Comparative adherence of macitentan versus ambrisentan and bosentan in Australian patients with pulmonary arterial hypertension: a retrospective real-world database study.

AIM: Bosentan, ambrisentan, and macitentan are endothelin receptor antagonists (ERAs), currently available in Australia for treatment of pulmonary arterial hypertension (PAH). This study assessed the comparative adherence of these ERAs for PAH in Australian patients. METHODS: This retrospective, observational study used data for adults with PAH from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset (01/2006-10/2020). The primary outcome was treatment adherence (i.e. receiving ≥80% of ERA doses over 12 months). Secondary outcomes were time to treatment change (add-on or switch) and overall survival. RESULTS: The study included 436 patients who took bosentan (n = 200), ambrisentan (n = 69), or macitentan (n = 167). Treatment adherence was significantly greater in patients who received macitentan (65.3%) versus ambrisentan (56.5%) and bosentan (58.0%), with odds ratios (ORs; 95% CI) of 0.51 (0.30-0.88; p = 0.016) for bosentan versus macitentan and 0.48 (0.24-0.96; p = 0.037) for ambrisentan versus macitentan. The median time to treatment change was 47.2 and 43.4 months for bosentan and ambrisentan, respectively (not calculated for macitentan because of insufficient duration of data). LIMITATIONS AND CONCLUSIONS: Real-world data for Australian patients with PAH showed that treatment adherence for ERAs was suboptimal. Adherence was higher for macitentan compared with ambrisentan and bosentan.

Comparative Treatment Persistence and Adherence to Endothelin Receptor Antagonists Among Patients with Pulmonary Arterial Hypertension in Japan: A Real-World Administrative Claims Database Study.

INTRODUCTION: Real-world data on the comparative effectiveness of endothelin receptor antagonists (ERAs; macitentan, bosentan, ambrisentan) for pulmonary arterial hypertension (PAH), particularly in Asian countries, are scarce. We evaluated the persistence of these ERAs before and after macitentan approval in Japan (2015). METHODS: We used real-world data from the Japanese Medical Data Vision administrative claims database between April 2008 and November 2020. Patients with PAH were identified from the dataset. Persistence to ERA treatment before and after approval of macitentan in Japan was defined as the time between start of the index ERA and treatment discontinuation or death. Propensity score adjustment was applied to minimize confounding effects among treatment groups. RESULTS: In the pre-macitentan approval cohort, 153 and 51 patients received bosentan and ambrisentan, respectively. In the post-macitentan approval cohort, 331, 284, and 91 patients received macitentan, bosentan, and ambrisentan, respectively. Unadjusted median persistence for ambrisentan- and bosentan-treated patients was 19 and 10 months, respectively (adjusted HR 0.87 [95% CI 0.61-1.24]; P = 0.434 [bosentan as reference]). In the post-macitentan approval cohort, unadjusted median persistence was 18 months for macitentan-treated patients versus 6 and 8 months for ambrisentan- and bosentan-treated patients, respectively. Adjusted HRs for ambrisentan and bosentan were 1.48 (95% CI 1.12-1.95; P = 0.006) and 1.63 (95% CI 1.30-2.04; P < 0.001 [macitentan as reference]), respectively. CONCLUSIONS: Real-world data for Japanese patients with PAH showed that persistence was significantly higher for macitentan, versus ambrisentan and bosentan, since its approval.

Amivantamab compared with real-world therapies in patients with advanced non-small cell lung cancer EGFR Exon 20 insertion mutations after platinum-based chemotherapy.

