included a total of 818 patients and 8924 serum PK observations, of which 3394 (38.0%) below the lower limit of quantitation (LLOQ); and hence the M3 method (maximizing the likelihood for data ≥ LLOQ and treating PK data < LLOQ as censored) was selected. Overall, the previous model developed for adults described the pediatric patients’ PK well. Besides the covariates identified in the adult model (BSA, RTX, diagnosis and BLSTPB), the current model also identified the effect of pediatric patients on kdes as a significant covariate. In the final model, InO typical value of CL1 was estimated to be 0.113 L/hr with 40% inter-individual variability (IIV); CL2 was estimated to be 0.384 L/hr with 74% IIV; and central volume of distribution (V1) was estimated to be 6.56 L with 41% IIV. The kdes was estimated to be 0.036 h-1 with 54% IIV. The inter-compartmental CL and peripheral volume of distribution were estimated to be 0.045 L/hr and 4.70 L, respectively. The simulated median Cmax and the accumulated area under the curve (AUC) at end of cycle 1 were 191 ng/mL and 24550 ng.hr/mL; 155 ng/mL and 18200 ng.hr/mL for pediatric and adult patients with ALL, respectively. The simulated median Cmax and accumulated AUC at end of cycle 2 were 284 ng/mL and 117830 ng.hr/mL; 217 ng/mL and 90270 ng.hr/mL for children and adults, respectively. CONCLUSIONS: InO PK is generally comparable between pediatric and adult patients with R/R ALL. This supports the same dosing regimen in these two populations at 1.8 mg/m2/cycle until remission then 1.5 mg/m2/cycle, the same as per our phase I and II trials. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

33463 Pooled efficacy and safety results from the DERMIS-1 and DERMIS-2 phase 3 trials of once-daily roflumilast cream 0.3% by baseline body surface area

Roflumilast cream 0.3% is a selective and potent phosphodiesterase-4 inhibitor under investigation as a once-daily treatment for psoriasis. Here we describe pooled efficacy and safety results from 2 identical phase 3 randomized controlled trials of roflumilast cream (DERMIS-1: NCT04211363 and DERMIS-2: NCT04211389) analyzed by baseline body surface area (BSA) affected ( 10%). Patients (≥2 years) with psoriasis involving 2-20% BSA were randomized to roflumilast (n = 576) or vehicle (n = 305) for 8 weeks.

Characteristics of New Biologic Users Among the Moderate-to-Severe Psoriasis Population-Retrospective Cohort Study Leveraging the Modernizing Medicine Data Services Database.

IntroductionBiologics have expanded the treatment options in the management of patients with moderate-to-severe psoriasis. The objective of this study was to describe patient characteristics and previous treatments in psoriasis patients newly treated with guselkumab, secukinumab, or ixekizumab.MethodsThis retrospective study included patients ≥ 18 years old with psoriasis in the USA who were newly treated with guselkumab, secukinumab, or ixekizumab between 1 July 2017 and 31 March 2019 in the Modernizing Medicine Data Services database (MMDS). Patients were indexed on their first prescription or injection record of guselkumab, secukinumab, or ixekizumab, and three mutually exclusive cohorts were created. Patients were required to have evidence of moderate-to-severe psoriasis, defined as Physician Global Assessment (PGA) score of 3 or 4, or body surface area (BSA) ≥ 10% on index date or within 12 months before index. Baseline characteristics, including treatment history, were reported for each cohort.ResultsThe study population included 461 guselkumab, 619 secukinumab, and 375 ixekizumab patients. The median age across cohorts was 51–52 years. Median baseline BSA ranged from 15% to 20%; 16.1–29.3% of patients had a PGA of 4 and over half of patients were obese prior to index. Approximately 40% of patients had comorbid cardiovascular disease and 20.8–24.2% of patients had a psychiatric disorder. About half of patients in each cohort had prior biologic use, of which adalimumab was most common (28.2–34.9%) across the cohorts.ConclusionThis real-world study describes the characteristics of patients with moderate-to-severe psoriasis receiving biologic treatments.

Clinical Tailoring of Baricitinib 2 mg in Atopic Dermatitis: Baseline Body Surface Area and Rapid Onset of Action Identifies Response at Week 16.

IntroductionBaricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, is indicated in the European Union and Japan for treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. In the ongoing, placebo-controlled, phase 3 trial BREEZE-AD5, once-daily oral baricitinib 2-mg monotherapy improved disease in moderate-to-severe AD patients who had an inadequate response or intolerance to topical corticosteroids. This post-hoc analysis aimed to identify responders to baricitinib 2 mg, using a proposed clinical tailoring approach based on baseline body surface area (BSA) affected and early clinical improvement, in BREEZE-AD5.MethodsClassification and regression tree method was used to evaluate baseline predictors for the proportion of patients achieving ≥ 75% improvement in Eczema Area and Severity Index (EASI75) at week 16 among baricitinib 2-mg-treated patients. Two-by-two contingency tables evaluated the association between early response, defined as ≥ 50% improvement in BSA or ≥ 3-point improvement in Itch Numeric Rating Scale from baseline at weeks 4 or 8, and response at week 16 for the proportion of patients achieving EASI75, validated Investigator Global Assessment for AD (vIGA-AD) score of 0 or 1, or ≥ 4-point improvement in Itch (Itch ≥ 4), respectively. Missing data were imputed as non-responder.ResultsAt week 16, EASI75 and vIGA-AD (0,1) were achieved by 37.5% and 31.7% of baricitinib 2-mg-treated patients with baseline BSA 10–50% compared with 9.5% and 4.8% with BSA > 50%. Early response in skin inflammation or itch at week 4 was associated with corresponding EASI75, vIGA-AD (0,1), and Itch ≥ 4 of 55.4%, 48.2%, and 39.3% at week 16, while early response at week 8 was associated with 66.7%, 56.1%, and 42.1% of patients achieving these endpoints.ConclusionBaseline BSA of 10–50% and early clinical improvement after 4 or 8 weeks of baricitinib 2-mg treatment may identify patients most likely to benefit from long-term baricitinib 2-mg therapy.Clinical Trial RegistrationNCT03435081.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00640-7.

27050 Efficacy of baricitinib 2-mg stratified by baseline body surface area in adults with moderate-to-severe atopic dermatitis

Background: Baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, improved disease severity in adults with moderate-to-severe atopic dermatitis (AD) in multiple Phase 3 trials. The objective of this post-hoc analysis was to evaluate the impact of baseline body surface area (BSA) on clinical responses to baricitinib monotherapy.

27620 Effects of ruxolitinib cream in patients with atopic dermatitis with baseline body surface area ≥10% and Eczema Area and Severity Index score ≥16: Pooled results from two phase 3 studies

Atopic dermatitis (AD), a highly pruritic inflammatory skin disease, is often stratified using objective (Investigator’s Global Assessment [IGA], Eczema Area and Severity Index [EASI], body surface area [BSA]) and subjective (eg, itch numerical rating scale [NRS]) assessment tools. Efficacy and safety of ruxolitinib cream, a Janus kinase (JAK) 1/JAK2 inhibitor, was investigated in two phase 3 randomized studies (TRuE-AD1 [NCT03745638]; TRuE-AD2 [NCT03745651]) that enrolled patients aged ≥12 years with AD for ≥2 years, an IGA score of 2 or 3, and 3%–20% affected BSA.