Biologics : Targets & Therapy最新文献

{"title":"<i>TNFSF13B</i> rs9514828 C>T Polymorphism is Associated with Incidence of Atherosclerosis and Therapeutic Outcomes in Patients with Systemic Lupus Erythematosus.","authors":"Desi Reski Fajar, Tina Rostinawati, Laniyati Hamijoyo, Edhyana Sahiratmadja, Riezki Amalia, Melisa Intan Barliana","doi":"10.2147/BTT.S452792","DOIUrl":"10.2147/BTT.S452792","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is a complex autoimmune disease with numerous clinical manifestations. Organ involvement can aggravate patients with SLE and cause comorbidities such as atherosclerosis. Recently, the <i>TNFSF13B</i> gene has been found to be linked with SLE events. This study aimed to analyze the association between single nucleotide polymorphisms of the <i>TNFSF13B</i> rs9514828 with incidence of atherosclerosis and therapeutic outcomes in patients with SLE.</p><p><strong>Patients and methods: </strong>This case-control study included 84 SLE patients, of whom 21 patients with SLE with atherosclerosis and 63 patients with SLE without atherosclerosis. Using enzyme-linked immunosorbent assay method, interleukin-6 and interferon gamma levels were quantified. The <i>TNFSF13B</i> gene polymorphism was evaluated using polymerase chain reaction followed by sequencing. The lupus low disease activity state (LLDAS) criteria were used to measure the therapeutic outcomes. Statistical analysis was conducted using binary logistic regression.</p><p><strong>Results: </strong>The genetic variations of <i>TNFSF13B</i> rs9514828 were CC = 35, CT = 41, and TT = 8. There was an association between <i>TNFSF13B</i> rs9514828 C>T polymorphism in patients with SLE with and without atherosclerosis (p = 0.03; odds ratio (OR) 4.72, 95% confidence interval [CI] 1.22-18.37). Furthermore, the <i>TNFSF13B</i> rs9514828 C>T polymorphism had association with the therapeutic outcomes of patients with SLE who manifested with LLDAS (p = 0.00; OR 7.58, 95% CI 2.61-21.99).</p><p><strong>Conclusion: </strong>The association of <i>TNFSF13B</i> rs9514828 C>T polymorphism and incidence of atherosclerosis as well as the therapeutic outcomes in patients with SLE indicate the potential utility of the gene variation as screening tool to employ personalized medicine to undertake preventive measures in order to prevent atherosclerosis and to predict a poor prognosis in SLE patient.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"18 ","pages":"95-106"},"PeriodicalIF":4.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MDMX in Cancer: A Partner of p53 and a p53-Independent Effector.","authors":"Wu Lin, Yuxiang Yan, Qingling Huang, Dali Zheng","doi":"10.2147/BTT.S436629","DOIUrl":"10.2147/BTT.S436629","url":null,"abstract":"<p><p>The p53 tumor suppressor protein plays an important role in physiological and pathological processes. MDM2 and its homolog MDMX are the most important negative regulators of p53. Many studies have shown that MDMX promotes the growth of cancer cells by influencing the regulation of the downstream target gene of tumor suppressor p53. Studies have found that inhibiting the MDMX-p53 interaction can effectively restore the tumor suppressor activity of p53. MDMX has growth-promoting activities without p53 or in the presence of mutant p53. Therefore, it is extremely important to study the function of MDMX in tumorigenesis, progression and prognosis. This article mainly reviews the current research progress and mechanism on MDMX function, summarizes known MDMX inhibitors and provides new ideas for the development of more specific and effective MDMX inhibitors for cancer treatment.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"18 ","pages":"61-78"},"PeriodicalIF":4.