-
International Journal of Molecular... Jun 2023Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for minimal residual disease (MRD) in CRC patients. Recent studies have shown... (Meta-Analysis)
Meta-Analysis Review
Circulating Tumor DNA as a Minimal Residual Disease Assessment and Recurrence Risk in Patients Undergoing Curative-Intent Resection with or without Adjuvant Chemotherapy in Colorectal Cancer: A Systematic Review and Meta-Analysis.
Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for minimal residual disease (MRD) in CRC patients. Recent studies have shown that the ability to detect MRD using ctDNA assay after curative-intent surgery will change how to assess the recurrence risk and patient selection for adjuvant chemotherapy. We performed a meta-analysis of post-operative ctDNA in stage I-IV (oligometastatic) CRC patients after curative-intent resection. We included 23 studies representing 3568 patients with evaluable ctDNA in CRC patient post-curative-intent surgery. Data were extracted from each study to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. Results showed that the pooled hazard ratio (HR) for recurrence-free survival (RFS) in post-surgical ctDNA-positive versus -negative patients in all stages was 7.27 (95% CI 5.49-9.62), < 0.00001. Subgroup analysis revealed pooled HRs of 8.14 (95% CI 5.60-11.82) and 4.83 (95% CI 3.64-6.39) for stages I-III and IV CRC, respectively. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA-positive versus -negative patients in all stages was 10.59 (95% CI 5.59-20.06), < 0.00001. Circulating tumor DNA (ctDNA) analysis has revolutionized non-invasive cancer diagnostics and monitoring, with two primary forms of analysis emerging: tumor-informed techniques and tumor-agnostic or tumor-naive techniques. Tumor-informed methods involve the initial identification of somatic mutations in tumor tissue, followed by the targeted sequencing of plasma DNA using a personalized assay. In contrast, the tumor-agnostic approach performs ctDNA analysis without prior knowledge of the patient's tumor tissue molecular profile. This review highlights the distinctive features and implications of each approach. Tumor-informed techniques enable the precise monitoring of known tumor-specific mutations, leveraging the sensitivity and specificity of ctDNA detection. Conversely, the tumor-agnostic approach allows for a broader genetic and epigenetic analysis, potentially revealing novel alterations and enhancing our understanding of tumor heterogeneity. Both approaches have significant implications for personalized medicine and improved patient outcomes in the field of oncology. The subgroup analysis based on the ctDNA method showed pooled HRs of 8.66 (95% CI 6.38-11.75) and 3.76 (95% CI 2.58-5.48) for tumor-informed and tumor-agnostic, respectively. Our analysis emphasizes that post-operative ctDNA is a strong prognostic marker of RFS. Based on our results, ctDNA can be a significant and independent predictor of RFS. This real-time assessment of treatment benefits using ctDNA can be used as a surrogate endpoint for the development of novel drugs in the adjuvant setting.
Topics: Humans; Circulating Tumor DNA; Neoplasm, Residual; Chemotherapy, Adjuvant; Colorectal Neoplasms; Biomarkers, Tumor; Neoplasm Recurrence, Local
PubMed: 37373376
DOI: 10.3390/ijms241210230 -
BMC Medicine Dec 2022Liquid biopsy has been widely researched for early diagnosis, prognostication and disease monitoring in lung cancer, but there is a need to investigate its clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Liquid biopsy has been widely researched for early diagnosis, prognostication and disease monitoring in lung cancer, but there is a need to investigate its clinical utility for early-stage non-small cell lung cancer (NSCLC).
METHODS
We performed a meta-analysis and systematic review to evaluate diagnostic and prognostic values of liquid biopsy for early-stage NSCLC, regarding the common biomarkers, circulating tumor cells, circulating tumor DNA (ctDNA), methylation signatures, and microRNAs. Cochrane Library, PubMed, EMBASE databases, ClinicalTrials.gov, and reference lists were searched for eligible studies since inception to 17 May 2022. Sensitivity, specificity and area under the curve (AUC) were assessed for diagnostic values. Hazard ratio (HR) with a 95% confidence interval (CI) was extracted from the recurrence-free survival (RFS) and overall survival (OS) plots for prognostic analysis. Also, potential predictive values and treatment response evaluation were further investigated.
