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Rheumatology and Therapy Jun 2021Peficitinib, a Janus kinase (JAK) inhibitor, is approved for clinical use in Japan, Korea, and Taiwan, but head-to-head comparisons versus other JAK inhibitors are...
INTRODUCTION
Peficitinib, a Janus kinase (JAK) inhibitor, is approved for clinical use in Japan, Korea, and Taiwan, but head-to-head comparisons versus other JAK inhibitors are lacking. We indirectly compared peficitinib, tofacitinib, and baricitinib for rheumatoid arthritis treatment.
METHODS
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and congress archives up until February 12, 2019, for randomized controlled trials of peficitinib, tofacitinib, and baricitinib. Efficacy (American College of Rheumatology responses, disease activity scores, modified total Sharp score, Simplified Disease Activity Index [SDAI]) and safety outcomes were compared using a Bayesian network meta-analysis. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results. A network meta-regression assessed the impact on outcomes of proportions of patients receiving concomitant methotrexate or of Asian ethnicity.
RESULTS
The network meta-analysis included 21 randomized controlled trials. At 12 weeks, all evaluable efficacy outcomes were comparable or improved with peficitinib 150 mg and 100 mg once daily, versus baricitinib 2 and 4 mg once daily and tofacitinib 5 mg twice daily. At 24 weeks, efficacy outcomes were comparable or improved for each peficitinib dose versus baricitinib and tofacitinib. Risk of adverse events and serious adverse events at 12 weeks were similar with peficitinib 100 and 150 mg versus baricitinib and tofacitinib. The proportion of patients receiving concomitant methotrexate had no effect on any outcome analyzed, but Asian ethnicity had a positive effect on multiple efficacy outcomes.
CONCLUSIONS
Peficitinib had comparable efficacy versus tofacitinib and baricitinib for reduction in disease activity as measured by SDAI, and for reduction in progression of joint damage as measured radiographically. No notable differences in safety outcomes were observed. Further studies are required to better characterize the impact of ethnicity on the efficacy of JAK inhibitors.
PubMed: 33725321
DOI: 10.1007/s40744-021-00284-1 -
Frontiers in Immunology 2024We performed a single-arm meta-analysis to evaluate the efficacy and safety of JAK inhibitors in the treatment of dermatomyositis (DM)/ polymyositis (PM). (Meta-Analysis)
Meta-Analysis
INTRODUCTION
We performed a single-arm meta-analysis to evaluate the efficacy and safety of JAK inhibitors in the treatment of dermatomyositis (DM)/ polymyositis (PM).
METHODS
Relevant studies from four databases were systematically searched until April 25, 2023. The primary endpoint was Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and other outcomes were Manual Muscle Testing (MMT) and Creatine Kinase (CK). According to the type of JAK and medication regimen, we conducted subgroup analyses. The registration number in PROSPERO was CRD42023416493.
RESULTS
According to the selection criteria, we identified 7 publications with a total of 91 patients. Regarding skin lesions, the CDASI decreased by 17.67 (95% CI: -20.94 ~ -14.41). The CK increased by 8.64 U (95% CI: -28.25 ~ 45.53). About muscle lesions, MMT increased by 10.31 (95% CI: -2.83 ~ 23.46). Subgroup analysis revealed that different types of JAK inhibitors had various degrees of reduction. CDASI in patients treated with RUX had the lowest one [-20.00 (95% CI: -34.9 ~ -5.1)], followed by TOF [-18.29 (95% CI: -21.8 ~ -14.78)] and BAR [-11.2 (95% CI: -21.51 ~ -0.89)]. Additionally, the mean reduction in CDASI in patients treated with TOF alone was 16.16 (95% CI: -21.21 ~ -11.11), in combination with other immunosuppressants was 18.59 (95% CI: -22.74 ~ -14.45). For safety evaluation, one patient developed Orolabial HSV, and two patients developed thromboembolism events.
DISCUSSION
In summary, this meta-analysis demonstrated that JAK inhibitors can potentially treat DM/PM without severe adverse reactions.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42023416493, identifier CRD42023416493.
Topics: Humans; Dermatomyositis; Immunosuppressive Agents; Janus Kinase Inhibitors; Polymyositis; Skin
PubMed: 38576610
DOI: 10.3389/fimmu.2024.1382728 -
Therapeutic Advances in Musculoskeletal... 2021To evaluate the comparative efficacy and safety of Janus kinase (JAK) inhibitors and biological disease-modifying antirheumatic drugs (bDMARDs) in patients with...
