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European Journal of Cancer (Oxford,... May 2022S-1 is an oral fluoropyrimidine that is increasingly used in Western countries for the treatment of metastatic colorectal cancer (mCRC). We conducted a non-inferiority... (Meta-Analysis)
Meta-Analysis Review
Systematic review and non-inferiority meta-analysis of randomised phase II/III trials on S-1-based therapy versus 5-fluorouracil- or capecitabine-based therapy in the treatment of patients with metastatic colorectal cancer.
BACKGROUND
S-1 is an oral fluoropyrimidine that is increasingly used in Western countries for the treatment of metastatic colorectal cancer (mCRC). We conducted a non-inferiority meta-analysis on the efficacy of S-1-based therapy versus 5-fluorouracil (5-FU)- or capecitabine-based therapy in the treatment of patients with mCRC.
METHODS
MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Opengrey were searched for randomised clinical trials until May 2021. Data were extracted for progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and adverse events. Pooled effect estimates, stratified by treatment line, with corresponding 99% confidence intervals (CI) were presented. For PFS, a pre-defined non-inferiority margin (ΔNI) of 1.25 was selected.
RESULTS
Ten studies (n = 2117) were included, of which six studies reported PFS and OS data and 10 studies reported ORR data. S-1-based therapy was shown to be non-inferior to 5-FU/capecitabine-based therapy in terms of PFS (HR 0.95, 99% CI 0.83-1.08) with its CI upper limit well below ΔNI, and at least as efficacious in terms of OS (HR 0.93, 99% CI 0.81-1.07), and ORR (RR 1.06, 99% CI 0.90-1.24).
CONCLUSIONS
S-1-based therapy is non-inferior to 5-FU/capecitabine-based therapy in the treatment of mCRC regarding PFS and at least as efficacious as 5-FU/capecitabine-based therapy in terms of ORR and OS. These data support the use of S-1 in mCRC patients who are intolerant to 5-FU/capecitabine-based treatment.
Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colorectal Neoplasms; Fluorouracil; Humans
PubMed: 35279472
DOI: 10.1016/j.ejca.2022.02.004 -
The Cochrane Database of Systematic... Dec 2014Current standard treatment for patients with cervical cancer who have locally advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage... (Review)
Review
BACKGROUND
Current standard treatment for patients with cervical cancer who have locally advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IVA) is concurrent chemoradiation therapy (CCRT). However, less than two-thirds of patients in this group survive for longer than five years post treatment. Adjuvant chemotherapy (ACT) can be given in an attempt to improve survival by eradicating residual disease in the pelvis and treating occult disease outside the pelvic radiation field. However, inconsistency in trial design, inclusion criteria for participants, interventions and survival benefit has been noted among trials of ACT after CCRT for locally advanced cervical cancer (LACC).
OBJECTIVES
To evaluate the effect of adjuvant chemotherapy (ACT) after concurrent chemoradiation (CCRT) on survival of women with locally advanced cervical cancer compared with CCRT alone.
SEARCH METHODS
We searched the Cochrane Gynaecological Review Group Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and conference proceedings to March 2014. We handsearched citation lists of relevant studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing CCRT alone versus CCRT plus ACT were included. Patients were diagnosed with cervical cancer FIGO stage IIB to IVA with a histopathology of squamous cell carcinoma, adenosquamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma.
DATA COLLECTION AND ANALYSIS
Two review authors (ST, KK) selected relevant trials, extracted data, assessed risk of bias independently, compared results and resolved disagreements by discussion.
