Brad Schenkel

Development of the IL-12/23 antagonist ustekinumab in psoriasis: past, present, and future perspectives

The development of ustekinumab as a first‐in‐class anti‐interleukin (IL) 12/23p40 therapeutic agent for psoriasis represents an important example of modern and rational drug design and development. Psoriasis is a chronic, systemic, immune‐mediated skin disorder with considerable clinical, psychosocial, and economic burden. Ustekinumab is a human monoclonal antibody (mAb) that binds the p40 subunit common to IL‐12 and IL‐23, key cytokines in psoriasis pathogenesis. The therapeutic mAb was developed using human gamma‐1 immunoglobulin (IgG)‐expressing transgenic mice, which created a molecule with endogenous IgG1 biologic properties and low immunogenicity. Ustekinumab was well tolerated in clinical studies and yielded rapid, significant, and sustained efficacy plus improved quality of life/work performance and reduced depression/anxiety. Its pharmacologic properties afford the most convenient dosing regimen among approved biologics, representing a significant advancement in the treatment of moderate to severe psoriasis. Ustekinumab also holds promise for other immune‐mediated disorders with significant unmet need.

A multicenter, non-interventional study to evaluate patient-reported experiences of living with psoriasis

Abstract Background: Moderate to severe plaque psoriasis (with or without psoriatic arthritis) places significant burden on patients’ lives. Objective: Explore and document patients’ experiences of living with psoriasis, including symptoms, treatments, impact on daily lives and patient-reported functioning. Methods: In a US-based, non-interventional study, narrative interviews were conducted at baseline and again within 16 weeks. In interviews, patients with moderate to severe psoriasis indicated symptoms, ranked symptoms according to level of bother and indicated areas of their lives affected by psoriasis. Transcripts of interviews were coded for themes. Measurements of psoriasis severity including BSA, PGA and PASI were recorded. Results: Symptoms reported most frequently included flaking/scaling (non-scalp areas), itching/scratching and rash, while the most bothersome symptoms were itching/scratching, flaking/scaling (non-scalp areas) and skin pain. Frequently reported impact areas were social and emotional. Conclusion: Broad-reaching interviews with patients with psoriasis show that these patients suffer in many aspects of their lives and in ways not indicated by typical psoriasis severity measures. Patients with psoriatic arthritis reported symptoms and disease-related complications at higher rates than those without arthritis. Physicians’ explorations of the effect of psoriasis on patients’ life events could aid in managing these patients.

Cost-efficacy comparison of biological therapies for patients with moderate to severe psoriasis in Japan

Background: Biological therapies have recently been introduced for patients with moderate to severe psoriasis in Japan. Objectives: This research aims to assess the cost efficacy of adalimumab, infliximab and ustekinumab treatments for psoriasis in a Japanese environment. Methods: A mixed-treatment comparison was performed to estimate the comparative efficacy of biological therapies using Psoriasis Area and Severity Index (PASI) scores based on data from randomized, double-blind, controlled studies. Costs included only the drug costs calculated by the approved dosing and schedule. Cost efficacy was determined by dividing the cost by the probability of achieving a PASI 75 response. Results: Infliximab had the highest probability of a PASI 75 response (83%), followed by ustekinumab 45 mg (74%) and adalimumab (59%). Infliximab was the most expensive biologic, whereas the costs of ustekinumab 45 mg and adalimumab were similar. In the first year of induction treatment, the lowest cost per responder was for ustekinumab 45 mg, followed by adalimumab and infliximab. In the subsequent year of maintenance treatment, the cost per responder of ustekinumab 45 mg remained the lowest while infliximab and adalimumab had similar cost efficacy. Conclusions: Ustekinumab was a more cost-efficient biological therapy than adalimumab or infliximab for psoriasis patients in a Japanese setting.

Impact of ustekinumab on health-related quality of life in Japanese patients with moderate-to-severe plaque psoriasis: results from a randomized, double-blind, placebo-controlled phase 2 / 3 trial.

