Five-year Maintenance of Clinical Response and Consistent Safety Profile for Guselkumab in Asian patients with Psoriasis from VOYAGE 1 and VOYAGE 2.

INTRODUCTION: Guselkumab is a human monoclonal antibody against IL-23 used in the treatment of moderate-to-severe psoriasis. This post-hoc analysis evaluated the efficacy and safety of guselkumab in the Asian subpopulation of VOYAGE 1 and VOYAGE 2 through 5 years. METHODS: The proportions of guselkumab-treated Asian patients (VOYAGE 1 and 2) achieving Psoriasis Area and Severity Index (PASI) 90 and PASI 100, Investigator's Global Assessment (IGA) scores of 0/1 and 0, and Dermatology Life Quality Index (DLQI) scores of 0/1 (week 100 through week 252) were assessed. Non-responders were patients who met the treatment failure rules. Efficacy endpoints were analyzed using the as-observed methodology (no missing data imputation) for both studies and using non-responder imputation (for patients with any missing data) in VOYAGE 1. Safety outcomes were based on pooled data through week 252. RESULTS: Response rates through week 252 for 199 Asian patients in the guselkumab group in VOYAGE 1 and VOYAGE 2, respectively, were 76.8% and 80.6% (PASI 90), 26.8% and 38.7% (PASI 100), 64.3% and 87.1% (IGA 0/1), and 26.8% and 45.2% (IGA 0). DLQI (0/1) at week 252 was achieved by 52.7% of patients in VOYAGE 1 and 61.3% in VOYAGE 2, while DLQI (0) at week 252 was achieved by 32.7% of patients in VOYAGE 1 and 40.3% in VOYAGE 2. The safety profile was similar to the global population and remained consistent through 5 years. Asian patients were followed for a total of 814 patient-years (PY). Over 85% of the guselkumab-treated patients continued treatment through week 264. The rate of serious adverse events (AEs) at week 252 was 3.07/100 PY. Rates of AEs of interest were low: serious infections, 0.74/100 PY; nonmelanoma skin cancer (NMSC), no patients; malignancies other than NMSC, 0.12/100 PY; and no major adverse cardiovascular events (MACE). CONCLUSION: These analyses confirm a continuous response over 5 years, indicating that guselkumab shows therapeutic longevity in Asian patients requiring long-term treatment for moderate-to-severe psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: VOYAGE 1 [NCT02207231] and VOYAGE 2 [NCT02207244].

Psoriasis­a long-term condition that causes a skin rash with scaly, itchy patches (plaques)­is becoming more prevalent in Asia. To control symptoms of moderate-to-severe psoriasis and achieve a strong improvement in the patient's quality of life, continuous treatment is usually needed. Guselkumab is a medicine that targets specific parts of the immune system to treat moderate-to-severe psoriasis. It is important to understand the long-term benefits of guselkumab in Asian patient populations. Our study analyzed the data from two randomized clinical trials (called VOYAGE 1 and VOYAGE 2) that studied people with moderate-to-severe plaque psoriasis. We examined results for the 199 people from Asia, including Korea and Taiwan, who took part in these studies. Overall, 162 of the 184 (86.6%) people from Asia treated with guselkumab incorporated into these studies continued the treatment for 5 years. Patients treated with guselkumab showed effective clinical responses (improvements measured by clinicians), including high skin clearance, meaning a large reduction in skin surface area affected by psoriasis. On guselkumab, patients also reported improvements in their skin-related health-related quality of life. These improvements and the efficacy of guselkumab were maintained over 5 years of follow-up. The safety results for guselkumab in the Asian subpopulation were similar to those for the global population, showing low rates of serious adverse effects, as expected from this type of medicine. Overall, our study found a favorable benefit­risk profile with continuous guselkumab treatment for 5 years in Asian people with moderate-to-severe psoriasis. This highlights that guselkumab treatment allows long-lasting control of this disease.

Efficacy of guselkumab in difficult-to-treat psoriasis regions: Data from VOYAGE 1 and VOYAGE 2 Asian subpopulations.

