Biologics : Targets & Therapy最新文献

{"title":"Two decades with omalizumab: what we still have to learn.","authors":"Cristoforo Incorvaia,&nbsp;Marina Mauro,&nbsp;Elena Makri,&nbsp;Gualtiero Leo,&nbsp;Erminia Ridolo","doi":"10.2147/BTT.S180846","DOIUrl":"https://doi.org/10.2147/BTT.S180846","url":null,"abstract":"<p><p>From its availability for clinical use nearly two decades ago for severe asthma, omalizumab has gained strong evidence of efficacy and safety in the treatment of severe asthma not controlled by standard-of-care therapy. It has been acknowledged by Global Initiative on Asthma guidelines as add-on therapy against severe uncontrolled asthma. Thanks to controlled trials supporting its efficacy, omalizumab has also been licensed for the treatment of chronic spontaneous urticaria. The optimal duration of treatment in either disease has not been established. Despite its high price, omalizumab appears to be cost-effective in severe uncontrolled asthma as well as in chronic urticaria. The literature suggests a wide range of applications for omalizumab in various disorders regardless of allergic or non-allergic pathophysiology.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"12 ","pages":"135-142"},"PeriodicalIF":4.0,"publicationDate":"2018-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S180846","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36705343","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":"Analysis of real-world treatment patterns in a matched rheumatology population that continued innovator infliximab therapy or switched to biosimilar infliximab.","authors":"Yusuf Yazici,&nbsp;Lin Xie,&nbsp;Adesuwa Ogbomo,&nbsp;Lorie A Ellis,&nbsp;Kavitha Goyal,&nbsp;Amanda Teeple,&nbsp;Ismail Simsek","doi":"10.2147/BTT.S172337","DOIUrl":"https://doi.org/10.2147/BTT.S172337","url":null,"abstract":"<p><strong>Purpose: </strong>This study compared treatment patterns of Turkish patients with a diagnosis of rheumatoid arthritis (RA) who were treated with innovator Remicade^® (infliximab [IFX]) and either continued IFX or switched to CT-P13.</p><p><strong>Materials and methods: </strong>Adult RA patients with ≥1 IFX claim were identified from the Turkish Ministry of Health database. Eligible patients initiated and continued IFX treatment (continuers cohort [CC]) or initiated IFX and switched to CT-P13 (switchers cohort [SC]) during the study period. The initial IFX claim date was defined as the index date. The switch/reference date was defined as the CT-P13 switch date for the SC or a random IFX date during the period of CT-P13 availability for the CC. Cohorts were matched by age, sex, and number of IFX prescriptions during baseline. Patient demographics, discontinuation, and switching were summarized. The baseline period was defined as the period from the index date to the switch/reference date. The follow-up period ranged from the switch/reference date to the end of data availability.</p><p><strong>Results: </strong>After matching, 697 patients were selected: 605 patients for the CC and 92 patients for the SC. Mean IFX duration for the baseline period was 422 days in the CC and 438 days in the SC. Median time on any infused tumor necrosis factor (TNF) antagonist therapy was 1,080 days in the CC and 540 days in the SC during the study period. During the follow-up period, discontinuation was lower in the CC (CC=33.9% vs SC=87.5%; <i>P</i><0.001). The mean time to discontinuation was longer in the CC (CC=276 days vs SC=132 days; <i>P</i><0.001). A switch to another biologic medication during the follow-up period was observed in 19.0% of patients in the CC (n=115) and 81.5% of patients in the SC (n=75; <i>P</i><0.001).</p><p><strong>Conclusion: </strong>Treatment patterns differed between patients prescribed IFX and CT-P13. In Turkey, RA patients maintained on IFX had greater treatment persistence (ie, fewer and later discontinuations) than those who initiated IFX and switched to CT-P13.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"12 ","pages":"127-134"},"PeriodicalIF":4.0,"publicationDate":"2018-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S172337","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36781958","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":"Designing of CD8⁺ and CD8⁺-overlapped CD4⁺ epitope vaccine by targeting late and early proteins of human papillomavirus.","authors":"Satyavani Kaliamurthi,&nbsp;Gurudeeban Selvaraj,&nbsp;Aman Chandra Kaushik,&nbsp;Ke-Ren Gu,&nbsp;Dong-Qing Wei","doi":"10.2147/BTT.S177901","DOIUrl":"https://doi.org/10.2147/BTT.S177901","url":null,"abstract":"<p><strong>Background and aim: </strong>Human papillomavirus (HPV) is an oncogenic agent that causes over 90% of cases of cervical cancer in the world. Currently available prophylactic vaccines are type specific and have less therapeutic efficiency. Therefore, we aimed to predict the potential species-specific and therapeutic epitopes from the protein sequences of HPV45 by using different immunoinformatics tools.