Safety of transdermal fentanyl (TF) in front-line approach to severe cancer pain. Meta-analysis of randomized clinical trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19627-19627
Author(s):  
M. Maltoni ◽  
E. Scarpi ◽  
B. Poggi ◽  
D. Tassinari
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Cancer Pain ◽  
Safety Profile ◽  
Mesh Term ◽  
Phase Iii ◽  
Front Line ◽  
Significant Difference ◽  
Opioid Administration ◽  
Gastrointestinal Side Effects

19627 Background: To assess the safety of TF when compared with Slow Releasing Oral Morphine (SROM) in the front-line approach to severe cancer pain. Methods: A systematic review of literature in the MEDLINE and EMBASE data bases from 1966 to October 2006, using “Administration, Cutaneous” [MeSH term], “Administration, Oral” [MeSH term], “Analgesic, Opioid/*administration & dosage/adverse effects” [MeSH term], “Delayed-Action Preparations” [MeSH term], “Fentanyl/*administration & dosage/adverse effects” [MeSH term], “Cancer Pain/*drug therapy” [MeSH term], “Morphine/*administration & dosage/adverse effects” [MeSH term] as search terms was performed independently by two authors (DT and MM). All the randomized phase III trials comparing TF and SROM were considered eligible and included into the analysis. The overall side effects odds ratio (OR) was the primary end point of the analysis; overall gastrointestinal side effects, constipation, nausea, somnolence, the patient's preference and the trial withdrawal pooled ORs the secondary ones. Heterogeneity between the trials was analysed using the Mantel-Haenszel test, and the outcome analysis was performed using a fixed effects model and an alpha error lower than 5%. Results: 3 trials met the selection criteria and were included into the analysis. The safety of TF and SROM was analysed in 373 patients (188 and 185 respectively treated with TF and SROM). A significant difference in favour of TF was observed for constipation (OR=0.42, p=0.002), somnolence (OR=0.559, p=0.018) and the preference of the patient (OR=0.39, p<0.001): no significant differences were observed for overall side effects (OR=0.82, p=0.51), overall gastrointestinal side effects (OR=0.87, p=0.6), nausea (OR=1.2, p=0.446) and trial withdrawal (OR=0.62, p=0.59). No heterogeneity was documented between the trials. Conclusion: Although no differences exist between TF and SROM in efficacy (with equianalgesic doses) and safety (when assessed as overall safety profile) on the whole, the differences in the peculiar safety profile of the two opiates seems to favour TF in patient's preference in the choice of front-line treatment of severe cancer pain. No significant financial relationships to disclose.

scholarly journals Investigation of the Frequency of Adverse Effects in Patients Treated with Favipiravir as SARS-CoV-2 Treatment

2021 ◽  
pp. 1-4
Author(s):  
Ebru Dogan ◽  
Sevil Alkan-Çeviker ◽  
Servan Vurucu ◽  
Alper Sener ◽  
Buse Yüksel ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Demographic Data ◽  
Antiviral Agents ◽  
Good Alternative ◽  
Long Term Effects ◽  
Cardiac Side Effects ◽  
Significant Difference ◽  
Gastrointestinal Side Effects ◽  
Treatment Agent

Objective: For 2019 and 2020, SARS-CoV-2 has been a sensational virus. Unfortunately, a treatment agent specific for SARS-CoV-2 has not been developed yet. Favipiravir is one of the antiviral agents used experimentally in the treatment of SARS-CoV-2. This study aimed to determine the frequency of side effects seen in patients hospitalized in our hospital and received favipiravir at any stage of their treatment. Methods: Our study is a retrospective observational study. Definite and probable COVID-19 cases hospitalized in our hospital between March 23, 2020, May 31, 2020, were determined, and those receiving favipiravir as initial or secondary therapy were included in the study. The demographic data, laboratory tests, observed side effects of the patients were recorded and analyzed statistically. Results: A total of 134 patients, 37.3% using favipiravir at the beginning and 62.7% as secondary, were included in the study. The mean age of the patients was 66.8±15.7 years. 38.1% (n=51) of the group were female. Side effects were detected in 17 (13%) patients in the whole group. Hepatotoxicity (4.5%), increased serum uric acid (4.5%), nephrotoxicity (1.5%), gastrointestinal side effects (1.5%), cardiac side effects (0.7%) were detected. There was no statistically significant difference in terms of adverse events between the patients who received favipiravir initially or later on disease course. Conclusions: Although some results support the short-term safety of favipiravir, more studies are needed for its long-term effects. Studies on hyperuricemia, QTc prolongation, use in pregnancy, use during lactation and use in children are insufficient. Therefore, although Favipiravir appears to be a good alternative in the treatment of COVID-19, it should be used carefully because the data on its safety is still insufficient. Key Words: Favipiravir, adverse effects, COVID-19, SARS-CoV-2

scholarly journals The Effect of Systemic Methotrexate and Cyclosporine Combination Therapy inPsoriasis Vulgaris Patients in Bandung, Indonesia

