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JAMA Network Open Jun 2023Alopecia areata (AA) is a common chronic tissue-specific autoimmune disease. Several studies have reported outcomes of Janus kinase (JAK) inhibitors for treating AA, but... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Alopecia areata (AA) is a common chronic tissue-specific autoimmune disease. Several studies have reported outcomes of Janus kinase (JAK) inhibitors for treating AA, but limited evidence has emerged.
OBJECTIVE
To evaluate the effectiveness and safety associated with JAK inhibitors for AA.
DATA SOURCES
MEDLINE, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) were searched from inception until August 2022.
STUDY SELECTION
Only randomized clinical trials (RCTs) were included. Pairs of reviewers independently and in duplicate selected the studies.
DATA EXTRACTION AND SYNTHESIS
Hartung-Knapp-Sidik-Jonkman random-effects models were used for meta-analysis. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
MAIN OUTCOMES AND MEASURES
The primary outcomes of interest were (1) proportion of patients who achieved 30%, 50%, and 90% improvement in Severity of Alopecia Tool (SALT) score from baseline, (2) change from baseline SALT score, and (3) treatment-related adverse event (AE).
RESULTS
Seven RCTs with 1710 patients (1083 females [63.3%]; mean [SD] age range, 36.3 [10.4] to 69.7 [16.2] years) were eligible and included in the study. JAK inhibitors were associated with more patients achieving 50% improvement (odds ratio [OR], 5.28 [95% CI, 1.69-16.46]; GRADE assessment: low certainty) and 90% improvement (OR, 8.15 [95% CI, 4.42-15.03]; GRADE assessment: low certainty) in SALT score from baseline compared with placebo. JAK inhibitors were associated with more lowered SALT scores from the baseline compared with placebo (mean difference [MD], -34.52 [95% CI, -37.80 to -31.24]; GRADE assessment: moderate certainty), and JAK inhibitors were not associated with more treatment-related AEs (relative risk [RR], 1.25 [95% CI, 1.00-1.57]; GRADE assessment: high certainty) compared with placebo. High certainty of evidence showed that JAK inhibitors may not be associated with more severe AEs compared with placebo (RR, 0.77; 95% CI, 0.41-1.43). The subgroup analysis showed that oral JAK inhibitors were more efficient than placebo (change from baseline SALT scores: MD, -36.80; 95% CI, -39.57 to -34.02), and no difference was found between external JAK inhibitors and placebo (change from baseline SALT scores: MD, -0.40; 95% CI, -11.30 to 10.50).
CONCLUSIONS AND RELEVANCE
Results of this systematic review and meta-analysis suggest that JAK inhibitors, compared with placebo, were associated with hair regrowth and that the outcome of oral JAK inhibitors was better than the external route of administration. Although the safety and tolerability of JAK inhibitors were acceptable, longer RCTs are needed to further assess the effectiveness and safety of these treatments for AA.
Topics: Female; Humans; Adult; Janus Kinase Inhibitors; Alopecia Areata; Chronic Disease; Network Meta-Analysis
PubMed: 37368402
DOI: 10.1001/jamanetworkopen.2023.20351 -
JAMA Dermatology Dec 2023Janus kinase (JAK) inhibitors are increasingly used across a range of dermatologic conditions. Adverse events of acne have been noted in some studies in clinical... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Janus kinase (JAK) inhibitors are increasingly used across a range of dermatologic conditions. Adverse events of acne have been noted in some studies in clinical practice, but the scope of this outcome across JAK inhibitors has not been established.
OBJECTIVE
To systematically analyze all published phase 2 and 3 placebo-controlled randomized clinical trials (RCTs) of JAK inhibitors for the risk of acne as an adverse effect of these medications.
DATA SOURCES
Comprehensive search of Ovid MEDLINE and PubMed databases through January 31, 2023.
