Analysis of the efficacy and safety of naloxegol administered to patients with cancer and opioid-induced constipation with laxative-inadequate response: A real-world 12 months of follow-up study.

e24155 Background: Naloxegol is a peripherally acting, µ-opioid receptor antagonist for treatment of opioid-induced constipation (OIC). The main objective of this study was to analyze the efficacy and safety of naloxegol in patients with cancer in a real-world 12-month follow-up study. Methods: An observational prospective study was conducted in 16 Spanish centers. Patients older than 18 years, with active oncological disease who were under treatment with opioids for pain control and Karnofsky ≥ 50 were selected. OIC with inadequate response to treatment with laxative (s) was the main diagnostic. All the patients received treatment with naloxegol according to clinical criteria. Efficacy was measured by the response rate and symptoms evolution measured by means of PAC-SYM questionnaire. Intensity of pain was measured by a 0-10-point visual analogue scale (VAS). Intent to treat last observation carried forward was applied. Results: A total of 126 patients were included in the study. About 58.7% were men, with a mean age of 61.5 years (34-89). Lung cancer was observed in 35.7%, breast cancer in 16.7%, 10.3% digestive cancer and 8.7% had prostate cancer. About 67.5% had metastases. Naloxegol at doses of 25 mg/day was administered to 88.1% and with concomitant laxatives in 48.4%. At 12 months, 77.8% of the patients were responders to naloxegol treatment: 78.6% at doses of 12.5 mg/day, and 78.4% with 25 mg/day. Furthermore, response was observed in 78.5% of patients without concomitant laxative treatment and 77% of patients with any concomitant laxative. PAC-SYM total score and all the dimensions improved from baseline (p < 0.0001). VAS pain intensity was reduced and controlled from baseline onwards (Baseline-12 months: 4.6 to 3.6, p < 0.001). A total of 28 adverse reactions mainly gastrointestinal were observed in 15.1% of the patients (19/126), 75% (21) mild, 17.9% (5) moderate and 7.1% (2) severe. Most adverse reactions (67.9%) were observed the first 15 days of treatment with naloxegol. Conclusions: The results of this first real-world-data study in patients with cancer confirm the long-term efficacy of naloxegol for the treatment of OIC in this group of patients. Naloxegol is safe and well tolerated in patients with cancer while maintaining pain control.

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One-year efficacy and safety of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: KYONAL study

BMJ Supportive & Palliative Care ◽

10.1136/bmjspcare-2020-002816 ◽

2021 ◽

pp. bmjspcare-2020-002816

Author(s):

Manuel Cobo Dols ◽

Carmen Beato Zambrano ◽

Luis Cabezón-Gutiérrez ◽

Rodolfo Chicas-Sett ◽

María Isabel Blancas López-Barajas ◽

...

Keyword(s):

Quality Of Life ◽

Real World ◽

Adverse Reactions ◽

Response To Treatment ◽

Inadequate Response ◽

Efficacy And Safety ◽

Patients With Cancer ◽

One Year

ObjectivesNaloxegol is a peripherally acting µ-opioid receptor antagonist (PAMORA) for treatment of opioid-induced constipation (OIC). The main objective was to analyse the long-term efficacy, quality of life (QOL) and safety of naloxegol in patients with cancer in a real-world study.MethodsThis one-year prospective study included patients older than 18 years, with active oncological disease who were under treatment with opioids for pain control and Karnofsky≥50 and OIC with inadequate response to treatment with laxative (s). All the patients received treatment with naloxegol according to clinical criteria. The main efficacy objectives were measured by the patient assessment of constipation QOL questionnaire (PAC-QOL), the PAC symptoms (PAC-SYM), the response rate at day 15, and months 1-3-6-12, and global QOL (EuroQoL-5D-5L).ResultsA total of 126 patients (58.7% males) with a mean age of 61.5 years (95% CI 59.4 to 63.7) were included. PAC-SYM and PAC-QOL total score and all their dimensions improved from baseline (p<0.0001). At 12 months, 77.8% of the patients were responders to naloxegol treatment. Global QOL was conserved from baseline. A total of 28 adverse reactions, mainly gastrointestinal were observed in 15.1% of the patients (19/126), being 75% (21) mild, 17.9% (5) moderate and 7.1% (2) severe. Most adverse reactions (67.9%) appeared the first 15 days of treatment.ConclusionThe results of this first long-term and real-world-data study in patients with cancer, showed the sustained efficacy and safety of naloxegol for the treatment of OIC in this group of patients.

