scholarly journals Modeling Diagnostic Strategies to Manage Toxic Adverse Events following Cancer Immunotherapy

2021 ◽  
pp. 0272989X2110027
Author(s):  
Frederik van Delft ◽  
Mirte Muller ◽  
Rom Langerak ◽  
Hendrik Koffijberg ◽  
Valesca Retèl ◽  
...  
Keyword(s):  
Palliative Care ◽  
Adverse Events ◽  
Scenario Analysis ◽  
Real World ◽  
Model Calibration ◽  
Positive Test ◽  
Test Accuracy ◽  
Test Sensitivity ◽  
False Positive Test ◽  
Test Outcomes

Background Although immunotherapy (IMT) provides significant survival benefits in selected patients, approximately 10% of patients experience (serious) immune-related adverse events (irAEs). The early detection of adverse events will prevent irAEs from progressing to severe stages, and routine testing for irAEs has become common practice. Because a positive test outcome might indicate a clinically manifesting irAE that requires treatment to (temporarily) discontinue, the occurrence of false-positive test outcomes is expected to negatively affect treatment outcomes. This study explores how the UPPAAL modeling environment can be used to assess the impact of test accuracy (i.e., test sensitivity and specificity), on the probability of patients entering palliative care within 11 IMT cycles. Methods A timed automata-based model was constructed using real-world data and expert consultation. Model calibration was performed using data from 248 non–small-cell lung cancer patients treated with nivolumab. A scenario analysis was performed to evaluate the effect of changes in test accuracy on the probability of patients transitioning to palliative care. Results The constructed model was used to estimate the cumulative probabilities for the patients’ transition to palliative care, which were found to match real-world clinical observations after model calibration. The scenario analysis showed that the specificity of laboratory tests for routine monitoring has a strong effect on the probability of patients transitioning to palliative care, whereas the effect of test sensitivity was limited. Conclusion We have obtained interesting insights by simulating a care pathway and disease progression using UPPAAL. The scenario analysis indicates that an increase in test specificity results in decreased discontinuation of treatment due to suspicion of irAEs, through a reduction of false-positive test outcomes.

Naldemedine for opioid-induced constipation in patients receiving palliative care: A real-world registry study (Phase-R OIC Study).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11582-11582
Author(s):  
Masaki Shimizu ◽  
Takaomi Kessoku ◽  
Hiroto Ishiki ◽  
Tetsuya Matsuura ◽  
Yusuke Hiratsuka ◽  
...  
Keyword(s):  
Palliative Care ◽  
Clinical Practice ◽  
Adverse Events ◽  
Real World ◽  
Bowel Movement ◽  
Cancer Site ◽  
Registry Study ◽  
Spontaneous Bowel Movement ◽  
Palliative Care Teams ◽  
Grade 3

11582 Background: Although naldemedine, a new peripherally-acting mu-opioid receptor antagonist, was approved for the management of opioid-induced constipation (OIC), its safety and effectiveness in real world clinical practice is unknown. Methods: We conducted a real world registry study in 14 hospital palliative care teams and inpatient palliative care units in Japan between April and December 2018. Consecutive cancer patients who received naldemedine for OIC were enrolled in a 7-day observational study. All treatment and assessment procedures were performed according to the accepted clinical practice. The primary outcome of the study was the proportion of patients who experienced spontaneous bowel movement within 24 hours after the initial administration of naldemedine. Adverse events, which indicated a possible or stronger causal relationship with naldemedine treatment, were reported according to the Common Terminology Criteria for Adverse Events (CTCAE) ver 4.0. Results: Overall, 204 patients were enrolled in the study. The mean age of the patients was 63±14 years, and 103 (50.5%) were male. The most common primary cancer site was lung (23.5%), followed by gastrointestinal (13.7%), and urological organs (9.3%). The proportion of patients undergoing active cancer treatment was 59.9%. Oxycodone was the most frequently used regular opioid (n = 115, 56.4%), and the median oral morphine-equivalent daily dose of opioids was 30 mg (interquartile range: 20-60 mg). Magnesium oxide (64.2%) and Senna (17.2%) were used as concomitant laxatives. All patients received 0.2 mg of naldemedine orally once daily. Most patients (90.2%) completed the 7-day observation. In 146 patients, spontaneous bowel movement was observed within 24 hour after the first administration of naldemedine (71.6%, 95% confidence interval 65.4-77.8%). Nearly two-thirds of the patients experienced increased frequency of spontaneous bowel movement in the week after naldemedine administration. The most prevalent adverse events were diarrhea (CTCAE grade 1-2, 35 cases; grade 3, 1 case) and abdominal pain (CTCAE grade 1-2, 10 cases; grade 3, 1 case). No serious adverse events including gastrointestinal perforation were reported. Conclusions: Naldemedine for opioid-induced constipation is safe and effective in the real world oncology and palliative care settings. Clinical trial information: UMIN000031381.

scholarly journals Internal Impingement of the Shoulder: A Risk of False Positive Test Outcomes in External Impingement Tests?

