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Psoriasis (Auckland, N.Z.) 2023Palmoplantar pustulosis (PPP) is a chronic, relapsing, inflammatory disease that can occur alone or in association with arthritis. There is still controversy about... (Review)
Review
Palmoplantar pustulosis (PPP) is a chronic, relapsing, inflammatory disease that can occur alone or in association with arthritis. There is still controversy about whether it should be separated from psoriasis or classified as pustular psoriasis. Furthermore, drug-induced paradoxical PPP is a special variant of PPP that differs from classic PPP in several ways. Treatment of PPP is still challenging, and there are a number of treatment-resistant cases. This review summarizes the risk factors for the development of PPP and the currently available treatment modalities. Female sex, smokers or ex-smokers, obesity, thyroid dysfunction, and treatment with a tumor necrosis factor (TNF)-α inhibitor have been identified as risk factors for the disease's development, severity, and course. Topical treatments and phototherapy are effective for some patients and are used as a first-line or adjuvant treatment modality. Conventional treatments including retinoids and fumaric acid show good effects and can increase the efficacy of treatment with psoralen + ultraviolet light therapy (PUVA). Ciclosporin is fast acting, but relapse mostly occurs immediately after cessation. TNF-α inhibitors are efficient, and an even better response can be achieved with IL-17 and IL-23 blockers as well as apremilast. The effect of Janus kinase inhibitors seems to be promising according to case reports, but further investigations with larger cohorts are needed.
PubMed: 37772169
DOI: 10.2147/PTT.S400402 -
Rheumatology and Therapy Dec 2023Baricitinib, an orally available small-molecule inhibitor of Janus kinase (JAK)1 and JAK2, is indicated to treat active moderate-to-severe rheumatoid arthritis (RA). (Review)
Review
INTRODUCTION
Baricitinib, an orally available small-molecule inhibitor of Janus kinase (JAK)1 and JAK2, is indicated to treat active moderate-to-severe rheumatoid arthritis (RA).
OBJECTIVE
This systematic review described the real-world clinical characteristics of baricitinib-treated patients with RA, prescription patterns, effectiveness, drug persistence, patient-reported outcomes (PROs; physical function, pain, health-related quality of life [HRQoL]), patient global assessment (PGA), and safety of baricitinib.
METHODS
A PRISMA systematic review of real-world studies was conducted to identify relevant literature published between January 2016 and September 2022 using MEDLINE®, EMBASE®, and evidence-based medicine review databases. Websites or online repositories of the American College of Rheumatology and the European Alliance of Associations for Rheumatology were searched manually to include relevant abstracts from conferences held between January 2016 and November 2022.
RESULTS
A total of 11,472 records were identified by searching online databases. Seventy studies were included in the study, of which 40 were abstracts. Most patients were older (51-71 years), female, and with mean RA duration of 4-19 years. Baricitinib was mostly used after the failure of one or more bDMARDs, and 4 mg dosing was prevalent in patients with RA (range 22-100%). Clinical effectiveness of baricitinib was reported in real-world settings regardless of prior biologic/targeted synthetic disease-modifying antirheumatic drug (DMARD) use and concomitant conventional synthetic DMARD use. Achievement of Clinical Disease Activity Index (CDAI) remission was reported in 8.7-60% of patients at week 12 and CDAI low disease activity (LDA) in 20.2-81.6% at week 24. The proportion of patients attaining Simple Disease Activity Index (SDAI) remission was reported in 12% at week 4 to 45.4% at 24 weeks. Drug persistence was high, similar, or equal to anti-tumor necrosis factor drugs. No new safety signals were identified.
CONCLUSION
Baricitinib demonstrated effectiveness in the real-world setting with a consistent safety profile observed in clinical studies. Better persistence rates for baricitinib compared to bDMARDs with improvement in PROs were reported, although baricitinib-treated patients had RA with poor prognostic characteristics.
PubMed: 37715917
DOI: 10.1007/s40744-023-00591-9 -
RMD Open Sep 2023To estimate the incidence of infections among patients with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA), two distinct phenotypes included in the large... (Meta-Analysis)
Meta-Analysis
Incidence of infections in patients with psoriatic arthritis and axial spondyloarthritis treated with biological or targeted disease-modifying agents: a systematic review and meta-analysis of randomised controlled trials, open-label studies and observational studies.
