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Clinical and Experimental Rheumatology Sep 2023Abatacept (Orencia) is a drug used to treat patients with rheumatoid arthritis. The agent improves patients' pain and joint inflammation through modulation of a... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Abatacept (Orencia) is a drug used to treat patients with rheumatoid arthritis. The agent improves patients' pain and joint inflammation through modulation of a co-stimulatory signal necessary for T cell activation. We aimed to analyse the efficacy and safety of abatacept in the management of rheumatoid arthritis using the Cochrane systematic review.
METHODS
We conducted a systematic search among PubMed, Cochrane central register of controlled trials, Web of Science, and Embase databases from the establishment of these databases to April 2022. The effectiveness and safety of abatacept in treating rheumatoid arthritis were assessed in terms of American College of Rheumatology (ACR) 20/50/70/90 responses, Disease Activity Score-28 for Rheumatoid Arthritis with C-reactive protein (DAS-28-CRP), and adverse events. The Relative Risks (RRs) of relative safety and efficacy and their corresponding 95 confidence intervals (CIs) were used to compute the pooled assessments of the outcomes. We used the review manager software version 5.4 to analyse our data, and the PRISMA checklist 2020 was used to ensure that our work conforms with the specification of meta-analysis.
RESULTS
Our study included 13 randomised control trials with a total of 5978 adult patients from different geographic regions and races. Following the combined analysis of these enrolled studies, the RRs for ACR 20/50/70/90 responses were 1.57 [95%CI 1.27, 1.93], 1.84 [95%CI 1.38, 2.44], 2.36 [95%CI 1.60, 3.47], and 2.95 [95%CI 1.88, 4.63], respectively. Such findings suggest that abatacept-treated patients were 1.57, 1.84, 2.36, and 2.95 times more likely to achieve ACR 20/50/70/90 responses, respectively, than those treated with placebo, conventional synthetic disease-modifying antirheumatic drugs, and or other biologic disease-modifying anti-rheumatic drugs. An exclusive comparison of abatacept and other biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) indicated that participants who were treated with abatacept could achieve better ACR responses than those treated with other b/tsDMARDs. Adverse events were less seen in abatacept-treated patients than in those who were given other b/tsDMARDs.
CONCLUSIONS
This meta-analysis concludes that in adult with rheumatoid arthritis, abatacept can achieve better health outcomes than other biologic drugs.
Topics: Adult; Humans; Abatacept; Methotrexate; Arthritis, Rheumatoid; Antirheumatic Agents; Biological Products; Randomized Controlled Trials as Topic
PubMed: 36912326
DOI: 10.55563/clinexprheumatol/2xjg0d -
Advances in Therapy Feb 2024Immune-mediated inflammatory diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial... (Review)
Review
Safety of Upadacitinib in Immune-Mediated Inflammatory Diseases: Systematic Literature Review of Indirect and Direct Treatment Comparisons of Randomized Controlled Trials.
INTRODUCTION
Immune-mediated inflammatory diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondylarthritis (nr-axSpA), atopic dermatitis (AD), ulcerative colitis (UC), and Crohn's disease (CD) pose a substantial burden on patients and their quality of life. Upadacitinib is an orally administered, selective, and reversible Janus kinase inhibitor indicated for seven conditions, but data on its safety versus other active treatments are limited. A systematic literature review of indirect and direct treatment comparisons of randomized controlled trials (RCTs) was conducted to assess the safety profile of upadacitinib.
METHODS
MEDLINE, Embase, and Cochrane Library databases were searched for indirect and direct treatment comparisons of RCTs that (1) included licensed upadacitinib dosages; (2) studied any of the seven conditions; (3) reported any adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, major adverse cardiovascular event, venous thromboembolism, malignancies, infections or serious infections, and death; and (4) were published between January 2018 and August 2022.
RESULTS
A total of 25 studies were eligible for inclusion. SAEs, AEs leading to discontinuation, and any AEs were commonly studied. RA was the most studied condition, followed by AD and UC. Most studies (16/25, 64%) reported no statistically significant difference in the studied safety outcomes between upadacitinib and other active treatments (e.g., tumor necrosis factor blockers, interleukin receptor antagonists, integrin receptor antagonists, T cell co-stimulation modulator), or placebo (placebo ± methotrexate or topical corticosteroids). Other studies (9/25, 36%) reported mixed results of no statistically significant difference and either statistically higher (8/25, 32%) or lower rates (1/25, 4%) on upadacitinib.
