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Cancers Feb 2024Cutaneous T-cell lymphomas (CTCLs) are a group of lymphoid neoplasms with high relapse rates and no curative treatment other than allogeneic stem cell transplantation... (Review)
Review
Cutaneous T-cell lymphomas (CTCLs) are a group of lymphoid neoplasms with high relapse rates and no curative treatment other than allogeneic stem cell transplantation (allo-SCT). CTCL is significantly influenced by disruption of JAK/STAT signaling. Therefore, Janus kinase (JAK) inhibitors may be promising for CTCL treatment. This study is a systematic review aiming to investigate the role of JAK inhibitors in the treatment of CTCL, including their efficacy and safety. Out of 438 initially searched articles, we present 13 eligible ones. The overall response rate (ORR) in the treatment with JAK inhibitors in clinical trials was 11-35%, although different subtypes of CTCL showed different ORRs. Mycosis fungoides showed an ORR of 14-45%, while subcutaneous-panniculitis-like T-cell lymphoma (SPTCL) displayed an ORR ranging from 75% to 100%. Five cases were reported having a relapse/incident of CTCL after using JAK inhibitors; of these, three cases were de novo CTCLs in patients under treatment with a JAK inhibitor due to refractory arthritis, and two cases were relapsed disease after graft-versus-host disease treatment following allo-SCT. In conclusion, using JAK inhibitors for CTCL treatment seems promising with acceptable side effects, especially in patients with SPTCL. Some biomarkers, like pS6, showed an association with better responses. Caution should be taken when treating patients with an underlying autoimmune disease and prior immunosuppression.
PubMed: 38473222
DOI: 10.3390/cancers16050861 -
International Immunopharmacology Jun 2024To evaluate the efficacy and safety of Janus kinases inhibitors (JAKi) for adult-onset Still's disease (AOSD) patients. (Review)
Review
OBJECTIVE
To evaluate the efficacy and safety of Janus kinases inhibitors (JAKi) for adult-onset Still's disease (AOSD) patients.
METHODS
We searched the Embase, PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and the China National Knowledge Infrastructure (CNKI) from inception up to 22 October 2023. The results were supplemented by a backward search of relevant publications. Two authors independently selected trials. The available studies were comprehensively reviewed and analysed.
RESULTS
A total of 9 studies with a total of 35 patients were included in the review. Of these patients, 17 (48.6%) patients were treated with tofacitinib, 14 (40%) with baricitinib, 4 (11.4%) with ruxolitinib and 1 (2.9%) with upadacitinib. After treatment with JAKi, 17 (48.6%) patients showed complete remission, 12 (34.3%) patients showed partial remission, and 7 (20%) patients showed loss of efficacy or relapse. The use of ruxolitinib showed a remission rate of 100% in AOSD patients with macrophage activation syndrome (MAS). The incidence of adverse events (AEs) reported were mild and rare overall. Most AEs were abnormal lipid parameters (9.7%), bacterial pneumonia (3.2%), organised pneumonia (3.2%), diarrhoea (3.2%), increased heart rate (3.2%), menometrorrhagia (3.2%) and leukopenia (3.2%). One patient died from bacterial pneumonia.
CONCLUSION
JAKi therapy may be an option for patients with AOSD, especially for refractory AOSD. For patients with AOSD complicated by MAS, ruxolitinib seems to be a better choice than other JAKi agents. Although our study shows that JAKi are well tolerated in AOSD patients, we still need to be on the lookout for fatal infections.
PubMed: 38870881
DOI: 10.1016/j.intimp.2024.112451 -
Clinical Microbiology and Infection :... Apr 2024Tuberculosis (TB) is a common complication associated with treatment with tumour necrosis factor (TNF) antagonists and Janus kinase (JAK) inhibitors. However, there is... (Review)
Review
BACKGROUND
Tuberculosis (TB) is a common complication associated with treatment with tumour necrosis factor (TNF) antagonists and Janus kinase (JAK) inhibitors. However, there is uncertainty about the risk of TB relapse in patients with TB and comorbidities requiring treatment with these agents.
