Long-term quality of life outcomes from a phase 4 study of tildrakizumab in patients with moderate-to-severe plaque psoriasis in a real-world setting.

BACKGROUND: Tildrakizumab is an anti-interleukin-23 p19 monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis. This report describes final primary results of a 64-week real-world study of the effect of tildrakizumab on patients' health-related quality of life (HRQoL). MATERIALS AND METHODS: In this open-label phase 4 study (NCT03718299), patients with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg at week 0, week 4, and every 12 weeks thereafter through week 52. The primary endpoint was improvement from baseline in HRQoL measured by Psychological General Well-Being Index (PGWBI) total score at weeks 28 and 52. Secondary HRQoL endpoints included change from baseline in Dermatology Life Quality Index (DLQI) score through week 64. Missing data were not imputed. RESULTS: Of 55 patients enrolled, 45 were assessed at week 64. Mean ± standard deviation (SD) total PGWBI score improved from 78.1 ± 14.1 at baseline to 85.2 ± 12.0 at week 52 (p < .001). Mean ± SD DLQI score improved from 9.4 ± 5.2 at baseline to 2.0 ± 2.6 (p < .001) at week 64 with 62.2% of patients having a DLQI score of 0 or 1 at week 64. CONCLUSIONS: Tildrakizumab improved long-term HRQoL in patients with psoriasis in a real-world setting.

Real-world treatment patterns of OTX-101 ophthalmic solution, cyclosporine ophthalmic emulsion, and lifitegrast ophthalmic solution in patients with dry eye disease: a retrospective analysis.

BACKGROUND: Dry eye disease (DED) is a disorder characterized by loss of tear film homeostasis that causes ocular surface inflammation and damage. The incidence of DED increases with age. Cyclosporine ophthalmic solution 0.09% (CEQUA®; OTX-101), cyclosporine ophthalmic emulsion 0.05% (Restasis®; CsA), and lifitegrast ophthalmic solution 5% (Xiidra®; LFT) are anti-inflammatory agents indicated for DED. This analysis compared treatment patterns in patients with DED receiving OTX-101, CsA, or LFT. METHODS: This real-world, retrospective, longitudinal cohort study utilized Symphony Health Integrated Dataverse claims from July 2019 to June 2021. The dataset included all patients with OTX-101 claims and patients with CsA or LFT claims randomly selected 2:1 to OTX-101. Patients were sorted into 3 cohorts based on index treatment. Index date was that of first treatment claim, and follow-up period was from index date to end of clinical activity or data availability. Time to treatment discontinuation (TTD), probability of discontinuation, and treatment persistence were assessed for OTX-101 vs. CsA, then OTX-101 vs. LFT. Subgroup analysis was performed based on age and prior DED treatment. Kaplan-Meier analysis and log-rank test were used to examine TTD. A logistic model evaluated association between index treatment and discontinuation. Unadjusted and adjusted odds ratios, 95% confidence intervals, and P-values were reported, with statistically significant associations based on P-values < 0.05. RESULTS: Overall, 7102 patients (OTX-101 n = 1846; CsA n = 2248; LFT n = 3008) were eligible. Median TTD was 354 days for patients receiving OTX-101 vs. 241 days for CsA and 269 days for LFT. Log-rank test indicated TTD was significantly longer for patients on OTX-101 vs. CsA (P = 0.033). Patients on CsA were 35% more likely to discontinue treatment than patients on OTX-101; OTX-101 and LFT groups had similar discontinuation rates. After 360 days, 49.8% of patients receiving OTX-101 remained on treatment vs. 39.4% of patients on CsA (P = 0.036) and 44.0% of patients on LFT (P = 0.854). CONCLUSIONS: Patients receiving OTX-101 remained on treatment significantly longer and were significantly less likely to discontinue treatment than patients on CsA. Older patients remained on OTX-101 significantly longer than CsA. These findings highlight treatment pattern differences in patients with DED receiving these anti-inflammatory agents.

Real-World Effectiveness and Safety of Tildrakizumab in Patients With Moderate-to-Severe Psoriasis: Week 28 Interim Analysis of a Phase 4 Study.

