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The British Journal of Dermatology May 2024Primary endpoint measures in clinical trials are typically measures of disease severity, with patient reported outcome measures (PROMs) relegated as secondary endpoints....
BACKGROUND
Primary endpoint measures in clinical trials are typically measures of disease severity, with patient reported outcome measures (PROMs) relegated as secondary endpoints. However validation of some PROMs may be more rigorous than that of disease severity measures, arguing for a primary role for PROMs.
OBJECTIVES
This study reports on 24 peer reviewed journal articles that used the Dermatology Life Quality Index (DLQI) as primary outcome, derived from a systematic review of randomised controlled trials (RCTs) utlising DLQI covering all diseases and interventions.
MATERIALS AND METHOD
The study protocol was prospectively published on the PROSPERO database, and the study followed PRISMA guidelines. Searches were made with Medline, Cochrane library, EMBASE, Web of Science, SCOPUS, CINAHL(EBSCO) and PsycINFO databases and records combined into an Endnote database. Records were filtered for duplicates and selected by study inclusion/exclusion criteria. Full text articles were sourced and data was extracted by two reviewers into a bespoke REDCap database, with a third reviewer adjudicating differences. The Jadad scoring method was used to determine risk of bias.
RESULTS
Of the 3,220 publications retrieved from online searching, 457 articles met eligibility criteria and included 198,587 patients. DLQI scores were primary outcomes in 24 (5.3%) of these studies comprising 15 different diseases and 3,436 patients. Most study interventions (17/24 studies, 68%) were systemic drugs with biologics (liraglutide, alefacept, secukinumab, ustekinumab, adalimumab) accounting for five out of 25 pharmacological interventions (20%). Topical treaments comprised 32% (8 studies) whereas non-pharmacological interventions (8) were 24% of the total interventions (33). Three studies used non-traditional medicines. Eight studies were multicentred (33.3%), with trials conducted in at least 14 different countries, and four (16.7%) were conducted in multiple countries. The Jadad risk of bias scale showed that bias was uncertain or low, as 87.5% of studies had Jadad scores of ≥3.
CONCLUSIONS
This study provides evidence for use of the DLQI as primary outcome in clinical trials to inform researchers' and clinicians' decisions for its further use.
PubMed: 38819233
DOI: 10.1093/bjd/ljae228 -
Dermatologic Clinics Jul 2024Pediatric psoriasis is a chronic inflammatory skin condition. Current treatment modalities include topical medications, phototherapy, and systemic drugs, including... (Review)
Review
Pediatric psoriasis is a chronic inflammatory skin condition. Current treatment modalities include topical medications, phototherapy, and systemic drugs, including biological agents. In cases of moderate-to-severe psoriasis recalcitrant to other therapies, biological therapies are often an attractive option given their dosing schedules, safety profiles, and need for less frequent laboratory monitoring, when compared with traditional systemic therapies. This article reviews biological treatment options approved for pediatric psoriasis and identifies others actively under investigation.
Topics: Humans; Psoriasis; Child; Adalimumab; Biological Products; Ustekinumab; Dermatologic Agents; Biological Therapy; Infliximab; Antibodies, Monoclonal, Humanized; Etanercept; Antibodies, Monoclonal; Rituximab; Interleukin 1 Receptor Antagonist Protein; Alefacept; Certolizumab Pegol
PubMed: 38796269
DOI: 10.1016/j.det.2024.02.003 -
Skin Research and Technology : Official... Mar 2024The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine,... (Review)
Review
AIMS AND OBJECTIVES
The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions.
METHOD
Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles.
RESULTS
In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%).
CONCLUSION
Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.
Topics: Humans; Methotrexate; Azathioprine; Vitiligo; Mycophenolic Acid; Minocycline; Alefacept; Cyclosporine; Adrenal Cortex Hormones; Hypopigmentation; Simvastatin; Zinc; Purines; Pyrazoles; Sulfonamides; Azetidines; Thalidomide
PubMed: 38454597
DOI: 10.1111/srt.13642 -
JCI Insight Nov 2023Variation in the preservation of β cell function in clinical trials in type 1 diabetes (T1D) has emphasized the need to define biomarkers to predict treatment response....
