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Skin Research and Technology : Official... Mar 2024The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine,... (Review)
Review
AIMS AND OBJECTIVES
The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions.
METHOD
Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles.
RESULTS
In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%).
CONCLUSION
Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.
Topics: Humans; Methotrexate; Azathioprine; Vitiligo; Mycophenolic Acid; Minocycline; Alefacept; Cyclosporine; Adrenal Cortex Hormones; Hypopigmentation; Simvastatin; Zinc; Purines; Pyrazoles; Sulfonamides; Azetidines; Thalidomide
PubMed: 38454597
DOI: 10.1111/srt.13642 -
BMC Cancer Feb 2024To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung... (Meta-Analysis)
Meta-Analysis
Identifying optimal ALK inhibitors in first- and second-line treatment of patients with advanced ALK-positive non-small-cell lung cancer: a systematic review and network meta-analysis.
OBJECTIVES
To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung cancer (NSCLC).
METHODS
The included RCTs were identified through a systematic search of PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and major cancer conferences. The assessment of progression-free survival (PFS), intracranial PFS, overall survival (OS), and patient-reported outcomes (PROs) was carried out using restricted mean survival time (RMST) model, fractional polynomial model and Royston-Parmar model. Time-invariant hazard ratio (HR) models were also used to validate and supplement the primary analysis. Objective response rate (ORR) and adverse events with any grade, grade 3-5 were assessed through a Bayesian network meta-analysis. The primary measures for OS, PFS, and PROs were HR and RMST. The odds ratio was the metric for evaluating safety, ORR, 12-month PFS rate, 24-month OS rate, and the 12-month non-deterioration rate of PROs. Subgroup analyses based on patient characteristics were performed.
RESULTS
A total of fourteen studies (ten for first-line, four for second-line) consisting of nine treatments (chemotherapy, crizotinib, alectinib [600mg BID], low-dose alectinib [300mg BID], brigatinib, ceritinib, ensartinib, envonalkib, and lorlatinib) were included. In the first-line setting, alectinib showed a significant advantage over crizotinib and had the longest OS among all ALK-inhibitors. Compared to crizotinib, lorlatinib had the best efficacy regarding PFS for global patients, followed closely by alectinib and brigatinib. For Asian patients, alectinib significantly improved PFS compared to other treatments. In second-line, alectinib had the highest PFS for patients pretreated with crizotinib, followed by brigatinib, ceritinib and chemotherapy. Alectinib, irrespective of the dose, was the safest first-line option, whereas lorlatinib, brigatinib, and ceritinib showed poorer safety profiles. Alectinib was also the safest ALK-inhibitor for crizotinib-resistant patients. Brigatinib had the best performance in terms of PROs.
CONCLUSIONS
Considering both efficacy and safety, alectinib appears to be the preferable treatment in first-line and second-line, particularly for Asian patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Crizotinib; Lung Neoplasms; Network Meta-Analysis; Bayes Theorem; Quality of Life; Anaplastic Lymphoma Kinase; Protein Kinase Inhibitors; Carbazoles; Sulfones; Aminopyridines; Lactams; Pyrimidines; Pyrazoles; Organophosphorus Compounds
PubMed: 38331773
DOI: 10.1186/s12885-024-11916-4 -
Pharmacotherapy Dec 2020To conduct a systematic review and meta-analysis investigating the effect of tofacitinib and baricitinib on venous thromboembolism (VTE) risk. Search of PubMed, EMBASE,... (Meta-Analysis)
Meta-Analysis
