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Journal of the American Academy of... Jul 2023New evidence has emerged since the 2014 guidelines that further informs the management of atopic dermatitis (AD) with topical therapies. These guidelines update the 2014...
BACKGROUND
New evidence has emerged since the 2014 guidelines that further informs the management of atopic dermatitis (AD) with topical therapies. These guidelines update the 2014 recommendations for management of AD with topical therapies.
OBJECTIVE
To provide evidence-based recommendations related to management of AD in adults using topical treatments.
METHODS
A multidisciplinary workgroup conducted a systematic review and applied the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach for assessing the certainty of evidence and formulating and grading recommendations.
RESULTS
The workgroup developed 12 recommendations on the management of AD in adults with topical therapies, including nonprescription agents and prescription topical corticosteroids (TCS), calcineurin inhibitors (TCIs), Janus kinase (JAK) inhibitors, phosphodiesterase-4 inhibitors (PDE-4), antimicrobials, and antihistamines.
LIMITATIONS
The pragmatic decision to limit the literature review to English-language randomized trials may have excluded data published in other languages and relevant long-term follow-up data.
CONCLUSIONS
Strong recommendations are made for the use of moisturizers, TCIs, TCS, and topical PDE-4 and JAK inhibitors. Conditional recommendations are made for the use of bathing and wet wrap therapy and against the use of topical antimicrobials, antiseptics, and antihistamines.
Topics: Adult; Humans; Dermatitis, Atopic; Calcineurin Inhibitors; Dermatologic Agents; Administration, Topical; Glucocorticoids; Anti-Infective Agents, Local; Histamine Antagonists
PubMed: 36641009
DOI: 10.1016/j.jaad.2022.12.029 -
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 -
The Journal of Allergy and Clinical... Dec 2023Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes.
OBJECTIVE
We sought to systematically synthesize the benefits and harms of AD systemic treatments.
METHODS
For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna).
RESULTS
The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain.
CONCLUSIONS
Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.
Topics: Humans; Dermatitis, Atopic; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic; Eczema; Asthma; Treatment Outcome
PubMed: 37678577
DOI: 10.1016/j.jaci.2023.08.029 -
The Journal of Allergy and Clinical... Dec 2023Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects.
OBJECTIVE
We sought to systematically synthesize the benefits and harms of AD prescription topical treatments.
METHODS
For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT databases to September 5, 2022, for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using 7 groups-group 1 being most potent. This review is registered in the Open Science Framework (https://osf.io/q5m6s).
RESULTS
The 219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty evidence, pimecrolimus improved 6 of 7 outcomes-among the best for 2; high-dose tacrolimus (0.1%) improved 5-among the best for 2; low-dose tacrolimus (0.03%) improved 5-among the best for 1. With moderate- to high-certainty evidence, group 5 TCS improved 6-among the best for 3; group 4 TCS and delgocitinib improved 4-among the best for 2; ruxolitinib improved 4-among the best for 1; group 1 TCS improved 3-among the best for 2. These interventions did not increase harm. Crisaborole and difamilast were intermediately effective, but with uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus.
CONCLUSIONS
For individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective.
Topics: Humans; Dermatitis, Atopic; Tacrolimus; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic; Dermatologic Agents; Asthma; Eczema; Anti-Bacterial Agents
PubMed: 37678572
DOI: 10.1016/j.jaci.2023.08.030 -
Annals of the Rheumatic Diseases May 2024New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the...
OBJECTIVE
New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA.
METHODS
Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined.
RESULTS
The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed.
CONCLUSION
These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.
Topics: Arthritis, Psoriatic; Humans; Antirheumatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Methotrexate; Biological Products
PubMed: 38499325
DOI: 10.1136/ard-2024-225531 -
Rheumatology (Oxford, England) Nov 2023To evaluate the effectiveness and safety of current treatment strategies for the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome.
OBJECTIVES
To evaluate the effectiveness and safety of current treatment strategies for the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome.
METHODS
A protocolized systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. Three databases were searched for reports on treatment strategies for VEXAS. Data from the included publications was extracted and a narrative synthesis was performed. Treatment response was recorded as complete (CR), partial (PR) or none (NR) depending on changes in clinical symptoms and laboratory parameters. Patient characteristics, safety data and previous treatments were analysed.
