Josef S Smolen1, Stanley B Cohen2, Hans-Peter Tony3, Morton Scheinberg4, Alan Kivitz5, Andra Balanescu6, Juan Gomez-Reino7, Liyi Cen8, Johann Poetzl9, Tamas Shisha10, Dmitrij Kollins9. 1. Department of Rheumatology, Medical University of Vienna, Vienna, Austria. 2. Department of Rheumatology, Metroplex Clinical Research Center, Dallas, TX, USA. 3. Department of Internal Medicine, Rheumatology/Clinical Immunology, University Hospital of Wuerzburg, Wuerzburg, Germany. 4. Rheumatology Section, Orthopedic Department, Hospital Israelita Albert Einstein, Sao Paulo, Brazil. 5. Altoona Center for Clinical Research, Altoona Arthritis and Osteoporosis Center, Duncansville, PA, USA. 6. Sf. Maria Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. 7. Fundacion IDIS, Hospital Clinico Universitario, Santiago, Spain. 8. Biostatistics Biosimilars Analytics, Novartis Pharmaceuticals Corp, East Hanover, NJ, USA. 9. Biosimilar Clinical Development, Hexal AG, Holzkirchen, Germany. 10. Translational Medicine, Novartis Institute of Biomedical Research, Basel, Switzerland.
Abstract
OBJECTIVES: This report provides data for the extent of B cell depletion and recovery, efficacy, safety and immunogenicity of Sandoz rituximab (SDZ-RTX; GP2013; Rixathon®) compared with reference rituximab (Ref-RTX) up to week 52 of the ASSIST-RA study. METHODS: Patients were randomized to SDZ-RTX or Ref-RTX in combination with methotrexate according to the RTX label. The primary endpoint was analysed at week 24. Responders (28-joint DAS [DAS28] decrease from baseline >1.2) at week 24 with residual disease activity (DAS28 ≥2.6) were eligible for a second treatment course between week 24 and 52. Endpoints after week 24 included change from baseline in peripheral B cells, DAS28, ACR 20% response rate (ACR20), Clinical and Simplified Disease Activity Indexes (CDAI, SDAI) and HAQ disability index (HAQ-DI). Safety and immunogenicity were assessed by the incidence of adverse events and antidrug antibodies. RESULTS: Primary and secondary endpoints up to week 24 were met. Overall, 260/312 randomized patients completed treatment up to week 52. SDZ-RTX resulted in B cell concentrations over time similar to Ref-RTX. The efficacy of SDZ-RTX was similar to Ref-RTX up to week 52, as measured by DAS28, ACR20/50/70, CDAI, SDAI and HAQ-DI. Safety of SDZ-RTX was similar to Ref-RTX regarding frequency, type and severity of adverse events, which were consistent with the known Ref-RTX safety profile. The incidence of antidrug antibodies was low and transient similarly across treatment groups. CONCLUSION:SDZ-RTX demonstrated similar B cell concentrations over time, efficacy, safety and immunogenicity to Ref-RTX over 52 weeks of the ASSIST-RA study.
RCT Entities:
OBJECTIVES: This report provides data for the extent of B cell depletion and recovery, efficacy, safety and immunogenicity of Sandozrituximab (SDZ-RTX; GP2013; Rixathon®) compared with reference rituximab (Ref-RTX) up to week 52 of the ASSIST-RA study. METHODS:Patients were randomized to SDZ-RTX or Ref-RTX in combination with methotrexate according to the RTX label. The primary endpoint was analysed at week 24. Responders (28-joint DAS [DAS28] decrease from baseline >1.2) at week 24 with residual disease activity (DAS28 ≥2.6) were eligible for a second treatment course between week 24 and 52. Endpoints after week 24 included change from baseline in peripheral B cells, DAS28, ACR 20% response rate (ACR20), Clinical and Simplified Disease Activity Indexes (CDAI, SDAI) and HAQ disability index (HAQ-DI). Safety and immunogenicity were assessed by the incidence of adverse events and antidrug antibodies. RESULTS: Primary and secondary endpoints up to week 24 were met. Overall, 260/312 randomized patients completed treatment up to week 52. SDZ-RTX resulted in B cell concentrations over time similar to Ref-RTX. The efficacy of SDZ-RTX was similar to Ref-RTX up to week 52, as measured by DAS28, ACR20/50/70, CDAI, SDAI and HAQ-DI. Safety of SDZ-RTX was similar to Ref-RTX regarding frequency, type and severity of adverse events, which were consistent with the known Ref-RTX safety profile. The incidence of antidrug antibodies was low and transient similarly across treatment groups. CONCLUSION:SDZ-RTX demonstrated similar B cell concentrations over time, efficacy, safety and immunogenicity to Ref-RTX over 52 weeks of the ASSIST-RA study.