</p><p><strong>Methods: </strong>Initially, we determined the antigenic potential of late (L1 and L2) and early (E1, E2, E4, E5, E6, and E7) proteins. Then, major histocompatibility complex class I-restricted CD8⁺ T-cell epitopes were selected based on their immunogenicity. In addition, epitope conservancy, population coverage (PC), and target receptor-binding affinity of the immunogenic epitopes were determined. Moreover, we predicted the possible CD8⁺, nested interferon gamma (IFN-γ)-producing CD4⁺, and linear B-cell epitopes. Further, antigenicity, allergenicity, immunogenicity, and system biology-based virtual pathway associated with cervical cancer were predicted to confirm the therapeutic efficiency of overlapped epitopes.</p><p><strong>Results: </strong>Twenty-seven immunogenic epitopes were found to exhibit cross-protection (≥55%) against the 15 high-risk HPV strains (16, 18, 31, 33, 35, 39, 51, 52, 56, 58, 59, 68, 69, 73, and 82). The highest PC was observed in Europe (96.30%), North America (93.98%), West Indies (90.34%), North Africa (90.14%), and East Asia (89.47%). Binding affinities of 79 docked complexes observed as global energy ranged from -10.80 to -86.71 kcal/mol. In addition, CD8⁺ epitope-overlapped segments in CD4⁺ and B-cell epitopes demonstrated that immunogenicity and IFN-γ-producing efficiency ranged from 0.0483 to 0.5941 and 0.046 to 18, respectively. Further, time core simulation revealed the overlapped epitopes involved in pRb, p53, COX-2, NF-X1, and HPV45 infection signaling pathways.</p><p><strong>Conclusion: </strong>Even though the results of this study need to be confirmed by further experimental peptide sensitization studies, the findings on immunogenic and IFN-γ-producing CD8⁺ and overlapped epitopes provide new insights into HPV vaccine development.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"12 ","pages":"107-125"},"PeriodicalIF":4.0,"publicationDate":"2018-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S177901","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36577942","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":"A descriptive analysis of real-world treatment patterns of innovator (Remicade^®) and biosimilar infliximab in an infliximab-naïve Turkish population.","authors":"Yusuf Yazici,&nbsp;Lin Xie,&nbsp;Adesuwa Ogbomo,&nbsp;Lorie A Ellis,&nbsp;Kavitha Goyal,&nbsp;Amanda Teeple,&nbsp;Ece A Mutlu,&nbsp;Ismail Simsek","doi":"10.2147/BTT.S172241","DOIUrl":"https://doi.org/10.2147/BTT.S172241","url":null,"abstract":"<p><strong>Purpose: </strong>Biosimilar IFX (CT-P13) received marketing approval in Turkey for treatment of rheumatologic diseases, including ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Population data on real-world treatment patterns of CT-P13 following marketing approval in European countries are largely unreported. This study examined the prescribing and medication utilization patterns of innovator infliximab (IFX) and CT-P13 in Turkey for patients with RA or IBD naïve to either IFX.</p><p><strong>Materials and methods: </strong>Adult patients with ≥1 diagnosis claim for RA or IBD and ≥1 claim for IFX or CT-P13 were identified in the Turkish Ministry of Health database during the following identification periods: 1 Oct 2014-30 May 2015 (RA) and 1 Oct 2014-31 Dec 2015 (IBD). Continuous medical and pharmacy coverage for ≥12 months before and after the date of the first dose (index) IFX or CT-P13 was also required. Separate analyses were done for each population.</p><p><strong>Results: </strong>Seven hundred and seventy nine adult RA and 581 IBD patients met the selection criteria. The majority of RA (74%; n=575) and IBD patients (87%; n=504) were initiated on IFX. The average study observation period was 16 months for the RA and 12 months for the IBD population. Over the observation periods, discontinuation among RA patients occurred in 42% of IFX and 63% of CT-P13 while discontinuation in the IBD cohort occurred in 38% of IFX; and 62% of CT-P13.</p><p><strong>Conclusion: </strong>In this population-based study, more IFX-naïve RA and IBD patients were initially treated with IFX than CT-P13. Discontinuation and switching were observed more often and earlier among patients treated with CT-P13 regardless of disease state. Further studies are needed to understand the reasons for these observed differences.