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European Neurology 2017Gait impairment is one of the most disabling symptoms in people with multiple sclerosis (PwMS). Fampridine, has demonstrated a positive effect on gait speed in PwMS... (Review)
Review
BACKGROUND
Gait impairment is one of the most disabling symptoms in people with multiple sclerosis (PwMS). Fampridine, has demonstrated a positive effect on gait speed in PwMS after 14 days of treatment but the long-term effects have not yet been demonstrated. This study reviews the long-term effects of fampridine on gait in PwMS.
SUMMARY
This systematic review was conducted according to the PRISMA statement. Studies were considered long term if treatment exceeded 28 days. From the 498 studies identified, 18 (2,200 patients) fulfilled all eligibility criteria. Only 3 studies followed-up patients for >1 year and one of these showed a non-significant improvement in the gait speed. Key Messages: Fampridine seems to be beneficial at improving gait speed in PwMS in the long term. Further long-term studies are needed on related gait and functional parameters.
Topics: 4-Aminopyridine; Adult; Female; Gait; Gait Disorders, Neurologic; Humans; Male; Middle Aged; Multiple Sclerosis; Potassium Channel Blockers
PubMed: 28992626
DOI: 10.1159/000480729 -
European Journal of Pediatrics Feb 2024To evaluate milrinone's impact on pediatric cardiac function, focusing on its specific role as an inotrope and lusitrope, while considering its systemic and pulmonary... (Meta-Analysis)
Meta-Analysis
UNLABELLED
To evaluate milrinone's impact on pediatric cardiac function, focusing on its specific role as an inotrope and lusitrope, while considering its systemic and pulmonary vasodilatory effects. Search of PubMed, EMBASE, and the Cochrane Library up to August 2023. We included all studies that evaluated milrinone in children under 18 years old in neonatal, pediatric, or cardiac intensive care units. We excluded case reports, studies that did not provide tabular information on milrinone's outcomes, and studies focused on non-intensive care populations. We extracted data on the research design, objectives, study sample, and results of each study, including the impact of milrinone and any associated factors. We screened a total of 9423 abstracts and 41 studies were ultimately included. Milrinone significantly improved left ventricular ejection fraction (WMD 3.41 [95% CI 0.61 - 6.21]), left ventricle shortening fraction (WMD 4.25 [95% CI 3.43 - 5.08]), cardiac index (WMD 0.50 [95% CI 0.32 to 0.68]), left ventricle output (WMD 55.81 [95% CI 4.91 to 106.72]), serum lactate (WMD -0.59 [95% CI -1.15 to -0.02]), and stroke volume index (WMD 2.95 [95% CI 0.09 - 5.82]). However, milrinone was not associated with improvements in ventricular myocardial performance index (WMD -0.01 [95% CI -0.06 to 0.04]) and ventricular longitudinal strain (WMD -2.14 [95% CI -4.56 to 0.28]). Furthermore, milrinone was not associated with isovolumetric relaxation time reduction (WMD -8.87 [95% CI -21.40 to 3.66]).
CONCLUSION
Our meta-analysis suggests potential clinical benefits of milrinone by improving cardiac function, likely driven by its systemic vasodilatory effects. However, questions arise about its inotropic influence and the presence of a lusitropic effect. Moreover, milrinone's pulmonary vasodilatory effect appears relatively weaker compared to its systemic actions. Further research is needed to elucidate milrinone's precise mechanisms and refine its clinical applications in pediatric practice.
WHAT IS KNOWN
• Milrinone is a phosphodiesterase III inhibitor that has been used to treat a variety of pediatric and neonatal conditions. • Milrinone is believed to exert its therapeutic effects by enhancing cardiac contractility and promoting vascular relaxation.
WHAT IS NEW
• Milrinone may not have a significant inotropic effect. • Milrinone's pulmonary vasodilatory effect is less robust than its systemic vasodilatory effect.
Topics: Adolescent; Child; Humans; Infant, Newborn; Cardiotonic Agents; Heart Failure; Hypertension, Pulmonary; Milrinone; Stroke Volume; Ventricular Function, Left; Infant; Child, Preschool
PubMed: 37999764
DOI: 10.1007/s00431-023-05342-0 -
International Journal of Chronic... 2016Current evidence suggests that roflumilast is efficacious in treating COPD, especially in preventing the acute exacerbation of COPD. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Current evidence suggests that roflumilast is efficacious in treating COPD, especially in preventing the acute exacerbation of COPD.
