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Efficacy and safety of ruxolitinib in steroid-refractory graft-versus-host disease: A meta-analysis.Frontiers in Immunology 2022Ruxolitinib is an important treatment for steroid refractory graft-versus-host disease (SR-GVHD). Therefore, we reported the updated results of a systematic review and... (Meta-Analysis)
Meta-Analysis
Ruxolitinib is an important treatment for steroid refractory graft-versus-host disease (SR-GVHD). Therefore, we reported the updated results of a systematic review and meta-analysis of ruxolitinib as treatment for SR-GVHD. In addition, we wanted to compare the efficacy and safety between children and adults with SR-GVHD. Overall response rate (ORR) after ruxolitinib treatment was chosen as the primary end point. Complete response rate (CRR), infection, myelosuppression, and overall survival (OS) were chosen as secondary end points. A total of 37 studies were included in this meta-analysis, and 1,580 patients were enrolled. ORR at any time after ruxolitinib treatment was 0.77 [95% confidence interval (CI): 0.68-0.84] and 0.78 (95% CI: 0.74-0.81), respectively, for SR-aGVHD and SR-cGVHD. CRR at any time after ruxolitinib treatment was 0.49 (95% CI: 0.40-0.57) and 0.15 (95% CI: 0.10-0.23), respectively, for SR-aGVHD and SR-cGVHD. The ORRs at any time after treatment was highest in mouth SR-cGVHD, followed by skin, gut, joints and fascia, liver, eyes, esophagus, and lung SR-cGVHD. The incidence rate of infections after ruxolitinib treatment was 0.61 (95% CI: 0.45-0.76) and 0.47 (95% CI: 0.31-0.63), respectively, for SR-aGVHD and SR-cGVHD. The incidence rates of overall (grades I-IV) and severe (grades III-IV) cytopenia were 53.2% (95% CI: 16.0%-90.4%) and 31.0% (95% CI: 0.0-100.0%), respectively, for SR-aGVHD, and were 28.8% (95% CI:13.0%-44.6%) and 10.4% (95% CI: 0.0-27.9%), respectively, for SR-cGVHD. The probability rate of OS at 6 months after treatment was 63.9% (95% CI: 52.5%-75.2%) for SR-aGVHD. The probability rates of OS at 6 months, 1 year, and 2 years after treatment were 95% (95% CI: 79.5%-100.0%), 78.7% (95% CI: 67.2%-90.1%), and 75.3% (95% CI: 68.0%-82.7%), respectively, for SR-cGVHD. The ORR, CRR, infection events, and myelosuppression were all comparable between children and adults with SR-GVHD. In summary, this study suggests that ruxolitinib is an effective and safe treatment for SR-GVHD, and both children and adults with SR-GVHD could benefit from ruxolitinib treatment.
Topics: Adult; Child; Graft vs Host Disease; Humans; Nitriles; Pyrazoles; Pyrimidines; Steroids
PubMed: 35990629
DOI: 10.3389/fimmu.2022.954268 -
European Journal of Neurology Feb 2022New-onset refractory status epilepticus (NORSE) is a clinical presentation, neither a specific diagnosis nor a clinical entity. It refers to a patient without active... (Review)
Review
BACKGROUND AND PURPOSE
New-onset refractory status epilepticus (NORSE) is a clinical presentation, neither a specific diagnosis nor a clinical entity. It refers to a patient without active epilepsy or other pre-existing relevant neurological disorder, with a NORSE without a clear acute or active structural, toxic or metabolic cause. This study reviews the currently available evidence about the aetiology of patients presenting with NORSE and NORSE-related conditions.
METHODS
A systematic search was carried out for clinical trials, observational studies, case series and case reports including patients who presented with NORSE, febrile-infection-related epilepsy syndrome or the infantile hemiconvulsion-hemiplegia and epilepsy syndrome.