RESULTS
In this meta-analysis, there were 34 studies eligible for diagnostic assessment and 21 for prognostic analysis. The estimated diagnostic values of biomarkers for early-stage NSCLC with AUCs ranged from 0.84 to 0.87. The factors TNM stage I, T1 stage, N0 stage, adenocarcinoma, young age, and nonsmoking contributed to a lower tumor burden, with a median cell-free DNA concentration of 8.64 ng/ml. For prognostic analysis, the presence of molecular residual disease (MRD) detection was a strong predictor of disease relapse (RFS, HR, 4.95; 95% CI, 3.06-8.02; p < 0.001) and inferior OS (HR, 3.93; 95% CI, 1.97-7.83; p < 0.001), with average lead time of 179 ± 74 days between molecular recurrence and radiographic progression. Predictive values analysis showed adjuvant therapy significantly benefited the RFS of MRD + patients (HR, 0.27; p < 0.001), while an opposite tendency was detected for MRD - patients (HR, 1.51; p = 0.19). For treatment response evaluation, a strong correlation between pathological response and ctDNA clearance was detected, and both were associated with longer survival after neoadjuvant therapy.
CONCLUSIONS
In conclusion, our study indicated liquid biopsy could reliably facilitate more precision and effective management of early-stage NSCLC. Improvement of liquid biopsy techniques and detection approaches and platforms is still needed, and higher-quality trials are required to provide more rigorous evidence prior to their routine clinical application.
Topics: Humans; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Liquid Biopsy; Lung Neoplasms; Neoplasm Recurrence, Local
PubMed: 36514063
DOI: 10.1186/s12916-022-02681-x -
JAMA Oncology Dec 2020Measurable residual disease (MRD) refers to neoplastic cells that cannot be detected by standard cytomorphologic analysis. In patients with acute myeloid leukemia (AML),... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Measurable residual disease (MRD) refers to neoplastic cells that cannot be detected by standard cytomorphologic analysis. In patients with acute myeloid leukemia (AML), determining the association of MRD with survival may improve prognostication and inform selection of efficient clinical trial end points.
OBJECTIVE
To examine the association between MRD status and disease-free survival (DFS) and overall survival (OS) in patients with AML using scientific literature.
DATA SOURCES
Clinical studies on AML published between January 1, 2000, and October 1, 2018, were identified via searches of PubMed, Embase, and MEDLINE.
STUDY SELECTION
Literature search and study screening were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies that assessed DFS or OS by MRD status in patients with AML were included. Reviews, non-English-language articles, and studies reporting only outcomes after hematopoietic cell transplantation or those with insufficient description of MRD information were excluded.
DATA EXTRACTION AND SYNTHESIS
Study sample size, median patient age, median follow-up time, MRD detection method, MRD assessment time points, AML subtype, specimen source, and survival outcomes were extracted. Meta-analyses were performed separately for DFS and OS using bayesian hierarchical modeling.
MAIN OUTCOMES AND MEASURES
Meta-analyses of survival probabilities and hazard ratios (HRs) were conducted for OS and DFS according to MRD status.
RESULTS
Eighty-one publications reporting on 11 151 patients were included. The average HR for achieving MRD negativity was 0.36 (95% bayesian credible interval [CrI], 0.33-0.39) for OS and 0.37 (95% CrI, 0.34-0.40) for DFS. The estimated 5-year DFS was 64% for patients without MRD and 25% for those with MRD, and the estimated OS was 68% for patients without MRD and 34% for those with MRD. The association of MRD negativity with DFS and OS was significant for all subgroups, with the exception of MRD assessed by cytogenetics or fluorescent in situ hybridization.
CONCLUSIONS AND RELEVANCE
The findings of this meta-analysis suggest that achievement of MRD negativity is associated with superior DFS and OS in patients with AML. The value of MRD negativity appears to be consistent across age groups, AML subtypes, time of MRD assessment, specimen source, and MRD detection methods. These results support MRD status as an end point that may allow for accelerated evaluation of novel therapies in AML.
