Guselkumab-Treated Patients with Plaque Psoriasis Who Achieved Complete Skin Clearance for ≥ 156 Consecutive Weeks: A Post-Hoc Analysis From the VOYAGE 1 Clinical Trial.

BACKGROUND: Treatment of moderate-to-severe plaque psoriasis with biologics, such as guselkumab, has demonstrated greater efficacy over traditional non-biologic treatments. However, given patient diversity, greater understanding of the relationship between patient characteristics, positive clinical outcomes, and long-term response to biologics is crucial for optimizing treatment choices. MATERIALS AND METHODS: This post-hoc analysis of the 5-year VOYAGE 1 clinical trial compares baseline characteristics of patients maintaining a Psoriasis Area and Severity Index (PASI) score of 0 at all visits for ≥ 156 consecutive weeks (PASI = 0 group) with those that never achieve PASI = 0 (comparator group), using descriptive statistics and a multiple logistic regression model. Guselkumab plasma trough concentrations in both response groups were assessed from Weeks 4-156. RESULTS: Of patients who started guselkumab treatment at Week 0 or at Week 16 after switching from placebo, 22.7% (112/494) maintained PASI = 0 for ≥ 156 consecutive weeks. Numerical differences in baseline characteristics, including age, obesity, diabetes, PASI score, disease duration, smoking status, and psoriatic arthritis comorbidity, were identified between the PASI = 0 group and comparator group. Plasma guselkumab levels were consistently higher in the PASI = 0 group. Multiple logistic regression analysis revealed absence of diabetes, lower Dermatology Life Quality Index score at baseline, and higher Week 4 guselkumab plasma concentration as significantly (p < 0.05) associated with the PASI = 0 group. CONCLUSION: A substantial (22.7%) number of guselkumab-treated patients in the VOYAGE 1 clinical trial maintained complete skin clearance for a consecutive period of ≥ 156 weeks. Factors associated with this outcome may suggest clinical benefits of holistic treatment approaches. TRIAL REGISTRATION: NCT02207231.

FIRE Study: Real-World Effectiveness and Safety of Ibrutinib in Clinical Practice in Patients with CLL and MCL.

The FIRE study investigated the real-world effectiveness and safety of ibrutinib in prospectively observed patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL) in France. Patients were mostly relapsed/refractory with high-risk features. First-line CLL/SLL patients had del17p and/or TP53 mutations. In this interim analysis, the median follow-up time for patients with CLL/SLL and MCL was 17.7 and 15.1 months, respectively. In the effectiveness populations for CLL/SLL (n = 200) and MCL (n = 59), the median progression-free survival was not estimable and 12.4 months, respectively; the 12-month overall survival rates were 88.5% and 65.8%, respectively. Treatment-emergent adverse events of interest for patients with CLL/SLL (n = 202) and MCL (n = 59) included: infections and infestations (53.5% and 32.2%), major bleeding (5.0% and 5.1%), and atrial fibrillation (5.9% and 8.5%); 135 (66.8%) and 20 (33.9%) patients were continuing treatment at the time of data cutoff. Future analyses will report on longer-term follow-up (Trial registration: ClinicalTrials.gov, NCT03425591. Registered 1 February 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03425591 ).

Effectiveness and Safety of Ibrutinib for Chronic Lymphocytic Leukemia in Routine Clinical Practice: 3-Year Follow-up of the Belgian Ibrutinib Real-World Data (BiRD) Study.

The multicenter observational BiRD study investigated the real-world effectiveness and safety of ibrutinib in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia (WM) in Belgium. This interim analysis reports results for patients with CLL, with a median follow-up of 34 months. Overall, patients had predominantly relapsed/refractory disease (73%) and were elderly (median age 72 years) with high-risk features such as del17p and/or TP53 mutations (59%). Patients were included either prospectively or retrospectively, and the total patient population effectiveness results were adjusted with left truncation. In the effectiveness population (N = 221: prospective, n = 71; retrospective, n = 150), the overall response rate was 90.0%. Median progression-free survival was 38.3 months (prospective, not estimable; retrospective, 51.5 months) and median overall survival was not yet estimable in the total, prospective and retrospective groups. Treatment-emergent adverse events (TEAEs) for the prospective and retrospective groups are reported separately. Any-grade TEAEs of interest in the prospective/retrospective groups included infections (67.1%/60.1%), diarrhea (20.5%/10.5%), hypertension (16.4%/9.8%) and atrial fibrillation (12.3%/7.2%). Major bleeding was reported in 5.5%/3.3% of prospective/retrospective patients, with little difference observed between those receiving versus not receiving antithrombotic treatment. Discontinuations due to toxicity were reported in 10.5% of patients. Results from this interim analysis show treatment with ibrutinib to be effective and tolerable, with no new safety signals observed. Future analyses will report on longer-term follow-up.