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"12 ","pages":"97-106"},"PeriodicalIF":4.0,"publicationDate":"2018-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S172241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36577941","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":"Focus on biosimilar etanercept - bioequivalence and interchangeability.","authors":"Fabrizio Cantini, Maurizio Benucci","doi":"10.2147/BTT.S126854","DOIUrl":"10.2147/BTT.S126854","url":null,"abstract":"<p><strong>Background: </strong>The recent approval of reference etanercept (re-ETN) biosimilars SB4, GP2015, and HD203 produced relevant changes in the management of rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis due to the considerably lower cost of these products and the consequent savings.</p><p><strong>Aims: </strong>To review the pharmacodynamics, pharmacokinetics, efficacy, and safety of ETN biosimilars when employed as first-line therapy or after transition from re-ETN. Patients' acceptability was also addressed.</p><p><strong>Evidence review: </strong>The available literature was reviewed through a search of PubMed database, and abstract books of the American College for Rheumatology and European League Against Rheumatism annual meetings. SB4, GP2015, and HD203 were licensed by the US, European and South Korea regulatory agencies after the bioequivalence to re-ETN was demonstrated through pharmacodynamic and pharmacokinetic studies, and randomized, head to head, controlled trials. Based on the evidence of efficacy and safety of SB4 and HD203 in RA, and of GP2015 in psoriasis, by the extrapolation principle, the three biosimilars were approved for all indications licensed for re-ETN, and the regulatory agencies introduced the interchangeability from the originator to the biosimilar. Extrapolation of indications, and particularly interchangeability raised relevant concerns among the rheumatologists due to the low level of evidence supporting the switching strategy (or transition). Rheumatologists' concerns are oriented toward the relevant number of biosimilar discontinuations after the transition ranging from 7%-17% over a short-term follow-up period. As resulted from two studies, at least 20%-30% of the patients claimed more exhaustive information on the switching procedure.</p><p><strong>Conclusion: </strong>Based on the available evidence, re-ETN biosimilars may be a good option as first-line therapy, while further data are needed to definitively establish the efficacy, safety, and the economic reflexes of transitioning from re-ETN.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"12 ","pages":"87-95"},"PeriodicalIF":5.3,"publicationDate":"2018-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ff/97/btt-12-087.PMC6121755.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36485955","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":"Combined treatment with metformin and gefitinib overcomes primary resistance to EGFR-TKIs with EGFR mutation via targeting IGF-1R signaling pathway.","authors":"Yong-Hong Pan,&nbsp;Lin Jiao,&nbsp;Cai-Yu Lin,&nbsp;Cong-Hua Lu,&nbsp;Li Li,&nbsp;Heng-Yi Chen,&nbsp;Yu-Bo Wang,&nbsp;Yong He","doi":"10.2147/BTT.S166867","DOIUrl":"https://doi.org/10.2147/BTT.S166867","url":null,"abstract":"Aim Although EGFR tyrosine kinase inhibitors (TKIs) have shown dramatic effects against sensitizing EGFR mutations in non-small cell lung cancer (NSCLC), ~20%–30% of NSCLC patients with EGFR-sensitive mutation exhibit intrinsic resistance to EGFR-TKIs. The purpose of the current study was to investigate the enhanced antitumor effect of metformin (Met), a biguanide drug, in combination with gefitinib (Gef) in primary resistant human lung cancer cells and the associated molecular mechanism. Experimental design H1975 cell line was treated with Met and/or Gef to examine the inhibition of cell growth and potential mechanism of action by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Ki67 incorporation assay, flow cytometry analysis, small interfering RNA technology, Western blot analysis and xenograft implantation. Results Insulin-like growth factor-1 receptor (IGF-1R) signaling pathway was markedly activated in EGFR-TKI primary resistant H1975 cells as compared to EGFR-TKI acquired resistance cells (PC-9GR, H1650-M3) and EGFR-TKI sensitivity cells (PC-9, HCC827). Inhibition of IGF-1R activity by AG-1024 (a small molecule of IGF-1R inhibitor), as well as downregulation of IGF-1R by siRNA, significantly enhanced the ability of Gef to suppress proliferation and induce apoptosis in H1975 cells via the inhibition of AKT activation and subsequent upregulation of Bcl-2-interacting mediator of cell death (BIM). Interestingly, the observation showed