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Tim Leschinger ◽  
Christopher Wallraff ◽  
Dirk Müller ◽  
Matthias Hackenbroch ◽  
Henning Bovenschulte ◽  
...  
Keyword(s):  
Positive Test ◽  
Positive Test Result ◽  
Mechanical Contact ◽  
Open Mri ◽  
Pathologic Condition ◽  
Shoulder Impingement ◽  
Internal Impingement ◽  
False Positive Test ◽  
Test Outcomes ◽  
Test Result

Background. External impingement tests are considered as being particularly reliable for identifying subacromial and coracoid shoulder impingement mechanisms. The purpose of the present study was to evaluate if these tests are likely to provoke an internal shoulder impingement mechanism which, in cases of a pathologic condition, can lead to a positive test result.Method. In 37 subjects, the mechanical contact between the glenoid rim and the rotator cuff (RC) was measured quantitatively and qualitatively in external impingement test positions using an open MRI system.Results. Mechanical contact of the supraspinatus with the posterosuperior glenoid was present in 30 subjects in the Neer test. In the Hawkins test, the subscapularis was in contact with the anterosuperior glenoid in 33 subjects and the supraspinatus in 18. In the horizontal impingement test, anterosuperior contact of the supraspinatus with the glenoid was identified in 35 subjects.Conclusion. The Neer, Hawkins, and horizontal impingement tests are likely to provoke the mechanism of an internal shoulder impingement. A posterosuperior internal impingement mechanism is being provoked predominately in the Neer test. The Hawkins test narrows the distance between the insertions of the subscapularis and supraspinatus and the anterosuperior labrum, which leads to an anterosuperior impingement mechanism.

267-OR: Reduction in Self-Reported Adverse Events Related to Severe Hypoglycemia in Individuals Using a Predictive Low Glucose System: Results from a Real-World Setting

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 267-OR
Author(s):  
HARSIMRAN SINGH ◽  
MICHELLE L. MANNING ◽  
MOLLY MCELWEE-MALLOY ◽  
STEPHANIE HABIF
Keyword(s):  
Adverse Events ◽  
Real World ◽  
Severe Hypoglycemia ◽  
Real World Setting ◽  
Glucose System ◽  
Low Glucose

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 AB0649 REAL WORLD EFFICACY OF SECUKINUMAB: A SINGLE CENTRE EXPERIENCE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1619-1620
Author(s):  
G. Kasavkar ◽  
T. Blake ◽  
N. Gullick
Keyword(s):  
Clinical Trial ◽  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Adverse Events ◽  
Real World ◽  
Certolizumab Pegol ◽  
Tender Joint Count ◽  
Inadequate Response ◽  
Technology Appraisal ◽  
New Onset

Background:Secukinumab was approved by NICE for patients with active Ankylosing Spondylitis and Psoriatic Arthritis in 2017. Clinical trial data suggests secukinumab is a useful treatment option in both conditions, but often real world experience differs greatly from clinical trial results. In addition, patients with more refractory disease are often excluded from clinical trials.Objectives:To assess the response to secukinumab in patients with seronegative spondyloarthropathy receiving treatment at University Hospital Coventry and WarwickshireMethods:Patients starting secukinumab at UHCW were identified from the Blueteq funding database. Medical notes were reviewed retrospectively to assess response rates using BASDAI responses in Ankylosing spondylitis and PsARC responses in PsA. Patients who had previously had inadequate response to TNF inhibitors (PsA only) and severe psoriasis received 300mg secukinumab monthly; the remainder were prescribed 150mg monthly.Results:146 patients commenced secukinumab between June 2017 and January 2020 and had outcome data recorded. 73 patients (50%) had received previous biologic agents prior to secukinumab exposure. Patients with Ankylosing spondylitis had high BASDAI (6.8±1.4) and spinal pain (7.5±1.4). 48 patients had an initial response to treatment as per outcome measures done before and after Secukinumab inception. Secukinumab was effective in 89 patients (94%), and 87 (91%) continued treatment.In psoriatic arthritis, despite high levels of activity at baseline (mean tender joint count 10±8; swollen joint count 6±3) and 65% prior biologic exposure; high rates of response were seen. The majority of patients have continued treatment. Secukinumab was well tolerated in both patient groups with low rates of discontinuation due to adverse events (8 patients, 5%). Adverse events included recurrent infection (3), rash (1), mouth ulcers (1), vertigo (1), new onset cancer (1) and new onset Crohn’s (1) although rates were low overall. Patients with pre-existing uveitis did not develop exacerbations but low numbers of patients with prior uveitis were treated.PsA (n=51)AS (n=95)Age in years, mean (SD)53 (13)49(12)Male sex, n (%)21 (41)62 (65)Disease duration in years, mean (SD)8 (8)10.9 (9.2)Previous biologic exposure, n (%)30 (65)43 (48)Number of prior biologics, median (range)1 (1-4)1 (1-4)Responder, n (%)37 (72)*89 (93)Discontinuation, n(%)12 (24)8 (8.5)Adverse events62Lack of efficacy64Other02*Response could not be assessed in 3/51 PsA patients due to insufficient clinical data; these patients have been recorded as non respondersConclusion:Secukinumab demonstrates high levels of efficacy even in a cohort of patients with longstanding PSA and AS with high rates of inadequate responses to other biologics.Secukinumab is well tolerated with low rates of discontinuation due to adverse events.References:Certolizumab pegol and secukinumab for treating active psoriatic arthritis after inadequate response to DMARDs Technology appraisal guidance [TA445]Secukinumab for active ankylosing spondylitis after treatment with non-steroidal anti-inflammatory drugs or TNF-alpha inhibitors Technology appraisal guidance [TA407]Disclosure of Interests:None declared

