Efficacy and safety of HLX01 in patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy: a phase 3 study
Abstract Background To evaluate the efficacy and safety of HLX01, a rituximab biosimilar, as combination therapy with methotrexate in Chinese patients with active rheumatoid arthritis who had inadequate responses to methotrexate. Methods In this double-blind, placebo-controlled phase 3 trial, biolog...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-022-02821-x |
| _version_ | 1818218959059550208 |
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| author | Xiaofeng Zeng Ju Liu Xiumei Liu Lijun Wu Yi Liu Xiangping Liao Huaxiang Liu Jiankang Hu Xin Lu Linjie Chen Jian Xu Zhenyu Jiang Fu-ai Lu Huaxiang Wu Ying Li Qingyu Wang Jun Zhu the HLX01-RA03 Investigators |
| author_facet | Xiaofeng Zeng Ju Liu Xiumei Liu Lijun Wu Yi Liu Xiangping Liao Huaxiang Liu Jiankang Hu Xin Lu Linjie Chen Jian Xu Zhenyu Jiang Fu-ai Lu Huaxiang Wu Ying Li Qingyu Wang Jun Zhu the HLX01-RA03 Investigators |
| author_sort | Xiaofeng Zeng |
| collection | DOAJ |
| description | Abstract Background To evaluate the efficacy and safety of HLX01, a rituximab biosimilar, as combination therapy with methotrexate in Chinese patients with active rheumatoid arthritis who had inadequate responses to methotrexate. Methods In this double-blind, placebo-controlled phase 3 trial, biologic-naïve patients with moderate-to-severe active rheumatoid arthritis and inadequate responses to methotrexate were randomized 2:1 to receive 1000 mg HLX01 or placebo intravenously on days 1 and 15. On the first day of weeks 24 and 26, patients in both groups received 1000 mg HLX01 via intravenous infusion. The primary endpoint was the American College of Rheumatology (ACR) 20 response rate at week 24. Secondary endpoints including efficacy, safety, immunogenicity, pharmacokinetics and pharmacodynamics were assessed up to week 48. Results Between 28 May 2018 and 11 September 2020, 275 patients were randomized to the HLX01 group (n = 183) or the placebo group (n = 92). At week 24, the proportion of patients achieving ACR20 response was significantly greater in the HLX01 group compared with the placebo group in the intention-to-treat population (60.7% vs 35.9%; P < 0.001) and per-protocol set (60.3% vs 37.1%; P < 0.001). Most secondary efficacy endpoints favoured HLX01 when assessed at weeks 12, 24, 36 and 48. Incidences of treatment-emergent adverse events were similar between groups. Infusion-related reactions occurred more frequently following the initial two doses of HLX01 than the subsequent doses. Conclusions HLX01 plus methotrexate improved clinical outcomes compared with placebo in Chinese patients with rheumatoid arthritis who had inadequate responses to methotrexate. This treatment regimen was well tolerated, showing comparable safety profiles to placebo. Trial registration ClinicalTrials.gov , NCT03522415 . Registered on 11 May 2018. |
| first_indexed | 2024-12-12T07:32:02Z |
| format | Article |
| id | doaj.art-bf56f5286abe41569c25ccc9aaa15639 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-12-12T07:32:02Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-bf56f5286abe41569c25ccc9aaa156392022-12-22T00:32:59ZengBMCArthritis Research & Therapy1478-63622022-06-0124111110.1186/s13075-022-02821-xEfficacy and safety of HLX01 in patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy: a phase 3 studyXiaofeng Zeng0Ju Liu1Xiumei Liu2Lijun Wu3Yi Liu4Xiangping Liao5Huaxiang Liu6Jiankang Hu7Xin Lu8Linjie Chen9Jian Xu10Zhenyu Jiang11Fu-ai Lu12Huaxiang Wu13Ying Li14Qingyu Wang15Jun Zhu16the HLX01-RA03 InvestigatorsDepartment of Rheumatology, Peking Union Medical College HospitalDepartment of Rheumatology, Jiujiang No. 1 People’s HospitalDepartment of Rheumatology, First Hospital of Shanxi Medical UniversityDepartment of Rheumatology, People’s Hospital of Xinjiang Uygur Autonomous RegionDepartment of Rheumatology, West China Hospital of Sichuan UniversityDepartment of Nephrology, Chenzhou First People’s HospitalDepartment of Rheumatology, Qilu Hospital