BACKGROUND: Tildrakizumab is an anti­interleukin-23 p19 monoclonal antibody approved for the treatment of adults with moderate-to-severe plaque psoriasis. This analysis evaluated real-world effectiveness and safety of tildrakizumab for 28 weeks. METHODS: In this Phase 4 study (NCT03718299), adults with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg subcutaneously at week 0, week 4, and every 12 weeks thereafter. Clinical improvement was assessed from Psoriasis Area and Severity Index (PASI) score change from baseline; disease activity from body surface area (BSA) percentage affected, static Physician's Global Assessment (sPGA), and sPGA x BSA; and safety from adverse events (AEs). RESULTS: At week 28, 52/55 enrolled patients were assessed. Mean (standard deviation [SD]) PASI score decreased significantly (P<0.001) from 11.6 (7.1) at baseline to 1.8 (3.0; 82.1% improvement) at week 28; 55.8% of patients achieved PASI 90 response. From baseline to week 28, mean (SD) BSA decreased significantly from 14.5% (11.5%) to 2.9% (6.4%), sPGA from 3.2 (0.6) to 1.2 (0.9), and BSA x sPGA from 47.0 (41.5) to 6.8 (20.3; all P<0.001). Serious AEs were infrequent. No treatment-emergent AEs were considered related to tildrakizumab. Conclusions: Real-world tildrakizumab treatment significantly improved clinical status and reduced disease activity, with no new safety concerns. Heim J, Gabriel Vasquez J, Schenkel B, et al. Real-world effectiveness and safety of tildrakizumab in patients with moderate- to-severe psoriasis: week 28 interim analysis of a phase 4 study. J Drugs Dermatol. 2023;22(8):754-760. doi:10.36849/JDD.7471.

Quality of life and patient-reported symptoms in a Phase 4, real-world study of tildrakizumab in patients with moderate-to-severe psoriasis: Week 28 interim analysis.

BACKGROUND: Tildrakizumab is an anti-interleukin-23 p19 monoclonal antibody approved for the treatment of adults with moderate-to-severe plaque psoriasis. Little real-world evidence is available regarding the effects of tildrakizumab on patients' health-related quality of life (HRQoL) and patient-reported symptoms. OBJECTIVE: This real-world study of tildrakizumab evaluated changes in HRQoL and clinical symptoms in patients with psoriasis. MATERIALS AND METHODS: In this Week (W)28 interim analysis of a 64-week Phase 4 study (NCT03718299), patients received tildrakizumab 100 mg at W0, W4, and every 12 weeks thereafter. Endpoints were improvement from baseline in Psychological General Well-Being Index (PGWBI), Dermatology Life Quality Index (DLQI), and Itch-, Pain-, and Scaling-Numerical Rating Scale scores through W28. RESULTS: Of 55 patients enrolled, 53 were assessed at W28. Mean (standard deviation [SD]) total PGWBI score improved from baseline to W28 (change, 3.7 [12.4]; p = .033), as did the positive well-being (1.0 [2.9]; p = .018) and general health (1.5 [2.2]; p < .001) domain scores. Mean (SD) DLQI score improved by -3.9 (4.3) at W4 and by -7.6 (5.1) at W28 (p < .001). Patient-reported symptoms improved starting at W4 (p < .001). CONCLUSION: Tildrakizumab treatment improved HRQoL and patient-reported symptoms in patients with psoriasis in a real-world setting. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03718299.

Real-World nivolumab dosing patterns and safety outcomes in patients receiving adjuvant therapy for melanoma.

BACKGROUND: Nivolumab at a dose of 480 mg every 4 weeks (Q4W) is approved for the adjuvant treatment of melanoma. However, real-world data on this regimen are limited in this setting. METHODS: This retrospective observational study utilized data from the US Oncology Network iKnowMed electronic health record database and patient medical charts. Eligible patients were diagnosed with melanoma and received adjuvant nivolumab monotherapy from March to August 2018. Patients were grouped by dosing regimen: cohort 1 (C1), de novo nivolumab 480 mg Q4W; cohort 2 (C2), switched to nivolumab 480 mg Q4W after nivolumab 240 mg or 3 mg/kg every 2 weeks (Q2W); cohort 3 (C3), de novo nivolumab 3 mg/kg Q2W; or cohort 4 (C4), de novo nivolumab 240 mg Q2W. Patients were followed for up to 12 months. Duration of therapy and safety/tolerability were assessed. RESULTS: One hundred ninety-one patients were included (C1, n = 40; C2, n = 74; C3, n = 22; C4, n = 55). Duration of therapy was relatively consistent across cohorts (median, 10.3 months; range, 8.3-10.7). Likewise, proportions of patients experiencing treatment-related adverse events (TRAEs) were similar (range, 54.5%-60.1%), as were the most common events (fatigue, rash, diarrhea, hypothyroidism, nausea, and pruritus). However, proportions experiencing 'significant' TRAEs varied between cohorts. Proportions discontinuing treatment were relatively consistent across cohorts. Propensity score matching and sensitivity analyses generally supported the unadjusted findings. CONCLUSIONS: Real-world safety profiles of nivolumab 240 mg Q2W and 480 mg Q4W were similar, and both were comparable to the well-documented safety of weight-based dosing (3 mg/kg Q2W), further supporting their approval and use in the adjuvant setting for melanoma.