OBJECTIVE
To estimate the incidence of infections among patients with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA), two distinct phenotypes included in the large group of spondyloarthritis (SpA), treated with tumour necrosis-factor-inhibitors, interleukin-17-inhibitors, Janus kinase-inhibitors, IL-23 or IL-12/23-inhibitors (IL-12/23i), phosphodiesterase 4-inhibitors or cytotoxic T-lymphocyte associated protein 4-Ig.
METHODS
A meta-analysis of randomised controlled trials (RCTs), open-label extension and observational studies was conducted. Serious infections were defined as infections that were life-threatening, required intravenous antibiotics and/or hospitalisation. Non-serious infections did not meet these severity criteria. The incidence rates (IR) were reported for each diagnosis by treatment class and study type using random-effect model to create a 95% CI.
RESULTS
Among 23 333 PsA patients and 11 457 axSpA patients, there were 1.09 serious infections per 100 patient-years (PY) (95% CI 0.85 to 1.35) with similar IR in PsA (0.96 per 100 PY 95% CI 0.69 to 1.28) and axSpA (1.09 per 100 PY 95% CI 0.76 to 1.46). The IR was lower in RCTs (0.77 per 100 PY 95% CI 0.41 to 1.20) compared with observational studies (1.68 per 100 PY 95% CI 1.03 to 2.47). In PsA patients, the lowest IR value was observed with IL-12/23i (0.29 per 100 PY 95% CI 0.00 to 1.03). There were 53.0 non-serious infections per 100 PY (95% CI 43.47 to 63.55) in 7257 PsA patients and 5638 axSpA patients. The IR was higher in RCTs (69.95 per 100 PY 95% CI 61.59 to 78.84) compared with observational studies (15.37 per 100 PY 95% CI 5.11 to 30.97).
CONCLUSION
Serious infections were rare events in RCTs and real-life studies. Non-serious infections were common adverse events, mainly in RCTs.
PROSPERO REGISTRATION NUMBER
CRD42020196711.
Topics: Humans; Arthritis, Psoriatic; Incidence; Interleukin-12; Axial Spondyloarthritis; Research Design; Randomized Controlled Trials as Topic
PubMed: 37714666
DOI: 10.1136/rmdopen-2023-003064 -
Inflammation Research : Official... Sep 2023The therapeutic efficacy of systemic Janus kinase (JAK) inhibitors in moderate-to-severe atopic dermatitis (AD) is well established. However, the associated risk of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The therapeutic efficacy of systemic Janus kinase (JAK) inhibitors in moderate-to-severe atopic dermatitis (AD) is well established. However, the associated risk of incident acne, which is a prevalent adverse event in AD patients treated with systemic JAK inhibitors, has yet to be systematically analyzed.
METHODOLOGY
To evaluate the risk of incident acne in AD patients treated with systemic JAK inhibitors, an extensive database search (clinicaltrials.gov, PubMed) was performed to identify publications eligible for inclusion from January 2020 to October 2022. Five randomized clinical trials (RCTs) of abrocitinib, four RCTs of upadacitinib, and one RCT of baricitinib, encompassing a total of 7901 participants, were included in the analysis. The risk difference for incident acne between systemic JAK inhibitors and controls was assessed using Review Manager, version 5.3, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Meta-analysis elucidated a significant difference in the risk of incident acne between AD participants receiving 200 mg abrocitinib (Mantel-Haenszel risk difference, 3.69; 95% CI 1.60-8.48; P < 0.01), 15 mg upadacitinib (Mantel-Haenszel risk difference, 4.61; 95% CI 2.79-7.62; P < 0.00001), and 30 mg upadacitinib (Mantel-Haenszel risk difference, 6.82; 95% CI 4.59-10.13; P < 0.00001) compared with controls receiving placebo or dupilumab. In contrast, no significant difference was found in the risk of incident acne between participants receiving 100 mg abrocitinib, 2 mg baricitinib, and 4 mg baricitinib, as compared with controls.
CONCLUSIONS
Based on the current evidence, there is an increased risk of acne related to systemic JAK inhibitors, particularly with abrocitinib and upadacitinib. For patients predisposed to acne, the balance between the benefits of symptomatic relief from AD and the potential risk of acne may need to be carefully considered. This study contributes to a nuanced understanding of the risk profile of systemic JAK inhibitors and has the potential to guide personalized treatment decisions for AD patients.