2021 ◽  
Vol 33 (3) ◽  
pp. 200
Author(s):  
Oki Suwarsa ◽  
Fatima Aulia Khairani ◽  
Syawalika Ulya Isneny ◽  
Erda Avriyanti ◽  
Hartati Purbo Dharmadji ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Side Effects ◽  
Adverse Effects ◽  
Combination Therapy ◽  
Combination Treatment ◽  
Psoriasis Vulgaris ◽  
Severity Index ◽  
Dermatology Clinic ◽  
Significant Difference ◽  
Pasi Score

Background: Methotrexate (MTX) and cyclosporine have been used as effective systemic mono-therapy for psoriasis. Several factors are considered to switch monotherapy to combination therapy because monotherapy is no longer effective and has higher side effects. Hence,clinicians have avoided systemic therapy combinations due to its toxicity. However, some studies showed that this combination therapy could be usedeffectively for psoriasis patients. Purpose: This study aimed to analyze the efficacy and adverse effects of systemic MTX and cyclosporine combination therapy in Indonesian psoriasis vulgaris patients. Methods: The retrospective study assessed the effectiveness of 3 monthsmono-therapyand combination therapy of systemic MTX and cyclosporine in psoriasisvulgaris patients from 2016–2017 in Dermatology Clinic, Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia. Result: Psoriasis area and severity index (PASI) score 90 were achieved in the group MTX (50%) and cyclosporine group (50%), while none in the combination group.However, eight patients (50%) in group MTX and cyclosporine reached the primary endpoint of PASI 50. One patient in cyclosporine group had adverse effects on kidney profiles. Nonetheless, other patients had no biochemical changes. But, there was no significant difference in the change of PASI between each group (p=0.102). Conclusion: We propose that combination therapy of MTX and cyclosporine is relatively safe and efficacious in treating Indonesian psoriasis vulgaris patients. This combination treatment isas effective as MTX or cyclosporinemono-therapy.

High- versus low-dose leucovorin in 5-fluorouracil-based oxaliplatin- or irinotecan-containing regimen in metastatic colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15054-e15054
Author(s):  
E. Song ◽  
N. Lee ◽  
J. Kwak ◽  
H. Yhim ◽  
K. Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Large Scale ◽  
Low Dose ◽  
Palliative Chemotherapy ◽  
Optimal Dose ◽  
Phase Iii ◽  
High Dose ◽  
Significant Difference ◽  
Gastrointestinal Side Effects

e15054 Background: Although leucovorin (LV) is widely used as a modulator of 5-fluorouracil (5-FU) for the chemotherapy of advanced colorectal cancer, the optimal dose has not yet been established. Low-dose LV appears to be as active as high-dose LV in the several studies. So, we tried to compare the efficacy of high-versus low-dose LV in the commonly used palliative chemotherapy regimen. Methods: Between May 2003 and May 2008, 40 patients with metastatic colorectal cancer were randomly treated with high-LV (200mg/m2/i.v.) or low-LV (20mg/m2/i.v.) in 5-FU based oxaliplatin (FOLFOX-4) or irinotecan (FOLFIRI) containing regimen. The primary endpoint of the study was the comparison of response rates and the secondary endpoint was the assessment of survival and tolerability. Results: The response rate was 40% in low-LV group with 2 CR and 6 PR, and 35% in high-LV group with 2 CR and 5 PR, without any significant difference (P = 0.89). The median overall survival was 24.3 months in low-LV group and 25.2 months in high-LV group, with no difference between treatments. Toxicity mainly consisted of gastrointestinal side effects, which were rare and similar in the two groups. Conclusions: In this randomized phase II study, the low and high doses of LV appeared to be equivalent in palliative chemotherapy of metastatic colorectal cancer although large-scale phase III study are necessary. No significant financial relationships to disclose.