MAIN RESULTS
We identified two RCTs involving 978 women with cervical cancer stage IIB to IVA. As the trials were significantly different clinically, we did not perform meta-analyses. One industry-funded trial involving 515 women compared CCRT (cisplatin) versus CCRT (cisplatin and gemcitabine) plus ACT (two additional cycles). This trial reported significant improvement in progression-free survival (PFS) and overall survival (OS) in women who were given CCRT plus ACT compared with those treated with CCRT alone: Three-year PFS was 74.4% versus 65.0% (hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.49 to 0.95, P value 0.027), and three-year OS was 80% versus 69% (HR 0.68, 95% CI 0.49 to 0.95, P value 0.022). However, as the CCRT chemotherapy differed between the two arms, we considered the findings to be at high risk of bias.The second trial was a four-arm study from which we extracted data on 463 women in two study arms receiving CCRT (intravenous mitomycin C and oral 5-fluorouracil (5-FU)) or CCRT plus ACT (oral 5-FU for three cycles). The HR for OS in women who received ACT after CCRT compared with the HR for OS in those who were given CCRT alone was 1.309 (95% CI 0.795 to 2.157), and the HR for disease-free survival (DFS) was 1.125 (95% CI 0.799 to 1.586).Haematological adverse events were more common in the ACT arms of both trials. Quality of life (QoL) was not reported in either trial.
AUTHORS' CONCLUSIONS
With limited data from only two trials, we found insufficient evidence to support the use of ACT after CCRT. Future large trials are required to demonstrate efficacy, toxicities and QoL.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Cisplatin; Deoxycytidine; Female; Fluorouracil; Humans; Mitomycin; Neoplasm Staging; Randomized Controlled Trials as Topic; Uterine Cervical Neoplasms; Gemcitabine
PubMed: 25470408
DOI: 10.1002/14651858.CD010401.pub2 -
The Cochrane Database of Systematic... Jul 2017Patients prefer oral to intravenous (IV) palliative chemotherapy, provided that oral therapy is not less effective. We compared the efficacy and safety of oral and IV... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients prefer oral to intravenous (IV) palliative chemotherapy, provided that oral therapy is not less effective. We compared the efficacy and safety of oral and IV fluoropyrimidines for treatment of colorectal cancer (CRC).
OBJECTIVES
To compare the effects of oral and IV fluoropyrimidine chemotherapy in patients treated with curative or palliative intent for CRC.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 5), along with OVID MEDLINE, OVID Embase, and Web of Science databases, in June 2016. We also searched five clinical trials registers, several conference proceedings, and reference lists from study reports and systematic reviews. We contacted pharmaceutical companies to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing oral and IV fluoropyrimidine chemotherapy in patients treated with curative or palliative intent for CRC.
DATA COLLECTION AND ANALYSIS
Three review authors extracted data and assessed risk of bias independently. We assessed the seven domains in the Cochrane 'Risk of bias' tool and three additional domains: schedules of outcome assessment and/or follow-up; use of intention-to-treat analysis; and baseline comparability of treatment arms.
MAIN RESULTS
We included nine RCTs (total of 10,918 participants) that examined treatment with curative intent for CRC with neoadjuvant and/or adjuvant chemotherapy. We included 35 RCTs (total of 12,592 participants) that examined treatment with palliative intent for inoperable advanced or metastatic CRC with chemotherapy (31 first-line studies, two second-line studies, and two studies of first- or second-line chemotherapy). All studies included male and female participants, and no studies included participants younger than 18 years of age. Patients treated with curative intent for CRC with neoadjuvant and/or adjuvant chemotherapy • Disease-free survival (DFS): DFS did not differ between participants treated with oral versus IV fluoropyrimidines (hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.87 to 1.00; seven studies, 8903 participants; moderate-quality evidence).