Patients with psoriasis were randomized to guselkumab, placebo or adalimumab in the VOYAGE 1 and VOYAGE 2 studies. In this post hoc analysis, difficult-to-treat psoriasis regions in the Asian subpopulation for both the guselkumab and adalimumab groups were compared with placebo at week 16 and the active treatment groups were compared at week 24. Endpoints included patients achieving scores of 0 or 1 (clear or near clear) or 0 (clear) on the scalp-specific Investigator's Global Assessment (ss-IGA), Physician's Global Assessment of the hands and/or feet (hf-PGA), and fingernail PGA (f-PGA), and percentage improvement in target Nail Psoriasis Severity Index (NAPSI) score through week 24. Efficacy was also assessed by prior biologic experience at baseline. A total of 199 eligible Asian patients were included. The proportion of patients achieving "clear" or "near clear" with guselkumab was superior to adalimumab at week 24 for scalp psoriasis ss-IGA (Asian patients, 72 [85.7%] vs 35 [67.3%], P = 0.004), hands and/or feet psoriasis hf-PGA (29 [82.9%] vs 16 [61.5%], P = 0.054), and similar for fingernail psoriasis f-PGA (28 [63.6%] vs 17 [54.8%], P = 0.412). Guselkumab mean improvements in NAPSI were comparable to adalimumab (39.9% vs 35.9%, P = 0.618). Overall, the complete clearance response of scalp, and hands and/or feet at week 24 occurred in a greater proportion of patients in the guselkumab group, irrespective of baseline biologic status (treatment-naïve or treatment-experienced). Guselkumab was superior to adalimumab for the treatment of scalp, and hands and/or feet psoriasis, and proportionally higher for fingernail psoriasis. Findings were comparable to the global study population.

A Retrospective Cohort Study of Clinical Features and Treatment Patterns With Ustekinumab in Patients With Crohn Disease Utilizing a Health Care Database in Japan.

BACKGROUND: Biologics are used to treat moderate-to-severe Crohn disease (CD). In Japan, ustekinumab was approved for reimbursement for CD treatment in 2017. However, limited information describes utilization of ustekinumab in real-world settings. OBJECTIVE: To describe treatment patterns and clinical outcomes of patients with CD treated with ustekinumab in Japan. METHODS: A retrospective cohort drug utilization study was conducted using the Japan Medical Data Center employment insurance database. Patients with a diagnosis of CD who initiated treatment with ustekinumab (International Classification of Disease, Tenth Revision [ICD-10] K50.x) from January 1, 2017, to September 30, 2020, were enrolled. Eligible patients were followed up until disenrollment or study end (September 30, 2020). RESULTS: A total of 622 patients with CD initiated ustekinumab during the study period; 45.7% had no prior history of biologic use (bio-naive) and 54.3% had previously received ≥1 biologic (bio-experienced); 82.8% of patients received an induction dose of whom 97.5% received a dose within the recommended range (260-520 mg) and 90.8% of patients received their first maintenance dose within a 42- to 70-day interval. Median treatment duration was 14.8 months and 90.2% remained on ustekinumab at study end. Compared with the 12-month period prior to ustekinumab initiation, surgical procedures decreased by 88.0%, gastrointestinal complications by 64.6%, enteral nutrition requirements by 41.9%, and CD-related hospitalizations by 62.6% within 12 months after commencing ustekinumab. CONCLUSIONS: These first real-world data from Japan, where ustekinumab has been used longest for CD treatment, shows that a majority of patients initiated ustekinumab as per the recommended label. Indirect evidence of clinical impact could be relevant in other settings in Asia.

Persistence and Adherence to Biologics in Patients with Psoriasis in Taiwan: A New Biologics User Cohort Study.

Background: Biologics are used to treat moderate-to-severe psoriasis, and persistence to biologics may reflect clinical effectiveness. Limited information describing how biologics are used in patients with moderate-to-severe psoriasis in Asian countries is available. We conducted a population-based, retrospective, new user cohort study using the National Health Insurance Research Database (NHIRD) in Taiwan to assess treatment persistence and adherence to biologics. Methods: Adults with a diagnosis of psoriasis between 01 January 2015 and 31 December 2017 were identified in the NHIRD (ICD-9-CM 696.1; ICD-10 L40.0). New users were patients who initiated treatment with etanercept, adalimumab, ustekinumab or secukinumab between 01 January 2015 and 31 December 2017. All eligible patients were followed until 31 December 2018, death or disenrollment. Kaplan-Meier analysis was conducted to estimate persistence of treatment for index biologics. A Cox-proportional hazard regression model was used to compare risks of biologic discontinuation between biologic groups. Adjustments for potential confounding factors (age, gender and Charlson comorbidity index score) were made in the Cox model. Results: There were 1,397 new biologic users with psoriasis during the study period. The ratio men:women was approximately 4:1. Mean age of patients ranged from 44.6 to 47.7 years across exposure groups. The 1-year/2-years persistence rates were 94.2%/84.9% for ustekinumab, 96.2%/not calculated (due to too few patients at year 2) for secukinumab, 66.0%/29.9% for etanercept, and 59.8%/40.3% for adalimumab. The risk of discontinuation was significantly lower in patients initiating ustekinumab compared with adalimumab (hazard ratio adjusted for age, sex and co-morbidities 0.289, 95%CI 0.247-0.339, p < 0.0001). Drug survival was significantly higher for ustekinumab compared with adalimumab and etanercept (log-rank test p < 0.0001). The proportions of patients with 1-year/2-years medication possession ratios of ≥80% were 95.3%/92.0% for ustekinumab, 98.1%/not calculated for secukinumab, 89.4%/83.1% for etanercept, and 70.8%/59.4% for adalimumab. Limitations: Clinical improvement and response to treatment data were not available. Conclusion: There was relatively high persistence amongst biologic users with psoriasis in Taiwan. There is a trend towards greater persistence of ustekinumab compared to other biologics, the magnitude of which depends on the treatment gap used for its calculation. This study provides real-world evidence that may facilitate optimal treatment choice.