BACKGROUND: In the single-arm CHRYSALIS trial, advanced non-small cell lung cancer patients harboring epidermal growth factor receptor (EGFR) exon 20 insertion (Exon 20ins) showed durable responses to amivantamab, an EGFR-MET bispecific antibody targeting tumors with EGFR Exon 20ins. This study compared the effectiveness of amivantamab to real-world systemic anti-cancer therapies in Japan. PATIENTS AND METHODS: External control patients were selected by applying CHRYSALIS eligibility to Japanese patients from LC-SCRUM-Asia. External control patients were included for every qualifying line of therapy after platinum-based chemotherapy. Propensity score weighting was applied to external control patients to adjust for differences in baseline characteristics. Outcomes were compared between external control patients, and all and Asian-only CHRYSALIS patients using weighted Cox proportional hazards regression models for progression-free survival (PFS), time to next therapy (TTNT), and overall survival (OS), and generalized estimating equations with repeated measurements for overall response rate (ORR). RESULTS: One hundred fifteen CHRYSALIS and 94 external control patients were identified. Compared to external control patients, amivantamab-treated patients had significantly longer OS (median OS 19.88 vs 14.09 months, HR [95% CI] 0.59 [0.40-0.88]), PFS (median PFS 6.74 vs 4.73 months, HR 0.59 [0.45-0.78]), TTNT (median TTNT 12.16 vs 5.09 months, HR 0.39 [0.29-0.53]), and significantly higher ORR (41.7% vs 14.1%). Analyses of amivantamab-treated Asian patients (n = 61) showed similar clinical benefits. CONCLUSION: In the absence of clinical evidence from randomized clinical trials, this study reflects the benefit of amivantamab after platinum-based chemotherapy for advanced non-small cell lung cancer patients harboring EGFR Exon 20ins, compared to current real-world therapies.

Prevalence, patient characteristics and treatment patterns among SLE-PAH patients in real-world clinical practice: A retrospective analysis of Medical Data Vision Database in Japan.

OBJECTIVE: Real-world evidence regarding prevalence, patient characteristics and treatment patterns for pulmonary arterial hypertension (PAH) related to systemic lupus erythematosus (SLE) in Japan is limited. METHODS: We conducted a retrospective study analysing Japan's Medical Data Vision (MDV) database from April-2008 to September-2020. Prevalence, incidence, patient characteristics, treatment patterns and use of vasodilators by treatment line were evaluated. RESULTS: Prevalence of PAH was 0.392% in SLE patients (n=114/29,077). Cumulative incidence was 0.53% (3-years (y)) and 0.77% (5y). Of 114 SLE-PAH patients, 49% developed PAH <1 year from SLE diagnosis. SLE-PAH patients were more female (88% vs. 72%), had lower mean age at SLE diagnosis (53y vs. 56y) and more severe SLE (61% vs 25%), versus non-PAH SLE patients. Glucocorticoids (58%) and vasodilators (27%) were preferred first-line monotherapy for SLE-PAH. Glucocorticoids+immunosuppressants (19%) was predominant first-line combination therapy. Endothelin receptor antagonists (40% and 44%) and nitric oxide analogues (31% and 40%) were dominant first- and second-line vasodilators. CONCLUSION: SLE-PAH patients were more females, younger at diagnosis, had more severe SLE than non-PAH SLE patients. Most were diagnosed <1 year of SLE diagnosis. In Japan's real-world practice, initial treatment goal is SLE management, while vasodilators are preferred in advanced disease, as per MDV database.

A retrospective study on the incidence, management and risk factors of skin rash in patients with advanced prostate cancer in Japan.

