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Lung Cancer (Amsterdam, Netherlands) Feb 2023Thymic carcinoma (TC) is a rare cancer and patients failing initial chemotherapy (relapse/refractory) face limited therapeutic options given no approved options or... (Meta-Analysis)
Meta-Analysis Review
Thymic carcinoma (TC) is a rare cancer and patients failing initial chemotherapy (relapse/refractory) face limited therapeutic options given no approved options or consensus standard of care. This study aimed to identify and summarize clinical outcomes of all regimens evaluated in clinical trials of relapsed or refractory patients. Interventional trials enrolling advanced TC patients who failed first-line chemotherapy and reported outcomes in this group were eligible for inclusion in our systemic literature review (SLR). Between-study heterogeneity was assessed to determine the feasibility of pooling specific studies and treatments. Objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and duration of response (DOR) endpoints were of interest for meta-analysis. Nineteen trials were identified in the SLR. Three trials with one or two TC patients were removed from our assessment to reduce publication bias. Response rates among studies with at least ten TC patients varied from 9 % to 38 %. Pooled ORRs in patients receiving S-1 (46 patients), sunitinib (46 patients), or pembrolizumab (66 patients) were 28 %, 24 %, and 21 %, respectively. Prolonged duration of response with pembrolizumab was observed with a pooled median of 23.8 months (95 % confidence interval [CI]: 12, not reached). Median PFS of five months or greater was reported in patients treated with sunitinib, lenvatinib, pembrolizumab, capecitabine + gemcitabine, everolimus, or S-1. Median OS of 20 months or greater was reported in trials evaluating S-1 or pembrolizumab; this endpoint was not reached in trials evaluating lenvatinib, regorafenib, or sunitinib. Generalizability of treatment effects is challenging in the research of rare diseases and meta-analysis of clinical outcomes may help to increase precision and relevance of results to the larger TC population. Our study found limited treatment options upon relapse, demonstrating a need for further investigations into novel therapeutics and well-powered clinical trials to better inform on optimal treatments.
Topics: Humans; Sunitinib; Thymoma; Platinum; Neoplasm Recurrence, Local; Lung Neoplasms; Thymus Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36638588
DOI: 10.1016/j.lungcan.2023.01.003 -
European Review For Medical and... Nov 2021The phenomenon is that few randomized control trials (RCTs) directly compared the effects of bevacizumab with other types of standard treatments for recurrent... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The phenomenon is that few randomized control trials (RCTs) directly compared the effects of bevacizumab with other types of standard treatments for recurrent glioblastoma (GBM). We conducted a systematic review and meta-analysis to assess the efficacy of bevacizumab in recurrent GBM patients.
MATERIALS AND METHODS
We searched electronic databases (Medline, Embase, and Web of Science) contrasting the bevacizumab with standard treatments up to May 2021. For the continuous outcomes of median progression-free survival (PFS) and median overall survival (OS), we summarized the mean difference (MD) as the effective index. We used relative risk (RR) to estimate the data with a random-effects model to get the outcomes of objective response rate (ORR), 12-month OS, 6-month PFS, and any mentioned adverse events.
RESULTS
A total of 807 patients in 5 RCTs included into our systematic review and meta-analysis. The results showed bevacizumab could provide benefits of the ORR (RR, 2.67; 95% CI: 1.14-6.26, p = 0.02), median PFS (MD, 1.12 months; 95% CI: 0.35-1.90 months, p = 0.005), but not the median OS (MD, -0.19 months; 95% CI: -1.37-0.99 months, p = 0.75). Whereas the rates of the secondary outcomes of interest were similar between the bevacizumab group and control group, including 6 month-PFS (RR, 1.23; 95% CI, 0.82-1.84, p = 0.32) and 12 month-OS (RR, 0.93; 95% CI, 0.79-1.09, p = 0.36). As for adverse events, patients with bevacizumab showed higher rates of grade 3/4 and any grade hypertension compared with those with standard treatments (RR, 3.71; 95% CI: 1.17-11.76, p = 0.03; RR, 2.68; 95% CI: 1.26-5.76, p = 0.01, respectively).
CONCLUSIONS
This study provides clear proof of the beneficial effects of bevacizumab treatment in recurrent GBM patients. The only observed adverse event was grade 3/4 or any grade hypertension.
