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European Review For Medical and... Nov 2021This systematic review with network meta-analysis was performed to compare the effectiveness of oral anti-inflammatory drugs used in Brazil for osteoarthritis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This systematic review with network meta-analysis was performed to compare the effectiveness of oral anti-inflammatory drugs used in Brazil for osteoarthritis.
PATIENTS AND METHODS
Randomized clinical trials evaluating ultramicronised diclofenac, diclofenac, celecoxib, etodolac and placebo in patients with osteoarthritis were identified. A search was conducted in May 2021 through PubMed, Scopus and Web of Science databases. A network meta-analysis was developed for efficacy outcome related to analgesia measured by the pain subscale of the Western Ontario and McMaster Universities tool. In addition, surface under the cumulative ranking was performed to rank the drugs in relation to this outcome.
RESULTS
Twelve randomized clinical trials were included. Overall, ultramicronised diclofenac 105 mg/day (UD105) was better than all the others, including ultramicronised diclofenac 70 mg/day (UD70). In addition, surface under the cumulative ranking resulted in the following order: 1) ultramicronised diclofenac 105 mg/day (100%), 2) ultramicronised diclofenac 70 mg/day (80%), 3) celecoxib 200 mg/day (49%), 4) diclofenac 100 mg/day (48%), 5) placebo (19%) and 6) diclofenac 150 mg/day (6%).
CONCLUSIONS
Ultramicronised diclofenac demonstrated superior efficacy compared to other conventional anti-inflammatory drugs and placebo in relieving osteoarthritis pain.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Diclofenac; Humans; Network Meta-Analysis; Osteoarthritis; Pain; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34859865
DOI: 10.26355/eurrev_202111_27252 -
Journal of Medical Virology Apr 2022The benefits of baricitinib in coronavirus disease-2019 are inadequately defined. We performed a systematic review and meta-analysis of studies of baricitinib to... (Meta-Analysis)
Meta-Analysis
The benefits of baricitinib in coronavirus disease-2019 are inadequately defined. We performed a systematic review and meta-analysis of studies of baricitinib to determine its clinical efficacy and adverse events in patients with COVID-19. Databases were searched from their inception to September 5, 2021. The primary outcome was the coefficient of mortality. We also compared secondary indicators and adverse events between baricitinib treatment and placebo or other treatments. Twelve studies of 3564 patients were included and assessed qualitatively (modified Jadad and Newcastle-Ottawa Scale scores). Baricitinib effectively improved the mortality rate (relative risk of mortality = 0.56; 95% confidence interval: 0.46-0.69; p < 0.001; I = 2%), and this result was unchanged by subgroup analysis. Baricitinib improved intensive care unit admission, the requirement for invasive mechanical ventilation, and improved the oxygenation index. Data from these studies also showed that baricitinib slightly reduced the risk of adverse events. Regarding the choice of the drug dosage of baricitinib, the high-dose group appeared to have additional benefits for clinical efficacy. Our study shows that baricitinib may be a promising, safe, and effective anti-severe acute respiratory syndrome-coronavirus-2 drug candidate, with the advantages of low cost, easy production, and convenient storage.
Topics: Azetidines; COVID-19; Dose-Response Relationship, Drug; Humans; Purines; Pyrazoles; SARS-CoV-2; Sulfonamides; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34846766
DOI: 10.1002/jmv.27482 -
BMC Cancer Nov 2021Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant. Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC.
METHODS
We included all phase 2 and 3 randomised controlled trials (RCTs) comparing any two or three treatment options. Eligible studies reported at least one of the following outcomes: progression free survival (PFS), overall survival (OS), objective response rate (ORR), or adverse events of grade 3 or higher (Grade ≥ 3 AEs). Subgroup analysis was conducted according to central nervous system (CNS) metastases.
