scholarly journals Predictive factors for responses to primary medical treatment with lanreotide autogel 120 mg in acromegaly: post hoc analyses from the PRIMARYS study

Pituitary ◽  
2019 ◽  
Vol 23 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Stephan Petersenn ◽  
◽  
Aude Houchard ◽  
Caroline Sert ◽  
Philippe J. Caron
Keyword(s):  
Predictive Factors ◽  
Somatostatin Receptor ◽  
Area Under The Curve ◽  
Hormonal Control ◽  
Youden Index ◽  
Open Label ◽  
Treatment Responses ◽  
Post Hoc ◽  
Lanreotide Autogel

Abstract Purpose PRIMARYS (NCT00690898) was a 48-week, open-label, phase 3b study, evaluating treatment with the somatostatin receptor ligand lanreotide autogel (stable dose: 120 mg/28 days) in treatment-naïve patients with growth hormone (GH)-secreting pituitary macroadenoma. This post hoc analysis aimed to evaluate factors predictive of long-term responses. Methods Potential predictive factors evaluated were: sex, age, and body mass index at baseline; and GH, insulin-like growth factor-1 (IGF-1), and tumor volume (TV) at baseline and week 12, using univariate regression analyses. Treatment responses were defined as hormonal control (GH ≤ 2.5 µg/L and age- and sex-normalized IGF-1), tight hormonal control (GH < 1.0 µg/L and normalized IGF-1), or ≥ 20% TV reduction (TVR). Receiver-operating-characteristic (ROC) curves were constructed using predictive factors significant in univariate analyses. Cut-off values for predicting treatment responses at 12 months were derived by maximizing the Youden index (J). Results At baseline, older age, female sex, and lower IGF-1 levels were associated with an increased probability of achieving long-term hormonal control. ROC area-under-the curve (AUC) values for hormonal control were high for week-12 GH and IGF-1 levels (0.87 and 0.93, respectively); associated cut-off values were 1.19 μg/L and 110% of the upper limit of normal (ULN), respectively. Results were similar for tight hormonal control (AUC values: 0.92 [GH] and 0.87 [IGF-1]; cut-off values: 1.11 μg/L and 125% ULN, respectively). AUC and J values associated with TVR were low. Conclusions The use of predictive factors at baseline and week 12 of treatment could inform clinical expectations of the long-term efficacy of lanreotide autogel.

scholarly journals 14 Long-term Efficacy of Brexpiprazole in Patients with Schizophrenia with Clinically Relevant Levels of Negative Symptoms

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 180-180
Author(s):  
Catherine Weiss ◽  
Peter Zhang ◽  
Ross A Baker ◽  
Mary Hobart ◽  
Nanco Hefting ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Extension Study ◽  
Short Term ◽  
Open Label ◽  
Term Study ◽  
Post Hoc Analysis ◽  
Long Term Study ◽  
Open Label Extension ◽  
Post Hoc