• Overall survival (OS): OS did not differ between participants treated with oral versus IV fluoropyrimidines (HR 0.92, 95% CI 0.84 to 1.00; seven studies, 8902 participants analysed; high-quality evidence).• Grade ≥ 3 adverse events (AEs): Participants treated with oral fluoropyrimidines experienced less grade ≥ 3 neutropenia/granulocytopenia (odds ratio (OR) 0.14, 95% CI 0.11 to 0.16; seven studies, 8087 participants; moderate-quality evidence), stomatitis (OR 0.21, 95% CI 0.14 to 0.30; five studies, 4212 participants; low-quality evidence), and any grade ≥ 3 AEs (OR 0.82, 95% CI 0.74 to 0.90; five studies, 7741 participants; low-quality evidence). There was more grade ≥ 3 hand foot syndrome (OR 4.59, 95% CI 2.97 to 7.10; five studies, 5731 participants; low-quality evidence) in patients treated with oral fluoropyrimidines. There were no differences between participants treated with oral versus IV fluoropyrimidines in occurrence of grade ≥ 3 diarrhoea (OR 1.12, 95% CI 0.99 to 1.25; nine studies, 9551 participants; very low-quality evidence), febrile neutropenia (OR 0.59, 95% CI 0.18 to 1.90; four studies, 2925 participants; low-quality evidence), vomiting (OR 1.05, 95% CI 0.83 to 1.34; eight studies, 9385 participants; low-quality evidence), nausea (OR 1.21, 95% CI 0.97 to 1.51; seven studies, 9233 participants; low-quality evidence), mucositis (OR 0.64, 95% CI 0.25 to 1.62; four studies, 2233 participants; very low-quality evidence), and hyperbilirubinaemia (OR 1.67, 95% CI 0.52 to 5.38; three studies, 2757 participants; very low-quality evidence). Patients treated with palliative intent for inoperable advanced or metastatic CRC with chemotherapy • Progression-free survival (PFS): Overall, PFS was inferior in participants treated with oral versus IV fluoropyrimidines (HR 1.06, 95% CI 1.02 to 1.11; 23 studies, 9927 participants; moderate-quality evidence). Whilst PFS was worse in participants treated with oral compared with IV fluoropyrimidines when UFT/Ftorafur or eniluracil with oral 5-fluorouracil (5-FU) was used, PFS did not differ between individuals treated with oral versus IV fluoropyrimidines when capecitabine, doxifluridine, or S-1 was used.• OS: Overall, OS did not differ between participants treated with oral versus IV fluoropyrimidines (HR 1.02, 95% CI 0.99 to 1.05; 29 studies, 12,079 participants; high-quality evidence). OS was inferior in participants treated with oral versus IV fluoropyrimidines when eniluracil with oral 5-fluorouracil (5-FU) was used.• Time to progression (TTP): TTP was inferior in participants treated with oral versus IV fluoropyrimidines (HR 1.07, 95% CI 1.01 to 1.14; six studies, 1970 participants; moderate-quality evidence).• Objective response rate (ORR): ORR did not differ between participants treated with oral versus IV fluoropyrimidines (OR 0.98, 95% CI 0.90 to 1.06; 32 studies, 11,115 participants; moderate-quality evidence).• Grade ≥ 3 AEs: Participants treated with oral fluoropyrimidines experienced less grade ≥ 3 neutropenia/granulocytopenia (OR 0.17, 95% CI 0.15 to 0.18; 29 studies, 11,794 participants; low-quality evidence), febrile neutropenia (OR 0.27, 95% CI 0.21 to 0.36; 19 studies, 9407 participants; moderate-quality evidence), stomatitis (OR 0.26, 95% CI 0.20 to 0.33; 21 studies, 8718 participants; low-quality evidence), mucositis (OR 0.17, 95% CI 0.12 to 0.24; 12 studies, 4962 participants; low-quality evidence), and any grade ≥ 3 AEs (OR 0.83, 95% CI 0.74 to 0.94; 14 studies, 5436 participants; low-quality evidence). There was more grade ≥ 3 diarrhoea (OR 1.66, 95% CI 1.50 to 1.84; 30 studies, 11,997 participants; low-quality evidence) and hand foot syndrome (OR 3.92, 95% CI 2.84 to 5.43; 18 studies, 6481 participants; moderate-quality evidence) in the oral fluoropyrimidine arm. There were no differences between oral and IV fluoropyrimidine arms in terms of grade ≥ 3 vomiting (OR 1.18, 95% CI 1.00 to 1.40; 23 studies, 9528 participants; low-quality evidence), nausea (OR 1.16, 95% CI 0.99 to 1.36; 25 studies, 9796 participants; low-quality evidence), and hyperbilirubinaemia (OR 1.62, 95% CI 0.99 to 2.64; nine studies, 2699 participants; low-quality evidence).