Variation in the preservation of β cell function in clinical trials in type 1 diabetes (T1D) has emphasized the need to define biomarkers to predict treatment response. The T1DAL trial targeted T cells with alefacept (LFA-3-Ig) and demonstrated C-peptide preservation in approximately 30% of new-onset T1D individuals. We analyzed islet antigen-reactive (IAR) CD4+ T cells in PBMC samples collected prior to treatment from alefacept- and placebo-treated individuals using flow cytometry and single-cell RNA sequencing. IAR CD4+ T cells at baseline had heterogeneous phenotypes. Transcript profiles formed phenotypic clusters of cells along a trajectory based on increasing maturation and activation, and T cell receptor (TCR) chains showed clonal expansion. Notably, the frequency of IAR CD4+ T cells with a memory phenotype and a unique transcript profile (cluster 3) were inversely correlated with C-peptide preservation in alefacept-treated, but not placebo-treated, individuals. Cluster 3 cells had a proinflammatory phenotype characterized by expression of the transcription factor BHLHE40 and the cytokines GM-CSF and TNF-α, and shared TCR chains with effector memory-like clusters. Our results suggest IAR CD4+ T cells as a potential baseline biomarker of response to therapies targeting the CD2 pathway and warrant investigation for other T cell-related therapies.
Topics: Humans; Diabetes Mellitus, Type 1; CD4-Positive T-Lymphocytes; Alefacept; C-Peptide; Leukocytes, Mononuclear; Biomarkers; Receptors, Antigen, T-Cell
PubMed: 37751304
DOI: 10.1172/jci.insight.167881 -
Inflammopharmacology Jun 2023Psoriasis represents an immune-mediated disease with an unclear cause that's marked by inflammation triggered by dysfunction in the immune system, which results in... (Review)
Review
Psoriasis represents an immune-mediated disease with an unclear cause that's marked by inflammation triggered by dysfunction in the immune system, which results in inflammation in various parts of the skin. There could be obvious symptoms, such as elevated plaques; these plaques may appear differently depending on the type of skin. This disease can cause inflammation in the elbows, lower back, scalp, knees, or other regions of the body. It can begin at any age, although it most commonly affects individuals between the ages of 50 and 60. Specific cells (such as T cells) have been observed to play an obvious role in the pathogenesis of psoriasis, in addition to specific immunological molecules such as TNF-, IL-12, IL-23, IL-17, and other molecules that can aid in the pathogenesis of psoriasis. So, during the past two decades, biologists have created chemical drugs that target these cells or molecules and therefore prevent the disease from occurring. Alefacept, efalizumab, Adalimumab, Ustekinumab, and Secukinumab are a few examples of chemical drugs. It was discovered that these chemical drugs have long-term side effects that can cause defects in the patient's body, such as the development of the rare but life-threatening disorder progressive multifocal leukoencephalopathy (PCL). Its rapidly progressive infection of the central nervous system caused by the JC virus and other drugs may cause increased production of neutralising anti-drug antibodies (ADA) and the risk of infusion reactions like pruritus, flushing, hypertension, headache, and rash. So, our context intends to talk in our review about natural products or plants that may have therapeutic characteristics for this disease and may have few or no side effects on the patient's body.
Topics: Humans; Middle Aged; Antibodies, Monoclonal; Psoriasis; Adalimumab; Interleukin-12; Inflammation
PubMed: 36995575
DOI: 10.1007/s10787-023-01178-0 -
Psoriasis (Auckland, N.Z.) 2022The quality of life in psoriatic patients is significantly impaired. Since this century, there have been biologics as a treatment for psoriasis. These biologics reduce... (Review)
Review
BACKGROUND
The quality of life in psoriatic patients is significantly impaired. Since this century, there have been biologics as a treatment for psoriasis. These biologics reduce symptoms, but more knowledge is needed about potential improvements in quality of life. As a result, biological therapy may be more valuable for patients who experience a lot of burden from their chronic skin condition in daily life. The aim of this systematic review was to investigate the possible improvement of the Dermatology Life Quality Index (DLQI) in psoriatic patients using biologics.