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10839028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advancements in Reducing the Off-Target Effect of CRISPR-Cas9 Genome Editing.","authors":"Misganaw Asmamaw Mengstie, Muluken Teshome Azezew, Tadesse Asmamaw Dejenie, Assefa Agegnehu Teshome, Fitalew Tadele Admasu, Awgichew Behaile Teklemariam, Anemut Tilahun Mulu, Melaku Mekonnen Agidew, Dagnew Getnet Adugna, Habtamu Geremew, Endeshaw Chekol Abebe","doi":"10.2147/BTT.S429411","DOIUrl":"10.2147/BTT.S429411","url":null,"abstract":"<p><p>The CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)) and the associated protein (Cas9) system, a young but well-studied genome-editing tool, holds plausible solutions to a wide range of genetic disorders. The single-guide RNA (sgRNA) with a 20-base user-defined spacer sequence and the Cas9 endonuclease form the core of the CRISPR-Cas9 system. This sgRNA can direct the Cas9 nuclease to any genomic region that includes a protospacer adjacent motif (PAM) just downstream and matches the spacer sequence. The current challenge in the clinical applications of CRISPR-Cas9 genome-editing technology is the potential off-target effects that can cause DNA cleavage at the incorrect sites. Off-target genome editing confuses and diminishes the therapeutic potential of CRISPR-Cas9 in addition to potentially casting doubt on scientific findings regarding the activities of genes. In this review, we summarize the recent technological advancements in reducing the off-target effect of CRISPR-Cas9 genome editing.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"18 ","pages":"21-28"},"PeriodicalIF":5.3,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of N-Acetylcysteine on Cisplatin Toxicity: A Review of the Literature.","authors":"Angeles Citlali Zavala-Valencia, Liliana Velasco-Hidalgo, Armando Martínez-Avalos, Manuel Castillejos-López, Luz-María Torres-Espíndola","doi":"10.2147/BTT.S438150","DOIUrl":"10.2147/BTT.S438150","url":null,"abstract":"<p><p>N-acetylcysteine (NAC) is a membrane-permeable cysteine precursor capable of enhancing the intracellular cysteine pool, enhancing cellular glutathione (GSH) synthesis, and thus potentiating the endogenous antioxidant mechanism. Late administration of NAC after cisplatin has been shown in different in vivo studies to reduce the side effects caused by various toxicities at different levels without affecting the antitumor efficacy of platinum, improving total and enzymatic antioxidant capacity and decreasing oxidative stress markers. These characteristics provide NAC with a rationale as a potentially effective chemo protectant in cisplatin-based therapeutic cycles. NAC represents a potential candidate as a chemoprotective agent to decrease toxicities secondary to cisplatin treatment. It suggests that it could be used in clinical trials, whereby the effective dose, timing, and route should be adjusted to optimize chemoprotection. This review provides an overview of the effect of NAC on cisplatin toxicity, a drug widely used in the clinic in adults and children.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"18 ","pages":"7-19"},"PeriodicalIF":4.0,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10799624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful Response to Golimumab in a Case of Relapsing Polychondritis Overlapping with Ulcerative Colitis.","authors":"Shu Kojima, Satohiro Matsumoto, Yudai Koito, Takaya Miura, Masanari Sekine, Takeshi Uehara, Takeharu Asano, Yasuhiro Yamaguchi, Hirosato Mashima","doi":"10.2147/BTT.S436301","DOIUrl":"10.2147/BTT.S436301","url":null,"abstract":"<p><p>A 51-year-old Japanese man was diagnosed with left-sided ulcerative colitis (UC) at age 41. He was treated with mesalazine and azathioprine and maintained remission. At age 51, the patient developed bloody stools, abdominal pain, scleritis, arthritis, cough, bloody sputum, and pericardial effusion. Considering that pericardial effusion is an atypical extraintestinal complication of UC, and the patient met the diagnostic criteria for relapsing polychondritis (RP), a diagnosis of RP complicating a relapse of UC was made. Steroid therapy was administered, and both diseases improved. Golimumab, an anti-tumor necrosis factor-α inhibitor, was introduced as maintenance therapy for UC. All symptoms, including pericardial effusion, improved. Subsequently, no relapse of UC or RP was observed. As only a few cases of RP overlapping with UC have been reported and no treatment protocol has been established, we considered this case valuable and worthy of publication.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"18 ","pages":"1-6"},"PeriodicalIF":4.