OBJECTIVES
To assess the risk of TB relapse in patients (re-)started on TNF antagonists or JAK inhibitors.
METHODS
Systematic review.
DATA SOURCES
PubMed and Cochrane Library databases until 11 December 2023.
STUDY ELIGIBILITY CRITERIA
Randomized control trials, prospective and retrospective cohort studies, case reports and case series.
PARTICIPANTS
Patients with current or previous TB who were (re-)started on TNF antagonists or JAK inhibitors.
INTERVENTIONS
(Re-)introduction of TNF antagonists and JAK inhibitors.
ASSESSMENT OF RISK OF BIAS
All studies meeting entry criteria were included regardless of quality.
METHODS OF DATA SYNTHESIS
Categorical data are presented as frequencies and percentages. For non-normally distributed aggregated data, we calculated the pooled weighted median with 95% CI. For individual patient data, the median and interquartile range (IQR) were calculated.
RESULTS
Of 5018 articles screened for eligibility, 67 publications reporting on 368 TB patients who (re-)initiated treatment with TNF antagonists for underlying diseases were included. The median age was 42.5 years (95% CI: 40.4-42.5) and the proportion of female patients was 36.6% (n = 74) of patients whose sex was reported. A total of 14 patients (3.8%, 95% CI: 2.1-6.3%) developed TB relapse after a median of 8.5 months (interquartile range, 6.8-14.8 months) following (re-)initiation of anti-TNF treatment. Furthermore, among 251 articles screened for eligibility, 11 reports on TB patients who were (re-)started on JAK inhibitors for underlying diseases were identified. The median age was 62 years (interquartile range, 48.5-68.5 years) and 45.5% (n = 5) were female. Only one patient (9.1%; 95% CI: 0.2-41.3%) had TB reactivation 10 months after starting treatment with ruxolitinib. In addition, 94 patients who were treated with TNF antagonists and two patients temporarily treated with JAK inhibitors for the prevention or treatment of paradoxical reactions were analysed. None of the publications reported microbiological failure or worsening of TB-related symptoms.
CONCLUSIONS
(Re-)initiation of TNF antagonists and JAK inhibitors may be relatively safe in patients with current or previous TB and the need for further treatment of underlying diseases.
PubMed: 38663653
DOI: 10.1016/j.cmi.2024.04.011 -
Clinical Rheumatology Feb 2024Baricitinib is a selective Janus kinase inhibitor that has recently been approved for treating certain autoimmune disorders. This meta-analysis pooled the conflicting... (Meta-Analysis)
Meta-Analysis Review
Baricitinib is a selective Janus kinase inhibitor that has recently been approved for treating certain autoimmune disorders. This meta-analysis pooled the conflicting results from all published randomized controlled trials (RCTs) about the efficacy and safety of baricitinib in patients with systemic lupus erythematosus (SLE). We systemically searched four electronic databases. RCTs comparing baricitinib versus placebo were included. Our outcomes were pooled as the risk ratio (RR) in the random effects model. Our primary outcome was the proportion of patients who achieved a SLE Responder Index-4 (SRI-4) response. A total of three RCTs, comprising 1849 patients, were included. Baricitinib 4 mg was associated with a significantly higher proportion of patients who attained SRI-4 response at week 24 (RR = 1.19, 95% CI [1.05, 1.35], P < 0.01). However, this did not reach statistical significance with baricitinib 4 mg at week 52 and baricitinib 2 mg at both week 24 and week 52 (RR = 1.13, 95% CI [0.96, 1.34], P = 0.15; RR = 1.09, 95% CI [0.96, 1.24], P = 0.20; RR = 1.05, 95% CI [0.92, 1.19], P = 0.50, respectively). The risk for serious infections was higher in the baricitinib 4 mg group (RR = 2.23, 95% CI [1.13, 4.37], P = 0.02). Baricitinib 2 mg did not show any clinical benefit. In contrast, baricitinib 4 mg might have the potential to reduce SLE disease activity; however, further research is required to evaluate its long-term efficacy. Until higher-quality evidence is developed, the benefits and risks of baricitinib should be considered before initiating its therapy. Key Points • Baricitinib is a selective Janus kinase inhibitor that has recently been approved for treating certain autoimmune disorders; however, its efficacy in patients with systemic lupus erythematosus (SLE) is still inconclusive. • In our meta-analysis, baricitinib 2 mg did not show any clinical benefit. In contrast, baricitinib 4 mg significantly reduced SLE activity in terms of SRI-4 response at week 24. However, this did not reach statistical significance at week 52. • Further studies are required to investigate the long-term efficacy of baricitinib 4 mg in patients with SLE.