STUDY SELECTION
Inclusion criteria were phase 2 and 3 placebo-controlled RCTs of JAK inhibitors published in English with reported adverse events of acne.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently reviewed and extracted information from all included studies.
MAIN OUTCOMES AND MEASURES
The primary outcome of interest was the incidence of acne following JAK inhibitor use. A meta-analysis was conducted using random-effects models.
RESULTS
A total of 25 unique studies (10 839 unique participants; 54% male and 46% female) were included in the final analysis. The pooled odds ratio (OR) was calculated to be 3.83 (95% CI, 2.76-5.32) with increased ORs for abrocitinib (13.47 [95% CI, 3.25-55.91]), baricitinib (4.96 [95% CI, 2.52-9.78]), upadacitinib (4.79 [95% CI, 3.61-6.37]), deucravacitinib (2.64 [95% CI, 1.44-4.86]), and deuruxolitinib (3.30 [95% CI, 1.22-8.93]). Estimated ORs were higher across studies investigating the use of JAK inhibitors for the management of dermatologic compared with nondermatologic conditions (4.67 [95% CI, 3.10-7.05]) as well as for JAK1-specific inhibitors (4.69 [95% CI, 3.56-6.18]), combined JAK1 and JAK2 inhibitors (3.43 [95% CI, 2.14-5.49]), and tyrosine kinase 2 inhibitors (2.64 [95% CI, 1.44-4.86]).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, JAK inhibitor use was associated with an elevated odds of acne. Patients should be properly counseled on this potential adverse effect of these medications before treatment initiation. Future studies are needed to further elucidate the pathophysiology of this association.
Topics: Male; Female; Humans; Janus Kinase Inhibitors; Acne Vulgaris
PubMed: 37851459
DOI: 10.1001/jamadermatol.2023.3830 -
Acta Dermato-venereologica Aug 2022The aim of this study was to compare the efficacies of systemic treatments with dupilumab, tralokinumab and Janus kinase inhibitors for moderate-to-severe atopic... (Meta-Analysis)
Meta-Analysis
The aim of this study was to compare the efficacies of systemic treatments with dupilumab, tralokinumab and Janus kinase inhibitors for moderate-to-severe atopic dermatitis. A systematic review following Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines was performed using Medline, EMBASE and Cochrane library. All randomized controlled trials investigating the efficacy of systemic treatments for moderate-to-severe atopic dermatitis in adults were included. Primary outcomes were the proportion of patients with atopic dermatitis achieving 50%, 75%, and 90% improvement in Eczema Area and Severity Index (EASI) score after dupilumab, tralokinumab or Janus kinase inhibitors. Nineteen studies totalling 6,444 patients were included. In monotherapy studies, upadacitinib 30 mg once daily had the numerically highest efficacy regarding EASI-50, EASI-75 and EASI-90. In combination therapy studies with topical corticosteroids, dupilumab 300 mg once every other week had highest efficacy regarding EASI-50, and abrocitinib 200 mg once daily had the highest score regarding EASI-75 and EASI-90. Analysis provided evidence that dupilumab, tralokinumab and Janus kinase inhibitors all had an acceptable efficacy profile and resulted in clinically relevant improvements in EASI score. Furthermore, upadacitinib and abrocitinib seem to have great potential to treat patients with atopic dermatitis. However, further studies are needed to determine the long-term efficacy of Janus kinase inhibitors in adults with moderate-to-severe atopic dermatitis.
Topics: Adult; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Dermatitis, Atopic; Double-Blind Method; Humans; Janus Kinase Inhibitors; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 35818735
DOI: 10.2340/actadv.v102.2075 -
The Journal of Dermatological Treatment Feb 2022Vitiligo is an autoimmune disorder characterized by progressive loss of melanocytes, leading to cutaneous depigmentation. Vitiligo has significant psychosocial impacts... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Vitiligo is an autoimmune disorder characterized by progressive loss of melanocytes, leading to cutaneous depigmentation. Vitiligo has significant psychosocial impacts on patients and is challenging to manage with limited treatment options. Recent studies have suggested promising results for JAK1/3 inhibitors including tofacitinib and ruxolitinib.