MATERIALS AND METHODS
An online search was performed in the PubMed database to identify relevant articles. Inclusion criteria for studies were psoriatic patients, a measurement of DLQI with biologics and without biologics. Exclusion criteria for studies were abstracts not written in English, publications before 2012, full text unavailable, quality of life measurements other than DLQI. Results from the studies with different biologics were combined into the outcome measure: ≥5 points of improvement in the DLQI score. Results of the studies in which biologics were compared with (conventional) systemic therapy were combined in the outcome measure: improvement of the DLQI score is better with biologics than with systemic therapy.
RESULTS
There were nine included articles with a total of 19.926 patients. Adalimumab, alefacept, etanercept, infliximab, ustekinumab and secukinumab were included biologics. Six studies measured the change in DLQI of different biologics in number of points. Of these six studies, 22 sub-analyses were performed and 20 of them showed a DLQI improvement of ≥5 points. The improvement in DLQI was better with biologics than with systemic therapy in two of the three measured studies.
CONCLUSION
Quality of life of psoriatic patients will be improved by the studied biologics. In the future, more research is needed into biologics on patient and quality of life characteristics.
PubMed: 35637943
DOI: 10.2147/PTT.S356568 -
Medicine Mar 2022Given the high disability rate of multiple sclerosis (MS), there is a need for safer and more effective therapeutic agents. Existing literature highlights the prominent...
Given the high disability rate of multiple sclerosis (MS), there is a need for safer and more effective therapeutic agents. Existing literature highlights the prominent roles of miRNA in MS pathophysiology. Nevertheless, there are few studies that have explored the usefulness of existing drugs in treating MS through potential miRNA-modulating abilities.The current investigation identifies genes that may exacerbate the risk of MS due to their respective miRNA associations. These findings were then used to determine potential drug candidates through the construction of miRNA-regulated drug-pathway network through genes. We uncovered a total of 48 MS risk pathways, 133 MS risk miRNAs, and 186 drugs that can affect these pathways. Potential MS risk miRNAs that are also regulated by therapeutic candidates were hsa05215 and hsa05152. We analyzed the properties of the miRNA-regulated drug-pathway network through genes and uncovered a number of novel MS agents by assessing their respective Z-values.A total of 20 likely drug candidates were identified, including human immunoglobulin, aspirin, alemtuzumab, minocycline, abciximab, alefacept, palivizumab, bevacizumab, efalizumab, tositumomab, minocycline, etanercept, catumaxomab, and sarilumab. Each of these agents were then explored with regards to their likely mechanism of action in treating MS.The current investigation provides a fresh perspective on MS biological mechanisms as well as likely treatment strategies.
Topics: Alemtuzumab; Antineoplastic Agents; Drug Repositioning; Humans; MicroRNAs; Multiple Sclerosis
PubMed: 35356949
DOI: 10.1097/MD.0000000000029107 -
Diabetes Technology & Therapeutics Apr 2022Several immunotherapies have shown efficacy in slowing C-peptide decline in new-onset type 1 diabetes. Although most of these biologic drugs are expensive, they offer...