RESULTS
A total of 9 RCTs consisting of 2484 patients with 8 treatment options were included in the systematic review. Our analysis showed that alectinib (300 mg and 600 mg), brigatinib, lorlatinib and ensartinib yielded the most favorable PFS. Whereas there was no significant OS or ORR difference among the ALK-TKIs. According to Bayesian ranking profiles, lorlatinib, alectinib 600 mg and alectinib 300 mg had the best PFS (63.7%), OS (35.9%) and ORR (37%), respectively. On the other hand, ceritinib showed the highest rate of severe adverse events (60%).
CONCLUSION
Our analysis indicated that alectinib and lorlatinib might be associated with the best therapeutic efficacy in first-line treatment for major population of advanced NSCLC patients with ALK-rearrangement. However, since there is little comparative evidence on the treatment options, there is need for relative trials to fully determine the best treatment options as well as the rapidly evolving treatment landscape.
Topics: Aminopyridines; Anaplastic Lymphoma Kinase; Antineoplastic Agents; Carbazoles; Carcinoma, Non-Small-Cell Lung; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Gene Rearrangement; Humans; Lactams; Lung Neoplasms; Network Meta-Analysis; Organophosphorus Compounds; Piperazines; Piperidines; Progression-Free Survival; Protein Kinase Inhibitors; Pyrazoles; Pyridazines; Pyrimidines; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34836510
DOI: 10.1186/s12885-021-08977-0 -
Reviews in Medical Virology Nov 2021The current pandemic caused by SARS-CoV-2 virus infection is known as Covid-19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ...
The current pandemic caused by SARS-CoV-2 virus infection is known as Covid-19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ systems. Damage induced by the virus is related to dysfunctional activity of the immune system, but the activity of molecules such as C-reactive protein (CRP) as a factor capable of inducing an inflammatory status that may be involved in the severe evolution of the disease, has not been extensively evaluated. A systematic review was performed using the NCBI-PubMed database to find articles related to Covid-19 immunity, inflammatory response, and CRP published from December 2019 to December 2020. High levels of CRP were found in patients with severe evolution of Covid-19 in which several organ systems were affected and in patients who died. CRP activates complement, induces the production of pro-inflammatory cytokines and induces apoptosis which, together with the inflammatory status during the disease, can lead to a severe outcome. Several drugs can decrease the level or block the effect of CRP and might be useful in the treatment of Covid-19. From this review it is reasonable to conclude that CRP is a factor that can contribute to severe evolution of Covid-19 and that the use of drugs able to lower CRP levels or block its activity should be evaluated in randomized controlled clinical trials.
Topics: ADAM17 Protein; Angiotensin-Converting Enzyme 2; Anti-Inflammatory Agents; Biomarkers; C-Reactive Protein; COVID-19; Celecoxib; Complement System Proteins; Cytokine Release Syndrome; Cytokines; Disease Progression; Doxycycline; Gene Expression Regulation; Humans; Randomized Controlled Trials as Topic; SARS-CoV-2; Severity of Illness Index; Survival Analysis; COVID-19 Drug Treatment
PubMed: 34773448
DOI: 10.1002/rmv.2221 -
Annals of Palliative Medicine Oct 2021Riociguat therapy has been recommended for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), and it might have therapeutic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Riociguat therapy has been recommended for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), and it might have therapeutic significance for other types of pulmonary hypertension (PH). Our purpose was to evaluate the specific impact of riociguat on all types of PH.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the safety and efficacy of riociguat treatment for PH through databases of the Cochrane Library, PubMed, Embase, and Web of Science from inception to the present. Duplicate publications, studies with no full text, incomplete information or inability to extract data, animal experiments and reviews, and systematic reviews were excluded. The software RevMan 5.4 was used for data synthesis.
