The efficacy and safety of anti-PD-1/PD-L1 antibodies for treatment of advanced or refractory cancers: A meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23075-e23075 ◽  
Author(s):  
Tengfei Zhang ◽  
Ruitai Fan ◽  
Ni Shi ◽  
Wang Ma

e23075 Background: Immunotherapy based on anti-PD-1 (Programmed death 1)/PD-L1 (PD-1 Ligand 1) antibodies have achieved significant successes from bench to clinic. In this study, we systematically evaluate the overall efficacy and safety of current anti-PD-1/PD-L1 antibodies for treatment of patients with advanced or refractory cancer. Methods: Clinical trials reporting response or safety of anti-PD-1/PD-L1 antibodies for advanced or refractory cancer patients published were searched in PubMed and EMBASE database. Meta-analyses using random effects models were used to calculate the overall estimate. Results: Fifty-one trials including 6,800 patients were included. The overall response rates for melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) were 29% (95% CI: 1.53-2.41), 21% (95% CI: 17%-25%) and 21% (95% CI: 16%-27%) respectively. While the overall adverse effects rate for melanoma, NSCLC, RCC were 16% (95% CI: 6%-28%), 11% (95% CI: 8%-14%) and 20% (95% CI: 11%-32%) respectively. Tumor PD-L1 expression and patient smoking status might serve as biomarkers to predict response of anti-PD-1/PD-L1 antibody treatment. Compared to tumors with negative PD-L1 expression, tumors with positive PD-L1 expression had a significantly higher clinical response rate (41.4% versus 26.5%) with RR = 1.92 (95% CI: 1.53-2.41, P< 0.001). Smoker patients also showed a significantly higher response rate (33.7%) than patients who never smoked (4.2%) with RR = 6.02 (95% CI: 1.22-29.75, P= 0.028). Nivolumab and Pembrolizumab were associated with significantly increased response rate (RR = 2.89, 95% CI: 2.46-3.40, P< 0.001), reduced death risk (HR = 0.53; 95% CI: 0.48-0.57; P< 0.001), and decreased adverse effect rate (RR = 0.49, 95% CI: 0.30-0.80, P= 0.004) compared with other therapies. Conclusions: Anti-PD-1/PD-L1 antibodies have high response rates and low adverse effect rates for advanced or refractory cancers. PD-L1 expression was associated with better clinical response of anti-PD-1/PD-L1 antibody based immunotherapy.

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1020
Author(s):  
Ching-Yi Chen ◽  
Wang-Chun Chen ◽  
Chih-Cheng Lai ◽  
Tzu-Ping Shih ◽  
Hung-Jen Tang

This systematic review and meta-analysis of randomized controlled trials (RCTs) compared the clinical efficacy and safety of anti-MRSA cephalosporin and vancomycin-based treatment in treating acute bacterial skin and skin structure infections (ABSSSIs). PubMed, Embase, Cochrane Central Register of Controlled Trials, Turning Research into Practice, and ClinicalTrials.gov databases were searched for relevant articles from inception to 15 June 2020. RCTs comparing the clinical efficacy and safety of anti-MRSA cephalosporin with those of vancomycin-based regimens in treating adult patients with ABSSSIs were included. The primary and secondary outcomes were clinical response at the test-of-cure assessments and risk of adverse events (AEs), respectively. Eight RCTs were enrolled. The clinical response rate was not significantly different between anti-MRSA cephalosporin and vancomycin-based treatments (odds ratio [OR], 1.05; 95% CI, 0.90–1.23; I2 = 0%). Except for major cutaneous abscesses in which anti-MRSA cephalosporin-based treatment was associated with a lower clinical response rate than vancomycin-based treatment (OR, 0.62; 95% CI, 0.40–0.97; I2 = 0%), other subgroup analyses according to the type of cephalosporin (ceftaroline or ceftobiprole), type of infection, and different pathogens did not show significant differences in clinical response. Anti-MRSA cephalosporin-based treatment was only associated with a higher risk of nausea than vancomycin-based treatment (OR, 1.41; 95% CI, 1.07–1.85; I2 = 0%). In treating ABSSSIs, the clinical efficacy of anti-MRSA cephalosporin is comparable to that of vancomycin-based treatment, except in major cutaneous abscesses. In addition to nausea, anti-MRSA cephalosporin was as tolerable as vancomycin-based treatment.


Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 106
Author(s):  
Chao-Kun Chen ◽  
I-Ling Cheng ◽  
Yu-Hung Chen ◽  
Chih-Cheng Lai

This meta-analysis aimed to assess the efficacy and safety of sitafloxacin in treating acute bacterial infection. PubMed, Embase, and Cochrane databases were searched up to August 13, 2019. Only randomized controlled trials (RCTs) evaluating sitafloxacin and comparators in the treatment of acute bacterial infections were included. The outcomes were clinical and microbiological responses and the risk of adverse event (AE). Five RCTs were enrolled, including 375 and 381 patients who received sitafloxacin and the comparator, respectively. Overall, the clinical response rate of sitafloxacin in the treatment of acute bacterial infections was 94.6%, which was noninferior to that of the comparator (92.5%) (odds ratio (OR), 1.01; 95% CI, 0.24–4.32; I2 = 66%). For patients with complicated urinary tract infection (cUTI)/acute pyelonephritis (APN), the clinical response rate of sitafloxacin and the comparator was 96.9% and 91.3%, respectively (OR, 2.08; 95% CI, 0.35–12.44; I2 = 54%). For patients with pneumonia, the clinical response rate of sitafloxacin was 88.6%, which was comparable to that of the comparator (OR, 0.36; 95% CI, 0.11–1.21; I2 = 0%). The microbiological response of sitafloxacin was 82.0%, which was noninferior to that of the comparator (77.8%) (OR, 1.59; 95% CI, 0.77–3.28; I2 = 47%). The risk of treatment-emergent adverse event (TEAE), drug-related TEAE, and all-cause mortality were similar between sitafloxacin and the comparators (TEAE, OR, 1.14; 95% CI, 0.64–2.01, drug-related TEAE, OR, 1.14; 95% CI, 0.48–2.69, mortality, OR, 0.93; 95% CI, 0.09–9.44). In conclusion, sitafloxacin is noninferior to other commonly used antibiotics with respect to both clinical and microbiological response rates in patients with an acute bacterial infection, including cUTI/APN and pneumonia. In addition, sitafloxacin is also as safe as the comparators.


2018 ◽  
Vol 2018 ◽  
pp. 1-14
Author(s):  
Weihao Chen ◽  
Yurong Wang ◽  
Qiuer Liang ◽  
Yunfei Cai ◽  
Xudong Chen ◽  
...  

Objectives. To evaluate the efficacy and safety of Aidi injection (ADI) combined with transcatheter arterial chemoembolization (TACE) for primary hepatic carcinoma (PHCC). Methods. We conducted a literature search in EMBASE, PubMed, CENTRAL, MEDLINE, CNKI, Wanfang, and VIP databases from the earliest possible year to April 2018. Randomized controlled trials (RCTs) involving ADI combined with TACE versus TACE alone for patients with PHCC were included. The Cochrane Risk of Bias tool was applied for quality assessment. Results. 22 studies involving 1611 participants were included. The clinical response rate (RR = 1.28, 95% CI: 1.17-1.40; P < 0.00001), KPS score (RR = 1.78, 95% CI: 1.59-2.00; P < 0.00001), survival rate (RR = 1.27, 95% CI: 1.16-1.39; P < 0.00001), immune function (MD = 1.24, 95% CI: 0.98-1.51; P < 0.00001), and adverse effects (RR = 0.62, 95% CI: 0.57-0.68; P < 0.00001) of ADI plus TACE showed significant difference when compared with TACE alone. Conclusions. ADI combined with TACE in the treatment of PHCC improved the clinical response rate and safety compared to TACE alone. However, due to poor methodological quality of many of the included RCTs, more rigorously designed and large-scale RCTs are warranted to examine this beneficial effect in the future.


Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 137 ◽  
Author(s):  
Shao-Huan Lan ◽  
Wei-Ting Lin ◽  
Shen-Peng Chang ◽  
Li-Chin Lu ◽  
Chien-Ming Chao ◽  
...  