Comparative efficacy and safety of Janus kinase inhibitors and biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and network meta-analysis.
OBJECTIVE
To evaluate the comparative efficacy and safety of Janus kinase (JAK) inhibitors and biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and an inadequate response to at least one disease-modifying antirheumatic drug (DMARD).
METHODS
PubMed, Embase, Cochrane library and ClinicalTrials.gov were searched for relevant randomized controlled trials (RCTs) from inception to April 2020. The active drugs included three JAK inhibitors and eight bDMARDs while the control drugs included placebo or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Outcomes include American College of Rheumatology 20% response (ACR20), Disease Activity Score in 28 joints (DAS28), Health Assessment Questionnaire-Disability Index (HAQ-DI) and discontinuations for adverse events (AEs). We estimated summary odds ratios (ORs) and weighted mean differences (WMDs) using network meta-analysis with random effects.
RESULTS
Eighty-eight RCTs with 31,566 patients were included. All JAK inhibitors and bDMARDs were more effective than placebo in ACR20 (ORs ranging between 3.05 and 5.61), DAS28 (WMDs ranging between -1.91 and -0.80) and HAQ-DI (WMDs ranging between -0.34 and -0.21). Tocilizumab, certolizumab pegol and upadacitinib showed relatively good efficacy in these three outcomes according to their relative ranking. Notably, tocilizumab was more effective than other active drugs in DAS28 (WMDs ranging between -1.11 and -0.49). Compared with the lower recommended doses, increasing the doses of JAK inhibitors (baricitinib 4 mg 2 mg, tofacitinib 10 mg 5 mg and upadacitinib 30 mg 15 mg) cannot provide significant additional benefits. In terms of discontinuations for AEs, all active drugs showed no significant difference compared with placebo except certolizumab pegol [OR 1.65, 95% credible interval (CrI) 1.06-2.61] and rituximab (3.17, 1.11-10.80).
CONCLUSIONS
Tocilizumab, certolizumab pegol and upadacitinib may have relatively good efficacy in patients with RA after treatment failure with csDMARDs. RA patients taking a JAK inhibitor may have a preference for a lower recommended dose.
PubMed: 33815570
DOI: 10.1177/1759720X21999564 -
Dermatology Research and Practice 2021Atopic dermatitis (AD) is a complex, chronic, inflammatory skin disease characterized by pruritic, intense itching, and eczematous lesions affecting about 25% of... (Review)
Review
BACKGROUND
Atopic dermatitis (AD) is a complex, chronic, inflammatory skin disease characterized by pruritic, intense itching, and eczematous lesions affecting about 25% of children and 2% to 3% of adults worldwide. Abrocitinib is a selective inhibitor of Janus kinase-1 (JAK1) enzyme inhibiting the inflammatory process. Therefore, we aimed to assess the efficacy and safety of abrocitinib for moderate-to-severe AD.
METHODS
We systematically searched PubMed, Cochrane, Web of Science, Scopus, and EczemATrials till Feb 1, 2021, for reliable trials. The analysis was conducted using an inverse-variance method. The results were pooled as mean difference/event rate and 95% confidence interval.
RESULTS
Abrocitinib 100 mg and 200 mg were associated with higher IGA response, EASI-50% responders, EASI-75% responders, EASI-90% responders, number of participants with at least 4-point improvements in NRS, and quality of life measured by DLQI and CDLQI than placebo. Also, 100 mg and 200 mg were associated with lower SCORAD index, %BSA, PSAAD index, and POEM index than placebo. Abrocitinib 100 mg and 200 mg were not associated with adverse events such as upper respiratory tract infection, nasopharyngitis, dermatitis, atopic, any serious adverse events, and death.
CONCLUSION
Abrocitinib in dose 100 mg or 200 mg is an effective, well-tolerated, and promising drug in treating patients with moderate-to-severe atopic dermatitis. However, the analysis favored the efficacy of abrocitinib 200 mg over 100 mg, but side effects such as nausea and headache are likely to occur more with 200 mg.
PubMed: 34257642
DOI: 10.1155/2021/8382761 -
Frontiers in Pharmacology 2022The treatment of rheumatoid arthritis (RA), a chronic systemic inflammatory autoimmune disease, is based on disease-modifying anti-rheumatic drugs (DMARDs). Typically,...