Early non-response to certolizumab pegol in rheumatoid arthritis predicts treatment failure at one year. Data from a randomised phase III clinical trial.

OBJECTIVES: To compare different early clinical criteria of non-response determined at three months as predictors of clinical failure at one year in patients with rheumatoid arthritis starting therapy with certolizumab pegol. METHODS: Data were derived from a randomised Phase III clinical trial in patients with rheumatoid arthritis who failed to respond to methotrexate monotherapy. Patients included in this post-hoc analysis were treated with certolizumab pegol (400mg qd reduced to 200mg qd after one month) and with methotrexate. The study duration was twelve months. Response at three months was determined with the American College of Rheumatology-50, Disease Assessment Score-28 ESR, Health Assessment Questionnaire and the Clinical Disease Activity Index. The performance of these measures at predicting treatment failure at twelve months defined by the American College of Rheumatology-50 criteria was determined, using the positive predictive values as the principal evaluation criterion. RESULTS: Three hundred and eighty two patients were available for analysis and 225 completed the twelve-month follow-up. At Week 52, 149 (38.1%) patients met the American College of Rheumatology-50 response criterion. Positive predictive values ranged from 81% for a decrease in Health Assessment Questionnaire- Disability index score since baseline >0.22 to 95% for a decrease in Disease Assessment Score-28 score since baseline≥1.2. Sensitivity was≤70% in all cases. Performance of these measures was similar irrespective of the definition of treatment failure at 12months. CONCLUSIONS: Simple clinical measures of disease activity can predict future treatment failure reliably and are appropriate for implementing treat-to-target treatment strategies in everyday practice.

Modeling of the clinical and economic impact of a risk-sharing agreement supporting a treat-to-target strategy in the management of patients with rheumatoid arthritis in France.

OBJECTIVES: To evaluate the cost-effectiveness of a Treat-to-Target strategy with certolizumab pegol in patients with rheumatoid arthritis in the context of a pay-for-performance agreement in which medication costs are refunded in case of discontinuation during the first 3 months of treatment. METHODS: The Treat-to-Target strategy consisted of a systematic switch to second-line tumor necrosis factor (TNF)α inhibitor in case of an unmet ACR50 response at 3 months compared to current routine clinical practice. A reference cohort treated first-line with certolizumab pegol according to current practice without systematic switching was considered as the comparator. A decision-tree model was constructed to estimate clinical outcome (health assessment questionnaire-disability index or HAQ-DI score), time spent in ACR50 response (ACR 50), and direct costs of treatment over a 2-year period. HAQ scores were derived from American College of Rheumatology 50 (ACR50) responses. All TNFα inhibitors were assumed to have equivalent efficacy and tolerability. Costs were estimated at 2013 French retail prices (date of the pay-for-performance agreement). RESULTS: The mean duration of an ACR50 response was 1.23 years in the Treat-to-Target strategy certolizumab pegol cohort vs 0.98 years in the reference cohort, resulting in a mean gain in HAQ at 24 months of 0.117. The Treat-to-Target strategy with a mix of TNFα inhibitors as second-line therapy was more expensive than the reference strategy in absolute terms, but this difference was entirely offset by the pay-for-performance agreement. The Treat-to-Target strategy was, thus, cost-neutral over a 2-year period after the payback of CZP cost for patients not achieving the target at 3 months. CONCLUSIONS: In the context of a pay-for-performance agreement, the management of patients with rheumatoid arthritis using a Treat-to-Target strategy with certolizumab pegol in first line is dominant compared to standard use of this drug in the French setting in 2013.