Several immunotherapies have shown efficacy in slowing C-peptide decline in new-onset type 1 diabetes. Although most of these biologic drugs are expensive, they offer the opportunity to reduce downstream disease management costs and risk of complications. The objective of this study is to examine the cost-effectiveness of immunotherapies versus no treatment for patients with new-onset type 1 diabetes. Using Markov microsimulation modeling and efficacy data from immunotherapy trials, we examined the cost-effectiveness of six immunotherapies for new-onset type 1 diabetes, namely, low-dose (2.5 mg/kg) antithymocyte globulin (ATG), high-dose (6.5 mg/kg) ATG, abatacept, alefacept, rituximab, and teplizumab, versus no treatment. Effectiveness was measured by quality-adjusted life-years (QALYs). Costs were estimated from a health system perspective. Low-dose ATG treatment saves US$10,270, on average, over a patient's lifetime and generates 0.09 additional QALYs compared with no treatment. These cost savings arise as low-dose ATG generates downstream savings in disease management costs that more than offset its cost. In contrast, treatment with other immunotherapies yields smaller QALY gains (0.02-0.05 additional QALYs) and increases lifetime costs by US$9500-US$168,380 relative to no treatment, with incremental cost-effectiveness ratios that exceed the willingness-to-pay threshold of US$100,000 per QALY. Low-dose ATG treatment is both less costly and more effective relative to other immunotherapies and no treatment for new-onset type 1 diabetes.
Topics: Antilymphocyte Serum; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Humans; Immunotherapy; Quality-Adjusted Life Years
PubMed: 34704801
DOI: 10.1089/dia.2021.0329 -
Medicine Oct 2021Biological therapy is effective for the treatment of psoriasis and psoriatic arthritis; however, adverse effects related to immunosuppression, such as viral infections,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Biological therapy is effective for the treatment of psoriasis and psoriatic arthritis; however, adverse effects related to immunosuppression, such as viral infections, have been reported. Amongst these infections, herpes zoster (HZ) is common.
OBJECTIVE
To evaluate the risk of HZ in psoriasis and psoriatic arthritis patients treated with biological therapy.
DATA SOURCES
A comprehensive literature search of PubMed, Embase, and Web of Science was performed using certain keywords until October 9, 2020. Nine studies were included after a detailed assessment.
STUDY ELIGIBILITY CRITERIA
The eligibility criteria included randomized controlled trials (RCTs) and observational studies of patients with psoriasis or psoriatic arthritis treated with biological therapies; compared with non-biological therapies, non-biological systemic therapies, or controls; with the incidence of HZ reported in case and control groups. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of the RCTs and observational studies, respectively. Data were extracted from 9 eligible studies and then analyzed using Stata software (Version 12.0).
RESULTS
The risk of HZ in biological therapies was higher than that in non-biological (odds ratios [OR]: 1.48; 95% confidence interval [CI]: 1.18-1.86; I2 = 0%) and non-biological systemic (OR: 1.32; 95% CI: 1.02-1.71; I2 = 0%) therapies. Furthermore, the risk of HZ associated with tumor necrosis factor-α inhibitors increased significantly (OR: 1.50; 95% CI: 1.11-2.02; I2 = 0%). Notably, infliximab (OR: 2.43; 95% CI: 1.31-4.50; I2 = 0%) and etanercept (OR: 1.65; 95% CI: 1.07-2.56; I2 = 0%) increased the risk of HZ, while adalimumab (OR: 1.21; 95% CI: 0.64-2.30; I2 = 0%), ustekinumab (OR: 2.20; 95% CI: 0.89-5.44; I2 = 0%), alefacept (OR: 1.46; 95% CI: 0.20-10.47; I2 = 0%), and efalizumab (OR: 1.58; 95% CI: 0.22-11.34; I2 = 0%) did not.
LIMITATIONS
Few RCTs have reported HZ incidents; thus, our results require confirmation via large-scale RCTs.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
Biological therapies, especially tumor necrosis factor-α inhibitors, may lead to the risk of HZ in psoriasis and psoriatic arthritis patients. Amongst these agents, infliximab and etanercept have been shown to significantly increase the risk of HZ. Additionally, younger age and female sex may be risk factors.
SYSTEMATIC REVIEW REGISTRATION NUMBER
INPLASY202110027.
Topics: Adult; Aged; Antirheumatic Agents; Arthritis, Psoriatic; Biological Factors; Female; Herpes Zoster; Humans; Immunosuppression Therapy; Male; Middle Aged; Observational Studies as Topic; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 34622837
DOI: 10.1097/MD.0000000000027368