OBJECTIVES
This study was designed to evaluate the clinical effects and safety of roflumilast in the treatment of stable COPD using randomized clinical trial (RCT) data.
METHODS
A MEDLINE, EMBASE, and Cochrane Controlled Trials Register search was carried out. RCTs reporting the treatment effects of roflumilast in COPD were identified. Relevant data were extracted and a meta-analysis was performed.
RESULTS
A total of nine articles and 13 RCT studies were identified. Overall, 29.1% of the subjects in the roflumilast group showed evidence of exacerbation. The corresponding figure was 32.2% in the placebo group. According to pooled analysis, the use of roflumilast reduced COPD exacerbations in comparison to placebo (odds ratio [OR] =0.82, 95% confidence interval [CI] =0.75-0.9). The quality of life and spirometry were improved. For patients receiving baseline pre-bronchodilators, their average forced expiratory volume in the first second showed evidence of change when they took roflumilast (64.88 mL; 95% CI =54.09-75.66). Those who took placebo showed no evidence of change. Similar result was observed in patients receiving baseline (54.49 mL; 95% CI =44.04-64.94). As for the safety of roflumilast treatment, the overall cumulative incidence of adverse drug reaction was 54.2% in the roflumilast group and 48.2% in the placebo group (OR =1.36, 95% CI =1.13-1.65). The adverse effects included diarrhea, headache, nausea, weight loss, and insomnia.
CONCLUSION
The efficacy of roflumilast in the prevention of acute exacerbation of COPD is obvious. Roflumilast is proved to be able to improve spirometry of COPD patients. The adverse drug reaction did not increase significantly in the roflumilast group compared with the control group. COPD patients can benefit from roflumilast therapy. However, our results are limited by the cohort design of the selected studies and the degree of heterogeneity among them; hence, more randomized trials are needed to further support this conclusion.
Topics: Aminopyridines; Benzamides; Chi-Square Distribution; Cyclopropanes; Disease Progression; Forced Expiratory Volume; Humans; Lung; Odds Ratio; Phosphodiesterase 4 Inhibitors; Pulmonary Disease, Chronic Obstructive; Recovery of Function; Severity of Illness Index; Spirometry; Treatment Outcome; Vital Capacity
PubMed: 27418821
DOI: 10.2147/COPD.S106370 -
International Immunopharmacology Jan 2024Hidradenitis suppurativa (HS) is a challenging skin disease with an underlying inflammatory process. Substantial progress has been made in our understanding of HS over... (Review)
Review
BACKGROUNDS AND AIMS
Hidradenitis suppurativa (HS) is a challenging skin disease with an underlying inflammatory process. Substantial progress has been made in our understanding of HS over the last few years, with the advancement of novel treatment approaches. The current systematic review aims to evaluate the safety and efficacy of Janus kinase (JAK) inhibitors and spleen tyrosine kinase (Syk) inhibitors in treating HS.
METHOD
A thorough systematic search was performed on PubMed/Medline, Web of Science, and Ovid Embase databases up to September 23th, 2023. Clinical studies published in English were included.
RESULTS
Our search yielded ten articles with a total of 165 patients treated with four types of JAK inhibitors (upadacitinib, povorcitinib, tofacitinib, and baricitinib) and one Syk inhibitor (fostamatinib). Upadacitinib, povorcitinib, and tofacitinib improved clinical outcomes, with a significant reduction in hidradenitis suppurativa clinical response (HiSCR) and abscess and inflammatory nodule count (AN count) during the treatment period. Also, these drugs are well tolerated in most HS patients with minimal adverse events (AEs). Moreover, baricitinib depicted an amelioration in signs and symptoms of HS in one case report. Also, fostamatinib exhibited favorable tolerability throughout a 12-week in moderate-to-severe HS patients. The remarkable clinical improvement, as assessed through HiSCR and hidradenitis suppurativa severity (IHS4), corresponded closely with serological indicators of inflammation following fostamatinib administration was achieved.
