To assess the efficacy of adding subcutaneous TCZ to csDMARD therapy compared with adding oral prednisone (10 mg daily).
ID
Source
Brief title
Condition
- Synovial and bursal disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in CDAI from baseline to 6, 9, and 12 months
Secondary outcome
- Change in CDAI from baseline to 6 months - Change in SDAI and change in DAS28
from baseline to 12 months. - Drug retention rate, defined as the proportion of
patients at 12 months on the treatment (TCZ/prednisone) to which they were
allocated. - Switch rate, defined as the proportion of patients who switched
during the study period to treatment of the other arm. - Average dose of TCZ or
prednisone from baseline up to 12 months. - ACR20, ACR50, and ACR70 response
(using 28 joint counts), and EULAR good or moderate response (Appendix C.) -
Proportion of patients reaching a state of clinical remission at any time
during the study defined by different criteria: CDAI<=2.8 AND max 1 swollen
joint of the 28 joint count, CDAI<=2.8, SDAI<=3, DAS28<2.6, and ACR-EULAR Boolean
remission (defined by a tender joint count <=1, a swollen joint count <=1, a
C-reactive protein <=1mg/dL, and a patient global assessment <=1 on a 0-10
scale). - Time to reach a state of clinical remission defined by above
mentioned criteria. - Proportion of patients reaching a state of low disease
activity at any time during the study defined by different criteria: 2.8
Background summary
In rheumatoid arthritis (RA) patients with insufficient response to disease
modifying anti-rheumatic drugs (DMARDs) it is unknown whether addition of
tocilizumab (TCZ) to conventional synthetic (cs) DMARDs has superior efficacy
compared to addition of prednisone. If so, TCZ should be considered instead of
prednisone. On the other hand administration of prednisone may be a highly
cost-effective approach. Comparative trial data are lacking.
Study objective
To assess the efficacy of adding subcutaneous TCZ to csDMARD therapy compared
with adding oral prednisone (10 mg daily).
Study design
This study is a multicenter, pragmatic, randomized, open label trial
coordinated by the Department of Rheumatology & Clinical Immunology, University
Medical Center (UMC) Utrecht.
Intervention: Patients will be randomized in a 1:1 ratio to receive either TCZ
(subcutaneous 162 mg/week) or prednisone (oral 10 mg/day) in addition to
csDMARD therapy.
Intervention
Arm 1: Tocilizumab subcutaneously 162 mg/ week
Arm 2: Prednison orally 10 mg/day
Study burden and risks
Study visits will be performed at screening and at baseline and month 1, 2, 3,
6, 9 and 12 (8 in total). This schedule follows regular visits to the
outpatient clinic in standard of care for RA patients with active disease.
Joint examination will be performed. x-rays of hands and feet and a DEXA-scan
will be performed at baseline and at 12 months. Blood samples will be obtained
in accordance with clinical practice. In addition to clinical practice, IgM-RF
and anti-CCP will be determined. Also for the patients randomized to the
prednisone arm bDMARD screening will be done in addition to clinical practice:
determination of HBsAg and HCV, quantiferon test and X-thorax.
In the HandScan substudy, patients will also undergo a HandScan at the
3-monthly study visits. Also, patients will be asked to fill in 6
questionnaires at the 3-monthly study visits, which will take 20-30 minutes.
All patients will receive active medication with well-known mechanisms of
action and established effects in RA, used in clinical practice. Treatment
adjustments will be done according to the treat-to-target (T2T) principle
following predefined criteria. The treatment regimens administered are standard
clinical care and the assessments performed in this study are similar to
clinical care in this patient group. Overall, the risks in this study are
perceived to be similar to those of patients in clinical practice.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
- Able and willing to give written informed consent - Have sufficient knowledge
of the Dutch language to be able to comply with the requirements of the study
protocol - At least 18 years of age - Diagnosed as having RA and meeting the
2010 ACR/EULAR criteria for RA - Active RA defined by CDAI>10 and at least 1
swollen joint of the 28 joint count - For patients < 65 years of age: On stable
treatment with csDMARDs for >= 8 weeks prior to the screening visit - Are
eligible to start with a biological according to the 2019 EULAR guidelines for
management of RA: previous treatment with >=2 csDMARDs OR previous treatment
with >=1 csDMARD with presence of a prognostically unfavorable factor.
Exclusion criteria
• Having a contraindication for treatment with systemic GCs (as determined by
the treating rheumatologist, in line with regular care).
• Having a contraindication for treatment with TCZ, as determined by the
treating rheumatologist or as described in the Summary of Product
Characteristics (SPC) Paragraph 4.3, page 33. *Special warnings and precautions
for use* as described in the SPC Paragraph 4.4, page 33, should be strictly
followed.
• Use of systemic GCs (including i.a. GCs) within 4 weeks before the screening
visit.
• Current use of a bDMARD or tsDMARD;i.e. these need to be discontinued before
start of study medication. Wash out periods for bDMARDs and tsDMARDs should
follow routine care.
• Treatment with any investigational agent within 4 weeks prior to the
screening visit.
• Having any other inflammatory rheumatic disease than RA. Secondary Sjögren*s
syndrome will be allowed, as well as RA-overlap syndromes that are primarily
treated as RA at the time of screening.
• Female who is pregnant (by anamnesis) or breast feeding, or considering
becoming pregnant during the study period.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-003037-28-NL |
| CCMO | NL68492.041.19 |