The treatment of rheumatoid arthritis (RA), a chronic systemic inflammatory autoimmune disease, is based on disease-modifying anti-rheumatic drugs (DMARDs). Typically, it starts with conventional synthetic DMARDs (csDMARDs), and depending on the patient's response to the treatment and the adverse events experienced, biological DMARDs (bDMARDs) are initiated. bDMARDs are more specific to inflammatory factors than csDMARDs and more efficient in inducing remission and low disease activity. Thus, this study aimed to assess the effectiveness of biological therapy in patients with rheumatoid arthritis in administrative health databases. PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science databases were searched from inception to 21 October 2021, to identify observational studies that evaluated the effectiveness of biological therapy in patients with rheumatoid arthritis using administrative databases and real-world data. The methodological quality was assessed by the methodological index for non-randomized studies (MINORS). A fixed or random-effects model estimated risk ratios with 95% confidence intervals. The analysis was divided into four groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus TNFi (adalimumab, etanercept, and golimumab versus infliximab); bDMARDs versus Janus kinase inhibitors (JAKi); and bDMARDs monotherapy versus combination therapy (bDMARDs and MTX). Twenty-one records were eligible for inclusion in this systematic review and meta-analysis; seven population-based cohorts, eight prospective, and six retrospective cohort studies. Overall, 182,098 rheumatoid arthritis patients were evaluated. In the meta-analysis, lower effectiveness was observed among TNFi users than in non-TNFi (RR: 0.88; 95% CI: 0.81-0.95; < 0.01; I = 94.0%) and bDMARDs than in JAKi (RR: 0.86; 95% CI: 0.79-0.94; < 0.01; I = 93.0%). Higher effectiveness among adalimumab, etanercept, and golimumab than in infliximab (RR: 1.19; 95% CI: 1.05-1.36; < 0.01; I = 96.0%) was found. No significant differences in the effectiveness of bDMARD monotherapy compared to combination therapy (RR: 0.83; 95% CI: 0.68-1.00; < 0.01; I = 81.0%) was observed. E-value analysis indicated that the estimates were not robust against unmeasured confounding. According to the available real-world data, our results suggest that biological therapy effectively treats patients with rheumatoid arthritis, indicating higher effectiveness with non-TNFi and JAKi than with TNFi. https://www.crd.york.ac.uk/prospero/display_record.php?ID#CRD42020190838, identifier CRD42020190838.
PubMed: 36034836
DOI: 10.3389/fphar.2022.927179 -
International Journal of Molecular... Jan 2022Pain, fatigue, and physical activity are major determinants of life quality in rheumatoid arthritis (RA). Janus kinase (JAK) inhibitors have emerged as effective... (Meta-Analysis)
Meta-Analysis
Pain, fatigue, and physical activity are major determinants of life quality in rheumatoid arthritis (RA). Janus kinase (JAK) inhibitors have emerged as effective medications in RA and have been reported to exert direct analgesic effect in addition to reducing joint inflammation. This analysis aims to give an extensive summary of JAK inhibitors especially focusing on pain and patient reported outcomes (PRO). MEDLINE, CENTRAL, Embase, Scopus, and Web of Science databases were searched on the 26 October 2020, and 50 randomized controlled trials including 24,135 adult patients with active RA met the inclusion criteria. JAK inhibitors yielded significantly better results in all 36 outcomes compared to placebo. JAK monotherapy proved to be more effective than methotrexate in 9 out of 11 efficacy outcomes. In comparison to biological disease-modifying antirheumatic drugs, JAK inhibitors show statistical superiority in 13 of the 19 efficacy outcomes. Analgesic effect determined using the visual analogue scale and American College of Rheumatology (ACR) 20/50/70 response rates was significantly greater in the JAK group in all comparisons, and no significant difference regarding safety could be explored. This meta-analysis gives a comprehensive overview of JAK inhibitors and provides evidence for their superiority in improving PROs and disease activity indices in RA.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Databases, Factual; Humans; Janus Kinase Inhibitors; Janus Kinases; Methotrexate; Pain; Pain Management; Patient Reported Outcome Measures; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35163173
DOI: 10.3390/ijms23031246 -
Ecancermedicalscience 2020Cancer and transplant patients with COVID-19 have a higher risk of developing severe and even fatal respiratory diseases, especially as they may be treated with... (Review)
Review
BACKGROUND
Cancer and transplant patients with COVID-19 have a higher risk of developing severe and even fatal respiratory diseases, especially as they may be treated with immune-suppressive or immune-stimulating drugs. This review focuses on the effects of these drugs on host immunity against COVID-19.
