A multidimensional assessment of the burden of psoriasis: results from a multinational dermatologist and patient survey.

BACKGROUND: Psoriasis is a chronic, immune-mediated disease, characterized by symptoms that include itching and skin pain and is often associated with comorbidities. Patients have a substantial detriment to quality of life (QoL) and work productivity with associated cost burden. OBJECTIVES: To investigate the incremental burden of comorbidities, itch and affected body areas among systemic eligible patients with psoriasis, using a multinational survey of dermatologists and their patients with psoriasis. METHODS: Multinational data from the Growth from Knowledge (GfK) Disease Atlas Global Real-World Evidence program were used. Eligible patients were identified as those who were currently having or had ever had moderate-to-severe psoriasis, and must have been receiving prescription treatments at the time of the survey. Multivariable regression analyses were conducted to assess the incremental burden among psoriasis patients with physical and psychological comorbidities, itch and affected visible and sensitive body areas vs. psoriasis patients without these conditions, respectively. RESULTS: The study enrolled 3821 patients with psoriasis, from nine countries, with an average Psoriasis Area and Severity Index score of 6·4. The presence of comorbidities was associated with a significant increase in the likelihood of skin pain, lower QoL, greater work impairment and increased usage of medical resources (except in psoriasis patients with obesity and type 2 diabetes). Psoriasis patients suffering from itch and those with visible and sensitive affected body areas also had impaired QoL vs. those without these conditions. CONCLUSIONS: Psoriasis patients with physical and psychological comorbidities, itch and affected visible and sensitive body areas had lower QoL and greater work impairment compared to those without these conditions.

Differential effects of secukinumab vs. ustekinumab for treatment of psoriasis on quality of life, work productivity and activity impairment: a structural equation modelling analysis.

BACKGROUND: The appearance and lifelong, chronic nature of psoriasis result in considerable burden to patients, such as sleep impairment, depressive symptoms, negative self-esteem and reduced work productivity. OBJECTIVES: To examine direct and indirect (mediated) effects of secukinumab vs. ustekinumab on quality of life, work productivity and activity impairment based on psoriasis severity and symptoms. METHODS: Analyses were based on data from the CLEAR study. Structural equation modelling examined the effects of secukinumab vs. ustekinumab on the Dermatology Life Quality Index (DLQI) and on the Work Productivity and Activity Impairment (WPAI) questionnaire using Psoriasis Area and Severity Index (PASI) severity and symptoms (pain, itching and scaling) as potential mediators. Analyses were conducted primarily for patients achieving a PASI 90 response (90% or greater reduction in PASI from baseline) at week 16 (repeated at week 52) and for PASI 50, 75 and 100. RESULTS: Results at weeks 16 and 52 showed that the effect of treatment on change in DLQI score was mediated by the PASI 90 response and by improvements in itching, pain, and scaling. Achieving any PASI response as early as week 16 directly resulted in significantly better WPAI scores. At week 52, both PASI response and improvement in scaling directly resulted in significantly better WPAI scores. Pain, itching and scaling were correlated (r = 0·51-0·68); improvement in any of these had a significant effect (directly or indirectly) on WPAI. All results favoured secukinumab over ustekinumab. CONCLUSIONS: The results underscore the important role of both PASI response and reduction in symptoms on improvements in health-related quality of life and work and daily activity in favour of secukinumab vs. ustekinumab.

Cost-effectiveness of secukinumab as first biologic treatment, compared with other biologics, for moderate to severe psoriasis in Germany.

BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin 17A, has demonstrated strong and sustained efficacy in adults with moderate to severe psoriasis in clinical trials. OBJECTIVE: This analysis compared the cost per responder of secukinumab as first biologic treatment of moderate to severe psoriasis, with adalimumab, infliximab, etanercept and ustekinumab in Germany. METHODS: A 52-week decision-tree model was developed. Response to treatment was assessed based on the likelihood of achieving a predefined Psoriasis Area and Severity Index (PASI) response to separate the cohort into responders (PASI ≥75), partial responders (PASI 50 to 74) and non-responders (PASI <50). Responders at week 16 continued initial treatment, whereas partial responders and non-responders were switched to standard of care, which included methotrexate, cyclosporine, phototherapy and topical corticosteroids. Sustained response was defined as 16-week response maintained at week 52. A German healthcare system perspective was adopted. Clinical efficacy data were obtained from a mixed-treatment comparison; 2016 resource unit costs from national sources; and adverse events and discontinuation rates from the literature. We calculated cost per PASI 90 responder over week 16 and week 52, as well as cost per sustained responder between weeks 16 and 52. RESULTS: Secukinumab had the lowest cost per PASI 90 responder over 16 weeks (€18 026) compared with ustekinumab (€18 080), adalimumab (€23 499), infliximab (€29 599) and etanercept (€34 037). Over 52 weeks, costs per PASI 90 responder ranged from €42 409 (secukinumab) to €70 363 (etanercept). Likewise, secukinumab had the lowest cost per sustained 52-week PASI 90 responder (€22 690) compared with other biologic treatments. Sensitivity analyses, excluding patient copayments, showed similar results. CONCLUSIONS: First biologic treatment with secukinumab for moderate to severe psoriasis is cost-effective, with lowest cost per responder compared with other biologic treatments in Germany.