OBJECTIVE
To determine the expected response of vitiligo to JAK inhibitor therapy and factors which influence response rates.
METHODS
A systematic review and meta-analysis was performed according to PRISMA guidelines. Good response was defined as repigmentation >50% or a 'good' or 'excellent' outcome as described by authors. Partial response was defined as some repigmentation <50%.
RESULTS
From the 9 eligible studies, individual patient data from 45 cases were pooled. Good response was achieved in 57.8%, partial response in 22.2%, and none or minimal response in 20% of cases. When subgrouped according to site, facial vitiligo had the highest good response rate (70%), compared to extremities (27.3%) and torso/non-sun exposed areas (13.6%). Concurrent phototherapy was significant associated with higher rates of good overall response ( < .001) and good facial response ( < .001).
CONCLUSIONS
There is promising low-quality evidence regarding the effectiveness of JAK inhibitors in vitiligo. Concurrent UVB phototherapy appears to improve efficacy of JAK inhibitors for vitiligo.
Topics: Humans; Janus Kinase Inhibitors; Janus Kinases; Phototherapy; Skin Pigmentation; Treatment Outcome; Ultraviolet Therapy; Vitiligo
PubMed: 32096671
DOI: 10.1080/09546634.2020.1735615 -
Clinical and Experimental Rheumatology Mar 2023Dermatomyositis (DM) is an idiopathic inflammatory myopathy that commonly manifests with proximal muscle weakness and is associated with extramuscular pathology,... (Review)
Review
Dermatomyositis (DM) is an idiopathic inflammatory myopathy that commonly manifests with proximal muscle weakness and is associated with extramuscular pathology, including characteristic skin lesions such as Gottron's papules and heliotrope rash, as well as lung, gastrointestinal, joint, and cardiac involvement. Systemic corticosteroids are a cornerstone of therapy, and more recently intravenous immunoglobulin (IVIG; OCTAGAM®) has been approved by the US Food and Drug Administration for the treatment of adults with DM. Both steroids and IVIG represent nonspecific anti-inflammatory therapy, and more targeted approaches are lacking. Transcriptomics has identified upregulation of interferon (IFN)-regulated genes as key features of both adult DM and juvenile DM (JDM). Accordingly, blocking IFN signalling through inhibition of the Janus kinase (JAK) pathway represents a potential treatment option for DM. Placebo-controlled trial data assessing the use of JAK inhibitors for the treatment of DM are limited; as such, a systematic literature review was undertaken to assess the evidence of JAK inhibitors in the treatment of patients with DM. Terms related to DM and JAK inhibitors were searched using PubMed, Embase, Web of Science, Scopus, and Dimensions to identify peer-reviewed publications reporting patients with DM who were treated with a JAK inhibitor. Baseline demographics, clinical characteristics, and treatment outcome data were extracted. A total of 48 publications reporting 145 unique patients (adult DM, n=84; JDM, n=61) were identified. Among cases of adult DM, 61 of 84 (73%) had refractory skin disease at baseline, and all (61 of 61) reported improvement in cutaneous symptoms. Of patients with adult DM, 16 of 84 (19%) had refractory muscle disease at baseline, and all (16 of 16) reported improvement in muscle symptoms. In patients with adult DM complicated by interstitial lung disease (ILD; n=33), 31 (94%) patients improved with JAK inhibitor treatment. Among cases of JDM with refractory skin disease at baseline (60 of 61), most patients (57 of 60; 95%) showed improvements in skin symptoms after JAK inhibitor treatment. Of patients with JDM with refractory muscle disease at baseline (36 of 61), most (30 of 36; 83%) reported improvement in muscle symptoms. Four patients with JDM and ILD experienced improvement in lung disease activity following treatment with a JAK inhibitor. Among both DM and JDM cases, all patients (17 with DM and 16 with JDM) who had elevated serum IFN and/or IFN-stimulated gene expression at baseline showed reduction in IFN or IFN gene expression. Although the conclusions that can be drawn from this analysis are limited because of the differences in assessments used across publications, overall treatment of patients with DM or JDM with a JAK inhibitor was associated with significant improvement of a wide range of DM manifestations, including skin lesions, muscle weakness, and ILD. Our systematic literature review suggests that JAK inhibitors may be a viable treatment option for DM/JDM, and randomised controlled trials are necessary to confirm these findings.
