المؤلفون: Mease, Philip J., van der Heijde, Désirée, Ritchlin, Christopher T., Okada, Masato, Cuchacovich, Raquel S., Shuler, Catherine L., Lin, Chen-Yen, Braun, Daniel K., Lee, Chin H., Gladman, Dafna D.

المساهمون: Department of Medicine, IU School of Medicine

المصدر: PMC

مصطلحات موضوعية: DMARDs (biologic), Psoriatic arthritis, Spondyloarthritis, Treatment

الوصف: OBJECTIVE: To assess the safety and efficacy of ixekizumab, a monoclonal antibody that inhibits interleukin-17A, in a double-blind phase III trial enrolling patients with active psoriatic arthritis (PsA). METHODS: Patients naive to biologic therapy with active PsA were randomised to subcutaneous injections of placebo (N=106), adalimumab 40 mg once every 2 weeks (active reference; N=101), ixekizumab 80 mg once every 2 weeks (IXEQ2W) (N=103), or ixekizumab 80 mg once every 4 weeks (IXEQ4W) (N=107). Both ixekizumab regimens included a 160-mg starting dose. The primary objective was to assess the superiority of IXEQ2W or IXEQ4W versus placebo as measured by the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 24. RESULTS: Significantly more patients treated with ixekizumab achieved an ACR20 response with IXEQ2W (62.1%) or IXEQ4W (57.9%) than placebo (30.2%) (p≤0.001; non-responder imputation method). Disease activity and functional disability were significantly improved with both ixekizumab doses versus placebo at weeks 12 and 24, and there was significantly less progression of structural damage at week 24 (p≤0.01). Clearance of plaque psoriasis was greater with ixekizumab than placebo (p≤0.001). Efficacy results with adalimumab, the active reference arm, showed significant improvements versus placebo. Treatment-emergent adverse events were more frequent with ixekizumab (65.7-66.4%) and adalimumab (64.4%) than placebo (47.2%) (p<0.05). CONCLUSIONS: In biologic-naive patients with active PsA, ixekizumab treatment resulted in improvements in disease activity and physical function, as well as in the inhibition of structural damage progression. Overall, adverse events were more frequent in all active groups compared with placebo.

وصف الملف: application/pdf

العلاقة: Annals of the Rheumatic Diseases; Mease, P. J., van der Heijde, D., Ritchlin, C. T., Okada, M., Cuchacovich, R. S., Shuler, C. L., … Gladman, D. D. (2017). Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Annals of the Rheumatic Diseases, 76(1), 79–87. http://doi.org/10.1136/annrheumdis-2016-209709Test; https://hdl.handle.net/1805/13313Test

الإتاحة: https://doi.org/10.1136/annrheumdis-2016-209709Test
https://hdl.handle.net/1805/13313Test

المؤلفون: Strober, Bruce, Leonardi, Craig, Papp, Kim A., Mrowietz, Ulrich, Ohtsuki, Mamitaro, Bissonnette, Robert, Ferris, Laura K., Paul, Carle, Lebwohl, Mark, Braun, Daniel K., Mallbris, Lotus, Wilhelm, Stefan, Xu, Wen, Ljungberg, Anders, Acharya, Nayan, Reich, Kristian

المصدر: Journal of the American Academy of Dermatology ; volume 76, issue 3, page 432-440.e17 ; ISSN 0190-9622

مصطلحات موضوعية: Dermatology

الإتاحة: https://doi.org/10.1016/j.jaad.2016.09.026Test
https://api.elsevier.com/content/article/PII:S0190962216308684?httpAccept=text/plainTest
https://api.elsevier.com/content/article/PII:S0190962216308684?httpAccept=text/xmlTest

المؤلفون: Mease, Philip J, van der Heijde, Désirée, Ritchlin, Christopher T, Okada, Masato, Cuchacovich, Raquel S, Shuler, Catherine L, Lin, Chen-Yen, Braun, Daniel K, Lee, Chin H, Gladman, Dafna D