RESULTS
We identified 36 publications with a total of 116 patients; 113 (98.3%) were male. The identified reports included azacytidine (CR 9/36, 25%; PR 14/36, 38.9%), Janus kinase inhibitors (JAKi) (CR 11/33, 33%; PR 9/33, 27.3%), tocilizumab (CR 3/15, 20%; PR 6/15, 40%), allogeneic stem cell transplantation (CR 6/7, 85.7%; one patient died), anakinra (CR 4/5, 80%; NR 1/5, 20%), canakinumab (CR 1/2, 50%; PR 1/2, 50%) and glucocorticoid monotherapy (CR 1/6, 16.7%; PR 4/6, 66.7%). Individual reports were available for TNF inhibitors, rituximab and MTX. Data on adverse events were available for 67 patients (67/116, 57.8%) and included: pneumonia (12/67, 17.9%), other infections (9/67, 13.4%), venous thromboembolisms (6/67, 8.9%), cytopenias (4/67, 5.9%), and acute (4/67, 5.9%) and chronic graft-vs-host-disease (2/67, 2.9%).
CONCLUSION
Current data on VEXAS treatment are limited and inhomogeneous. Treatment decisions should be individualized. For the devolvement of treatment algorithms clinical trials are needed. Adverse events remain a challenge, especially an elevated risk for venous thromboembolism associated to JAKi treatment should be carefully considered.
Topics: Humans; Male; Female; Algorithms; Azacitidine; Bronchiolitis Obliterans Syndrome; Databases, Factual; Janus Kinase Inhibitors; Mutation
PubMed: 37233149
DOI: 10.1093/rheumatology/kead240 -
JAMA Dermatology Jan 2024Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions.
OBJECTIVE
To determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions.
DATA SOURCES
PubMed and ClinicalTrials.gov were searched from database inception to April 1, 2023.
STUDY SELECTION
This review included phase 3 randomized clinical trials with a placebo/active comparator group of JAK inhibitors used for a dermatologic indication with FDA approval or pending approval or with European Union or Japanese approval. Studies without a comparison group, case reports, observational studies, and review articles were excluded.
DATA EXTRACTION AND SYNTHESIS
This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Adverse events using odds ratios (ORs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Studies were screened, data abstracted, and quality assessed by 2 independent authors. The protocol was prospectively registered with PROSPERO.
MAIN OUTCOMES AND MEASURES
Primary outcomes were a composite of adjudicated MACE and all-cause mortality, and VTE.
RESULTS
The analysis included 35 randomized clinical trials with 20 651 patients (mean [SD] age, 38.5 [10.1] years; male, 54%) and a mean (SD) follow-up time of 4.9 (2.68) months. Findings did not show a significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI, 0.26-1.04).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, use of JAK inhibitors was not associated with increased risk of all-cause mortality, MACE, and VTE compared to the placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for dermatologic indications.
Topics: Humans; Male; Adult; Janus Kinase Inhibitors; Venous Thromboembolism; Arthritis, Rheumatoid; Dermatitis, Atopic; Treatment Outcome
PubMed: 37910098
DOI: 10.1001/jamadermatol.2023.4090 -
The American Journal of Gastroenterology Sep 2023Rapidity of symptom resolution informs treatment choice in patients with moderate-severe ulcerative colitis (UC). We conducted a systematic review and network... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Rapidity of symptom resolution informs treatment choice in patients with moderate-severe ulcerative colitis (UC). We conducted a systematic review and network meta-analysis comparing early symptomatic remission with approved therapies.
METHODS
Through a systematic literature review to December 31, 2022, we identified randomized trials in adult outpatients with moderate-severe UC treated with approved therapies (tumor necrosis factor α antagonists, vedolizumab, ustekinumab, janus kinase inhibitors, or ozanimod), compared with each other or placebo, reporting rates of symptomatic remission (based on partial Mayo score, with resolution of rectal bleeding and near-normalization of stool frequency) at weeks 2, 4, and/or 6. We performed random-effects network meta-analysis using a frequentist approach and estimated relative risk (RR) and 95% confidence interval values.
RESULTS
On network meta-analysis, upadacitinib was more effective than all agents in achieving symptomatic remission at weeks 2 (range of RR, 2.85-6.27), 4 (range of RR, 1.78-2.37), and 6 (range of RR, 1.84-2.79). Tumor necrosis factor α antagonists and filgotinib, but not ustekinumab and vedolizumab, were more effective than ozanimod in achieving symptomatic remission at week 2, but not at weeks 4 and 6. With approximately 10% placebo-treated patients achieving symptomatic remission at 2 weeks, we estimated 68%, 22%, 23.7%, 23.9%, 22.2%, 18.4%, 15.7%, and 10.9% of upadacitinib-, filgotinib-, infliximab-, adalimumab-, golimumab-, ustekinumab-, vedolizumab-, and ozanimod-treated patients would achieve early symptomatic remission, ustekinumab and vedolizumab achieving rapid remission only in biologic-naïve patients.