Feasibility of two schedules of weekly paclitaxel as (neo)adjuvant treatment for patients (PTS) with HER2-negative breast cancer (BC) in the Brazilian community setting.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 122-122
Author(s):  
Iuri Amorim Santana ◽  
Julia Andrade De Oliveira ◽  
Alan Alves Amaral ◽  
Laura Testa ◽  
Luciana Garcia Landeiro ◽  
...  
Keyword(s):  
Adverse Events ◽  
Safety Profile ◽  
Locally Advanced ◽  
Community Setting ◽  
Dose Intensity ◽  
Cost Effective ◽  
Phase Iii ◽  
Weekly Paclitaxel ◽  
Historical Cohort ◽  
Significant Difference

122 Background: Paclitaxel is one of the most active drugs in BC and the weekly administration has been shown more effective and better. GEICAM9906 was a phase III trial that demonstrated the effectiveness and safety of a pragmatic dose-dense schedule of 100mg/m2 of paclitaxel given over 8 consecutive weeks (w), without G-CSF support. This schedule has been adopted at our institution in 2009 for HER2 negative disease and herein we present the first off-trial experience and also compare its safety profile with that of a historical cohort of pts treated with the conventional 80mg/m2 x12w schedule. Methods: The study consists of a retrospective review of medical files from pts with locally advanced BC treated with (neo)adjuvant paclitaxel-based therapy with one of two schedules: (1) 80 mg/m² x 12w or (2) 100 mg/m² x 8w. Adverse events (AE) were graded according to Common Terminology Criteria for Adverse Events 4.0 (CTCAE). Results: We reviewed files from 326 women with a median age of 52 (±10.9). Seventy and 256 pts received schedule (1) and (2), respectively. No significant difference was observed in the incidence of G3/4 toxicity: pneumonitis (2.8% vs 0.3% p=0.097), neuropathy (2.8% vs 0.7% p=0.303); hand-foot syndrome (1.4% vs 0.3% p=0.538); anaemia (0 vs 0.6% p=0.624); neutropenia (5.7% vs 6.2% p=0.408) with only one case of febrile neutropenia in schedule (2) arm; without cases of grade 3/4 thrombocytopenia, nausea, mucositis or anaphylaxis in both groups. Also, no significant difference was seen when comparing all grades toxicty. The dose intensity of paclitaxel was higher in schedule (2) with 97.72 mg/m² per week vs 77.07 mg/m² per week (p<0.0001). Conclusions: Weekly paclitaxel given according to GEICAM9906 is a pragmatic and well tolerated schedule when used in the Brazilian community setting, with a safety profile comparable to the conventional 80mg/m2 x12w schedule. In addition to being convenient to pts, it may also be cost-effective because of a lower number of clinic visits and infusions.

Risk of infectious, hematological, and gastrointestinal side effects in patients treatedwith ibrutinib: A systematic review and meta-analysis of randomized controlled trials.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18265-e18265
Author(s):  
Myo Zaw ◽  
Kyaw Zin Thein ◽  
Aung Tun ◽  
Lukman Tijani ◽  
Elizabeth Guevara
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Adverse Effects ◽  
Randomized Controlled Trials ◽  
Chemokine Receptors ◽  
Meta Analysis ◽  
Controlled Trials ◽  
High Grade ◽  
Randomized Controlled ◽  
Gastrointestinal Side Effects

e18265 Background: Bruton’s tyrosine kinase (BTK) is essential for signaling of B-cell and chemokine receptors. Ibrutinib targets BTK and has become frontier in many hematologic malignancies. We undertook systematic review and pooled analysis of randomized controlled trials (RCTs) to determine infectious, hematological and gastrointestinal risks associated with ibrutinib. Methods: We performed a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts through December 31, 2016. The RCTs that mention infectious, hematological and gastrointestinal side effects as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Results: Four RCTs with a total of 1505 patients were eligible for the analysis. Studies compared Ibrutinib (I) vs ofatumumab, I vs chlorambucil, I+ bendamustine (B)+ rituximab (R) vs placebo + B+ R and I vs temsirolimus were included in the analysis. The relative risks (RR) of all-grade side effects were as follows: infection, 1.34 (95% CI: 1.04 – 1.74; p = 0.02); pneumonia, 1.16 (95% CI: 0.82–1.66; p = 0.38); anemia, 0.77 (95% CI: 0.64 – 0.93; p = 0.007); neutropenia, 0.99 (95% CI: 0.87 – 1.14; p = 0.98); thrombocytopenia, 0.86 (95% CI: 0.71 – 1.04; p = 0.12); diarrhea, 1.74 (95% CI: 1.48 – 2.05; p < 0.0001); nausea, 0.94 (95% CI: 0.80 – 1.10; p = 0.45); and vomiting, 0.98 (95% CI 0.74 – 1.30; p = 0.93). The RR of high-grade adverse effects were as follows: febrile neutropenia, 1.32 (95% CI: 0.84 – 2.08; p = 0.21); infection, 1.20 (95% CI: 0.73 – 1.98; p = 0.45); pneumonia, 1.22 (95% CI: 0.76–1.95; p = 0.39); anemia, 0.48 (95% CI: 0.33 – 0.71; p < 0.0001); neutropenia, 0.99 (95% CI: 0.86 – 1.15; p = 0.94); thrombocytopenia, 0.61 (95% CI: 0.47 – 0.81; p = 0.001); diarrhea, 1.72 (95% CI: 0.88 – 3.34;p = 0.10); nausea, 2.56 (95% CI: 0.59 – 10.99; p = 0.20); and vomiting, 0.42 (95% CI 0.11 – 1.63; p = 0.21). Conclusions: Ibrutinib increased the risk of all-grade diarrhea and infection whereas the risks of all-grade anemia, high-grade anemia and thrombocytopenia were significantly lower in the study arm, favoring ibrutinib.

Initial Experience with the IMPROVE Trial-a Phase III Analgesic Trial for Hospitalized Sickle Cell Painful Episodes

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2667-2667 ◽  
Author(s):  
Carlton Dampier ◽  
Wally R. Smith ◽  
Carrie Wager ◽  
Margaret Bell ◽  
James R. Eckman ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Effects ◽  
Sample Size ◽  
Sickle Cell ◽  
Average Length ◽  
Small Sample ◽  
Phase Iii ◽  
Constant Infusion ◽  
Acute Chest Syndrome ◽  
Opioid Administration

Abstract Abstract 2667 Background: Acute pain is the leading cause of hospitalization in both children and adults with sickle cell disease (SCD). Opioid analgesics are used for pain relief, but are associated with significant adverse effects that are bothersome to patients and may predispose to serious sickle-related pulmonary events. Evidence is limited for the most effective opioid administration strategy that maximizes analgesia and minimizes adverse effects. Patient Controlled Analgesia (PCA) has the potential advantage to allow a patient to optimize pain control without dependence on healthcare providers for administration. PCA generally consists of an opioid given by constant infusion with additional demand doses as needed; the proper dosing for each is largely unknown, particularly at high opioid doses. The SCDCRN conducted a multi-center phase III clinical trial comparing two alternative opioid PCA dosing strategies (HDLI-higher demand dose with low constant infusion or LDHI- lower demand dose and higher constant infusion). The required sample size for the trial was 278 subjects. Patients and Methods: SCD patients ≥ age 10 years hospitalized for significant pain (baseline pain VAS ≥ 4.5/10) who had received < 12 hours of previous analgesic therapy and provided informed consent were eligible; patients with renal/hepatic dysfunction, who received large amounts of oral opioids prior to admission, or who had evidence of acute chest syndrome were excluded. Investigators used standardized opioid dosing tables for morphine or hydromorphone, and for participants weighing ±50 kg. Opioid-related symptoms were assessed with a validated daily questionnaire; multimodal assessments of pain, physical function, and sleep were conducted by an assessor blinded to treatment assignment/dose level; because of safety concerns, individuals responsible for making dosing decisions were not blinded. The assigned PCA strategy was continued until patients were transitioned to oral analgesics. An intention to treat analysis was planned for the time to a significant (2.5 cm) improvement in average daily 10 cm pain VAS. Secondary endpoints included total opioid usage and frequency of opioid-related symptoms. Results: From January 1, 2010 to June 8, 2010, a total of 1050 patients age ≥ 10 years were hospitalized for pain; 216 were ineligible, 796 were missed for logistic/staffing issues at sites, and 38 subjects completed randomization prior to trial closure (due to inadequate time to complete enrollment prior to Network termination in March 2011). Average age of enrolled subjects was 23.9 ± 12.2 years (range 10–52 years), and 53% were female. The HDLI arm had 50% morphine and 40% pediatric subjects (10-17 years); the LDHI arm had 44% morphine and 50% pediatric subjects. Four subjects were withdrawn (1 parent permission withdrawal, 2 inadvertent withdrawals by PI, 1 ineligible). Baseline VAS was high (mean 7.5 cm HDLI, and 7.7 cm LDHI). A reduction in pain intensity during PCA treatment was observed in both treatment arms (mean difference from baseline ± SEM: 2.7 ±1.5 cm HDLI vs 2.8 ±2.0 cm LDHI; time to significant improvement 22.0 ±3.0 hours HDLI vs 22.1 ±3.8 hours LDHI), with 75% of the HDLI subjects and 79% of the LHDI experiencing a significant improvement in pain. Average length of hospitalization was 143.7 ±94.2 hours HDLI vs 102.4 ±42.6 hours LDHI. The reliability or significance of any similarities or differences noted in this descriptive analysis is limited by the small sample size. Opioid utilization in the two treatment arms is currently being analyzed. Opioid-related symptoms were well managed and similar in both treatment arms (mean daily opioid symptom severity score (1-4): 0.9 ± 0.6 HDLI vs 0.8 ± 0.6 LDHI). Four episodes of serious hypoxia, likely relate to exacerbation of pulmonary hypertension, developed in adult subjects during the study (2 HDLI, 2 LDHI). Conclusions: The premature closure of the study limits potential conclusions regarding safety and efficacy, or superiority of either treatment regimen. The data gathered will help resolve potential design issues related to the complexity of running an inpatient opiod PCA trial and help guide modification of subject selection and enrollment, optimization of opioid dosing and monitoring, and endpoint assessments. Given the clinical priority of adequate pain management and the challenges of opioid PCA therapy, completion of this trial is imperative. Supported by NHLBI. Disclosures: Dampier: Anthera Pharmaceuticals Inc:; Glycomimetics Inc:. Telen: GlycoMimetics: Consultancy, clinical trial sponsorship.

scholarly journals A randomized controlled trial on lactoferrin versus ferrous sulphate for the treatment of mild to moderate iron deficiency anaemia in pregnancy

2020 ◽  
Vol 9 (2) ◽  
pp. 562
Author(s):  
Swati Gawai ◽  
Michelle Fonseca ◽  
Deepali Kapote
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Controlled Trial ◽  
Ferrous Sulphate ◽  
Controlled Study ◽  
Promising Alternative ◽  
Randomized Controlled ◽  
Gastrointestinal Side Effects ◽  
Group A ◽  
Anaemia In Pregnancy

Background: One of the important factors associated with maternal and foetal complications during pregnancy is Anaemia. Various oral preparations of iron are available, and each has different bioavailability, efficacy and adverse effects. Lactoferrin is a naturally existing iron-binding multifunctional glycoprotein, and a member of a transferrin family, thus belonging to those proteins capable of binding and transferring iron. Lactoferrin has considerably less gastrointestinal side effects than ferrous sulfate and is very useful as well as promising alternative to ferrous sulphate.Methods: Prospective randomized controlled study. Total 100 females with 24 to 36 weeks of pregnancy with haemoglobin between 8 to 10 grams were included out of which 50 patients were given ferrous sulphate 200 mg BD and 50 patients were given lactoferrin 250 mg BD daily for 8 weeks. Various haematological parameters and the adverse effects of both the drugs were studied at registration, 4 weeks and 8 weeks and compared.Results: Thus, after this study authors can say that the rise in haemoglobin with lactoferrin was 1.58 g/dl while with ferrous sulphate it was 1.67 g/dl at 8 weeks. Adverse effects were much lesser in Group A taking lactoferrin compared to Group B.Conclusions: Thus, lactoferrin has the advantage over ferrous sulphate in having   less side effects and increasing the compliance and thus the efficacy of the drug compared to ferrous sulphate.

scholarly journals Randomized Trial of Erythromycin and Azithromycin for Treatment of Chlamydial Infection in Pregnancy

1995 ◽  
Vol 3 (6) ◽  
pp. 241-244 ◽  
Author(s):  
Marc F. Rosenn ◽  
George A. Macones ◽  
Neil S. Silverman
Keyword(s):  
Side Effects ◽  
Screening Tests ◽  
Number Of Patients ◽  
Significant Difference ◽  
Gastrointestinal Side Effects ◽  
The Cost ◽  
Cure Rates ◽  
To Receive ◽  
In Pregnancy

Objective:The purpose of this study was to compare erythromycin and azithromycin in the treatment of chlamydial cervicitis during pregnancy with regard to efficacy, side effects, and compliance.Methods:In a prospective manner, 48 pregnant patients with cervical chlamydial infections diagnosed by routine screening tests were randomly assigned to receive either erythromycin, 500 mg q.i.d. for 7 days (N = 24), or azithromycin, 1 g as a one-time dose (N = 24). All sexual partners were given prescriptions for doxycycline, 100 mg b.i.d. for 7 days. The treatment efficacy was assessed by follow-up chlamydia testing 3 weeks after the therapy was completed. The side effects, intolerance to therapy, and overall compliance were evaluated by means of a standardized posttreatment questionnaire.Results:There was no significant difference in cure rates noted between the erythromycin group and the azithromycin group (77% vs. 91%, respectively;P= 0.24). Gastrointestinal side effects were reported more frequently among patients treated with erythromycin compared with patients treated with azithromycin (45% vs. 17%, respectively;P= 0.004). The patients who received erythromycin reported intolerance to therapy secondary to side effects more frequently than patients who received azithromycin (23% vs. 4%, respectively;P= 0.07). Furthermore, the patients in the azithromycin group were more likely to complete their course of therapy as prescribed than the patients in the erythromycin group (100% vs. 61%, respectively;P= 0.002).Conclusions:Azithromycin is efficacious and well tolerated for the treatment of chlamydial cervicitis in pregnancy. Erythromycin, though efficacious, is poorly tolerated, as demonstrated by the number of patients reporting significant side effects during the course of therapy. Since the cost of azithromycin is comparable to that of generic erythromycin, the present study supports the use of azithromycin as an alternative to erythromycin for the treatment of chlamydial cervicitis in pregnancy.

scholarly journals Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Toxicity of Subcutaneous Ketamine in the Management of Cancer Pain

2012 ◽  
Vol 30 (29) ◽  
pp. 3611-3617 ◽  
Author(s):  
Janet Hardy ◽  
Stephen Quinn ◽  
Belinda Fazekas ◽  
John Plummer ◽  
Simon Eckermann ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Positive Outcome ◽  
Phase Iii ◽  
Additional Patient ◽  
Controlled Study ◽  
Net Benefit ◽  
Primary Analysis ◽  
Double Blind ◽  
Number Of Patients ◽  
Significant Difference

Purpose The anesthetic ketamine is widely used for pain related to cancer, but the evidence to support its use in this setting is weak. This study aimed to determine whether ketamine is more effective than placebo when used in conjunction with opioids and standard adjuvant therapy in the management of chronic uncontrolled cancer pain. Ketamine would be considered of net benefit if it provided clinically relevant improvement in pain with limited breakthrough analgesia and acceptable toxicity. Patients and Methods In this multisite, dose-escalation, double-blind, randomized, placebo-controlled phase III trial, ketamine or placebo was delivered subcutaneously over 3 to 5 days. Results In all, 185 participants were included in the primary analysis. There was no significant difference between the proportion of positive outcomes (0.04; 95% CI, −0.10 to 0.18; P = .55) in the placebo and intervention arms (response rates, 27% [25 of 92] and 31% [29 of 93]). Pain type (nociceptive v neuropathic) was not a predictor of response. There was almost twice the incidence of adverse events worse than baseline in the ketamine group after day 1 (incidence rate ratio, 1.95; 95% CI, 1.46 to 2.61; P < .001) and throughout the study. Those receiving ketamine were more likely to experience a more severe grade of adverse event per day (odds ratio, 1.09; 95% CI, 1.00 to 1.18; P = .039). The number of patients needed to treat for one additional patient to have a positive outcome from ketamine was 25 (95% CI, six to ∞). The number needed to harm, because of toxicity-related withdrawal, was six (95% CI, four to 13). Conclusion Ketamine does not have net clinical benefit when used as an adjunct to opioids and standard coanalgesics in cancer pain.

scholarly journals AB0306 EXPERIENCE WITH RITUXIMAB BIOSIMILAR BCD-020 IN PATIENTS WITH RHEUMATOID ARTHRITIS IN REAL-WORLD CLINICAL PRACTICE ACCORDING TO DATA FROM MOSCOW UNIFIED ARTHRITIS REGISTRY (MUAR)

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1452.1-1452
Author(s):  
G. Lukina ◽  
E. Koltsova ◽  
E. Shmidt ◽  
K. Lytkina ◽  
E. Zhilyaev
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trial ◽  
Clinical Practice ◽  
Safety Profile ◽  
Inflammatory Diseases ◽  
Phase Iii ◽  
Significant Difference ◽  
The Mean ◽  
The Stability ◽  
The Moment

Background:The introduction of perspective anti-rheumatic biologic agents into clinical practice has not only increased therapy efficacy and improved medical prognosis in patients with rheumatoid arthritis (RA), but also resulted in a dramatic increase in treatment cost and, therefore, in a reduced accessibility of the innovative treatment for patients. For this reason, over the last years, there has been a huge interest towards developing biosimilars [1,2].Objectives:To assess the effectiveness and safety of switching from reference rituximab (RTXref) to rituximab biosimilar (RTXbs) BCD-020 in patients with RA in real clinical practice according to the data from MUAR.Methods:Patients with RA who treated by RTXrefat the onset and then switched to RTXbs(BCD-020) were enrolled in the study. For all patients were performed: swollen and tender joints count, ESR, CRP, biochemistry and immunologic blood analyses. Assessment of dynamic of DAS28, RAPID3, HAQ-DI was performed. The great attention was given to the therapy safety assessment. RTXrefeffectiveness and safety profile was assessed at the moment of switching; data for RTXbs(BCD-020) were collected not earlier than 6 months after switching.Results:46 patients with RA were enrolled, 80.5% were women; the mean age was 59.5±12.2 years; 91.3% were RF-positive, 63% - ACCPA-positive, the disease activity at the moment of switching was moderate, the mean DAS28 was 3.5. The duration of RTXreftherapy until switching was 36.8 ± 26.8 months; the duration of the follow-up period for BCD-020 biosimilar was 12.1 ± 6.18 months. In 43.5% of patients, previously inefficiency or intolerance of other biologics was discovered. The proportion of patients who received concomitant therapy with glucocorticoids or methotrexate (MTX) was 45.7% and 43.5%, respectively. The mean MTX dose was 13.6 mg/wk. The mean dose of RTXref/BCD-020 was 1000 mg. The stability dynamic of clinical parameters was retained after switching to biosimilar (Tab.1) without significant difference between the rituximab products (р>0.05).Table 1.Comparison of Efficiency Parameters for the Reference Rituximab and Biosimilar BCD-020ParameterReference rituximabBiosimilar BCD-020DAS28 (ESR)3.393.34HAQ-DI1.481.44RAPID312.912.6The safety profile of RTXrefand RTXbs(BCD-020) was also similar. None of the patients discontinued BCD-020 therapy for reasons related to safety or inefficiency.Conclusion:Within the framework of routine clinical practice, switching from reference rituximab to BCD-020 biosimilar is not accompanied by a change in efficiency and safety profile of the therapy and does not pose a risk of discontinuation, which is coherent with the results of the registration clinical trial for BCD-020. [3]References:[1]Edwards CJ, et al. Switching to biosimilars: current perspectives in immune-mediated inflammatory diseases. Expert Opin Biol Ther. 2019 Oct;19(10):1001-1014. doi: 10.1080/14712598.2019.1610381. Epub 2019 May 6.[2]Dörner T, et al. The changing landscape of biosimilars in rheumatology. Ann Rheum Dis 2016;75:974–982. doi:10.1136/annrheumdis-2016-209166[3]Nasonov EL, et al. The results of a phase III comparative clinical trial of rituximab (Acellbia and MabThera) in rheumatoid arthritis (the BIORA study). Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(5):510-519 (In Russ.). doi:http://dx.doi.org/10.14412/1995-4484-2016-510-519Disclosure of Interests:Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Ekaterina Koltsova: None declared, Evgeniya Shmidt Speakers bureau: MSD, Novartis, Pfizer, Karine Lytkina Speakers bureau: Novartis, Eli Lilly, Pfizer, UCB, Abbvie, Biocad, MSD, Jonson&Jonson, Evgeniy Zhilyaev Speakers bureau: Novartis, UCB, Pfizer, Biocad, Abbvie, MSD, Roche

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