المساهمون: Eli Lilly and Company

المصدر: Annals of the Rheumatic Diseases ; volume 76, issue 1, page 79-87 ; ISSN 0003-4967 1468-2060

الوصف: Objective To assess the safety and efficacy of ixekizumab, a monoclonal antibody that inhibits interleukin-17A, in a double-blind phase III trial enrolling patients with active psoriatic arthritis (PsA). Methods Patients naive to biologic therapy with active PsA were randomised to subcutaneous injections of placebo (N=106), adalimumab 40 mg once every 2 weeks (active reference; N=101), ixekizumab 80 mg once every 2 weeks (IXEQ2W) (N=103), or ixekizumab 80 mg once every 4 weeks (IXEQ4W) (N=107). Both ixekizumab regimens included a 160-mg starting dose. The primary objective was to assess the superiority of IXEQ2W or IXEQ4W versus placebo as measured by the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 24. Results Significantly more patients treated with ixekizumab achieved an ACR20 response with IXEQ2W (62.1%) or IXEQ4W (57.9%) than placebo (30.2%) (p≤0.001; non-responder imputation method). Disease activity and functional disability were significantly improved with both ixekizumab doses versus placebo at weeks 12 and 24, and there was significantly less progression of structural damage at week 24 (p≤0.01). Clearance of plaque psoriasis was greater with ixekizumab than placebo (p≤0.001). Efficacy results with adalimumab, the active reference arm, showed significant improvements versus placebo. Treatment-emergent adverse events were more frequent with ixekizumab (65.7–66.4%) and adalimumab (64.4%) than placebo (47.2%) (p<0.05). Conclusions In biologic-naive patients with active PsA, ixekizumab treatment resulted in improvements in disease activity and physical function, as well as in the inhibition of structural damage progression. Overall, adverse events were more frequent in all active groups compared with placebo. Trial registration number NCT01695239; EudraCT2011-002326-49; Results.

الإتاحة: https://doi.org/10.1136/annrheumdis-2016-209709Test

المؤلفون: Braun, Daniel K., Pellett, Philip E., Hanson, Curtis A.

مصطلحات موضوعية: Concise Communications

الوصف: S100-positive, T cell chronic lymphoproliferative disease (S100-CLPD) is a rare and aggressive hematologic disorder in which the cytoplasmic protein S100 is expressed at high levels in abnormal lymphocytes. Using a DNA probe specific for human herpesvirus 6 (HHV-6), 2 cases of S100-CLPD were examined by DNA and RNA hybridization analysis. The results indicated that HHV-6 DNA was present in uncultured peripheral blood mononuclear cells (PBMC) and that a 1.3-kb viral transcript was expressed in both cases. Analysis of flow-sorted PBMC from 1 case demonstrated that HHV-6 DNA was present exclusively in the S100-positive fraction. Studies using other HHV-6 DNA probes suggested infection with HHV-6 variant B in both cases. Hybridization studies using DNA from PBMC of 27 cases of T cell chronic lymphoproliferative disease of other types showed no evidence of HHV-6. These studies suggest a possible specific association of HHV-6 with the unusual disorder S100-CLPD.

وصف الملف: text/html

العلاقة: http://jid.oxfordjournals.org/cgi/content/short/171/5/1351Test; http://dx.doi.org/10.1093/infdis/171.5.1351Test

الإتاحة: https://doi.org/10.1093/infdis/171.5.1351Test
http://jid.oxfordjournals.org/cgi/content/short/171/5/1351Test

المؤلفون: Walling, Dennis M., Clark, Nina M., Markovitz, David M., Frank, Thomas S., Braun, Daniel K., Eisenberg, Ellen, Krutchkoff, David J., Felix, David H., Raab-Traub, Nancy