DISCUSSION
In a systematic review and network meta-analysis, upadacitinib was most effective in achieving early symptomatic remission, whereas ozanimod was relatively slower acting.
Topics: Adult; Humans; Colitis, Ulcerative; Tumor Necrosis Factor-alpha; Network Meta-Analysis; Adalimumab; Ustekinumab; Treatment Outcome
PubMed: 36976548
DOI: 10.14309/ajg.0000000000002263 -
Journal of Crohn's & Colitis Nov 2023Oral small-molecule drugs [SMDs] are expanding the therapeutic landscape for inflammatory bowel disease [IBD]. This systematic review and meta-analysis summarizes the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Oral small-molecule drugs [SMDs] are expanding the therapeutic landscape for inflammatory bowel disease [IBD]. This systematic review and meta-analysis summarizes the efficacy and safety of JAK inhibitor [JAKi] and sphingosine-1-phosphate [S1P] receptor modulator treatments for ulcerative colitis [UC] and Crohn's disease [CD].
METHODS
MEDLINE, Embase, and CENTRAL were searched from inception to May 30, 2022. Randomized controlled trials [RCTs] of JAKi and S1P receptor modulators in adults with UC or CD were eligible. Clinical, endoscopic, histological, and safety data were pooled and analysed using a random-effects model.
RESULTS
Thirty-five RCTs [26 UC, nine CD] were included. In UC, JAKi therapy was associated with induction of clinical (risk ratio [RR] 3.16, 95% confidence interval [CI] 2.03-4.92; I2 = 65%) and endoscopic [RR 3.99, 95% CI 2.36-6.75; I2 = 36%] remission compared to placebo. Upadacitinib was associated with histological response [RR 2.63, 95% CI 1.97-3.53]. S1P modulator therapy was associated with induction of clinical [RR 2.52, 95% CI 1.88-3.39; I2 = 1%] and endoscopic [RR 2.39, 95% CI 1.07-5.33; I2 = 0%] remission relative to placebo. Ozanimod was superior to placebo for inducing histological remission in UC [RR 2.20, 95% CI 1.43-3.37; I2 = 0%], while etrasimod was not [RR 2.36, 95% CI 0.71-7.88; I2 = 0%]. In CD, JAKi therapy was superior to placebo for induction of clinical remission [RR 1.53, 95% CI 1.19-1.98; I2 = 31%], and endoscopic remission [RR 4.78, 95% CI 1.63-14.06; I2 = 43%] compared to placebo. The risk of serious infections was similar for oral SMDs and placebo.
CONCLUSION
JAKi and S1P receptor modulator therapies are effective in IBD for inducing clinical and endoscopic remission and, in some circumstances, histological response.
Topics: Adult; Humans; Sphingosine-1-Phosphate Receptors; Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative; Remission Induction; Janus Kinase Inhibitors
PubMed: 37317532
DOI: 10.1093/ecco-jcc/jjad100 -
Journal of Drugs in Dermatology : JDD Jul 2023This article describes the clinical trial, safety, and efficacy of ruxolitinib 1.5% cream or repigmentation in patients with vitiligo.
BACKGROUND
This article describes the clinical trial, safety, and efficacy of ruxolitinib 1.5% cream or repigmentation in patients with vitiligo.
DATA SOURCES
A systematic review was done using ruxolitinib or Opzelura in MEDLINE (PubMed) and EMBASE.
CLINICALTRIALS
gov was used to identify ongoing or unpublished studies.
STUDY SELECTION AND DATA EXTRACTION
Studies included were written in English and relevant to pharmacology, clinical trials, safety, and efficacy.
DATA SYNTHESIS
In two 52-week phase 3 trials, 52.0% of subjects had at least 75% improvement in their Facial Vitiligo Area Scoring Index (F-VASI).
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Ruxolitinib is a topical Janus kinase (JAK) inhibitor newly approved by the US Food and Drug Administration for repigmentation in patients with vitiligo.
CONCLUSION
Topical ruxolitinib is the first medication approved for repigmentation in patients with vitiligo. It is a safe and effective treatment; however, cost may be a barrier to some patients when prescribing this medication. Trials to compare the efficacy and side effect profile of topical ruxolitinib with other topical treatments are still needed. Grossmann MC, Haidari W, Feldman SR. A Review on the use of topical ruxolitinib for the treatment of vitiligo. J Drugs Dermatol. 2023;22(7):664-667. doi:10.36849/JDD.7268.
Topics: Humans; Vitiligo; Pyrimidines; Nitriles; Pyrazoles; Treatment Outcome; Janus Kinase Inhibitors
PubMed: 37410047
DOI: 10.36849/JDD.7268