Effectiveness of brodalumab in improving itching and skin pain in Japanese patients with psoriasis: The ProLOGUE study.

Itching and skin pain are bothersome symptoms of psoriasis, but evidence is limited regarding the treatment effectiveness on these symptoms in daily clinical settings. We assessed the changes in the levels of itching and skin pain after brodalumab treatment in Japanese patients with psoriasis using patient-reported outcomes (PROs). Patients with psoriasis who have inadequate response to existing treatments were enrolled in the single-arm, open-label, multicenter, prospective ProLOGUE study and received brodalumab 210 mg subcutaneously in daily clinical practice. Psoriasis Area and Severity Index (PASI) and PRO assessments were performed at baseline and weeks 12 and 48. Seventy-three patients (men, 82.2%; median age, 54.0 years) were enrolled. The Itch Numeric Rating Scale (NRS; p < 0.0001 at weeks 12 and 48) and Skin Pain NRS (week 12, p = 0.0004; week 48, p < 0.0001) scores significantly decreased from baseline. The Itch NRS score was significantly higher in patients with a Dermatology Life Quality Index (DLQI) score of ≥2 (vs. 0/1; p < 0.0001 at weeks 12 and 48) and in patients with a Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) global satisfaction domain score of ≤70% (vs. >70%; week 12, p = 0.0120; week 48, p = 0.0348). The Itch NRS score cutoff value for achieving a PASI score of ≤2, DLQI score of 0/1, and TSQM-9 global satisfaction domain score of >70% was 1 at week 12 and 0 at week 48. Brodalumab treatment was associated with improvement in itching and skin pain in Japanese patients with psoriasis. An Itch NRS score of 0 can be a long-term treatment goal for psoriasis (Japan Registry of Clinical Trials identifier: jRCTs031180037).

Itch as a critical factor in impaired health-related quality of life in patients with plaque psoriasis achieving clear or almost-clear skin: Analysis of the single-arm, open-label, multicenter, prospective ProLOGUE study.

Background: Patients with psoriasis report impaired health-related quality of life (HRQoL; Dermatology Life Quality Index score ≥ 2) even after achieving clear or almost-clear skin with biologic treatment. Objective: To assess the effectiveness of brodalumab in HRQoL improvement and the factors associated with incomplete HRQoL improvement in Japanese patients with psoriasis. Methods: As a part of the single-arm, open-label, multicenter, prospective ProLOGUE study (Japan Registry of Clinical Trials identifier: jRCTs031180037), patients were treated with 210 mg of subcutaneous brodalumab in daily clinical practice until week 48. The absolute Psoriasis Area and Severity Index scores and patient-reported outcomes were assessed at baseline and weeks 12 and 48. Results: Seventy-three patients (male, 82.2%; median age, 54.0 years) were enrolled. The Dermatology Life Quality Index and European Quality of Life 5-Dimension 5-Level Utility Index scores significantly improved from baseline to weeks 12 and 48. At week 48, all 13 patients with a Dermatology Life Quality Index score of ≥2 and an absolute Psoriasis Area and Severity Index score of 0 to ≤2 reported itching. Limitations: Unclear generalizability of the results to other biologics. Conclusion: Treatment with brodalumab improved HRQoL in patients with psoriasis. Itching may contribute to incomplete HRQoL improvement in patients who have achieved clear or almost-clear skin.

Work productivity in real-life employed patients with plaque psoriasis: Results from the ProLOGUE study.

Psoriasis poses a substantial economic burden by reducing the work productivity of affected patients. We aimed to evaluate the negative impact of plaque psoriasis on work productivity and effectiveness of brodalumab in improving work productivity impairment in real-life employed patients. This analysis was conducted in employed patients from ProLOGUE, an open-label, multicenter, prospective cohort study (Japan Registry of Clinical Trials identifier: jRCTs031180037). Outcomes included association of Work Productivity and Activity Impairment-Psoriasis (WPAI-PSO) domain scores with scores from various patient-reported outcome measures or Psoriasis Area and Severity Index (PASI) scores at baseline. Change from baseline in WPAI-PSO domain scores following brodalumab treatment was also evaluated. Of the 73 patients enrolled, 51, 48, and 40 patients were considered employed at baseline, Week 12, and Week 48 of brodalumab treatment, respectively. In the model adjusted by age and sex, the work productivity loss score correlated with the Dermatology Life Quality Index (DLQI), itch Numeric Rating Scale (NRS), Patient Health Questionnaire-8 (PHQ-8), and skin pain NRS scores (partial Spearman correlation coefficient [ρ] = 0.608, 0.510, 0.461, and 0.424, respectively); presenteeism score correlated with the DLQI, itch NRS, and skin pain NRS scores (ρ = 0.568, 0.500, and 0.403, respectively); and activity impairment score correlated with the DLQI and PHQ-8 scores (ρ = 0.530 and 0.414, respectively). None of the WPAI-PSO domain scores correlated with the PASI score. All WPAI-PSO domain scores (except absenteeism) significantly reduced from baseline to Weeks 12 (p < 0.0001) and 48 (p < 0.001) with brodalumab treatment. In conclusion, work productivity impairment in psoriasis was associated with various subjective symptoms that can be captured using patient-reported outcome measures. Brodalumab treatment improved work productivity in real-life employed patients with plaque psoriasis.