Topics: Bayes Theorem; Hematopoietic Stem Cell Transplantation; Humans; In Situ Hybridization, Fluorescence; Leukemia, Myeloid, Acute; Neoplasm, Residual; Prognosis
PubMed: 33030517
DOI: 10.1001/jamaoncol.2020.4600 -
Cancer Treatment Reviews Mar 2022Circulating tumor DNA (ctDNA) is increasingly being used as a biomarker in early breast cancer (EBC). We performed a systematic review and meta-analysis to investigate... (Meta-Analysis)
Meta-Analysis Review
Circulating tumor DNA (ctDNA) is increasingly being used as a biomarker in early breast cancer (EBC). We performed a systematic review and meta-analysis to investigate the prognostic value of ctDNA in patients with EBC treated with neoadjuvant therapy (NAT). We searched Medline, Web of Science and Embase for observational or interventional studies that included patients with EBC undergoing NAT, reported outcomes related to the predefined endpoints, and had full text articles available. Study selection followed the PRISMA guidelines and quality assessment the REMARK tool for biomarker studies. Primary endpoint was impact of ctDNA detection in different time points (baseline, on-treatment, and after NAT) on relapse-free survival (RFS) and overall survival (OS). Secondary endpoints included the association of ctDNA detection with pathologic complete response (pCR), and the positive and negative predictive value of ctDNA detection in predicting residual disease after NAT. From the 2908 studies initially identified, 11 met the eligibility criteria and were included in the meta-analysis. Detection of ctDNA, both at baseline and after completion of NAT, significantly associated to worse RFS (HR 4.22, 95% CI: 1.29-13.82 and HR 5.67, 95% CI: 2.73-11.75, respectively) and worse OS (HR 19.1, 95% CI: 6.9-53.04 and HR 4.00, 95% CI: 1.90-8.42, respectively). In contrast, detection of ctDNA did not associate with the probability of achieving a pCR. Our results suggest that ctDNA assessment during NAT for EBC merits further evaluation as a stratification risk factor in prospective trials, in order to better individualize patient's treatment.
Topics: Breast Neoplasms; Circulating Tumor DNA; Female; Humans; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Prognosis; Prospective Studies
PubMed: 35219090
DOI: 10.1016/j.ctrv.2022.102362 -
JAMA Otolaryngology-- Head & Neck... Apr 2022Papillary microcarcinomas of the thyroid (mPTCs) account for an increasing proportion of thyroid cancers in past decades. The use of radiofrequency ablation (RFA) has... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Papillary microcarcinomas of the thyroid (mPTCs) account for an increasing proportion of thyroid cancers in past decades. The use of radiofrequency ablation (RFA) has been investigated as an alternative to surgery. The effectiveness and safety of RFA has yet to be determined.
OBJECTIVE
To evaluate the effectiveness and safety of RFA for low-risk mPTC.
DATA SOURCES
Embase, MEDLINE via Ovid, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and the top 100 references of Google Scholar were searched from inception to May 28, 2021.
STUDY SELECTION
Articles reporting on adult patients with mPTC treated with RFA were included. Studies that involved patients with pre-ablation lymph node or distant metastases, recurrence of disease, or extrathyroidal extension were excluded. Final article selection was conducted by multiple reviewers based on consensus. The proportion of eligible articles was 1%.
DATA EXTRACTION AND SYNTHESIS
This meta-analysis was conducted in accordance with the MOOSE guidelines. Random and fixed-effect models were applied to obtain pooled proportions and 95% CIs.
MAIN OUTCOMES AND MEASURES
The primary outcome was the complete disappearance rate of mPTC. Secondary outcomes were tumor progression and complications.
RESULTS
Fifteen studies were included in this meta-analysis. A total of 1770 patients (1379 women [77.9%]; mean [SD] age, 45.4 [11.4] years; age range, 42.5-66.0 years) with 1822 tumors were treated with RFA; 49 tumors underwent 1 additional RFA session and 1 tumor underwent 2 additional RFA sessions. Mean (SD) follow-up time was 33.0 (11.4) months (range, 6-131 months). The pooled complete disappearance rate at the end of follow-up was 79% (95% CI, 65%-94%). The overall tumor progression rate was 1.5% (n = 26 patients), local residual mPTC in the ablation area was found in 7 tumors (0.4%), new mPTC in the thyroid was found in 15 patients (0.9%), and 4 patients (0.2%) developed lymph node metastases during follow-up. No distant metastases were detected. Three major complications occurred (2 voice changes lasting >2 months and 1 cardiac arrhythmia). Minor complications were described in 45 patients.
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-analysis suggest that RFA is a safe and efficient method to treat selected low-risk mPTCs. Radiofrequency ablation could be envisioned as step-up treatment after local tumor growth under active surveillance for an mPTC or initial treatment in patients with mPTCs with anxiety about active surveillance.