مصطلحات موضوعية: Major Articles

الوصف: Human immunodeficiency virus-associated oral hairy leukoplakia (HLP) is characterized by coinfection with multiple types and strains of Epstein-Barr virus (EBV) and recombination within the EBV genome. HIV-seronegative immunosuppressed and immunocompetent patients with HLP were examined to determine the pathogenic contribution of EBV coinfection and recombination to the development of HLP. Multiple coinfecting EBV strains were detected in both HLP specimens and peripheral blood lymphocytes (PBL) of HIV-seronegative persons with HLP. One specific EBV strain was detected in HLP specimens from 3 of 4 patients. Also, viral recombination during productive replication within HLP generated variants of the latent membrane protein-l (LMP-l) and nuclear antigen-Z (EBNA-2) genes. Some variants were also detected within PBL. Thus, EBV coinfection and recombination are consistent findings in persons with HLP regardless of immune status. Virally mediated determinants may be important features of EBV pathogenesis.

وصف الملف: text/html

العلاقة: http://jid.oxfordjournals.org/cgi/content/short/171/5/1122Test; http://dx.doi.org/10.1093/infdis/171.5.1122Test

الإتاحة: https://doi.org/10.1093/infdis/171.5.1122Test
http://jid.oxfordjournals.org/cgi/content/short/171/5/1122Test

المؤلفون: Lin, Vivian H., Parekh, Rulan S., McQuillan, Mark A., Braun, Daniel K., Markovitz, David M.

مصطلحات موضوعية: Notes

الوصف: We report the case of a patient with mixed connective tissue disease who presented with two very unusual manifestations of meningococcal disease, cellulitis and endocarditis, concurrently. We also review the literature concerning Neisseria meningitidis as a causative agent of cellulitis or endocarditis. While meningococcal endocarditis or cellulitis is very rare, autoimmune disease predisposes patients to meningococcal infection. Therefore, unusual infections with this organism should be considered in the differential diagnosis of fever and rash in patients with connective tissue diseases.

وصف الملف: text/html

العلاقة: http://cid.oxfordjournals.org/cgi/content/short/21/4/1023Test; http://dx.doi.org/10.1093/clinids/21.4.1023Test

الإتاحة: https://doi.org/10.1093/clinids/21.4.1023Test
http://cid.oxfordjournals.org/cgi/content/short/21/4/1023Test

المؤلفون: Clark, Nina M., Braun, Daniel K., Pasternak, Andy, Chenoweth, Carol E.

مصطلحات موضوعية: Clinical Articles

الوصف: Organisms of the genus Nocardia cause a variety of illnesses in humans and other mammals. Nocardiae normally enter the body via the respiratory tract, but they may also be directly inoculated into the skin, causing primary cutaneous disease. Nocardia otitidiscaviarum is one of the less commonly isolated species of Nocardia , but it can produce localized or disseminated infection. We report a case of primary cutaneous N. otitidiscaviarum infection and review the clinical and microbiological features of other reported cases. Cutaneous N. otitidiscaviarum infection usually occurs in the setting of trauma, most often in otherwise healthy hosts. The manifestations of N. otitidiscaviarum skin infection range from cellulitis and abscess formation to the development of mycetomas. Cutaneous infection by N. otitidiscaviarum can mimic disease caused by more common pyogenic organisms, often leading to delay in diagnosis and treatment. Appropriate antibiotic therapy, usually with a sulfa drug-containing regimen, is generally successful.

وصف الملف: text/html

العلاقة: http://cid.oxfordjournals.org/cgi/content/short/20/5/1266Test; http://dx.doi.org/10.1093/clinids/20.5.1266Test

الإتاحة: https://doi.org/10.1093/clinids/20.5.1266Test
http://cid.oxfordjournals.org/cgi/content/short/20/5/1266Test

المؤلفون: Mitchell, Mark A., Markovitz, David M., Killen, Paul D., Braun, Daniel K.