BACKGROUND: Worldwide, prostate cancer (PC) is the second most diagnosed cancer and the fifth leading cause of cancer death in men. Hormonal therapies, commonly used for PC, are associated with a range of treatment-emergent adverse events (TEAEs). The population from Japan seems to be at higher risk of developing TEAEs of skin rash compared to the overall global population. This study was conducted to get a better insight into the incidence, management, and risk factors for skin rash during active treatment for advanced PC in Japan. METHODS: A retrospective cohort of PC patients was identified and subsequently categorized, into non-metastatic and metastatic castration-resistant prostate cancer patients (nmCRPC and mCRPC), and metastatic castration-naïve prostate cancer patients (mCNPC). The analysis was based on a dataset from the Medical Data Vision (MDV) database. Descriptive statistics were determined, and a multivariate Cox proportional hazards model was used to the associated risk factors for the onset of rash. RESULTS: Overall, 1,738 nmCRPC patients, 630 mCRPC patients, and 454 mCNPC patients were included in this analysis. The median age was 78 years old and similar across the three cohorts. The skin rash incidence was 19.97% for nmCRPC cohort, 28.89% for mCRPC cohort, and 28.85% for mCNPC cohort. The median duration of skin rash ranged from 29 to 42 days. Statistically significant risk factors for developing skin rash included a history of allergy or hypersensitivity (all cohorts), increased age (nmCRPC and mCRPC), a body mass index (BMI) of < 18.5 (nmCRPC and mCRPC), and a PSA level higher than the median (nmCRPC). Skin rash was commonly managed with systemic and topical corticosteroids which ranged from 41.76% to 67.03% for all cohorts. Antihistamines were infrequently used. CONCLUSION: This study provides a better understanding of the real-world incidence, onset, duration, management and risk factors of skin rash in patients on active PC treatment in Japan. It was observed that approximately 20-30% of PC patients experience skin rash. Development of skin rash was associated with previous allergy or hypersensitivity, BMI of < 18.5, increased age and higher PSA levels, and was usually treated with corticosteroids.

Assessing the correlation between second progression-free survival (PFS2) and overall survival (OS) in advanced prostate cancer patients using medical data vision (MDV) claims database in Japan.

OBJECTIVE: To assess the correlation between PFS2 and OS among patients with advanced prostate cancer (PC) in a real-world setting for Japan. METHODS: This was a retrospective analysis using the Japanese MDV database. Patients with nmCRPC (non-metastatic Castration-Resistant PC), mCRPC (metastatic Castration-Resistant PC), and mCNPC (metastatic Castration-Naïve PC) were identified and their medical records were investigated for PFS2 and death. Association between PFS2 and OS was determined using the Pearson's, Spearman's, Kendall's Tau, and Fleischers' correlation coefficients. RESULTS: A total of 386,484 patients with PC were identified from the database, of which, 1,783 patients with nmCRPC, 630 with mCRPC, and 454 with mCNPC met the predefined eligibility criteria. Significant correlation between PFS2 and OS was observed in patients with nmCRPC (Pearson's r = 0.873; 95% CI: 0.849-0.897, Spearman's r = 0.909; 95% CI: 0.893-0.925; Kendall's Tau r = 0.831; 95% CI: 0.812-0.850, Fleischers' r = 0.682; 95% CI: 0.601-0.764), mCRPC (Pearson's r = 0.812; 95% CI: 0.758-0.865, Spearman's r = 0.895; 95% CI: 0.868-0.923, Kendall's Tau r = 0.789; 95% CI: 0.755-0.823, Fleischers' r= 0.439; 95% CI: 0.334-0.544), and mCNPC (Pearson's r = 0.931; 95% CI: 0.899-0.964, Spearman's r = 0.943; 95% CI: 0.922-0.964, Kendall's Tau r = 0.866; 95% CI: 0.836-0.896, Fleischers' r = 0.756; 95% CI: 0.624-0.888). CONCLUSIONS: The results of this study indicate a significant correlation between PFS2 and OS, which adds additional evidence to the existing literature of using PFS2 as a surrogate endpoint for OS in patients with PC.

Differences in Clinical Responses to Ustekinumab Treatment among Body Regions: Results from a Real-World Prospective, Observational, and Multi-Center Study in Korea.

BACKGROUND: In psoriasis treatment, not all body regions improve simultaneously after clinical interventions. OBJECTIVE: This study was aimed at evaluating clinical responses across body regions, which may differentially influence patient treatment plans. METHODS: This prospective, observational, and multi-center study was conducted in Koreans who adhered to ustekinumab treatment based on criteria per local label and reimbursement guidelines. A total of 581 were included in this analysis. RESULTS: The mean (±standard deviation) psoriasis area severity index (PASI) score at baseline, age, disease duration, and body surface area (%) were 18.9±9.69, 44.2±13.29 years, 11.3±9.65 years, and 27.8±17.83, respectively. Across the head and neck, upper extremities, trunk, and lower extremities, the correlation between the PASI sub-scores for the upper and lower extremities was the highest (r=0.680). The mean PASI sub-score for the lower extremities was the highest at baseline. PASI90 and PASI100 scores were the highest for the head and neck region, indicating the highest response rates, while those for the lower extremities were consistently low at all visits. CONCLUSION: We found differences in regional ustekinumab responses, with the lower extremities being the most difficult to treat. These findings should be considered in psoriasis treatment.