This study evaluates the effect of ustekinumab on health‐related quality of life (HRQoL) in Japanese patients with moderate‐to‐severe plaque psoriasis through 64 weeks. A total of 158 patients were randomized to receive subcutaneous injections of ustekinumab 45 mg (n = 64) or 90 mg (n = 62) at weeks 0, 4, and every‐12‐weeks, or placebo (n = 32) with crossover to ustekinumab at week 12. Secondary study endpoints included change in Dermatology Life Quality Index (DLQI) at week 12. Other assessments included the 36‐item Short Form health survey to assess Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, and Psoriasis Disability Index (PDI), a psoriasis‐specific instrument to assess HRQoL. Baseline demographic and disease characteristics were similar across randomized treatment groups. Ustekinumab‐treated patients had significantly greater mean improvements in DLQI from baseline to week 12 (45 mg: 8.0 ± 6.5; 90 mg: 7.4 ± 6.5) than placebo‐treated patients (0.3 ± 5.3; P < 0.0001 for each), and these improvements were maintained through week 64. Also at week 12, significant improvements from baseline in PDI scores were observed in ustekinumab‐treated patients (45 mg: 8.6 ± 9.6; 90 mg: 12.0 ± 11.8) compared with placebo‐treated patients (−0.1 ± 4.2). Improvements in the PCS (45 mg: 7.8 ± 14.5; 90 mg: 5.1 ± 12.0) and MCS (45 mg: 5.3 ± 9.8; 90 mg: 5.8 ± 10.5) scores were also observed in ustekinumab‐treated patients at week 12. Placebo‐treated patients who crossed‐over to ustekinumab achieved improvements in HRQoL comparable to those observed in patients originally randomized to ustekinumab. Ustekinumab significantly improves HRQoL in Japanese patients with moderate‐to‐severe plaque psoriasis through week 64.

Ustekinumab dosing, persistence, and discontinuation patterns in patients with moderate-to-severe psoriasis

Abstract Objectives: Ustekinumab is the most recently approved biologic for the treatment of moderate-to-severe psoriasis. Real-world dosing patterns of ustekinumab are yet to be fully characterized. Methods: A retrospective, observational study was conducted using MarketScan Commercial and Medicare databases. A cohort of psoriasis patients treated with ustekinumab between 25 September 2009 and 31 October 2010 was evaluated. Main outcomes included ustekinumab dosing and treatment patterns. Kaplan–Meier estimates were calculated to adjust for the censoring of data. Subgroup analysis was conducted for biologic-experienced patients and biologic-naïve patients. Results: One thousand ustekinumab patients were included, of whom 60% were biologic-experienced. The average age was 49.0 and 53.9% were male. 63.3% of patients initiated ustekinumab with a 45 mg dose and 34.5% initiated with a 90 mg dose. Mean (median) days from initial dose to second dose was 31.1 (28.0). During maintenance therapy, dose intervals spanned from 80.6 to 81.2 (84.0) days. About 81.4% of patients were persistent during the variable-length follow-up period. Conclusions: The majority of patients received the 45 mg ustekinumab dose. The mean dosing intervals were consistent with the US prescribing guidelines. Biologic-naïve and biologic-experienced patients had similar dosing patterns. Ustekinumab treatment achieved a persistency rate as high as 81.4% over an average of 186.5 (SD 114.2) days of follow-up.

Budget impact analysis of ustekinumab in the management of moderate to severe psoriasis in Greece