Topics: Adult; Humans; Dermatomyositis; Janus Kinase Inhibitors; Immunoglobulins, Intravenous; Muscular Diseases; Muscle Weakness; Lung Diseases, Interstitial
PubMed: 35766013
DOI: 10.55563/clinexprheumatol/hxin6o -
Acta Dermato-venereologica Jan 2023The aim of this study was to compare the efficacy and safety of treatment with Janus kinase inhibitors for alopecia areata, measured by change in Severity of Alopecia... (Meta-Analysis)
Meta-Analysis
The aim of this study was to compare the efficacy and safety of treatment with Janus kinase inhibitors for alopecia areata, measured by change in Severity of Alopecia Tool (SALT) score. A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was performed using Medline, EMBASE and Cochrane library. All studies investigating the efficacy of treatments for alopecia areata were included. Primary outcomes were the proportion of patients with alopecia areata achieving 30%, 50%, 75%, 90% and 100% improvement in SALT score after treatment with a Janus kinase inhibitor. A meta-analysis was performed including all randomized controlled trials investigating Janus kinase inhibitors. A total of 37 studies matched the inclusion criteria and were included. Meta-analysis was performed based on 5 randomized studies. Regarding patients with alopecia areata defined as ≥ 50% scalp hair loss, baricitinib 4 mg once daily demonstrated the highest efficacy. However, among patients with alopecia areata defined as a SALT score ≥ 50, oral deuruxolitinib 12 mg twice daily demonstrated the highest efficacy. Deuruxolitinib and baricitinib appear to be promising drugs for the treatment of alopecia areata. However, the response depends on the dosage of the drug. More randomized trials, with identical inclusion criteria and dose and duration of treatment, are required to confirm these findings.
Topics: Humans; Alopecia Areata; Janus Kinase Inhibitors; Alopecia; Pyrazoles
PubMed: 36695751
DOI: 10.2340/actadv.v103.4536 -
Clinical Rheumatology Jun 2023To evaluate the efficacy and safety of Janus kinase (JAK) inhibitors (Jakinibs) in the treatment of psoriasis and psoriatic arthritis (PsA). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To evaluate the efficacy and safety of Janus kinase (JAK) inhibitors (Jakinibs) in the treatment of psoriasis and psoriatic arthritis (PsA).
METHODS
Databases including PubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials on the efficacy and safety of Jakinibs in treating psoriasis and PsA from inception to July 2021. A systematic review and meta-analysis were performed to estimate pooled relative risk (RR) and 95% confidence interval (CI).
RESULTS
Seventeen clinical trials (16 publications) comprising 6802 patients were included. All Jakinibs demonstrated significantly higher response rates compared with placebo (ACR20: RR 2.09, 95% CI 1.90-2.30; PASI75: RR 4.03, 95% CI 3.13-5.18). Within the subgroup analysis, the response rates defined by ACR20 were highest for filgotinib (RR 2.40, 95% CI 1.67-3.45), followed by upadacitinib, tofacitinib, and deucravacitinib. The proportion of patients achieving PASI75 response in the tofacitinib 10 mg twice daily group was significantly higher than that in the tofacitinib 5 mg group. Regarding safety, the incidence of adverse events (AEs) was significantly higher for Jakinibs compared with placebo (RR 1.17, 95% CI 1.11-1.23). Of note, a considerable increase in the risk of infections including upper respiratory tract and herpes zoster infection was observed among patients in the treatment group. For tofacitinib, upadacitinib, and filgotiniband, infection was the most prevalent AE. Moreover, AEs in the 10 mg tofacitinib group were higher than those in the 5 mg tofacitinib group.
