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The Cochrane Database of Systematic... Sep 2014Vaginal dilation therapy is advocated after pelvic radiotherapy to prevent stenosis (abnormal narrowing of the vagina), but can be uncomfortable and psychologically... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vaginal dilation therapy is advocated after pelvic radiotherapy to prevent stenosis (abnormal narrowing of the vagina), but can be uncomfortable and psychologically distressing.
OBJECTIVES
To assess the benefits and harms of different types of vaginal dilation methods offered to women treated by pelvic radiotherapy for cancer.
SEARCH METHODS
Searches included the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 5), MEDLINE (1950 to June week 2, 2013), EMBASE (1980 to 2013 week 24) and CINAHL (1982 to 2013).
SELECTION CRITERIA
Comparative data of any type, which evaluated dilation or penetration of the vagina after pelvic radiotherapy treatment for cancer.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We found no trials and therefore analysed no data.
MAIN RESULTS
We identified no studies for inclusion in the original review or for this update. However, we felt that some studies that were excluded warranted discussion. These included one randomised trial (RCT), which showed no improvement in sexual scores associated with encouraging women to practise dilation therapy; a recent small RCT that did not show any advantage to dilation over vibration therapy during radiotherapy; two non-randomised comparative studies; and five correlation studies. One of these showed that objective measurements of vaginal elasticity and length were not linked to dilation during radiotherapy, but the study lacked power. One study showed that women who dilated tolerated a larger dilator, but the risk of objectivity and bias with historical controls was high. Another study showed that the vaginal measurements increased in length by a mean of 3 cm after dilation was introduced 6 to 10 weeks after radiotherapy, but there was no control group; another case series showed the opposite. Three recent studies showed less stenosis associated with prophylactic dilation after radiotherapy. One small case series suggested that dilation years after radiotherapy might restore the vagina to a functional length.
AUTHORS' CONCLUSIONS
There is no reliable evidence to show that routine, regular vaginal dilation during radiotherapy treatment prevents stenosis or improves quality of life. Several observational studies have examined the effect of dilation therapy after radiotherapy. They suggest that frequent dilation practice is associated with lower rates of self reported stenosis. This could be because dilation is effective or because women with a healthy vagina are more likely to comply with dilation therapy instructions compared to women with strictures. We would normally suggest that a RCT is needed to distinguish between a casual and causative link, but pilot studies highlight many reasons why RCT methodology is challenging in this area.
Topics: Anti-Inflammatory Agents; Benzydamine; Brachytherapy; Constriction, Pathologic; Dilatation; Estrogens; Female; Humans; Hyperbaric Oxygenation; Pelvis; Radiation Injuries; Radiotherapy; Rupture; Sexual Dysfunction, Physiological; Time Factors; Vagina
PubMed: 25198150
DOI: 10.1002/14651858.CD007291.pub3 -
Systematic Reviews Apr 2024Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA.
METHODS
We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis.
RESULTS
A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58-2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60-2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75-1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83-4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08-3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85-2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15-2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93-2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46-1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics.
CONCLUSION
EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events.
Topics: Humans; Immunosuppressive Agents; Anemia, Aplastic; Immunosuppression Therapy; Benzoates; Pathologic Complete Response; Treatment Outcome; Hydrazines; Pyrazoles
PubMed: 38576005
DOI: 10.1186/s13643-024-02515-2 -
Pain Nov 2022Burrowing behaviour is used to assess pain-associated behaviour in laboratory rodents. To gain insight into how models of disease-associated persistent pain and... (Meta-Analysis)
Meta-Analysis
Burrowing behaviour is used to assess pain-associated behaviour in laboratory rodents. To gain insight into how models of disease-associated persistent pain and analgesics affect burrowing behaviour, we performed a systematic review and meta-analysis of studies that assessed burrowing behaviour. A systematic search in March 2020 and update in September 2020 was conducted in 4 databases. Study design characteristics and experimental data were extracted, followed by a random-effects meta-analysis. We explored the association between burrowing and monofilament-induced limb withdrawal. Dose response relationship was investigated for some analgesics. Forty-five studies were included in the meta-analysis, in which 16 model types and 14 drug classes were used. Most experiments used rat (79%) and male (72%) animals. Somatic inflammation and trauma-induced neuropathy models were associated with reduced burrowing behaviour. Analgesics (nonsteroidal anti-inflammatory drug and gabapentinoids) attenuated burrowing deficits in these models. Reporting of measures to reduce risk of bias was unclear except for randomisation which was high. There was not a correlation ( R2 = 0.1421) between burrowing and monofilament-induced limb withdrawal. Opioids, gabapentin, and naproxen showed reduced burrowing behaviour at high doses, whereas ibuprofen and celecoxib showed opposite trend. The findings indicate that burrowing could be used to assess pain-associated behaviour. We support the use of a portfolio of composite measures including spontaneous and stimulus-evoked tests. The information collected here could help in designing experiments involving burrowing assessment in models of disease-associated pain.
Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Celecoxib; Disease Models, Animal; Gabapentin; Ibuprofen; Male; Naproxen; Pain; Rats; Rodentia
PubMed: 35353780
DOI: 10.1097/j.pain.0000000000002632 -
The Cochrane Database of Systematic... Jan 2009Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a rare neurodegenerative disease. Approximately 5% to 7% of ALS/MND patients report a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a rare neurodegenerative disease. Approximately 5% to 7% of ALS/MND patients report a family history of a similarly affected relative. Superoxide dismutase-1 gene mutations are the cause in about 20% of familial cases. In those with non-familial (sporadic) ALS/MND the cause is unknown. Also unknown is whether patients with familial and sporadic ALS/MND respond differently to treatment.
OBJECTIVES
To systematically review the literature and to answer the specific question: 'Is there a difference in the response to treatment between patients with sporadic and familial forms of ALS?'
SEARCH STRATEGY
In May 2006 we searched the Cochrane Neuromuscular Disease Group Trials Register, MEDLINE (January 1966 to May 2006) and EMBASE (January 1980 to May 2006) for randomized controlled trials (RCTs). Two review authors read the titles and abstracts of all articles and reviewed the full text of all possibly relevant articles. We scanned references of all included trials to identify additional relevant articles. For all trials eligible for inclusion we contacted the authors to request the necessary raw data.
SELECTION CRITERIA
Studies had to meet two criteria: (a) randomized controlled study design, and (b) inclusion of patients with both familial and sporadic ALS/MND.
DATA COLLECTION AND ANALYSIS
We attempted to contact authors of all trials that met inclusion criteria. We obtained data regarding ALS/MND type (sporadic versus familial), treatment assignment (active versus placebo), survival and ALS Functional Rating Scale scores for four large RCTs that included 822 sporadic and 41 familial ALS patients. We could not obtain data from 25 potentially eligible studies (17 trial authors could not be contacted and eight were unwilling to provide data).
MAIN RESULTS
There was no statistical evidence for a different response to treatment in patients with familial ALS/MND compared to those with sporadic ALS/MND. The pooled estimate of the hazard ratio for the interaction term (treatment x familial ALS) suggested a more beneficial response with respect to survival among patients with familial ALS/MND, but the result was not statistically significant. Estimates of the rate of decline on the ALS Functional Rating Scale also suggested a slightly better response to treatment among those with familial ALS/MND, but the result was not statistically significant.
AUTHORS' CONCLUSIONS
Future RCTs should document whether patients with familial ALS/MND are included and the presence or absence of a mutation in the superoxide dismutase-1 gene amongst those with familial ALS/MND.
Topics: Amyotrophic Lateral Sclerosis; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Creatine; Fructose; Humans; Motor Neuron Disease; Neuroprotective Agents; Pyrazoles; Randomized Controlled Trials as Topic; Sulfonamides; Topiramate
PubMed: 19160266
DOI: 10.1002/14651858.CD006153.pub2 -
BMJ (Clinical Research Ed.) Aug 2013To summarise and compare the efficacy and safety of various oral anticoagulants (dabigatran, rivaroxaban, apixaban, and vitamin K antagonists) and antiplatelet agents... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: systematic review and network meta-analysis.
OBJECTIVE
To summarise and compare the efficacy and safety of various oral anticoagulants (dabigatran, rivaroxaban, apixaban, and vitamin K antagonists) and antiplatelet agents (acetylsalicylic acid) for the secondary prevention of venous thromboembolism.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Literature search using Medline (1950 to present), Embase (1980 to present), and the Cochrane Register of Controlled Trials using the OVID interface. Publications from potentially relevant journals were also searched by hand.
REVIEW METHODS
Randomised controlled trials of patients receiving anticoagulants, antiplatelet drugs, or placebo or observation for secondary prevention of venous thromboembolism. Selected outcomes were rates of recurrent venous thromboembolism and major bleeding. Two reviewers independently extracted data onto standardised forms.