Topics: Humans; Janus Kinase Inhibitors; Randomized Controlled Trials as Topic; Lupus Erythematosus, Systemic; Azetidines; Treatment Outcome; Purines; Pyrazoles; Sulfonamides
PubMed: 37581759
DOI: 10.1007/s10067-023-06731-4 -
The Canadian Journal of Hospital... 2024The pathophysiology of COVID-19 involves a signalling pathway based on the Janus kinases (JAKs) and the signal transducer and activator of transcription (STAT) family of... (Review)
Review
BACKGROUND
The pathophysiology of COVID-19 involves a signalling pathway based on the Janus kinases (JAKs) and the signal transducer and activator of transcription (STAT) family of proteins. As such, there has been growing interest in exploring JAK inhibitors as potential therapeutic agents for this disease.
OBJECTIVE
To provide a comprehensive summary of the efficacy of JAK inhibitors in the treatment of COVID-19 through a systematic review and meta-analysis.
DATA SOURCES
A systematic literature search was conducted in multiple electronic databases (PubMed, Scopus, and the Cochrane Central Register of Controlled Trials) and preprint repositories, without language restrictions, to identify relevant studies published up to December 31, 2023.
STUDY SELECTION AND DATA EXTRACTION
The primary outcome of interest was all-cause mortality. Randomized controlled trials (RCTs) investigating the administration of JAK inhibitors in patients with COVID-19 were included.
DATA SYNTHESIS
Through the systematic literature search, a total of 20 RCTs meeting the inclusion criteria were identified. A random-effects model was employed to estimate the pooled odds ratio for death with administration of a JAK inhibitor relative to non-administration of such an agent, with 95% confidence interval. Meta-analysis of these trials revealed a significant reduction in mortality among patients with COVID-19 who received JAK inhibitors relative to those who did not receive these agents (pooled odds ratio 0.70, 95% confidence interval 0.58-0.84).
CONCLUSIONS
The results of this systematic review and meta-analysis suggest that JAK inhibitors, specifically baricitinib, may address the urgent need for effective treatments in the ongoing COVID-19 pandemic by reducing the risk of death among affected patients. However, further research, including larger-scale RCTs, is needed to establish the efficacy and safety of other JAK inhibitors in the treatment of COVID-19 and to generate more robust evidence regarding their use in this specific patient population.
PubMed: 38868321
DOI: 10.4212/cjhp.3493 -
Arthritis & Rheumatology (Hoboken, N.J.) May 2024Anterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Anterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA.
METHODS
We conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti-tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti-interleukin-17 (anti-IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool.
RESULTS
Forty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti-IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0-8.5; etanercept: 5.4, 95% CI 0-16.0; anti-IL-17: 2.8, 95% CI 1.6-4.1; JAKi: 1.5, 95% CI 0.0-3.0; and placebo: 10.8, 95% CI 7.4-14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10-1.04; etanercept 0.42, 95% CI 0.08-2.38; anti-IL-17: 0.43, 95% CI 0.19-0.98; and JAKi: 0.32, 95% CI 0.06-1.67. Comparisons between anti-TNF mAb, anti-IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti-IL-17, and etanercept. All treatments were ranked superior to placebo.