مصطلحات موضوعية: Clinical Infectious Disease Articles

الوصف: Malacoplakia is a rare inflammatory disorder seen most often in the urinary tract, where it is highly associated with coliform infection. Although first recognized by pathologists in 1902, it has received little attention from the infectious disease community. While there remains much uncertainty regarding the specific cause of malacoplakia, it appears to be associated with a defect in intracellular killing of ingested microorganisms by macrophages. We report a case of bilateral renal parenchymal malacoplakia that presented as fever of unknown origin, and we review 33 previously identified cases. Renal malacoplakia has traditionally been associated with high morbidity and mortality. More recently, treatment with antimicrobial agents such as trimethoprim or ciprofloxacin has yielded a better outcome than had been documented with other therapy. Malacoplakia should be considered in the evaluation of fever of unknown origin or of relapsing or refractory urinary tract infection. Therapy with antimicrobial agents capable of intracellular penetration is recommended.

وصف الملف: text/html

العلاقة: http://cid.oxfordjournals.org/cgi/content/short/18/5/704Test; http://dx.doi.org/10.1093/clinids/18.5.704Test

الإتاحة: https://doi.org/10.1093/clinids/18.5.704Test
http://cid.oxfordjournals.org/cgi/content/short/18/5/704Test

المؤلفون: Griffiths, CEM, Lebwohl, Mark, van de Kerkhof, Peter, Menter, Alan, Cameron, Gregory S, Erickson, Janelle, Zhang, Lu, Secrest, Roberta J, Ball, Susan, Braun, Daniel K, Osuntokun, Olawale O, Heffernan, Michael P, Nickoloff, Brian J, Kerr, David J, Birbara, Charles, Ko, William T, Koltun, William D, Dosik, Jonathan S, Lewis, Derek, Ehrlich, Alison, Strober, Bruce E, George, Rosalyn E, Gillum, Paul, Hamilton, Tiffani K, Hoekstra, John A, Abramovits, William, Lebwohl, Mark G, Lee, Patricia C, Podda, Maurizio, Rieken, Tilmann, Grigat, Christine, Norgauer, Johannes, Carus, Carl Gustav, Wozel, Gottfried, Koerber, Andreas, Rosenbach, Thomas, Chodorowska, Grazyna, Maleszka, Romuald, Kaszuba, Andrzej, Rudnicka, Lidia, Szymanska, Elzbieta B, Klujszo, Elzbieta, Nowicki, Roman, Wasik, Grazyna, Thorla, Ira H, Moore, Angela, Grande, Kimberly, Sobell, Jeffrey M, Lockshin, Benjamin, Humeniuk, John M, Rankin, Bruce G, Delamo, Joseph G, Pariser, David M, Leonardi, Craig L, Davis, Steven A, Ferris, Laura K, Rendon, Marta I, Weisman, Jamie D, Fromowitz, Jeffrey S, Jazayeri, S Sasha, Nossa, Robert, Solovan, Caius, Mihalache, Dorin, Tiplica, George-Sorin, Zbranca-Toporas, Anca, Florea, Ion, Beti, Horia, Wainwright, Nicholas, Griffiths, Christopher, McBride, Sandy, Burden, David, Foerster, John, Butt, Aamir, Messenger, Andrew, Lim, Adrian, Su, John, Hall, Stephen, Cooper, Alan, Parish, Lawrence C, Carrasco, Daniel A, McCune, Mark A, Werschler, William P, Belasco, Kevin T, Marcadis, Abe, Gardner, Timothy L, Guenthner, Scott T, Nelson, Christopher G, Barankin, Ben, Albrecht, Lorne, Gooderham, Melinda, Poulin, Yves, Rosoph, Leslie, Gauthier, Jean Sebastien, Vender, Ronald, Wasel, Norman, Sidhu, Shireen, Rubel, Diana, Foley, Peter, Spelman, Lynda, Bodokh, Isaac, Duval-Modeste, Anne-Benedicte, Guillet, Gerard, Paul, Carle, Lacour, Jean-Philippe, Aubin, Francois, Chaby, Guillaume, Grob, Jean-Jacques, Van