To conduct a systematic review and meta-analysis investigating the effect of tofacitinib and baricitinib on venous thromboembolism (VTE) risk. Search of PubMed, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, LILACS, and Google Scholar databases to identify controlled observational and clinical trials reporting on adverse effects in patients treated with oral tofacitinib or baricitinib up to July 2020. The outcome measure was occurrence of VTE events. We analyzed 59 studies involving 14,335 patients treated with tofacitinib or baricitinib and 11,612 patients who received another active drug or placebo. The meta-analysis showed an odds ratio (OR) for VTE events of 0.29 (95% confidence interval [CI] = 0.10-0.84) overall for tofacitinib based on data from 10 clinical trials with 15 treatment arms; similar ORs were observed for the 10 mg/d dose (OR = 0.18; 95% CI = 0.02-1.60) and the 20 mg/d dose (OR = 0.19; 95% CI = 0.04-0.91). The ORs for VTE events for baricitinib were 3.39 (95% CI = 0.82-14.04) overall, 3.05 (95% CI = 0.12-75.43) for 2 mg, 3.64 (95% CI = 0.59-22.46) for 4 mg, and 3.0 (95% CI = 0.12-76.49) for 7 mg. The indirect meta-analysis comparing tofacitinib with baricitinib (10 clinical trials with 15 treatment arms) showed an OR for VTE events of 0.086 (95% CI = 0.02-0.51) for tofacitinib and a superior safety profile for VTE events. In the meta-regression analysis (19 clinical trials with 21 treatment arms), the effect was 0.02 (95% CI = -0.04 to 0.08) for tofacitinib and -0.01 (95% CI = -1.29 to 1.26 for baricitinib. Plotting of the data for tofacitinib showed that VTE risk increased with high doses. The effect, however, was less than 1 for the 10-mg and 20-mg doses, indicating a protective effect. This effect was not observed for baricitinib. Tofacitinib is not associated with an increased risk of VTE and has a superior safety profile to baricitinib in this respect. Tofacitinib may exert a protective effect against VTE.
Topics: Antirheumatic Agents; Azetidines; Humans; Piperidines; Purines; Pyrazoles; Pyrimidines; Risk Factors; Sulfonamides; Venous Thromboembolism
PubMed: 33064892
DOI: 10.1002/phar.2472 -
Korean Journal of Anesthesiology Dec 2023Cesarean section is associated with moderate to severe pain and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed. The optimal NSAID, however, has not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cesarean section is associated with moderate to severe pain and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed. The optimal NSAID, however, has not been elucidated. In this network meta-analysis and systematic review, we compared the influence of control and individual NSAIDs on the indices of analgesia, side effects, and quality of recovery.
METHODS
CDSR, CINAHL, CRCT, Embase, LILACS, PubMed, and Web of Science were searched for randomized controlled trials comparing a specific NSAID to either control or another NSAID in elective or emergency cesarean section under general or neuraxial anesthesia. Network plots and league tables were constructed, and the quality of evidence was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis.
RESULTS
We included 47 trials. Cumulative intravenous morphine equivalent consumption at 24 h, the primary outcome, was examined in 1,228 patients and 18 trials, and control was found to be inferior to diclofenac, indomethacin, ketorolac, and tenoxicam (very low quality evidence owing to serious limitations, imprecision, and publication bias). Indomethacin was superior to celecoxib for pain score at rest at 8-12 h and celecoxib + parecoxib, diclofenac, and ketorolac for pain score on movement at 48 h. In regard to the need for and time to rescue analgesia COX-2 inhibitors such as celecoxib were inferior to other NSAIDs.
CONCLUSIONS
Our review suggests the presence of minimal differences among the NSAIDs studied. Nonselective NSAIDs may be more effective than selective NSAIDs, and some NSAIDs such as indomethacin might be preferable to other NSAIDs.
Topics: Humans; Pregnancy; Female; Diclofenac; Ketorolac; Celecoxib; Cesarean Section; Network Meta-Analysis; Anti-Inflammatory Agents, Non-Steroidal; Indomethacin; Pain
PubMed: 37066603
DOI: 10.4097/kja.23014 -
European Journal of Clinical... Jun 2023Inflammation is closely related to cancer prognosis. The effect of celecoxib, a nonsteroidal anti-inflammatory drug, on the prognosis of patients with cancer remains... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inflammation is closely related to cancer prognosis. The effect of celecoxib, a nonsteroidal anti-inflammatory drug, on the prognosis of patients with cancer remains uncertain. To assess the association between celecoxib plus standard chemotherapy and cancer prognosis, we conducted a systematic review and meta-analysis of published studies.