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Analysis of the efficacy of naloxegol in a real-world 12 weeks of follow-up study, in patients with cancer and opioid-induced constipation with laxative-inadequate response

Annals of Oncology ◽

10.1093/annonc/mdz265.066 ◽

2019 ◽

Vol 30 ◽

pp. v740

Author(s):

M. Cobo Dols ◽

M.D.C. Beato Zambrano ◽

L. Cabezón Gutiérrez ◽

R. Chicas Sett ◽

I. Blancas ◽

...

Keyword(s):

Real World ◽

Inadequate Response ◽

Patients With Cancer ◽

Follow Up Study

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It Matters: Reference Indicator Selection in Measurement Invariance Tests

Educational and Psychological Measurement ◽

10.1177/0013164420926565 ◽

2020 ◽

pp. 001316442092656

Author(s):

Yutian T. Thompson ◽

Hairong Song ◽

Dexin Shi ◽

Zhengkui Liu

Keyword(s):

Measurement Invariance ◽

Real World ◽

Quantitative Methods ◽

Simulated Data ◽

Selection Methods ◽

Real World Data ◽

Large Sample ◽

World Data ◽

Follow Up Study

Conventional approaches for selecting a reference indicator (RI) could lead to misleading results in testing for measurement invariance (MI). Several newer quantitative methods have been available for more rigorous RI selection. However, it is still unknown how well these methods perform in terms of correctly identifying a truly invariant item to be an RI. Thus, Study 1 was designed to address this issue in various conditions using simulated data. As a follow-up, Study 2 further investigated the advantages/disadvantages of using RI-based approaches for MI testing in comparison with non-RI-based approaches. Altogether, the two studies provided a solid examination on how RI matters in MI tests. In addition, a large sample of real-world data was used to empirically compare the uses of the RI selection methods as well as the RI-based and non-RI-based approaches for MI testing. In the end, we offered a discussion on all these methods, followed by suggestions and recommendations for applied researchers.

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Real-World Data with the Use of Caplacizumab in the Treatment of Acquired Thrombotic Thrombocytopenic Purpura (aTTP)

Blood ◽

10.1182/blood-2020-142987 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 14-16

Author(s):

M Moraima Jimenez ◽

Sabela Bobillo ◽

Ana Pérez ◽

Pamela Arenas ◽

Alba Cabirta ◽

...

Keyword(s):

Real World ◽

Clinical Characteristics ◽

Randomized Clinical Trials ◽

Immunosuppressive Agents ◽

Response To Treatment ◽

Lower Percentage ◽

Neurological Involvement ◽

Control Group ◽

Real World Data

INTRODUCTION For more than two decades, the treatment of aTTPconsisted of therapeutic plasma exchange (TPE) and immunosuppressive agents. The addition of caplacizumab, a nano-antibody that binds to the A1 domain of the von Willebrand factor, inhibiting platelet aggregation, has been shown to reduce the time to resolution of thrombocytopenia, the rate of recurrence and the aTTP-related death. Real-world evidence of the effectiveness of caplacizumab is limited yet. The objective of our study was to assess the results of the introduction of caplacizumab in our internal protocol and to compare those results with the patients treated before the drug was available. METHODS A single-center retrospective observational study that evaluates the clinical characteristics and response to treatment of 18 consecutively diagnosed aTTP patients between May/14 to May/20. All patients received initial treatment with TPE and prednisone (PDN) 1 mg/Kg; the control group did not receive any other initial therapy, whereas nine patients received caplacizumab in addition to PEX and PDN once ADAMTS-13 deficiency was confirmed. Complete response (CR) was defined as the second of two consecutive days with platelets ≥150x109/L, refractoriness as the lack of platelet increase despite optimal therapy after 7 days, exacerbation as the decrease in platelet count during the first 30 days of discontinuation of TPE, and relapse as a new episode of aTTP beyond 30 days after the last TPE. All results are given as median (interquartile range). Statistical analysis was conducted using STATA/IC software. RESULTS The clinical characteristics at diagnosis of patients treated with or without caplacizumab were similar, except for a lower percentage of males and lower neurological involvement in the caplacizumab group (Table 1). Caplacizumab was started at a median of 3 days after diagnosis following ADAMTS-13 deficiency determination, and was administered during a median of 39 days (IQR 33-39). Adverse events related to caplacizumab were mild: 1 patient presented mild metrorrhagia, 1 developed pain and erythema at the puncture area and 1 suffered an urticarial dermatitis, the last case leading to the suspension of the drug since levels of ADAMTS-13 were recovered. The caplacizumab group achieved CR after a median of 4 days (IQR 3-4) vs. 6 days (IQR 5-14) in the control group (p = 0.016). Likewise, the number of TPE was lower with caplacizumab (Figure 1), with a median of 10 TPE (IQR 9-11) vs. 19 (IQR 16-23) (p = 0.001). Hospitalization time was also shorter in the caplacizumab group with a median of 12 days (IQR 12-14) vs. 26 (IQR 20-27) (p = 0.002). Finally the time of hospitalization into the intensive care unit was shorter in the caplacizumab group with a median of 3 days (IQR 2-4) vs. 4 (IQR 3-13) (p=0.1). In the caplacizumab group (median follow-up of 6.8 months), there were no refractory cases. There was 1 exacerbation before initiation of caplacizumab and 1 relapse. Both cases were treated with rituximab. In contrast, in the control group (median follow-up of 51.8 months), we observed 4 refractory cases (1 aTTP-related death), 3 exacerbations and 1 relapse; rituximab was necessary in 8 patients and a 3rd line with vincristine was administered in 4 cases. CONCLUSIONS The observed benefits of caplacizumab in our series are in line with the ones identified in randomized clinical trials. Caplacizumab can be used in combination with other therapies to attain a faster response and reduce aTTP-related complications. Disclosures Bosch: Hoffmann-La Roche: Research Funding.