This meta-analysis aims to assess the efficacy and safety of tedizolid, compared to linezolid, in the treatment of acute bacterial skin and skin structure infection (ABSSSI). PubMed, Web of Science, EBSCO (Elton B. Stephens Co.), Cochrane Library, Ovid Medline and Embase databases were accessed until 18 July 2019. Only randomized controlled trials (RCTs) comparing the efficacy of tedizolid with linezolid for adult patients with ABSSSIs were included. The outcomes included the clinical response, microbiological response, and risk of adverse events (AEs). A total of four RCTs involving 2056 adult patients with ABSSSI were enrolled. The early clinical response rate was 79.6% and 80.5% for patients receiving tedizolid and linezolid, respectively. The pooled analysis showed that tedizolid had a non-inferior early clinical response rate to linezolid (odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.77–1.19, I2 = 0%). The early response rate was similar between tedizolid and linezolid among patients with cellulitis/erysipelas (75.1% vs. 77.1%; OR = 0.90, 95% CI = 0.64–1.27, I2 = 25%), major cutaneous abscess (85.1% vs. 86.8%; OR = 0.93, 95% CI = 0.42–2.03, I2 = 37%) and wound infection (85.9% vs. 82.6%; OR = 1.29, 95% CI = 0.66–2.51, I2 = 45%). For methicillin-resistant Staphylococcus aureus patients, tedizolid had a favorable microbiological response rate of 95.2% which was comparable to linezolid (94%) (OR = 1.19, 95% CI = 0.49–2.90, I2 = 0%). In addition to the similar risk of treatment-emergent AEs (a serious event, the discontinuation of the study drug due to AEs and mortality between tedizolid and linezolid), tedizolid was associated with a lower risk of nausea, vomiting and abnormal neutrophil count than linezolid. In conclusion, once-daily tedizolid (200 mg for six days) compared to linezolid (600 mg twice-daily for 10 days) was non-inferior in efficacy in the treatment of ABSSSI. Besides, tedizolid was generally as well tolerated as linezolid, and had a lower incidence of gastrointestinal AEs and bone marrow suppression than linezolid.


Author(s):  
Sangmin Lee ◽  
M Ellen Kuenzig ◽  
Amanda Ricciuto ◽  
Ziyu Zhang ◽  
Hang Hock Shim ◽  
...  

Abstract Background and Aims Cigarette smoking worsens prognosis of Crohn’s disease [CD]. We conducted a systematic review and meta-analysis to examine the association between smoking and induction of clinical response or remission with anti-tumour necrosis factor [TNF] therapy. Methods MEDLINE, EMBASE, PubMed, and Cochrane CENTRAL [June 2019] were searched for studies reporting the effect of smoking on short-term clinical response and remission to anti-TNF therapy [≤16 weeks following the first treatment] in patients with CD. Risk ratios [RR] with 95% confidence intervals [CI] were calculated using random-effects models. Results Eighteen observational studies and three randomised controlled trials [RCT] were included. Current smokers and non-smokers [never or former] had similar rates of clinical response [observational studies RR: 0.96; 95% CI: 0.88, 1.05; RCTs RR: 1.09; 95% CI: 0.84, 1.41]. When restricted to studies clearly defining the smoking exposure, smokers treated with anti-TNF were less likely to achieve clinical response than non-smokers [smokers defined as having ≥5 cigarettes/day for ≥6 months RR: 0.63; 95% CI: 0.48, 0.83; lifetime never smokers vs ever smokers excluding former smokers RR: 0.81; 95% CI: 0.71, 0.93]. Current smokers were also less likely to achieve clinical remission in observational studies [RR: 0.75; 95% CI: 0.57, 0.98], though this association was not seen in RCTs [RR: 1.04; 95% CI: 0.89, 1.21]. Conclusions Smoking is significantly associated with a reduction in the ability of infliximab or adalimumab to induce short-term clinical response and remission when pooling studies where smoking status was clearly defined. When patients with CD are treated with highly effective therapy, including anti-TNF agents, concurrent smoking cessation may improve clinical outcomes.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S521-S521
Author(s):  
M Khorshid Fasge ◽  
A Cordie ◽  
S Abd-Elsalam

