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Frontiers in Pharmacology 2024To systematically compare the efficacy and safety of biologics [tumor necrosis factor inhibitors (TNFi), interleukin (IL) inhibitors, phosphodiesterase-4 inhibitors...
To systematically compare the efficacy and safety of biologics [tumor necrosis factor inhibitors (TNFi), interleukin (IL) inhibitors, phosphodiesterase-4 inhibitors (PDE4i), and Janus kinase inhibitors (JAKi)] for biological-naïve patients with psoriatic arthritis (PsA). PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched until 12 March 2023. Only head-to-head active comparison studies were included, and placebo-controlled studies without active biologic comparators were excluded. Outcomes included musculoskeletal endpoint [American College of Rheumatology (ACR) 20/50/70, resolution of enthesitis, resolution of dactylitis], function endpoint [Health Assessment Questionnaire-Disability Index (HAQ-DI) change, ∆ HAQ-DI ≥ 0.35], composite index endpoint [ACR 50 + Psoriasis Area Severity Index (PASI) 100], and adverse events. The Jadad scale and Newcastle-Ottawa scale (NOS) were adopted to evaluate the quality of eligible studies. Totally 17 studies with head-to-head comparisons of these biologics were included in this systematic review and network meta-analysis. Compared with IL-17A inhibitors (IL-17Ai), TNFi were associated with a lower rate of achieving ACR 20 response [pooled risk ratios (RR) = 0.92, 95% credibility interval (CrI): 0.86, 0.98]. JAKi had the greatest possibility of achieving ACR 20 (50.25%) and ACR 50 (83.03%). The JAKi group had a higher rate of achieving ACR 70 response than the IL-17Ai group (pooled RR = 1.25, 95%CrI: 1.00, 1.57); TNFi were less effective than JAKi in terms of ACR 70 (pooled RR = 0.77, 95%CrI: 0.64, 0.94). ACR 70 was most likely to be achieved in patients using JAKi (97.48%). The IL-17Ai group had a higher rate of enthesitis resolution than the TNFi group [pooled RR = 1.22, 95% confidence interval (CI): 1.02, 1.47]. Compared with IL-17Ai, TNFi were associated with a lower rate of enthesitis resolution (pooled RR = 0.80, 95%CrI: 0.72, 0.88). Patients receiving IL-17Ai had the highest likelihood of achieving enthesitis resolution (82.76%), dactylitis resolution (58.66%) and the greatest HAQ-DI change (59.74%). IL-17Ai had a similar impact in achieving ∆ HAQ-DI ≥ 0.35 to TNFi (pooled RR = 1.15, 95%CI: 0.93, 1.41). Individuals receiving IL-17Ai had a higher rate of achieving combined ACR 50 and PASI 100 response than those receiving TNFi (pooled RR = 1.56, 95%CI: 1.29, 1.88). Patients receiving PDE4i were least likely to have adverse events (41.59%). In 2023, considering both efficacy and safety, IL-17Ai may be the better treatment option for biological-naïve patients with PsA requiring biological therapy.
PubMed: 38545545
DOI: 10.3389/fphar.2024.1279525 -
Annals of Hematology Jun 2024Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between... (Meta-Analysis)
Meta-Analysis
Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between JAK2V617F allele burden (also known as variant allele frequency) and the relevant clinical characteristics. Numerous studies have reported associations between allele burden and both hematologic and clinical features. While there are strong indications linking high allele burden in PV patients with symptoms and clinical characteristics, not all associations are definitive, and disparate and contradictory findings have been reported. Hence, this study aimed to synthesize existing data from the literature to better understand the association between JAK2V617F allele burden and relevant clinical correlates. Out of the 1,851 studies identified, 39 studies provided evidence related to the association between JAK2V617F allele burden and clinical correlates, and 21 studies were included in meta-analyses. Meta-analyses of correlation demonstrated that leucocyte and erythrocyte counts were significantly and positively correlated with JAK2V617F allele burden, whereas platelet count was not. Meta-analyses of standardized mean difference demonstrated that leucocyte and hematocrit were significantly higher in patients with higher JAK2V617F allele burden, whereas platelet count was significantly lower. Meta-analyses of odds ratio demonstrated that patients who had higher JAK2V617F allele burden had a significantly greater odds ratio for developing pruritus, splenomegaly, thrombosis, myelofibrosis, and acute myeloid leukemia. Our study integrates data from approximately 5,462 patients, contributing insights into the association between JAK2V617F allele burden and various hematological parameters, symptomatic manifestations, and complications. However, varied methods of data presentation and statistical analyses prevented the execution of high-quality meta-analyses.