CONCLUSION
JAK and Syk inhibitors are potentially efficacious in managing moderate-to-severe HS since the proinflammatory cytokines are mediated by JAK and Syk signaling pathways. However, further research with a more rigorous examination is mandatory to evaluate such medication's long-term safety and efficacy.
Topics: Humans; Hidradenitis Suppurativa; Adalimumab; Janus Kinase Inhibitors; Tyrosine Kinase Inhibitors; Spleen; Syk Kinase; Treatment Outcome; Severity of Illness Index; Aminopyridines; Pyrazoles; Sulfonamides; Azetidines; Purines; Pyrimidines; Morpholines
PubMed: 38150881
DOI: 10.1016/j.intimp.2023.111435 -
Respiratory Research Feb 2016Effects of roflumilast on lung function, symptoms, acute exacerbation and adverse events in patients with chronic obstructive pulmonary disease (COPD) are controversial.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Effects of roflumilast on lung function, symptoms, acute exacerbation and adverse events in patients with chronic obstructive pulmonary disease (COPD) are controversial. We aimed to further clarify the efficacy and safety of roflumilast in treatment of moderate-to-severe COPD.
METHODS
From 1946 to November 2015, we searched the Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials, ISI Web of Science and American College of Physician using "roflumilast" and "chronic obstructive pulmonary disease" or "COPD". Randomized controlled trials that reported forced expiratory volume in one second (FEV1), forced vital capacity (FVC), transition dyspnea index (TDI), St George's Respiratory Questionnaire (SGRQ), and incidence of COPD exacerbations and adverse events were eligible. We conducted the heterogeneities test and sensitivity analysis, and random-effects or fixed-effects model was applied to calculate risk ratio (RR) and mean difference (MD) for dichotomous and continuous data respectively. Cochrane systematic review software, Review Manager (RevMan), was used to test the hypothesis by Mann-Whitney U-test.
RESULTS
Thirteen trials with a total of 14,563 patients were pooled in our final studies. Except for SGRQ (I (2) = 63 %, χ (2) = 1.71, P = 0.07) and adverse events (I (2) = 94 %, χ (2) = 0.03, P < 0.001), we did not find statistical heterogeneity in outcome measures. The pooled MD of pre- and post-bronchodilator FEV1 was 54.60 (95 % confidence interval (CI) 46.02 ~ 63.18) and 57.86 (95 % CI 49.80 ~ 65.91), and both showed significant improvement in patients with roflumilast (z = 12.47, P <0.001; z = 14.07, P < 0.001), so did in FVC (MD 90.37, 95 % CI 73.95 ~ 106.78, z = 10.79, P < 0.001). Significant alleviation of TDI (MD 0.30, 95 % CI 0.14 ~ 0.46, z = 3.67, P < 0.001) and decrease of acute exacerbation (RR 0.86, 95 % CI 0.81 ~ 0.91, z = 5.54, P < 0.001) were also identified in treatment of roflumilast, but without significant difference in SGRQ (MD -1.30, 95 % CI -3.16 ~ 0.56, z = 1.37, P = 0.17). Moreover, roflumilast significantly increased the incidence of adverse events compared with placebo (RR 1.31, 95 % CI 1.16 ~ 1.47, z = 4.32, P < 0.001).
CONCLUSIONS
Roflumilast can be considered as an alternative therapy in selective patients with moderate-to-severe COPD.
Topics: Adult; Aged; Aged, 80 and over; Aminopyridines; Benzamides; Cyclopropanes; Female; Humans; Male; Middle Aged; Phosphodiesterase 4 Inhibitors; Prevalence; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Risk Factors; Severity of Illness Index; Treatment Outcome
PubMed: 26887407
DOI: 10.1186/s12931-016-0330-y -
The Cochrane Database of Systematic... Sep 2017Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea and a reduction in lung function, quality of life and life... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea and a reduction in lung function, quality of life and life expectancy. Apart from smoking cessation, there are no other treatments that slow lung function decline. Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This is an update of a Cochrane review first published in 2011 and updated in 2013.
OBJECTIVES
To evaluate the efficacy and safety of oral PDE inhibitors in the management of stable COPD.