Abstract Background This systematic review and meta-analysis was designed to estimate the safety and effectiveness of ustekinumab in the treatment for Crohn’s disease (CD) in clinical trials and observational studies. Methods We retrieved all the related publications from PubMed, Cochrane, EBSCO, Google Scholar and EMBASE using a systematic search strategy. We only included the clinical trials and observational studies that were published in English. Results Only 31 studies that met the eligibility criteria out of the 733 identified studies were included. Twenty-one studies reported the clinical response rate; three of these were clinical trials, and the other 18 were cohort studies. The overall clinical response rate in the cohort studies was 0.539, 95% CI (0.419–0.659) with significant heterogeneity (I2 = 96.22%, P &lt; 0.001) and that in the clinical trials was 0.428, 95% CI (0.356–0.501). The pooled clinical remission rate was 0.399, 95% CI (0.295–0.503) in randomised control trials (RCTs) and 0.440, 95% CI (0.339–0.542) in cohort studies. Twenty-one studies reported the incidence of adverse effects. The rate of adverse effects was 0.158, 95% CI (0.109–0.207) in cohort studies and 0.690, 95% CI (0.633–0.748) in RCTs. Three RCTs had an infection rate of 0.275, 95% CI (0.245–0.295), while the 18 cohort studies had a rate of 0.076, 95% CI (0.047–0.105). Only ten studies reported the incidence of injection or infusion reaction; it was 0.035, 95% CI (0.027–0.043) for RCTs and 0.012, 95% CI (0.002–0.022) for cohort studies. Conclusion Ustekinumab is effective in the treatment of CD. However, more research is required on the safety profiles because there was considerable variation among the included studies.


Cephalalgia ◽  
2021 ◽  
pp. 033310242110181
Author(s):  
Florian Frank ◽  
Hanno Ulmer ◽  
Victoria Sidoroff ◽  
Gregor Broessner

Background The approval of monoclonal antibodies for prevention of migraine has revolutionized treatment for patients. Oral preventatives are still considered first line treatments as head-to-head trials comparing them with antibodies are lacking. Methods The main purpose of this study was to provide a comparative overview of the efficacy of three commonly prescribed migraine preventative medication classes. For this systematic review and meta-analysis, we searched the databases CENTRAL, EMBASE, and MEDLINE until 20 March 2020. We included RCTs reporting the 50% response rates for topiramate, Botulinum Toxin Type A and monoclonal antibodies against CGRP(r). Studies were excluded if response rates were not reported, treatment allocation was unclear, or if study quality was insufficient. Primary outcome measure were the 50% response rates. The pooled odds ratios with 95% confidence intervals were calculated with the random effects model. The study was registered at PROSPERO (CRD42020222880). Findings We identified 6552 reports. Thirty-two were eligible for our review. Studies assessing monoclonal antibodies included 13,302 patients and yielded pooled odds ratios for the 50% response rate of 2.30 (CI: 2.11–2.50). Topiramate had an overall effect estimate of 2.70 (CI: 1.97–3.69) with 1989 included patients and Botulinum Toxin Type A achieved 1.28 (CI: 0.98–1. 67) with 2472 patients included. Interpretation Topiramate, botulinum toxin type A and monoclonal antibodies showed higher odds ratios in achieving a 50% response rate compared to placebo. Topiramate numerically demonstrated the greatest effect size but also the highest drop-out rate.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yaping Wang ◽  
Bin Liu ◽  
Xiuqiong Fu ◽  
Tiejun Tong ◽  
Zhiling Yu