Topics: Polycythemia Vera; Janus Kinase 2; Humans; Alleles; Gene Frequency; Amino Acid Substitution; Mutation, Missense
PubMed: 38652240
DOI: 10.1007/s00277-024-05754-4 -
Indian Journal of Dermatology,... Jun 2024Background Janus kinase (JAK)/tyrosine kinase 2 (TYK2) inhibitors are novel treatments for moderate-to-severe plaque psoriasis. Objective To perform a network... (Review)
Review
Background Janus kinase (JAK)/tyrosine kinase 2 (TYK2) inhibitors are novel treatments for moderate-to-severe plaque psoriasis. Objective To perform a network meta-analysis to compare the efficacy and safety of TYK2 inhibitors with other oral drugs in moderate-to-severe psoriasis. Methods Eligible randomised clinical trials (RCTs) were identified from public databases (published before November 2, 2023). Random-effect frequentist network meta-analysis was performed with ranking based on the surface under the cumulative ranking curve (SUCRA) of Physician's Global Assessment of "clear" or "almost clear" (PGA 0/1), 75% reduction from baseline in Psoriasis Area and Severity Index (PASI-75). Results Twenty RCTs containing 7,564 patients with moderate-to-severe psoriasis were included. Deucravacitinib at all dose levels (except for 3 mg every other day) and tofacitinib (10 mg BID) ranked best in achieving PGA 0/1 and PASI-75 at 12- 16 weeks. Tofacitinib (10 mg BID) was considered the most unsafe. Analysis of Ranking according to efficacy and safety showed deucravacitinib (3 mg QD and 3 mg BID) was the best treatment. Analysis of Ranking according to efficacy and safety showed deucravacitinib (3 mg QD and 3 mg BID) was the best treatment. Limitations Insufficiency of eligible data and no long-term follow-up data. Conclusion Deucravacitinib showed superior efficacy and safety for treating moderate-to-severe psoriasis over other included drugs.
PubMed: 38899421
DOI: 10.25259/IJDVL_775_2023 -
Journal of Crohn's & Colitis Jun 2024Extraintestinal manifestations are frequent in patients with inflammatory bowel disease and have a negative impact on quality of life. Currently, however, there is no... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Extraintestinal manifestations are frequent in patients with inflammatory bowel disease and have a negative impact on quality of life. Currently, however, there is no evidence available to determine which drug should be recommended for these patients beyond anti-tumour necrosis factor [anti-TNF] treatment. We aimed to analyse the frequency of new extraintestinal manifestations and the behaviour of pre-existing extraintestinal manifestations during advanced therapy.
METHODS
We conducted a systematic search on November 15, 2022, and enrolled randomized controlled trials, cohorts, and case series reporting the occurrence and behaviour of extraintestinal manifestations in patients with inflammatory bowel disease receiving advanced therapy [non-TNF inhibitor biologicals and JAK inhibitors]. Proportions of new, recurring, worsening, and improving extraintestinal manifestations were calculated with 95% confidence intervals [CIs]. The risk of bias was assessed with the QUIPS tool.
RESULTS
Altogether, 61 studies comprising 13,806 patients reported eligible data on extraintestinal manifestations. The overall proportion of new extraintestinal manifestations was 8% [95% CI, 6-12%] during advanced therapy. There was no significant difference between the frequency of new extraintestinal manifestations during vedolizumab and ustekinumab therapy [11%, 95% CI, 8-15% vs 6%, 95% CI, 3-11%, p = 0.166]. The improvement of pre-existing manifestations was comparable between vedolizumab- and ustekinumab-treated patients, except for joint involvement [42%, 95% CI, 32-53% vs 54%, 95% CI, 42-65%, p = 0.029].
CONCLUSION
The proportion of new extraintestinal manifestations was low during advanced therapy. Furthermore, the improvement of pre-existing manifestations was comparable between advanced therapies, except for pre-existing joint manifestations.