BackgroundThe purpose of this study was to estimate the annual and per-patient budget impact of the treatment of moderate to severe psoriasis in Greece before and after the introduction of ustekinumab.MethodsA budget impact model was constructed from a national health system perspective to depict the clinical and economic aspects of psoriasis treatment over 5 years. The model included drug acquisition, monitoring, and administration costs for both the induction and maintenance years for patients in a treatment mix with etanercept, adalimumab, infliximab, with or without ustekinumab. It also considered the resource utilization for non-responders. Greek treatment patterns and resource utilization data were derived from 110 interviews with dermatologists conducted in February 2009 and evaluated by an expert panel of 18 key opinion leaders. Officially published sources were used to derive the unit costs. Costs of adverse events and indirect costs were excluded from the analysis. Treatment response was defined as the probability of achieving a PASI 50, PASI 75, or PASI 90 response, based on published clinical trial data.ResultsThe inclusion of ustekinumab in the biological treatment mix for moderate to severe psoriasis is predicted to lead to total per-patient savings of €443 and €900 in years 1 and 5 of its introduction, respectively. The cost savings were attributed to reduced administration costs, reduced hospitalizations for non-responders, and improved efficacy. These results were mainly driven by the low number of administrations required with ustekinumab over a 5 year treatment period (22 for ustekinumab, compared with 272 for etanercept, 131 for adalimumab, and 36 for infliximab).ConclusionsThe inclusion of ustekinumab in the treatment of moderate to severe psoriasis in Greece is anticipated to have short- and long-term health and economic benefits, both on an annual and per-patient basis.

Sa1211 Assessment of Sleep Impairment in Patients With Crohn's Disease: Results From the Ustekinumab Certifi Study

Introduction To describe the extent of sleep impairment reported in CERTIFI (Ph2 evaluating UST in inducing & maintaining clinical response & remisison)using Jenkins Sleep Evaluation Questionnaire (JSEQ) & establish a clinically meaningful improvement threshold for JSEQ. Methods Pts with moderate-to-severe CD(CDAI ≥220 & ≤450) who had previously failed or were intolerant to ≥1 anti-TNF were randomised to PBO/UST induction at wk0. Primary endpt was clinical response (≥100-pt reduction in CDAI from BL) at wk6. Sleep impairment assessed using JSEQ (total score 0–20; higher scores indicate greater sleep impairment) at BL&wk6. Relationships between BL sleep impairment, clinical disease activity (CDAI), & HRQoL impact(IBDQ) evaluated using Pearson correlation. Clinically meaningful improvement threshold of JSEQ was established with the anchor-based [clinical response by reduction in CDAI of ≥70-pt or clinically meaningful improvement (≥16-pt) in IBDQ] & distribution-based (change by one-half of the standard deviation [SD] of BL JSEQ score) methods. Prop of pts who achieved clinically meaningful improvements in JSEQ at wk6 was determined & compared. Results At BL,both grps(n = 526) experienced similar degree of moderate sleep impairment, with JSEQ scores (mean±SD) of 11.0 ± 4.30(PBO)&11.0 ± 4.59(UST),resp. About 60% were “waking up feeling tired and worn out”; about 30–35% of pts had trouble falling asleep, staying asleep,& woke up several times during the night for 15–30 days in the previous month. At BL, JSEQ was correlated with CDAI (r = 0.19, p 2 or > 3 points from BL JSEQ score at wk6) were derived. More pts who received UST induction achieved both thresholds at wk6(Table). Conclusion Pts experience significant sleep problems as measured by JSEQ; magnitude of impairment correlates with disease activity. Both anchor- &distribution-based methods derive similar thresholds representative of clinically meaningful improvements in JSEQ. UST induction resulted in a greater proportion of pts achieving clinically meaningful improvements in sleep impairments. Disclosure of Interest C. Gasink Employee of: Janssen R&D, LLC, D. Chan Employee of: Janssen R&D, LLC, L.-L. Gao Employee of: Janssen R&D, LLC, B. Schenkel Employee of: Janssen Scientific Affairs, LLC, C. Han Employee of: 3. Janssen Pharmaceutical Services

Real-world treatment patterns and health care resource utilization (HRU) among patients with chronic lymphocytic leukemia (CLL) by regimen.