Efficacy and safety of guselkumab compared with placebo and adalimumab in Korean patients with moderate-to-severe psoriasis: post-hoc analysis from the phase III, double-blind, placebo- and active-comparator-controlled VOYAGE 1/2 trials.

BACKGROUND: The phase 3 studies, VOYAGE 1 and 2, were conducted to assess guselkumab in the treatment of patients with moderate-to-severe psoriasis. OBJECTIVES: To investigate the efficacy and safety of guselkumab in Korean patients. METHODS: The Korean sub-population of VOYAGE 1 and 2 study patients were included in this analysis. Efficacy and safety were evaluated through Weeks 24 and 28, respectively. RESULTS: Of 126 randomized Korean patients, 30, 63, and 33 received placebo, guselkumab, and adalimumab, respectively. At Week 16, guselkumab was superior to placebo in achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (cleared or minimal; 90.5 vs. 20.0%, p<.001) and a Psoriasis Area and Severity Index (PASI) 90 response (71.4 vs. 3.3%, p<.001). At week 24, a significantly higher proportion of guselkumab-treated patients achieved PASI 75 and IGA 0 (clear skin) responses compared to adalimumab-treated patients (PASI 75: 93.7 vs. 66.7%, p<.001; IGA 0: 52.4 vs. 21.2%, p=.004). Through Week 28, guselkumab and adalimumab showed comparable safety profiles. CONCLUSION: The efficacy and safety of guselkumab in Korean psoriasis patients through 28 weeks were consistent with findings for the overall VOYAGE 1 and 2 study population.

Clinical outcomes in adult patients with plaque psoriasis treated with ustekinumab under real-world practice in Korea: A prospective, observational, multi-center, postmarketing surveillance study.

Postmarketing surveillance is conducted to establish drug safety and effectiveness under real-world practice. We aimed to validate the effectiveness and safety of ustekinumab in the treatment of adult Korean patients with plaque psoriasis under real-world practice. This was a prospective, observational, and multi-center study. Subjects aged 18 years or older who were treated with ustekinumab for plaque psoriasis were enrolled. We enrolled 977 patients; 654 (66.9%) were men, with mean body surface area (BSA, ± standard deviation) of 27.0 ± 18.3% and mean psoriasis area severity index (PASI) score of 18.1 ± 9.7. The effectiveness analysis was performed in 581 patients who had at least one follow-up assessment and met treatment criteria per local label and reimbursement guidelines. Of these patients, 287 had effectiveness data for visit 6 at 53.7 ± 2.1 weeks. At visit 6, 91.6% (263/287), 51.2% (147/287), and 9.4% (27/287) patients achieved PASI 75, 90, and 100 responses, respectively. Adverse events (AEs) occurred in 112 of the 977 (11.5%) patients with an incidence rate of 21.5 per 100 patient-years (PYs). Serious AEs occurred in eight (0.8%) patients with an incidence rate of 1.2 per 100 PYs. The estimated 1-year drug survival rate was 87.7%. The multiple logistic regression analysis showed that higher baseline PASI score and no prior biologic exposure were significant predictors for PASI 90 response at visit 6. Ustekinumab was effective and safe, and displayed a high survival rate in the treatment of adult Korean patients with plaque psoriasis in real-world practice.

Usefulness of the Psoriatic Arthritis Screening and Evaluation Questionnaire to Monitor Disease Activity in Management of Patients with Psoriasis: Findings from the EPI-PSODE Study.

