Clinical trial NCT01120366: Success of Tocilizumab in RA Patients With Remission Induction and Sustained Efficacy After Discontinuation
Official title: Success of Tocilizumab in RA Patients With Remission Induction and Sustained Efficacy After Discontinuation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Lead sponsor: SURPRISE Study Group
Sponsor class: NETWORK
First posted: 2010-05-10
Enrollment: 233
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to investigate the efficacy and safety of the humanized anti-human IL-6 receptor monoclonal antibody tocilizumab (TCZ) either in monotherapy or in combination therapy with methotrexate (MTX) in patients with an inadequate response to treatment with MTX.

Furthermore, in patients who have been able to achieve control of disease activity via the above therapy, we investigate the possibility of stopping TCZ and verify safety when TCZ is restarted after disease recurrence.

Detailed description: In this study, we aim to prospectively and randomly evaluate efficacy for changes in clinical remission and joint destruction in RA patients in treatment with TCZ monotherapy(SWITCH) and in combination therapy with MTX(ADD-ON), and also to investigate the best therapeutic approach to achieve discontinuation.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with RA in accordance with the 1987 classification criteria of ACR
* Aged 20 to 75 years inclusive at enrolment (within 2 weeks before starting treatment with the investigational drug)
* Treated with MTX at ≥6 mg/week for at least 8 weeks immediately before enrolment
* Rheumatoid arthritis of duration ≤10 years
* DAS28-ESR ≥3.2 (within 2 weeks before starting treatment with the investigational drug)
* Having received and thoroughly understood an adequate explanation about participation in the study, patients who have personally and voluntarily provided written informed consent

Major exclusion criteria:

* Patients who were Steinbrocker Class IV.
* Patients who received leflunomide within 12 weeks, DMARDs other than MTX within 8 weeks , or tacrolimus within 4 weeks before the 1st TCZ infusion.
* Patients who previously received biologic DMARDs including TCZ.

