scholarly journals Comparison of second-line therapy in IVIg-refractory Kawasaki disease: a systematic review

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Courtney B. Crayne ◽  
Chace Mitchell ◽  
Timothy Beukelman
Keyword(s):  
Systematic Review ◽  
Kawasaki Disease ◽  
Outcome Data ◽  
Second Line ◽  
Inclusion Criteria ◽  
Second Line Therapy ◽  
Ivig Infusion ◽  
English Only ◽  
Line Therapy ◽  
Mesh Terms

Abstract Background Evidence remains contradictory regarding second-line therapy in patients with Kawasaki disease (KD) refractory to initial intravenous immunoglobulin (IVIg). The objective of this study aims to evaluate the efficacy and safety of three treatments [i.e. a second IVIg infusion, methylprednisolone (IVMP), and infliximab (IFX)] in patients with refractory KD. Methods A systematic search of PubMed, Embase, Cochrane, and ClinicalTrials.gov using predefined MeSH terms was performed from 1990 through 2017. Relevance screening was performed by two independent reviewers. Inclusion criteria included English-only, original clinical data. Eight studies met the inclusion criteria. Fever resolution, coronary lesions, and adverse event outcomes were extracted and pooled for analysis. Results Of the 388 patients included from the 8 studies analyzed, a majority received a second IVIg dose (n = 263, 68%). Fever resolution was comparable between IVIg (72%) and IVMP (73%). IFX (88%) significantly increased fever resolution by approximately 20% compared to IVIg re-dose (RR 1.2; [95% CI: 1.1–1.4]; p = 0.03) and IVMP (RR 1.2; [95% CI: 1.0–1.5]; p = 0.04). Clinical significance of differences in coronary outcomes remains unclear. Conclusions This combined analysis was limited due to variability in design and data reporting methods between the studies and risk of bias. In the absence of a clinical trial, IFX monotherapy as second-line treatment should be considered in patients who fail to respond to initial IVIg. This conclusion is based on a systematic review of the literature with pooled outcome data analysis suggesting IFX is more effective in fever resolution compared to a second IVIg dose and IVMP.

Abstract O.43: Partial and Complete Non-response to Intravenous Immunoglobulin in the Acute Treatment of Kawasaki Disease: A Matched Case-control Study

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Mallory L Downie ◽  
Cedric Manlhiot ◽  
Giuseppe A Latino ◽  
Tanveer H Collins ◽  
Nita Chahal ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Temperature Profile ◽  
Intravenous Immunoglobulin ◽  
Ivig Treatment ◽  
Second Line ◽  
Second Line Therapy ◽  
Ivig Infusion ◽  
Total N ◽  
Line Therapy ◽  
Hourly Temperature

Introduction: Patients non-responsive to intravenous immunoglobulin (IVIG) in the acute phase of Kawasaki disease (KD) are usually considered a single patient group; however, response to second-line therapy varies significantly. We sought to characterize the pattern of temperature response to IVIG infusion, and to define whether the profile was associated with response to second-line therapy in non-responders. Methods: Patients non-responsive to IVIG (temperature >37.5°C >24 hours after the end of IVIG) were identified. Each IVIG non-responder was matched to a IVIG-responsive control patient of the same age and gender, and with the same duration of fever prior to IVIG. Hourly temperature profiles were obtained from immediately before the start of the IVIG infusion until complete defervescence. Results: n=202 patients non-responsive to IVIG were matched (total n=404). For all, temperature reduced by 0.17 (0.06)°C per g/hr IVIG (p=0.006). Important variation in the temperature profile was noted for patients who did not defervesce with IVIG. Thus, non-responders were further classified as partial non-responders (31%) (temperature decreased to <37.5°C within 24 hours of the end of IVG infusion, but fever recurred) and complete non-responders (69%) (temperature consistently >37.5°C throughout IVIG treatment). The temperature profile during IVIG infusion was similar between complete and partial responders [(EST: -0.26 (0.11)°C per g/hr IVIG (p=0.02) for complete responders vs. EST: -0.20 (0.09)°C (p=0.02) for IVIG responders (responders vs. partial non-responders, p=0.65)]. In complete non-responders, IVIG was not associated with significant decreases in temperature (EST: -0.11 (0.14)°C, p=0.43). Factors associated with complete (vs. partial) non-response included presence of infectious symptoms, differences in multiple laboratory values and IVIG brand. Defervescence in partial non-responders was achieved with a second IVIG dose for 88% of patients compared to only 47% of complete non-responder (p<0.001). Conclusions: Non-response to initial IVIG can be further characterized by the temperature profile, and complete non-responders may require more aggressive second-line therapy.