BACKGROUND: Psoriasis and psoriatic arthritis (PsA) are included in the group of immune-mediated inflammatory diseases (IMIDs) caused by systemic inflammation; however, indicators for monitoring inflammatory activity in patients with psoriasis, such as the Psoriasis Area and Severity Index (PASI), are limited. OBJECTIVE: To determine whether the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire can be used to monitor disease activity in patients with psoriasis. METHODS: This was a multicenter, noninterventional, cross-sectional study. Demographic factors and PASI and PASE scores were collected to investigate associations between each. RESULTS: PASE data were available for 1,255 patients, of whom 498 (39.7%) had a score of ≥37. Compared with the group with PASE score <37, the group with score ≥37 had a higher proportion of women (34.9% vs. 48.8%, p<0.0001), older mean age at diagnosis (36.4 vs. 41.7 years, p<0.0001), more severe disease activity using PASI and body surface area measures (p=0.0021 and p=0.0008, respectively), and higher mean body mass index (23.7 vs. 24.1, p=0.0411). In a multiple linear regression model, PASE score was positively associated with cutaneous disease activity (p<0.0001). CONCLUSION: After risk-adjustment, PASE was positively associated with PASI, which suggests that PASE can be sensitive to disease activity. Since psoriasis is regarded as one of the IMIDs, PASE may be utilized as a tool not only to screen PsA but also to monitor disease activity.

Baseline extent of damage predicts spinal radiographic progression in Korean patients with ankylosing spondylitis treated with golimumab.

BACKGROUND/AIMS: For patients with ankylosing spondylitis (AS), golimumab has consistent efficacy in controlling disease activity over 5 years but its benefit in preventing radiographic progression was less clear at 4 years. To predict radiographic progression, we analyzed the baseline characteristics of AS patients in a Korean population. METHODS: Sixty-eight Korean patients with AS participated in the phase 3, multicenter, randomized, placebo-controlled, double-blind trial (GO-RAISE) which has previously been described. Baseline modified stoke AS spine score (mSASSS) and change in mSASSS from baseline (ΔmSASSS) until week 208 were analyzed in the Korean patients enrolled in the GO-RAISE study. RESULTS: Although Korean patients had lower baseline mSASSS compared to non-Korean patients and received active management, radiographic progression was not prevented. Korean patients who did not undergo radiographic progression of spinal lesions of AS were younger and had shorter symptomatic duration, lower Bath AS functional and metrology indices, better chest expansion, and lower baseline mSASSS. The baseline mSASSS and ΔmSASSS were positively correlated in Korean AS patients (p < 0.001). Radiographic progression was more prevalent (80.0%) when baseline mSASSS > 10 and less common (13.0%) with baseline mSASSS = 0. CONCLUSIONS: In Korean AS patients, radiographic progression of the spine after 4 years was predicted effectively by the initial severity of the spinal lesion(s) in patients treated with golimumab.

The Clinical Profile of Patients with Psoriasis in Korea: A Nationwide Cross-Sectional Study (EPI-PSODE).

BACKGROUND: Psoriasis is an immune-mediated, chronic inflammatory disease affecting multiple aspects of patients' lives. Its epidemiology varies regionally; however, nationwide epidemiologic data on psoriasis depicting profile of Korean patients has not been available to date. OBJECTIVE: To understand nationwide epidemiologic characteristics and clinical features of adult patients with psoriasis visited university hospitals in Korea. METHODS: This multicenter, non-interventional, cross-sectional study recruited 1,278 adult patients with psoriasis across 25 centers in Korea in 2013. Various clinical data including PASI, BSA, DLQI, SF-36 and PASE were collected. RESULTS: A total of 1,260 patients completed the study (male:female=1.47:1). The mean age was 47.0 years with a distribution mostly in the 50s (24.9%). Early onset (<40 years) of psoriasis accounted for 53.9% of patients. The mean disease duration was 109.2 months; mean body mass index was 23.9 kg/m2; and 12.7% of patients had a family history of psoriasis. Plaque and guttate types of psoriasis accounted for 85.8% and 8.4%, respectively. Patients with PASI ≥10 accounted for 24.9%; patients with body surface area ≥10 were 45.9%. Patients with DLQI ≥6 accounted for 78.8%. Between PASI <10 and PASI ≥10 groups, significant difference was noted in age at diagnosis, disease duration, blood pressure, waist circumference of female, and treatment experiences with phototherapy, systemic agents, and biologics. CONCLUSION: This was the first nationwide epidemiologic study of patients with psoriasis in Korea and provides an overview of the epidemiologic characteristics and clinical profiles of this patient population.