RESULTS
Four hundred and fifty records were initially identified, of which 197 were included in the review. The selected studies were retrospective case-control (n = 11), case series (n = 83) and case reports (n = 103) and overall described 1334 patients both of paediatric and adult age. Aetiology remains unexplained in about half of the cases, representing the so-called 'cryptogenic NORSE'. Amongst adult patients without cryptogenic NORSE, the most often identified cause is autoimmune encephalitis, either non-paraneoplastic or paraneoplastic. Infections are the prevalent aetiology of paediatric non-cryptogenic NORSE. Genetic and congenital disorders can have a causative role in NORSE, and toxic, vascular and degenerative conditions have also been described.
CONCLUSIONS
Far from being a unitary condition, NORSE is a heterogeneous and clinically challenging presentation. The development and dissemination of protocols and guidelines to standardize diagnostic work-up and guide therapeutic approaches should be implemented. Global cooperation and multicentre research represent priorities to improve the understanding of NORSE.
Topics: Adult; Child; Drug Resistant Epilepsy; Encephalitis; Epileptic Syndromes; Humans; Retrospective Studies; Status Epilepticus
PubMed: 34661330
DOI: 10.1111/ene.15149 -
International Journal of Radiation... Jan 2024Radiation necrosis (RN) secondary to stereotactic radiosurgery is a significant cause of morbidity. The optimal management of corticosteroid-refractory brain RN remains... (Review)
Review
A Systematic Review Informing the Management of Symptomatic Brain Radiation Necrosis After Stereotactic Radiosurgery and International Stereotactic Radiosurgery Society Recommendations.
Radiation necrosis (RN) secondary to stereotactic radiosurgery is a significant cause of morbidity. The optimal management of corticosteroid-refractory brain RN remains unclear. Our objective was to summarize the literature specific to efficacy and toxicity of treatment paradigms for patients with symptomatic corticosteroid-refractory RN and to provide consensus guidelines for grading and management of RN on behalf of the International Stereotactic Radiosurgery Society. A systematic review of articles pertaining to treatment of RN with bevacizumab, laser interstitial thermal therapy (LITT), surgical resection, or hyperbaric oxygen therapy was performed. The primary composite outcome was clinical and/or radiologic stability/improvement (ie, proportion of patients achieving improvement or stability with the given intervention). Proportions of patients achieving the primary outcome were pooled using random weighted-effects analysis but not directly compared between interventions. Twenty-one articles were included, of which only 2 were prospective studies. Thirteen reports were relevant for bevacizumab, 5 for LITT, 5 for surgical resection and 1 for hyperbaric oxygen therapy. Weighted effects analysis revealed that bevacizumab had a pooled symptom improvement/stability rate of 86% (95% CI 77%-92%), pooled T2 imaging improvement/stability rate of 93% (95% CI 87%-98%), and pooled T1 postcontrast improvement/stability rate of 94% (95% CI 87%-98%). Subgroup analysis showed a statistically significant improvement favoring treatment with low-dose (below median, ≤7.5 mg/kg every 3 weeks) versus high-dose bevacizumab with regards to symptom improvement/stability rate (P = .02) but not for radiologic T1 or T2 changes. The pooled T1 postcontrast improvement/stability rate for LITT was 88% (95% CI 82%-93%), and pooled symptom improvement/stability rate for surgery was 89% (95% CI 81%-96%). Toxicity was inconsistently reported but was generally low for all treatment paradigms. Corticosteroid-refractory RN that does not require urgent surgical intervention, with sufficient noninvasive diagnostic testing that favors RN, can be treated medically with bevacizumab in carefully selected patients as a strong recommendation. The role of LITT is evolving as a less invasive image guided surgical modality; however, the overall evidence for each modality is of low quality. Prospective head-to-head comparisons are needed to evaluate the relative efficacy and toxicity profile among treatment approaches.