AbstractBackgroundEffective treatments for patients with high levels of negative symptoms of schizophrenia are lacking. Brexpiprazole is a serotonin–dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors, all with subnanomolar potency. Long-term treatment with brexpiprazole demonstrated broad efficacy across all five Marder factor groupings, including positive, negative, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression. This post-hoc analysis of long-term effects of brexpiprazole in patients with clinically relevant levels of negative symptoms of schizophrenia is based on data from two similarly designed short-term, placebo-controlled studies (Vector; NCT01396421 or Beacon; NCT01393613) for the brexpiprazole-treated patients who continued into an open-label extension study (Zenith; NCT01397786).MethodsIn the short-term studies, patients with acute schizophrenia were randomly assigned to fixed once-daily doses of brexpiprazole 0.25mg (Vector), 1mg (Beacon), 2mg , 4mg or placebo for 6weeks. The long-term study was an open-label, 52-week (amended to 26weeks), safety extension study with flexible-dose (1–4mg/day) brexpiprazole. The post-hoc analyses were performed on brexpiprazole-treated patients from the short-term studies who continued into the long-term study, and who had clinically relevant negative symptoms, defined as PANSS Factor Score for Negative Symptoms (PANSS-FSNS; N1, N2, N3, N4, G7, G16) of ≥24, and score of ≥4 on at least two of three core negative symptom PANSS items at randomization in the parent study. The outcome of the analysis included change from baseline to up to 58weeks in PANSS-FSNS, PANSS Total, and PSP. Safety was also assessed.ResultsA total of 187 patients with clinically relevant levels of negative symptoms in the parent study rolled-over into the open-label extension study and were available for analysis. Eighty-three of these patients remained in the studies for 58weeks. Due to the study amendment, not all patients had the opportunity of complete 52weeks of open-label treatment. Baseline PANSS Total score was 104.4, while baseline PANSS-FSNS was 27.6 and baseline PSP Total score was 41.3. Mean change (SD) from baseline in PANSS-FSNS was –10.9 (5.0), and –44.2 (17.5) for PANSS Total score at Week 58. Change from baseline (SD) to Week 58 for PSP Total score was 24.8 (12.9) with improvement in all domains (socially useful activities, personal and social relationship, self-care, and disturbing and aggressive behaviors). The TEAEs reported ≥5% were schizophrenia (18.9%), insomnia (8.6%), weight increased (5.9%) and akathisia (5.9%).ConclusionThis post-hoc analysis suggests that brexpiprazole has long-term effectiveness on negative symptoms and functioning in patients with schizophrenia and clinically relevant levels of negative symptoms.Funding Acknowledgements: The study was funded by Otsuka Pharmaceutical Development & Commercialization Inc. and H. Lundbeck A/S

Response, Survival, and Long-Term Toxicity After Therapy With the Radiolabeled Somatostatin Analogue [90Y-DOTA]-TOC in Metastasized Neuroendocrine Cancers

2011 ◽  
Vol 29 (17) ◽  
pp. 2416-2423 ◽  
Author(s):  
Anna Imhof ◽  
Philippe Brunner ◽  
Nicolas Marincek ◽  
Matthias Briel ◽  
Christian Schindler ◽  
...  
Keyword(s):  
Clinical Response ◽  
Renal Toxicity ◽  
Somatostatin Receptor ◽  
Somatostatin Analogue ◽  
Receptor Imaging ◽  
Open Label ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Neuroendocrine Cancers

Purpose To investigate response, survival, and safety profile of the somatostatin-based radiopeptide 90yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([90Y-DOTA]-TOC) in neuroendocrine cancers. Patients and Methods In a clinical phase II single-center open-label trial, patients with neuroendocrine cancers were treated with repeated cycles of [90Y-DOTA]-TOC. Each cycle consisted of a single intravenous injection of 3.7GBq/m2 body-surface [90Y-DOTA]-TOC. Additional cycles were withheld in case of tumor progression and/or permanent toxicity. Results Overall, 1,109 patients received 2,472 cycles of [90Y-DOTA]-TOC (median, two; range, one to 10 cycles per patient). Of the 1,109 patients, 378 (34.1%) experienced morphologic response; 172 (15.5%), biochemical response; and 329 (29.7%), clinical response. During a median follow-up of 23 months, 491 patients (44.3%) died. Longer survival was correlated with each: morphologic (hazard ratio [HR], 0.46; 95% CI, 0.38 to 0.56; median survival, 44.7 v 18.3 months; P < .001), biochemical (HR, 0.75; 95% CI, 0.59 to 0.96; 35.3 v 25.7 months; P = .023), and clinical response (HR, 0.68; 95% CI, 0.56 to 0.82; 36.8 v 23.5 months; P < .001). Overall, 142 patients (12.8%) developed grade 3 to 4 transient hematologic toxicities, and 103 patients (9.2%) experienced grade 4 to 5 permanent renal toxicity. Multivariable regression revealed that tumoral uptake in the initial imaging study was predictive for overall survival (HR, 0.45; 95% CI, 0.29 to 0.69; P < .001), whereas the initial kidney uptake was predictive for severe renal toxicity (HR, 1.59; 95% CI, 1.17 to 2.17; P = .003). Conclusion This study documents the long-term outcome of [90Y-DOTA]-TOC treatment in a large cohort. Response to [90Y-DOTA]-TOC is associated with longer survival. Somatostatin receptor imaging is predictive for both survival after [90Y-DOTA]-TOC treatment and occurrence of renal toxicity.

scholarly journals Long-Term Safety and Efficacy of Belimumab in Japanese Patients with SLE: a 7-Year Open-Label Continuation Study