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

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.

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

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.

Effect of infliximab on health-related quality of life and disease activity by body region in patients with moderate-to-severe psoriasis and inadequate response to etanercept: results from the PSUNRISE trial.

BACKGROUND: Treatment with tumor necrosis factor (TNF)-α antagonists is effective in patients with moderate-to-severe plaque psoriasis, including those with impaired health-related quality of life (HRQoL). METHODS: PSUNRISE is a multicenter, open-label, prospective study evaluating the efficacy and safety of switching from etanercept to infliximab in psoriasis patients with an inadequate response to etanercept. Patients received intravenous infusions of infliximab 5 mg/ kg at weeks 0, 2, 6, 14, and 22. HRQoL was assessed using the Dermatology Life Quality Index (DLQI), the 36-item Short-Form Health Survey (SF-36), and the EuroQoL (EQ-5D) index and EQ-5D visual analog scale (VAS; 0-100 cm) among patients receiving at least one infliximab infusion. Subgroup analyses (t- test) were performed to compare mean DLQI improvement between patients who achieved and did not achieve clinical response (Physician's Global Assessment [PGA] 0/1 and at least a 75% improvement in the Psoriasis Area and Severity Index [PASI 75]) at weeks 10 and 26. RESULTS: A total of 215 patients received at least one infliximab infusion. A DLQI score of 0 or 1 (no negative effect on HRQoL) was achieved by 3.7%, 44.2%, and 41.4% of patients at weeks 0, 10 and 26, respectively. Mean changes in SF-36 Physical Component Summary scores were 1.8 (week 10) and 2.4 (week 26); corresponding changes in Mental Component Summary scores were 4.5 and 5.0. The mean change in EQ-5D index score was 0.08 at week 10 and 0.09 at week 26; respective mean changes in EQ-5D VAS score were 7.73 and 9.49. Mean improvements in DLQI were significantly higher for patients achieving versus those not achieving PGA 0/1 (P=0.0193 [week 10] and P=0.0010 [week 26]) and PASI 75 response (P<0.0001 [week 10]; P=0.0012 [week 26]). CONCLUSION: Psoriasis patients with prior inadequate response to etanercept demonstrated sustained improvements in HRQoL after switching to infliximab, and HRQoL improvements were associated with clinical responses.

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.

Ustekinumab improves health-related quality of life in Korean and Taiwanese patients with moderate to severe psoriasis: results from the PEARL trial.

BACKGROUND: The PEARL study showed that the proportion of psoriasis patients achieving the primary endpoint (at least 75% improvement from baseline to week 12 in the Psoriasis Area and Severity Index) was significantly higher in ustekinumab-treated patients compared with placebo. There is a paucity of data regarding the impact of psoriasis and its treatment on health-related quality of life (HRQoL) in Asian patients. OBJECTIVES: To evaluate the effect of ustekinumab on HRQoL in Korean/Taiwanese patients with moderate to severe psoriasis enrolled in the phase III, randomized, double-blind, placebo-controlled PEARL study. METHODS: In the PEARL study, 121 patients were randomized to receive ustekinumab 45 mg at weeks 0, 4, and 16 (n=61) or placebo at weeks 0 and 4 with crossover to ustekinumab at weeks 12 and 16 (n=60). A major secondary endpoint was the change in Dermatology Life Quality Index (DLQI) from baseline at week 12. Other endpoints included the change in individual DLQI domains, proportion of patients achieving DLQI ≤ 1 (no negative effect), and proportion of patients achieving ≥ 5-point reduction in DLQI (clinically meaningful improvement) at week 12. RESULTS: At baseline, psoriasis had a very large effect on HRQoL (average DLQI, 15.7). At week 12, patients treated with ustekinumab 45 mg had significantly greater improvement from baseline in DLQI scores compared with placebo (mean decrease, 11.2 vs 0.5 (P<0.001). Likewise, 32.2% and 1.7% of patients receiving ustekinumab 45 mg and placebo, respectively, achieved a DLQI ≤ 1, and 81.4% and 18.3% achieved ≥ 5-point reduction (both P<0.001 vs placebo). Individual DLQI domains in the ustekinumab group were significantly improved compared with placebo (P<0.001). For ustekinumab-randomized patients, HRQoL improvements were sustained through week 28. Placebo patients who crossed over to ustekinumab experienced similar improvements compared with those randomized to ustekinumab. CONCLUSIONS: Ustekinumab significantly improves HRQoL in Korean/Taiwanese patients with moderate to severe psoriasis.