CONCLUSION
Jakinibs are efficacious interventions for the treatment of psoriasis and PsA, but they are associated with an increased risk of AEs when compared with placebo. The long-term efficacy and safety data require further evaluation. Key Points • This systematic review investigated and compared the efficacy and safety of different Jakinibs including the novel selective TYK2 inhibitors. • Jakinibs are efficacious interventions for the treatment of psoriasis and PsA. • A relatively higher dosing schedule of Jakinibs is associated with increased toxicity.
Topics: Humans; Arthritis, Psoriatic; Janus Kinase Inhibitors; Psoriasis; Incidence; Treatment Outcome
PubMed: 36763226
DOI: 10.1007/s10067-023-06529-4 -
JAMA Dermatology Nov 2022The risk of venous thromboembolism (VTE) among patients with atopic dermatitis (AD), especially when receiving treatment with Janus kinase (JAK) inhibitors, is unclear. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The risk of venous thromboembolism (VTE) among patients with atopic dermatitis (AD), especially when receiving treatment with Janus kinase (JAK) inhibitors, is unclear.
OBJECTIVE
To determine the association of AD with incident VTE and evaluate the risk of incident VTE among patients with AD who were receiving treatment with JAK inhibitors.
DATA SOURCES
The MEDLINE, Embase, Cochrane Library, and Web of Science databases were searched with no restrictions on language nor geographic locations from their respective inception to February 5, 2022.
STUDY SELECTION
Cohort studies examining the association of AD with incident VTE and randomized clinical trials (RCTs) reporting VTE events in participants with AD receiving JAK inhibitors were included. Around 0.7% of initially identified articles met the selection criteria.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The risk of bias of included cohort studies and RCTs was assessed by the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool 2, respectively. A random-effects model meta-analysis was conducted to calculate the pooled hazard ratio (HR) and risk difference for incident VTE.
MAIN OUTCOMES AND MEASURES
The HRs for incident VTE associated with AD and risk difference for incident VTE between participants with AD who were receiving treatment with JAK inhibitors and controls receiving placebo or dupilumab.
RESULTS
Two cohort studies and 15 RCTs with a total of 466 993 participants were included. The meta-analysis found no significant association of AD with incident VTE (HR, 0.95; 95% CI 0.62-1.45; incidence rate of VTE, 0.23 events/100 patient-years). Overall, 3 of 5722 patients with AD (0.05%) who were receiving treatment with JAK inhibitors experienced VTE compared with 1 of 3065 patients with AD (0.03%) receiving placebo or dupilumab (Mantel-Haenszel risk difference, 0; 95% CI, 0-0). The incidence rate of VTE was 0.15 and 0.12 events per 100 patient-years in participants with AD receiving JAK inhibitors and placebo, respectively. The findings were similar in 4 unique JAK inhibitors (abrocitinib, baricitinib, upadacitinib, and SHR0302).
CONCLUSIONS AND RELEVANCE
The results of this systematic review and meta-analysis suggest that the currently available evidence does not detect an increased risk of VTE associated with AD or treatment with JAK inhibitors. These findings may provide a reference for clinicians in prescribing JAK inhibitors for patients with AD.
Topics: Humans; Venous Thromboembolism; Janus Kinase Inhibitors; Dermatitis, Atopic
PubMed: 36001310
DOI: 10.1001/jamadermatol.2022.3516 -
Pharmacology 2022Janus kinase (JAK) inhibitors and secukinumab have been demonstrated to be effective treatments for ankylosing spondylitis (AS). However, there have been no head-to-head... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Janus kinase (JAK) inhibitors and secukinumab have been demonstrated to be effective treatments for ankylosing spondylitis (AS). However, there have been no head-to-head trials comparing the effectiveness and safety characteristics of JAK inhibitors with secukinumab. This study aimed to evaluate the relative effectiveness and safety of JAK inhibitors and secukinumab in patients with active AS.