AUTHORS' CONCLUSIONS
Results of this review should provide confidence that treatment for CRC with most of the oral fluoropyrimidines commonly used in current clinical practice is similarly efficacious to treatment with IV fluoropyrimidines. Treatment with eniluracil with oral 5-FU was associated with inferior PFS and OS among participants treated with palliative intent for CRC, and eniluracil is no longer being developed. Oral and IV fluoropyrimidines have different patterns of side effects; future research may focus on determining the basis for these differences.
Topics: Administration, Oral; Adult; Antineoplastic Agents; Camptothecin; Capecitabine; Chemotherapy, Adjuvant; Colorectal Neoplasms; Disease-Free Survival; Female; Floxuridine; Fluorouracil; Humans; Injections, Intravenous; Irinotecan; Male; Neoadjuvant Therapy; Organoplatinum Compounds; Palliative Care; Pyridines; Pyrimidines; Randomized Controlled Trials as Topic; Tegafur; Uracil
PubMed: 28752564
DOI: 10.1002/14651858.CD008398.pub2 -
Antioxidants & Redox Signaling Apr 20168-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative... (Meta-Analysis)
Meta-Analysis Review
SIGNIFICANCE
8-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative damage of DNA because guanosine is the most oxidized among the DNA nucleobases. In several pathological conditions, high urinary levels of oxidized DNA-derived metabolites have been reported (e.g., cancer, atherosclerosis, hypertension, and diabetes).
RECENT ADVANCES
Even if published studies have shown that DNA damage is significantly associated with the development of atherosclerosis, the exact role of this damage in the onset and progression of this pathology is not fully understood, and the association of oxidative damage to DNA with cardiovascular disease (CVD) still needs to be more extensively investigated. We performed a meta-analysis of the literature to investigate the association among 8-OHdG levels and CVD.
CRITICAL ISSUES
Fourteen studies (810 CVD patients and 1106 controls) were included in the analysis. We found that CVD patients showed higher 8-OHdG levels than controls (SMD: 1.04, 95%CI: 0.61, 1.47, p < 0.001, I(2) = 94%, p < 0.001). The difference was confirmed both in studies in which 8-OHdG levels were assessed in urine (MD: 4.43, 95%CI: 1.71, 7.15, p = 0.001) and in blood samples (MD: 1.42, 95%CI: 0.64, 2.21, p = 0.0004). Meta-regression models showed that age, hypertension, and male gender significantly impacted on the difference in 8-OHdG levels among CVD patients and controls.
FUTURE DIRECTIONS
8-OHdG levels are higher in patients with CVD than in controls. However, larger prospective studies are needed to test 8-OHdG as a predictor of CVD.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Deoxyguanosine; Humans; Oxidation-Reduction; Oxidative Stress; Prognosis; Publication Bias; Regression Analysis
PubMed: 26650622
DOI: 10.1089/ars.2015.6508 -
Alimentary Pharmacology & Therapeutics Oct 2014Major adjuvant therapies for biliary tract cancer (BTC) include fluorouracil, gemcitabine and chemoradiation (CRT), but the optimum regimen remains inconclusive. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Major adjuvant therapies for biliary tract cancer (BTC) include fluorouracil, gemcitabine and chemoradiation (CRT), but the optimum regimen remains inconclusive.
AIM
To compare these therapies in terms of patient survival rates after resection and toxic effects.
METHODS
We searched PubMed for controlled trials comparing the above three therapies with each other or observation alone until 31 January 2014. We estimated the hazard ratios (HRs) for death and odds ratios (ORs) for toxic effects among different therapies. Subgroup analyses based on positive lymph node or resection margin were also performed.
