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The Journal of Rheumatology Feb 2023Axial involvement in patients with psoriatic arthritis (PsA) is a common subset of this condition, but a unanimous definition has yet to be established. It has been...
OBJECTIVE
Axial involvement in patients with psoriatic arthritis (PsA) is a common subset of this condition, but a unanimous definition has yet to be established. It has been defined by using different criteria, ranging from the presence of at least unilateral grade 2 sacroiliitis to those used for ankylosing spondylitis (AS), or simply the presence of inflammatory low back pain (IBP). Our aim was to identify and evaluate the efficacy of therapeutic interventions for treatment of axial disease in PsA.
METHODS
This systematic review is an update of the axial PsA (axPsA) domain of the treatment recommendations project by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).
RESULTS
The systematic review of the literature showed that new biologic and targeted synthetic disease-modifying antirheumatic drug classes, namely interleukin (IL)-17A and Janus kinase inhibitors, could be considered for the treatment of axPsA. This would be in addition to previously recommended treatments such as nonsteroidal antiinflammatory drugs, physiotherapy, simple analgesia, and tumor necrosis factor inhibitors. Conflicting evidence still remains regarding the use of IL-12/23 and IL-23 inhibitors.
CONCLUSION
Further studies are needed for a better understanding of the treatment of axPsA, as well as validated outcome measures.
Topics: Humans; Arthritis, Psoriatic; Psoriasis; Spondylitis, Ankylosing; Anti-Inflammatory Agents, Non-Steroidal; Interleukin-23; Low Back Pain
PubMed: 36318999
DOI: 10.3899/jrheum.220309 -
Journal of Clinical Medicine Apr 2023Biological disease-modifying anti-rheumatic drugs (bDMARDs) targeting interleukin (IL)-6 and IL-1β represent a steroid-sparing first-line therapy used in systemic-onset...
INTRODUCTION
Biological disease-modifying anti-rheumatic drugs (bDMARDs) targeting interleukin (IL)-6 and IL-1β represent a steroid-sparing first-line therapy used in systemic-onset juvenile idiopathic arthritis (sJIA). Recently, the occurrence of pulmonary alveolar proteinosis (PAP) in sJIA patients was reported with early-onset and exposure to bDMARDs as potential risk factors. We report on a new case with longitudinal immunomonitoring successfully treated by Janus Kinase inhibitors (JAKi) and review past clinical descriptions of this new entity.
METHODS
We report one case of pulmonary alveolar proteinosis and macrophage activation syndrome (PAP-MAS) with longitudinal immunomonitoring. We then conducted a review of the literature of seven publications reporting 107 cases of PAP-MAS sJIA, and included the main characteristics and evolution under treatment.
RESULTS
Of the seven articles analyzed, the incidence of PAP-MAS among sJIA patients varied from 1.28% to 12.9%. We report here a single case among a cohort of 537 sJIA patients followed in the pediatric department of the Hospices Civils de Lyon over the last 15 years. This child presented with all clinical and immunological characteristics of PAP-MAS. After several lines of treatment, he benefited from JAKi and improved with respect to both systemic symptoms and lung disease. In the literature, strategies with monoclonal antibodies targeting either INF-γ or IL-1β/IL-18 have been tested with variable results. Orally taken JAKi presents the advantage of targeting multiple cytokines and avoiding parenteral injections of monoclonal antibodies that may contribute to the pathogenesis.
CONCLUSIONS
JAKi represent a promising option in the treatment of lung disease associated with sJIA.
PubMed: 37048785
DOI: 10.3390/jcm12072702 -
Frontiers in Pharmacology 2022Janus kinase inhibitors (JAK-i), a class of targeted synthetic disease-modifying antirheumatic drugs (tDMARDs), are suggested as second or third-line therapies in...