15 Background: Few studies examine HRU of CLL, the most common hematologic malignancy in adults. This study describes HRU by the most common regimens among CLL patients (pts). METHODS A retrospective study using a large, national U.S. claims database from 1/2007-10/2013 was conducted. Adult CLL pts (≥2 claims for CLL) with ≥1 claim for systemic anticancer therapy (SACT) were identified; first SACT claim date was the index date. Pts had to have a CLL diagnosis ≤3 months (m) prior to the index date and be continuously enrolled (CE) in the health plan for 24m pre- and ≥6m post-index date. Pregnant pts and those with SACT in the pre-index period were excluded. A line of therapy (LOT) started with the first SACT; regimens included all agents received in the first 60 days. LOTs ended at the earliest of, start of a new drug, ≥60-day gap in receipt of initial regimen drugs, death or CE end. All-cause HRU was examined by regimen. RESULTS There were 946 CLL pts identified. Mean age was 68 years, 63% were male, and by insurance type, 41% were Medicare Advantage vs. 59% commercially insured. During the first LOT, 96% and 78% of pts had ≥1 office or hospital outpatient visit with mean per patient per month (PPPM) visits of 4.3 (standard deviation, SD = 2.8) and 2.2 (SD = 2.8), respectively. 31% and 25% had ≥1 ER visit or inpatient stay with mean PPPM visits of 0.2 (SD = 0.4) and 0.1 (SD = 0.3), respectively. Mean PPPM count of inpatient stay days was 1.4 (SD = 8.0). In first LOT, the top 3 regimens accounted for 56% of pts: FCR: fludarabine, cyclophosphamide, rituximab (19%); R: rituximab (19%); BR: bendamustine, rituximab (18%). During the study period, 318 pts (34%) started a second LOT. The top 3 LOT2 regimens accounted for 52% of pts: R (30%); BR (14%); chlorambucil (8%). CONCLUSIONS HRU of CLL pts varied by initial regimen received. Future studies should examine influences of regimen choice and whether regimen choice is associated with differences in outcomes. [Table: see text].

Real-world treatment patterns, health care resource utilization (HRU), and costs among patients with Waldenstrom macroglobulinemia (WM) initiating therapy.

17 Background: WM is a rare, indolent B-cell lymphoma with 1000 to 1500 new cases diagnosed annually in the US. The disease is incurable with current therapy. Prior to January 2015 when ibrutinib was approved by the US FDA for WM, there were no therapies approved in this indication. This study describes initial systemic anti-cancer therapy (SACT) and HRU among WM patients (pts). METHODS A retrospective study using a large, national US claims database from 1/2007-10/2013 was conducted. Adult WM pts ( ≥ 2 claims for WM) with ≥ 1 claim for SACT were identified; the first SACT claim date was the index date. Pts were required to have a WM diagnosis within 3 months (m) prior to the index date and be continuously enrolled (CE) in the health plan for 12m pre- and ≥ 6m post-index date. Pregnant pts and those with SACT in the pre-index period were excluded. The first line of therapy (LOT1) period was examined; the LOT started at index date and the regimen included all drugs received within 60 days. The LOT ended at the earliest of, start of a new drug, ≥ 60-day gap in receipt of initial drug regimen, death or CE end. All-cause HRU and costs during LOT1 were examined. RESULTS There were 161 WM pts identified. 66% of pts were ≥ 65 yrs (mean age 69), 55% were male, and by insurance type, 49% were Medicare Advantage pts vs. 51% commercially insured. Mean total follow-up time was 23m, and mean duration of LOT1 was 4.7m. The top 4 most common LOT1 regimens accounted for 71% of patients: Rituximab (R) only (39%); bortezomib+ R (14%); bendamustine+ R (9%) and cyclophosphamide+ R (9%). No other regimens identified accounted for more than 4% of pts. Overall, 96% and 81% of pts had ≥ 1 office or hospital outpatient visit with mean per patient per month (PPPM) visits of 3.55 (standard deviation, SD = 2.41) and 2.60 (SD = 3.06), respectively. Approximately 25% and 21% had ≥ 1 ER visit or inpatient stay with mean PPPM visits of 0.11 (SD = 0.24) and 0.06 (SD = 0.16), respectively. Total mean PPPM healthcare costs during LOT1 was

Evaluation of health care resource utilization (HRU) in real-world patients treated for chronic lymphocytic leukemia (CLL).

13,589 (SD =