RESULTS
There were 8 RCTs included in our study, involving 1,606 participants. For PAH and CTEPH patients, riociguat treatment extended 6-minute walk distance (6MWD) by 39.84 meters, decreased mean pulmonary arterial pressure (PAP) by 4.20 mmHg, lowered pulmonary vascular resistance (PVR) by 218.76 dynes/sec/cm-5, cut down right atrial pressure (RAP) by 0.9 mmHg, increased cardiac index (CI) by 0.49 L/min/m2, improved cardiac output (CO) by 0.89 L/min, reduced N-terminal pro-type B natriuretic peptide (NT-proBNP) by 436.21 pg/mL, and decreased adverse events and clinical worsening as compared with placebo. For other types of PH including PH due to left heart disease and PH due to lung disease, riociguat was reported as having improved CI by 0.42 L/min/m2 and CO was increased by 0.92 L/min compared with placebo. Other efficacy outcomes and safety outcomes did not attain statistical difference in other types of PH.
CONCLUSIONS
For PAH and CTEPH, riociguat treatment is safe and effective, but for other types of PH, it can only improve some hemodynamic parameters.
Topics: Chronic Disease; Humans; Hypertension, Pulmonary; Pyrazoles; Pyrimidines
PubMed: 34763472
DOI: 10.21037/apm-21-2656 -
Annals of the Rheumatic Diseases Jan 2022To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19.
OBJECTIVES
To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19.
METHODS
According to the EULAR standardised operating procedures, a systematic literature review up to 14 July 2021 was conducted and followed by a consensus meeting of an international multidisciplinary task force. The new statements were consolidated by formal voting.
RESULTS
We updated 2 overarching principles and 12 PtC. Evidence was only available in moderate to severe and critical patients. Glucocorticoids alone or in combination with tocilizumab are beneficial in COVID-19 cases requiring oxygen therapy and in critical COVID-19. Use of Janus kinase inhibitors (baricitinib and tofacitinib) is promising in the same populations of severe and critical COVID-19. Anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma may find application in early phases of the disease and in selected subgroups of immunosuppressed patients. There was insufficient robust evidence for the efficacy of other immunomodulators with further work being needed in relation to biomarker-based stratification for IL-1 therapy CONCLUSIONS: Growing evidence supports incremental efficacy of glucocorticoids alone or combined with tocilizumab/Janus kinase inhibitors in moderate to severe and critical COVID-19. Ongoing studies may unmask the potential application of other therapeutic approaches. Involvement of rheumatologists, as systemic inflammatory diseases experts, should be encouraged in clinical trials of immunomodulatory therapy in COVID-19.
Topics: Antibodies, Monoclonal, Humanized; Azetidines; Consensus Development Conferences as Topic; Drug Therapy, Combination; Glucocorticoids; Humans; Immunomodulating Agents; Immunomodulation; Janus Kinase Inhibitors; Piperidines; Purines; Pyrazoles; Pyrimidines; SARS-CoV-2; Sulfonamides; COVID-19 Drug Treatment
PubMed: 34620584
DOI: 10.1136/annrheumdis-2021-221366 -
Aging Sep 2021Many recent studies have investigated the role of drug interventions for coronavirus disease 2019 (COVID-19) infection. However, an important question has been raised... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many recent studies have investigated the role of drug interventions for coronavirus disease 2019 (COVID-19) infection. However, an important question has been raised about how to select the effective and secure medications for COVID-19 patients. The aim of this analysis was to assess the efficacy and safety of the various medications available for severe and non-severe COVID-19 patients based on randomized placebo-controlled trials (RPCTs).
METHODS
We did an updated network meta-analysis. We searched the databases from inception until July 31, 2021, with no language restrictions. We included RPCTs comparing 49 medications and placebo in the treatment of severe and non-severe patients (aged 18 years or older) with COVID-19 infection. We extracted data on the trial and patient characteristics, and the following primary outcomes: all-cause mortality, the ratios of virological cure, and treatment-emergent adverse events. Odds ratio (OR) and their 95% confidence interval (CI) were used as effect estimates.