Janus kinase inhibitors (JAK-i), a class of targeted synthetic disease-modifying antirheumatic drugs (tDMARDs), are suggested as second or third-line therapies in rheumatoid arthritis (RA). Synthesized cost-effective evidence would aid in informed decision-making given the similar clinical effectiveness of JAKi, but incongruent cost-effectiveness reports. Literature search was conducted in PubMed, Embase, Scopus, and Tufts Medical Centers' cost-effective analysis registry. We pooled the incremental net benefit (INB) with 95% confidence interval (CI) using random-effects model and the heterogeneity was assessed using Cochrane-Q test and I2 statistic. Modified economic evaluation bias checklist was used to assess the quality of selected studies. Publication bias was assessed using a funnel plot and Egger's test. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) assessment was performed to assess the certainty of outcomes presented. We included seventeen relevant studies for systematic review, of which fifteen were eligible for meta-analysis. The meta-analysis results showed that JAK-i is cost-effective compared to csDMARDS/bDMARDs with a pooled INB (INBp) of $19,886 (95% CI, 1,635 to 38,137) but with considerable heterogeneity (I2 = 99.14). As a second-line treatment for csDMARD failed RA, JAK-i is cost-effective than csDMARD/bDMARD with a pooled INB of $23,144 (74.1-46,214) and high heterogeneity (I2 = 99.67). But on a separate analysis JAK-i as second-line treatment is not cost-effective than TNF-a-i (INBp = $25,813, -5,714 to 57,340). However, leave-one-out analysis found that omitting a single outlier makes JAK-i cost-effective. Further, JAK-i is not cost-effective as a third-line treatment for csDMARD-TNF-a-I failed RA, compared to csDMARDs/bDMARDs with INBp $26,157 (-7,284 to 59,598). Meta-analysis suggests that JAK-i is cost-effective when used after csDMARD failure but not cost-effective when used after csDMARD-TNF-a-i failure with low certainty of evidence. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021222541, identifier CRD42021222541.
PubMed: 36582538
DOI: 10.3389/fphar.2022.1090361 -
Biomedical Reports May 2024Abrocitinib is a highly selective Janus kinase 1 (JAK1) inhibitor that can block a multitude of inflammatory signaling pathways that underlie atopic dermatitis (AD). In...
Effects of abrocitinib on pruritus and eczema symptoms and tolerance in patients with moderate‑to‑severe atopic dermatitis in randomized, double‑blind and placebo‑controlled trials: A systematic review and a meta‑analysis.
Abrocitinib is a highly selective Janus kinase 1 (JAK1) inhibitor that can block a multitude of inflammatory signaling pathways that underlie atopic dermatitis (AD). In addition, abrocitinib inhibits JAK1 signaling in sensory neurons to alleviate acute and chronic pruritus during AD. However, substantial variations in efficacy and safety risks remain due to variations in doses applied in clinical use. Therefore for the present study, differences in the efficacy and tolerability of 100 and 200 mg abrocitinib for treating pruritus and eczema symptoms in patients with moderate-to-severe AD were evaluated compared with placebo. Specifically, randomized controlled trials (RCTs) of abrocitinib compared with placebo for the treatment of moderate-to-severe AD were searched on Pubmed, E.B. Stephens Company, China National Knowledge Infrastructure, Wanfang Medical network, Web of Science and related Clinical Trials Registry up to November 2023. In total, two researchers evaluated the quality of the included literature according to the Cochrane Handbook of Systematic Reviews. RevMan 5.3 software was used to conduct a meta-analysis of the efficacy and safety indicators in a cross-comparison of the effects exerted by placebo and 100 and 200 mg abrocitinib. A total of 1,825 patients with moderate-to-severe AD were included across five double-blind, placebo RCTs. Compared with the placebo group, during the double-blind trial period, significant improvements were observed in the investigator's global assessment score, response rate of eczema area and severity index (EASI)-50, EASI-75, EASI-90 and pruritus numerical rating scale (P-NRS) in the 100 and 200 mg abrocitinib groups (P<0.05). However, pairwise control analysis of the 100 and 200 mg group yielded significant differences (P<0.05) in all of the aforementioned therapeutic indicators except for the P-NRS score. In terms of safety, compared with the placebo group, there were significantly higher incidence of nausea, upper respiratory tract viral infection, infections and infestations in the 100 mg abrocitinib group (P<0.05). In addition, there were significantly higher incidence of nausea, gastrointestinal disorder, headache and dizziness in the 200 mg group (P<0.05). There were also significant differences in the incidence of nausea, gastrointestinal disorder and dizziness between the 100 and 200 mg groups (P<0.05). For patients with moderate-to-severe AD, oral administration of 100 or 200 mg abrocitinib once/day was concluded to ameliorate skin pruritus and eczema symptoms to varying degrees, with the efficacy significantly superior at the 200 mg dose. However, the risk of a number of adverse reactions, such as headache, dizziness, nausea and gastrointestinal dysfunction, is also significantly increased. Therefore, patients should be made aware of the risk of adverse drug effects prior to the administration of long-term high abrocitinib doses. Furthermore, large-scale, multi-center, rigorous clinical trials remain necessary to validate the findings from the present study.