SEARCH METHODS
We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search October 2016). We found other trials from web-based clinical trials registers.
SELECTION CRITERIA
We included RCTs if they compared oral PDE inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy.
DATA COLLECTION AND ANALYSIS
One review author extracted data and a second review author checked the data. We reported pooled data in Review Manager as mean differences (MD), standardised mean differences (SMD) or odds ratios (OR). We converted the odds ratios into absolute treatment effects in a 'Summary of findings' table.
MAIN RESULTS
Thirty-four separate RCTs studying roflumilast (20 trials with 17,627 participants) or cilomilast (14 trials with 6457 participants) met the inclusion criteria, with a duration of between six weeks and one year. These included people across international study centres with moderate to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades II-IV), with a mean age of 64 years.We considered that the methodological quality of the 34 published and unpublished trials was acceptable overall. Treatment with a PDE inhibitor was associated with a significant improvement in forced expiratory volume in one second (FEV) over the trial period compared with placebo (MD 51.53 mL, 95% confidence interval (CI) 43.17 to 59.90, 27 trials with 20,585 participants, moderate-quality evidence due to moderate levels of heterogeneity and risk of reporting bias). There were small improvements in quality of life (St George's Respiratory Questionnaire (SGRQ), MD -1.06 units, 95% CI -1.68 to -0.43, 11 trials with 7645 participants, moderate-quality evidence due to moderate levels of heterogeneity and risk of reporting bias) and COPD-related symptoms, but no significant change in exercise tolerance. Treatment with a PDE inhibitor was associated with a reduced likelihood of COPD exacerbation (OR 0.78, 95% CI 0.73 to 0.83; 23 trials with 19,948 participants, high-quality evidence). For every 100 people treated with PDE inhibitors, five more remained exacerbation-free during the study period compared with placebo (number needed to treat for an additional beneficial outcome (NNTB) 20, 95% CI 16 to 26). More participants in the treatment groups experienced non-serious adverse events compared with controls, particularly a range of gastrointestinal symptoms such as diarrhoea, nausea, vomiting or dyspepsia. For every 100 people treated with PDE inhibitors, seven more suffered from diarrhoea during the study period compared with placebo (number needed to treat for an additional harmful outcome (NNTH) 15, 95% CI 13 to 17). Roflumilast in particular was associated with weight loss during the trial period and an increase in insomnia and depressive mood symptoms. There was no significant effect of treatment on non-fatal serious adverse events (OR 0.99, 95% CI 0.91 to 1.07) or mortality (OR 0.97, 95% CI 0.76 to 1.23), although mortality was a rare event during the trials. Participants treated with PDE inhibitors were more likely to withdraw from the trials because of adverse effects; on average 14% in the treatment groups withdrew compared with 8% in the control groups.
AUTHORS' CONCLUSIONS
In people with COPD, PDE inhibitors offered benefit over placebo in improving lung function and reducing the likelihood of exacerbations; however, they had little impact on quality of life or symptoms. Gastrointestinal adverse effects and weight loss were common, and safety data submitted to the US Food and Drug Administration (FDA) have raised concerns over psychiatric adverse events with roflumilast. The findings of this review give cautious support to the use of PDE inhibitors in COPD. They may be best used as add-on therapy in a subgroup of people with persistent symptoms or exacerbations despite optimal COPD management. This is in accordance with the GOLD 2017 guidelines. Longer-term trials are needed to determine whether or not PDE inhibitors modify FEV decline, hospitalisation or mortality in COPD.
Topics: Administration, Oral; Aminopyridines; Benzamides; Cyclohexanecarboxylic Acids; Cyclopropanes; Disease Progression; Forced Expiratory Volume; Humans; Nitriles; Phosphodiesterase 4 Inhibitors; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 28922692
DOI: 10.1002/14651858.CD002309.pub5 -
Expert Opinion on Drug Safety 2023Thrombosis is the second leading cause of mortality in cancer patients. This study aimed to investigate the association between cyclin-dependent kinase 4 and 6... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thrombosis is the second leading cause of mortality in cancer patients. This study aimed to investigate the association between cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) and thrombosis.