Topics: Humans; Inflammatory Bowel Diseases; Antibodies, Monoclonal, Humanized; Janus Kinase Inhibitors; Ustekinumab; Gastrointestinal Agents; Biological Products; Skin Diseases
PubMed: 38189533
DOI: 10.1093/ecco-jcc/jjae002 -
PloS One 2024Cicatricial alopecia (CA) refers to various conditions that result in permanent hair loss. Treatment of CA has always been challenging. Regarding immune-mediated...
BACKGROUND
Cicatricial alopecia (CA) refers to various conditions that result in permanent hair loss. Treatment of CA has always been challenging. Regarding immune-mediated pathophysiology for many CA subtypes, the administration of Janus kinase (JAK) and tumor necrosis factor (TNF) inhibitors have potentiated the treatments of CA.
METHODS
After a thorough systematic search in PubMed/Medline, Embase, Web of Science, Scopus, Google Scholar, ClinicalTrials.gov, and WHO ICTRP, a total of 3,532 relevant records were retrieved and screened. Accordingly, 56 studies met the eligibility criteria and entered the review.
RESULTS
Among JAK inhibitors, oral tofacitinib was the most frequently reported and the most effective treatment in improving signs and symptoms of CA with minimal adverse effects (AEs). Baricitinib was another JAK inhibitor with sustained improvement while causing mild AEs. As a TNF inhibitor, adalimumab induced a rapid and stable improvement in signs and symptoms in most patients with rare, tolerable AEs. Thalidomide was the other frequently reported yet controversial TNF inhibitor, which caused a rapid and significant improvement in the condition. However, it may result in mild to severe AEs, particularly neuropathies. Infliximab is a TNF inhibitor with mostly favorable results, albeit in a few patients caused treatable dermatological AEs. Apremilast and certolizumab pegol caused an incomplete amelioration of signs and symptoms with no AEs. Lenalidomide is another TNF inhibitor that can induce temporary improvement in CA with probable AEs. It is noteworthy that utilizing adalimumab, infliximab, etanercept, golimumab, and an anonymous TNF inhibitor has induced paradoxical CA and other A.E.s in some patients.
CONCLUSION
Recent studies have recommended JAK and TNF inhibitors, especially oral tofacitinib and adalimumab, as a new modality or adjuvant therapy to previous medications for primary CA. Nonetheless, monitoring AEs on a regular basis is suggested, and further extensive studies are required before definitive recommendations.
Topics: Humans; Adalimumab; Janus Kinase Inhibitors; Tumor Necrosis Factor Inhibitors; Infliximab; Antibodies, Monoclonal, Humanized; Alopecia; Tumor Necrosis Factor-alpha
PubMed: 38335182
DOI: 10.1371/journal.pone.0293433 -
Journal of Orthopaedic Surgery and... Mar 2024Many KOA patients have not reached indications for surgery, thus we need to find effective non-surgical treatments. Acupuncture is thought to have the potential to... (Meta-Analysis)
Meta-Analysis
Efficacy and immune-inflammatory mechanism of acupuncture-related therapy in animal models of knee osteoarthritis: a preclinical systematic review and network meta-analysis.
BACKGROUND
Many KOA patients have not reached indications for surgery, thus we need to find effective non-surgical treatments. Acupuncture is thought to have the potential to modulate inflammation and cytokines in KOA through the immune system. However, the mechanisms have not been elucidated, and there is no network Meta-analysis of acupuncture on KOA animals. So we evaluate the effect and mechanism of acupuncture-related therapy in KOA animals.
METHODS
A comprehensive search was conducted in multiple databases including PubMed, Web of Science, Embase, CBM, CNKI, WanFang, and VIP Database to identify relevant animal studies focusing on acupuncture therapy for KOA. The included studies were assessed for risk of bias using SYRCLE's Risk of Bias tool. Subsequently, pair-wise meta-analysis and network meta-analysis were performed using Stata 15.0 software, evaluating outcomes such as Lequesne index scale, Mankin score, IL-1β, TNF-α, MMP3, and MMP13.