Topics: Angiogenesis Inhibitors; Bevacizumab; Brain Neoplasms; Glioblastoma; Humans; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34787852
DOI: 10.26355/eurrev_202111_27092 -
Clinical Sarcoma Research 2020Osteosarcoma is a very aggressive primary bone tumour, affecting mainly young populations. Most cases diagnosed have distant macro- and micro-metastases at the time of... (Review)
Review
BACKGROUND
Osteosarcoma is a very aggressive primary bone tumour, affecting mainly young populations. Most cases diagnosed have distant macro- and micro-metastases at the time of diagnosis. Surgical resection with neoadjuvant and adjuvant therapies improves the overall and disease-free survival of patients. Doxycycline, a synthetic tetracycline, has been found to act either as an antibiotic drug or as a chemotherapeutic agent. Its anti-neoplastic role has been found to be significant, in vitro and in vivo laboratory trials, in various types of cancer, such as prostate, intestinal, central neural system cancers and osteosarcoma. Inhibition of metalloproteinases (MMPs) in different stages of tumour expansion is the most well-understood mechanism. MMPs are secreted molecules from various normal cells, such as fibroblasts, leucocytes and vascular smooth muscles, as well as from cells with high proliferative potential, such as tumour cells. In osteosarcoma, MMPs have been found to be overexpressed. MMPs help osteosarcoma cells survive, grow and produce metastases in distant sites, mainly in the lungs. Doxycycline blocks extracellular matrix and basic membrane degradation by suppressing MMP function. As a consequence, osteosarcoma cells lose their ability to invade and metastasize. Additionally, doxycycline eliminates the secretion of vascular endothelial growth factor (VEGF) and deprives the supply of circulating nutrients by its anti-angiogenesis action. The aim of this review is to evaluate doxycycline's action against osteosarcoma cells as an MMP-inhibitor and interpret its usage as a chemotherapeutic agent.
METHODS
We checked PubMed and Google Scholar for recently published data, on the tumour-supportive role of MMPs and VEGF in osteosarcoma cells. We further studied published experimental trials on the role of doxycycline as a tumour-suppressive agent via MMPs and VEGF inhibition.
RESULTS
MMPs and VEGF have been found to play a fundamental role in osteosarcoma cells survival and high aggressiveness by in vitro, in vivo and clinical trials. Nevertheless, doxycycline has proved its tumour-suppressive effect by in vivo experimental trials in various cancers but not yet in osteosarcoma.
CONCLUSION
Doxycycline remains a promising chemotherapeutic agent against osteosarcoma via MMP inhibition, showing the need for further in vivo and clinical trials to be carried out in the future.
PubMed: 32377334
DOI: 10.1186/s13569-020-00128-6 -
BMC Cancer Aug 2016Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis.
BACKGROUND
Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin. This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC).
METHODS
Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were overall survival and progression-free survival. Data extracted from the studies were combined by using hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI).
RESULTS
The final analysis included 9 trials comprising 3,914 patients. Patients who received the combined treatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003) with heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher overall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse events and severe toxicities (grade ≥ 3), the group receiving the combined therapy had higher rates of hypertension (RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal perforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to 1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003).
CONCLUSION
The combination of chemotherapy with bevacizumab increased the response rate, progression-free survival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free survival (PFS) and overall survival (OS) were comparatively higher in those subgroups of patients receiving bolus 5-FU or capecitabine-based chemotherapy plus bevacizumab, when compared to patients treated with infusional %-FU plus bevacizumab (no difference in PFS and OS). Regarding the type of cytotoxic scheme, regimens containing irinotecan and fluoropyrimidine monotherapy showed superior efficacy results when combined to bevacizumab.
Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Humans; Survival Analysis
PubMed: 27558497
DOI: 10.1186/s12885-016-2734-y -
Acta Ophthalmologica Mar 2023Intravitreally injected anti-vascular endothelial growth factor (anti-VEGF) agents are first-line treatment for neovascular age-related macular degeneration (nAMD).... (Review)
Review
Intravitreally injected anti-vascular endothelial growth factor (anti-VEGF) agents are first-line treatment for neovascular age-related macular degeneration (nAMD). Phase 3 trials demonstrated non-inferiority of anti-VEGF therapy with brolucizumab compared with aflibercept in best corrected visual acuity (BCVA) gains, with superior anatomical outcomes after brolucizumab. The purpose of the review was to summarize real-world efficacy and safety data on brolucizumab in patients with nAMD. The review protocol was registered with PROSPERO (ID: CRD42021290530). We conducted systematic searches in Embase, Medline and key ophthalmology congress websites (19 October 2021). Original reports of efficacy and/or safety in patients receiving brolucizumab to treat nAMD in clinical practice were eligible. The descriptive summary includes reports describing at least 10 brolucizumab-treated eyes. In total, 2907 brolucizumab-treated eyes from 26 studies were included. Outcomes were available for treatment-naive eyes (six studies), eyes switched to brolucizumab from other anti-VEGFs (16 studies), and/or treatment-naive and switch eyes combined (eight studies). Follow-up time points ranged from 4 weeks to 1 year post-brolucizumab initiation. For BCVA, significant improvements compared with brolucizumab initiation were reported in four of six studies in treatment-naive eyes (mean BCVA improvement, range: +3.7 to +11.9 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and in three of 12 studies in switch eyes (range: +9.0 to +15 ETDRS letters) (all p < 0.05); remaining studies reported no significant post-brolucizumab BCVA changes. For central subfield thickness (CST), improvements post-brolucizumab initiation were reported in all six studies in treatment-naive eyes (mean CST improvement, range: -113.4 to -150.1 μm) and in eight of 11 studies in switch eyes (range: -26 to -185.7 μm) (all p < 0.05). The 14 studies reporting on intraretinal, subretinal and/or total fluid observed improvements post-brolucizumab initiation. The four studies comparing treatment intervals observed extension of the interval between injections after switching to brolucizumab from other anti-VEGFs. Incidence of intraocular inflammation ranged from 0% to 19%. In conclusion, real-world efficacy and safety data concur with brolucizumab pivotal trials. Additionally, reduction of disease activity in anti-VEGF switch eyes was demonstrated by fluid reduction and/or visual acuity gain, along with prolongation of the interval between injections.
Topics: Humans; Ranibizumab; Angiogenesis Inhibitors; Vascular Endothelial Growth Factor A; Intravitreal Injections; Macular Degeneration; Receptors, Vascular Endothelial Growth Factor; Diabetic Retinopathy; Recombinant Fusion Proteins; Wet Macular Degeneration
PubMed: 36117281
DOI: 10.1111/aos.15242 -
Clinical Colorectal Cancer Jun 2017Whether bevacizumab represents a feasible option for the first-line treatment of unfit and elderly patients with metastatic colorectal cancer (mCRC) remains... (Meta-Analysis)
Meta-Analysis Review
Efficacy and Safety of Bevacizumab Combined With Fluoropyrimidine Monotherapy for Unfit or Older Patients With Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.
BACKGROUND
Whether bevacizumab represents a feasible option for the first-line treatment of unfit and elderly patients with metastatic colorectal cancer (mCRC) remains controversial. The present systematic review and meta-analysis evaluated the efficacy and safety data of bevacizumab combined with first-line fluoropyrimidine monochemotherapy for these complex patients.
PATIENTS AND METHODS
A systematic search of the published data was conducted through May 31, 2016. The random-effects model was used to combine the effect estimates and the I index to quantify the between-study heterogeneity unexplained by sampling error.
RESULTS
We included 3 randomized controlled trials, 4 single-arm phase II trials, and 1 prospective cohort study in the present meta-analysis (n = 782). The monochemotherapy administered was capecitabine in 531 patients (67.9%) and 5-fluorouracil in 251 (32.1%); 500 (63.9%) also received bevacizumab. The median age was 75 years, 441 patients (56.4%) were men, and the Eastern Cooperative Oncology Group performance status was 0 to 1 in 684 patients (87.7%). The combination with bevacizumab produced advantages in terms of both progression-free survival (hazard ratio, 0.52; 95% confidence interval, 0.43-0.64; P < .00001; I = 0%) and overall survival (HR, 0.79; 95% CI, 0.64-0.98; P = .03; I = 0%). The pooled effect estimates of the randomized controlled trials have been previously reported. As expected, all-grade hypertension (27% vs. 4.9%), bleeding (24% vs. 6.4%), thromboembolic events (10% vs. 5%), and proteinuria (25.6% vs. 8.2%) were more frequent in the bevacizumab combination group.