of Shandong UniversityDepartment of Rheumatology, Jiangxi Pingxiang People’s HospitalDepartment of Rheumatology, China-Japan Friendship HospitalDepartment of Rheumatology, The First Affiliated Hospital of Bengbu Medical CollegeDepartment of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical UniversityDepartment of Rheumatology, The First Hospital of Jilin UniversityDepartment of Rheumatology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and TechnologyDepartment of Rheumatology, The Second Affiliated Hospital Zhejiang University School of MedicineShanghai Henlius Biotech, Inc.Shanghai Henlius Biotech, Inc.Shanghai Henlius Biotech, Inc.Abstract Background To evaluate the efficacy and safety of HLX01, a rituximab biosimilar, as combination therapy with methotrexate in Chinese patients with active rheumatoid arthritis who had inadequate responses to methotrexate. Methods In this double-blind, placebo-controlled phase 3 trial, biologic-naïve patients with moderate-to-severe active rheumatoid arthritis and inadequate responses to methotrexate were randomized 2:1 to receive 1000 mg HLX01 or placebo intravenously on days 1 and 15. On the first day of weeks 24 and 26, patients in both groups received 1000 mg HLX01 via intravenous infusion. The primary endpoint was the American College of Rheumatology (ACR) 20 response rate at week 24. Secondary endpoints including efficacy, safety, immunogenicity, pharmacokinetics and pharmacodynamics were assessed up to week 48. Results Between 28 May 2018 and 11 September 2020, 275 patients were randomized to the HLX01 group (n = 183) or the placebo group (n = 92). At week 24, the proportion of patients achieving ACR20 response was significantly greater in the HLX01 group compared with the placebo group in the intention-to-treat population (60.7% vs 35.9%; P < 0.001) and per-protocol set (60.3% vs 37.1%; P < 0.001). Most secondary efficacy endpoints favoured HLX01 when assessed at weeks 12, 24, 36 and 48. Incidences of treatment-emergent adverse events were similar between groups. Infusion-related reactions occurred more frequently following the initial two doses of HLX01 than the subsequent doses. Conclusions HLX01 plus methotrexate improved clinical outcomes compared with placebo in Chinese patients with rheumatoid arthritis who had inadequate responses to methotrexate. This treatment regimen was well tolerated, showing comparable safety profiles to placebo. Trial registration ClinicalTrials.gov , NCT03522415 . Registered on 11 May 2018.https://doi.org/10.1186/s13075-022-02821-xRheumatoid arthritisRituximabMethotrexatePhase 3Biologic disease-modifying anti-rheumatic drug |
| spellingShingle | Xiaofeng Zeng Ju Liu Xiumei Liu Lijun Wu Yi Liu Xiangping Liao Huaxiang Liu Jiankang Hu Xin Lu Linjie Chen Jian Xu Zhenyu Jiang Fu-ai Lu Huaxiang Wu Ying Li Qingyu Wang Jun Zhu the HLX01-RA03 Investigators Efficacy and safety of HLX01 in patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy: a phase 3 study Arthritis Research & Therapy Rheumatoid arthritis Rituximab Methotrexate Phase 3 Biologic disease-modifying anti-rheumatic drug |
| title | Efficacy and safety of HLX01 in patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy: a phase 3 study |
| title_full | Efficacy and safety of HLX01 in patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy: a phase 3 study |
| title_fullStr | Efficacy and safety of HLX01 in patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy: a phase 3 study |
| title_full_unstemmed | Efficacy and safety of HLX01 in patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy: a phase 3 study |
| title_short | Efficacy and safety of HLX01 in patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy: a phase 3 study |
| title_sort | efficacy and safety of hlx01 in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy a phase 3 study |
| topic | Rheumatoid arthritis Rituximab Methotrexate Phase 3 Biologic disease-modifying anti-rheumatic drug |
| url | https://doi.org/10.1186/s13075-022-02821-x |
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