RESULTS
From 3,869 publications, we included 61 articles related to 73 RPCTs (57 in non-severe COVID-19 patients and 16 in severe COVID-19 patients), comprising 20,680 patients. The mean sample size was 160 (interquartile range 96-393) in this study. The median duration of follow-up drugs intervention was 28 days (interquartile range 21-30). For increase in virological cure, we only found that proxalutamide (OR 9.16, 95% CI 3.15-18.30), ivermectin (OR 6.33, 95% CI 1.22-32.86), and low dosage bamlanivimab (OR 5.29, 95% CI 1.12-24.99) seemed to be associated with non-severe COVID-19 patients when compared with placebo, in which proxalutamide seemed to be better than low dosage bamlanivimab (OR 5.69, 95% CI 2.43-17.65). For decrease in all-cause mortality, we found that proxalutamide (OR 0.13, 95% CI 0.09-0.19), imatinib (OR 0.49, 95% CI 0.25-0.96), and baricitinib (OR 0.58, 95% CI 0.42-0.82) seemed to be associated with non-severe COVID-19 patients; however, we only found that immunoglobulin gamma (OR 0.27, 95% CI 0.08-0.89) was related to severe COVID-19 patients when compared with placebo. For change in treatment-emergent adverse events, we only found that sotrovimab (OR 0.21, 95% CI 0.13-0.34) was associated with non-severe COVID-19 patients; however, we did not find any medications that presented a statistical difference when compared with placebo among severe COVID-19 patients.
CONCLUSION
We conclude that marked variations exist in the efficacy and safety of medications between severe and non-severe patients with COVID-19. It seems that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. Clinical decisions to use preferentially medications should carefully consider the risk-benefit profile based on efficacy and safety of all active interventions in patients with COVID-19 at different levels of infection.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azetidines; COVID-19; Humans; Imatinib Mesylate; Immunologic Factors; Network Meta-Analysis; Oxazoles; Purines; Pyrazoles; SARS-CoV-2; Severity of Illness Index; Sulfonamides; Thiohydantoins; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34531332
DOI: 10.18632/aging.203522 -
Indian Journal of Dermatology,... 2021Tofacitinib and ruxolitinib have been used off-label to treat alopecia areata. Although a number of case reports and small studies have been published, there are no... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tofacitinib and ruxolitinib have been used off-label to treat alopecia areata. Although a number of case reports and small studies have been published, there are no comprehensive reviews examining the outcomes of using tofacitinib and ruxolitinib for the treatment of alopecia areata.
AIMS
The aim of the study was to examine the outcome of patients with alopecia areata treated with oral tofacitinib or ruxolitinib in previously published studies.
METHODS
A search of MEDLINE, Embase and Cochrane library was conducted. A systematic review and meta-analysis were performed focusing on the Severity of Alopecia Tool 50 achievement rate, the frequency of adverse events and recurrence after discontinuation of treatment.
RESULTS
A total of 1244 studies were identified of which only 12 studies met the inclusion criteria. Of the 346 patients in these 12 studies, 288 had received oral tofacitinib and 58 had received oral ruxolitinib. The overall Severity of Alopecia Tool50 achievement rate was 66% (95% confidence interval, 54%-76%). Subgroup analysis revealed that drug choice, mean age, sex ratio and alopecia areata subtype ratio did not significantly affect the treatment response. Infections and laboratory abnormalities were the most common adverse events (98 and 65 cases of 319 patients, respectively). Patients treated for more than six months had a greater frequency of laboratory abnormalities as compared to those treated for shorter durations (24% vs. 7%; P = 0.04). Recurrence of alopecia areata was observed within three months after discontinuation of treatment in the majority (74%) of patients.
LIMITATIONS
This analysis was limited by the small number of observational studies available for review, the heterogeneity of patient characteristics and the lack of long-term data.
CONCLUSION
Both oral tofacitinib and ruxolitinib are effective and well tolerated in the treatment of alopecia areata. Clinicians should be aware of the expected efficacy, adverse events and high recurrence rate of oral JAK inhibitors for alopecia areata to effectively counsel these patients before starting therapy.