P089 REAL-WORLD EXPERIENCE: CLINICAL AND ENDOSCOPIC EFFECTIVENESS OF STANDARD VEDOLIZUMAB DOSING AND MODIFIED MAINTENANCE DOSING IN PATIENTS WITH MODERATE-SEVERE CROHN’S DISEASE

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S75-S75
Author(s):  
Scott D Lee ◽  
Anand Singla ◽  
Caitlin Kerwin ◽  
Kindra Clark-Snustad
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Real World ◽  
Clinical Remission ◽  
Mucosal Healing ◽  
Clinical Disease ◽  
Endoscopic Remission ◽  
Starting Dose

Abstract Background Vedolizumab (VDZ) is an effective treatment for Crohn’s disease (CD); however, inadequate and loss of response is common. Pivotal VDZ trials evaluated alternative dosing intervals, demonstrating numeric but not statistical superiority in efficacy as compared to FDA-approved dosing. The safety and effectiveness of FDA-approved and modified-dosing schedules in a real-world population are unknown. We aimed to evaluate clinical and endoscopic effectiveness & safety of standard and modified maintenance VDZ dosing in a real world cohort. Methods We retrospectively reviewed CD patients (pts) treated with &gt;3 months VDZ, assessing Harvey Bradshaw Index (HBI), Simple Endoscopic Score for Crohn’s disease (SESCD), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), C-reactive protein (CRP), albumin and hematocrit prior to and following standard VDZ dosing, and prior to and following modified VDZ maintenance dosing. We measured duration on therapy and adverse events. Results We identified 226 eligible pts, mean age 41.5 years, 55.3% female, median disease duration 10 years, 88.9% with prior biologic exposure. Mean duration on VDZ was 28.3 months. Standard VDZ dosing: 61.5% of pts with active clinical disease and adequate follow up data achieved clinical response after 3–12 months; 41.0% had clinical remission. 51.9% of pts with active endoscopic disease and adequate follow up data achieved mucosal improvement; 42.3% had endoscopic remission; 26.0% had mucosal healing after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized CRP after 3–12 months. Modified maintenance dosing: 72 non-remitters to standard VDZ dosing received modified VDZ maintenance dosing. 51.5% of pts with active clinical disease prior to starting dose modification and adequate follow up data achieved clinical response after 3–12 months of modified maintenance dosing; 42.4% had clinical remission. 22.2% of pts with SESCD ≥3 prior to starting dose modification achieved mucosal improvement after 3–24 months; 22.2% had mucosal healing. 26.7% of pts with SESCD ≥4 prior to starting modified dosing had endoscopic remission after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized their CRP after 3–12 months. Safety: 82.7% of pts reported ≥1 adverse events, most commonly infection and worsening CD symptoms. Discussion Standard VDZ dosing resulted in clinical and endoscopic improvement in pts with moderate-severe CD, with prior exposure to multiple advanced therapies. For non-remitters to standard dosing, modified VDZ maintenance dosing improved clinical disease activity in ∼50% of pts and improved endoscopic disease activity in ∼20% of pts, suggesting that for pts who did not achieve remission with standard VDZ dosing, modified VDZ dosing may result in clinical and endoscopic improvement.

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