PubMed: 38628626
DOI: 10.3892/br.2024.1772 -
International Immunopharmacology Oct 2021This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of Janus kinase (JAK) inhibitors... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of Janus kinase (JAK) inhibitors for COVID-19 patients.
METHODS
PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to July 12, 2021. RCTs comparing the clinical efficacy and safety of JAK inhibitors with a placebo or standard care in treating COVID-19 patients were included. The primary outcome was all-cause mortality rate at day 28.
RESULTS
Three RCTs were included in this meta-analysis. The all-cause mortality rate at day 28 was lower among the patients receiving JAK inhibitors than among the controls (4.1% [28/647] versus 7.0% [48/684], OR, 0.57; 95% CI, 0.36-0.92, I = 0). The clinical recovery rate was higher among the patients receiving JAK inhibitors than among the controls (85.1% (579/680) versus 80.0% [547/684], OR, 1.45; 95% CI, 1.09-1.93, I = 0). Additionally, the use of JAK inhibitors was associated with a shorter time to recovery than among the controls (MD, -2.84; 95% CI, -5.56 to -0.12; I = 50%). The rate of invasive mechanical ventilation (MV) was lower in the patients who used JAK inhibitors than among the controls. Finally, no significant difference was observed between the patients who used JAK inhibitors and the controls in the risk of any adverse events (OR, 0.92; 95% CI, 0.64-1.34; I = 33%) and serious adverse events (OR, 0.80; 95% CI, 0.45-1.44; I = 46%).
CONCLUSIONS
JAK inhibitors can lead to a better clinical outcome of hospitalized COVID-19 patients, and they are a safe agent in the treatment of COVID-19.
Topics: Azetidines; Humans; Janus Kinase Inhibitors; Nitriles; Piperidines; Purines; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; SARS-CoV-2; Sulfonamides; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34343937
DOI: 10.1016/j.intimp.2021.108027 -
Journal of Immunology Research 2021To evaluate the effectiveness of Janus kinase (JAK) inhibitors for the treatment of patients with autoimmune disease and associated inflammatory ocular diseases. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the effectiveness of Janus kinase (JAK) inhibitors for the treatment of patients with autoimmune disease and associated inflammatory ocular diseases.
METHODS
We identified relevant literature by screening the MEDLINE, PubMed, and Cochrane databases for randomized controlled trials, cohort studies, case controls, and case reports.
RESULTS
Seven studies, including 11 patients, were included in the final systematic analysis. Of the 11 patients, there were 5 cases of juvenile idiopathic arthritis- (JIA-) associated uveitis, 1 case of rheumatoid arthritis- (RA-) associated keratitis, 1 case of RA-associated scleritis, 1 case of psoriasis-associated conjunctivitis, 2 cases of noninfectious scleritis, and 1 case of uveitis with suspected autoimmune disease. None of these 11 patients responded adequately to conventional treatments, including biological agents; these were all refractory cases and switched to JAK inhibitor therapy. Irrespective of whether they were suffering from uveitis, scleritis, or other types of ocular inflammation, all 11 patients showed an improvement to JAK inhibitors without significant side effects. Different types of JAK inhibitors might be associated with different responses when used to treat ocular inflammation.
CONCLUSIONS
JAK inhibitors may represent an alternative treatment option for patients with autoimmune ocular inflammation.