RESULTS
Twelve eligible articles were included. Gemcitabine improved 5-year survival (HR 2.12, 95% CI, confidence interval 1.23-4.02, P = 0.01), whereas fluorouracil (HR 1.61, 95% CI 0.74-3.67) and CRT (HR 1.55, 95% CI 0.82-3.32) provided a poorer survival outcome compared with gemcitabine after 1 year. Similarly, for 5-year survival rates, although differing, CRT did not provide a significant improvement in survival (HR 0.46, 95% CI 0.20-0.97) compared with gemcitabine. Fluorouracil did not appear to provide benefit over gemcitabine (HR 1.56, 95% CI 0.77-3.35). CRT was ranked highest for toxic effects including haematological (OR 5.45, 95% CI 0.01-483.85) and nonhaematological (OR 5.77, 95% CI 0.01-3807.40).
CONCLUSIONS
Chemotherapy with gemcitabine is the optimum adjuvant treatment with a balanced benefit-toxicity ratio for resected biliary tract cancer. Chemoradiation was more likely to cause toxic effects.
Topics: Antimetabolites, Antineoplastic; Biliary Tract Neoplasms; Chemoradiotherapy, Adjuvant; Deoxycytidine; Fluorouracil; Humans; Gemcitabine
PubMed: 25099956
DOI: 10.1111/apt.12900 -
Danish Medical Journal Dec 2016Refractory coeliac disease (RCD) is a rare and severe malabsorptive disease. The condition has two subtypes: RCDI and RCDII. Different treatments have been tested: and... (Review)
Review
INTRODUCTION
Refractory coeliac disease (RCD) is a rare and severe malabsorptive disease. The condition has two subtypes: RCDI and RCDII. Different treatments have been tested: and because RCD has a poor prognosis due to progress to enteropathy-associated T-cell lymphoma, the aim was to review the epidemiologic aspects and the therapeutic options for RCD.
METHODS
A systematic literature search was performed in 18 databases, and 122 records were identified. Incidence, prevalence, treatment methods and their efficacy were evaluated.
RESULTS
Among coeliac disease patients, the cumulative incidence of RCD is 1-4% per ten-year period and the prevalence is 0.31-0.38%. In the general population, the prevalence of RCD is 0.002%. Treatment of RCDI is azathioprine (effect 100%), mesalamine (effect 60%) or tioguanine (effect 83%). Treatment for RCDII is the antimetabolite cladribine (effect 81%) and autologous haematopoetic stem cell transplantation (effect 85%).
CONCLUSION
RCD is a very rare disease. The current evidence for RCDI treatment includes prednisolone in combination with the immunosuppressants azathioprine, mesalamine or tioguanine. The current evidence for RCDII treatment documents use of the antimetabolite cladribine, and if there is no effect, autologous haematopoetic stem cell transplantation may be attempted. In the future, there is a need for more effective treatments which will also prevent further progression to enteropathy-associated T-cell lymphoma.
Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Celiac Disease; Cladribine; Drug Therapy, Combination; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Incidence; Mesalamine; Prednisolone; Prevalence; Thioguanine
PubMed: 27910801
DOI: No ID Found -
Nutrients Jan 2022Because pharmacokinetic changes in antiretroviral drugs (ARV), due to their concurrent administration with food or nutritional products, have become a clinical... (Meta-Analysis)
Meta-Analysis Review
Because pharmacokinetic changes in antiretroviral drugs (ARV), due to their concurrent administration with food or nutritional products, have become a clinical challenge, it is necessary to monitor the therapeutic efficacy of ARV in people living with the human immunodeficiency virus (PLWH). A systematic review and meta-analysis were conducted to clarify the pharmacokinetic outcomes of the interaction between supplements such as food, dietary supplements, and nutrients, and ARV. Twenty-four articles in both healthy subjects and PLWH were included in the qualitative analysis, of which five studies were included in the meta-analysis. Food−drug coadministration significantly increased the time to reach maximum concentration (tmax) (p < 0.00001) of ARV including abacavir, amprenavir, darunavir, emtricitabine, lamivudine, zidovudine, ritonavir, and tenofovir alafenamide. In addition, the increased maximum plasma concentration (Cmax) of ARV, such as darunavir, under fed conditions was observed. Area under the curve and terminal half-life were not significantly affected. Evaluating the pharmacokinetic aspects, it is vital to clinically investigate ARV and particular supplement interaction in PLWH. Educating patients about any potential interactions would be one of the effective recommendations during this HIV epidemic.