Effectiveness of brodalumab in achieving treatment satisfaction for patients with plaque psoriasis: The ProLOGUE study.

BACKGROUND: Real-life evidence on the quality of treatment with brodalumab in patients with plaque psoriasis based on patient-reported outcomes remains limited. OBJECTIVE: To assess the effectiveness of brodalumab in achieving treatment satisfaction for real-life Japanese patients with psoriasis. METHODS: As part of a single-arm, open-label, multicenter, prospective study (ProLOGUE), Psoriasis Area and Severity Index (PASI) scores, body surface area (BSA), and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) domain scores were assessed at baseline and Weeks 12 and 48 of brodalumab treatment. Patient Global Assessment (PtGA) scores were captured at Weeks 12 and 48. RESULTS: Seventy-five patients were enrolled, of whom 73 received brodalumab. PASI scores and BSA significantly reduced from baseline at Weeks 12 and 48 (all P < 0.0001). Most (90%) patients felt the treatment was effective on the PtGA scale at Weeks 12 and 48. TSQM-9 domain scores significantly improved at Weeks 12 and 48 (all P < 0.0001). A PASI score of ≤ 2 was suggested as a treatment goal for biologic treatment of psoriasis from a receiver operating characteristic curve analysis, although some of the TSQM-9 domain scores did not improve in patients achieving this goal. No new safety signals were observed. CONCLUSION: Treatment with brodalumab was associated with improved objective symptoms and satisfaction in Japanese patients with psoriasis. A PASI score of ≤ 2 as a goal for biologic treatment of psoriasis may be feasible, although achieving this PASI goal alone may be insufficient to clearly improve long-term patient satisfaction (Japan Registry of Clinical Trials identifier: jRCTs031180037).

Medical Director Practice of Advising Increased Dietary Protein Intake in Hemodialysis Patients With Hyperphosphatemia: Associations With Mortality in the Dialysis Outcomes and Practice Patterns Study.

OBJECTIVES: Patients undergoing hemodialysis (HD) may have poor nutritional status and hyperphosphatemia. Nephrologists sometimes manage hyperphosphatemia by prescribing phosphate binders and/or recommending restriction of dietary phosphate including protein-rich foods; the later may, however, adversely affect nutritional status. DESIGN AND METHODS: The analysis includes 8805 HD patients on dialysis ≥ 120 days in 12 countries in Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 4 (2009-2011), from 248 facilities. The primary exposure variable was response to the following question: "For patients with serum albumin 3.0 g/dL and phosphate 6.0 mg/dL, do you recommend to (A) increase or (B) decrease/no change in dietary protein intake (DPI)?". The association between medical director's practice of recommending an increase in DPI and all-cause mortality was analyzed with Cox regression adjusted for potential confounders. Linear and logistic regressions were used to model the cross-sectional associations between DPI advice practice and intermediate markers of patient nutrition. RESULTS: Median follow-up was 1.6 years. In the case scenario, 91% of medical directors in North America had a practice of recommending DPI increase compared to 58% in Europe (range = 36%-83% across 7 countries) and 56% in Japan. The practice of advising DPI increase was weakly associated with lower mortality [HR (95% CI): 0.88 (0.76-1.02)]. The association tended to be stronger in patients with age 70+ years [HR (95% CI): 0.82 (0.69-0.97), P = .12 for interaction]. The practice of advising DPI increase was associated with 0.276 mg/dL higher serum creatinine levels (95% CI: 0.033-0.520) after adjustment for case mix. CONCLUSIONS: Medical director's practice of recommending an increase in DPI for HD patients with low albumin and high phosphate levels was associated with higher serum creatinine levels and potentially lower all-cause mortality. To recommend protein intake liberalization in parallel with phosphate management by physicians may be a critical practice for better nutritional status and outcomes in HD patients.