Topics: Humans; Radiosurgery; Bevacizumab; Prospective Studies; Brain Neoplasms; Brain; Radiation Injuries; Necrosis; Adrenal Cortex Hormones; Retrospective Studies
PubMed: 37482137
DOI: 10.1016/j.ijrobp.2023.07.015 -
The Cochrane Database of Systematic... Sep 2021Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer of the lymphatic system. About 30% to 40% of people with DLBCL experience relapse and 10% are refractory to... (Review)
Review
BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer of the lymphatic system. About 30% to 40% of people with DLBCL experience relapse and 10% are refractory to first-line treatment usually consisting of R-CHOP chemotherapy. Of those eligible for second-line treatment, commonly consisting of salvage chemotherapy followed by autologous stem-cell transplantation (ASCT), around 50% experience relapse. With a median overall survival of less than six to 12 months, the prognosis of individuals who relapse or are refractory (r/r) to advanced lines of treatment or of those who are ineligible for ASCT, is very poor. With the introduction of chimeric antigen receptor (CAR) T-cell therapy, a novel treatment option for these people is available.
OBJECTIVES
To assess the benefits and harms of chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory (r/r) DLBCL.
SEARCH METHODS
An experienced information specialist performed a systematic database search for relevant articles on CENTRAL, MEDLINE and Embase until September 11th, 2020. We also searched trial registries and reference lists of identified studies up to this date. All search results were screened by two authors independently and a third author was involved in case of discrepancies.
SELECTION CRITERIA
We included prospectively planned trials evaluating CAR T-cell therapy for people with r/r DLBCL. We had planned to include randomised controlled trials (RCTs) and we flexibly adapted eligibility criteria to the most reliable study designs available. We excluded studies involving fewer than 10 participants with r/r DLBCL and studies with a proportion of participants with r/r DLBCL below 70%, unless data were reported separately for this subgroup.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data and performed risk of bias ratings independently. A third author was involved in case of disagreements. As our search did not yield any completed RCTs, prospective controlled non-randomised studies of interventions (NRSIs) or prospective observational studies with a control group, we did not meta-analyse data and reported all results narratively. We adopted the GRADE approach to assess the certainty of the evidence for prioritised outcomes.
MAIN RESULTS
We identified 13 eligible uncontrolled studies evaluating a single or multiple arms of CAR T-cell therapies. We also identified 38 ongoing studies, including three RCTs. Ten studies are awaiting classification due to completion with no retrievable results data or insufficient data to justify inclusion. The mean number of participants enrolled, treated with CAR T-cell therapy and evaluated in the included studies were 79 (range 12 to 344; data unavailable for two studies), 61 (range 12 to 294; data unavailable for one study) and 52 (range 11 to 256), respectively. Most studies included people with r/r DLBCL among people with other haematological B-cell malignancies. Participants had received at least a median of three prior treatment lines (data unavailable for four studies), 5% to 50% had undergone ASCT (data unavailable for five studies) and, except for two studies, 3% to 18% had undergone allogenic stem-cell transplantation (data unavailable for eight studies). The overall risk of bias was high for all studies, in particular, due to incomplete follow-up and the absence of blinding. None of the included studies had a control group so that no adequate comparative effect measures could be calculated. The duration of follow-up varied substantially between studies, in particular, for harms. Our certainty in the evidence is very low for all outcomes. Overall survival was reported by eight studies (567 participants). Four studies reported survival rates at 12 months which ranged between 48% and 59%, and one study reported an overall survival rate of 50.5% at 24 months. The evidence is very uncertain about the effect of CAR T-cell therapy on overall survival. Two studies including 294 participants at baseline and 59 participants at the longest follow-up (12 months or 18 months) described improvements of quality of life measured with the EuroQol 5-Dimension 5-Level visual analogue scale (EQ-5D-5L VAS) or Function Assessment of Cancer Therapy-Lymphoma (FACT-Lym). The evidence is very uncertain about the effect of CAR T-cell therapy on quality of life. None of the studies reported treatment-related mortality. Five studies (550 participants) reported the occurrence of adverse events among participants, ranging between 99% and 100% for any grade adverse events and 68% to 98% for adverse events grade ≥ 3. In three studies (253 participants), 56% to 68% of participants experienced serious adverse events, while in one study (28 participants), no serious adverse events occurred. CAR T-cell therapy may increase the risk of adverse events and serious adverse events but the evidence is very uncertain about the exact risk. The occurrence of cytokine release syndrome (CRS) was reported in 11 studies (675 participants) under use of various grading criteria. Five studies reported between 42% and 100% of participants experiencing CRS according to criteria described in Lee 2014. CAR T-cell therapy may increase the risk of CRS but the evidence is very uncertain about the exact risk. Nine studies (575 participants) reported results on progression-free survival, disease-free survival or relapse-free survival. Twelve-month progression-free survival rates were reported by four studies and ranged between 44% and 75%. In one study, relapse-free survival remained at a rate of 64% at both 12 and 18 months. The evidence is very uncertain about the effect of CAR T-cell therapy on progression-free survival. Thirteen studies (620 participants) provided data on complete response rates. At six months, three studies reported complete response rates between 40% and 45%. The evidence is very uncertain about the effect of CAR T-cell therapy on complete response rates.