METHODS
PubMed, EMBASE, and the Cochrane Library were searched from inception until July 2022 for randomized controlled trials reporting the prognosis of patients with cancer treated with celecoxib plus standard chemotherapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Meta-analysis was performed using Review Manager software version 5.4. The following search terms were used in the databases: ((((celecoxib)) AND ((((((((cancer) OR (carcinoma)) OR (sarcoma)) OR (neoplasms)) OR (tumor)) OR (tumour)) OR (tumors)) OR (tumours))) AND ((survival) OR (mortality))) AND (((Clinical Trials, Randomized) OR (Trials, Randomized Clinical)) OR (Controlled Clinical Trials, Randomized)).
RESULTS
Overall, 13 randomized controlled trials, including 8957 patients with cancer, were included in the analysis. Compared to conventional chemotherapy alone, 1-year OS and 1-year PFS rates were not significantly improved with celecoxib adjuvant therapy (OS: p = .38; PFS: p = .65). In addition, no differences were observed between the celecoxib and placebo groups in 3-year overall (p = .98), 3-year progression-free (p = .40), 5-year overall (p = .59), or 5-year progression-free (p = .56) survival rates. An increase in the risk ratio of leukopenia (p = .02) and thrombocytopenia (p = .05) was also observed, suggesting that celecoxib promotes hematologic toxicity. No increased risk of cardiovascular (p = .96) and gastrointestinal (p = .10-.91) events was observed.
CONCLUSIONS
The addition of celecoxib to standard chemotherapy did not improve OS or PFS rates of patients with cancer. Additionally, celecoxib can increase hematologic toxicity without increasing the risk of gastrointestinal or cardiovascular reactions. Further randomized controlled trials are necessary to clarify its effects and applications.
Topics: Humans; Celecoxib; Neoplasms; Anti-Inflammatory Agents, Non-Steroidal; Combined Modality Therapy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36807298
DOI: 10.1111/eci.13973 -
Leukemia Research Oct 2022Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk molecular subtype with a gene expression profile similar to Philadelphia-positive ALL, but... (Review)
Review
Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk molecular subtype with a gene expression profile similar to Philadelphia-positive ALL, but not harboring the BCR-ABL1 gene fusion. We aimed to investigate the efficacy of target therapy with the Janus kinase inhibitor, ruxolitinib, in patients with Ph-like ALL and molecular signature of JAK-STAT signaling pathway. A systematic search of the literature was performed to identify reports concerning administration of ruxolitinib in Ph-like ALL patients. Additionally, Polish Pediatric ALL registries were searched for patients with Ph-like ALL treated with ruxolitinib. Extracted information included epidemiological background, somatic aberrations, treatment response, and patient outcome. After PubMed database search, twelve patients were identified, and one was identified in the Polish Pediatric ALL registry. In nine patients gene fusions affecting JAK2 (n = 7) and EPOR (n = 2) were detected. Surface overexpression of CRLF2 and IKZF1 deletions were observed in two and three patients, respectively. Induction failure occurred in all the patients. Therapy with ruxolitinib led to complete (n = 7) and partial (n = 2) remission, in three individuals no information was found. Based on the limited number of studies describing the efficacy of ruxolitinib as an additional compound administrated with standard ALL therapy, we conclude that this approach can be considered in patients with aberrations activating JAK-STAT pathway.
Topics: Child; Humans; Janus Kinase Inhibitors; Janus Kinases; Nitriles; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrazoles; Pyrimidines; STAT Transcription Factors; Signal Transduction
PubMed: 35939887
DOI: 10.1016/j.leukres.2022.106925 -
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 -
Systematic Reviews Apr 2024Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA.
METHODS
We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis.
RESULTS
A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58-2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60-2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75-1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83-4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08-3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85-2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15-2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93-2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46-1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics.
CONCLUSION
EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events.