METHODS
Using Ovid MEDLINE, we reviewed current evidence for immune-suppressing or -stimulating drugs: cytotoxic chemotherapy, low-dose steroids, tumour necrosis factorα (TNFα) blockers, interlukin-6 (IL-6) blockade, Janus kinase (JAK) inhibitors, IL-1 blockade, mycophenolate, tacrolimus, anti-CD20 and CTLA4-Ig.
RESULTS
89 studies were included. Cytotoxic chemotherapy has been shown to be a specific inhibitor for severe acute respiratory syndrome coronavirus in in vitro studies, but no specific studies exist as of yet for COVID-19. No conclusive evidence for or against the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of COVID-19 patients is available, nor is there evidence indicating that TNFα blockade is harmful to patients in the context of COVID-19. COVID-19 has been observed to induce a pro-inflammatory cytokine generation and secretion of cytokines, such as IL-6, but there is no evidence of the beneficial impact of IL-6 inhibitors on the modulation of COVID-19. Although there are potential targets in the JAK-STAT pathway that can be manipulated in treatment for coronaviruses and it is evident that IL-1 is elevated in patients with a coronavirus, there is currently no evidence for a role of these drugs in treatment of COVID-19.
CONCLUSION
The COVID-19 pandemic has led to challenging decision-making about treatment of critically unwell patients. Low-dose prednisolone and tacrolimus may have beneficial impacts on COVID-19. The mycophenolate mofetil picture is less clear, with conflicting data from pre-clinical studies. There is no definitive evidence that specific cytotoxic drugs, low-dose methotrexate for auto-immune disease, NSAIDs, JAK kinase inhibitors or anti-TNFα agents are contraindicated. There is clear evidence that IL-6 peak levels are associated with severity of pulmonary complications.
PubMed: 32256705
DOI: 10.3332/ecancer.2020.1022 -
Journal of Ethnopharmacology Jan 2023Plant essential oils (PEOs) extracted from aromatic compounds of the plant contain complex mixtures of volatile and lipophilic bioactive compounds. In ancient Egypt,... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Plant essential oils (PEOs) extracted from aromatic compounds of the plant contain complex mixtures of volatile and lipophilic bioactive compounds. In ancient Egypt, Arabia, Greece, and China, PEOs were traditional used in aromatherapy for various health disorders, including pain and inflammation.
AIM OF THE STUDY
In this review, we provide an overview of the anti-inflammatory effects of PEOs and the underlying mechanisms associated with anti-inflammatory effects using in vitro and in vivo models. Further, clinical trials associated with PEOs were explored.
MATERIALS AND METHODS
The literature search was performed using various web-based tools and databases like Google Scholar, Web of Science, PubMed, CNKI and SCOPUS. The keywords used for conducting the literature review were general terms like "essential oils" followed by (AND) the subject of interest like "in vitro and/or in vivo anti-inflammatory models," "inflammatory response," "inflammatory indicators," "pro-inflammatory cytokines," "signaling pathway," "anti-inflammatory mechanism," "toxicology and side effects" and "clinical trials." The articles selected were published between 2017 and 2022. The articles prior to 2017 were only considered if they were associated with molecular mechanisms or signaling pathways involved in the inflammatory responses.
RESULTS
In vitro and in vivo inflammation models have been used to study the anti-inflammatory effects of 48 PEOs. Studies have reported that PEOs targets and inhibit multiple dysregulated signaling pathways associated with inflammation, including Toll-like receptors, nuclear transcription factor-κ B, mitogen-activated protein kinases, Nod-like receptor family pyrin domain containing 3, and auxiliary pathways like the nuclear factor erythroid 2-related factor 2/antioxidant response element and Janus kinase/signal transducers and activators of transcription) signaling pathways.
CONCLUSION
PEOs extracted from different plant materials had varied qualitative and quantitative compositions of biologically active compounds. Different anti-inflammatory potentials and different molecular signal transduction have been attributed to PEOs-derived bioactive compounds with different chemical structures. The data on therapeutic efficacy and the long-term side effects of PEOs as an anti-inflammatory drug are still unknown due to the lack of clinical trials on PEOs. There is still insufficient evidence to draw conclusions on anti-inflammatory properties of PEOs without promising outcomes from clinical trials.