AUTHORS' CONCLUSIONS
The available evidence on the benefits and harms of CAR T-cell therapy for people with r/r DLBCL is limited, mainly because of the absence of comparative clinical trials. The results we present should be regarded in light of this limitation and conclusions should be drawn very carefully. Due to the uncertainty in the current evidence, a large number of ongoing investigations and a risk of substantial and potentially life-threatening complications requiring supplementary treatment, it is critical to continue evaluating the evidence on this new therapy.
Topics: Cell- and Tissue-Based Therapy; Humans; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Neoplasm Recurrence, Local; Observational Studies as Topic; Receptors, Chimeric Antigen
PubMed: 34515338
DOI: 10.1002/14651858.CD013365.pub2 -
Frontiers in Immunology 2022Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune diseases with various subtypes, myositis-specific antibodies, and affect multiple... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune diseases with various subtypes, myositis-specific antibodies, and affect multiple systems. The treatment of IIMs remains challenging, especially for refractory myositis. In addition to steroids and traditional immunosuppressants, rituximab (RTX), a B cell-depleting monoclonal antibody, is emerging as an alternative treatment for refractory myositis. However, the therapeutic response to RTX remains controversial. This meta-analysis aimed to systematically evaluate the efficacy and safety of RTX in patients with IIMs, excluding sporadic inclusion body myositis.
METHODS
PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and WanFang Data were searched for relevant studies. The overall effective rate, complete response rate, and partial response rate were calculated to assess the efficacy of RTX. The incidences of adverse events, infection, severe adverse events, severe infection, and infusion reactions were collected to evaluate the safety of RTX. Subgroup analyses were performed using IIM subtypes, affected organs, continents, and countries. We also performed a sensitivity analysis to identify the sources of heterogeneity.
RESULTS
A total of 26 studies were included in the quantitative analysis, which showed that 65% (95% confidence interval [CI]: 54%, 75%) of patients with IIMs responded to RTX, 45% (95% CI: 22%, 70%) of patients achieved a complete response, and 39% (95% CI: 26%, 53%) achieved a partial response. Subgroup analyses indicated that the overall efficacy rates in patients with refractory IIMs, dermatomyositis and polymyositis, as well as anti-synthetase syndrome were 62%, 68%, and 62%, respectively. The overall efficacy rates for muscle, lungs, and skin involvement were 59%, 65%, and 81%, respectively. In addition, studies conducted in Germany and the United States showed that patients with IIMs had an excellent response to RTX, with an effective rate of 90% and 77%, respectively. The incidence of severe adverse events and infections was 8% and 2%, respectively.
CONCLUSION
RTX may be an effective and relatively safe treatment choice in patients with IIMs, especially for refractory cases. However, further verification randomized controlled trials is warranted.