CONCLUSION
Adding bevacizumab to first-line fluoropyrimidine monochemotherapy significantly improved progression-free and overall survival in unfit and elderly patients with mCRC, with a manageable safety profile and no unexpected toxicities.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Colorectal Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Male; Neoplasm Metastasis; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 27687553
DOI: 10.1016/j.clcc.2016.08.006 -
The Cochrane Database of Systematic... Mar 2023Proliferative diabetic retinopathy (PDR) is an advanced complication of diabetic retinopathy that can cause blindness. It consists of the presence of new vessels in the... (Review)
Review
BACKGROUND
Proliferative diabetic retinopathy (PDR) is an advanced complication of diabetic retinopathy that can cause blindness. It consists of the presence of new vessels in the retina and vitreous haemorrhage. Although panretinal photocoagulation (PRP) is the treatment of choice for PDR, it has secondary effects that can affect vision. Anti-vascular endothelial growth factor (anti-VEGF), which produces an inhibition of vascular proliferation, could improve the vision of people with PDR.
OBJECTIVES
To assess the effectiveness and safety of anti-VEGFs for PDR and summarise any relevant economic evaluations of their use.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 6); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov, and the WHO ICTRP. We did not use any date or language restrictions. We last searched the electronic databases on 1 June 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing anti-VEGFs to another active treatment, sham treatment, or no treatment for people with PDR. We also included studies that assessed the combination of anti-VEGFs with other treatments. We excluded studies that used anti-VEGFs in people undergoing vitrectomy.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias (RoB) for all included trials. We calculated the risk ratio (RR) or the mean difference (MD), and 95% confidence intervals (CI). We used GRADE to assess the certainty of evidence.
MAIN RESULTS
We included 15 new studies in this update, bringing the total to 23 RCTs with 1755 participants (2334 eyes). Forty-five per cent of participants were women and 55% were men, with a mean age of 56 years (range 48 to 77 years). The mean glycosylated haemoglobin (Hb1Ac) was 8.45% for the PRP group and 8.25% for people receiving anti-VEGFs alone or in combination. Twelve studies included people with PDR, and participants in 11 studies had high-risk PDR (HRPDR). Twelve studies were of bevacizumab, seven of ranibizumab, one of conbercept, two of pegaptanib, and one of aflibercept. The mean number of participants per RCT was 76 (ranging from 15 to 305). Most studies had an unclear or high RoB, mainly in the blinding of interventions and outcome assessors. A few studies had selective reporting and attrition bias. No study reported loss or gain of 3 or more lines of visual acuity (VA) at 12 months. Anti-VEGFs ± PRP probably increase VA compared with PRP alone (mean difference (MD) -0.08 logMAR, 95% CI -0.12 to -0.04; I = 28%; 10 RCTS, 1172 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP may increase regression of new vessels (MD -4.14 mm, 95% CI -6.84 to -1.43; I = 75%; 4 RCTS, 189 eyes; low-certainty evidence) and probably increase a complete regression of new vessels (RR 1.63, 95% CI 1.19 to 2.24; I = 46%; 5 RCTS, 405 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP probably reduce vitreous haemorrhage (RR 0.72, 95% CI 0.57 to 0.90; I = 0%; 6 RCTS, 1008 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP may reduce the need for vitrectomy compared with eyes that received PRP alone (RR 0.67, 95% CI 0.49 to 0.93; I = 43%; 8 RCTs, 1248 eyes; low-certainty evidence). Anti-VEGFs ± PRP may result in little to no difference in the quality of life compared with PRP alone (MD 0.62, 95% CI -3.99 to 5.23; I = 0%; 2 RCTs, 382 participants; low-certainty evidence). We do not know if anti-VEGFs ± PRP compared with PRP alone had an impact on adverse events (very low-certainty evidence). We did not find differences in visual acuity in subgroup analyses comparing the type of anti-VEGFs, the severity of the disease (PDR versus HRPDR), time to follow-up (< 12 months versus 12 or more months), and treatment with anti-VEGFs + PRP versus anti-VEGFs alone. The main reasons for downgrading the certainty of evidence included a high RoB, imprecision, and inconsistency of effect estimates.