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

Since the original publication of the article "Development of the IL-12/23 antagonist ustekinumab in psoriasis: Past, present and future perspectives" in March 2011 (see Appendix),(1) there have been several new publications and developments of note. A number of new reports from the ustekinumab psoriasis clinical development program have been published. The analysis of efficacy and safety in the PHOENIX 1 long-term extension demonstrated that continuous stable maintenance dosing of ustekinumab was generally well tolerated and sustained durable efficacy through up to three years of treatment.(2) Pooled safety data from the phase 2 and phase 3 global trials showed that the safety profile of long-term continuous ustekinumab treatment through up to three years(3,4) and four years(5) of follow-up was favorable and comparable to what has been reported previously in the shorter-term ustekinumab psoriasis studies.(6-8) This represents the greatest exposure and longest follow-up of psoriasis patients treated with a biologic published to date. Additional phase 3 trials in Asian populations demonstrated similar high levels of efficacy and favorable safety profiles in Japanese,(9,10) Korean,(11,12) and Taiwanese(11,12) patients as those observed in trials conducted in mostly White populations in North America and Europe.(6-8) These data support the positive benefit:risk profile and consistency of response to ustekinumab over years of usage, and in multiple ethnic groups. Results from up to five years of treatment with ustekinumab in the long-term extensions of the phase 3 trials, and the efficacy, safety, and effect on quality of life in Chinese patients will be available in 2012. In addition to clinical trials of ustekinumab for the treatment of psoriasis, 24-week data from one phase 3 study of ustekinumab for the treatment of psoriatic arthritis has recently been presented(13) and another study is ongoing. A Phase 2b trial in Crohn's disease has also been presented,(14) and three phase 3 studies in Crohn's disease are currently in progress.

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

BACKGROUND: The 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. METHODS: A 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. RESULTS: The 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). CONCLUSIONS: The 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.

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.

Cost utility analysis based on a head-to-head Phase 3 trial comparing ustekinumab and etanercept in patients with moderate-to-severe plaque psoriasis: a Canadian perspective.

OBJECTIVE: A head-to-head comparator study has shown that the clinical efficacy of ustekinumab is superior to that of etanercept over a 12-week period in patients with psoriasis. Economic models are often hindered by the lack of trials directly comparing outcomes between relevant alternative therapies. The aim of this analysis was to evaluate the cost-effectiveness of ustekinumab versus etanercept among adults with moderate-to-severe plaque psoriasis based on a Phase 3 head-to-head trial. METHODS: The Markov model incorporates trial data from the Active Comparator (CNTO 1275/Enbrel) Psoriasis Trial study (ustekinumab 45 mg at Weeks 0 and 4; etanercept 50 mg biweekly) to follow patient response to initial treatment using the modeling approach developed by the Centre for Reviews and Dissemination, University of York, and often cited by others conducting economic analyses of psoriasis. Beyond the initial trial period, the Canadian model extrapolates results up to 10 years. RESULTS: Over the 10-year time horizon of the model, the mean annual costs were $16,807 for ustekinumab (45 mg) and $19,525 for etanercept (50 mg). The incremental difference in costs and utilities remained in favour of ustekinumab across a range of sensitivity analyses. CONCLUSIONS: This model highlights the advantage of having head-to-head comparative trial data relevant to the at-risk population. Our model shows that ustekinumab is more cost-effective than etanercept for patients with moderate-to-severe plaque psoriasis.

Increased prevalence of psychiatric disorders and health care-associated costs among patients with moderate-to-severe psoriasis.

