Rheumatoid Arthritis Clinical Trial
Official title:
Therapeutic Drug Monitoring of Tocilizumab in Rheumatoid Arthritis
Rationale: A wide range of serum trough concentrations is observed in tocilizumab-treated
rheumatoid arthritis (RA) patients, while 1 mg/L tocilizumab is sufficient to block systemic
interleukin-6 receptor. A substantial proportion of patients has higher serum tocilizumab
concentrations and is likely to be overexposed. We expect that patients can at least reduce
the dose aiming for a concentration of 5 mg/L without reducing efficacy.
Objective: To evaluate the feasibility of the study after 20 weeks of follow-up, this
includes the evaluation of the dose-reduction algorithm in tocilizumab-treated patients with
RA.
Study design: Double-blind randomized controlled pilot study with a follow up of 20 weeks.
Study population: Consecutive RA patients that are treated with tocilizumab intravenously
every four weeks for at least 24 weeks. Patients are screened for tocilizumab concentration
after signing informed consent.
Intervention: Patients with a concentration below 5 mg/L will continue the dose. Those
patients with a tocilizumab concentration above 5 mg/L are randomly assigned (2:1) to dose
reduction or to continuation of the standard care tocilizumab dose. In the intervention
group, the precise dose-reduction is calculated per patient in order to achieve a tocilizumab
concentration of 5 mg/L (range 4-6 mg/L).
Main study parameters/endpoints:
The feasibility of the study logistics is evaluated according to the dropout rate and
patients opinion about the study. Second, the proportion of patients achieving the targeted
tocilizumab concentration after dose reduction is evaluated.
Nature and extent of the burden and risks associated with participation, benefit and group
relatedness:
Dose-reduction will lead to lower drug costs and possibly to reduce the risk of adverse
events. Since we lower the tocilizumab concentration in a proportion of the patients, risk of
a exacerbation of the disease exists. In this case, patients will receive their original
dose. Previous studies showed that disease activity is controlled adequately after returning
to the standard dose. However, our algorithm is designed to reach concentrations of 5 mg/L
(range 4-6 mg/L) and studies showed that 1 mg/L of tocilizumab is sufficient to maintain
clinical effect. The expected burden of this study is low, since study visits are planned at
the time of infusion and therefore do not take extra time. The additional burden consists of
an extra blood sample taken every visit and the fingerprick that is performed once.
Status | Recruiting |
Enrollment | 80 |
Est. completion date | December 2019 |
Est. primary completion date | June 30, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - RA according to the ACR 1987 or 2010 criteria; - Current use of tocilizumab IV, with a consistent interval of 4 weeks for at least 24 weeks. - 18 years of age and older. Exclusion Criteria: - A potential subject will be excluded from participation in case of a scheduled surgery in the next 20 weeks or other preplanned reasons for treatment discontinuation. - Children, pregnant women and individuals with a lack of judgement. |
Country | Name | City | State |
---|---|---|---|
Israel | Department of Rheumatology, Tel Aviv Medical Center | Tel Aviv |
Lead Sponsor | Collaborator |
---|---|
Tel-Aviv Sourasky Medical Center | Amsterdam Rheumatology and Immunology Center |
Israel,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Disease flare rate | Percent of patients experiencing a flare in RA disease activity according to DAS28-ESR score from week 0 until week 20. | 20 weeks | |
Primary | Drop-out rate | Percentage of patients completing 20-weeks on assigned treatment arm without withdrawing from the trial. | 20 weeks | |
Secondary | DAS28 score | The DAS28 (Disease Activity Score 28) is a system developed and validated by the EULAR (European League Against Rheumatism) to measure the progress and improvement of Rheumatoid Arthritis. DAS28 is often used in clinical trials for the development of RA. DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS 28 below the value of 2.6 is interpreted as Remission. "28" describes the number of different joints including in the measurement: proximal interphalangeal joints (10 joints), metacarpophalangeal joints (10), wrists (2), elbows (2), shoulders (2), knees (2). When looking at these joints, both the number of joints with tenderness upon touching and swelling are counted. In addition, the erythrocyte sedimentation rate is measured. Also, the patient makes a subjective assessment of disease activity during the preceding 7 days on a scale between 0 and 100, where 0 is "no activity" and 100 is "highest activity possible". |
20 weeks | |
Secondary | SDAI score | Disease activity according to Simplified Disease Activity Index (SDAI) score. The simplified disease activity index (SDAI) is an established instruments to measure disease activity in rheumatoid arthritis (RA). The SDAI is the sum of five outcome parameters tender joint count based on a 28-joint assessment swollen joint count based on a 28-joint assessment patient global assessment of disease activity on a visual analogue scale (VAS) investigator global assessment of disease activity on a visual analogue scale (VAS) CRP:level of CRP (C-reactive protein) measured in mg/dl |
20 weeks | |
Secondary | CDAI score | Disease activity according to Clinical Disease Activity Index (CDAI) score. The clinical disease activity index (CDAI) is an established instrument to measure disease activity in rheumatoid arthritis (RA). The CDAI is composite index calculated as the sum of four outcome parameters tender joint count based on a 28-joint assessment swollen joint count based on a 28-joint assessment patient global assessment of disease activity on a visual analogue scale (VAS) investigator global assessment of disease activity on a visual analogue scale (VAS) |
20 weeks | |
Secondary | Swollen joint count | Number of swollen joints out of a total of 66 joints. | 20 weeks | |
Secondary | Tender joint count | Number of swollen joints out of a total of 68 joints. | 20 weeks | |
Secondary | patient pain VAS | Quantification of joint pain in the past week by the patient according to the patient pain visual analogue score (VAS). The VAS is self-completed by the patient. The respondent is asked to place a 10 cm line perpendicular to the VAS line at the point that represents their pain intensity. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the "no pain" anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity. |
20 weeks | |
Secondary | physician global VAS | Quantification of general state of the patient in the past week, by the physician, according to the physician global visual analogue score (VAS). The VAS is completed by the physician. The respondent is asked to place a 10 cm line perpendicular to the VAS line at the point that represents all the ways arthritis affects the patient. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the "no affect" anchor and the physician's mark, providing a range of scores from 0-100. A higher score indicates a worse disase state. |
20 weeks | |
Secondary | patient disease activity VAS | Quantification of overall disease activity in the past week by the patient according to the patient disease activity visual analogue score (VAS). Quantification of diseasse activity in the past week by the patient according to the patient disease activity visual analogue score (VAS). The VAS is self-completed by the patient. The respondent is asked to place a 10 cm line perpendicular to the VAS line at the point that represents t all the ways arthritis affects the patient. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the "no affect" anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates worse disease activity. |
20 weeks | |
Secondary | sHAQ | Functional status assessed with the simplified Health Assessment Questionnaire (sHAQ). The sHAQ is a general index. In the context of Rheumatoid arthritis, this index considers how arthritis has an impact on everyday life. The questionnaire is designed to be completed by the patient himself, without the help of a doctor. The value of the sHAQ index can be interpreted in terms of three categories: from 0 to 1: mild difficulties to moderate disability, from 1 to 2: disability moderate to severe, from 2 to 3: severe to very severe disability. |
20 weeks | |
Secondary | RAPID-3 | Disease activity according to the RAPID-3 questionnaire completed by the patient. RAPID3 or Routine Assessment of Patient Index Data 3 is a disease activity index that is computed from a short and simple questionnaire. It assesses the effect of arthritis on daily life. RAPID3 is designed to be quick and easy to fill by a patient, without requiring the help of a practitioner. Although it is quite simple, this index accurately captures the disease activity and is sensitive to change. |
20 weeks |
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