RESULTS
12 articles met our inclusion criteria, with 11,999 patients evaluated for efficacy and 12,167 for safety. All treatments reduced the risk of recurrent venous thromboembolism. Compared with placebo or observation, vitamin K antagonists at a standard adjusted dose (target international normalised ratio 2.0-3.0) showed the highest risk difference (odds ratio 0.07; 95% credible interval 0.03 to 0.15) and acetylsalicylic acid showed the lowest risk difference (0.65; 0.39 to 1.03). Risk of major bleeding was higher with a standard adjusted dose of vitamin K antagonists (5.24; 1.78 to 18.25) than with placebo or observation. Fatal recurrent venous thromboembolism and fatal bleeding were rare. Detailed subgroup and individual patient level data were not available.
CONCLUSIONS
All oral anticoagulants and antiplatelet agents investigated in this analysis were associated with a reduced recurrence of venous thromboembolism compared with placebo or observation, although acetylsalicylic acid was associated with the lowest risk reduction. Vitamin K antagonists given at a standard adjusted dose was associated with the greatest risk reduction in recurrent venous thromboembolism, but also the greatest risk of major bleeding.
Topics: Anticoagulants; Aspirin; Benzimidazoles; Dabigatran; Hemorrhage; Humans; Morpholines; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Thiophenes; Venous Thromboembolism; Vitamin K; beta-Alanine
PubMed: 23996149
DOI: 10.1136/bmj.f5133 -
International Journal of Surgery... Dec 2016A systematic review and meta-analysis of published randomized controlled trials was performed to update the present evidence about the safety and efficacy of... (Meta-Analysis)
Meta-Analysis Review
Dexamethasone combined with other antiemetics versus single antiemetics for prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy: An updated systematic review and meta-analysis.
OBJECTIVE
A systematic review and meta-analysis of published randomized controlled trials was performed to update the present evidence about the safety and efficacy of dexamethasone combined with other antiemetics versus single antiemetics for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy.
METHODS
A computer literature search of PubMed, Scopus, Web of Science and Embase was conducted to identify the relevant randomized controlled trials. In addition, a manual search of reference lists of the retrieved articles was conducted. Relevant outcomes were pooled as odds ratio (OR) by RevMan version 5.3 for windows.
RESULTS
Pooled data from 14 RCTs (1542 patients) favored dexamethasone combined with other antiemetics over single antiemetics as a prophylaxis against postoperative nausea and vomiting after laparoscopic cholecystectomy in the early postoperative period (OR = 0.39, 95% CI [0.27 to 0.54], p < 0.00001), late postoperative period (OR = 0.36, 95% CI [0.23 to 0.56], p < 0.00001), and overall postoperative period (OR = 0.34, 95% CI [0.23 to 0.51], p < 0.00001). Subsequently, rescue antiemetic usage was significantly lower in the combination group (OR = 0.25, 95% CI [0.16 to 0.41], p < 0.00001). Subgroup analysis showed that all combinations of dexamethasone and other antiemetics were superior to corresponding singel antiemetics except for the combination of dexamethasone and ramosetron which was not superior to ramosetron alone in all postoperative periods and the combination of dexamethasone and granisetron which was not superior to granisetron alone in the early postoperative period (OR = 0.26, 95% CI [0.07 to 1.01], p = 0.05). For all adverse events, there was no significant difference between the two groups.
CONCLUSION
Dexamethasone combined with other antiemetics provided better prophylaxis than single antiemetics against postoperative nausea and vomiting after laparoscopic cholecystectomy. The underlying mechanism of dexamethasone action and its optimal dose should be further investigated.
Topics: Antiemetics; Benzimidazoles; Cholecystectomy, Laparoscopic; Dexamethasone; Drug Therapy, Combination; Granisetron; Humans; Isoquinolines; Metoclopramide; Ondansetron; Palonosetron; Postoperative Nausea and Vomiting; Quinuclidines; Randomized Controlled Trials as Topic
PubMed: 27793640
DOI: 10.1016/j.ijsu.2016.10.034 -
PloS One 2022Hematopoietic stem cell transplantation (HSCT) for haematological disorders. Graft-versus-host disease (GVHD), a cause of morbidity and mortality is treated with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hematopoietic stem cell transplantation (HSCT) for haematological disorders. Graft-versus-host disease (GVHD), a cause of morbidity and mortality is treated with corticosteroids. However, patients with steroid-refractory GVHD after HSCT have a poor prognosis. Ruxolitinib, a selective Janus kinase inhibitor, is a novel treatment strategy for steroid-refractory GVHD.
OBJECTIVES
To assess the efficacy of ruxolitinib for the treatment of steroid-refractory GVHD and analyse its adverse effects.
