Fenebrutinib Versus Placebo or Adalimumab in Rheumatoid Arthritis: A Randomized, Double‐Blind, Phase II Trial. Issue 9 (28th August 2020)

• Record Type: Journal Article
• Authors: Cohen, Stanley; Tuckwell, Katie; Katsumoto, Tamiko R.; Zhao, Rui; Galanter, Joshua; Lee, Chin; Rae, Julie; Toth, Balazs; Ramamoorthi, Nandhini; Hackney, Jason A.; Berman, Alberto; Damjanov, Nemanja; Fedkov, Dmytro; Jeka, Slawomir; Chinn, Leslie W.; Townsend, Michael J.; Morimoto, Alyssa M.; Genovese, Mark C.
• Other Names: Berman Alberto investigator.; Porto Alejandro investigator.; Granel Amelia investigator.; Asnal Cecilia investigator.; Mysler Eduardo Fabian investigator.; Testa Gladys Alicia investigator.; Zamora Jose Luis Velasco investigator.; Moreno Jose Luis Cristian investigator.; Gulin Juan Pablo investigator.; Hofman Julio investigator.; Ulla Maria Rosa investigator.; Sabelli Mirtha investigator.; Mannucci Pablo Alejandro investigator.; Maid Pablo Jorge investigator.; Melazzi Ana Cláudia Cauceglia investigator.; Scotton Antônio Scafuto investigator.; Ximenes Antônio Carlos investigator.; Funes Elisete investigator.; Gimenez Emerson Alves investigator.; Marcolino Flora Maria D'Andrea investigator.; Neto João Francisco Marques investigator.; Keiserman Mauro Waldemar investigator.; Radominski Sebastião Cézar investigator.; Lima Sônia Maria Alvarenga Anti Loduca investigator.; Pavan Thaís Rohde investigator.; Azevedo Valderílio Feijó investigator.; Koleva Aneliya investigator.; Toncheva Antoaneta investigator.; Bichovska Daniela investigator.; Ivanova Delina investigator.; Penev Dimitar investigator.; Dimitrov Emil investigator.; Mihaylova Mariyana investigator.; Kapandjieva Nadezhda investigator.; Marinova Natalia investigator.; Aleksieva Tanya investigator.; Tsvetanova Tanya investigator.; Petranova Tsvetanka investigator.; Popova Valentina investigator.; Spasov Yuliy investigator.; Toro Carlos Enrique investigator.; Arteaga Unigarro Carlos Ernesto investigator.; Jauregui Edwin investigator.; Hernandez Javier Dario Marquez investigator.; Raad Juan Jose Jaller investigator.; Sanchez Patricia Julieta Velez investigator.; Lee Chang Keun investigator.; Suh Chang‐Hee investigator.; Lee Eun Young investigator.; Lee Sang‐Heon investigator.; Kang Seong Wook investigator.; Lee Shin‐Seok investigator.; Lee Yun Jong investigator.; Montiel Beatriz Elena Zazueta investigator.; Pinzon de la O Blanca Irma investigator.; Friedmann Daniel Xibille investigator.; Lopez Francisco Rosas investigator.; Torres Isaura Rodriguez investigator.; Quezada Luis Jara investigator.; Ceceña Marco Maradiaga investigator.; Hernandez Miguel Cortes investigator.; Salinas Miguel Saavedra investigator.; Rapa Agnieszka investigator.; Pawtel Agnieszka investigator.; Zielinska Agnieszka investigator.; Dudek Anna investigator.; Rychlewska‐Hanczewska Anna investigator.; Strzelecka Anna investigator.; Racewicz Artur investigator.; Stasiuk Barbara investigator.; Gruszecka Katarzyna investigator.; Dworak Krystyna investigator.; Jeka Slawomir investigator.; Lowenhoff Tomasz investigator.; Maslyanskiy Alexey investigator.; Rebrov Andrey investigator.; Krechikova Diana investigator.; Zhugrova Elena investigator.; Shmidt Evgeniya investigator.; Matsievskaya Galina investigator.; Vinogradova Irina investigator.; Ler Irina investigator.; Eliseeva Larisa investigator.; Savina Ludmila investigator.; Stanislav Marina investigator.; Sandin Mikhail investigator.; Zyablova Natalia investigator.; Korshunov Nikolay investigator.; Mosesova Nino investigator.; Polovnikova Oksana investigator.; Nesmeyanova Olga investigator.; Samigullina Ruzana investigator.; Moiseev Sergey investigator.; Noskov Sergey investigator.; Raskina Tatiana investigator.; Popova Tatiana investigator.; Marchenko Valeriy investigator.; Jovanovski Aleksandar investigator.; Stamenkovic Bojana investigator.; Ristic Gorica investigator.; Lazarevic Milijanka investigator.; Veselinovic Mirjana investigator.; Vujasinovic‐Stupar Nada investigator.; Damjanov Nemanja investigator.; Ostojic Predrag investigator.; Yagensky Andriy investigator.; Gnylorybov Andriy investigator.; Rekalov Dmytro investigator.; Reshotko Dmytroo investigator.; Fedkov Dmytro investigator.; Dzyak Georgiy investigator.; Gasanov Iurii investigator.; Khimion Ludmila investigator.; Stanislavchuk Mykola investigator.; Prykhodko Natalya investigator.; Nadashkevych Oleg investigator.; Bortkevych Oleg investigator.; Abrahamovych Orest investigator.; Yatsyshyn Roman investigator.; Turyanytsya Samvel investigator.; Smiyan Svitlana investigator.; Vizir Vadym investigator.; Kachur Victoria investigator.; Tseluyko Vira investigator.; Povoroznyuk Vladyslav investigator.; Koshlia Volodymyr investigator.; Zhdan Vyacheslav investigator.; Lymar Yurii investigator.; Mostovoy Yuriy investigator.; Hawkes Angela investigator.; Mabaquiao Arthur investigator.; Chu Cong‐Qiu investigator.; Scoville Craig investigator.; Wyatt David investigator.; Weinstein Debra investigator.; McIlwain Harris investigator.; Vo Jacqueline investigator.; Poiley Jeffrey investigator.; Forstot Joseph investigator.; Dao Kathryn investigator.; Turner Mark investigator.; Genovese Mark investigator.; Borofsky Michael investigator.; Caldron Paul investigator.; Waller Philip investigator.; Levin Robert investigator.; Metyas Samy investigator.; Stein Scott investigator.; Shroff Sharukh investigator.; Pang Shirley investigator.; Cohen Stanley investigator.; Syed Tauseef investigator.; Chindalore Vishala investigator.;
• Is Part Of: Arthritis & rheumatology. Volume 72:Issue 9(2020)
• Page Start: 1435
• Page End: 1446
• Publication Date: 2020-08-28
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.41275
• Languages: English
• ISSNs: 2326-5191

Abstract

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.