Topics: Humans; Rituximab; Myositis; Polymyositis; Immunosuppressive Agents; Autoimmune Diseases
PubMed: 36578492
DOI: 10.3389/fimmu.2022.1051609 -
JAMA Network Open May 2021Hematopoietic stem cell transplant (HSCT) is an advisable option for refractory or relapsed peripheral T-cell lymphoma (R/R-PTCL), but whether allogeneic HSCT or... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of Allogeneic Stem Cell Transplant and Autologous Stem Cell Transplant in Refractory or Relapsed Peripheral T-Cell Lymphoma: A Systematic Review and Meta-analysis.
IMPORTANCE
Hematopoietic stem cell transplant (HSCT) is an advisable option for refractory or relapsed peripheral T-cell lymphoma (R/R-PTCL), but whether allogeneic HSCT or autologous HSCT is more beneficial is unknown.
OBJECTIVE
To compare the effectiveness and safety of allogeneic HSCT vs autologous HSCT in patients with R/R-PTCL.
DATA SOURCES
A systematic search of the PubMed, Embase, the Cochrane Central Register of Controlled Trials, Wanfang, and China National Knowledge Infrastructure databases with the search items refractory or relapsed peripheral T-cell lymphoma, ASCT/autologous stem-cell transplantation, allo-HSCT/allogeneic stem-cell transplantation, therapeutic effect, and treatment was conducted for articles published from January 12, 2001, to October 1, 2020.
STUDY SELECTION
After duplicate and irrelevant publications were discarded, 329 were ineligible according to the inclusion (clinical trials or retrospective studies with >10 samples) and exclusion criteria (articles without overall survival [OS], progression-free survival [PFS], and transplantation-related mortality [TRM]). Thirty trials were included in the meta-analysis. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
DATA EXTRACTION AND SYNTHESIS
Data on study design, individual characteristics, and outcomes were extracted. All statistics were pooled by applying a random-effects model.
MAIN OUTCOMES AND MEASURES
The prespecified main outcomes were OS, PFS, and TRM.
RESULTS
Of 6548 articles, data extracted from the 30 studies (including 880 patients who underwent allogeneic HSCT and 885 who underwent autologous HSCT) were included in this meta-analysis. In the allogeneic HSCT group, a 3-year OS of 50% (95% CI, 41%-60%) and PFS of 42% (95% CI, 35%-51%), a 5-year OS of 54% (95% CI, 47%-62%) and PFS of 48% (95% CI, 40%-56%), and a 3-year TRM of 32% (95% CI, 27%-37%) were observed. In the autologous HSCT group, a 3-year OS of 55% (95% CI, 48%-64%) and PFS of 41% (95% CI, 33%-51%), a 5-year OS of 53% (95% CI, 44%-64%) and PFS of 40% (95% CI, 24%-58%), and a 3-year TRM of 7% (95% CI, 2%-23%) were observed.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, OS and PFS were similar in the allogeneic HSCT and autologous HSCT groups; however, allogeneic HSCT was associated with specific survival benefits among patients with R/R-PTCL.