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1868P Efficacy and safety of naloxegol in patients with cancer with opioid-induced constipation with laxative-inadequate response: A long-term, real-world study

Annals of Oncology ◽

10.1016/j.annonc.2020.08.1515 ◽

2020 ◽

Vol 31 ◽

pp. S1066

Author(s):

C. Beato Zambrano ◽

M. Cobo Dols ◽

L. Cabezón Gutiérrez ◽

R. Chicas-Sett ◽

M.I. Blancas López-Barajas ◽

...

Keyword(s):

Real World ◽

Inadequate Response ◽

Efficacy And Safety ◽

Patients With Cancer

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Safety and efficacy of direct acting oral anticoagulants and vitamin K antagonists in nonvalvular atrial fibrillation – a network meta-analysis of real-world data

VASA ◽

10.1024/0301-1526/a000746 ◽

2019 ◽

Vol 48 (2) ◽

pp. 134-147 ◽

Cited By ~ 8

Author(s):

Mirko Hirschl ◽

Michael Kundi

Keyword(s):

Real World ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Efficacy And Safety ◽

Nonvalvular Atrial Fibrillation ◽

Real World Data ◽

Hazard Ratios ◽

Direct Acting ◽

Event Rates

Abstract. Background: In randomized controlled trials (RCTs) direct acting oral anticoagulants (DOACs) showed a superior risk-benefit profile in comparison to vitamin K antagonists (VKAs) for patients with nonvalvular atrial fibrillation. Patients enrolled in such studies do not necessarily reflect the whole target population treated in real-world practice. Materials and methods: By a systematic literature search, 88 studies including 3,351,628 patients providing over 2.9 million patient-years of follow-up were identified. Hazard ratios and event-rates for the main efficacy and safety outcomes were extracted and the results for DOACs and VKAs combined by network meta-analysis. In addition, meta-regression was performed to identify factors responsible for heterogeneity across studies. Results: For stroke and systemic embolism as well as for major bleeding and intracranial bleeding real-world studies gave virtually the same result as RCTs with higher efficacy and lower major bleeding risk (for dabigatran and apixaban) and lower risk of intracranial bleeding (all DOACs) compared to VKAs. Results for gastrointestinal bleeding were consistently better for DOACs and hazard ratios of myocardial infarction were significantly lower in real-world for dabigatran and apixaban compared to RCTs. By a ranking analysis we found that apixaban is the safest anticoagulant drug, while rivaroxaban closely followed by dabigatran are the most efficacious. Risk of bias and heterogeneity was assessed and had little impact on the overall results. Analysis of effect modification could guide the clinical decision as no single DOAC was superior/inferior to the others under all conditions. Conclusions: DOACs were at least as efficacious as VKAs. In terms of safety endpoints, DOACs performed better under real-world conditions than in RCTs. The current real-world data showed that differences in efficacy and safety, despite generally low event rates, exist between DOACs. Knowledge about these differences in performance can contribute to a more personalized medicine.

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