RESEARCH DESIGN AND METHODS
A retrospective pharmacovigilance analysis based on real-world data combined with a systematic review was used to explore the thrombotic risk profiles of CDK4/6i. The study has been registered with Prospero (CRD42021284218).
RESULT
In the pharmacovigilance analysis, CDK4/6i showed a higher rate of reported venous thromboembolism (VTE) (ROR = 2.78, 95% CI = 2.64-2.92), with the highest signal for trilaciclib (ROR = 27.55, 95% CI = 13.43-56.52) but only 9 cases, followed by abemaciclib (ROR = 3.73, 95% CI = 3.19-4.37). For arterial thromboembolism (ATE), only ribociclib increased the reporting rate (ROR = 2.14, 95% CI = 1.91-2.41). In the meta-analysis, palbociclib, abemaciclib, and trilaciclib all increased the risk of VTE (OR = 2.23, 3.17, and 3.90). In the subgroup analysis, only abemaciclib increased the risk of ATE (OR = 2.11, 95% CI = 1.12-3.99) .
CONCLUSIONS
CDK4/6i had different profiles of thromboembolism. Palbociclib, abemaciclib, or trilaciclib increased the risk of VTE. Ribociclib and abemaciclib showed a weak association with the risk of ATE.
Topics: Humans; Female; Cyclin-Dependent Kinase 4; Venous Thromboembolism; Pharmacovigilance; Retrospective Studies; Aminopyridines; Thrombosis; Protein Kinase Inhibitors; Breast Neoplasms
PubMed: 36794339
DOI: 10.1080/14740338.2023.2181338 -
Scientific Reports Feb 2024Individual trials of abemaciclib, palbociclib, and ribociclib show a similar impact on progression-free survival yet differing statistical significance for overall... (Meta-Analysis)
Meta-Analysis
Individual trials of abemaciclib, palbociclib, and ribociclib show a similar impact on progression-free survival yet differing statistical significance for overall survival (OS). A robust comparative evaluation of OS, safety, and tolerability of the three drugs is warranted. A systematic literature search identified phase 3 randomized clinical trials reporting OS of CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy in ER-positive/HER2-negative advanced breast cancer. Trial-level data on OS and common and serious adverse events (AE) were extracted for each drug. In the absence of direct comparisons, a network meta-analysis was performed to evaluate pairwise comparative efficacy, safety, and tolerability of each of the CDK4/6i. Seven studies comprising of 4415 patients met the inclusion criteria. Median follow-up was 73.3 months (range: 48.7-97.2 months). There were no statistically significant differences in OS between any of the CDK4/6i. Compared to palbociclib, ribociclib and abemaciclib both showed significantly higher GI toxicity (grade 1-2 vomiting OR 1.87 [95% CI 1.37-2.56] and OR 2.27 [95% CI 1.59-3.23] respectively). Compared to palbociclib, abemaciclib was associated with more grade 3-4 diarrhea OR 118.06 [95% CI 7.28-1915.32]. In contrast, palbociclib was associated with significantly more neutropenia than ribociclib and abemaciclib but significantly lower risk of grade 3-4 infections. Abemaciclib had significantly less grade 3-4 transaminitis and grade 3-4 neutropenia than ribociclib. Treatment discontinuation and death due to AE were significantly higher with abemaciclib than palbociclib and ribociclib. There is no statistically significant difference in OS between CDK4/6i despite differing statistical significance levels of individual trials. Real-world data analyses may help to identify if there is a meaningful inter-drug difference in efficacy. Significant differences between CDK4/6i are observed for safety and tolerability outcomes.