Topics: Animals; Autoimmune Diseases; Disease Management; Disease Susceptibility; Eye Diseases; Humans; Inflammation; Janus Kinase Inhibitors; Molecular Targeted Therapy; Treatment Outcome
PubMed: 34966823
DOI: 10.1155/2021/2324400 -
Clinical Rheumatology Apr 2022Myasthenia gravis is an autoimmune disease affecting the neuromuscular junction, often associated with other autoimmune diseases, including rheumatoid arthritis.... (Review)
Review
INTRODUCTION
Myasthenia gravis is an autoimmune disease affecting the neuromuscular junction, often associated with other autoimmune diseases, including rheumatoid arthritis. Patients with rheumatoid arthritis present an increased prevalence of myasthenia gravis compared to the general population. While these two diseases share some therapeutic options, such as glucocorticoids, methotrexate, and rituximab, there are no guidelines for treating concomitant disease. We aim to review the available evidence and to discuss the efficacy and safety of the therapeutic options in patients with rheumatoid arthritis associated with myasthenia gravis.
METHOD
We described three patients with rheumatoid arthritis associated with myasthenia gravis and we performed a systematic review of the associated literature.
RESULTS
A 48-year-old man and two women (48 and 55 years old) with concomitant diagnoses of active rheumatoid arthritis and well-controlled myasthenia gravis are described. They were treated with methotrexate, leflunomide, upadacitinib, and adalimumab. None of them experienced changes in their myasthenic symptoms. We found 9 additional cases from our literature review. Methotrexate, rituximab, upadacitinib, diphenyl sulfone, auranofin, and loxoprofen sodium did not show an impact on the seven patients with previously well-controlled myasthenia. Glucocorticoids, methotrexate, and rituximab proved effective in active myasthenia gravis and arthritis. Conflicting data emerged for Tumor-necrosis factor inhibitors.
CONCLUSIONS
Although the available evidence remains scarce, we consider glucocorticoids, methotrexate, and rituximab as safe and effective options. The role of tumor-necrosis factor inhibitors remains uncertain. Eventually, Janus Kinase inhibitors are a novel interesting option for these patients. Key Points • To date, the only evidence on the treatment of patients with rheumatoid arthritis and concomitant myasthenia gravis derives from case reports. • Based on the review of the available case reports and on the cases we described, we consider glucocorticoids, methotrexate, and rituximab as safe and effective options, while the role of Tumor-necrosis factor inhibitors remains uncertain. • Based on the cases we described, Janus Kinase inhibitors are a novel interesting option for patients with concomitant rheumatoid arthritis and myasthenia gravis.
Topics: Adalimumab; Arthritis, Rheumatoid; Female; Humans; Janus Kinase Inhibitors; Male; Methotrexate; Middle Aged; Myasthenia Gravis
PubMed: 35031874
DOI: 10.1007/s10067-022-06062-w -
Annals of the Rheumatic Diseases Jun 2020To perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA).
Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis.
OBJECTIVE
To perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA).
METHODS
This is a systematic literature research of 2015-2018 publications on all DMARDs in patients with PsA, searching Medline, Embase and the Cochrane Library. Efficacy was assessed in randomised controlled trials. For safety, cohort studies, case-control studies and long-term extensions (LTEs) were analysed.
RESULTS
56 publications (efficacy: n=33; safety n=23) were analysed. The articles were on tumour necrosis factor (TNF) inhibitors (n=6; golimumab, etanercept and biosimilars), interleukin (IL)-17A inhibitors (n=10; ixekizumab, secukinumab), IL-23-p19 inhibitors (n=2; guselkumab, risankizumab), clazakizumab (IL-6 inhibitor), abatacept (CD80/86 inhibitor) and ABT-122 (anti-TNF/IL-17A), respectively. One study compared ustekinumab (IL-12/23i) with TNF inhibitor therapy in patients with entheseal disease. Three articles investigated DMARD tapering. Trials on targeted synthetic DMARDs investigated apremilast (phosphodiesterase-4 inhibitor) and Janus kinase inhibitors (JAKi; tofacitinib, filgotinib). Biosimilar comparison with bio-originator showed non-inferiority. Safety was evaluated in 13 LTEs, 9 cohort studies and 1 case-control study investigating malignancies, infections, infusion reactions, multiple sclerosis and major cardiovascular events, as well as efficacy and safety of vaccination. No new safety signals were identified; however, warnings on the risk of venous thromboembolic events including pulmonary embolism when using JAKi were issued by regulators based on other studies.