Topics: Humans; Dermatitis, Atopic; Janus Kinase Inhibitors; Acne Vulgaris; Janus Kinase 1
PubMed: 37707560
DOI: 10.1007/s00011-023-01789-x -
Autoimmunity Reviews Dec 2023Janus kinase (JAK) inhibitors have been proven to be effective and safe in various autoimmune diseases. However, there is still a lack of comprehensive evidence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Janus kinase (JAK) inhibitors have been proven to be effective and safe in various autoimmune diseases. However, there is still a lack of comprehensive evidence regarding their efficacy and safety in systemic and cutaneous lupus erythematosus.
METHODS
We searched for systemic and cutaneous lupus erythematosus patients who were treated with JAK inhibitors in PubMed, Embase, Web of Science, and the Cochrane Library until February 28, 2023. The quality of clinical trials was assessed using the Cochrane risk-of-bias tool. Meta-analysis was conducted when at least three studies had comparable measures of outcome. If meta-analysis was not feasible, a descriptive review was carried out.
RESULTS
We included 30 studies, consisting of 10 randomized controlled trials and 20 case series or reports, with a total of 2,460 patients. JAK inhibitors were found to be more effective than placebo in systemic lupus erythematosus (SLE) based on the percentage of achieving SLE Responder Index (SRI)-4 response (RR = 1.18; 95% CI 1.07 to 1.31; p = 0.001), British Isles Lupus Assessment Group -based Composite Lupus Assessment (BICLA) response (RR = 1.16; 95% CI 1.02 to 1.31; p = 0.02), Lupus Low Disease Activity State (LLDAS) (RR = 1.28; 95% CI 1.07 to 1.54; p = 0.008), and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) remission of arthritis or rash (RR = 1.09; 95% CI 1.00 to 1.18; p = 0.04), particularly in treating musculoskeletal and mucocutaneous involvement. However, the effect of JAK inhibitors on cutaneous lupus erythematosus was uncertain. JAK inhibitors and placebo had a similar incidence of adverse events (RR = 1.01; 95% CI 0.97 to 1.04; p = 0.65).
CONCLUSION
JAK inhibitors could be a potential treatment option for systemic and cutaneous lupus erythematosus, particularly in treating cutaneous and musculoskeletal lesions of SLE. JAK inhibitors had a safe profile.
Topics: Humans; Janus Kinase Inhibitors; Lupus Erythematosus, Systemic; Arthritis; Lupus Erythematosus, Cutaneous; Skin; Treatment Outcome
PubMed: 37678618
DOI: 10.1016/j.autrev.2023.103440 -
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 -
Current Rheumatology Reviews 2024Up to 30% of patients with RA are being treated with biologic (b)-disease modifying anti-rheumatic drugs (DMARDs) as monotherapy. Monotherapy with Interleukin (IL)-6...
BACKGROUND
Up to 30% of patients with RA are being treated with biologic (b)-disease modifying anti-rheumatic drugs (DMARDs) as monotherapy. Monotherapy with Interleukin (IL)-6 inhibitors(i) and Janus-kinase (JAK)-i has been shown to be effective. Whether patients can taper targeted therapy (bDMARDs and JAK-i) used as monotherapy (targeted monotherapy) is unknown.
OBJECTIVE
To determine the feasibility of tapering of targeted monotherapy in patients with controlled RA.
METHODS
We conducted a literature search in Medline, Embase and Cochrane Library for prospective studies reporting remission outcomes after tapering targeted monotherapy in RA patients, from 1/2014 - 8 /2021.
RESULTS
5 randomized studies which met our inclusion criteria, evaluating tapering of monotherapy with tumor necrosis factor-inhibitors, tocilizumab, abatacept and baricitinib in RA. Studies were heterogeneous. Three trials studied early RA. Three studies gradually tapered therapy, including 1 dose reduction study. Three studies tapered both biological and conventional-synthetic (cs)-DMARDs. No study compared stopping targeted monotherapy to continuing it. Remission rates were low 14-28% across all studies that stopped targeted monotherapy. The highest remission rate of 72% was reported by the dose reduction study. Trials that studied early RA reported remission rates after tapering ranging 27-72%. Trials tapering therapy in established RA reported rates of remission from 14-20%.
CONCLUSION
There is a crucial gap in published literature to inform on tapering targeted monotherapy in patients with RA. Stopping targeted monotherapy is unlikely to maintain disease control in RA. Dose reduction strategies and early treatment of disease may be associated with more successful tapering, and warrant future study.