Topics: Anti-Retroviral Agents; Darunavir; Dietary Supplements; Drug Interactions; Emtricitabine; Humans
PubMed: 35276881
DOI: 10.3390/nu14030520 -
Virology Journal Apr 2016To assess the potential effects of telbivudine (LdT) and entecavir (ETV) on renal function in patients with chronic hepatitis B (CHB), we performed a meta-analysis of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To assess the potential effects of telbivudine (LdT) and entecavir (ETV) on renal function in patients with chronic hepatitis B (CHB), we performed a meta-analysis of the relevant data available on these agents to evaluate their effects on the estimated glomerular filtration rate (eGFR) during treatment.
METHODS
The PubMed, EMBASE, Scopus, CNKI (China National Knowledge Infrastructure), Cochrane Library, and WanFang databases were searched for relevant articles appearing in the literature up to July 1, 2015. A total of 6 studies (1960 CHB patients) with 1-year eGFR outcomes were retrieved and analyzed.
RESULTS
Generally, the results of the 6 studies analyzed showed that eGFR was improved after LdT treatment, but was decreased after ETV treatment. Using a fixed-effects approach, the change in eGFR was found to be significantly different between LdT and ETV treatment (Z = 3.64; P = 0.0003). Whereas the eGFR was slightly decreased with ETV compared with baseline (-1.45 mL/min/1.73 m(2)), the eGFR was improved with LdT (2.99 mL/min/1.73 m(2)) after 1 year of treatment. An overall test of effect in the meta-analysis showed that the eGFR in LdT-treated patients was significantly improved after 1-year of treatment (Z = 3.71; P = 0.0002).
CONCLUSION
This meta-analysis has confirmed that LdT has a renal protective effect whereas ETV does not. However, whether the benefit on renal function outweighs the occurrence of resistance in specific clinical situations is not yet clear.
Topics: Antiviral Agents; China; Guanine; Hepatitis B, Chronic; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Telbivudine; Thymidine
PubMed: 27062520
DOI: 10.1186/s12985-016-0522-6 -
The Lancet. Child & Adolescent Health Oct 2022Abacavir is a nucleoside reverse transcriptase inhibitor recommended in paediatric HIV care. We assessed the safety and efficacy profile of abacavir used in first,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Abacavir is a nucleoside reverse transcriptase inhibitor recommended in paediatric HIV care. We assessed the safety and efficacy profile of abacavir used in first, second, or subsequent lines of treatment for infants, children, and adolescents living with HIV to inform 2021 WHO paediatric ART recommendations.
METHODS
In this systematic review and meta-analysis, we included observational and experimental studies conducted in infants aged 0-1 year, children aged 1-10 years, and adolescents aged 10-19 years living with HIV; with data on safety or efficacy, or both, of abacavir-based antiretroviral therapy (ART); published in English or French between Jan 1, 2009, and Oct 1, 2020, plus an updated search to incorporate studies published between Oct 1, 2020, and May 15, 2022. Studies could be non-randomised or non-comparative and include patients who are treatment-naive or those who previously received abacavir (only if abacavir was combined with other ART). Case studies, studies in adults aged 18 years or older, and those assessing the effect of maternal ART exposure were excluded. We extracted data related to study identifier, study design, study period, setting, population characteristics, ART treatment, and safety (any hypersensitivity reaction, death, grade 3 or 4 adverse events, treatment discontinuation, any other morbidities, and serious adverse events), and efficacy outcomes (HIV viral load and CD4 counts reported at 6 and 12 months after ART initiation). Using random-effect models, we estimated weighted pooled incidence and relative risk (RR) of outcomes. The protocol is published in PROSPERO (CRD42022309230).