SUMMARY
A Bayesian network meta-analysis was conducted using direct and indirect data from randomized controlled trials (RCTs) that examined the efficacy and safety of tofacitinib 5 mg, upadacitinib 15 mg, filgotinib 200 mg, and secukinumab 150 mg in patients with active AS who had a poor response or intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs) and were tumor necrosis factor (TNF) inhibitor-naïve. Data from six RCTs comprising 937 patients were analyzed. The Assessment of SpondyloArthritis International Society 20 (ASAS20) response rates were significantly higher in the JAK inhibitors and secukinumab groups than in the placebo group. The surface under the cumulative ranking curve (SUCRA)-based ranking probability based on the ASAS20 response rate suggested that tofacitinib 5 mg had the highest likelihood of being the best treatment for achieving the ASAS20 response rate, followed by filgotinib 200 mg, upadacitinib 15 mg, secukinumab 150 mg, and placebo. The SUCRA-based ranking probability based on the ASAS20 response rate suggested that tofacitinib 5 mg had the highest likelihood of being the best treatment for achieving the ASAS40 response rate, followed by upadacitinib 15 mg, secukinumab 150 mg, filgotinib 200 mg, and placebo.
KEY MESSAGES
Tofacitinib 5 mg was the most effective treatment for AS, whereas JAK inhibitors and secukinumab 150 mg were effective treatments in patients with active AS who had a poor response or intolerance to NSAIDs and were TNF inhibitor-naïve.
Topics: Humans; Janus Kinase Inhibitors; Spondylitis, Ankylosing; Antirheumatic Agents; Treatment Outcome; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 35817017
DOI: 10.1159/000525627 -
Journal of the European Academy of... Apr 2023Management options for moderate-to-severe alopecia areata (AA) are limited owing to a lack of safe and effective treatments suitable for long-term use. However, newer... (Review)
Review
Management options for moderate-to-severe alopecia areata (AA) are limited owing to a lack of safe and effective treatments suitable for long-term use. However, newer agents have the potential to induce and maintain hair regrowth in patients with a better side-effects profile compared to systemic steroids or conventional systemic agents. In this article, we conducted a systematic review of newer agents, including Janus kinase (JAK) inhibitors, biologics and phosphodiesterase-4 (PDE-4) inhibitors, for the treatment of AA in adult patients evaluated in randomized controlled trials (RCTs) using the Severity of Alopecia Tool score. A literature search was performed on PubMed and ClinicalTrials.gov, which identified 106 items with 12 RCTs eligible for review. Information regarding the treatment regimen, duration, endpoints, efficacy and adverse events were extracted; product monograph information was also summarized for approved agents with or without indications for AA. Overall, current data suggest the oral JAK inhibitors (baricitinib, ritlecitinib, deuruxolitinib, brepocitinib) as a promising new class of agents that can induce significant hair regrowth, with mild to moderate adverse effects. Baricitinib recently received US FDA approval for the treatment of severe AA, while ritlecitinib and deuruxolitinib have received the breakthrough therapy designation for AA. In contrast, PDE-4 inhibitors (apremilast) and the biologics (dupilumab, secukinumab and aldesleukin) appear to have limited efficacy thus far. Results from ongoing and future long-term studies could shed light on the utility of the newer agents in altering the progression of AA.
Topics: Adult; Humans; Alopecia Areata; Janus Kinase Inhibitors; Phosphodiesterase 4 Inhibitors; Cyclic Nucleotide Phosphodiesterases, Type 4; Biological Products; Alopecia; Protein Kinase Inhibitors
PubMed: 36478475
DOI: 10.1111/jdv.18810