CONCLUSION
Most studies suggested that upadacitinib has no statistically significant difference in the studied safety outcomes compared to active treatments or placebo in patients with RA, PsA, AS, AD, UC, and CD. A few studies reported higher rates, but findings were inconsistent with limited interpretation.
Topics: Humans; Arthritis, Psoriatic; Arthritis, Rheumatoid; Colitis, Ulcerative; Heterocyclic Compounds, 3-Ring; Methotrexate; Randomized Controlled Trials as Topic; Spondylitis, Ankylosing
PubMed: 38169057
DOI: 10.1007/s12325-023-02732-6 -
A Systematic Review and Bayesian Network Meta-Analysis of Medical Therapies for Lichen Planopilaris.Dermatology (Basel, Switzerland) 2024Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia. Unfortunately, current available treatments are not fully effective to stop hair loss, and the level of evidence for medical interventions is weak.
OBJECTIVES
The present article aimed to determine the efficacy of the different medical interventions in LPP through a network meta-analysis (NMA).
METHODS
A systematic review and meta-analysis were performed including randomized trials that report the outcomes of lichen planopilaris activity index (LPPAI). These articles were pooled and a NMA was conducted.
RESULTS
A total of seven studies were identified and included in meta-analysis, comprising 251 LPP patients. The NMA showed the mean difference in LLPAI was significantly superior with the combination of clobetasol plus N-acetylcysteine (mean difference: -2.0, 95% CI = -3.43 to -0.51) and the combination of clobetasol plus pentoxifylline (mean difference: -1.62, 95% CI = -3.0 to -0.25) compared to the treatment of reference (clobetasol). The NMA showed cyclosporine (mean difference: 2.05 95% CI = 0.68-3.49), methotrexate (mean difference: 1.95 95% CI = 1.23-3.17), the combination of methotrexate plus prednisolone (mean difference: 1.56 95% CI = 0.25-2.96) were significantly worse than hydroxychloroquine according to the differences in LLPAI.
CONCLUSION
This work is the first NMA in LPP and hence, it can be helpful in serving as an initial step toward better evidence-based decisions in the treatment of this challenging condition. We propose a triple-combined approach consisting of topical clobetasol, hydroxychloroquine, and N-acetylcysteine as resulted in the most effective approach. Considering the poor outcomes observed with pioglitazone, mycophenolate mofetil, and cyclosporine, it is advisable to contemplate the use of these medications in patients who have not responded adequately to more efficacious alternatives.
Topics: Humans; Clobetasol; Methotrexate; Network Meta-Analysis; Acetylcysteine; Bayes Theorem; Hydroxychloroquine; Lichen Planus; Cyclosporine; Alopecia; Chronic Disease
PubMed: 37852211
DOI: 10.1159/000534364 -
Cutaneous Rosai-Dorfman disease: a systematic review and reappraisal of its treatment and prognosis.Archives of Dermatological Research Jun 2024Cutaneous Rosai Dorfman disease (CRDD) is a rare histiocytic disorder that shows distinctive clinical presentation and prognosis. Sufficient data is currently lacking... (Review)
Review
Cutaneous Rosai Dorfman disease (CRDD) is a rare histiocytic disorder that shows distinctive clinical presentation and prognosis. Sufficient data is currently lacking regarding evidence-based management of CRDD. This systematic review aims to provide a comprehensive overview of CRDD, focusing on treatment approaches and outcomes. PubMed and Scopus databases were searched for studies on CRDD from June 1st, 2013 to May 31st, 2023. Articles describing cases of CRDD confirmed with histological examination were eligible for inclusion. All interventions for CRDD were analyzed. The primary outcome measure was the response of cutaneous lesions to treatment including complete response (CR), partial response (PR), and no response. The secondary outcome measures were mortality rate, relapse rate, and the occurrence of adverse events related to CRDD treatment. Eighty-seven articles describing 118 CRDD cases were included. The mean age was 48.2±16.8 years. The sex ratio (F/M) was 1.53. Nodular (46.6%) erythematous (45.3%) lesions, located on the face (38.1%) were the most prevalent presentations. Associated hematological malignancies were noted in 8 (6.8%) cases. Surgical excision was the most prevalent intervention (51 cases) with CR in 48 cases. Systemic corticosteroids were used in 32 cases with 20 CR/PR, retinoids in 10 cases with 4 CR/PR, thalidomide in 9 cases with 5 CR/PR, methotrexate in 8 cases with 7 CR/PR while observation was decided in 10 cases with 6 CR/PR. Factors independently associated with the absence of response to treatment were facial involvement (OR = 0.76, p = 0.014), and cutaneous lesion size (OR = 1.016, p = 0.03). This systematic review shows distinctive clinical characteristics of CRDD and provides insights into the appropriate management of the disease. It allowed a proposal of a treatment algorithm that should be interpreted in the context of current evidence and would help practitioners in treating this rare disease.