Secukinumab significantly reduces psoriasis-related work impairment and indirect costs compared with ustekinumab and etanercept in the United Kingdom.

BACKGROUND: Psoriasis causes work productivity impairment that increases with disease severity. Whether differential treatment efficacy translates into differential indirect cost savings is unknown. OBJECTIVE: To assess work hours lost and indirect costs associated with secukinumab versus ustekinumab and etanercept in the United Kingdom (UK). METHODS: This was a post hoc analysis of work impairment data collected in the CLEAR study (secukinumab vs. ustekinumab) and applied to the FIXTURE study (secukinumab vs. etanercept). Weighted weekly and annual average indirect costs per patient per treatment were calculated from (i) overall work impairment derived from Work Productivity and Activity Impairment data collected in CLEAR at 16 and 52 weeks by Psoriasis Area and Severity Index (PASI) response level; (ii) weekly/annual work productivity loss by PASI response level; (iii) weekly and annual indirect costs by PASI response level, based on hours of work productivity loss; and (iv) weighted average indirect costs for each treatment. In the primary analysis, work impairment data for employed patients in CLEAR at Week 16 were used to compare secukinumab and ustekinumab. Secondary analyses were conducted at different time points and with patient cohorts, including FIXTURE. RESULTS: In CLEAR, 452 patients (67%) were employed at baseline. At Week 16, percentages of weekly work impairment/mean hours lost decreased with higher PASI: PASI < 50: 22.8%/7.60 h; PASI 50-74: 13.3%/4.45 h; PASI 75-89: 6.4%/2.14 h; PASI ≥ 90: 4.9%/1.65 h. Weighted mean weekly/annual work hours lost were significantly lower for secukinumab than ustekinumab (1.96/102.51 vs. 2.40/125.12; P = 0.0006). Results were consistent for secukinumab versus etanercept (2.29/119.67 vs. 3.59/187.17; Ρ<0.0001). Average annual indirect cost savings with secukinumab were £355 vs. ustekinumab and £1061 versus etanercept. Results at 52 weeks were similar. CONCLUSIONS: Secukinumab significantly reduced work impairment and associated indirect costs of psoriasis compared with ustekinumab and etanercept at Week 16 through 52 in the United Kingdom.

Patient-dermatologist agreement in psoriasis severity, symptoms and satisfaction: results from a real-world multinational survey.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disease, which often requires lifelong treatment. A strong partnership between the patient and healthcare practitioners should help to achieve effective treatment outcomes. OBJECTIVE: To assess concordance of views between patients with psoriasis and their treating dermatologists relative to psoriasis severity, presence of symptoms and satisfaction with disease control achieved. METHODS: We used data from the Growth from Knowledge (GfK) Disease Atlas real-world evidence program, a syndicated, retrospective, cross-sectional survey among dermatologists and their systemic therapy eligible patients with psoriasis, conducted across nine countries. Concordance was measured through patients and their dermatologist's identical answers to the same survey questions. Concordance was evaluated using percentage agreement between dermatologists and their patients, and Cohen's kappa (κ) statistic. The level of concordance was defined as 'none' (κ ≤ 0), 'none to slight' (0.01-0.20), 'fair' (0.21-0.40), 'moderate' (0.41-0.60), 'substantial' (0.61-0.80) and 'almost perfect' (>0.8). The analysis was conducted for the overall population and for each participating country. RESULTS: Overall, 524 dermatologists and 3821 patients with psoriasis were included in the survey. Concordance of patient and dermatologist perceptions of psoriasis severity was fair both at diagnosis, and at the time of the survey (61% agreement, κ = 0.326 and 55% agreement, κ = 0.370, respectively). Higher levels of concordance were reported when patients assessed their psoriasis as moderate-to-severe (using Investigator's Global Assessment/Physician's Global Assessment [IGA/PGA] 5-point scale of 3 or 4). Concordance regarding symptoms ranged from fair to moderate (κ = 0.241-0.575). Satisfaction with psoriasis control was fair (39% agreement, κ = 0.213). Results showed different patterns of concordance across the participating countries although a low concordance was observed on the satisfaction with psoriasis control in all of them. CONCLUSION: Results from this multinational real-world survey indicate different perceptions between patients with psoriasis and their dermatologist with respect to psoriasis severity, symptoms and disease control.