Topics: Humans; Immunosuppressive Agents; Anemia, Aplastic; Immunosuppression Therapy; Benzoates; Pathologic Complete Response; Treatment Outcome; Hydrazines; Pyrazoles
PubMed: 38576005
DOI: 10.1186/s13643-024-02515-2 -
Hematology/oncology and Stem Cell... Apr 2023Renal cell carcinoma (RCC) is the most common kidney cancer in adults (approximately 90%), and clear cell RCC (ccRCC) is the most frequent histologic subtype... (Review)
Review
Renal cell carcinoma (RCC) is the most common kidney cancer in adults (approximately 90%), and clear cell RCC (ccRCC) is the most frequent histologic subtype (approximately 75%). We reviewed the safety and efficacy of checkpoint inhibitors (CPIs) in ccRCC, identifying 5927 articles in PubMed, Embase, Cochrane, and Web of Science. Ten randomized control (N = 7765) and 10 non-randomized (N = 572) studies were included. Overall, 4819 patients treated with CPI combinations were compared with everolimus, sunitinib, or placebo. Overall response rates (ORR) were 9-25% with nivolumab (niv), 42% with niv + ipilimumab (ipi), 55.7% with niv + cabozantinib, 56% with niv + tivozanib vs. 5% with everolimus. ORR was 51.5-58% with avelumab + axitinib vs. 25.5% with sunitinib. ORR was 59.3-73% with pembrolizumab + tyrosine kinase inhibitor vs. 25.7% with sunitinib. ORR was 32-36% with atezolizumab + bevacizumab vs. 29-33% with sunitinib. In patients with PD-L1+ve and -ve ccRCC, niv, atezolizumab, ipi, and pembrolizumab were safe and effective alone and when combined with cabozantinib, tivozanib, axitinib, levantinib, and pegilodecakin. Atezolizumab + bevacizumab was safe and effective in ccRCC with high PD-L1 expression. Pembrolizumab was safe and effective in preventing recurrence in ccRCC patients with nephrectomy. Additional randomized, double-blind, multicenter clinical trials are needed to confirm these results.
Topics: Adult; Humans; Carcinoma, Renal Cell; Sunitinib; Axitinib; Everolimus; B7-H1 Antigen; Bevacizumab; Kidney Neoplasms; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37023219
DOI: 10.56875/2589-0646.1027 -
Pain Nov 2022Burrowing behaviour is used to assess pain-associated behaviour in laboratory rodents. To gain insight into how models of disease-associated persistent pain and... (Meta-Analysis)
Meta-Analysis
Burrowing behaviour is used to assess pain-associated behaviour in laboratory rodents. To gain insight into how models of disease-associated persistent pain and analgesics affect burrowing behaviour, we performed a systematic review and meta-analysis of studies that assessed burrowing behaviour. A systematic search in March 2020 and update in September 2020 was conducted in 4 databases. Study design characteristics and experimental data were extracted, followed by a random-effects meta-analysis. We explored the association between burrowing and monofilament-induced limb withdrawal. Dose response relationship was investigated for some analgesics. Forty-five studies were included in the meta-analysis, in which 16 model types and 14 drug classes were used. Most experiments used rat (79%) and male (72%) animals. Somatic inflammation and trauma-induced neuropathy models were associated with reduced burrowing behaviour. Analgesics (nonsteroidal anti-inflammatory drug and gabapentinoids) attenuated burrowing deficits in these models. Reporting of measures to reduce risk of bias was unclear except for randomisation which was high. There was not a correlation ( R2 = 0.1421) between burrowing and monofilament-induced limb withdrawal. Opioids, gabapentin, and naproxen showed reduced burrowing behaviour at high doses, whereas ibuprofen and celecoxib showed opposite trend. The findings indicate that burrowing could be used to assess pain-associated behaviour. We support the use of a portfolio of composite measures including spontaneous and stimulus-evoked tests. The information collected here could help in designing experiments involving burrowing assessment in models of disease-associated pain.
Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Celecoxib; Disease Models, Animal; Gabapentin; Ibuprofen; Male; Naproxen; Pain; Rats; Rodentia
PubMed: 35353780
DOI: 10.1097/j.pain.0000000000002632