The Efficacy and Safety of Tofacitinib (TF) With Iguratimod (IGU) on RA

Qilu Hospital of Shandong University100 enrolled

Overview

RA is a common autoimmune disease that causes joint damage.It is necessary to reach the standard as soon as possible and give effective drugs according to the patient's disease activity to avoid disability. Tofacitinib(TF) is a new type of oral tyrosine kinase inhibitor (JAKi) for the treatment of moderate to severe active RA. However, there is alack of Chinese data on the joint scheme, long-term use, maintenance and stop of TF in the real world. We will use the new JAK combination regimen to treat RA patients, and carry out long-term clinical follow-up for 30 weeks.

Objective: To observe the clinical efficacy and safety of TF combined with/ without IGU for 30 weeks in patients with moderate to severe active RA with different clinical characteristics and subgroups by using a prospective cohort , and to find the best combination scheme of TF.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

100

Conditions

Arthritis, Rheumatoid

Interventions

IguratimodDRUG

Iguratimod tablet，25mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint.

TofacitinibDRUG

Tofacitinib,5mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint.

PredDRUG

Pred, 0-10mg, po, once per day (Qd) prescribed if needed and adjusted due to patient response.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: Patients who meet the following inclusion criteria will be eligible to participate in the study: 1. Patients who meet RA standards in 1987 and 2010 or ERA standards in 2012; 2. Age \> 18 years old; 3. the extrapulmonary manifestations of RA were stable; 4. Patients with NSAIDs tolerance; 5. DAS28-ESR is highergreater than 2.6. Exclusion Criteria: Patients who meet any of the following criteria will be excluded from the study: 1. Patients with acute and chronic infection; 2. Platelet count \< 80\*10\^9/L, or white blood cell \< 3\*10\^9/L; 3. ALT or AST is 2 times higher than the upper limit of normal value; 4. Renal insufficiency: serum Cr ≥ 176 umol/L; 5. Pregnant or lactating women (breastfeeding); 6. Have a history of malignant tumor (the cure time is less than 5 years); 7. Patients with severe hypertension and cardiac insufficiency; 8. Other diseases or conditions in which immune suppressants cannot be used; 9. People who are allergic to TF.

Locations (1)

Qilu Hospital

Jinan, Shandong, China

Outcomes

Primary Outcomes

The percentage of patients who achieve clinical remission at week 30 using European League Against Rheumatism (EULAR) response criteria DAS28

The percentage of patients whose Disease Activity Score in 28 Joints (DAS28) achieve remission（DAS28-ESR≤ 2.6）and Low Disease Activity (DAS28-ESR ≤ 3.2). The DAS28 is a composite score derived from 4 of these measures，that is the count of tender joint count（TJC, 0-28）and swollen joint count（SJC, 0-28）, measure erythrocyte sedimentation rate (ESR, mm/h) or C reactive protein (CRP, mg/L) and to make a patient assessment of disease activity i.e. 'global assessment of health' (GH) using a 100 mm visual analogue scale (VAS) with 0 = best, 100 = worst. DAS28 values were calculated as follows: DAS28- ESR = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 x GH. High disease activity: DAS28-ESR \> 5.1; Moderate disease activity: 5.1≥ DAS28 \> 3.2 to 5.1; Low disease activity (LDA) and Remission mean Clinical remission.

Time frame: week 30

Secondary Outcomes

The percentage of patients who achieve clinical remission using DAS28-ESR at week 18

The percentage of patients whose DAS28 achieve remission（DAS28-ESR≤ 2.6）and Low Disease Activity (DAS28-ESR ≤ 3.2) at week 18.

Time frame: week 18

The percentage of patients who achieve clinical remission using DAS28-ESR at week 6

The percentage of patients whose DAS28 achieve remission（DAS28-ESR≤ 2.6）and Low Disease Activity (DAS28-ESR ≤ 3.2) at week 18.

Time frame: week 6

Percentage of Disease Activity Score 28 (DAS28) -ESR Criteria Responders at week 30

△DAS28 indicates the decline of DAS28-ESR from the baseline to week 30. EULAR response states were classified as follows: good responders were patients with an improvement from baseline (△DAS28-ESR) of \> 1.2 and a DAS28-ESR at week 30 ≤ 3.2. Moderate responders: △DAS28 \> 1.2 and still DAS28 \> 3.2 at week 30, or 1.2 ≥△DAS28 \> 0.6 and DAS28 ≤ 5.1 at week 30. Nonresponders：△DAS28 ≤0.6 or DAS28 \>5.1 at week 30. DAS28-defined remission was classified as a score of \<2.6.