de Kerkhof, Peter, Ziekenhuis, Amphia, de Kort, Wim, Van Doorn, Martiin Bastiaan, Riedl, Elisabeth, Strohal, Robert, Schmuth, Matthias, Salmhofer, Wolfgang, Lasko, Benjamin, Toma, Azhar, Woolner, Derek, Barber, Kirk, Guenther, Lyn, Lynde, Charles, Hanna, Sam, Gupta, Aditya, Kunynetz, Rodion, Hoffmann, Matthias, Werfel, Thomas, Reich, Kristian, Brau, Beate, Ghoreschi, Kamran, Moessn, Rotraut, Arenberger, Petr, Vasku, Vladimir, Machovcova, Alena, Ferrandiz, Carlos, Bran Eduardo, Lopez, Puig Sanz, Lluis, Herrera Ceballos, Enrique, Lopez Estebaranz, Jose, Belinchon Romero, Isabel, Pujol, Ramon, Vanaclocha Sebastian, Francisco, Carretero Hernandez, Gregorio, Ferrandiz Pulido, Lara, Blauvelt, Andrew, Bukhalo, Michael, Stoll, David, Crowley, Jeffrey, Helfrich, Yolanda, Miller, Stephen, Rafal, Elyse, Solomon, James, Schleicher, Stephen, Schlessinger, Joel, Sofen, Howard, Draelos, Zoe Diana, Woodson, Johnnie, Stoessel, Janna, Konig, Hans, Bruning, Harald, Piechatzek, Richard, Lohrbacher-Kozak, Irina, Contzen, Christel, Khariouzov, Andrei, Heymer, Peter, Kreutzmann, Kristen, Ockenfels, Hans-Michael, Wildfeuer, Thomas, Virchow, Rudolf, Reinhold, Uwe, Kurzen, Hjalmar, Termeer, Christian, Rothhaar, Alex, Radny, Peter, Coggi, James, Lenz, Jeffrey, Kuettel, Kevin, Galal, Salem, Tschen, Eduardo, Gilboa, Ruth, Fretzin, Scott, Fleischer, Alan, Forsha, Douglass, Knoepp, Theresa, Nahm, Walter, Mehlis, Stephanie, Menter, Martin, Yamauchi, Paul, Savin, Ronald, Gellrich, Sylke, Kardorff, Bernd, Rütter, Anita, Ludolph-Hauser, Dagmar, Sebastian, Michael, Tsianakas, Athanasios, Wolf, Doerte, Ludwig-Peitsch, Wiebke, Philipp, Sandra, Augustin, Mathias, Yankova, Rumyana, Kazandjieva, Jana, Tsingov, Iliya, Vlaeva, Tzetza, Sadick, Neil, Fowler, Joseph, Truett, Artis, Wu, Jashin, Bernhardt, Michael, Lee, Mark, Bagel, Jerry, Behringer, Frederick, Kircik, Leon, Alonso-Llamazares, Javier, Hole, Susan, Rich, Phoebe, Gordon, Kenneth, Campbell, James, Kadurina, Miroslava, Poznanska, Maria, Rajzer, Lidia, Padlewska, Kamila, Gonzalez Soto, Remigio F, Gonzalez, Javier A, Kemeny, Lajos, Remenyik, Eva, Karolyi, Zsuzsanna, Bakos, Noemi, Nemes, Edina, Kovago, Levente, Telegdy, Eniko, Callis-Duffin, Kristina, Gottlieb, Alice, Soung, Jennifer, Armstrong, April, Norris, David, Thomas, Richard, Adams, Stewart, Papp, Kim, Langley, Richard, Delorme, Isabelle, Robern, Michael, Zhou, Youwen, Tan, Jerry, Raman, Mani, Sharma, Shakti, Maari, Catherine, Gyulai, Rolland, Varszegi, Dalma, Orojan, Ivan, Piroska, Dosa, Vincze, Ildiko, Melegh, Eva, Cholmy, Krylatskie, Perlamutrov, Yuriy N, Kray, Krasnodarskiy, Murashkin, Nikolay, Sukharev, Alexey, Edin, Anton, Smirnova, Yana, Rudinskiy, Kirill, Popp, Georg, Vanscheidt, Wolfgang, Medizin, Fachbereich, Wolfgang, Johann, Kaufmann, Roland, Thaci, Diamant, Benoit, Sandrine, Thron, Andrea, Kast, Petra, Studien, Klinische, Kaatz, Martin, Schopf, Rudolf, Theis, Elisabeth, Paschen, Christine, Stratmann, Liebhild, Graefe, Andrea, Kreutzmann, Kristin, Degtyareva, Elizaveta, Raznatovskiy, Konstantin, Stetsiouk, Olga, Givirovskiy, Stanislav, Chizhov, Petr, Valenzuela, Fernando, Fernandez, Unknown, Gonzalez, Pablo, Galimberti, Ricardo Luis, Magarinos, Gabriel Alejandro