AUTHORS' CONCLUSIONS
Anti-VEGFs ± PRP compared with PRP alone probably increase visual acuity, but the degree of improvement is not clinically meaningful. Regarding secondary outcomes, anti-VEGFs ± PRP produce a regression of new vessels, reduce vitreous haemorrhage, and may reduce the need for vitrectomy compared with eyes that received PRP alone. We do not know if anti-VEGFs ± PRP have an impact on the incidence of adverse events and they may have little or no effect on patients' quality of life. Carefully designed and conducted clinical trials are required, assessing the optimal schedule of anti-VEGFs alone compared with PRP, and with a longer follow-up.
Topics: Aged; Female; Humans; Male; Middle Aged; Diabetes Mellitus; Diabetic Retinopathy; Ranibizumab; Vascular Endothelial Growth Factor A; Vitreous Hemorrhage
PubMed: 36939655
DOI: 10.1002/14651858.CD008721.pub3 -
Eye (London, England) Aug 2023The aim of this systematic literature review is twofold, (1) detail the impact of retinal biomarkers identifiable via optical coherence tomography (OCT) on disease... (Review)
Review
UNLABELLED
The aim of this systematic literature review is twofold, (1) detail the impact of retinal biomarkers identifiable via optical coherence tomography (OCT) on disease progression and response to treatment in neovascular age-related macular degeneration (nAMD) and (2) establish which biomarkers are currently identifiable by artificial intelligence (AI) models and the utilisation of this technology. Following the PRISMA guidelines, PubMed was searched for peer-reviewed publications dated between January 2016 and January 2022.
POPULATION
Patients diagnosed with nAMD with OCT imaging.
SETTINGS
Comparable settings to NHS hospitals.
STUDY DESIGNS
Randomised controlled trials, prospective/retrospective cohort studies and review articles. From 228 articles, 130 were full-text reviewed, 50 were removed for falling outside the scope of this review with 10 added from the author's inventory, resulting in the inclusion of 90 articles. From 9 biomarkers identified; intraretinal fluid (IRF), subretinal fluid, pigment epithelial detachment, subretinal hyperreflective material (SHRM), retinal pigmental epithelial (RPE) atrophy, drusen, outer retinal tabulation (ORT), hyperreflective foci (HF) and retinal thickness, 5 are considered pertinent to nAMD disease progression; IRF, SHRM, drusen, ORT and HF. A number of these biomarkers can be classified using current AI models. Significant retinal biomarkers pertinent to disease activity and progression in nAMD are identifiable via OCT; IRF being the most important in terms of the significant impact on visual outcome. Incorporating AI into ophthalmology practice is a promising advancement towards automated and reproducible analyses of OCT data with the ability to diagnose disease and predict future disease conversion.
SYSTEMATIC REVIEW REGISTRATION
This review has been registered with PROSPERO (registration ID: CRD42021233200).
Topics: Humans; Tomography, Optical Coherence; Artificial Intelligence; Retrospective Studies; Prospective Studies; Fluorescein Angiography; Biomarkers; Macular Degeneration; Disease Progression; Wet Macular Degeneration; Angiogenesis Inhibitors
PubMed: 36526863
DOI: 10.1038/s41433-022-02360-4 -
Scientific Reports May 2023To better understand the efficacy of intravitreal dexamethasone implant (Ozurdex) versus antivascular endothelial growth factor (anti-VEGF) treatment in patients with... (Meta-Analysis)
Meta-Analysis
Efficacy and safety profile of intravitreal dexamethasone implant versus antivascular endothelial growth factor treatment in diabetic macular edema: a systematic review and meta-analysis.
To better understand the efficacy of intravitreal dexamethasone implant (Ozurdex) versus antivascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular edema (DME). A systematic review and meta-analysis. The study included randomized control trials (RCTs) and non-randomized control trials (Non-RCTs) before December 2021 that compare the efficacy of Ozurdex-related therapyand anti-VEGF therapy. We searched PubMed, Cochrane Library, and EMBASE. The quality of the included studies was assessed carefully. 30 studies were included. Regarding BCVA change, the overall result revealed no significant differences between Ozurdex and anti-VEGF therapies in patients with nonresistant DME, but Ozurdex group had significantly more VA improvement than anti-VEGF therapies in patients with resistant DME (MD 0.12, 95% CI 0.02-0.21). In terms of central retinal thickness (CRT) decrease, there was a significant difference between Ozurdex therapy and anti-VEGF therapy in patients with nonresistant DME (MD 48.10, 95% CI 19.06-77.13) and resistant DME (MD 65.37, 95% CI 3.62-127.13). Overall, Ozurdex therapy resulted in significantly greater VA improvement and CRT decrease than anti-VEGF therapy in resistant DME patients. Ozurdex therapy was not inferior to anti-VEGF therapy in patients with nonresistant DME.