Clinical factors predicting the therapeutic response to ustekinumab in patients with moderate to severe chronic plaque psoriasis.

While ustekinumab has been widely used as an effective biologic for the treatment of chronic plaque psoriasis, no prospective studies have specifically investigated the clinical factors that may influence treatment outcomes with ustekinumab. This post-hoc analysis aimed to identify specific clinical factors that may influence treatment outcomes with ustekinumab in psoriasis patients. In the MARCOPOLO study, 102 Korean patients with moderate to severe psoriasis were analyzed to assess the influence of baseline characteristics as clinical factors on clinical response (improvement in Psoriasis Area and Severity Index by ≥75%/90% [PASI75/PASI90]) to ustekinumab. In addition, differences in PASI75 and PASI90 responses between the responder group and non-responders were evaluated at weeks 28 and 52. Multiple logistic regression analysis was used to determine adjusted clinical factors predicting treatment outcomes among patient characteristics. At week 28, there was a significant difference in PASI75/PASI90 response based on prior biologic experience, although the difference did not persist at week 52. In addition, after adjusting for the effects of relevant clinical factors, biologic experience was significantly associated with less PASI75 (odds ratio [OR] = 0.14, P = 0.001) and PASI90 (OR = 0.22, P = 0.036) responses at week 28. The presence of comorbidities was higher among non-responders than among PASI75/PASI90 responders at both weeks 28 and 52, but was not statistically significant. Previous biologic use was the only clinical factor predicting less response at week 28, although it did not influence the clinical response after week 52. Further studies are warranted to investigate the association between presence of comorbidities and clinical response.

Rheumatoid arthritis patients fulfilling Korean National Health Insurance reimbursement guidelines for anti-tumor necrosis factor-α treatment and comparison to other guidelines.

The aim of this study was to compare anti-tumor necrosis factor-α (TNFα) treatment status in rheumatoid arthritis (RA) patients with the Korean National Health Insurance (KNHI) reimbursement eligibility criteria and with American College of Rheumatology (ACR) recommendations, Japan College of Rheumatology (JCR) guidelines and British Society for Rheumatology (BSR) guidelines. Between December 2011 and August 2012, outpatients from 17 South Korean general hospitals diagnosed with RA according to the 1987 ACR criteria were enrolled into a noninterventional, cross-sectional, observational study. Of 1700 patients (1414 female (83.2 %), mean age of 56.6 ± 12.0, mean disease duration 97.9 ± 91.8 months), 306 (18.0 %) had used anti-TNFα agents, and 224 (13.2 %) were currently using an anti-TNFα agent. Of 1394 anti-TNFα-naive patients, 32 (2.3 %) met KNHI reimbursement guidelines, 148 (10.6 %) met ACR recommendations, and 127 (9.1 %) and 126 (9.0 %) were considered eligible for anti-TNFα agents according to JCR and BSR guidelines, respectively. The main discrepancy was the higher active joint count required by the KNHI eligibility criteria. In the opinion of treating rheumatologists, the KNHI reimbursement criteria ineligibility accounted for 15.3 % (n = 213) of the reasons for not initiating anti-TNFα agents in anti-TNFα-naive group. The anti-TNFα user group showed significantly higher disease activity than the anti-TNFα-naive group based on DAS28 score. In comparison with the ACR recommendations and JCR and BSR guidelines, fewer patients met KNHI reimbursement eligibility criteria for anti-TNFα agents. The current amendment of the KNHI criteria based on DAS28 score will improve an access to biologic agents including anti-TNFα treatment for South Korean patients with active RA.