CONCLUSION
Anti-TNF mAbs, JAKi, and anti-IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.
Topics: Humans; Biological Products; Incidence; Antirheumatic Agents; Network Meta-Analysis; Axial Spondyloarthritis; Antibodies, Monoclonal; Interleukin-17; Etanercept; Janus Kinase Inhibitors; Uveitis, Anterior; Tumor Necrosis Factor-alpha; Randomized Controlled Trials as Topic; Uveitis
PubMed: 38116697
DOI: 10.1002/art.42788 -
Journal of the American Academy of... Jul 2024
Meta-Analysis
Elevation of creatine phosphokinase in moderate-to-severe atopic dermatitis is associated with the use of JAK inhibitors but not dupilumab: A systematic review and meta-analysis.
Topics: Humans; Dermatitis, Atopic; Antibodies, Monoclonal, Humanized; Janus Kinase Inhibitors; Severity of Illness Index; Creatine Kinase; Nitriles; Pyrimidines; Piperidines
PubMed: 38554937
DOI: 10.1016/j.jaad.2024.03.027 -
Journal of Cutaneous Medicine and... 2024
Review
Topics: Humans; Psoriasis; Janus Kinase Inhibitors; Piperidines; Pyrimidines
PubMed: 38497281
DOI: 10.1177/12034754241238707 -
Journal of Cutaneous Medicine and... 2024
Meta-Analysis
Topics: Humans; Dermatitis, Atopic; Janus Kinase Inhibitors
PubMed: 37968918
DOI: 10.1177/12034754231211805 -
Mediterranean Journal of Rheumatology Mar 2024The aim of this study was to compare the risk of major cardiovascular events (MACE) and venous thromboembolic events (VTE) between tumour necrosis factor (TNF) and Janus...
Risk of Major Adverse Cardiovascular Events and Venous Thromboembolism with JAK Inhibitors versus TNF Inhibitors in Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis.
OBJECTIVE
The aim of this study was to compare the risk of major cardiovascular events (MACE) and venous thromboembolic events (VTE) between tumour necrosis factor (TNF) and Janus kinase (JAK) inhibitors in patients with rheumatoid arthritis (RA).
METHODS
We researched PubMed, Scopus, Cochrane Library, and clinicaltrials.gov until December of 2023 for randomised controlled trials (RCTs) and observational studies. The outcomes studied were MACE (stroke, heart attack, myocardial infarction, sudden cardiac death) and VTE (deep vein thrombosis, pulmonary embolism). We pooled data using random effects model. Risk for the reported outcomes was expressed as odds ratio (OR) with a 95% confidential interval (CI). We performed a subgroup analysis based on study design.
RESULTS
We identified 23 studies, 20 of which compared the odds for MACE and 14 the odds for VTE between JAK and TNF inhibitors in RA patients. Ten studies were RCTs and the rest were observational. Regarding MACE risk we pooled data from a total of 215,278 patients (52,243 were treated with JAK inhibitors, while the rest 163,035 were under TNF inhibitors). Compared with TNF inhibitors, the OR for JAK inhibitors in regards with MACE risk was 0.87 (0.64-1.17, p<0.01). Regarding VTE, a total of 176,951 patients were analysed (41,375 JAK inhibitors users and 135,576 TNF inhibitors users). The OR for VTE for JAK inhibitors compared with TNF inhibitors was 1.28 (0.89-1.84, p<0.01).
CONCLUSION
According to our results, there is no statistically significant difference for MACE or VTE in RA patients who receive either JAK or TNF inhibitors.
PubMed: 38756933
DOI: 10.31138/mjr.171023.rof