OBJECTIVE: To characterize the prevalence of psychiatric disorders in patients with moderate-to-severe psoriasis and compare health care costs between patients with and without psychiatric comorbidities. METHODS: In a retrospective, matched case-control study, data for services from nearly 75 health care plans in the United States (U.S.) were collected from PharMetrics Patient Centric Database using International Classification of Diseases, Ninth Revision Clinical Modification codes, identifying a total of 39,855 adults with moderate-to-severe psoriasis (n=7,971) and without (controls; n=31,884). Patients with psoriasis had at least one psoriasis health care claim and received at least one medical/prescription treatment claim within two consecutive years. Psychiatric comorbidities and treatments among patients and controls were determined by claims. Annual inpatient, outpatient, emergency room, and prescription costs for those with and without psoriasis and those with and without psychiatric disorders were compared. RESULTS: Patients had significantly higher prevalence of anxiety (6.9% versus 4.4%), depression (9.2% versus 5.3%), bipolar disorder (1.1% versus 0.5%), or delirium (0.3% versus 0.1%; P is less than 0.05) than controls (others P is less than 0.0001). Significantly higher proportions of patients with psoriasis received antidepressants (6.1% versus 0.9%), anxiolytics (5.0% versus 0.8%), or antipsychotics (5.9% versus 0.9%) compared with controls (each P is less than 0.0001). Total health care costs for patients with psoriasis (US $11, 369.47) were significantly higher than for controls ($3,427.60; P is less than 0.001). Psoriasis patients with psychiatric disorders had significantly higher health care costs ($17,637.66) than those without psychiatric disorders ($10,362.80; P is less than 0.001). CONCLUSION: The prevalence of psychiatric disorders is higher in patients with moderate-to-severe psoriasis than in controls. Annual health care costs are higher in psoriasis patients with psychiatric disorders than in those without psychiatric disorders.

The value to patients of reducing lesion severity in plaque psoriasis.

Plaque psoriasis is associated with significant psychosocial, quality-of-life, and economic burden. The objective of this study was to quantify the value to patients of reducing the severity and size of plaque psoriasis lesions. Subjects included individuals with a self-reported diagnosis of plaque psoriasis from a nationally representative US household panel. Subjects completed a web-based conjoint analysis survey and chose between hypothetical treatments in a series of questions. Each alternative was defined by lesion severity, percentage of body surface area (BSA) covered by lesions, type of treatment, injection discomfort or pain (if treatment included injections), risk of serious lung infection, and monthly out-of-pocket cost. 28,200 panelists were invited to participate. 18,330 responded, 503 qualified, and 419 completed the survey. Mean age was 54.5 years and 52% were female. 64% (35%) of patients reported psoriasis severity as mild or mild to moderate (moderate to very severe). Patients were willing to pay $486.73 out-of-pocket per month to eliminate severe lesions covering 25% BSA on the arms and legs and $444.80 out-of-pocket per month to eliminate moderate lesions covering 4% BSA on the face. Individuals with plaque psoriasis are willing to pay substantial amounts to reduce lesion severity and percentage of BSA covered by lesions.

Epidemiology and comorbidities of psoriasis patients in a national database in Taiwan.

BACKGROUND: Recent findings in psoriasis research have shown that psoriasis is frequently associated with systemic comorbidities. OBJECTIVES: This study aims to describe the epidemiology of psoriasis and the prevalence of comorbidities in patients with psoriasis in Taiwan. METHODS: Patients who had at least one outpatient visit or admission with ICD-9-CM diagnosis code 696.0-1 in the Taiwan National Health Insurance (NHI) claims database during 2006 were identified as psoriasis cases. The cases were further classified into moderate to severe psoriasis (sPsO) for those who had previously received systemic therapy during the study period and mild psoriasis (mPsO) for those who had not. The cases were matched in a 1:4 ratio with controls from a sample cohort of 997,771 enrolees representative of the Taiwan population. Matching variables included age, gender and residential area. Prevalence of comorbidities was assessed using prevalence relative risk (RR) based upon a Cox proportional regression model. RESULTS: 51,800 psoriasis cases were identified (prevalence=0.235%; mean age=46.4±18.6; male:female=1.6:1) and 17.5% of cases were sPsO type. Psoriasis was associated with a significantly increased prevalence ratio (RR; [95% confidence interval]) for hypertension (1.51; [1.47, 1.56]), diabetes (1.64; [1.58, 1.70]), hyperglyceridaemia (1.61; [1.54, 1.68]), heart disease (1.32; [1.26, 1.37]), hepatitis B viral infection (1.73; [1.47, 2.04]), hepatitis C viral infection (2.02; [1.67, 2.44]), rheumatoid arthritis (3.02; [2.68, 3.41]), systemic lupus erythematosus (6.16; [4.70, 8.09]), vitiligo (5.94; [3.79, 9.31]), pemphigoid (14.75; [5.00, 43.50]), pemphigus (41.81; [12.41, 140.90]), alopecia areata (4.71; [2.98, 7.45]), lip, oral cavity and pharynx cancer (1.49; [1.22, 1.80]), digestive organs and peritoneum cancer (1.57; [1.41, 1.74]), depression (1.50; [1.39, 1.61]), fatty liver (2.27; [1.90, 2.71]), chronic airways obstruction (1.47; [1.34, 1.61]), sleep disorder (3.89; [2.26, 6.71]), asthma (1.29; [1.18, 1.40]), and allergic rhinitis (1.25; [1.18, 1.33]). Conversely, psoriasis was not associated with an increased risk of Crohn's disease. CONCLUSIONS: Psoriasis was associated with a significantly increased risk of comorbidities, especially for those patients with moderate to severe disease. These health associations should be taken into consideration when evaluating the burdens of psoriasis and designing effective treatment plans.