Topics: Female; Humans; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Cyclin-Dependent Kinase Inhibitor Proteins; Neutropenia; Purines; Clinical Trials, Phase III as Topic; Randomized Controlled Trials as Topic
PubMed: 38326452
DOI: 10.1038/s41598-024-53151-8 -
Cellular and Molecular Biology... Mar 2023Cardiovascular failure is the main cause of death in industrialized societies. The results of recent studies have shown that some mutations in the MEFV gene are common... (Meta-Analysis)
Meta-Analysis
Cardiovascular failure is the main cause of death in industrialized societies. The results of recent studies have shown that some mutations in the MEFV gene are common in heart failure patients. For this reason, the study of mutations and genetic factors has been of great help in the treatment of this disease, but despite this, due to the heterogeneity of clinical symptoms, multiple pathophysiological processes, and environmental genetic factors, the complete understanding of the genetic causes of this disease is very complicated. As the new generation of phosphodiesterase (PDE) III inhibitor, olprinone, the inhibition of human heart PDE III by olprinone is highly selective. It is suitable for the treatment of acute heart failure (HF) and acute cardiac insufficiency after cardiac surgery. In this study Olprinone, milrinone, PDE inhibitors, cardiac failure, and HF were selected as the search terms to retrieve articles published between January 1999 and March 2022. RevMan5.3 and Stata were employed to analyze and evaluate the risk bias of the included articles. Besides, the Q test and heterogeneity were utilized to evaluate the heterogeneity between articles. The results of this research showed No heterogeneity was found between each research group. The sensitivity (Sen) and specificity (Spe) of the two methods were compared. Olprinone showed more significant therapeutic effects than other PDE inhibitors. Besides, the therapeutic effect on the patients with HF in the two groups was obvious. The incidence of postoperative adverse reactions among the patients without relieving HF was low. The influences on urine flow of the two group's demonstrated heterogeneity, and its effect revealed no statistical meaning. The meta-analysis confirmed that the Spe and Sen of olprinone treatment were higher than those of other PDE inhibitors. In terms of hemodynamics, there was little difference between various treatment methods.
Topics: Humans; Heart Failure; Imidazoles; Milrinone; Phosphodiesterase Inhibitors; Pyridones
PubMed: 37300686
DOI: 10.14715/cmb/2023.69.3.11 -
BMJ Open Sep 2022To systematically evaluate the efficacy and safety of anaplastic lymphoma kinase (ALK) inhibitors in ALK-rearranged positive non-small cell lung cancer (NSCLC) with... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically evaluate the efficacy and safety of anaplastic lymphoma kinase (ALK) inhibitors in ALK-rearranged positive non-small cell lung cancer (NSCLC) with brain metastases, and update the overall survival (OS) outcomes of the second-generation and third-generation ALK (ALK-2G/3G) inhibitors versus first-generation (ALK-1G) inhibitors.
DESIGN
The study is in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Randomised controlled trials (RCTs) published up to 3 November 2021 were retrieved from PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov.
SETTING
RCTs from any country and healthcare setting.
PARTICIPANTS
Patients with advanced ALK-positive NSCLC with or without brain metastases.
INTERVENTIONS AND COMPARISONS
The interventions were ALK-2G/3G; the control arm was ALK-1G or crizotinib.
PRIMARY AND SECONDARY OUTCOME MEASURES
Primary outcomes included median progression-free survival and median OS. Secondary outcomes included systemic objective response rate, intracranial response rate and rate of grade ≥3 adverse events (AEs).
RESULTS
A total of 12 RCTs involving 3156 patients were analysed. Compared with ALK-1G (crizotinib), ALK-2G (alectinib, brigatinib, ceritinib and ensartinib) significantly improved the OS (HR: 0.72, 95% CI: 0.57 to 0.90, p=0.004) and intracranial response of patients with any brain metastases, especially with measurable (diameter ≥10 mm) brain metastases. Network meta-analysis demonstrated that ALK-3G (lorlatinib) had superior efficacy for patients with brain lesions, but performed a distinct side-effect profile. Moreover, alectinib showed superior efficacy and lower toxicity in ALK-positive NSCLC.
CONCLUSION
Treatment with ALK-2G inhibitors significantly improved OS compared with crizotinib, and alectinib has less severe AEs than any other ALK inhibitors with moderate-high efficacy. The limited OS follow-up and inadequate sample sizes might contribute to having no statistically significant difference in OS of lorlatinib versus crizotinib. More high-quality and longer follow-up RCTs are warranted to prove our findings.
PROSPERO REGISTRATION NUMBER
CRD42021292245.
Topics: Aminopyridines; Anaplastic Lymphoma Kinase; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Crizotinib; Humans; Lactams; Lactams, Macrocyclic; Lung Neoplasms; Network Meta-Analysis; Protein Kinase Inhibitors; Pyrazoles
PubMed: 36123063
DOI: 10.1136/bmjopen-2022-060782