Topics: Humans; Macular Edema; Ranibizumab; Glucocorticoids; Endothelial Growth Factors; Bevacizumab; Vascular Endothelial Growth Factor A; Dexamethasone; Diabetic Retinopathy; Intravitreal Injections; Diabetes Mellitus
PubMed: 37156823
DOI: 10.1038/s41598-023-34673-z -
Rheumatology International Feb 2018To assess the comparative effectiveness and safety of novel biologic therapies in psoriatic arthritis (PsA) and to establish the position of the non-anti-tumor necrosis... (Meta-Analysis)
Meta-Analysis Review
To assess the comparative effectiveness and safety of novel biologic therapies in psoriatic arthritis (PsA) and to establish the position of the non-anti-tumor necrosis factor α (TNF-α) biologic drugs in the treatment regimen of the disease. A systematic review and network meta-analysis (NMA) was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) requirements. Two investigators identified the studies, abstracted data, and assessed the risk of bias independently. The NMA was conducted for efficacy [American College of Rheumatology (ACR) criteria, ACR20 and ACR50; psoriasis area and severity index (PASI), PASI75] and safety outcomes [any adverse events (AEs) and serious adverse events (SAEs)]; treatments were ranked using the P score for each outcome. The PROSPERO registration number was 42017072200. MEDLINE/PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from the inception of each database to July 10, 2017. Randomized controlled trials (RCTs) for abatacept, apremilast, secukinumab or ustekinumab in adults with moderate and severe PsA were included. The overall PsA population and anti-TNF-α-naive, anti-TNF-α-failure, or anti-TNF-α-experienced subpopulations were considered. We identified eight eligible RCTs and included them in the systematic review and NMA. Significant differences in ACR20 response rate were revealed between secukinumab 150 mg and apremilast 20 mg [relative risk; RR = 2.55 (CI-confidence interval; 1.24, 5.23)] and between secukinumab 300 mg and apremilast 20 or 30 mg [RR = 3.57 CI (1.48, 8.64) and RR = 2.84 CI (1.18, 6.86), respectively]. Any AEs occurred more often in apremilast 20 and 30 mg compared with placebo [RR = 0.58 CI (0.45, 0.74) and RR = 0.58 CI (0.45, 0.75), respectively] but also compared with secukinumab 150 mg [RR = 0.54 CI (0.35, 0.81) and RR = 0.45 CI (0.35, 0.82), respectively]. No significant differences were revealed for SAEs among biologics and between biologics and placebo. In the overall population, as well as in the anti-TNF-α-naive subpopulation, secukinumab at a dose of 300 and 150 mg was ranked the highest for the ACR20 endpoint, while in the anti-TNF-α-experienced subpopulation, secukinumab 300 mg and apremilast 30 mg revealed the highest rank. Secukinumab 75 mg was the safest drug in terms of any AEs, but for SEAs the safest was ustekinumab 90 mg. Our study revealed no significant differences among non-anti-TNF-α biologics in the treatment of PsA in the comparisons performed with regards to the highest efficacy and safety. Both in the overall population and in the analyzed subpopulations, secukinumab 300 mg was ranked the highest for the ACR20 response rate. Secukinumab 300 mg was the safest drug in terms of any AEs, and ustekinumab 90 mg presented the lowest overall risk of SAEs. Head-to-head trials and evaluation of comparative efficacy and safety between non-TNF-α biologics are warranted to inform clinical decision making with a relevant treatment paradigm.
Topics: Abatacept; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Psoriatic; Biological Products; Comparative Effectiveness Research; Humans; Remission Induction; Thalidomide; Time Factors; Treatment Outcome; Ustekinumab
PubMed: 29285605
DOI: 10.1007/s00296-017-3919-7