Real-world Treatment Sequencing in Patients with Metastatic Castration-resistant Prostate Cancer: Results from the Prospective, International, Observational Prostate Cancer Registry.

Background: Prostate cancer has a multifaceted treatment pattern. Evidence is lacking for optimal treatment sequences for metastatic castration-resistant prostate cancer (mCRPC). Objective: To increase the understanding of real-world treatment pathways and outcomes in patients with mCRPC. Design setting and participants: A prospective, noninterventional, real-world analysis of 3003 patients with mCRPC in the Prostate Cancer Registry (PCR; NCT02236637) from June 14, 2013 to July 9, 2018 was conducted. Intervention: Patients received first- and second-line hormonal treatment and chemotherapy as follows: abiraterone acetate plus prednisone (abiraterone)-docetaxel (ABI-DOCE), abiraterone-enzalutamide (ABI-ENZA), abiraterone-radium-223 (ABI-RAD), docetaxel-abiraterone (DOCE-ABI), docetaxel-cabazitaxel (DOCE-CABA), docetaxel-enzalutamide (DOCE-ENZA), and enzalutamide-docetaxel (ENZA-DOCE). Outcome measurements and statistical analysis: Baseline patient characteristics, quality of life, mCRPC treatments, and efficacy outcomes (progression and survival) were presented descriptively. Results and limitations: Data from 727 patients were eligible for the analysis (ABI-DOCE n = 178, ABI-ENZA n = 99, ABI-RAD n = 27, DOCE-ABI n = 191, DOCE-CABA n = 74, DOCE-ENZA n = 116, and ENZA-DOCE n = 42). Demographics and disease characteristics among patients between different sequences varied greatly. Most patients who started on abiraterone or enzalutamide stopped therapy because of disease progression. No randomisation to allow treatment/sequence comparisons limited this observational study. Conclusions: The real-world PCR data complement clinical trial data, reflecting more highly selected patient populations than seen in routine clinical practice. Baseline characteristics play a role in mCRPC first-line treatment selection, but other factors, such as treatment availability, have an impact. Efficacy observations are limited and should be interpreted with caution. Patient summary: Baseline characteristics appear to have a role in the first-line treatment selection of metastatic castration-resistant prostate cancer in the real-world setting. First-line abiraterone acetate plus prednisone seems to be the preferred treatment option for older patients and those with lower Gleason scores, first-line docetaxel for younger patients and those with more advanced disease, and first-line enzalutamide for patients with fewer metastases and more favourable performance status. The benefit to patients from these observations remains unknown.

LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma.

Despite treatment advances, patients with multiple myeloma (MM) often progress through standard drug classes including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs). LocoMMotion (ClinicalTrials.gov identifier: NCT04035226) is the first prospective study of real-life standard of care (SOC) in triple-class exposed (received at least a PI, IMiD, and anti-CD38 mAb) patients with relapsed/refractory MM (RRMM). Patients (N = 248; ECOG performance status of 0-1, ≥3 prior lines of therapy or double refractory to a PI and IMiD) were treated with median 4.0 (range, 1-20) cycles of SOC therapy. Overall response rate was 29.8% (95% CI: 24.2-36.0). Median progression-free survival (PFS) and median overall survival (OS) were 4.6 (95% CI: 3.9-5.6) and 12.4 months (95% CI: 10.3-NE). Treatment-emergent adverse events (TEAEs) were reported in 83.5% of patients (52.8% grade 3/4). Altogether, 107 deaths occurred, due to progressive disease (n = 74), TEAEs (n = 19), and other reasons (n = 14). The 92 varied regimens utilized demonstrate a lack of clear SOC for heavily pretreated, triple-class exposed patients with RRMM in real-world practice and result in poor outcomes. This supports a need for new treatments with novel mechanisms of action.

Real-World Safety and Efficacy Outcomes with Abiraterone Acetate Plus Prednisone or Prednisolone as the First- or Second-Line Treatment for Metastatic Castration-Resistant Prostate Cancer: Data from the Prostate Cancer Registry.