RESULTS
56 RCTs with 2394 animals were included. Meta-analysis showed that among the 6 outcomes, there were significant differences between acupuncture and model group; the overall results of network meta-analysis showed that the normal group or sham operation group performed the best, followed by the acupotomy, acupuncture, and medicine group, and the model group had the worst effect, and there were significant differences between 6 interventions.
CONCLUSIONS
Acupuncture-related therapy can be a possible treatment for KOA. The mechanism involves many immune-inflammatory pathways, which may be mediated by DAMPs/TLR/NF-κB/MAPK,PI3K/Akt/NF-κB pathway, or IFN-γ/JAK-STAT pathway. It needs to be further confirmed by more high-quality animal experiments or meta-analysis.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO identifier: CRD42023377228.
Topics: Animals; Humans; Osteoarthritis, Knee; Network Meta-Analysis; Janus Kinases; NF-kappa B; Phosphatidylinositol 3-Kinases; STAT Transcription Factors; Signal Transduction; Acupuncture Therapy; Models, Animal
PubMed: 38459553
DOI: 10.1186/s13018-024-04660-9 -
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 -
Biomedical Reports May 2024Abrocitinib is a highly selective Janus kinase 1 (JAK1) inhibitor that can block a multitude of inflammatory signaling pathways that underlie atopic dermatitis (AD). In...
Effects of abrocitinib on pruritus and eczema symptoms and tolerance in patients with moderate‑to‑severe atopic dermatitis in randomized, double‑blind and placebo‑controlled trials: A systematic review and a meta‑analysis.
Abrocitinib is a highly selective Janus kinase 1 (JAK1) inhibitor that can block a multitude of inflammatory signaling pathways that underlie atopic dermatitis (AD). In addition, abrocitinib inhibits JAK1 signaling in sensory neurons to alleviate acute and chronic pruritus during AD. However, substantial variations in efficacy and safety risks remain due to variations in doses applied in clinical use. Therefore for the present study, differences in the efficacy and tolerability of 100 and 200 mg abrocitinib for treating pruritus and eczema symptoms in patients with moderate-to-severe AD were evaluated compared with placebo. Specifically, randomized controlled trials (RCTs) of abrocitinib compared with placebo for the treatment of moderate-to-severe AD were searched on Pubmed, E.B. Stephens Company, China National Knowledge Infrastructure, Wanfang Medical network, Web of Science and related Clinical Trials Registry up to November 2023. In total, two researchers evaluated the quality of the included literature according to the Cochrane Handbook of Systematic Reviews. RevMan 5.3 software was used to conduct a meta-analysis of the efficacy and safety indicators in a cross-comparison of the effects exerted by placebo and 100 and 200 mg abrocitinib. A total of 1,825 patients with moderate-to-severe AD were included across five double-blind, placebo RCTs. Compared with the placebo group, during the double-blind trial period, significant improvements were observed in the investigator's global assessment score, response rate of eczema area and severity index (EASI)-50, EASI-75, EASI-90 and pruritus numerical rating scale (P-NRS) in the 100 and 200 mg abrocitinib groups (P<0.05). However, pairwise control analysis of the 100 and 200 mg group yielded significant differences (P<0.05) in all of the aforementioned therapeutic indicators except for the P-NRS score. In terms of safety, compared with the placebo group, there were significantly higher incidence of nausea, upper respiratory tract viral infection, infections and infestations in the 100 mg abrocitinib group (P<0.05). In addition, there were significantly higher incidence of nausea, gastrointestinal disorder, headache and dizziness in the 200 mg group (P<0.05). There were also significant differences in the incidence of nausea, gastrointestinal disorder and dizziness between the 100 and 200 mg groups (P<0.05). For patients with moderate-to-severe AD, oral administration of 100 or 200 mg abrocitinib once/day was concluded to ameliorate skin pruritus and eczema symptoms to varying degrees, with the efficacy significantly superior at the 200 mg dose. However, the risk of a number of adverse reactions, such as headache, dizziness, nausea and gastrointestinal dysfunction, is also significantly increased. Therefore, patients should be made aware of the risk of adverse drug effects prior to the administration of long-term high abrocitinib doses. Furthermore, large-scale, multi-center, rigorous clinical trials remain necessary to validate the findings from the present study.
PubMed: 38628626
DOI: 10.3892/br.2024.1772 -
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 -
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