Secukinumab sustains good efficacy and favourable safety in moderate-to-severe psoriasis after up to 3 years of treatment: results from a double-blind extension study.

BACKGROUND: Secukinumab has demonstrated significant efficacy with a good safety profile through 1 year in plaque psoriasis. Given the chronic nature of this disease, long-term follow-up is needed to evaluate psoriasis therapies fully. OBJECTIVES: To determine the long-term (3-year) efficacy and safety of secukinumab in moderate-to-severe psoriasis. METHODS: Patients completing 52 weeks of secukinumab treatment in the SCULPTURE core study entered an extension in which they continued the same double-blind regimens. Dosing regimens included a fixed-interval schedule (FI; every 4 weeks) and retreatment as needed (RAN), in which patients were withdrawn from secukinumab and received placebo until the start of relapse, at which time secukinumab every 4 weeks was reinitiated. The study was registered with number NCT01640951. RESULTS: In total 168 patients receiving secukinumab 300 mg FI and 172 receiving secukinumab 300 mg RAN entered the extension. Secukinumab 300 mg FI sustained high efficacy: at the end of year 3, the proportion of responders achieving ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) was 63·8%, and of PASI 100 responders it was 42·6%. The mean absolute PASI remained low (2-4) from week 52 to week 152 with 300 mg FI, with approximately two-thirds of patients reporting no impact of skin disease on their lives (Dermatology Life Quality Index of 0 or 1). Improvements in overall and subscale scores on all quality-of-life instruments were well sustained. As in the core study, FI dosing was consistently more efficacious than RAN. No new safety signals were identified to year 3. CONCLUSIONS: Secukinumab 300 mg FI sustained high responses and improved quality of life with no new safety concerns through 3 years.

Incremental burden of cardiovascular comorbidity and psoriatic arthritis among adults with moderate-to-severe psoriasis in five European countries.

BACKGROUND: Moderate-to-severe psoriasis is associated with reduced health-related quality of life (HRQoL). Individuals with psoriasis are at increased risk for other medical conditions, but little information quantifies the incremental burden of psoriasis-associated comorbidity among European adults, and data have generally been limited to clinical samples. OBJECTIVE: To quantify the incremental burden of cardiovascular comorbidity and psoriatic arthritis among adults with moderate-to-severe psoriasis in the general population of France, Germany, Italy, Spain and the United Kingdom (EU5). METHODS: All measures were self-reported and came from the 2010-2013 EU5 National Health and Wellness Surveys (NHWS). Moderate-to-severe psoriasis was identified by >10% body surface area affected by psoriasis and/or use of therapies for moderate-severe disease. Outcomes were SF-12v2/SF-36v2 mental and physical component summary scores (MCS and PCS, respectively), SF-6D health utility, Work Productivity and Activity Impairment (WPAI) questionnaire and healthcare use in the past 6 months. Generalized linear models compared across cardiovascular comorbidity (CV) or psoriatic arthritis (PsA) groups vs. non-CV or non-PsA groups with appropriate link functions to adjust for covariates. RESULTS: Among moderate-to-severe psoriasis respondents (n = 957), 19.8% (n = 190) reported CV comorbidity and 12.3% (n = 118) reported PsA. After adjustment for covariates, CV comorbidity was associated with 3.0 points lower MCS, 3.4 points lower PCS and 0.05 points lower SF-6D (all P < 0.01). Likewise, they had greater mean work impairment (48% vs. 33%), more activity impairment (48% vs. 37%), and more healthcare provider visits (8.8 vs. 6.9), emergency room visits (0.65 vs. 0.31) and hospitalizations (0.61 vs. 0.22) (all P < 0.05). Compared to non-PsA respondents, PsA respondents also had worse mean MCS (2.6 points), PCS (6.3 points) and SF-6D scores (0.07 points), and more work impairment (52% vs. 34%), activity impairment (54% vs. 38%) and healthcare provider visits (10.5 vs. 6.9) (all P < 0.05). CONCLUSION: CV comorbidity and PsA were associated with significant incremental burden among EU5 adults with moderate-to-severe psoriasis.