that Met combined with Gef treatment had similar tumor growth suppression effects in comparison with the addition of AG-1024 to therapy with Gef. A clear synergistic antiproliferative interaction between Met and Gef was observed with a combination index (CI) value of 0.65. Notably, IGF-1R silencing mediated by RNA interference (RNAi) attenuated anticancer effects of Met without obviously resensitizing H1975 cells to Gef. Finally, Met-based combinatorial therapy effectively blocked tumor growth in the xenograft with TKI primary resistant lung cancer cells. Conclusion Our findings demonstrated that Met combined with Gef would be a promising strategy to overcome EGFR-TKI primary resistance via suppressing IGF-1R signaling pathway in NSCLC.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"12 ","pages":"75-86"},"PeriodicalIF":4.0,"publicationDate":"2018-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S166867","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36437904","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":"Efficacy of ustekinumab against infliximab-induced psoriasis and arthritis associated with Crohn's disease.","authors":"Satohiro Matsumoto,&nbsp;Hirosato Mashima","doi":"10.2147/BTT.S169326","DOIUrl":"https://doi.org/10.2147/BTT.S169326","url":null,"abstract":"<p><p>Anti-TNFα drugs have been shown to be effective for maintaining stable remission in patients with Crohn's disease. However, some problems have been identified during clinical use of this class of drugs, such as secondary treatment failure, in which the drugs become progressively less effective with time, and the development of paradoxical reactions such as psoriatic skin symptoms. Thus, while anti-TNFα drugs are used to treat psoriasis, they can sometimes also cause paradoxical psoriasis, characterized by the appearance of psoriasis-like eruptions, which has recently begun to attract attention. Furthermore, inflammatory bowel disease is not only associated with intestinal lesions, but also with a variety of extraintestinal manifestations, of which arthritis is relatively common. We encountered a case of Crohn's disease with arthritis, as an extraintestinal manifestation, and paradoxical psoriasis caused by infliximab treatment, in which ustekinumab proved extremely effective, not only for alleviating the arthritis, but also against the skin manifestations. To the best of our knowledge, this is the first reported case of the efficacy of ustekinumab against paradoxical psoriasis and arthritis in a patient with Crohn's disease.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"12 ","pages":"69-73"},"PeriodicalIF":4.0,"publicationDate":"2018-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S169326","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36347543","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 conundrum of indeterminate QuantiFERON-TB Gold results before anti-tumor necrosis factor initiation.","authors":"Shahrad Hakimian,&nbsp;Yevgeniy Popov,&nbsp;Abbas H Rupawala,&nbsp;Karen Salomon-Escoto,&nbsp;Steven Hatch,&nbsp;Randall Pellish","doi":"10.2147/BTT.S150958","DOIUrl":"https://doi.org/10.2147/BTT.S150958","url":null,"abstract":"<p><strong>Background: </strong>Tumor necrosis factor alpha (TNFα) is a key cytokine in both the pathogenesis of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) and the host defense against tuberculosis (TB). Consequently, anti-TNFα medications result in an increased risk of latent TB infection (LTBI) reactivation. Here, we sought to evaluate the factors affecting the results of QuantiFERON-TB Gold In-Tube (QFT-GIT) assay as a screening tool for LTBI.</p><p><strong>Methods: </strong>We conducted an observational, retrospective study in patients with IBD and RA who underwent LTBI screening using QFT-GIT at UMass Memorial Medical Center between 2008 and 2016 prior to initiation of anti-TNF medications.</p><p><strong>Results: </strong>We included 107 and 89 patients with IBD and RA, respectively. We found that a higher proportion of IBD patients had indeterminate QFT-GIT result compared to RA patients. Furthermore, we found that the majority of patients with indeterminate results were tested during an acute flare of IBD (88%) and while taking corticosteroids. Of all patients receiving ≥20 mg equivalent prednisone dose (n=32), 63% resulted in indeterminate QFT-GIT, compared to only 6% indeterminate testing in patients receiving <20 mg of equivalent prednisone dose (n=164, <i>P</i><0.001). There was no correlation between indeterminate results and age, gender, disease duration, or distribution, or smoking status within each population.