2021 ◽  
Author(s):  
Yoshiya Tanaka ◽  
Paula Curtis ◽  
Kathleen DeRose ◽  
Regina Kurrasch ◽  
Kyoko Kinoshita ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Japanese Patients ◽  
Organ Damage ◽  
Open Label ◽  
Open Label Extension ◽  
Secondary Endpoints ◽  
Treatment Responses ◽  
Favorable Safety ◽  
Over Time

Abstract Objectives Evaluate long-term safety, tolerability and efficacy of belimumab in Japanese patients with systemic lupus erythematosus (SLE). Methods This was a subgroup analysis of Japanese patients who completed studies BEL113750 or BEL112341 and were enrolled in a Phase 3, open-label extension study (BEL114333; NCT01597622). Eligible patients received intravenous belimumab 10 mg/kg every 28 days for ≤7 years. Primary endpoint: safety and tolerability. Secondary endpoints included SLE responder index (SRI)-4 response rate, SRI-4 components, severe SLE flare, use of corticosteroids/other SLE-related treatments. Analyses were based on observed data from first parent or current study belimumab dose through to study end. Results Of 71 Japanese patients enrolled, 69.0% completed the study. Overall, 98.6% patients had adverse events (AEs); 32.4% had serious AEs. The proportion of SRI-4 responders increased progressively (Year 1, Week 24: 40.9% [27/66]; Year 7, Week 48: 84.6% [11/13]) as did the proportion of SELENA-SLEDAI responders. The proportion of patients with no worsening in PGA (91.2−100.0%) and no new organ damage (92.6−100.0%) remained stable over time. Severe SLE flare was experienced by 11.3% (8/71) of patients. Corticosteroid and immunosuppressant use decreased over time. Conclusion : Favorable safety profile and treatment responses with belimumab were maintained for ≤7 years in Japanese patients with SLE.

scholarly journals Evaluation of the Safety of Deutetrabenazine at Higher Doses to Treat Chorea in Huntington’s Disease

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 162-163
Author(s):  
Samuel Frank ◽  
Christina Vaughan ◽  
David Stamler ◽  
David Oakes ◽  
Mat D. Davis ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Drug Exposure ◽  
Open Label ◽  
Titration Period ◽  
Open Label Extension ◽  
Pharmaceutical Industries ◽  
Post Hoc ◽  
Higher Doses

AbstractBackgroundIn the First-HD pivotal trial, the maximum deutetrabenazine dose evaluated to treat chorea associated with Huntington’s disease (HD chorea) was 48 mg/d, which is the approved maximum dose for this population. In ARC-HD, an open-label extension study evaluating the long-term efficacy and safety of deutetrabenazine to treat HD chorea, dosage ranged from 6 mg/d to 72 mg/d, with doses ≥12 mg/d administered twice daily. Doses in ARC-HD were increased by 6 mg/d per week in a response-driven manner based on efficacy and tolerability until 48 mg/d (Week 8). At the investigator’s discretion, further increases were permitted by 12 mg/d per week to a maximum of 72 mg/d. This post-hoc analysis evaluates the safety and tolerability of deutetrabenazine >48 mg/d compared to ≤48 mg/d to treat HD chorea in ARC-HD.MethodsPatient counts and safety assessments were attributed to patients when they received a dose of either ≤48 mg/d or >48 mg/d. For 9 selected adverse events (AEs), we compared AE rates adjusted for duration of drug exposure (as number of AEs/year) at ≤48 mg/d or >48 mg/d. The AE rates were determined after titration when participants were on stable doses of deutetrabenazine.ResultsAll 113 patients were exposed to doses ≤48 mg/d (177.1 patient-years) and 49 patients were ever exposed to doses >48 mg/d (74.1 patient-years). In patients taking deutetrabenazine >48 mg/d compared to ≤48 mg/d after the titration period, there were no apparent differences in exposure-adjusted AE rates.ConclusionsBased on clinical experience, some patients with HD may benefit from doses higher than 48 mg/d to adequately control chorea. These doses were tolerated without apparent increase in the exposure-adjusted rates of selected AEs after titration. This analysis does not address the occurrence of other AEs or whether adequate efficacy was achieved at lower doses, factors that may have influenced dose increases.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel

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