BACKGROUND: Despite standard-of-care androgen-deprivation therapy and an increasing number of treatment options, the mortality rate for prostate cancer remains high. Progress to metastatic castration-resistant prostate cancer (mCRPC) necessitates additional treatments. Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients. OBJECTIVE: To evaluate the real-world safety and efficacy of AAP as first-line and second-line [post-docetaxel only (AAP-PD)] treatment in patients with mCRPC. PATIENTS AND METHODS: The Prostate Cancer Registry (PCR) was a prospective, international, observational study of patients with mCRPC in routine clinical practice. Men aged ≥ 18 years with confirmed mCRPC were included. Baseline characteristics, safety (treatment-emergent adverse events, treatment-emergent severe adverse events), and efficacy [progression-free survival (PFS) and overall survival (OS)] were analyzed. RESULTS: At baseline, patients who received first-line AAP (n = 754) were generally older than patients who received AAP-PD (n = 354); median age was 76 years and 70 years, respectively. However, the rate of visceral metastasis was higher in the AAP-PD cohort than in the AAP cohort (17.7% vs. 9.6%, respectively). Demographics and disease characteristics of patients with baseline cardiovascular disease were similar to those of the overall registry population. Efficacy outcomes were similar for all patients, regardless of the line of AAP therapy. For first-line AAP and AAP-PD, respectively, the median PFS was 8.9 and 5.8 months for all patients and 9.1 and 6.0 months for patients with cardiovascular comorbidities; median OS was 27.1 and 23.4 months for all patients, and 27.4 and 23.1 months for patients with cardiovascular comorbidities. There were no unexpected adverse events in any patient subgroup. CONCLUSIONS: These real-world data complement the findings from randomized controlled trials, indicating that first- and second-line AAP is well tolerated and effective in patients with mCRPC, including those with underlying CV comorbidities. TRIAL REGISTRATION NUMBER: NCT02236637, registered 8 September 2014.

Real-World Outcomes in First-Line Treatment of Metastatic Castration-Resistant Prostate Cancer: The Prostate Cancer Registry.

BACKGROUND: Metastatic prostate cancer has a 30% 5-year survival rate despite recent therapeutic advances. There is a need to improve the clinical understanding and treatment of this disease, particularly in the real-world setting and among patients who are under-represented in clinical trials. OBJECTIVE: We aimed to evaluate the characteristics and clinical outcomes of patients who received their first treatment for metastatic castration-resistant prostate cancer (mCRPC) in routine clinical practice, independent of treatment used, including subgroups with baseline cardiac disease, diabetes mellitus, or visceral metastases. PATIENTS AND METHODS: Prospective, noninterventional analysis of patient record data in the multicenter Prostate Cancer Registry (PCR) of men with mCRPC. The data were collected in 16 countries with the aim of recruiting more than 3000 patients between 2013 and 2016. The study end date was 9 July 2018. Data evaluated included baseline characteristics, treatment exposure, and efficacy outcomes [overall survival (OS) and time to progression (TTP)] of patients treated with abiraterone acetate plus prednisone or prednisolone (collectively, "abiraterone"), enzalutamide, or docetaxel. Descriptive outcomes are reported from the overall patient population and subgroups of patients with baseline cardiovascular disease, diabetes mellitus, or visceral metastases. The treatment effects for time to progression were compared for the overall patient population. RESULTS: The study enrollment period lasted 2.5 years, and each patient was followed for a maximum of 3 years. A total of 1874 patients in the PCR had not received previous mCRPC treatment at baseline, although they had received androgen-deprivation therapy. Prevalent co-morbidities included cardiovascular disease in 65.4% and diabetes mellitus in 17.4% of patients. Baseline characteristics suggested that patients with more advanced disease received docetaxel treatment. In the overall patient population, the median time to progression with abiraterone, enzalutamide, and docetaxel as first-line mCRPC therapy was 9.6, 10.3, and 7.6 months, respectively, and median OS was 27.1, 27.1, and 27.9 months, respectively. Outcomes in the subgroups of patients with cardiovascular disease or diabetes mellitus were similar to those of the whole population in the analysis. As expected, patients with visceral metastases had shorter TTP and OS than patients in the overall population. CONCLUSIONS: This analysis shows, for the first time, the effectiveness in parallel of first-line abiraterone, enzalutamide, and docetaxel in mCRPC, including in patients with co-morbidities such as cardiovascular disease or diabetes mellitus or in patients with visceral metastases. These real-world findings from the PCR provide meaningful information to help manage mCRPC, particularly in patients under-represented in clinical studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02236637; registered September 2014.

A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-α in anemic patients with low-risk MDS.