STUDY DESIGN
Meta-analysis.
SEARCH METHODS
Randomised controlled trials (RCTs) and non-RCTs of ruxolitinib-based therapy in patients with steroid-refractory GVHD were found in the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and Web of Science in March 2021. Outcomes included overall response rate, survival, and adverse effects. The Methodological Index for Non-randomised Studies (MINORS) and the Cochrane collaboration risk-of-bias tool were used to assess methodological quality. Funnel plots, Egger's test, and the trim and fill method were used to assess publication bias.
RESULTS
In total, 1470 studies were identified; 19 studies (17 non-RCTs, 2 RCTs) involving 1358 patients met our inclusion criteria. Survival rates at the longest follow-up in non-RCTs, were 57.5% (95% CI 46.9-67.4) and 80.3% (95% CI 69.7-87.9) for acute GVHD (aGVHD) and chronic GVHD (cGVHD), respectively. In non-RCTs, the overall response was 74.9% (95% CI 66.6-81.8, I2 = 49%) in aGVHD and 73.1% (95% CI 62.5-81.6, I2 = 49%) in cGVHD. In aGVHD, the response rates were gastrointestinal, 61.4-90.2%; skin, 52.5-80.6%; and liver, 41.8-71.8%. In cGVHD, the response rates were gastrointestinal, 30.1-70.4%; skin, 30.1-84.4%; lung, 27.0-83.0%; and mouth 3.5-98.1%. In addition, a lower aGVHD grade and moderate cGVHD were associated with a better clinical response. Common adverse events were cytopenia and infectious complications.
CONCLUSIONS
Our systematic review and meta-analysis indicated that ruxolitinib therapy could be a potentially effective and safe treatment for patients with steroid-refractory GVHD.
Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Nitriles; Pyrazoles; Pyrimidines; Steroids
PubMed: 35905125
DOI: 10.1371/journal.pone.0271979 -
Respiratory Medicine Oct 2022There are conflicting reports on the results of several of the latest clinical trials related to the use of baricitinib in the management of COVID-19 patients. The aim... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are conflicting reports on the results of several of the latest clinical trials related to the use of baricitinib in the management of COVID-19 patients. The aim of the current systematic review and meta-analysis was to evaluate the efficacy of baricitinib in COVID-19 patients.
METHODS
Databases like ScienceDirect, PubMed/Medline, Publons, Google Scholar and other sources like ClinicalTrials.gov, Cochrane, medRxiv, Research Square and reference lists were thoroughly searched.
RESULTS
Fifteen (15) articles which met the inclusion criteria were qualitatively and quantitatively analysed. Based on Cochrane and Newcastle-Ottawa Scale (NOS) risk of bias (RoB) analyses, 14/15 articles are grouped as high-quality. Meta-analyses revealed that randomised control trials (RCTs) and non-randomised control trials (nRCTs) statistically significantly reduced the mortality rate in COVID-19 patients, with a risk ratio (RR) in the fixed-effect model was RR = 0.64 [95% CI: 0.51 to 0.79; p < 0.0001] and RR = 0.58 [95% CI: 0.45 to 0.73; p < 0.00001], respectively, with insignificant heterogeneity and no publication bias found. For block/reduce disease progression (BDP), baricitinib did not statistically significantly reduce disease progression for RCTs. The RR in the random effect model was RR = 0.80 [95% CI: 0.58 to 1.10: p = 0.17], with significant heterogeneity, where I was 60%. On the other hand, baricitinib statistically significantly reduced disease progression in nRCTs, as the RR of the fixed effect model was RR = 0.54 [95% CI: 0.37 to 0.78; p = 0.001] with insignificant heterogeneity.
CONCLUSION
The current meta-analyses revealed that baricitinib statistically significantly reduced mortality rate and disease progression in COVID-19 patients.
PROSPERO REGISTRATION NUMBER
CRD42021281556.
Topics: Azetidines; Disease Progression; Humans; Purines; Pyrazoles; SARS-CoV-2; Sulfonamides; COVID-19 Drug Treatment
PubMed: 36150282
DOI: 10.1016/j.rmed.2022.106986 -
The Cochrane Database of Systematic... Oct 2013This is an update of a review first published in The Cochrane Library in Issue 4, 2008, and updated in Issue 3, 2012. Celecoxib is a selective cyclo-oxygenase-2 (COX-2)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of a review first published in The Cochrane Library in Issue 4, 2008, and updated in Issue 3, 2012. Celecoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor usually prescribed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis. Celecoxib is believed to be associated with fewer upper gastrointestinal adverse effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). Its effectiveness in acute pain was demonstrated in the earlier reviews.