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia Inducible Factor-1α Through ROS/NLRP3 Pathway Regulates the Mechanism of Acute Ischemic Stroke Microglia Scorching Mechanism.","authors":"Xin Ma, Junxia Jiao, Mayila Aierken, Hong Sun, Li Chen","doi":"10.2147/BTT.S444714","DOIUrl":"https://doi.org/10.2147/BTT.S444714","url":null,"abstract":"<p><strong>Purpose: </strong>In vitro experiments explored how the hypoxia-induced factor-1α (HIF-1α) regulates the regulation of pyroptosis in microglial cells (BV 2) in acute ischemic stroke through ROS/NLRP3 pathway.</p><p><strong>Methods: </strong>The microglia acute phase oxygen-glucose deprivation/reoxygenation (OGD/R) was established, CCK-8 was applied to determine the optimal timing of intervention modeling. HIF-1α was overexpressed with stabilizer GF-4592 and HIF-1α small molecule interfering RNA (HIF-1α-siRNA), which was divided into group A (blank group), group B (OGD/R model group), group C (model+FG-4592 intervention group), group D (model+siRNA negative control group) and group E (model+HIF-1α-siRNA group). Cell proliferation of different groups was measured by CCK-8 assay. Pyroptosis and intracellular ROS levels were measured by flow cell technology. IL-18, IL-1β levels were measured by ELISA. HIF-1α, GSDMD-D, GSDMD-N, clean-Caspase-1 and NLRP3 protein expression levels were measured by Western blot. On the above experiments, ROS and NLRP3 response experiments were performed to explore how HIF-1α regulates pyroptosis through ROS/NLRP3 pathway.</p><p><strong>Results: </strong>Hypoxia for 6 h then reoxygenation for 12 h was the optimal intervention time. Compared with groups B and D, cell proliferation in group C was significantly enhanced, pyroptosis, intracellular levels of ROS, IL-18, IL-1β and the expression of GSDMD-D, GSDMD-N, clean-Caspase-1, and NLRP3 proteins were significantly decreased in group C (<i>P</i> < 0.05). However, in group E, the performance of these test indicators were exactly the opposite, and the difference was statistically significant (<i>P</i> < 0.05). Through ROS and NLRP3 response experiments, it was found that HIF-1α Inhibition of Pyroptosis by inhibiting ROS/NLRP3 pathway.</p><p><strong>Conclusion: </strong>Overexpression of HIF-1α factor can inhibit microglia pyroptosis. HIF-1α factor has an inhibitory effect on the ROS/NLRP 3 pathway, which can inhibit the pyroptotic process in microglia.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"167-180"},"PeriodicalIF":4.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10748736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Two Years of Secukinumab Treatment on Bone Metabolism in Patients with Radiographic Axial Spondyloarthritis: Results from Daily Clinical Practice.","authors":"Mark Siderius, Stan C Kieskamp, Freke Wink, Frans G M Kroese, Suzanne Arends, Anneke Spoorenberg","doi":"10.2147/BTT.S434318","DOIUrl":"10.2147/BTT.S434318","url":null,"abstract":"<p><strong>Background: </strong>Our objective was to explore bone-related outcome and bone turnover markers (BTM) during 2 years of secukinumab treatment in patients with radiographic axial spondyloarthritis (r-axSpA) in daily clinical practice.</p><p><strong>Methods: </strong>Included were consecutive r-axSpA outpatients from the Groningen Leeuwarden axSpA (GLAS) cohort treated with secukinumab for 2 years. At baseline and 2 years, spinal radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS; 0-72), cervical facet joint involvement according the \"de Vlam\" scoring method (0-15) and radiographic vertebral fractures (VF) using the \"Genant\" method (grade 0-3). At all visits, BTM reflecting collagen resorption (serum type I collagen C-telopeptide; sCTX), collagen formation (procollagen type 1 N-terminal peptide; PINP) and bone mineralization (bone-specific alkaline phosphatase; BALP) were measured and expressed in Z-scores to correct for the normal influence of age and gender.</p><p><strong>Results: </strong>17 r-axSpA patients were included; 53% male, mean age was 47±15 years, mean Ankylosing Spondylitis Disease Activity Score (ASDAS) 3.9±1.2, and 53% was biological naïve. The median 2-year progression rates were 1.1 for mSASSS and 0.5 for facet joints, which was less than the smallest detectable change. One traumatic VF (grade 3) occurred. Serum levels of sCTX and PINP remained stable during secukinumab treatment and BALP decreased significantly after 2 years, with median 0-2 year change in Z-scores of +0.1, -0.4, and -1.2, respectively.