1. Fenebrutinib versus Placebo or Adalimumab in Rheumatoid Arthritis: A Randomized, Double-Blind, Phase II Trial (ANDES Study)
- Author
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Stanley Cohen, Katie Tuckwell, Tamiko R. Katsumoto, Rui Zhao, Joshua Galanter, Chin Lee, Julie Rae, Balazs Toth, Nandhini Ramamoorthi, Jason A. Hackney, Alberto Berman, Nemanja Damjanov, Dmytro Fedkov, Slawomir Jeka, Leslie W. Chinn, Michael J. Townsend, Alyssa M. Morimoto, Mark C. Genovese, Alejandro Porto, Amelia Granel, Cecilia Asnal, Eduardo Fabian Mysler, Gladys Alicia Testa, Jose Luis Velasco Zamora, Jose Luis Cristian Moreno, Juan Pablo Gulin, Julio Hofman, Maria Rosa Ulla, Mirtha Sabelli, Pablo Alejandro Mannucci, Pablo Jorge Maid, Ana Cláudia Cauceglia Melazzi, Antônio Scafuto Scotton, Antônio Carlos Ximenes, Elisete Funes, Emerson Alves Gimenez, Flora Maria D’Andrea Marcolino, João Francisco Marques Neto, Mauro Waldemar Keiserman, Sebastião Cézar Radominski, Sônia Maria Alvarenga Anti Loduca Lima, Thaís Rohde Pavan, Valderílio Feijó Azevedo, Aneliya Koleva, Antoaneta Toncheva, Daniela Bichovska, Delina Ivanova, Dimitar Penev, Emil Dimitrov, Mariyana Mihaylova, Nadezhda Kapandjieva, Natalia Marinova, Tanya Aleksieva, Tanya Tsvetanova, Tsvetanka Petranova, Valentina Popova, Yuliy Spasov, Carlos Enrique Toro, Carlos Ernesto Arteaga Unigarro, Edwin Jauregui, Javier Dario Marquez Hernandez, Juan Jose Jaller Raad, Patricia Julieta Velez Sanchez, Chang Keun Lee, Chang‐Hee Suh, Eun Young Lee, Sang‐Heon Lee, Seong Wook Kang, Shin‐Seok Lee, Yun Jong Lee, Beatriz Elena Zazueta Montiel, Blanca Irma Pinzon de la O, Daniel Xibille Friedmann, Francisco Rosas Lopez, Isaura Rodriguez Torres, Luis Jara Quezada, Marco Maradiaga Ceceña, Miguel Cortes Hernandez, Miguel Saavedra Salinas, Agnieszka Rapa, Agnieszka Pawtel, Agnieszka Zielinska, Anna Dudek, Anna Rychlewska‐Hanczewska, Anna Strzelecka, Artur Racewicz, Barbara Stasiuk, Katarzyna Gruszecka, Krystyna Dworak, Tomasz Lowenhoff, Alexey Maslyanskiy, Andrey Rebrov, Diana Krechikova, Elena Zhugrova, Evgeniya Shmidt, Galina Matsievskaya, Irina Vinogradova, Irina Ler, Larisa Eliseeva, Ludmila Savina, Marina Stanislav, Mikhail Sandin, Natalia Zyablova, Nikolay Korshunov, Nino Mosesova, Oksana Polovnikova, Olga Nesmeyanova, Ruzana Samigullina, Sergey Moiseev, Sergey Noskov, Tatiana Raskina, Tatiana Popova, Valeriy Marchenko, Aleksandar Jovanovski, Bojana Stamenkovic, Gorica Ristic, Milijanka Lazarevic, Mirjana Veselinovic, Nada Vujasinovic‐Stupar, Predrag Ostojic, Andriy Yagensky, Andriy Gnylorybov, Dmytro Rekalov, Dmytroo Reshotko, Georgiy Dzyak, Iurii Gasanov, Ludmila Khimion, Mykola Stanislavchuk, Natalya Prykhodko, Oleg Nadashkevych, Oleg Bortkevych, Orest Abrahamovych, Roman Yatsyshyn, Samvel Turyanytsya, Svitlana Smiyan, Vadym Vizir, Victoria Kachur, Vira Tseluyko, Vladyslav Povoroznyuk, Volodymyr Koshlia, Vyacheslav Zhdan, Yurii Lymar, Yuriy Mostovoy, Angela Hawkes, Arthur Mabaquiao, Cong‐Qiu Chu, Craig Scoville, David Wyatt, Debra Weinstein, Harris McIlwain, Jacqueline Vo, Jeffrey Poiley, Joseph Forstot, Kathryn Dao, Mark Turner, Mark Genovese, Michael Borofsky, Paul Caldron, Philip Waller, Robert Levin, Samy Metyas, Scott Stein, Sharukh Shroff, Shirley Pang, Tauseef Syed, and Vishala Chindalore
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Immunology ,Rheumatoid Arthritis ,Placebo ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,medicine ,Adalimumab ,Immunology and Allergy ,Rheumatoid factor ,Adverse effect ,business.industry ,medicine.disease ,3. Good health ,030104 developmental biology ,030220 oncology & carcinogenesis ,Rheumatoid arthritis ,Cohort ,Original Article ,Methotrexate ,business ,medicine.drug - Abstract
Objective To evaluate fenebrutinib, an oral and highly selective noncovalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthritis (RA). Methods Patients with RA and an inadequate response to methotrexate (MTX) (cohort 1; n = 480) were randomized to receive fenebrutinib (50 mg once daily, 150 mg once daily, or 200 mg twice daily), adalimumab (40 mg every other week), or placebo. Patients with RA and an inadequate response to tumor necrosis factor inhibitors (cohort 2; n = 98) received fenebrutinib (200 mg twice daily) or placebo. Both cohorts continued MTX therapy. Results In cohort 1, the percentages of patients in whom American College of Rheumatology 50% improvement criteria (ACR50) was achieved at week 12 were similar in the fenebrutinib 50 mg once daily and placebo groups, and were higher in the fenebrutinib 150 mg once daily group (28%) and 200 mg twice daily group (35%) than in the placebo group (15%) (P = 0.016 and P = 0.0003, respectively). Fenebrutinib 200 mg twice daily and adalimumab (36%) were comparable (P = 0.81). In cohort 2, ACR50 was achieved in more patients receiving fenebrutinib 200 mg twice daily (25%) than placebo (12%) (P = 0.072). The most common adverse events in the fenebrutinib groups included nausea, headache, anemia, and upper respiratory tract infections. Fenebrutinib had significant effects on myeloid and B cell biomarkers (CCL4 and rheumatoid factor). Fenebrutinib and adalimumab caused overlapping as well as distinct changes in B cell and myeloid biomarkers. Conclusion Fenebrutinib demonstrates efficacy comparable to adalimumab in patients with an inadequate response to MTX, and safety consistent with existing immunomodulatory therapies for RA. These data support targeting both B and myeloid cells via this novel mechanism for potential efficacy in the treatment of RA.
- Published
- 2020