المؤلفون: Werth, Victoria P, Fleischmann, Roy, Robern, Michael, Touma, Zahi, Tiamiyu, Iyabode, Gurtovaya, Oksana, Pechonkina, Alena, Mozaffarian, Afsaneh, Downie, Bryan, Matzkies, Franziska, Wallace, Daniel

المساهمون: Gilead Sciences

المصدر: Rheumatology ; volume 61, issue 6, page 2413-2423 ; ISSN 1462-0324 1462-0332

الوصف: Objectives To explore the safety and efficacy of filgotinib (FIL), a Janus kinase 1 inhibitor, and lanraplenib (LANRA), a spleen kinase inhibitor, in cutaneous lupus erythematosus (CLE). Methods This was a phase 2, randomized, double-blind, placebo-controlled, exploratory, proof-of-concept study of LANRA (30 mg), FIL (200 mg) or placebo (PBO) once daily for 12 weeks in patients with active CLE. At week 12, PBO patients were rerandomized 1:1 to receive LANRA or FIL for up to 36 additional weeks. Results Of 47 randomized patients, 45 were treated (PBO, n = 9; LANRA, n = 19; FIL, n = 17). The primary endpoint [change from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score at week 12] was not met. The least squares mean CLASI-A score change from baseline was −5.5 (s.e. 2.56) with PBO, −4.5 (1.91) with LANRA and −8.7 (1.85) with FIL. Numerical differences between FIL and PBO were greater in select subgroups. A ≥5-point improvement in the CLASI-A score at week 12 was achieved by 50.0%, 56.3% and 68.8% in the PBO, LANRA and FIL arms, respectively. A numerically greater proportion of patients in the FIL arm (50%) also achieved ≥50% improvement in the CLASI-A score at week 12 (37.5% PBO, 31.3% LANRA). Most adverse events (AEs) were mild or moderate in severity. Two serious AEs were reported with LANRA and one with FIL. Conclusion The primary endpoint was not met. Select subgroups displayed a numerically greater treatment response to FIL relative to PBO. LANRA and FIL were generally well tolerated. Trial registration ClinicalTrials.gov identifier NCT03134222

الإتاحة: https://doi.org/10.1093/rheumatology/keab685Test
https://academic.oup.com/rheumatology/article-pdf/61/6/2413/43891516/keab685.pdfTest

المؤلفون: Papp, Kim, Gooderham, Melinda, Robern, Michael, Shaffelburg, Michael, Sajic, Dusan, Garcia-Rodriguez, Juan C., Taveras, Carmen, Nigen, Simon, Taraska, Victoria, Vieira, Antonio, Rihakova, Lenka, Zaraa, Ines

المصدر: Annales de Dermatologie et de Vénéréologie - FMC ; volume 1, issue 8, page A353-A354 ; ISSN 2667-0623

مصطلحات موضوعية: Ocean Engineering, Safety, Risk, Reliability and Quality

الإتاحة: https://doi.org/10.1016/j.fander.2021.09.426Test
https://api.elsevier.com/content/article/PII:S2667062321007030?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2667062321007030?httpAccept=text/plainTest

المؤلفون: Papp, Kim, Gooderham, Melinda, Robern, Michael, Shaffelburg, Michael, Sajic, Dusan, Garcia-Rodriguez, Juan C., Taveras, Carmen, Nigen, Simon, Taraska, Victoria, Vieira, Antonio, Rihakova, Lenka

المصدر: Journal of the American Academy of Dermatology ; volume 85, issue 3, page AB145 ; ISSN 0190-9622

مصطلحات موضوعية: Dermatology

الإتاحة: https://doi.org/10.1016/j.jaad.2021.06.593Test
https://api.elsevier.com/content/article/PII:S0190962221016972?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0190962221016972?httpAccept=text/plainTest

المؤلفون: Werth, Victoria P, Fleischmann, Roy, Robern, Michael, Touma, Zahi, Tiamiyu, Iyabode, Gurtovaya, Oksana, Pechonkina, Alena, Mozaffarian, Afsaneh, Downie, Bryan, Matzkies, Franziska, Wallace, Daniel