Topics: Humans; Lymphoma, T-Cell, Peripheral; Neoplasm Recurrence, Local; Stem Cell Transplantation; Transplantation, Autologous; Transplantation, Homologous; Treatment Failure
PubMed: 34042995
DOI: 10.1001/jamanetworkopen.2021.9807 -
Blood Advances Jun 2019The terminology applied to autoimmune hemolytic anemia (AIHA) seems inconsistent. We aimed to evaluate the consistency of definitions used for diagnosis and treatment.... (Comparative Study)
Comparative Study
The terminology applied to autoimmune hemolytic anemia (AIHA) seems inconsistent. We aimed to evaluate the consistency of definitions used for diagnosis and treatment. In this systematic review of literature from January 2006 to December 2015, we assessed heterogeneity in the definition of AIHA and its subtypes, refractory disease, disease phase, severity, criteria for treatment response, and response durability. A Medline search for anemia, hemolytic, autoimmune was supplemented with keyword searches. Main exclusions were conference abstracts, animal and non-English studies, and studies with <10 cases. Of 1371 articles retrieved, 1209 were excluded based on titles and abstracts. Two authors independently reviewed 10% and 16% of abstracts and full papers, respectively. After full-paper review, 84 studies were included. AIHA was most frequently (32 [52%] of 61) defined as hemolytic anemia with positive direct antiglobulin test (DAT) and exclusion of alternatives, but 10 of 32 also recognized DAT-negative AIHA. A lower threshold for diagnosis of DAT-negative AIHA was observed in literature on chronic lymphocytic leukemia. Definitions of anemia, hemolysis, and exclusion criteria showed substantial variation. Definitions of primary/secondary cold agglutinin disease/syndrome were not consistent. Forty-three studies provided criteria for treatment response, and other than studies from 1 center, these were almost entirely unique. Other criteria were rarely defined. Only 7, 0, 3, 2, 2, and 3 studies offered definitions of warm AIHA, paroxysmal cold hemoglobinuria, mixed AIHA, AIHA severity, disease phase, and refractory AIHA, respectively. Marked heterogeneity in the time period sampled indicates the need to standardize AIHA terminology.
Topics: Anemia, Hemolytic, Autoimmune; Coombs Test; Erythrocytes; Hemoglobinuria, Paroxysmal; Hemolysis; Humans; Immunoglobulin G; Publications; Severity of Illness Index; Terminology as Topic
PubMed: 31235526
DOI: 10.1182/bloodadvances.2019000036 -
Medical Principles and Practice :... 2022Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V associated with chronic cannabis use among...
INTRODUCTION
Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V associated with chronic cannabis use among adults and older patients have been reported named cannabis hyperemesis syndrome (CHS). CHS is a condition that leads to repeated and severe N/V in long-term users of cannabinoids.
OBJECTIVE
The aim of this study was to outline current treatments for the management of CHS.
METHODS
A systematic review was conducted using PubMed, Ovid MEDLINE, Cochrane Central, EMBASE, and Google Scholar. Databases were used to search for articles on CHS published from January 2009 to June 2021, yielding 225 results of which 17 were deemed relevant and underwent review by 2 separate reviewers.
RESULTS
The duration of cannabis administration ranged between 6 months to 11 years may precipitate symptoms of CHS. The Rome IV diagnostic criteria of CHS require cannabinoid use and persistence of N/V symptoms for at least the past 6 months. Cannabis cessation is noted to be the most successful management, but other treatments also demonstrated symptom relief; these include hot water hydrotherapy, topical capsaicin cream, haloperidol, droperidol, benzodiazepines, propranolol, and aprepitant administration.
CONCLUSION
More research on CHS is needed to enhance knowledge translation, education, and create awareness in the medical community on the side effects of cannabinoids and to propose the best treatment options.
Topics: Adult; Analgesics; Cannabinoids; Cannabis; Humans; Marijuana Abuse; Syndrome; Vomiting
PubMed: 34724666
DOI: 10.1159/000520417 -
International Journal of Medical... 2021Multiple myeloma (MM) is incurable in spite of recent treatment improvements, highlighting the development of new therapies. Chimeric antigen receptor (CAR) T-cell... (Meta-Analysis)
Meta-Analysis
Multiple myeloma (MM) is incurable in spite of recent treatment improvements, highlighting the development of new therapies. Chimeric antigen receptor (CAR) T-cell therapy has dramatically changed the therapeutic effectiveness in high-risk B-cell malignancies. For relapsed/refractory multiple myeloma (RRMM), preclinical evaluations of CAR-T therapy have shown promising efficacy, thus various active clinical trials are under way. Herein, we conducted this review to summarize efficacy and safety of CAR-T therapy and provide more evidence to guide clinical treatments. We systematically searched literature based on databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials), and conference abstracts reported from American Society of Hematology (ASH), European Hematology Association (EHA) and American Society of Clinical Oncology (ASCO), in addition to other sources (www.clinicaltrials.gov, article citations). Data assessed efficacy and safety of CAR-T therapy in patients with RRMM were extracted and evaluated, and then systematically analyzed by Comprehensive Meta-analysis 3.0 (CMA 3.0). A total of 23 studies including 350 participants from different countries, diagnosed as RRMM and treated with CAR-T therapy (containing 7 antigens targeted by CARs) were combined. In summary, we discovered the pooled overall response rate (77%), complete response rate (37%) and minimal residual disease (MRD) negativity rate within responders (78%). Furthermore, the pooled relapse rate of responders was 38% and median progression-free survival was 8 months. The pooled survival rate was 87% at last follow-up (median, 12 months). In addition, the pooled grade 3-4 rates of cytokine release syndrome (CRS) and neurologic toxicities (NT) were 14% and 13%, respectively. Our study suggests that CAR-T therapy has demonstrated efficacy and safety in RRMM patients. BCMA-targeted CAR-T and anti-BCMA contained regimen have shown better efficacy.