Data from ClinicalTrials.gov

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Percentage of Disease Activity Score 28 (DAS28) -ESR Criteria Responders at week 18

EULAR response states were classified as follows: DAS28-ESR Good responders: △DAS28 \> 1.2 and DAS28 ≤3.2 at week 18. Moderate responders：△DAS28 \> 1.2 and still DAS28 \> 3.2 at week 18; or 1.2 ≥△DAS28 \> 0.6 and DAS28 ≤ 5.1 at week 18. Nonresponders：△DAS28 ≤0.6，or DAS28 \>5.1 at week 18. DAS28-defined remission was classified as a score of \<2.6.

Time frame: week 18

Percentage of Disease Activity Score 28 (DAS28) -ESR Criteria Responders at week 6

EULAR response states were classified as follows: DAS28-ESR Good responders: △DAS28 \> 1.2 and DAS28 ≤3.2 at week 6. Moderate responders：△DAS28 \> 1.2 and still DAS28 \> 3.2 at week 6; or 1.2 ≥△DAS28 \> 0.6 and DAS28 ≤ 5.1 at week 6. Nonresponders：△DAS28 ≤0.6，or DAS28 \>5.1 at week 6. DAS28-defined remission was classified as a score of \<2.6.

Time frame: week 6

Percentage of participants achieving ACR/EULAR remission at week 30

If all of the following 4 parameters are fulfilled, it is defined as remission: TJC ≤ 1, SJC ≤ 1, CRP ≤ 1 mg/dL, Patient global assessment（PGA） ≤ 1 cm (on a visual analog scale ranging from 0-10 cm, with higher scores indicating severe disease).

Time frame: week 30

Percentage of participants achieving ACR/EULAR remission at week 18

Time frame: week 18

Percentage of participants achieving ACR/EULAR remission at week 6

Time frame: week 6

Change from baseline Simplified Disease Activity Index (SDAI)

The SDAI is a composite score derived from these measures，that is the count of tender joint count（TJC, 0-28）, swollen joint count（SJC, 0-28）, C-reactive protein (CRP, mg/L), Patient global assessment（PGA）and physician global assessment（PHGA）, each of the last two was assessed on a visual analog scale ranging from 0-10 cm, with higher scores indicating severe disease. SDAI score will be calculated with formula SDAI = TJC + SJC + PGA+PHGA+ CRP. SDAI score exceeding 26 is considered high disease activity; 11 \<SDAI ≤26，moderate disease activity; 3.3 \<SDAI ≤11, low disease activity; remission is SDAI score ≤ 3.3.

Time frame: up to week 30

Change from baseline Clinical Disease Activity Index (CDAI)

Change from baseline Clinical Disease Activity Index (CDAI) CDAI is a composite score derived from these measures，that is the count of tender joint count（TJC, 0-28）, swollen joint count（SJC, 0-28）, Patient global assessment（PGA）and physician global assessment（PHGA）, each of the last two was CDAI score will be calculated with formula CDAI = TJC + SJC + PGA + PHGA. CDAI \> 22 is considered high disease activity; 10 \<CDAI ≤ 22, moderate disease activity; 2.8 \<CDAI ≤10, low disease activity; remission is CDAI score ≤2.8.

Time frame: up to week 30

Change From Baseline in C-reactive Protein (CRP)

Change from Baseline in C-reactive Protein (CRP), a component index of ACR20 and SDAI, CRP will be measured with blood samples.

Time frame: up to week 30

Change From Baseline in Erythrocyte Sedimentation Rate (ESR)

Change from Baseline in ESR, that is a component index of ACR20, DAS28-ESR and SDAI, ESR will be measured with blood samples.

Time frame: up to week 30

Change from baseline Health Assessment Questionnaire Disability Index (HAQ-DI)

Change from Baseline in HAQ-DI, a participant assessed measure of health assessment, shaveing eight dimensions of functional activity: pruning, dressing, rising, eating, walking, personal hygiene, reach, grip, and other routine activities. Each item on a single scale has 4 degrees ranging from 0 (no functional difficulty) to 3 (unable to do), with higher scores indicating severe disease.

Time frame: up to week 30

Percentage of American College of Rheumatology [ACR] 20 Criteria Responders every time

Percentage of American College of Rheumatology \[ACR\] 20 Criteria Responders every time

Time frame: up to week 30

Incidence of participant withdrawal

Percentage of participants who withdraw from this study.

Time frame: up to week 30

Number of participants with"adverse events (AEs)"

An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with"adverse events (AEs)"i.e. physical exam abnormalities，vital sign abnormalities，laboratory value abnormalities，symptom or disease (new or exacerbated) temporally associated with the use of a medicinal product.

Time frame: up to week 30