المصدر: Rheumatology; Jun2022, Vol. 61 Issue 6, p2413-2423, 11p

مصطلحات موضوعية: THERAPEUTIC use of antineoplastic agents, DRUG efficacy, RESEARCH, LUPUS erythematosus, JANUS kinases, PROTEIN-tyrosine kinase inhibitors, RANDOMIZED controlled trials, SEVERITY of illness index, BLIND experiment, DESCRIPTIVE statistics, NEUROTRANSMITTER uptake inhibitors, STATISTICAL sampling

مصطلحات جغرافية: UNITED States, CANADA

مستخلص: Objectives To explore the safety and efficacy of filgotinib (FIL), a Janus kinase 1 inhibitor, and lanraplenib (LANRA), a spleen kinase inhibitor, in cutaneous lupus erythematosus (CLE). Methods This was a phase 2, randomized, double-blind, placebo-controlled, exploratory, proof-of-concept study of LANRA (30 mg), FIL (200 mg) or placebo (PBO) once daily for 12 weeks in patients with active CLE. At week 12, PBO patients were rerandomized 1:1 to receive LANRA or FIL for up to 36 additional weeks. Results Of 47 randomized patients, 45 were treated (PBO, n  = 9; LANRA, n  = 19; FIL, n  = 17). The primary endpoint [change from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score at week 12] was not met. The least squares mean CLASI-A score change from baseline was −5.5 (s. e. 2.56) with PBO, −4.5 (1.91) with LANRA and −8.7 (1.85) with FIL. Numerical differences between FIL and PBO were greater in select subgroups. A ≥5-point improvement in the CLASI-A score at week 12 was achieved by 50.0%, 56.3% and 68.8% in the PBO, LANRA and FIL arms, respectively. A numerically greater proportion of patients in the FIL arm (50%) also achieved ≥50% improvement in the CLASI-A score at week 12 (37.5% PBO, 31.3% LANRA). Most adverse events (AEs) were mild or moderate in severity. Two serious AEs were reported with LANRA and one with FIL. Conclusion The primary endpoint was not met. Select subgroups displayed a numerically greater treatment response to FIL relative to PBO. LANRA and FIL were generally well tolerated. Trial registration ClinicalTrials.gov identifier NCT03134222 [ABSTRACT FROM AUTHOR]

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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: Papp, Kim A., DeKoven, Joel, Parsons, Laurie, Pirzada, Syed, Robern, Michael, Robertson, Lynne, Tan, Jerry K.L.

المصدر: Journal of Cutaneous Medicine and Surgery ; volume 16, issue 3, page 153-168 ; ISSN 1203-4754 1615-7109

مصطلحات موضوعية: Dermatology, Surgery

الوصف: Background: Previous publications have described practical considerations for initiating biologic therapy in psoriasis patients. However, most publications have focused on anti–tumor necrosis factor (TNF) therapy. Objective: To create an evidence-based, practical tool that provides guidance on patient management for all biologics currently approved in Canada and the United States. Methods: Psoriasis publications regarding safety issues in the initiation or monitoring of adalimumab, alefacept, etanercept, infliximab, or ustekinumab therapy were identified through a PubMed search. Phase III trials and open-label extensions (regardless of indication) and relevant guidelines from Health Canada were used to compile this review. Results: Although these biologic agents have demonstrated efficacy in patients with psoriasis and are generally considered safe and well tolerated, rare but serious safety issues (ie, demyelination, infection, tuberculosis, malignancy, lymphoma, cardiovascular outcomes, hepatitis, pregnancy, surgery, and vaccination) have been observed. Attention to specific aspects of patient management (ie, prescreening requirements, symptoms to watch for, appropriate treatment, and referrals) is required to mitigate risk. Conclusion: Much of the evidence regarding the long-term safety of these agents has been based on experience in other patient populations. However, it does serve to guide us in understanding the risks that may impact the management of psoriasis patients.

الإتاحة: https://doi.org/10.1177/120347541201600305Test