Topics: Humans; Histiocytosis, Sinus; Prognosis; Treatment Outcome; Female; Skin; Male; Middle Aged; Adrenal Cortex Hormones; Retinoids; Skin Diseases; Methotrexate; Adult
PubMed: 38878198
DOI: 10.1007/s00403-024-02982-6 -
World Neurosurgery Nov 2023Methotrexate is an immunosuppressant commonly used to treat inflammatory conditions, such as rheumatoid arthritis. However, albeit exceedingly rare, it can have serious... (Review)
Review
BACKGROUND
Methotrexate is an immunosuppressant commonly used to treat inflammatory conditions, such as rheumatoid arthritis. However, albeit exceedingly rare, it can have serious adverse effects within the central nervous system (CNS), such as methotrexate-associated lymphoproliferative disorder (MTX-LPD). Literature describing the natural history, treatment options, and clinical outcomes of patients with CNS MTX-LPD remains sparse.
METHODS
We present a systematic literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and a case illustration of CNS MTX-LPD.
RESULTS
A systematic review of the literature revealed 12 published cases of CNS MTX-LPD, plus the case presented herein, for a total of 13 included cases. The most common indication for MTX was rheumatoid arthritis. The most common treatment for the LPD was MTX cessation (12, 92.3%), adjunct chemotherapy (2, 15.4%), total tumor resection (3, 23.1%), or steroid therapy (1, 7.7%). Treatment usually led to improvement of neurological symptoms (9, 69.2%) along with regression of the lesions (3, 23.1%) with no recurrence (6, 46.2%). Death was reported in four cases (30.8%) with a mean time from onset of 11 months.
CONCLUSIONS
CNS MTX-LPD should be considered in the differential diagnosis for patients who are taking MTX presenting with neurologic symptoms, as immediate withdrawal of MTX has demonstrated good prognosis.
Topics: Humans; Methotrexate; Arthritis, Rheumatoid; Immunosuppressive Agents; Lymphoproliferative Disorders; Central Nervous System Diseases; Central Nervous System
PubMed: 37574195
DOI: 10.1016/j.wneu.2023.08.018 -
Journal of Lower Genital Tract Disease Jan 2024Lichen sclerosus (LS) is a chronic, inflammatory process affecting predominantly anogenital skin, with extragenital involvement in up to 20% of cases. The mainstay of...
BACKGROUND
Lichen sclerosus (LS) is a chronic, inflammatory process affecting predominantly anogenital skin, with extragenital involvement in up to 20% of cases. The mainstay of therapy for anogenital LS is topical immunosuppression. However, in treatment-refractory cases, severe, or hypertrophic disease, systemic modalities may be used. Currently, there are no guidelines for systemic therapy in LS.
OBJECTIVE
This study aimed to provide a review of the current literature on use of systemic therapies for LS, including demographic and clinical features of LS, as well as reported outcomes.
METHODS
A primary literature search was conducted using the following databases: PubMed, Ovid, Scopus, and Web of Science, from the year the journal was published until June 2022.
RESULTS
Ultimately, 71 studies consisting of 392 patients were included. Of these, 65% (n = 254) had anogenital disease, 9% (n = 36) had extragenital disease, and 19% (n = 73) had both anogenital and extragenital disease, and in 7% (n = 29) of cases, location was not specified. The most frequent therapies, stratified by total cases, included oral retinoids (n = 227), methotrexate (n = 59), hydroxychloroquine (n = 36), and systemic steroids (prednisone, methylprednisolone, prednisolone, oral triamcinolone, and other systemic steroids) (n = 60). Overall, 76% (n = 194) of anogenital, 94% (n = 34) of extragenital, and 81% (n = 59) of patients with both anogenital and extragenital involvement were reported to have clinical or symptomatic improvement.