</p><p><strong>Conclusion: </strong>We observed that high-dose corticosteroids may affect QFT-GIT outcomes leading to a high proportion of indeterminate results. We propose that IBD patients should be tested prior to initiation of corticosteroids to avoid equivocal results and prevent potential delays in initiation of anti-TNF medications.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"12 ","pages":"61-67"},"PeriodicalIF":4.0,"publicationDate":"2018-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S150958","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35897076","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":"New frontiers in oncolytic viruses: optimizing and selecting for virus strains with improved efficacy.","authors":"Kenneth Lundstrom","doi":"10.2147/BTT.S140114","DOIUrl":"https://doi.org/10.2147/BTT.S140114","url":null,"abstract":"<p><p>Oncolytic viruses have demonstrated selective replication and killing of tumor cells. Different types of oncolytic viruses - adenoviruses, alphaviruses, herpes simplex viruses, Newcastle disease viruses, rhabdoviruses, Coxsackie viruses, and vaccinia viruses - have been applied as either naturally occurring or engineered vectors. Numerous studies in animal-tumor models have demonstrated substantial tumor regression and prolonged survival rates. Moreover, clinical trials have confirmed good safety profiles and therapeutic efficacy for oncolytic viruses. Most encouragingly, the first cancer gene-therapy drug - Gendicine, based on oncolytic adenovirus type 5 - was approved in China. Likewise, a second-generation oncolytic herpes simplex virus-based drug for the treatment of melanoma has been registered in the US and Europe as talimogene laherparepvec.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"12 ","pages":"43-60"},"PeriodicalIF":4.0,"publicationDate":"2018-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S140114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35832634","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":"Correlation between HLA haplotypes and the development of antidrug antibodies in a cohort of patients with rheumatic diseases.","authors":"Maurizio Benucci,&nbsp;Arianna Damiani,&nbsp;Francesca Li Gobbi,&nbsp;Francesca Bandinelli,&nbsp;Maria Infantino,&nbsp;Valentina Grossi,&nbsp;Mariangela Manfredi,&nbsp;Guillaume Noguier,&nbsp;Francesca Meacci","doi":"10.2147/BTT.S145941","DOIUrl":"https://doi.org/10.2147/BTT.S145941","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this study was to investigate the correlation between human leukocyte antigen (HLA) haplotypes and the development of antidrug antibodies (ADAs) in a cohort of patients with rheumatic diseases.</p><p><strong>Patients and methods: </strong>We evaluated the presence of ADAs in 248 patients with inflammatory rheumatic diseases after 6 months of treatment with anti-TNF drugs: 26 patients were treated with infliximab (IFX; three with rheumatoid arthritis [RA], 13 with ankylosing spondylitis [AS], 10 with psoriatic arthritis [PsA]); 83 treated with adalimumab (ADA; 24 with RA, 36 with AS, 23 with PsA); 88 treated with etanercept (ETA; 35 with RA, 27 with AS, 26 with PsA); 32 treated with certolizumab (CERT; 25 with RA, two with AS, five with PsA); and 19 treated with golimumab (GOL; three with RA, seven with AS, nine with PsA). Serum drug and ADA levels were determined using Lisa-Tracker Duo, the ADA-positive samples underwent an inhibition test, and the true-positive samples underwent genetic HLA typing. To have a homogeneous control population, we also performed genetic HLA typing of 11 ADA-negative patients.</p><p><strong>Results: </strong>After inhibition test, the frequency of ADAs was 2/26 patients treated with IFX (7.69%), 4/83 treated with ADA (4.81%), 0/88 treated with ETA (0%), 4/32 treated with CERT (12.5%), and 1/19 treated with GOL (5.26%). The frequency of HLA alleles in the examined patients was HLA-DRβ-11 0.636, HLA-DQ-03 0.636, and HLA-DQ-05 0.727. The estimated relative risks between the ADA-positive patients and the ADA-negative patients were HLA-DRβ-11 2.528 (95% CI 0.336-19.036), HLA-DQ-03 1.750 (95% CI 0.289-10.581), and HLA-DQ-05 2.424 (95% CI 0.308-15.449).</p><p><strong>Conclusion: </strong>This is the first study that shows an association between HLA and genetic factors associated with the occurrence of ADAs in patients with rheumatic diseases, but the number of samples is too small to draw any definite conclusion.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"12 ","pages":"37-41"},"PeriodicalIF":4.0,"publicationDate":"2018-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S145941","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35820239","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}