Topics: B-Cell Maturation Antigen; Clinical Trials as Topic; Drug Resistance, Neoplasm; Follow-Up Studies; Humans; Immunotherapy, Adoptive; Multiple Myeloma; Neoplasm Recurrence, Local; Progression-Free Survival; Receptors, Chimeric Antigen
PubMed: 33746596
DOI: 10.7150/ijms.46811 -
JAMA Oct 2023Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough.
OBJECTIVE
To evaluate the efficacy and tolerability of gefapixant for the treatment of adults with refractory or unexplained chronic cough.
DATA SOURCES
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science from November 2014 to July 2023.
STUDY SELECTION
Two reviewers independently screened for parallel and crossover randomized clinical trials (RCTs) that compared, in patients with refractory or unexplained chronic cough, either gefapixant with placebo, or 2 or more doses of gefapixant with or without placebo.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data. A frequentist random-effects dose-response meta-analysis or pairwise meta-analysis was used for each outcome. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in whether patients would perceive the effects as important (greater than the minimal important difference [MID]) or small (less than the MID).
MAIN OUTCOMES AND MEASURES
Cough frequency (measured using the VitaloJAK cough monitor; MID, 20%), cough severity (measured using the 100-mm visual analog scale [VAS]; higher score is worse; MID, 30 mm), cough-specific quality of life (measured using the Leicester Cough Questionnaire [LCQ]; score range, 3 [maximal impairment] to 21 [no impairment]; MID, 1.3 points), treatment-related adverse events, adverse events leading to discontinuation, and taste-related adverse events.
RESULTS
Nine RCTs including 2980 patients were included in the primary analysis. Compared with placebo, gefapixant (45 mg twice daily) had small effects on awake cough frequency (17.6% reduction [95% CI, 10.6%-24.0%], moderate certainty), cough severity on the 100-mm VAS (mean difference, -6.2 mm [95% CI, -4.1 to -8.4]; high certainty), and cough-specific quality of life on the LCQ (mean difference, 1.0 points [95% CI, 0.7-1.4]; moderate certainty). Compared with placebo, gefapixant (45 mg twice daily) probably caused an important increase in treatment-related adverse events (32 more per 100 patients [95% CI, 13-64 more], moderate certainty) and taste-related adverse events (32 more per 100 patients [95% CI, 22-46 more], high certainty). High-certainty evidence suggests that gefapixant (15 mg twice daily) had small effects on taste-related adverse events (6 more per 100 patients [95% CI, 5-8 more]).
CONCLUSIONS AND RELEVANCE
Compared with placebo, gefapixant (45 mg orally twice daily) led to modest improvements in cough frequency, cough severity, and cough-specific quality of life but increased taste-related adverse events.
Topics: Adult; Humans; Cough; Pyrimidines; Quality of Life; Sulfonamides; Dose-Response Relationship, Drug; Treatment Outcome; Chronic Disease; Taste
PubMed: 37694849
DOI: 10.1001/jama.2023.18035