Primary outcomes:
measure: DAS28-ESR remission at 24 weeks
timeFrame: at 24 week
measure: Changes over time in the number of patients maintaining discontinuation (maintenance rate)
timeFrame: Week 52 to Week 104
Secondary outcomes:
measure: Change in TSS score
timeFrame: at 52 weeks (after treatment initiation)
measure: Change of DAS28-ESR remission rate
timeFrame: Week 0 to Week 52
measure: Change of ACR response rate
timeFrame: Week 0 to Week 52
measure: EQ5D scores over time
timeFrame: Week 0 to Week 52
measure: J-HAQ/HAQ scores over time
timeFrame: Week 0 to Week 52
measure: SDAI, CDAI, and Boolean remission rates
timeFrame: Week 0 to Week 52
measure: TNF-α over time
timeFrame: Week 0 to Week 52
measure: Between-group comparison of the discontinuation rate after an achievement of remission
timeFrame: Week 0 to Week 104
measure: Factor analysis of patients maintaining discontinuation
timeFrame: Week 0 to Week 104
measure: Time course of DAS28 after restarting TCZ (between-group comparison)
timeFrame: Week 52 to Week 104
measure: Change in TSS score
timeFrame: Week 52 to Week 104
measure: Time course of DAS28 after restarting MTX following suspension of discontinuation in the TCZ monotherapy group in Step 1
timeFrame: Week 52 to Week 104
measure: SDAI, CDAI, and Boolean remission rates
timeFrame: Week 52 to Week 104
Other outcomes:
measure: Adverse events
timeFrame: During the study period
Locations:
city: Sapporo
country: Japan
facility: Hokkaido Medical Center for Rheumatic Diseases Hospital
state: Hokkaido
city: Ayautagun
country: Japan
facility: Utazu Hama Clinic
city: Bunkyo-ku
country: Japan
facility: Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
city: Fukushima
country: Japan
facility: Fukushima Red-Cross Hospital
city: Higashihiroshima
country: Japan
facility: Higashihiroshima Memorial Hospital
city: Ichikawa
country: Japan
facility: Tokyo Dental College Ichikawa General Hospital
city: Itabashi-ku
country: Japan
facility: Itabashi Medical Center
city: Izumo
country: Japan
facility: Shimane University Faculty of Medicine
city: Kawagoe
country: Japan
facility: Saitama Medical Center, Saitama Medical University
city: Kida-gun
country: Japan
facility: Kagawa University
city: Kitakyusyu
country: Japan
facility: University of Occupational and Environmental Health Hospital
city: Kurashiki
country: Japan
facility: Kurashiki Sweet Hospital
city: Kyoto
country: Japan
facility: Kyoto University Graduate School of Medicine
city: Matsumoto
country: Japan
facility: Marunouchi Hospital
city: Matsuyama
country: Japan
facility: Dogo Spa Hospital
city: Miyazaki
country: Japan
facility: Zenjinkai Shimin-no-mori Hospital
city: Nagasaki
country: Japan
facility: Nagasaki University Graduate School of Biomedical Sciences
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center
city: Niigata
country: Japan
facility: Niigata University Graduate School of Medical and Dental Sciences
city: Nishinomiya
country: Japan
facility: Department of Internal Medicine, Hyogo College of Medicine
city: Oita
country: Japan
facility: Oribe Rheumatism and Internal Medicine Clinic
city: Sapporo
country: Japan
facility: Hokkaido University Graduate School of Medicine
city: Sasebo
country: Japan
facility: Sasebo Chuo Hospital
city: Shibata
country: Japan
facility: Niigata Rheumatic Center
city: Suita
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: Institute of Rheumatology, Tokyo Women's Medical University
city: Tokyo
country: Japan
facility: Keio University Hospital
city: Tokyo
country: Japan
facility: The University of Tokyo Graduate School of Medicine
city: Tomishiro
country: Japan
facility: Tomishiro Chuo Hospital
city: Yokohama
country: Japan
facility: Yokohama Minami Kyousai Hospital
Study officials:
affiliation: Keio University
name: Tsutomu Takeuchi
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kato M, Kaneko Y, Tanaka Y, Inoo M, Kobayashi-Haraoka H, Amano K, Miyata M, Murakawa Y, Yasuoka H, Hirata S, Nagasawa H, Tanaka E, Miyasaka N, Yamanaka H, Yamamoto K, Yokota I, Atsumi T, Takeuchi T. Predictive value of serum amyloid a levels for requirement of concomitant methotrexate in tocilizumab initiation: A post hoc analysis of the SURPRISE study. Mod Rheumatol. 2020 May;30(3):442-449. doi: 10.1080/14397595.2019.1621026. Epub 2019 Jun 7.
citation: Kaneko Y, Kato M, Tanaka Y, Inoo M, Kobayashi-Haraoka H, Amano K, Miyata M, Murakawa Y, Yasuoka H, Hirata S, Tanaka E, Miyasaka N, Yamanaka H, Yamamoto K, Takeuchi T; SURPRISE study group. Tocilizumab discontinuation after attaining remission in patients with rheumatoid arthritis who were treated with tocilizumab alone or in combination with methotrexate: results from a prospective randomised controlled study (the second year of the SURPRISE study). Ann Rheum Dis. 2018 Sep;77(9):1268-1275. doi: 10.1136/annrheumdis-2018-213416. Epub 2018 May 31.
citation: Kaneko Y, Atsumi T, Tanaka Y, Inoo M, Kobayashi-Haraoka H, Amano K, Miyata M, Murakawa Y, Yasuoka H, Hirata S, Nagasawa H, Tanaka E, Miyasaka N, Yamanaka H, Yamamoto K, Takeuchi T. Comparison of adding tocilizumab to methotrexate with switching to tocilizumab in patients with rheumatoid arthritis with inadequate response to methotrexate: 52-week results from a prospective, randomised, controlled study (SURPRISE study). Ann Rheum Dis. 2016 Nov;75(11):1917-1923. doi: 10.1136/annrheumdis-2015-208426. Epub 2016 Jan 5.