Secukinumab demonstrates greater sustained improvements in daily activities and personal relationships than ustekinumab in patients with moderate-to-severe plaque psoriasis: 52-week results from the CLEAR study.

BACKGROUND: Psoriasis can greatly impact patients' lives by influencing clothing worn as well as by impairing sexual functioning. Secukinumab, a human monoclonal antibody selectively neutralizing interleukin-17A, has demonstrated good efficacy and safety in the treatment of moderate-to-severe psoriasis and psoriatic arthritis with a rapid onset of action and sustained response. OBJECTIVE: This analysis using the CLEAR study, a phase 3b double-blind study comparing the efficacy and safety of secukinumab vs. ustekinumab in adults with moderate-to-severe plaque psoriasis, evaluated the treatment effects on patient's daily activities and personal relationships. METHODS: Impact on daily activities (interference with home/shopping/garden, and influence on clothes worn) and impact on personal relationships (problems with partner/others, and sexual difficulties) as well as their corresponding subscales were selected from the Dermatology Life Quality Index scale and evaluated for patients treated with secukinumab vs. ustekinumab from the CLEAR study. Treatment differences in mean scores and proportions of responders (score = 0, indicating no impact) were evaluated through 52 weeks. Time to response was evaluated through Week 16. RESULTS: Significant differences between secukinumab and ustekinumab were observed for daily activities and personal relationships at Week 16 and sustained through Week 52 (Week 52 response rates for daily activities: 82.9% vs. 73.5%, including interference with home/shopping/garden: 88.5% vs. 78.2%, and influence on clothes worn: 85.6% vs. 74.4%; personal relationships: 86.1% vs. 73.7%, including problems with partner/others: 86.6% vs. 74.8%, and sexual difficulties: 88.5% vs. 74.3%; all P < 0.01). The median time to response was 4 weeks for secukinumab vs. 8 weeks for ustekinumab for daily activities and personal relationships (both P < 0.05). CONCLUSION: Secukinumab treatment helps patients with moderate-to-severe plaque psoriasis have a more normal life faster when compared to ustekinumab, by providing greater and sustained improvement in clothing choice and sexual functioning.

Effect of nivolumab on health-related quality of life in patients with treatment-naïve advanced melanoma: results from the phase III CheckMate 066 study.

BACKGROUND: Nivolumab has shown significant survival benefit and a favorable safety profile compared with dacarbazine chemotherapy among treatment-naïve patients with metastatic melanoma in the CheckMate 066 phase III study. Results from the health-related quality of life (HRQoL) analyses from CheckMate 066 are presented. PATIENTS AND METHODS: HRQoL was evaluated at baseline and every 6 weeks while on treatment using the European Organisation for Research and Treatment of Care (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and the EuroQoL Five Dimensions Questionnaire (EQ-5D). Via a multi-step statistical plan, data were analyzed descriptively, cross-sectionally, and longitudinally, adjusting for baseline covariates, in patients having baseline plus ≥1 post-baseline assessment. RESULTS: Baseline-adjusted completion rates for all HRQoL questionnaires across treatment arms were 65% and 70% for dacarbazine and nivolumab, respectively, and remained similar throughout treatment. The mean baseline HRQoL scores were similar for patients treated with nivolumab and dacarbazine. Baseline HRQoL levels with nivolumab were maintained over time. This exploratory analysis showed a between-arm difference in favor of nivolumab on the EQ-5D utility index and clinically meaningful EQ-5D improvements from baseline at several time points for patients receiving nivolumab. Patients treated with nivolumab did not show increased symptom burden as assessed by the EORTC QLQ-C30. No HRQoL change was noted with dacarbazine patients up to week 43, although the high attrition rate after week 13 did not allow any meaningful analyses. Patients receiving nivolumab deteriorated significantly later than those receiving dacarbazine on several EORTC QLQ-C30 scales and the EQ-5D utility index. CONCLUSIONS: In addition to prolonged survival, these exploratory HRQoL results show that nivolumab maintains baseline HRQoL levels to provide long-term quality of survival benefit, compared with dacarbazine in patients with advanced melanoma.