Topics: Humans; Prospective Studies; Biological Products; Arthritis, Rheumatoid; Antirheumatic Agents
PubMed: 37641998
DOI: 10.2174/1573397119666230828160108 -
Frontiers in Pharmacology 2023Janus kinase (JAK) inhibitors are a novel class of drugs that have shown efficacy in treating immune-mediated inflammatory diseases (IMIDs). However, their safety...
Janus kinase (JAK) inhibitors are a novel class of drugs that have shown efficacy in treating immune-mediated inflammatory diseases (IMIDs). However, their safety profile in terms of herpes zoster infection remains unclear. We aimed to evaluate the risk of herpes zoster associated with JAK inhibitors in patients with IMIDs. A systematic search of electronic databases was conducted to identify randomized controlled trials (RCTs) that evaluated the safety of JAK inhibitors in patients with IMIDs including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriasis (PsO), and psoriatic arthritis (PsA). The primary outcome of interest was the incidence of herpes zoster infection. Network meta-analysis was performed to compare the risk of herpes zoster among different JAK inhibitors and placebo. A network meta-analysis was conducted using data from 47 RCTs including 24,142 patients. In patients with IMIDs, peficitinib 100 mg QD was associated with the highest risk of herpes zoster infection in patients with IMIDs, followed by baricitinib 4 mg QD and upadacitinib 30 mg QD. No difference in herpes zoster risk was found for other JAK inhibitors compared with placebo. Subgroup analysis indicated that higher incidence of herpes zoster was found in patients treated by baricitinib 4 mg QD, peficitinib 100 mg QD, and upadacitinib 30 mg QD only in patients with RA. Our study suggests that some JAK inhibitors, particularly peficitinib, baricitinib, and tofacitinib, are associated with a higher risk of herpes zoster infection in patients with IMIDs.
PubMed: 37614317
DOI: 10.3389/fphar.2023.1241954 -
Frontiers in Pharmacology 2023Janus kinase (JAK) inhibitors have emerged as a progressively utilized therapeutic approach for the management of rheumatoid arthritis (RA). However, the complete...
Janus kinase (JAK) inhibitors have emerged as a progressively utilized therapeutic approach for the management of rheumatoid arthritis (RA). However, the complete determination of their cardiovascular safety remains inconclusive. Hence, the primary objective of this network meta-analysis is to meticulously assess and juxtapose the cardiovascular risks linked to distinct JAK inhibitors employed in RA patients. A systematic review and network meta-analysis were meticulously conducted, encompassing a collection of randomized controlled trials (RCTs) that focused on investigating the incidence of major adverse cardiovascular events (MACE) and all-cause mortality associated with Janus kinase (JAK) inhibitors administered to patients with rheumatoid arthritis (RA). Extensive exploration was performed across multiple electronic databases, incorporating studies published until March 2023. To be included in this analysis, the RCTs were required to involve adult participants diagnosed with RA who received treatment with JAK inhibitors. To ensure accuracy, two authors independently undertook the selection of eligible RCTs and meticulously extracted aggregate data. In order to examine the outcomes of MACE and all-cause mortality, a frequentist graph theoretical approach within network meta-analyses was employed, utilizing random-effects models. Third study has been registered on PROSPERO under the reference CRD42022384611. A specific selection encompassing a total of 14 meticulously chosen randomized controlled trials was undertaken, wherein 13,524 patients were assigned randomly to distinct treatment interventions. The analysis revealed no notable disparity in the occurrence of major adverse cardiovascular events (MACE) between the interventions and the placebo group. However, in comparison to adalimumab, the employment of JAK inhibitors exhibited an association with higher rates of all-cause mortality [odds ratio (OR): 1.7, 95% confidence interval (CI): 1.02-2.81]. This observed increase in risk primarily stemmed from the usage of tofacitinib (OR: 1.9, 95% CI: 1.12-3.23). None of the other JAK inhibitors exhibited a statistically significant variance in all-cause mortality when compared to adalimumab. Our study suggests that JAK inhibitors may not increase the risk of MACE in RA patients but may be associated with a higher risk of all-cause mortality compared to adalimumab, primarily due to tofacitinib use. Rheumatologists should carefully consider the cardiovascular risks when prescribing JAK inhibitors, particularly tofacitinib, for RA patients. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=384611, CRD42022384611.
PubMed: 37614310
DOI: 10.3389/fphar.2023.1237234