FINDINGS
Of 1777 records identified, 1475 (83%) were screened after removing duplicates and a further 1421 (96%) were excluded. Of 54 full-text articles assessed for eligibility, 33 (61%) were excluded. Four records were identified from grey literature plus one duplicate from database searching, resulting in 24 studies included (two randomised controlled trials, one single-arm trial, 12 prospective cohorts, seven retrospective cohorts, and two cross-sectional studies). 19 studies described safety data and 15 described efficacy data. 18 (75%) studies were conducted in ART-naive participants. The risk of bias was considered moderate to high for most studies, and all outcomes had significant between-study heterogeneity. Data from 24 265 participants were included, of whom 7236 (30%) received abacavir. Abacavir hypersensitivity reaction was reported in nine (38%) studies, with an incidence ranging from 0·00% to 8·26% (I=85%; p<0·0001). The incidence of death (reported in seven studies) following abacavir treatment varied from 0·00% to 5·49% (I=58%; p=0·026). Viral suppression (<400 copies per mL) varied from 50% to 70% at 6 months (I=92%, p<0·0001) and from 57% to 78% at 12 months (I=88%, p<0·0001).
INTERPRETATION
Toxic effects due to abacavir use remain rare and manageable. Despite scarce data on efficacy, this meta-analysis supports the use of abacavir as a preferred first-line regimen for infants and children living with HIV.
FUNDING
WHO.
Topics: Adolescent; Adult; Anti-HIV Agents; Child; Cross-Sectional Studies; Cyclopropanes; Dideoxyadenosine; HIV Infections; Humans; Infant; Nucleosides; Observational Studies as Topic; Prospective Studies; Retrospective Studies; Reverse Transcriptase Inhibitors
PubMed: 36058225
DOI: 10.1016/S2352-4642(22)00213-9 -
Journal of Pharmacy & Pharmaceutical... 2015This study aimed to systematically review and quantitatively synthesize the association between HLA-B*5701 and abacavir-induced hypersensitivity reaction (ABC-HSR). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study aimed to systematically review and quantitatively synthesize the association between HLA-B*5701 and abacavir-induced hypersensitivity reaction (ABC-HSR).
METHODS
We searched for studies that investigated the association between HLA-B genotype and ABC-HSR and provided information about the frequency of carriers of HLA-B genotypes among cases and controls. We then performed a meta-analysis with a random-effects model to pool the data and to investigate the sources of heterogeneity.
RESULTS
From 1,026 articles identified, ten studies were included. Five using clinical manifestation as their diagnostic criteria, 409 and 1,883 subjects were included as cases and controls. Overall OR was 23.6 (95% CI = 15.4 - 36.3). Whereas, the another five studies using confirmed immunologic test as their diagnostic criteria, 110 and 1,968 subjects were included as cases and controls, respectively. The association of ABC-HSR was strong in this populations with HLA-B*5701. Overall OR was 1,056.2 (95% CI = 345.0 - 3,233.3).
CONCLUSIONS
Using meta-analysis technique, the association between HLA-B*5701 and ABC-HSR is strong in the studies using immunologic confirmation to identify ABC-HSR. These results support the US FDA recommendations for screening HLA-B*5701 allele before initiating abacavir therapy.
Topics: Alleles; Anti-HIV Agents; Dideoxynucleosides; Drug Hypersensitivity; Genotype; HLA-B Antigens; Humans
PubMed: 25877443
DOI: 10.18433/j39s3t