المصدر: Griffiths , CEM , Lebwohl , M , van de Kerkhof , P , Menter , A , Cameron , G S , Erickson , J , Zhang , L , Secrest , R J , Ball , S , Braun , D K , Osuntokun , O O , Heffernan , M P , Nickoloff , B J , Kerr , D J , Birbara , C , Ko , W T , Koltun , W D , Dosik , J S , Lewis , D , Ehrlich , A , Strober , B E , George , ....

الوصف: BACKGROUND: Ixekizumab is a humanised monoclonal antibody against the proinflammatory cytokine interleukin 17A. We report two studies of ixekizumab compared with placebo or etanercept to assess the safety and efficacy of specifically targeting interleukin 17A in patients with widespread moderate-to-severe psoriasis. METHODS: In two prospective, double-blind, multicentre, phase 3 studies (UNCOVER-2 and UNCOVER-3), eligible patients were aged 18 years or older, had a confirmed diagnosis of chronic plaque psoriasis at least 6 months before baseline (randomisation), 10% or greater body-surface area involvement at both screening and baseline visits, at least a moderate clinical severity as measured by a static physician global assessment (sPGA) score of 3 or more, and a psoriasis area and severity index (PASI) score of 12. Participants were randomly assigned (1:2:2:2) by computer-generated random sequence with an interactive voice response system to receive subcutaneous placebo, etanercept (50 mg twice weekly), or one injection of 80 mg ixekizumab every 2 weeks, or every 4 weeks after a 160 mg starting dose. Blinding was maintained with a double-dummy design. Coprimary efficacy endpoints were proportions of patients achieving sPGA score 0 or 1 and 75% or greater improvement in PASI at week 12. Analysis was by intention to treat. These trials are registered with ClinicalTrials.gov, numbers NCT01597245 and NCT01646177. FINDINGS: Between May 30, 2012, and Dec 30, 2013, 1224 patients in UNCOVER-2 were randomly assigned to receive subcutaneous placebo (n=168), etanercept (n=358), or ixekizumab every 2 weeks (n=351) or every 4 weeks (n=347); between Aug 11, 2012, and Feb 27, 2014, 1346 patients in UNCOVER-3 were randomly assigned to receive placebo (n=193), etanercept (n=382), ixekizumab every 2 weeks (n=385), or ixekizumab every 4 weeks (n=386). At week 12, both primary endpoints were met in both studies. For UNCOVER-2 and UNCOVER-3 respectively, in the ixekizumab every 2 weeks group, PASI 75 was achieved by 315 (response ...

الإتاحة: https://doi.org/10.1016/S0140-6736Test(15)60125-8
https://research.manchester.ac.uk/en/publications/5c04afbb-f9b1-4f83-b38f-df20bdfda055Test

المؤلفون: Faludi, Peter, Brodows, Robert, Burger, Jude, Ivanyi, Tibor, Braun, Daniel K.

المصدر: Peptides ; volume 30, issue 9, page 1771-1774 ; ISSN 0196-9781

مصطلحات موضوعية: Cellular and Molecular Neuroscience, Endocrinology, Physiology, Biochemistry

الإتاحة: https://doi.org/10.1016/j.peptides.2009.06.026Test
https://api.elsevier.com/content/article/PII:S0196978109002642?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0196978109002642?httpAccept=text/plainTest