CONCLUSION
Overall, we found many therapies that have been used with reported success for extragenital and genital LS. However, future studies are needed to better define treatment outcomes and directly compare efficacy of different therapies for LS.
Topics: Humans; Lichen Sclerosus et Atrophicus; Methotrexate; Treatment Outcome; Skin; Steroids
PubMed: 37924260
DOI: 10.1097/LGT.0000000000000775 -
Musculoskeletal Care Dec 2023Patient education (PE) is a key role of nurses, which includes providing information, training, and support about methotrexate (MTX), an anchor drug in rheumatology.... (Review)
Review
INTRODUCTION
Patient education (PE) is a key role of nurses, which includes providing information, training, and support about methotrexate (MTX), an anchor drug in rheumatology. However, there is a wide variation in the access to rheumatology nurse consultations in Europe, and there is a lack of consensus regarding the delivery, context and timing of PE in these cases. This study aimed to provide a comprehensive overview of the existing research on nurse education of MTX for children/youth and adults with Rheumatic and Musculoskeletal Diseases (RMDs).
METHODS
This scoping review was conducted in accordance with Arksey and O'Malley's framework. A search on PubMed (MEDLINE), Scopus and Cochrane Database, and CINAHL, from inception until March 2022 was conducted. Articles on PE with a focus on MTX exclusively were included. Published and unpublished studies, from any world region, conducted with a qualitative, quantitative, or mixed-methods design and focused on defined research questions, were eligible for inclusion. Broad inclusion criteria were used if a research paper on PE focused on MTX for people with RMDs (PE or patient engagement, self-management, medication knowledge, or health literacy in patients). The reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Extension for Scoping Reviews (PRISMA-ScR) checklist. Two independent reviewers performed standardized data extraction and synthesis.
RESULTS
From 292 references identified, the total number of studies which met the inclusion criteria was relatively small (n = 14). The results identified that knowledge of MTX improves when education by nurses is provided.
CONCLUSION
This scoping review showed that there is no universal worldwide strategy for MTX education of children/youths and adults with RMDs. However, PE regarding MTX can be delivered in different forms, resulting in better satisfaction and adherence. More randomized controlled trials with powered samples are required.
Topics: Adult; Child; Humans; Adolescent; Methotrexate; Consensus; Musculoskeletal Diseases; Education, Nursing; Europe
PubMed: 37587575
DOI: 10.1002/msc.1804 -
European Journal of Clinical... Jul 2024Methotrexate is widely utilized in the chemotherapy of malignant tumors and autoimmune diseases in the pediatric population, but dosing can be challenging. Several... (Review)
Review
BACKGROUND AND OBJECTIVES
Methotrexate is widely utilized in the chemotherapy of malignant tumors and autoimmune diseases in the pediatric population, but dosing can be challenging. Several population pharmacokinetic models were developed to characterize factors influencing variability and improve individualization of dosing regimens. However, significant covariates included varied across studies. The primary objective of this review was to summarize and discuss population pharmacokinetic models of methotrexate and covariates that influence pharmacokinetic variability in pediatric patients.
METHODS
Systematic searches were conducted in the PubMed and EMBASE databases from inception to 7 July 2023. Reporting Quality was evaluated based on a checklist with 31 items. The characteristics of studies and information for model construction and validation were extracted, summarized, and discussed.
RESULTS
Eighteen studies (four prospective studies and fourteen retrospective studies with sample sizes of 14 to 772 patients and 2.7 to 93.1 samples per patient) were included in this study. Two-compartment models were the commonly used structural models for methotrexate, and the clearance range of methotrexate ranged from 2.32 to 19.03 L/h (median: 6.86 L/h). Body size and renal function were found to significantly affect the clearance of methotrexate for pediatric patients. There were limited reports on the role of other covariates, such as gene polymorphisms and co-medications, in the pharmacokinetic parameters of methotrexate pediatric patients. Internal and external evaluations were used to assess the performance of the population pharmacokinetic models.
CONCLUSION
A more rigorous external evaluation needs to be performed before routine clinical use to select the appropriate PopPK model. Further research is necessary to incorporate larger cohorts or pool analyses in specific susceptible pediatric populations to improve the understanding of predicted exposure profiles and covariate identification.
