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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 -
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 -
Clinical Gastroenterology and... Mar 2024There are limited data on the safety of immunosuppressive therapy use in individuals with immune-mediated diseases with a history of malignancy, particularly with newer... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
There are limited data on the safety of immunosuppressive therapy use in individuals with immune-mediated diseases with a history of malignancy, particularly with newer biologic and small-molecule treatments.
METHODS
We performed a systematic search of PubMed and Embase databases to identify studies examining the impact of immunosuppressive therapies on cancer recurrence across several immune-mediated diseases. Studies were pooled together using random-effects meta-analysis and stratified by type of treatment. Primary outcome was occurrence of incident cancers, defined as new or recurrent.
RESULTS
Our meta-analysis included 31 studies (17 inflammatory bowel disease, 14 rheumatoid arthritis, 2 psoriasis, and 1 ankylosing spondylitis) contributing 24,328 persons and 85,784 person-years (p-y) of follow-up evaluation. Rates of cancer recurrence were similar among individuals not on immunosuppression (IS) (1627 incident cancers, 43,765 p-y; 35 per 1000 p-y; 95% CI, 27-43), receiving an anti-tumor necrosis factor (571 incident cancers, 17,772 p-y; 32 per 1000 p-y; 95% CI, 25-38), immunomodulators (1104 incident cancers, 17,018 p-y; 46 per 1000 p-y; 95% CI, 31-61), combination immunosuppression (179 incident cancers, 2659 p-y; 56 per 1000 p-y; 95% CI, 31-81). Patients receiving ustekinumab (5 incident cancers, 213 p-y; 21 per 1000 p-y; 95% CI, 0-44) and vedolizumab (37 incident cancers, 1951 p-y; 16 per 1000 p-y; 95% CI, 5-26) had numerically lower rates of cancer. There were no studies on Janus kinase inhibitors. Stratification of studies by timing of immunosuppression initiation did not reveal a medication effect based on early (<5 years) or delayed treatment initiation.
CONCLUSIONS
In patients with immune-mediated diseases and a history of malignancy, we observed similar rates of cancer recurrence in those on no immunosuppression compared with different immunosuppressive treatments.
Topics: Humans; Immunosuppressive Agents; Immunosuppression Therapy; Immunologic Factors; Ustekinumab; Recurrence; Neoplasms; Inflammatory Bowel Diseases
PubMed: 37579866
DOI: 10.1016/j.cgh.2023.07.027 -
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 -
Journal of Drugs in Dermatology : JDD Feb 2024There is contrasting evidence regarding the efficacy and safety of JAK (Janus kinase) inhibitors in the treatment of psoriasis. This systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
There is contrasting evidence regarding the efficacy and safety of JAK (Janus kinase) inhibitors in the treatment of psoriasis. This systematic review and meta-analysis assessed deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, as the therapy of choice for moderate-to-severe psoriasis. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials, including patients with moderate-to-severe psoriasis. Outcomes of interest were serious adverse events (SAEs), the severity of illness, as measured by the validated questionnaires: Psoriasis Area and Severity Index (PASI) and scalp-specific Physician's Global Assessment (ss-PGA); and quality of life, measured by the Dermatology Life Quality Index (DLQI). Four studies with 1663 patients were included in the meta-analysis, of whom 1123 (67.5%) were treated with deucravacitinib during a 12-to-16-week follow-up. The mean age was 45.4 ± 13.3 years, and 70.2% were male. Two-thirds had a history of scalp psoriasis. Achievement of PASI 75 was significantly higher in the deucravacitinib group, as compared with placebo (RR 5.7; 95% CI 4.32-7.53; P<0.001). Similarly, ss-PGA 0/1 (RR 3.86; 95%CI 3.02-4.94; P<0.001) and DLQI 0/1 (RR 3.89; 2.89-5.22; P<0.001) were also significantly more frequent in the deucravacitinib group. The incidence of SAEs was similar between groups. These findings suggest that patients with moderate-to-severe psoriasis treated with deucravacitinib for 12 to 16 weeks had significantly decreased severity of illness and improved quality of life, without a concerning increase in the incidence of SAEs. J Drugs Dermatol. 2024;23(2):67-73. doi:10.36849/JDD.7539.
Topics: Humans; Heterocyclic Compounds; Psoriasis; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 38306122
DOI: 10.36849/JDD.7539 -
Journal of Cutaneous Medicine and... Jun 2024
PubMed: 38859662
DOI: 10.1177/12034754241260021 -
PloS One 2024This study aims to evaluate the efficacy and safety of JAK inhibitors in the treatment of patients with RA. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aims to evaluate the efficacy and safety of JAK inhibitors in the treatment of patients with RA.
METHODS
The databases CNKI, VIP, Wanfang, CBM, and PubMed, Embase, Cochrane Library and Web of Science were searched to identify relevant randomized controlled trials (RCTs), all from the time of database creation to April 2024. Screening, data extraction, and risk of bias assessment (using Review Manager-5.3 software) were independently performed by at least two authors. The network meta-analysis was conducted using R 4.1.3 software. PROSPERO registration number: CRD42022370444.
RESULTS
Thirty-three RCTs included 15,961 patients The experimental groups involved six JAK inhibitors (filgotinib, tofacitinib, decernotinib, baricitinib, upadacitinib and peficitinib) and 12 interventions (different doses of the six JAK inhibitors), and the control group involved adalimumab (ADA) and placebo. Compared with placebo, all JAK inhibitors showed a significant increase in efficacy measures (ACR20/50/70). Compared with ADA, only tofacitinib, low-dose decernotinib, and high-dose peficitinib showed a significant increase in ACR20/50/70. Decernotinib ranked first in the SUCRA ranking of ACR20/50/70. In terms of safety indicators, only those differences between low-dose filgotinib and high-dose upadacitinib, low-dose tofacitinib and high-dose upadacitinib were statistically significant. Low-dose filgotinib ranked first in the SUCRA ranking with adverse events as safety indicators. Only the efficacy and safety of tofacitinib ranked higher among different SUCRA rankings.
CONCLUSION
Six JAK inhibitors have better efficacy than placebo. The superior efficacy of decernotinib and safety of low-dose filgotinib can be found in the SUCRA. However, there are no significant differences in safety between the different JAK inhibitors. Head-to-head trials, directly comparing one against each other, are required to provide more certain evidence.
Topics: Humans; Arthritis, Rheumatoid; Janus Kinase Inhibitors; Bayes Theorem; Pyrimidines; Piperidines; Network Meta-Analysis; Azetidines; Purines; Pyrroles; Pyrazoles; Sulfonamides; Randomized Controlled Trials as Topic; Treatment Outcome; Heterocyclic Compounds, 2-Ring; Niacinamide; Benzamides; Heterocyclic Compounds, 3-Ring; Antirheumatic Agents; Triazoles; Adamantane; Pyridines; Valine
PubMed: 38905267
DOI: 10.1371/journal.pone.0305621 -
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