Topics: Carcinoma, Papillary; Female; Humans; Male; Radiofrequency Ablation; Thyroid Neoplasms
PubMed: 35142816
DOI: 10.1001/jamaoto.2021.4381 -
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 -
Blood Advances Dec 2020The prognostic value of minimal residual disease (MRD) for progression-free survival (PFS) and overall survival (OS) was evaluated in a large cohort of patients with... (Meta-Analysis)
Meta-Analysis
The prognostic value of minimal residual disease (MRD) for progression-free survival (PFS) and overall survival (OS) was evaluated in a large cohort of patients with multiple myeloma (MM) using a systematic literature review and meta-analysis. Medline and EMBASE databases were searched for articles published up to 8 June 2019, with no date limit on the indexed database. Clinical end points stratified by MRD status (positive or negative) were extracted, including hazard ratios (HRs) on PFS and OS, P values, and confidence intervals (CIs). HRs were estimated based on reconstructed patient-level data from published Kaplan-Meier curves. Forty-four eligible studies with PFS data from 8098 patients, and 23 studies with OS data from 4297 patients were identified to assess the association between MRD status and survival outcomes. Compared with MRD positivity, achieving MRD negativity improved PFS (HR, 0.33; 95% CI, 0.29-0.37; P < .001) and OS (HR, 0.45; 95% CI, 0.39-0.51; P < .001). MRD negativity was associated with significantly improved survival outcomes regardless of disease setting (newly diagnosed or relapsed/refractory MM), MRD sensitivity thresholds, cytogenetic risk, method of MRD assessment, depth of clinical response at the time of MRD measurement, and MRD assessment premaintenance and 12 months after start of maintenance therapy. The strong prognostic value of MRD negativity and its association with favorable outcomes in various disease and treatment settings sets the stage to adopt MRD as a treatment end point, including development of therapeutic strategies. This large meta-analysis confirms the utility of MRD as a relevant surrogate for PFS and OS in MM.
Topics: Cytogenetics; Humans; Multiple Myeloma; Neoplasm, Residual; Prognosis; Treatment Outcome
PubMed: 33284948
DOI: 10.1182/bloodadvances.2020002827 -
Clinical Lymphoma, Myeloma & Leukemia Apr 2021Acute lymphoblastic leukemia (ALL) typically responds better when treated with multiagent chemotherapy in the pediatric and young adolescent populations. Treatment of... (Meta-Analysis)
Meta-Analysis
Systematic Review and Meta-analysis of CD19-Specific CAR-T Cell Therapy in Relapsed/Refractory Acute Lymphoblastic Leukemia in the Pediatric and Young Adult Population: Safety and Efficacy Outcomes.
Acute lymphoblastic leukemia (ALL) typically responds better when treated with multiagent chemotherapy in the pediatric and young adolescent populations. Treatment of relapsed/refractory (RR) ALL remains a challenge. Even after stem-cell transplantation and intensive chemotherapy, the prognosis of RR-ALL remains grave. The advent of chimeric antigen receptors has demonstrated promising results in RR-ALL. Chimeric antigen receptor-modified T cells (CAR-T) and engineered T cells are used to target cancer cells. In 2017, the US Food and Drug Administration approved CD19-specific CAR-T (tisagenlecleucel) therapy for RR-B-cell ALL in patients under 25 years old. In this systematic review, we discuss the efficacy and safety of CD19-specific CAR-T therapy in RR-B-cell ALL in the pediatric and young adult population. We searched the PubMed, Embase, Web of Science, Cochrane Library, and clinical trials databases. A total of 448 patients received a CD19-specific CAR-T product, and 446 patients had evaluable data. The age range was 0 to 30 years. The incidence rate of complete remission was 82%. The cumulative incidence of relapse after CD19-specific CAR-T therapy is 36%. Similarly, the incidence rate of grade 3 or higher adverse events of neutropenia, thrombocytopenia, neurotoxicity, infections, and cytokine release syndrome were 38%, 23%, 18%, 29%, and 19%, respectively. Our subgroup analysis shows the incidence rate of minimal residual negative complete remission was 69% with the CD28z costimulatory domain, 81% with the 4-1BB domain, and 77% with fourth-generation CD19-specific CAR-T therapy.