Topics: Methotrexate; Humans; Child; Models, Biological; Antimetabolites, Antineoplastic; Adolescent; Neoplasms
PubMed: 38498098
DOI: 10.1007/s00228-024-03665-x -
European Journal of Clinical... Jan 2024To develop a population pharmacokinetic (PPK) model for methotrexate (MTX) dosage for all ages, assess the association between concentration and clearance, and determine... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To develop a population pharmacokinetic (PPK) model for methotrexate (MTX) dosage for all ages, assess the association between concentration and clearance, and determine covariates affecting MTX disposition.
METHODS
We compared MTX PK profiles among neonates, children, and adults by performing a systematic literature search for published population MTX models and conducted a Monte Carlo-based meta-analysis. Subsequently, we evaluated study quality and covariates significantly affecting dosage regimens and compared LDMTX and HDMTX PK profiles.
RESULTS
Of the total 40 studies included, 34 were HDMTX, and six were LDMTX studies. For HDMTX, three studies involving neonates reported estimated apparent clearances (median, range) of 0.53 (0.27-0.77) L/kg/h; for 14 studies involving children, 0.23 (0.07-0.23) L/kg/h; and for 13 involving adults, 0.11 (0.03-0.22) L/kg/h. Neonates had a higher volume of distribution than children and adults. For LDMTX studies, apparent clearance was 0.085 (0.05-1.68) L/kg/h, and volume of distribution was 0.25 (0.018-0.47) L/kg, lower than those of HDMTX studies, with large between-subject variability. Bodyweight significantly influenced apparent clearance and volume of distribution, whereas renal function mainly influenced clearance. Mutations in certain genes reduced MTX clearance by 8-35.3%, whereas those in others increased it by 15-48%. Body surface area (BSA) significantly influenced apparent clearance with a median reduction of 51% when BSA increased in pediatric patients.
CONCLUSIONS
Methotrexate dosage regimens were primarily based on body surface area and renal function. Further studies are needed to evaluate MTX pharmacokinetics and pharmacodynamics in both children (especially infants) and adults.
Topics: Adult; Infant; Infant, Newborn; Humans; Child; Methotrexate; Antimetabolites, Antineoplastic
PubMed: 37934204
DOI: 10.1007/s00228-023-03579-0 -
Biological Research For Nursing Jan 2024To retrospectively analyze the effects of different treatments on cognitive functioning, anxiety, and depression in patients with primary central nervous system lymphoma...
OBJECTIVE
To retrospectively analyze the effects of different treatments on cognitive functioning, anxiety, and depression in patients with primary central nervous system lymphoma (PCNSL).
METHODS
A comprehensive literature search was conducted in multiple databases including the Cochrane Library, CINAHL, PubMed, Web of Science, EMBASE, Sino Med, Wei Pu, Wan Fang, CNKI, and Google Scholar. The search included studies published through June 20, 2023, focusing on cognitive function, anxiety, and depression in adult patients newly diagnosed with PCNSL. Various measurement tools and scales were used to assess the primary outcomes. Descriptive systematic reviews were conducted to integrate the literature and summarize the effects of different treatment modalities on cognitive functioning, anxiety, and depression in PCNSL patients. This review was registered with PROSPERO (CRD42022370250).
RESULTS
A total of 43 studies were included. Induction chemotherapy was associated with improved cognitive function and reduced anxiety and depression in the majority of patients. Whole-brain radiotherapy (WBRT) was found to lead to cognitive impairment, particularly in executive, attention, memory, and motor function. Low-dose WBRT, autologous stem cell transplantation (ASCT), and blood-brain barrier disruption (BBBD) treatments did not result in significant cognitive impairment. Anxiety and depression were observed to decrease over the long term.
CONCLUSIONS
Overall, the cognitive functioning, anxiety, and depression of patients with PCNSL can be improved with appropriate treatments. However, patients treated with WBRT are at a higher risk of cognitive decline compared to those receiving other treatment modalities. Therefore, special attention should be given to patients undergoing WBRT, and a comprehensive analysis should be conducted to reduce neurotoxicity and address early cognitive problems in these patients.
Topics: Adult; Humans; Hematopoietic Stem Cell Transplantation; Combined Modality Therapy; Retrospective Studies; Transplantation, Autologous; Cognition; Brain; Anxiety; Lymphoma; Antineoplastic Combined Chemotherapy Protocols; Methotrexate
PubMed: 37540088
DOI: 10.1177/10998004231190073