</p><p><strong>Conclusion: </strong>This explorative study of r-axSpA patients treated with secukinumab in daily clinical practice showed low radiographic spinal progression during 2 years of follow-up. Collagen resorption and formation markers remained stable, whereas mineralization marker BALP decreased significantly after 2 years. Our results are in line with the results of in vitro studies demonstrating that inhibition of IL17-A resulted in suppression of osteogenic differentiation with significant decrease in mineralization.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"161-166"},"PeriodicalIF":4.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10728592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138798406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tocilizumab Vs Methotrexate in a Cohort of Patients Affected by Active GCA: A Comparative Clinical and Ultrasonographic Study.","authors":"Silvia Grazzini, Edoardo Conticini, Paolo Falsetti, Miriana D'Alessandro, Jurgen Sota, Riccardo Terribili, Caterina Baldi, Claudia Fabiani, Elena Bargagli, Luca Cantarini, Bruno Frediani","doi":"10.2147/BTT.S431818","DOIUrl":"10.2147/BTT.S431818","url":null,"abstract":"<p><strong>Introduction: </strong>No head-to-head study has assessed the superiority of tocilizumab versus methotrexate in giant cell arteritis (GCA), and few studies have demonstrated its effectiveness in terms of ultrasonographic findings, but without a control group. The primary endpoint was to assess whether tocilizumab was superior to methotrexate in inducing normalization of US findings, whereas the secondary endpoint was to assess the effectiveness of precocious withdrawal of glucocorticoids.</p><p><strong>Methods: </strong>We prospectively enrolled all the patients with active GCA at our clinic. The inclusion criteria were clinical diagnosis of GCA; active disease; and clinical, laboratory, and US data, evaluated using the halo count (HC) and OMERACT GCA Ultrasonography Score (OGUS). Evaluations were repeated at 3, 6, and 12 months.</p><p><strong>Results: </strong>Twenty patients were treated with Tocilizumab and 9 with Methotrexate. All but three tocilizumab-treated patients achieved remission at six months, whereas at 12 months, all patients were in glucocorticoid-free remission. Up to three of the nine methotrexate patients experienced a lack of efficacy or minor relapses. Tocilizumab-treated patients showed a statistically significant difference between baseline and all follow-ups in terms of OGUS and HC, whereas the difference in the Methotrexate group was significant after 1 year. The mean glucocorticoid dosage significantly decreased in both groups. No severe adverse events or major relapses were reported.</p><p><strong>Conclusion: </strong>Our study demonstrates the superiority in terms of rapidity of a tocilizumab-based scheme over a methotrexate-based scheme in inducing clinical and US remission. Precocious withdrawal of glucocorticoids did not increase the risk of relapse.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"151-160"},"PeriodicalIF":4.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10697083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138497679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum LINC00152 and UCA1 in HCV-Induced Hepatocellular Carcinoma: Clinical Significance and Prognostic Value.","authors":"Somaia Shehab-Eldeen,&nbsp;Abdallah Essa,&nbsp;Eman Salah Arafat,&nbsp;Asmaa Shaaban Sleem,&nbsp;Amal Abdelrasoul Alhosary,&nbsp;Ehab Darwish,&nbsp;Ali Essa,&nbsp;Omar Ahmed Al-Omair,&nbsp;Emad Ali Al-Khoufi,&nbsp;Abdulrhman Khaled Al Abdulqader,&nbsp;Ali Nada","doi":"10.2147/BTT.S433872","DOIUrl":"https://doi.org/10.2147/BTT.S433872","url":null,"abstract":"<p><strong>Background: </strong>Despite significant advancements in the molecular characterization of hepatocellular carcinoma (HCC), no oncogene addiction has been discovered. Long noncoding RNAs (lncRNAs) have a lot of promise as cancer biomarkers. LINC00152 and UCA1 have shown potential as diagnostic, prognostic, and therapeutic targets for human cancers.</p><p><strong>Aim: </strong>To investigate the diagnostic and prognostic potential of serum LINC00152 and UCA1 in hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>The expression levels of LINC00152 and UCA1 in blood samples from 120 patients (60 with HCC, 60 with liver cirrhosis) and 40 healthy subjects were assessed using real-time qRT-PCR.