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 IgG(1) 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.

Cost per responder analysis of ustekinumab and etanercept for moderate to severe plaque psoriasis.

OBJECTIVE: To compare the cost per responder of ustekinumab with etanercept based on data from the active comparator ACCEPT trial. METHODS: In ACCEPT, patients received ustekinumab 45 mg (n = 209) or 90 mg (n = 347) at weeks 0 and 4 or etanercept 50 mg (n = 347) twice weekly for 12 weeks. The proportions of patients achieving ≥75% improvement in the Psoriasis Area and Severity Index [PASI 75] were determined at week 12. The cost per PASI 75 responder was determined for week 16, a time coinciding with treatment coverage of both drugs and accounting for the different dosing intervals. Costs for 16 weeks of therapy were based on the Wholesale Acquisition Cost (WAC) in the United States. The analysis used weight-based efficacy results for ustekinumab (45 mg for patients ≤ 100 kg; 90 mg for patients > 100 kg) and overall efficacy for etanercept, consistent with the approved dosages. RESULTS: A total of 28% of patients weighed > 100 kg. The PASI 75 response rates at week 12 were 72.2% for the ustekinumab 45 mg group in patients ≤ 100 kg, 65.0% for the ustekinumab 90 mg group in patients > 100 kg, and 56.8% for the etanercept group. At week 16, the cost per responder was $17,842 for ustekinumab and $20,077 for etanercept. CONCLUSION: The cost per responder was lower for ustekinumab than for etanercept through 16 weeks in psoriasis patients.

Ustekinumab decreases work limitations, improves work productivity, and reduces work days missed in patients with moderate-to-severe psoriasis: results from PHOENIX 2.

OBJECTIVE: To assess the effect of ustekinumab on productivity and work limitations among 1230 psoriasis patients treated with ustekinumab 45 mg or 90 mg or placebo during the Phase III PHOENIX 2 trial. METHODS: The self-administered Work Limitations Questionnaire (WLQ) was used to determine the on-the-job limitations at baseline and weeks 12 and 24. Productivity was assessed using a Visual Analog Scale (VAS), and the number of work days missed due to psoriasis was recorded. RESULTS: At baseline, work limitations and productivity were similar across treatment groups. At week 12, improvement in productivity VAS scores was significantly (p < 0.001) higher in the 45 mg (72.6%) and 90 mg (71.4%) ustekinumab groups versus placebo (no change), and the proportion of patients who missed work days was significantly lower (2.0% for each ustekinumab group vs 8.3% for placebo; p < 0.001). Mean improvements from baseline to week 12 were greater with ustekinumab than with placebo for WLQ domains, including time management (6.6/9.1 vs -0.7), mental-interpersonal (7.8/7.5 vs -1.1), and output demands (6.8/7.0 vs -1.1) (p < 0.001 for ustekinumab 45 mg/90 mg vs placebo). Improvements were maintained through week 24. CONCLUSIONS: Ustekinumab 45 mg or 90 mg significantly increased productivity, reduced work days missed, and improved work limitations compared with placebo in patients with moderate-to-severe psoriasis.