OBJECTIVES
To assess analgesic efficacy and adverse effects of a single oral dose of celecoxib for moderate to severe postoperative pain in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Database, and ClinicalTrials.gov. The most recent search was to 31 May 2013.
SELECTION CRITERIA
We included randomised, double-blind, placebo-controlled trials (RCTs) of adults prescribed any dose of oral celecoxib or placebo for acute postoperative pain.
DATA COLLECTION AND ANALYSIS
Two review authors assessed studies for quality and extracted data. We converted summed pain relief (TOTPAR) or pain intensity difference (SPID) into dichotomous information, yielding the number of participants with at least 50% pain relief over four to six hours. We used this to calculate the relative benefit (RB) and number needed to treat to benefit (NNT), for one patient to achieve at least 50% of maximum pain relief with celecoxib who would not have done so with placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use.
MAIN RESULTS
Ten studies (1785 participants) met the inclusion criteria. The two new studies in this update had been identified in the earlier update, but data were not available. There remain three potentially relevant unpublished studies for which data are not available at this time.The NNT for celecoxib 200 mg and 400 mg compared with placebo for at least 50% of maximum pain relief over four to six hours was 4.2 (95% confidence interval (CI) 3.4 to 5.6) and 2.6 (95% CI 2.3 to 3.0) respectively. The median time to use of rescue medication was 6.6 hours with celecoxib 200 mg, 8.4 hours with celecoxib 400 mg, and 2.3 hours with placebo. The proportion of participants requiring rescue medication over 24 hours was 74% with celecoxib 200 mg, 63% for celecoxib 400 mg, and 91% for placebo. The NNT to prevent one patient using rescue medication was 4.8 (95% CI 3.5 to 7.7) and 3.5 (95% CI 2.9 to 4.6) for celecoxib 200 mg and 400 mg respectively. Adverse events were generally mild to moderate in severity, and were experienced by a similar proportion of participants in the celecoxib and placebo groups. One serious adverse event that was probably related to celecoxib was reported.
AUTHORS' CONCLUSIONS
Single-dose oral celecoxib is an effective analgesic for postoperative pain relief. Indirect comparison suggests that the 400 mg dose has similar efficacy to ibuprofen 400 mg.
Topics: Acute Pain; Administration, Oral; Adult; Celecoxib; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Humans; Pain, Postoperative; Pyrazoles; Randomized Controlled Trials as Topic; Sulfonamides
PubMed: 24150982
DOI: 10.1002/14651858.CD004233.pub4 -
American Journal of Hematology Mar 2018Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of... (Meta-Analysis)
Meta-Analysis
Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of estimating the risk of infections in patients treated with ruxolitinib. Studies were identified by electronic search of MEDLINE and EMBASE database. Differences in the incidence of infectious events between ruxolitinib and comparison groups were expressed as odds ratios (ORs) and 95% confidence intervals (95% CI). Five phase III randomized clinical trials (RCTs) (3 phase IIIa with their extended phase and 2 phase IIIb), 6 phase IV studies and 28 case reports were included in this systematic review. Ruxolitinib was associated with a statistically significant increased risk of herpes zoster infection compared to control group in 3 RCTs including patients with polycythemia vera (OR 7.39 [1.33, 41.07]) and in a pooled analysis of the extended phase IIIa RCTs (OR 5.20 [95%CI 1.27, 21.18]). In the larger phase IV post-marketing study, the incidence of the most frequent infections was 8% for herpes zoster, 6.1% for bronchitis and 6% for urinary tract infections. In the published case reports, the most frequent infections were tuberculosis (N = 10), hepatitis B reactivation (N = 5) and pneumocystis jeroveci infection (N = 2). Evidence is not solid enough to accurately estimate the risk of infection in ruxolitinib-treated patients. However, published data clearly suggest that the infection risk may be clinically relevant. Well-designed studies are warranted to evaluate the risk of ruxolitinib-associated infection, in order to identify the most appropriate antimicrobial prophylactic strategy.
Topics: Antibiotic Prophylaxis; Bacterial Infections; Clinical Trials, Phase III as Topic; Confidence Intervals; Disease Susceptibility; Herpes Zoster; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidence; Infections; Janus Kinase 1; Janus Kinase 2; Mycoses; Nitriles; Odds Ratio; Product Surveillance, Postmarketing; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; Risk
PubMed: 29150886
DOI: 10.1002/ajh.24976