Topics: Humans; Oils, Volatile; Plant Oils; Anti-Inflammatory Agents; Cytokines; Inflammation; NF-kappa B; Plant Extracts
PubMed: 36252876
DOI: 10.1016/j.jep.2022.115829 -
Frontiers in Medicine 2022JAK (Janus kinases) inhibitors have been proposed as a promising treatment option for the coronavirus disease-2019 (COVID-19). However, the benefits of JAK inhibitors...
BACKGROUND
JAK (Janus kinases) inhibitors have been proposed as a promising treatment option for the coronavirus disease-2019 (COVID-19). However, the benefits of JAK inhibitors and the optimum thereof for COVID-19 have not been adequately defined.
METHODS
Databases were searched from their inception dates to 17 June 2022. Eligible studies included randomized controlled trials and observational studies. Extracted data were analyzed by pairwise and network meta-analysis. The primary outcome was the coefficient of mortality.
RESULTS
Twenty-eight studies of 8,206 patients were included and assessed qualitatively (modified Jadad and Newcastle-Ottawa Scale scores). A pairwise meta-analysis revealed that JAK inhibitors effectively reduced the mortality (OR = 0.54; 95% CI: 0.46-0.63; < 0.00001; = 32%) without increasing the risk of adverse events (OR = 1.02; 95% CI: 0.88-1.18; = 0.79; = 12%). In a network meta-analysis, clinical efficacy benefits were seen among different types of JAK inhibitors (baricitinib, ruxolitinib, and tofacitinib) without the observation of a declined incidence of adverse events. The assessment of rank probabilities indicated that ruxolitinib presented the greatest likelihood of benefits regarding mortality and adverse events.
CONCLUSION
JAK inhibitors appear to be a promising treatment for COVID-19 concerning reducing mortality, and they do not increase the risk of adverse events vs. standard of care. A network meta-analysis suggests that mortality benefits are associated with specific JAK inhibitors, and among these, ruxolitinib presents the greatest likelihood of having benefits for mortality and adverse events.
SYSTEMATIC REVIEW REGISTRATION
[www.crd.york.ac.uk/prospero], identifier [CRD42022343338].
PubMed: 36507538
DOI: 10.3389/fmed.2022.973688 -
BMC Infectious Diseases Jan 2021The spread of a highly pathogenic, novel coronavirus (SARS-CoV-2) has emerged as a once-in-a-century pandemic, having already infected over 63 million people worldwide.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The spread of a highly pathogenic, novel coronavirus (SARS-CoV-2) has emerged as a once-in-a-century pandemic, having already infected over 63 million people worldwide. Novel therapies are urgently needed. Janus kinase-inhibitors and Type I interferons have emerged as potential antiviral candidates for COVID-19 patients due to their proven efficacy against diseases with excessive cytokine release and their direct antiviral ability against viruses including coronaviruses, respectively.
METHODS
A search of MEDLINE and MedRxiv was conducted by three investigators from inception until July 30th 2020 and included any study type that compared treatment outcomes of humans treated with Janus kinase-inhibitor or Type I interferon against controls. Inclusion necessitated data with clearly indicated risk estimates or those that permitted their back-calculation. Outcomes were synthesized using RevMan.
RESULTS
Of 733 searched studies, we included four randomized and eleven non-randomized trials. Five of the studies were unpublished. Those who received Janus kinase-inhibitor had significantly reduced odds of mortality (OR, 0.12; 95% CI, 0.03-0.39, p< 0.001) and ICU admission (OR, 0.05; 95% CI, 0.01-0.26, p< 0.001), and had significantly increased odds of hospital discharge (OR, 22.76; 95% CI, 10.68-48.54, p< 0.00001) when compared to standard treatment group. Type I interferon recipients had significantly reduced odds of mortality (OR, 0.19; 95% CI, 0.04-0.85, p< 0.05), and increased odds of discharge bordering significance (OR, 1.89; 95% CI, 1.00-3.59, p=0.05).
CONCLUSIONS
Janus kinase-inhibitor treatment is significantly associated with positive clinical outcomes in terms of mortality, ICU admission, and discharge. Type I interferon treatment is associated with positive clinical outcomes in regard to mortality and discharge. While these data show promise, additional well-conducted RCTs are needed to further elucidate the relationship between clinical outcomes and Janus kinase-inhibitors and Type I interferons in COVID-19 patients.
Topics: COVID-19; Humans; Interferon Type I; Janus Kinase Inhibitors; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33430799
DOI: 10.1186/s12879-020-05730-z