scholarly journals P1011CARDIOVASCULAR OUTCOME TRIALS (CVOT) USING NEW ANTI-DIABETIC AGENTS IN CHRONIC KIDNEY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Nadia Sarween ◽  
Nuvreen Phagura ◽  
Adnan Sharif
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Meta Analysis ◽  
Second Line ◽  
Second Line Therapy ◽  
Receptor Agonists ◽  
Line Therapy

Abstract Background and Aims The latest consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommends metformin and lifestyle intervention as first-line therapy for type 2 diabetes. Second-line therapy recommendation is the use sodium-glucose cotransporter 2 (SGLT 2) inhibitors (if estimated glomerular filtration rate [eGFR] is adequate) or GLP-1 receptor agonists if eGFR is inadequate (or SGLT-2 inhibitors not tolerated). No recommendation is made for dipeptidyl peptidase-4 (DPP-4) inhibitors. Therapy choices are limited for patients with both type 2 diabetes and moderate-to-severe chronic kidney disease (CKD) and it is unclear from published data if observed cardiovascular benefits of new anti-diabetic agents extend to the CKD cohort. The aim of this study was to undertake a systematic review of all published CVOT trials using new anti-diabetic agents (GLP-1 receptor agonist, DPP-4 inhibitor, SGLT 2 inhibitor). Method We searched MEDLINE (via PubMed and the Cochrane Central Register of Controlled Trials) up to 1st December 2019. Data was stratified by trial entry eGFR into normal (eGFR ≥60 ml/min) and CKD (eGFR &lt;60 ml/min), with data extracted for primary major cardiovascular event (MACE) rates such as cardiovascular death, stroke and/or myocardial infarct. A meta-analysis with random effects model was performed to estimate overall hazard ratios (HRs) for MACE with new anti-diabetic agents stratified by eGFR. Inter-study heterogeneity was assessed with the I2 index and Cochran’s Q test. Results We analysed 13 studies from 16 that were eligible after our search strategy, with 2 excluded due lack of data stratified by eGFR and 1 excluded due to combined MACE/renal outcomes. The studies (GLP-1 agonists, n=6; DPP-4 inhibitors, n=4; SGLT 2 inhibitors, n=3) had a combined total of 128,266 participants (22.1% with eGFR &lt;60 ml/min). HR for MACE with GLP-1 agonists for participants with eGFR ≥60 ml/min was 0.87 (95% CI 0.77-0.98; p=0.02) and for participants with eGFR &lt;60 ml/min was 0.90 (95% CI 0.78-1.04; p=0.14). HR for MACE with DPP-4 inhibitors for participants with eGFR ≥60 ml/min was 0.99 (95% CI 0.92-1.07; p=0.86) and for participants with eGFR &lt;60 ml/min was 0.99 (95% CI 0.91-1.08; p=0.86). HR for MACE with SGLT 2 inhibitors for participants with eGFR ≥60 ml/min was 0.98 (95% CI 0.88-1.10; p=0.78) and for participants with eGFR &lt;60 ml/min was 0.82 (95% CI 0.70-0.96; p=0.01). Significant heterogeneity was observed in the meta-analyses for each new anti-diabetic therapy drug class stratified by eGFR. Conclusion Among the new anti-diabetic agents, our study suggests efficacy for prevention of MACE in the setting of CKD exists only for SGLT 2 inhibitors and not with GLP-1 receptor agonists or DPP-4 inhibitors. Targeted CVOT studies incorporating participants with diabetes and CKD are critical to guide glycaemic management in these high-risk patients. Until then, we suggest recommendations for second-line therapy in patients with type 2 diabetes and renal impairment should be amended to reflect the current evidence base supporting prevention of MACE with SGLT 2 inhibitors versus other new anti-diabetic agents.

scholarly journals Beyond second-line therapy in patients with metastatic colorectal cancer: a systematic review

2018 ◽  
Vol 29 (4) ◽  
pp. 835-856 ◽  
Author(s):  
D. Arnold ◽  
G.W. Prager ◽  
A. Quintela ◽  
A. Stein ◽  
S. Moreno Vera ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Metastatic Colorectal Cancer ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

Paclitaxel, ifosfamide & cisplatin (TIP) as second-line therapy for germ cell tumors (GCT):Long-term follow-up and expansion cohort.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 386-386
Author(s):  
Jack Patrick Gleeson ◽  
Andrea Knezevic ◽  
Maria Bromberg ◽  
Sujata Patil ◽  
Joel Sheinfeld ◽  
...  
Keyword(s):  
Risk Factors ◽  
Second Line ◽  
Inclusion Criteria ◽  
Second Line Therapy ◽  
Original Cohort ◽  
Line Therapy ◽  
Long Term Follow Up ◽  
Expansion Cohort