Abstract Background The traditional Chinese medicine formula Si-Jun-Zi-Tang (SJZT) has a long history of application in the treatment of functional dyspepsia (non-ulcer dyspepsia, FD)-like symptoms. SJZT-based therapies have been claimed to be beneficial in managing FD. This study aimed to assess the efficacy and safety of SJZT-based therapies in treating FD by meta-analysis. Methods Systematic searches for RCTs were conducted in seven databases (up to February 2019) without language restrictions. Data were analyzed using Cochrane RevMan software version 5.3.0 and Stata software version 13.1, and reported as relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs). The primary outcome was response rate and the secondary outcomes were gastric emptying, quality of life, adverse effects and relapse rate. The quality of evidence was evaluated according to criteria from the Cochrane risk of bias. Results A total of 341 potentially relevant publications were identified, and 12 RCTs were eligible for inclusion. For the response rate, there was a statically significant benefit in favor of SJZT-based therapies (RR = 1.23; 95% CI 1.17 to 1.30). However, the benefit was limited to modified SJZT (MSJZT). The relapse rate of FD patients received SJZT-based therapies was lower than that of patients who received conventional medicines (OR = 0.23; 95% CI 0.10 to 0.51). No SJZT-based therapies-related adverse effect was reported. Conclusion SJZT-based prescriptions may be effective in treating FD and no serious side-effects were identified, but the effect on response rate appeared to be limited to MSJZT. The results should be interpreted with caution as all the included studies were considered at a high risk of bias. Standardized, large-scale and strictly designed RCTs are needed to further validate the benefits of SJZT-based therapies for FD management. Trial registration Systematic review registration: [PROSPERO registration: CRD42019139136].


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1005.1-1005
Author(s):  
Y. H. Lee ◽  
G. G. Song

Background:Methotrexate (MTX), an effective disease-modifying antirheumatic drug (DMARD) [2], is the most widely used DMARD for the treatment of rheumatoid arthritis (RA). However, not all patients are responsive to the drug; 30% of the patients discontinue therapy within 1 year of commencing the treatment, usually because of the lack of efficacy or undesirable adverse effects Small-molecule Janus kinase inhibitors are clinically developed for the treatment of RA.Objectives:The aim of this study is to investigate the relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in comparison with adalimumab in patients with active RA and having inadequate responses to MTX.Methods:We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib, and adalimumab in RA patients having inadequate responses to MTX.Results:Four RCTs, comprising 5,451 patients, met the inclusion criteria. The baricitinib 4mg+MTX and upadacitinib 15mg+MTX group showed a significantly higher American College of Rheumatology 20% (ACR20) response rate than the adalimumab 40mg+MTX group. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that baricitinib 4mg+MTX had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by upadacitinib 15mg+MTX, tofacitinib 5mg+MTX, filgotinib 200mg+MTX, filgotinib 100mg+MTX, adalimumab 40mg+MTX, and placebo+MTX. The upadacitinib 15mg+MTX and baricitinib 4mg+MTX groups showed significantly higher ACR50 and ACR70 response rates than adalimumab 40mg+MTX. In terms of Herpes zoster infection, the ranking probability based on the SUCRA indicated that placebo+MTX were likely to be the safest treatments, followed by filgotinib 200mg+MTX, filgotinib 100mg+MTX, adalimumab 40mg+MTX, tofacitinib 5mg+MTX, upadacitinib 15mg+MTX, and baricitinib 4mg+MTX. Regarding safety analysis, no statistically significant differences were found between the respective intervention groups.Conclusion:In RA patients with an inadequate response to MTX, baricitinib 4mg+MTX and upadacitinib 15mg+MTX showed the highest ACR response rates, suggesting a difference in efficacy among the different JAK inhibitors.References:[1]Fleischmann R, Mysler E, Hall S, Kivitz AJ, Moots RJ, Luo Z, DeMasi R, Soma K, Zhang R, Takiya LJTL (2017) Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. 390:457-468[2]Taylor PC, Keystone EC, van der Heijde D et al (2017) Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med 376:652-662[3]Fleischmann R, Pangan AL, Mysler E, Bessette L, Peterfy C, Durez P, Ostor A, Li Y, Zhou Y, Othman AA (2018) A phase 3, randomized, double-blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate. ARTHRITIS & RHEUMATOLOGY. WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, pp[4]Combe B, Kivitz A, Tanaka Y, van der Heijde D, Matzkies F, Bartok B, Ye L, Guo Y, Tasset C, Sundy J (2019) LB0001 EFFICACY AND SAFETY OF FILGOTINIB FOR PATIENTS WITH RHEUMATOID ARTHRITIS WITH INADEQUATE RESPONSE TO METHOTREXATE: FINCH1 PRIMARY OUTCOME RESULTS. BMJ Publishing Group Ltd, ppDisclosure of Interests:None declared


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