Topics: Administration, Oral; Alopecia Areata; Humans; Nitriles; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Recurrence
PubMed: 34379968
DOI: 10.25259/IJDVL_975_19 -
International Immunopharmacology Oct 2021This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of Janus kinase (JAK) inhibitors... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of Janus kinase (JAK) inhibitors for COVID-19 patients.
METHODS
PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to July 12, 2021. RCTs comparing the clinical efficacy and safety of JAK inhibitors with a placebo or standard care in treating COVID-19 patients were included. The primary outcome was all-cause mortality rate at day 28.
RESULTS
Three RCTs were included in this meta-analysis. The all-cause mortality rate at day 28 was lower among the patients receiving JAK inhibitors than among the controls (4.1% [28/647] versus 7.0% [48/684], OR, 0.57; 95% CI, 0.36-0.92, I = 0). The clinical recovery rate was higher among the patients receiving JAK inhibitors than among the controls (85.1% (579/680) versus 80.0% [547/684], OR, 1.45; 95% CI, 1.09-1.93, I = 0). Additionally, the use of JAK inhibitors was associated with a shorter time to recovery than among the controls (MD, -2.84; 95% CI, -5.56 to -0.12; I = 50%). The rate of invasive mechanical ventilation (MV) was lower in the patients who used JAK inhibitors than among the controls. Finally, no significant difference was observed between the patients who used JAK inhibitors and the controls in the risk of any adverse events (OR, 0.92; 95% CI, 0.64-1.34; I = 33%) and serious adverse events (OR, 0.80; 95% CI, 0.45-1.44; I = 46%).
CONCLUSIONS
JAK inhibitors can lead to a better clinical outcome of hospitalized COVID-19 patients, and they are a safe agent in the treatment of COVID-19.
Topics: Azetidines; Humans; Janus Kinase Inhibitors; Nitriles; Piperidines; Purines; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; SARS-CoV-2; Sulfonamides; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34343937
DOI: 10.1016/j.intimp.2021.108027 -
Blood Cancer Journal Jul 2021Myelofibrosis is a myeloproliferative neoplasm associated with constitutional symptoms, increasing splenomegaly, and worsening cytopenias. Janus kinase (JAK) inhibitors... (Meta-Analysis)
Meta-Analysis
Myelofibrosis is a myeloproliferative neoplasm associated with constitutional symptoms, increasing splenomegaly, and worsening cytopenias. Janus kinase (JAK) inhibitors have been used for the treatment of myelofibrosis for several years, but there is a lack of comparative information between those treatments. A systematic review and network meta-analysis was performed on randomized controlled trials in patients with myelofibrosis receiving JAK inhibitor or placebo or control. Primary outcomes were efficacy on spleen volume reduction and total symptom score reduction. Additional analyses were conducted on anemia and thrombopenia events. Seven studies were included in the network meta-analysis including 1953 patients randomly assigned to four JAK inhibitors-ruxolitinib, fedratinib, pacritinib, momelotinib-or control. In first-line therapy, momelotinib and fedratinib were associated with comparable efficacy to ruxolitinib, and with less toxicity on erythrocytes and platelets, respectively. Pacritinib was less effective on splenomegaly than ruxolitinib as a first-line treatment but seemed effective in second line, after ruxolitinib exposure. Fedratinib and ruxolitinib that are FDA approved in myelofibrosis have both confirmed being valuable option to treat splenomegaly and constitutional symptoms, and their slightly different tolerance-profiles can guide therapeutic choice for first-line treatment, according to patient profile. Momelotinib could be another option especially due to its positive effect on anemia.
Topics: Bridged-Ring Compounds; Humans; Janus Kinase Inhibitors; Nitriles; Primary Myelofibrosis; Pyrazoles; Pyrimidines; Pyrrolidines; Splenomegaly; Sulfonamides; Treatment Outcome
PubMed: 34315858
DOI: 10.1038/s41408-021-00526-z