386 Background: TIP was established as an effective second-line regimen in a phase II study of 46 patients (pts) with relapsed GCT and favorable risk factors (Kondagunta, JCO 2005). Here, we report long-term follow up from this trial and outcomes for additional pts who subsequently received TIP off protocol. Methods: Eligiblepts included those who received TIP on the original phase II trial (original cohort) or who received TIP following study closure but would have met the trial inclusion criteria (expansion cohort). An additional exploratory cohort was comprised of pts with unfavorable risk factors who would not have met the original trial criteria. The primary endpoint was favorable response rate (FRR), which included complete responses (CR) and partial responses with negative markers (PR-). Overall survival (OS), progression free survival (PFS), and relapse rates were also evaluated. Results: Of 204 pts who received TIP for GCT at our institution from 5/1994 to 7/2019, 87 (original cohort, n=46; expansion cohort, n=41) met the inclusion criteria and were evaluable for the main analysis. An additional 17 pts were analyzed in the exploratory cohort (unfavorable risk factor: PR- lasting <6months or IR, n=13; prior adjuvant therapy, n=4). 100 pts were excluded due to participation in an ongoing clinical trial (n=17), receipt of TIP as their first regimen (n=74) or in the adjuvant (n=3) setting, or insufficient data (n=6). Baseline characteristics and efficacy data are displayed in the table below. In the main cohort, 70/87 (80%) pts achieved a favorable response. With median follow-up of 10.2 years (yrs) [original, 14.3 yrs; expansion 6.5 yrs] 26 deaths were observed. 5yr and 10yr OS rates were 72% (95% CI 63, 83) and 69% (95% CI 59, 80) respectively. 5yr and 10yr PFS were 70% (95% CI 61, 81) and 67% (95% CI 57, 78). In the exploratory cohort, there were 7 deaths at median follow-up of 6.2 yrs with 5yr OS of 56% (95% CI 35, 87) and 5yr PFS of 59% (95% CI 40, 88). Conclusions: Long-term follow-up and additional experience supports the use of TIP as second-line therapy for GCT. Similar outcomes were seen for our exploratory and main cohorts, suggesting benefit with TIP outside of those with a favorable prognosis. [Table: see text]

scholarly journals Second line therapy in malignant pleural mesothelioma: A systematic review

Lung Cancer ◽  
2015 ◽  
Vol 89 (3) ◽  
pp. 223-231 ◽  
Author(s):  
Wieneke A. Buikhuisen ◽  
Birgitta I. Hiddinga ◽  
Paul Baas ◽  
Jan P. van Meerbeeck
Keyword(s):  
Systematic Review ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

scholarly journals Clinical and Pathological Characteristics of Metastatic Renal Cell Carcinoma Patients Needing a Second-Line Therapy: A Systematic Review

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3634
Author(s):  
Nicola Longo ◽  
Marco Capece ◽  
Giuseppe Celentano ◽  
Roberto La Rocca ◽  
Gianluigi Califano ◽  
...  
Keyword(s):  
Systematic Review ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Group Performance ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

A high percentage of patients with metastatic renal cell carcinoma (mRCC) require a second-line option. We aimed to summarize available evidences about the clinicopathological profile of mRCC patients who receive a second-line therapy. A systematic review was performed in August 2020. We included papers that met the following criteria: original research; English language; human studies; enrolling mRCC patients entering a second-line therapy. Twenty-nine studies enrolling 7650 patients (73.5% male, mean age: 55 to 70 years) were included. Clear cell histology was reported in 74.4% to 100% of cases. Tyrosine kinase inhibitors, immunotherapy, bevacizumab, mTOR inhibitors, and chemotherapy were adopted as first line option in 68.5%, 29.2%, 2.9%, 0.6%, and 0.2% of patients, respectively. Discontinuation of first-line therapy was due to progression and toxicity in 18.4% to 100% and in 17% to 48.8% of patients, respectively. Eastern Cooperative Oncology Group performance status score was 0 or 1 in most cases. Most prevalent prognostic categories according to the International Metastatic RCC Database Consortium and Memorial Sloan–Kettering Cancer Centre score were intermediate and good. About 77.8% of patients harboured ≥2 metastatic sites. In conclusion, patients who enter a second-line therapy are heterogeneous in terms of a clinical-pathological profile. Tailoring of second-line treatment strategies is strongly advocated.

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