Relationship between serum trough levels and efficacy of brodalumab from a post hoc exploratory analysis of a Japanese study in patients with plaque psoriasis.

Previous clinical studies have shown that efficacy and serum brodalumab levels are dose dependent in patients with psoriasis receiving the same dose of brodalumab during the study. This study aimed to investigate the association between dosage, serum levels, and efficacy of brodalumab in Japanese patients with plaque psoriasis with dosage variations during the study. This was a post hoc exploratory analysis of a 108-week, multicenter, open-label extension study, which changed into a post-marketing surveillance study following brodalumab approval in Japan. Eligible patients with plaque psoriasis (n = 129) received brodalumab 140 mg every 4 weeks on Day 1; dosage change at physician's discretion from 140 mg every 8 weeks to 210 mg every 2 weeks was permitted; patients switched to 210 mg every 2 weeks during the post-marketing surveillance study. Exploratory endpoints included serum brodalumab levels at Weeks 28 and 108, its association with Psoriasis Area and Severity Index score, and Psoriasis Area and Severity Index score in patients receiving brodalumab 210 mg every 2 weeks at end of study. Median brodalumab trough levels were significantly higher (P < 0.05) at higher vs. lower dosages at Weeks 28 (n = 126) and 108 (n = 111) except for 140 mg every 2 weeks vs. 210 mg every 2 weeks at Week 108 and higher in patients with lower Psoriasis Area and Severity Index scores-significantly different only for Psoriasis Area and Severity Index score 0 vs. >2 at Week 28 (P = 0.0153). Of 100 patients receiving 210 mg every 2 weeks at end of study, 89% had a Psoriasis Area and Severity Index score ≤2. In patients with plaque psoriasis, brodalumab efficacy may depend upon sustained serum trough levels and can be restored by using the approved dose.

A Pooled Analysis From Phase 2b and 3 Studies in Japan of Istradefylline in Parkinson's Disease.

BACKGROUND: Characterization of patient factors associated with istradefylline efficacy may facilitate personally optimized treatment. OBJECTIVES: We aimed to examine which patient factors are associated with favorable istradefylline treatment outcomes in PD patients with motor complications. METHODS: We performed a pooled analysis of data from two identical phase 2b and 3 Japanese studies of istradefylline. Logistic regression models were used to assess the association of 12 patient characteristics with favorable outcomes. RESULTS: Off time reduction and increased good on time with istradefylline provided a significantly favorable response in patients aged ≥65 years. Off time reduction was more favorable in patients with ≥8-hour daily off time at baseline. Improvement in UPDRS Part III was favorable in patients with UPDRS Part III baseline score ≥ 20. CONCLUSIONS: Several patient factors influenced the effect of istradefylline on motor fluctuations, motor function, activities of daily living, and clinical impression. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Effect of heat-treatment on the pH sensitivity of stainless-steel electrodes as pH sensors.

Effect of heat-treatment on the pH sensitivity of uncoated stainless-steel electrodes was investigated to comprehend the pH sensitivity of metal-oxide coated stainless-steel electrodes as novel pH sensors. The pH sensitivity of stainless-steel electrodes as-received and heat-treated at 500 °C, 600 °C and 700 °C for 24 h were 91 %, 94 %, 102 % and 91 %, respectively. The pH sensitivity tended to increase with increasing heat-treatment time at a given temperature. Thus, the most suitable heat-treatment condition for the stainless-steel electrodes was 600 °C for 24 h. The austenite phase (fcc) was the main phase on the surface of the heat-treated stainless-steel electrodes. Unexpectedly, the change in the martensite phase (bcc) as the second phase with heat-treatment temperature was similar to the pH sensitivity, with the martensite phase affecting the pH sensitivity. Therefore, it appeared that the pH sensitivity of the metal-oxide coated stainless-steel electrodes was affected by the underlying stainless-steel as well as the outer metal-oxide film coating. A prototype stainless-steel tube electrode was used as a working electrode for demonstrating the depth profiling of pH. The stainless-steel tube electrode showed good performance for measuring pH depth profiles compared to commercially available glass electrodes.