Erythropoiesis-stimulating agents are first choice for treating anemia in low-risk MDS. This double-blind, placebo-controlled study assessed the efficacy and safety of epoetin-α in IPSS low- or intermediate-1 risk (i.e., low-risk) MDS patients with Hb ≤ 10.0 g/dL, with no or moderate RBC transfusion dependence (≤4 RBC units/8 weeks). Patients were randomized, 2:1, to receive epoetin-α 450 IU/kg/week or placebo for 24 weeks, followed by treatment extension in responders. The primary endpoint was erythroid response (ER) through Week 24. Dose adjustments were driven by weekly Hb-levels and included increases, and dose reductions/discontinuation if Hb > 12 g/dL. An independent Response Review Committee (RRC) blindly reviewed all responses, applying IWG-2006 criteria but also considering dose adjustments, drug interruptions and longer periods of observation.A total of 130 patients were randomized (85 to epoetin-α and 45 to placebo). The ER by IWG-2006 criteria was 31.8% for epoetin-α vs 4.4% for placebo (p < 0.001); after RRC review, the ER was 45.9 vs 4.4% (p < 0.001), respectively. Epoetin-α reduced RBC transfusions and increased the time-to-first-transfusion compared with placebo.Thus, epoetin-α significantly improved anemia outcomes in low-risk MDS. IWG-2006 criteria for ER may require amendments to better apply to clinical studies.

Pharmacotherapy of disruptive behavior and item changes on a standardized rating scale: pooled analysis of risperidone effects in children with subaverage IQ.

BACKGROUND: Disruptive behavior disorders (DBDs), excluding attention deficit/hyperactivity disorder (ADHD), are characterized by a repetitive pattern of antisocial, aggressive, and defiant behavior involving major violations of age-appropriate norms, resulting in significant functional impairment. Risperidone is licensed for the treatment of DBDs in children, adolescents, and adults in several countries. The aim of this study was to determine the effect of risperidone in a clinical setting on the symptom items of the Nisonger Child Behavior Rating Form (N-CBRF), used for the assessment of DBD patients. METHOD: Data from two 6-week, randomized, double-blind, placebo-controlled trials of risperidone oral solution (0.02-0.06 mg/kg/day) in children with DBDs and subaverage IQ (mild, moderate mental retardation and borderline IQ) were pooled for analysis. RESULTS: Risperidone produced improvement in both the Social Competence and the Problem Behavior N-CBRF subscales. Risperidone reduced symptoms in the Problem Behavior subscales (e.g., Conduct Problem, Insecure/Anxious) but also improved positive behaviors on the Social Competence subscales. Unlike most problem-behavior items, certain items reflecting "Affective insecurity" (e.g., shy, timid; clings to adults; crying, tearful episodes) failed to improve. This was also true of social disinterest and certain rituals. No items showed any worsening of symptoms with active medication. CONCLUSION: Whereas most categories of problem behavior improved with risperidone, items reflecting "affective insecurity" and some infrequently endorsed items were unaffected in these children with DBDs and subaverage IQ. These data may provide a more refined knowledge of risperidone's therapeutic effects in such children.

Long-acting injectable risperidone and oral antipsychotics in patients with schizophrenia: results from a prospective, 1-year, non-interventional study (InORS).

OBJECTIVE: To explore differences in outcomes for patients with schizophrenia treated with risperidone long-acting treatment (RLAT) or oral antipsychotics (oAP). METHODS: The International Observational Registry on Schizophrenia (InORS) explored flexible doses of newly initiated RLAT and oAPs for adults with schizophrenia, exploring 6-month retrospective hospitalization data and 12-month prospective medication use, outcomes, and tolerability. Efficacy outcomes included hospitalizations, the Clinical Global Impression of Schizophrenia (CGI-SCH), and the Global Assessment of Functioning (GAF). Medication switch patterns were also analysed. RESULTS: Data were analysed from 1083 patients (561 RLAT, 522 oAP). At baseline, RLAT patients had higher symptom severity, greater functional impairment, and poorer compliance. Percentages of patients hospitalized were similar between groups, and median duration per hospitalization decreased after RLAT initiation and with oAP. The difference in duration of hospitalization between the retrospective and prospective period was significantly better with RLAT (P = 0.002). Mean CGI-SCH change from baseline was significantly better for RLAT vs. oAP patients for overall, positive, and negative symptom scores (P < 0.05). Mean functional improvement from baseline was significantly higher with RLAT vs. oAP (P < 0.001). CONCLUSIONS: Hospitalizations and symptomatic and functional outcomes were better with RLAT vs. oAP; frequent medication switches were associated with less favourable outcomes.

Time course of adverse events in patients with localization-related epilepsy receiving topiramate added to carbamazepine.

PURPOSE: To explore the time course of treatment-emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy. METHODS: Post hoc analyses were performed by using data from a large (264 subjects) multicenter, double-blind, placebo-controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment-resistant partial-onset seizures. The daily incidence and mean duration of the most common (> or =5% incidence) AEs were calculated for patients completing the 12-week study. RESULTS: The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits. CONCLUSIONS: This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy.