scholarly journals Safety and efficacy of repeat Y90 radioembolization to the same hepatic arterial territory

2021 ◽  
pp. 20200752
Author(s):  
Wali Badar ◽  
Thuong Van Ha ◽  
Steven Zangan ◽  
Rakesh Navuluri ◽  
Anjana Pillai ◽  
...  
Keyword(s):  
Adverse Events ◽  
Meld Score ◽  
P Value ◽  
Glass Microspheres ◽  
Safety And Efficacy ◽  
Repeat Treatment ◽  
Kaplan Meier ◽  
Cumulative Activity ◽  
Y90 Radioembolization ◽  
Modified Recist

Objective: To study the efficacy and safety of repeat transarterial radioembolization (TARE) to similar hepatic arterial territories. Methods: Between 3/2011 and 4/2019, 26 patients (25 males and 1 Female, Mean Age: 65 yo, SD: 11.7 yo, Range: 18–83.0 yo) received TARE with Y90 glass microspheres to treat recurrent or residual primary disease in similar hepatic arterial lobe or segments. Tumor response was evaluated by imaging using the modified-RECIST criteria. Incidence of RILD and adverse events were categorized by a standardized scale using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Results: Mean cumulative activity after the first treatment was 2.50 GBq (SD:1.04 GBq, Range:0.61–4.93 GBq) and second treatment was 2.27 GBq (SD:1.01 GBq, Range:0.92–5.46 GBq). Mean interval time between initial and repeat treatments was 9.6 months (Range: 1–53 months). Tumor responses were complete, partial, or progression in 73% (n = 19/26), 23% (n = 6/26), and 4% (n = 1/26) in repeat treatment patients, respectively. The incidence of RILD was 0%. Toxicity after first and second treatment was seen in 19% (n = 5/26) & 23% (n = 6/26) patients, respectively, and were all of CTCAE Grade 2. No significant predictors of treatment toxicity for repeat treatment were identified except increased MELD score (p = 0.04). Kaplan-Meier survival analysis in patients with repeat treatment showed a median survival of 15.0 months (95% CI 8.8–21.1 months) and 19.0 months (95% CI 8.1–29.9 months) in patients who only received one treatment with a p value of 0.485. Conclusion: Repeat TARE with glass microspheres was an effective and safe treatment strategy for disease management in patients with residual or recurrent disease to the similar hepatic arterial territories without any major treatment related toxicity. Advances in knowledge: Although safety and efficacy of repeat radioembolism has been studied, no study has focused on repeat treatment to similar hepatic arterial territories. The current study shows that repeat treatment to the same hepatic arterial territory is as safe as single treatment to the same territory.

Tolerance, survival and adherence to treatment with methotrexate in patients with rheumatoid arthritis

2019 ◽  
pp. 13-17
Author(s):  
J.M. Sevillano Gutierrez ◽  
D. Capelusnik ◽  
E.E. Schneeberger ◽  
G. Citera
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Descriptive Statistics ◽  
P Value ◽  
Multiple Logistic Regression ◽  
Adherence To Treatment ◽  
Exact Test ◽  
Cumulative Survival ◽  
Kaplan Meier ◽  
Chi2 Test

Background: Methotrexate (MTX) is the most frequently used medication in patients with Rheumatoid Arthritis (RA). However, several authors have questioned its success due to the presence of adverse events and the lack of adherence. Objectives: to determine cumulative survival of MTX, frequency and type of adverse events and causes of discontinuation in patients with RA. Methods: consecutive patients 18 years and older with a diagnosis of RA (ACR/EULAR 2010 criteria), who had begun treatment with MTX during their disease were included. Sociodemographic, clinical and therapeutic data were collected. Date of initiation and suspension of MTX, route of administration, concomitant treatments, consumption of coffee and tobacco, presence of adverse events (AE) were all consigned. Adherence was evaluated using the Compliance Questionnaire Rheumatology questionnaire 5-item summary version (CQR5). Statistical analysis: descriptive statistics. Chi2 test or Fisher’s exact test; Survival of treatment by Kaplan-Meier and log Rank. Multiple logistic regression. A p value <0.05 was considered significant.

scholarly journals Thigh intramuscular fat predicts the prognosis in patients in non-ischemic cardiomyopathy with reduced ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Yoshida ◽  
A Shibata ◽  
A Tanihata ◽  
H Hayashi ◽  
Y Ichikawa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Ischemic Cardiomyopathy ◽  
Cox Regression ◽  
Intramuscular Fat ◽  
Left Ventricular ◽  
Skeletal Muscle Atrophy ◽  
Measured Quantity ◽  
Ectopic Fat ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Abstract Background Skeletal muscle atrophy is an independent prognostic predictor for patients with chronic heart failure, and the concept of sarcopenia is drawing attention. Furthermore, the importance of not only muscle mass but also intramuscular fat (IMF) has been pointed out. However, there is a lack of consensus on the implications of ectopic fat for the prognosis in patients with non-ischemic cardiomyopathy. Purpose We investigated whether ectopic fat in the thigh affects the prognosis with non-ischemic cardiomyopathy. Methods We recruited 105 patients who were diagnosed with non-ischemic cardiomyopathy by cardiac catheterization and echocardiographic date between September 2017 and November 2019. Finally 73 patients with reduced EF (EF 40% or less) enrolled in this prospective study. Functional status was evaluated by using cardiopulmonary exercise test at baseline. All patients were measured quantity of epicardial fat and thigh IMF percentage (%IMF) using computed tomography scan. Demographic, laboratory and echocardiographic date were collected from the patients' medical records. Clinical endpoints were unexpected readmission. Results During the follow-up period 18 patients had adverse events. The %IMF was significantly higher in the group with adverse events than without (5.57±5.70 and 3.02±2.44%, respectively; p&lt;0.01). Spearman correlation coefficient analysis showed a modest correlation between %IMF and lower limb extension strength (Spearman r=−0.280; p=0.0315), but there was no significant correlation between %IMF and exercise tolerance such as anaerobic threshold and peak oxygen uptake. Patients were divided into 2 groups according to the median values of %IMF. Kaplan-Meier analysis demonstrated that events were significantly higher in the high %IMF group (log-rank p=0.033). Multivariate Cox regression analysis adjusted for left ventricular end-diastolic diameter and peak ventricular oxygen consumption found %IMF as an independent factor of adverse events (hazard ratio 1.545; 95% confidential interval 1.151–2.087; p=0.004). Conclusions In non-ischemic cardiomyopathy patients with reduced EF, %IMF may have important adverse consequences such as increased cardiac-related events. Kaplan-Meier curves Funding Acknowledgement Type of funding source: None

scholarly journals Modified STOP-Bang for predicting perioperative adverse events in the Thai population

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lisa Sangkum ◽  
Chama Wathanavaha ◽  
Visasiri Tantrakul ◽  
Munthana Pothong ◽  
Cherdkiat Karnjanarachata
Keyword(s):  
High Risk ◽  
Adverse Events ◽  
Oxygen Therapy ◽  
Elective Surgery ◽  
Low Risk ◽  
Perioperative Outcomes ◽  
P Value ◽  
Icu Admission ◽  
Obstructive Sleep ◽  
Postanesthetic Care Unit

Abstract Background Undiagnosed obstructive sleep apnea (OSA) is associated with adverse perioperative outcomes. The STOP-Bang questionnaire is a validated screening tool for OSA. However, its precision may vary among different populations. This study determined the association between high-risk OSA based on the modified STOP-Bang questionnaire and perioperative adverse events. Methods This cross-sectional study included patients undergoing elective surgery from December 2018 to February 2019. The modified STOP-Bang questionnaire includes a history of Snoring, daytime Tiredness, Observed apnea, high blood Pressure, Body mass index > 30 kg/m2, Age > 50, Neck circumference > 40 cm, and male Gender. High risk for OSA was considered as a score ≥ 3. Results Overall, 400 patients were included, and 18.3% of patients experienced perioperative adverse events. On the basis of modified STOP-Bang, the incidence of perioperative adverse events was 23.2 and 13.8% in patients with high risk and low risk (P-value 0.016) (Original STOP-Bang: high risk 22.5% vs. low risk 14.7%, P-value 0.043). Neither modified nor original STOP-Bang was associated with perioperative adverse events (adjusted OR 1.91 (95% CI 0.99–3.66), P-value 0.055) vs. 1.69 (95%CI, 0.89–3.21), P-value 0.106). Modified STOP-Bang ≥3 could predict the incidence of difficult ventilation, laryngoscopic view ≥3, need for oxygen therapy during discharge from postanesthetic care unit and ICU admission. Conclusions Neither modified nor original STOP-Bang was significantly associated with perioperative adverse events. However, a modified STOP-Bang ≥3 can help identify patients at risk of difficult airway, need for oxygen therapy, and ICU admission. Trial registrations This study was registered on Thai Clinical Trials Registry, identifier TCTR20181129001, registered 23 November 2018 (Prospectively registered).

scholarly journals AB0799 REAL-WORLD EXPERIENCE OF SECUKINUMAB FOR PSORIATIC ARTHRITIS WITH AXIAL INVOLVEMENT.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1699.3-1699
Author(s):  
M. Martin Lopez ◽  
B. Joven-Ibáñez ◽  
J. L. Pablos
Keyword(s):  
Psoriatic Arthritis ◽  
Adverse Events ◽  
Real World ◽  
Spinal Pain ◽  
Tender Joint Count ◽  
P Value ◽  
X Ray ◽  
Activity Assessment ◽  
Real World Setting ◽  
Axial Involvement

Background:Evidence on the efficacy of biologics in the treatment of psoriatic arthritis (PsA) patients with axial manifestations affecting 30-70% of PsA patients is limited. Secukinumab (SEC) has provided significant and sustained improvement in the signs and symptoms of active PsA and ankylosing spondylitis.Objectives:This study aims to analyze the experience of using SEC for PsA patients with axial involvement in real-world setting.Methods:Multicentric observational, longitudinal, retrospective study conducted in a tertiary hospital between January 2016 and December 2019. Patients with PsA (CASPAR criteria) and clinical and/or image diagnosis of axial involvement receiving at least one dose of SEC were included. Patients with non-pathological sacroiliacs x-ray and MRI had to have spinal pain VAS ≥4/10 after failure to NSAIDs, prior to the onset of SEC, to be included. Medical records were reviewed to collect demographic and clinical data, features of PsA (manifestations, treatments and activity assessment). Descriptive statistics and then a comparative analysis with the Studentt-test to analyze the effectiveness of SEC were performed.Results:Of 98 PsA patients treated with SEC, 58 (59.2%) had axial involvement, of which 41 (71%) female. Mean age was 54 y.o (SD 10) and average duration of the disease was 10 years (SD 8). All 58 patients had peripheral disease (33% joint erosions), 55 (95%) had psoriasis, 20 (34%) showed dactilitis and 39 (67%) had enthesitis. Sacroiliacs x-ray was damaged in 38 (66%) patients (grade I-IV) and 23 (40%) pathological MRI, with HLAB27+ at 8 (14%) patients. Average BMI was 29 (SD 8), with an obesity rate of 33% (19 pt). Observed comorbidities were hypertension (27 pt, 47%), diabetes mellitus (6 pt, 10%), dyslipidemia (23 pt, 40%), active smoking (18 pt, 31%) and malignancy (6 pt, 10%). Regarding previous treatments, 90% had received cDMARDs, particularly methotrexate (86%) and 40 (69%) had been exposed to at least one bDMARD (15 pt to one, 9 to two, 6 to three and 10 to four or more). 7 patients were on 300 mg dose and 51 patients on 150 mg dose (dose escalation to 300 mg was performed in 16 patients and 44% respond and maintain SEC). Average drug survival time was 1.4 (SD 1) years. At 6 months of SEC therapy, tender and swollen joint count, spinal pain VAS, CRP, ASDAS-CRP and DAPSA had significantly decreased (Table 1). 29 (50%) patients suspended SEC during follow-up due to primary ineffectiveness (8), secondary ineffectiveness (16), adverse events (3), latex allergy (1) and remission (1). Adverse events do not differ from those reported in clinical trials.Table 1.Disease activity assessment at 6 months of secukinumab therapy.Baseline6 months after SECMean differenceP valueSJC4,8±5,41,9±3,1-2,8 (IC95% -3,9 a -1,7)p<0,0001TJC7,7±5,83,9±4,1-3,8 (IC95% -5,1 a -2,4)p<0,0001Spinal pVAS6,1±3,24,2±2,9-1,9 (IC95% -2,4 a -1,4)p<0,0001CRP (mg/L)7,7±9,94,9±5,9-2,9 (IC95% -4,5 a -1,2)p=0,0009ASDAS-CRP2,5±1,91,8±1,3-0,7 (IC95% -0,9 a -0,4)p<0,0001DAPSA27,7±12,116,7±10,4-11 (IC95% -15,3 a -6,8)p<0,0001SJC: swollen joint count, TJC: tender joint count, Spinal pVAS: spinal pain visual analog scale, CRP: C-reactive protein, SEC: secukinumab.Conclusion:Secukinumab in real-world setting provided improvements in the axial and peripheral manifestations of PsA, using both the 150 mg and 300 mg doses.Disclosure of Interests:MARIA MARTIN LOPEZ: None declared, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, José Luis Pablos: None declared

scholarly journals Cardiovascular safety and efficacy of metformin-SGLT2i versus metformin-sulfonylureas in type 2 diabetes: systematic review and meta-analysis of randomized controlled trials

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Desye Gebrie ◽  
Desalegn Getnet ◽  
Tsegahun Manyazewal
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Adverse Events ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Safety And Efficacy ◽  
Randomized Controlled ◽  
Sodium Glucose Cotransporter

AbstractDiabetes is a serious threat to global health and among the top 10 causes of death, with nearly half a billion people living with it worldwide. Treating patients with diabetes tend to become more challenging due to the progressive nature of the disease. The role and benefits of combination therapies for the management of type 2 diabetes are well-documented, while the comparative safety and efficacy among the different combination options have not been elucidated. We aimed to systematically synthesize the evidence on the comparative cardiovascular safety and efficacy of combination therapy with metformin-sodium-glucose cotransporter-2 inhibitors versus metformin-sulfonylureas in patients with type 2 diabetes. We searched MEDLINE-PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to 15 August 2019 without restriction in the year of publication. We included randomized controlled trials of patients with type 2 diabetes who were on metformin-sodium-glucose cotransporter-2 inhibitors or metformin-sulphonylureas combination therapy at least for a year. The primary endpoints were all-cause mortality and serious adverse events, and the secondary endpoints were cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hypoglycemia, and changes in glycated hemoglobin A1c (HbA1c), body weight, fasting plasma glucose, blood pressure, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. We used a random-effects meta-analysis model to estimate mean differences for continuous outcomes and risk ratio for dichotomous outcomes. We followed PICOS description model for defining eligibility and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for reporting results. Of 3,190 citations, we included nine trials involving 10,974 participants. The pooled analysis showed no significant difference in all-cause mortality (risk ration [RR] = 0.93, 95% CI [0.52, 1.67]), serious adverse events (RR = 0.96, 95% CI [0.79, 1.17]) and adverse events (RR = 1.00, 95% CI [0.99, 1.02]) between the two, but in hypoglycemia (RR = 0.13, 95% CI [0.10, 0.17], P < 0.001). Participants taking metformin-sodium glucose cotransporter-2 inhibitors showed a significantly greater reduction in HbA1c (mean difference [MD] = − 0.10%, 95% CI [− 0.17, − 0.03], body weight (MD = − 4.57 kg, 95% CI [− 4.74, − 4.39], systolic blood pressure (MD = − 4.77 mmHg, 95% CI [− 5.39, − 4.16]), diastolic blood pressure (MD = − 2.07 mmHg, 95% CI [− 2.74, − 1.40], and fasting plasma glucose (MD = − 0.55 mmol/L, 95% CI [− 0.69, − 0.41]), p < 0.001. Combination therapy of metformin and sodium-glucose cotransporter-2 inhibitors is a safe and efficacious alternative to combination therapy of metformin and sulphonylureas for patients with type 2 diabetes who are at risk of cardiovascular comorbidity. However, there remains a need for additional long-term randomized controlled trials as available studies are very limited and heterogeneous.

scholarly journals AB0337 TOFACITINIB MONOTHERAPY OR COMBINED WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS SHOW SIMILAR RETENTION OVER FOUR YEARS. REPORT FROM RHUMADATA ®

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1467.1-1467
Author(s):  
D. Choquette ◽  
L. Bessette ◽  
L. Choquette Sauvageau ◽  
I. Ferdinand ◽  
B. Haraoui ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Real World ◽  
Treatment Initiation ◽  
Retention Rate ◽  
Janus Kinase ◽  
P Value ◽  
Research Support ◽  
Medication Discontinuation ◽  
Kaplan Meier

Background:Since the introduction of biologic agents around the turn of the century, the scientific evidence shows that the majority of agents, independent of the therapeutic target, have a better outcome when used in combination with methotrexate (MTX). In 2014, tofacitinib (TOFA), an agent targeting Janus kinase 1 and 3, has reached the Canadian market with data showing that the combination with MTX may not be necessary [1,2].Objectives:To evaluate the efficacy and retention rate of TOFA in real-world patients with rheumatoid arthritis (RA).Methods:Two cohorts of patients prescribed TOFA was created. The first cohort was formed of patients who were receiving MTX concomitantly with TOFA (COMBO) and the other of patients using TOFA in monotherapy (MONO). MONO patients either never use MTX or were prescribed MTX post-TOFA initiation for at most 20% of the time they were on TOFA. COMBO patients received MTX at the time of TOFA initiation or were prescribed MTX post-TOFA initiation for at least 80% of the time. For all those patients, baseline demographic data definitions. Disease activity score and HAQ-DI were compared from the initiation of TOFA to the last visit. Time to medication discontinuation was extracted, and survival was estimated using Kaplan-Meier calculation for MONO and COMBO cohorts.Results:Overall, 194 patients were selected. Most were women (83%) on average younger than the men (men: 62.6 ± 11.0 years vs. women: 56.9 ± 12.1 years, p-value=0.0130). The patient’s assessments of global disease activity, pain and fatigue were respectively 5.0 ± 2.7, 5.2 ± 2.9, 5.1 ± 3.1 in the COMBO group and 6.2 ± 2.5, 6.5 ± 2.6, 6.3 ± 2.8 in the MONO group all differences being significant across groups. HAQ-DI at treatment initiation was 1.3 ± 0.7 and 1.5 ± 0.7 in the COMBO and MONO groups, respectively, p-value=0.0858. Similarly, the SDAI score at treatment initiation was 23.9 ± 9.4 and 25.2 ± 11.5, p-value=0.5546. Average changes in SDAI were -13.4 ± 15.5 (COMBO) and -8.9 ± 13.5 (MONO), p-value=0.1515, and changes in HAQ -0.21 ± 0.63 and -0.26 ± 0.74, p-value 0.6112. At treatment initiation, DAS28(4)ESR were 4.4 ± 1.4 (COMBO) and 4.6 ± 1.3 (MONO), p-value 0.5815, with respective average changes of -1.06 ± 2.07 and -0.70 ± 1.96, p-value=0.2852. The Kaplan-Meier analysis demonstrated that the COMBO and MONO retention curves were not statistically different (log-rank p-value=0.9318).Conclusion:Sustainability of TOFA in MONO or COMBO are not statistically different as are the changes in DAS28(4)ESR and SDAI. Despite this result, some patients may still benefit from combination with MTX.References:[1]Product Monograph - XELJANZ ® (tofacitinib) tablets for oral administration Initial U.S. Approval: 2012.[2] Reed GW, Gerber RA, Shan Y, et al. Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors as Monotherapy and Combination Therapy for Treatment of Rheumatoid Arthritis [published online ahead of print, 2019 Nov 9].Rheumatol Ther. 2019;6(4):573–586. doi:10.1007/s40744-019-00177-4.Disclosure of Interests:Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Loïc Choquette Sauvageau: None declared, Isabelle Ferdinand Consultant of: Pfizer, Abbvie, Amgen, Novartis, Speakers bureau: Pfizer, Amgen, Boulos Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, and UCB, Consultant of: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Pfizer, Roche, and UCB, Speakers bureau: Pfizer, Speakers bureau: Amgen, BMS, Janssen, Pfizer, and UCB, Frédéric Massicotte Consultant of: Abbvie, Janssen, Lilly, Pfizer, Speakers bureau: Janssen, Jean-Pierre Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica, Speakers bureau: TRB Chemedica and Mylan, Jean-Pierre Raynauld Consultant of: ArthroLab Inc., Marie-Anaïs Rémillard Consultant of: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Paid instructor for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Diane Sauvageau: None declared, Édith Villeneuve Consultant of: Abbvie, Amgen, BMS, Celgene, Pfizer, Roche, Sanofi-Genzyme,UCB, Paid instructor for: Abbvie, Speakers bureau: AbbVie, BMS, Pfizer, Roche, Louis Coupal: None declared

scholarly journals The Clinical Effect of Oral Vitamin D2 Supplementation on Psoriasis: A Double-Blind, Randomized, Placebo-Controlled Study

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Wareeporn Disphanurat ◽  
Wongsiya Viarasilpa ◽  
Panlop Chakkavittumrong ◽  
Padcha Pongcharoen
Keyword(s):  
Vitamin D ◽  
Placebo Group ◽  
Adverse Events ◽  
Clinical Effect ◽  
Vitamin D Supplementation ◽  
P Value ◽  
Vitamin D2 ◽  
Oral Vitamin ◽  
Pasi Score ◽  
The Mean

Background. There are limited randomized controlled trials of oral vitamin D supplementation in psoriasis, especially in Asia, and the results are inconclusive. Objective. To investigate the clinical effect of oral vitamin D supplementation on psoriasis. Methods. Patients with psoriasis were randomized to receive vitamin D2 60,000 IU or similar-looking placebo pills once every 2 weeks for 6 months. The primary outcome was improvement of the Psoriasis Area and Severity Index (PASI) score at 3 and 6 months after treatment. Serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone, and C-reactive protein and adverse events were monitored. The chi-square test, Fisher’s exact test, Student’s t-test, and Spearman’s correlation analysis were used in statistical analysis. Results. Of 50 subjects screened, 45 were eligible and randomized to the oral vitamin D2 group (n=23) or placebo group (n=22). At enrollment, the mean PASI score was 4.45, and 26.7% of patients had vitamin D deficiency. At 3 months, the oral vitamin D2 group had significantly higher PASI improvement than the placebo group (mean PASI improvement: 1.43 versus [vs.] -0.33, p-value=0.034; mean %PASI improvement: 34.21% vs. -1.85%, p-value=0.039). The mean serum 25(OH)D level was significantly higher in the oral vitamin D group than in the placebo group (27.4 vs. 22.4 ng/mL, p-value=0.029). Serum 25(OH)D concentrations were significantly inversely correlated with PASI scores at the 6-month follow-up. No major adverse event was observed overall. Conclusion. Oral vitamin D2 supplementation in patients with psoriasis increased the serum vitamin D level and significantly improved the treatment outcome without increasing adverse events. Trial Registration. This trial is registered with Thai Clinical Trials Registry TCTR20180613001.

191 Association of immune related adverse events with the efficacy of immune checkpoint inhibitors in metastatic renal cell carcinoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A205-A206
Author(s):  
Vasilii Bushunow ◽  
Leonard Appleman ◽  
Roby Thomas
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier

BackgroundImmune checkpoint inhibitors (ICI) are first-line therapy for tumors including metastatic renal cell carcinoma (mRCC). Use of ICI is complicated by diverse immune-related adverse events (irAEs), which can add significant morbidity but are also associated with improved efficacy of therapy.1 2 Risk factors for development of irAE are still poorly understood. We hypothesized that patients with mRCC treated with ICI as first-line therapy have higher rates of developing irAE’s than patients previously treated with other therapies.MethodsWe conducted a single-institution, retrospective medical record review of patients with mRCC treated with immune-checkpoint inhibitors from March 2011 through April 15, 2020. We identified therapy duration, and presence, severity, and treatment of adverse events. We defined overall survival as time elapsed from date of diagnosis until death or until completion of study. We classified severity of adverse events according to CTCAE guidelines. Statistical methods included univariate Cox proportional hazards and logistic regression models, and Kaplan-Meier curves were plotted for subgroups.ResultsA total of 64 unique charts were reviewed. 18 patients (28%) of patients were treated with ICI as first-line therapy. 28 patients (44%) experienced immune-related adverse events with a total of 40 irAE’s identified. Most irAE were grade I-II (78%), with 7 (17%) grade III and 1 (2.4%) grade IV irAE’s. Most common sites were skin (29%), thyroid (20%) and gastrointestinal (15%). Patients with irAE had increased survival compared to those who did not have irAE (median survival not reached, vs 139 weeks, p=0.0004) (figure 1). This finding remained after excluding patients who had only experienced dermatologic irAE (median survival not reached in non-derm irAE subgroup, vs 144 weeks for dermatologic or no irAE, p=0.01) (figure 2). Patients treated with ICI as first line therapy had greater rates of developing irAE (72%) than those who had prior therapies (32%) (OR 5.4; p = 0.006). There was no association between histology type and rate of irAE.Abstract 191 Figure 1Kaplan-Meier survival plot of OS between patients with any irAE and those without any irAEAbstract 191 Figure 2Kaplan-Meier survival plot of OS between patients with non-dermatologic irAE and those without any irAE or only dermatologic irAEConclusionsThe development of irAE’s in patients with mRCC treated with ICI is associated with longer survival. This study joins the growing body of evidence showing that presence of irAE’s is associated with increased treatment efficacy. Use of ICI as first-line therapy is associated with higher risk of irAE. Given growing use of ICI as first-line therapy, further study to predict onset and severity of irAE’s is required.AcknowledgementsHong Wang, PhD, for statistical support.Ethics ApprovalThis study was approved by the University of Pittsburgh Institutional Review Board. Approval number STUDY19100386.ReferencesElias R, Yan N, Singla N, Levonyack N, Formella J, Christie A, et al. Immune-related adverse events are associated with improved outcomes in ICI-treated renal cell carcinoma patients. J Clin Oncol 2019;37(7):S645.Verzoni E, Cartenì G, Cortesi E, et al. Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program. J Immunother Cancer 2019;7(1):99.

scholarly journals Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure

Blood ◽  
2012 ◽  
Vol 119 (15) ◽  
pp. 3403-3412 ◽  
Author(s):  
H. Jean Khoury ◽  
Jorge E. Cortes ◽  
Hagop M. Kantarjian ◽  
Carlo Gambacorti-Passerini ◽  
Michele Baccarani ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Phase 1 ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
Cytogenetic Response ◽  
Abl Tyrosine Kinase ◽  
Kaplan Meier

Bosutinib, a dual Src/Abl tyrosine kinase inhibitor (TKI), has shown potent activity against chronic myeloid leukemia (CML). This phase 1/2 study evaluated the efficacy and safety of once-daily bosutinib 500 mg in leukemia patients after resistance/intolerance to imatinib. The current analysis included 118 patients with chronic-phase CML who had been pretreated with imatinib followed by dasatinib and/or nilotinib, with a median follow-up of 28.5 months. In this subpopulation, major cytogenetic response was attained by 32% of patients; complete cytogenetic response was attained by 24%, including in one of 3 patients treated with 3 prior TKIs. Complete hematologic response was achieved/maintained in 73% of patients. On-treatment transformation to accelerated/blast phase occurred in 5 patients. At 2 years, Kaplan-Meier–estimated progression-free survival was 73% and estimated overall survival was 83%. Responses were seen across Bcr-Abl mutations, including those associated with dasatinib and nilotinib resistance, except T315I. Bosutinib had an acceptable safety profile; treatment-emergent adverse events were primarily manageable grade 1/2 gastrointestinal events and rash. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option for patients with chronic-phase CML after treatment with multiple TKIs. This trial was registered at www.clinicaltrials.gov as NCT00261846.

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