</p><p><strong>Results: </strong>Serum LINC00152 and UCA1 expression were considerably higher in HCC patients compared to patients with liver cirrhosis and the healthy controls (p<0.001 and p<0.001 respectively). And their expressions in the liver cirrhosis group were significantly higher than in healthy controls. Both lncRNAs performed well in the ROC analysis, distinguishing HCC patients from patients with liver cirrhosis. Higher levels of LINC00152 expression were linked to lesions in both lobes of the liver (p=0.02), while higher levels of UCA1 expression were linked to vascular invasion and the late stage (p=0.01, p=0.03 respectively). The multivariate analysis showed that a high level of LINC00152 in the blood was an independent indicator of a bad outcome for HCC patients (HR=2.23, 95% CI= 1.30-5.29, p=0.03).</p><p><strong>Conclusion: </strong>Serum LINC00152 and UCA1 expression were upregulated in patients with HCC, suggesting their use as non-invasive biomarkers for HCC. Furthermore, LINC00152 has the potential to serve as a prognostic indicator.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"137-149"},"PeriodicalIF":4.0,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/68/ac/btt-17-137.PMC10581015.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49674073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment Persistence of Apremilast Among Patients with Psoriatic Arthritis.","authors":"Amir Haddad,&nbsp;Nili Stein,&nbsp;Idit Lavi,&nbsp;Lisa Shynkar,&nbsp;Irina Bergman,&nbsp;Ilan Feldhamer,&nbsp;Arnon Dov Cohen,&nbsp;Walid Saliba,&nbsp;Devy Zisman","doi":"10.2147/BTT.S425693","DOIUrl":"10.2147/BTT.S425693","url":null,"abstract":"<p><strong>Introduction: </strong>Persistence in drug therapy reflects treatment effectiveness and tolerability. We aim to estimate the persistence of apremilast prescribed to patients with psoriatic arthritis (PsA) and to identify characteristics associated with treatment discontinuation in a real-world setting.</p><p><strong>Methods: </strong>Patients with PsA treated with apremilast from January 2016 were identified from a large health database and followed until medication stop date (using 3-months grace period), death or the end of observation period (June 2021). Demographic data, Charlson comorbidity index and concomitant and previous use of conventional and biologic DMARDs were extracted. The reasons for drug discontinuation were manually retrieved from patient charts. Time to discontinuation was estimated using survival analysis using Kaplan-Meier functions.</p><p><strong>Results: </strong>Overall, 568 PsA patients treated with apremilast were identified. The mean age was 55.3±14.0 years, of whom 332 (58.5%) were females, 38.4% were obese (BMI>30), 75.2% had a Charlson comorbidity index>1, 24.1% were on concomitant treatment with methotrexate and 72.4% were biologic naïve. The median persistent period was 6.1,95% CI (5.2-6.9) months in which only 16.9% remained persistent on apremilast. No difference was found with regard to age, sex, socioeconomic status, ethnicity and obesity between patients who were persistent compared to patients who discontinued apremilast. Concomitant treatment with methotrexate and prior history of biologic therapy did not affect drug persistency (log rank P=0.957 and 0.082, respectively). Causes for treatment discontinuation were due to lack of skin efficacy in 19.4%, lack of joint efficacy in 33.3%, combined skin and joint inefficacy at 2.3% and due to side effects in 24.1%.</p><p><strong>Conclusion: </strong>In this large observational retrospective cohort of patients treated with apremilast, a relatively low drug persistence was observed with 6-month and 1-year survival rates of 50.3% and 31.3%, respectively. Treatment discontinuation was mainly due to joint inefficacy, advocating for more studies for proper patient selection to assure treatment effectiveness and persistency.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"129-136"},"PeriodicalIF":4.0,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d9/bd/btt-17-129.PMC10560465.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}