Alan Kivitz1,2, Ewa Olech3,4, Michael A Borofsky3,4, Beatriz Zazueta3,4, Federico Navarro-Sarabia3,4, Sebastião C Radominski3,4, Joan T Merrill3,4, César Pacheco-Tena3,4, Jinglan Pei3,4, Clare Nasmyth-Miller3,4, Janet E Pope3,4. 1. From the Altoona Center for Clinical Research, Duncansville, Pennsylvania; University of Nevada School of Medicine, Las Vegas, Nevada; Clinical Research Center of Reading, Reading, Pennsylvania; Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma; Genentech, South San Francisco, California, USA; Universidad Autónoma de Chihuahua, Chihuahua; Centro de Investigacion en Enfermedades Reumaticas, Mexicali, Baja California, Mexico; Hospital Virgen Macarena, Servicio de Reumatología, Sevilla, Spain; Universidade Federal do Paraná, Curitiba, Brazil; Roche Pharmaceuticals, Welwyn Garden City, London, UK; St. Joseph's Health Centre, Western University, London, Ontario, Canada. ajkivitz@yahoo.com. 2. F. Navarro-Sarabia received consulting fees and speakers bureau fees from Roche Pharmaceuticals. S.C. Radominski received research grants from Roche Pharmaceuticals. J.T. Merrill received consulting fees from Roche Pharmaceuticals and Genentech. J. Pei is an employee of Genentech. C. Nasmyth-Miller is an employee of Roche Pharmaceuticals. A. Kivitz, MD, Altoona Center for Clinical Research; E. Olech, MD, University of Nevada School of Medicine; M.A. Borofsky, MD, Clinical Research Center of Reading; B. Zazueta, MD, Centro de Investigacion en Enfermedades Reumaticas; F. Navarro-Sarabia, MD, Hospital Virgen Macarena, Servicio de Reumatología; S.C. Radominski, MD, Universidade Federal do Paraná; J.T. Merrill, MD, Oklahoma Medical Research Foundation; C. Pacheco-Tena, MD, Universidad Autónoma de Chihuahua; J. Pei, BS, Genentech; C. Nasmyth-Miller, DPhil, Roche Pharmaceuticals; J.E. Pope, MD, St. Joseph's Health Centre, Western University. ajkivitz@yahoo.com. 3. From the Altoona Center for Clinical Research, Duncansville, Pennsylvania; University of Nevada School of Medicine, Las Vegas, Nevada; Clinical Research Center of Reading, Reading, Pennsylvania; Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma; Genentech, South San Francisco, California, USA; Universidad Autónoma de Chihuahua, Chihuahua; Centro de Investigacion en Enfermedades Reumaticas, Mexicali, Baja California, Mexico; Hospital Virgen Macarena, Servicio de Reumatología, Sevilla, Spain; Universidade Federal do Paraná, Curitiba, Brazil; Roche Pharmaceuticals, Welwyn Garden City, London, UK; St. Joseph's Health Centre, Western University, London, Ontario, Canada. 4. F. Navarro-Sarabia received consulting fees and speakers bureau fees from Roche Pharmaceuticals. S.C. Radominski received research grants from Roche Pharmaceuticals. J.T. Merrill received consulting fees from Roche Pharmaceuticals and Genentech. J. Pei is an employee of Genentech. C. Nasmyth-Miller is an employee of Roche Pharmaceuticals. A. Kivitz, MD, Altoona Center for Clinical Research; E. Olech, MD, University of Nevada School of Medicine; M.A. Borofsky, MD, Clinical Research Center of Reading; B. Zazueta, MD, Centro de Investigacion en Enfermedades Reumaticas; F. Navarro-Sarabia, MD, Hospital Virgen Macarena, Servicio de Reumatología; S.C. Radominski, MD, Universidade Federal do Paraná; J.T. Merrill, MD, Oklahoma Medical Research Foundation; C. Pacheco-Tena, MD, Universidad Autónoma de Chihuahua; J. Pei, BS, Genentech; C. Nasmyth-Miller, DPhil, Roche Pharmaceuticals; J.E. Pope, MD, St. Joseph's Health Centre, Western University.
Abstract
OBJECTIVE: To evaluate the longterm efficacy and safety of subcutaneous tocilizumab (TCZ-SC) every 2 weeks (q2w) over 2 years in patients with rheumatoid arthritis who have an inadequate response to disease-modifying antirheumatic drugs (DMARD). METHODS:Patients (n = 656) were randomized 2:1 to TCZ-SC 162 mg q2w or placebo-SC q2w plus DMARD. After a 24-week double-blind period, patients (n = 457) werererandomized to open-label TCZ-SC q2w by means of prefilled syringe or autoinjector. Escape therapy with weekly TCZ-SC was available for patients with inadequate efficacy from Week 12. Maintenance of response and safety to 2 years was assessed. Analyses used nonresponder imputation. RESULTS: The American College of Rheumatology (ACR) 20 response after TCZ-SC was maintained beyond Week 24 and was > 70% at each timepoint. ACR50/70, 28-joint Disease Activity Score remission, and ≥ 0.30 decrease from baseline in the Health Assessment Questionnaire-Disability Index response rates were also maintained after Week 24 in the TCZ-SC arm (≥ 50%, > 25%,> 32% and > 56%, respectively). Following escape for inadequate efficacy, many patients achieved ACR20 at the end of the study, 35% after escape from TCZ-SC, and 63% from placebo. The rates of serious adverse events [(11.20/100 patient-years (PY)] including serious infections (3.25/100 PY) were stable through Week 96. No association between anti-TCZ antibody development and loss of efficacy or adverse events was observed. CONCLUSION:Efficacy and safety of TCZ-SC q2w was maintained up to 2 years and remained comparable with previously published data for intravenous TCZ. Dose escalation to weekly TCZ-SC was associated with ACR responses in prior nonresponders and was well tolerated.
RCT Entities:
OBJECTIVE: To evaluate the longterm efficacy and safety of subcutaneous tocilizumab (TCZ-SC) every 2 weeks (q2w) over 2 years in patients with rheumatoid arthritis who have an inadequate response to disease-modifying antirheumatic drugs (DMARD). METHODS:Patients (n = 656) were randomized 2:1 to TCZ-SC 162 mg q2w or placebo-SC q2w plus DMARD. After a 24-week double-blind period, patients (n = 457) were rerandomized to open-label TCZ-SC q2w by means of prefilled syringe or autoinjector. Escape therapy with weekly TCZ-SC was available for patients with inadequate efficacy from Week 12. Maintenance of response and safety to 2 years was assessed. Analyses used nonresponder imputation. RESULTS: The American College of Rheumatology (ACR) 20 response after TCZ-SC was maintained beyond Week 24 and was > 70% at each timepoint. ACR50/70, 28-joint Disease Activity Score remission, and ≥ 0.30 decrease from baseline in the Health Assessment Questionnaire-Disability Index response rates were also maintained after Week 24 in the TCZ-SC arm (≥ 50%, > 25%,> 32% and > 56%, respectively). Following escape for inadequate efficacy, many patients achieved ACR20 at the end of the study, 35% after escape from TCZ-SC, and 63% from placebo. The rates of serious adverse events [(11.20/100 patient-years (PY)] including serious infections (3.25/100 PY) were stable through Week 96. No association between anti-TCZ antibody development and loss of efficacy or adverse events was observed. CONCLUSION: Efficacy and safety of TCZ-SC q2w was maintained up to 2 years and remained comparable with previously published data for intravenous TCZ. Dose escalation to weekly TCZ-SC was associated with ACR responses in prior nonresponders and was well tolerated.