Secukinumab effects on disease burden, patient needs and benefits, and treatment satisfaction in patients with plaque psoriasis across European regions: patient perspective data from the PROSE study.

BACKGROUND: Cross-cultural differences in healthcare policies and patient-physician communication may influence the quality of care and patients' perceived benefits and satisfaction with psoriasis treatment. OBJECTIVES: To compare the disease burden and patient needs at baseline, and patient benefits and satisfaction with secukinumab treatment across Europe. METHODS: PROSE was an open-label, prospective, non-randomized, stratified multicentre study of 52 weeks of secukinumab treatment, in 16 European countries. Secondary analysis of the PROSE study data by European regions was performed to identify cross-cultural differences in disease burden and patient needs at baseline, and in clinical improvement, patient-reported treatment benefits and satisfaction at 52 weeks post-treatment. RESULTS: At baseline, Dermatology Life Quality Index impairment was reported to be greater in patients from Eastern Europe (EE: 15.4 ± 7.1) vs. Northern Europe (NE: 13.3 ± 6.7) and Western Europe (WE: 13.6 ± 6.9), but while differences were statistically significant (F-test = 5.5, P < 0.001), their clinical significance is uncertain. There were no significant differences between regions in Psoriasis Area and Severity Index at baseline (F-test = 1.6). There were considerable differences in patients' needs (Patient Need Questionnaire) between geographical regions, with WE focused more on reducing physical impairment [vs. Southern Europe (SE)/EE], EE on reducing social impairment (vs. NE/WE) and SE on reducing impairment due to therapy (vs. NE/WE). At Week 52, patients from EE reported more benefits (Patient Benefit Index) with secukinumab treatment (vs. WE/SE), while patients from NE reported higher global treatment satisfaction (vs. SE). CONCLUSIONS: Differences in patients' needs and treatment satisfaction across Europe are likely a result of diverse medical systems, socio-economic status and infrastructural access. A patient-centred approach to treating psoriasis may fulfil patient needs and maximize treatment satisfaction. (NCT02752776).

Long-acting pasireotide improves clinical signs and quality of life in Cushing's disease: results from a phase III study.

PURPOSE: Cushing's disease (CD) is associated with significant clinical burden, increased mortality risk, and impaired health-related quality of life (HRQoL). This analysis explored the effect of long-acting pasireotide on clinical signs of hypercortisolism and HRQoL in a large subset of patients with CD. METHODS: In this phase III study (clinicaltrials.gov: NCT01374906), 150 adults with CD and a mean urinary free cortisol (mUFC) level between 1.5 and 5.0 times the upper limit of normal (ULN) started long-acting pasireotide 10 or 30 mg every 28 days with dose increases/decreases permitted based on mUFC levels/tolerability (minimum/maximum dose: 5/40 mg). Changes in clinical signs of hypercortisolism and HRQoL were assessed over 12 months of treatment and were stratified by degree of mUFC control for each patient. RESULTS: Patients with controlled mUFC at month 12 (n = 45) had the greatest improvements from baseline in mean systolic (- 8.4 mmHg [95% CI - 13.9, - 2.9]) and diastolic blood pressure (- 6.0 mmHg [- 10.0, - 2.0]). Mean BMI, weight, and waist circumference improved irrespective of mUFC control. Significant improvements in CushingQoL total score of 5.9-8.3 points were found at month 12 compared with baseline, irrespective of mUFC control; changes were driven by improvements in physical problem score, with smaller improvements in psychosocial score. CONCLUSIONS: Long-acting pasireotide provided significant improvements in clinical signs and HRQoL over 12 months of treatment, which, in some cases, occurred regardless of mUFC control. Long-acting pasireotide represents an effective treatment option and provides clinical benefit in patients with CD. CLINICAL TRIAL REGISTRATION NUMBER: NCT01374906.

Rates of peripheral arterial occlusive disease in patients with chronic myeloid leukemia in the chronic phase treated with imatinib, nilotinib, or non-tyrosine kinase therapy: a retrospective cohort analysis.

Peripheral arterial occlusive disease (PAOD) occurs in patients with chronic phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs). The risk of developing PAOD on TKI therapy is unknown and causality has not been established. Patients with CML-CP from three randomized phase III studies (IRIS, TOPS and ENESTnd) were divided into three cohorts: no TKI (cohort 1; n=533), nilotinib (cohort 2; n=556) and imatinib (cohort 3; n=1301). Patients with atherosclerotic risk factors were not excluded. Data were queried for terms indicative of PAOD. Overall, 3, 7 and 2 patients in cohorts 1, 2 and 3, respectively, had PAOD; 11/12 patients had baseline PAOD risk factors. Compared with that of cohort 1, exposure-adjusted risks of PAOD for cohorts 2 and 3 were 0.9 (95% CI, 0.2-3.3) and 0.1 (95% CI, 0.0-0.5), respectively. Multivariate logistic regression revealed that nilotinib had no impact on PAOD rates compared with no TKI, whereas imatinib had decreased rates of PAOD compared with no TKI. Nilotinib was associated with higher rates of PAOD versus imatinib. Baseline assessments, preferably within clinical studies, of PAOD and associated risk factors should occur when initiating TKI therapy in CML; patients should receive monitoring and treatment according to the standard of care for these comorbidities.

Zoledronic acid efficacy and safety over five years in postmenopausal osteoporosis.

UNLABELLED: In a 5-year study involving 119 postmenopausal women, zoledronic acid 4 mg given once-yearly for 2, 3 or 5 years was well tolerated with no evidence of excessive bone turnover reduction or any safety signals. BMD increased significantly. Bone turnover markers decreased from baseline and were maintained within premenopausal reference ranges. INTRODUCTION: After completion of the core study, two consecutive, 2-year, open-label extensions investigated the efficacy and safety of zoledronic acid 4 mg over 5 years in postmenopausal osteoporosis. METHODS: In the core study, patients received 1 to 4 mg zoledronic acid or placebo. In the first extension, most patients received 4 mg per year and then patients entered the second extension and received 4 mg per year or calcium only. Patients were divided into three subgroups according to years of active treatment received (2, 3 or 5 years). Changes in BMD and bone turnover markers (bone ALP and CTX-I) were assessed. RESULTS: All subgroups showed substantial increases in BMD and decreases in bone markers. By the end of the core study, 37.5% of patients revealed a suboptimal reduction (< 30%) of bone ALP levels. After subsequent study drug administration during the extensions, there was no evidence of progressive reduction of bone turnover markers. Furthermore, increased marker levels after treatment discontinuation demonstrates preservation of bone remodelling capacity. CONCLUSIONS: This study showed that zoledronic acid 4 mg once-yearly was well tolerated and effective in reducing biomarkers over 5 years. Detailed analysis of bone marker changes, however, suggests that this drug regimen causes insufficient reduction of remodelling activity in one third of patients.