CONCLUSION
Many drugs in PsA are available and have demonstrated efficacy against placebo. Efficacy varies across PsA manifestations. Safety must also be taken into account. This review informed the development of the European League Against Rheumatism 2019 updated PsA management recommendations.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Biological Products; Humans; Interleukin-17; Interleukin-23 Subunit p19; Molecular Targeted Therapy; Synthetic Drugs; Tumor Necrosis Factor-alpha
PubMed: 32381564
DOI: 10.1136/annrheumdis-2020-217163 -
Expert Review of Anti-infective Therapy Mar 2022Currently, JAK-inhibitors are repurposed for therapy of Covid-19 because of their ability in restraining immune response, yet the corroboration regarding their advantage... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, JAK-inhibitors are repurposed for therapy of Covid-19 because of their ability in restraining immune response, yet the corroboration regarding their advantage is still unclear. This study sought to analyze the efficacy of JAK-inhibitors to ameliorate the outcomes of Covid-19 sufferer. Using specific keywords, we comprehensively go through the potential articles on ClinicalTrials.gov, Europe PMC, and PubMed sources until June 2, 2021. All published studies on JAK-inhibitors and Covid-19 were collected.
RESULTS
There were 14 studies with 4,363 Covid-19 patients contained in the meta-analysis. Based on our data, we suggested that JAK-inhibitors corresponded with increased recovery rate (RR 1.17; 95%CI: 1.01-1.36, = 0.040, = 91%, random-effect modeling); shortened time to recovery (mean difference -0.96; 95%CI: -1.15, -0.77, < 0.00001, = 28%, random-effect modeling); reduction of clinical deterioration risk (RR 0.66; 95%CI: 0.48-0.89, = 0.008, = 57%, random-effect modeling); and reduction of Covid-19 mortality (RR 0.52; 95%CI: 0.36-0.76, = 0.0006, = 33%, random-effect modeling).
CONCLUSIONS
This study propose that JAK-inhibitors perhaps provide advantageous effects on Covid-19 outcomes. JAK-inhibitors may be given during 1-2 weeks of disease to optimize its beneficial effects in halting the exaggerated immune response.
Topics: Europe; Humans; Janus Kinase Inhibitors; Janus Kinases; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34538216
DOI: 10.1080/14787210.2021.1982695 -
Infectious Diseases and Therapy Feb 2022Many immunomodulators have been studied in clinical trials for the treatment of coronavirus disease 2019 (COVID-19). However, data identifying the most effective and...
INTRODUCTION
Many immunomodulators have been studied in clinical trials for the treatment of coronavirus disease 2019 (COVID-19). However, data identifying the most effective and safest treatment are lacking. We conducted a systematic review and network meta-analysis to rank immunomodulators in the treatment of COVID-19 according to their efficacy and safety.
METHODS
Published and peer-reviewed randomized controlled trials assessing the efficacy of immunomodulators in hospitalized patients with COVID-19 were searched up to June 30, 2021. Direct and network meta-analyses were applied to assess the outcomes. The probability of efficacy and safety was estimated, and the drugs were awarded a numerical ranking.
RESULTS
Twenty-six studies were eligible. Compared with standard of care, dexamethasone and tocilizumab had significantly lower mortality rates with pooled risk ratios (RRs) of 0.91 (95% confidence interval [CI] 0.84-0.99) and 0.88 (95% CI 0.82-0.96), respectively. Meanwhile, the most effective corticosteroid, interleukin-6 antagonist, and Janus kinase (JAK) inhibitor were hydrocortisone, sarilumab, and ruxolitinib, respectively. However, when superimposed infection was considered, ruxolitinib was the best treatment followed by baricitinib. Moreover, methylprednisolone had the worst combined efficacy and safety among the examined treatments.
CONCLUSIONS
Overall, immunomodulators were more effective than standard of care. Important differences exist among immunomodulators regarding both efficacy and safety in favor of ruxolitinib and baricitinib. Further well-conducted randomized controlled trials should focus on JAK inhibitors. Methylprednisolone use should be discouraged because of its poor efficacy and high risk of superimposed infection. TRIAL REGISTRATION: PROSPERO registration identifier CRD 42021257421.
PubMed: 34757578
DOI: 10.1007/s40121-021-00545-0