Topics: Adolescent; Antigens, CD19; Child; Cytokine Release Syndrome; Drug Resistance, Neoplasm; Humans; Immunotherapy, Adoptive; Neoplasm Recurrence, Local; Neurotoxicity Syndromes; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Progression-Free Survival; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; Remission Induction; Thrombocytopenia; Young Adult
PubMed: 33573914
DOI: 10.1016/j.clml.2020.12.010 -
World Neurosurgery Aug 2022The role of stereotactic radiosurgery (SRS) in the management of recurrent and residual intracranial primary melanocytomas (PMC) remains unclear. The aim of this study... (Review)
Review
OBJECTIVE
The role of stereotactic radiosurgery (SRS) in the management of recurrent and residual intracranial primary melanocytomas (PMC) remains unclear. The aim of this study is to evaluate the safety and efficacy of SRS in the management of these rare tumors.
METHODS
One patient treated with SRS in our institution for an intracranial PMC was retrospectively identified. Additionally, a systematic review of English articles using MEDLINE was performed to identify studies reporting on treatment and tumor characteristics and patient outcomes following SRS-management of intracranial PMC.
RESULTS
Including our institution's patient, a total of 13 patients (11 male and 2 female) met the inclusion criteria and were analyzed. The median age at SRS treatment was 49 years (interquartile range [IQR] 27). At a median follow-up of 24 (IQR 48) months, the aggregate local tumor-control rate was 76.9%. Progression occurred in 3 patients and was managed with repeat SRS (1 of 13) or salvage resection (2 of 13). One case of malignant transformation to melanoma leading to leptomeningeal dissemination and death was noted.
CONCLUSIONS
SRS appears to be a reasonable treatment option for recurrent and residual melanocytomas. A higher prescription dose might be reasonable in the treatment of intermediate grade or recurring PMC. Close longitudinal follow-up for recurrence or malignant transformation of melanocytomas after SRS is recommended.
Topics: Brain Neoplasms; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Radiosurgery; Retrospective Studies; Salvage Therapy; Treatment Outcome
PubMed: 35552031
DOI: 10.1016/j.wneu.2022.04.136 -
Annals of the Rheumatic Diseases Jun 2020To inform the 2019 update of the European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA).
Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis.
OBJECTIVES
To inform the 2019 update of the European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA).
METHODS
A systematic literature research (SLR) to investigate the efficacy of any disease-modifying antirheumatic drug (DMARD) (conventional synthetic (cs)DMARD, biological (b) and biosimilar DMARD, targeted synthetic (ts)DMARD) or glucocorticoid (GC) therapy in patients with RA was done by searching MEDLINE, Embase and the Cochrane Library for articles published between 2016 and 8 March 2019.
RESULTS
234 abstracts were selected for detailed assessment, with 136 finally included. They comprised the efficacy of bDMARDs versus placebo or other bDMARDs, efficacy of Janus kinase (JAK) inhibitors (JAKi) across different patient populations and head-to-head of different bDMARDs versus JAKi or other bDMARDs. Switching of bDMARDs to other bDMARDs or tsDMARDs, strategic trials and tapering studies of bDMARDs, csDMARDs and JAKi were assessed. The drugs evaluated included abatacept, adalimumab, ABT-122, baricitinib, certolizumab pegol, SBI-087, CNTO6785, decernotinib, etanercept, filgotinib, golimumab, GCs, GS-9876, guselkumab, hydroxychloroquine, infliximab, leflunomide, mavrilimumab, methotrexate, olokizumab, otilimab, peficitinib, rituximab, sarilumab, salazopyrine, secukinumab, sirukumab, tacrolimus, tocilizumab, tofacitinib, tregalizumab, upadacitinib, ustekinumab and vobarilizumab. The efficacy of many bDMARDs and tsDMARDs was shown. Switching to another tumour necrosis factor inhibitor (TNFi) or non-TNFi bDMARDs after TNFi treatment failure is efficacious. Tapering of DMARDs is possible in patients achieving long-standing stringent clinical remission; in patients with residual disease activity (including patients in LDA) the risk of flares is increased during the tapering. Biosimilars are non-inferior to their reference products.
CONCLUSION
This SLR informed the task force regarding the evidence base of various therapeutic regimen for the development of the update of EULAR's RA management recommendation.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Biosimilar Pharmaceuticals; Drug Substitution; Drug Therapy, Combination; Glucocorticoids; Humans; Janus Kinase Inhibitors; Randomized Controlled Trials as Topic; Synthetic Drugs; Tumor Necrosis Factor-alpha
PubMed: 32033937
DOI: 10.1136/annrheumdis-2019-216656