Targeted treatment early with etanercept and methotrexate or methotrexate with treat to target (standard) care for treatment-naive early rheumatoid arthritis patients, based on baseline naive T-cell frequency.

Targeted treatment early with etanercept (biosimilar) plus methotrexate or methotrexate with T2T care for DMARD-naïve early RA patients. A prospective, longitudinal cohort study with an embedded pilot randomised controlled trial to assess treatment rationalisation based on naïve CD4+ T-cell stratification. - TEEMS

Status

Not yet recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-002344-16-GB

Enrollment

106

Registered

2017-11-29

Start date

2018-06-28

Completion date

Unknown

Last updated

2019-06-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Interventions

Trade Name: Benepali Product Name: Benepali Pharmaceutical Form: Solution for injection in pre-filled pen INN or Proposed INN: ETANERCEPT

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Subject has a diagnosis of RA as defined by the new ACR/EULAR 2010 classification criteria 2. Newly diagnosed (within 12 weeks) 3. Active disease at screening (DAS28ESR =3.2) 4. Anti-citrillunated peptide protein antibody positive (ACPA) 5. Male & female subjects =18 years old. 6. DMARD-naïve 7. No use of intra-muscular/Intra-articular or oral corticosteroids 4 weeks prior to screening. 8. All male and female subjects biologically capable of having children must agree to use a reliable method of contraception for the duration of the study and 24 weeks after the end of the study period. Acceptable methods of contraception are surgical sterilisation, oral, implantable or injectable hormonal methods, intrauterine devices or barrier contraceptives. 9. Patients must have the capacity and be willing to provide written informed consent and comply with the requirements of the protocol. 10. Subjects deemed to be in good health with respect to clinical examination and screening blood tests, including full blood count (FBC), urea and electrolytes (U&E), and liver functions tests (LFT)- See below exclusion criteria Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0

Exclusion criteria

Exclusion criteria: 1. Use of any additional investigational medications or products within 4 weeks of screening. 2. Use of intramuscular, intra-articular or oral corticosteroids within 4 weeks prior to screening. 3. Pregnant/lactating women or planning pregnancy within 24 weeks of last protocol treatment 4. Planned surgery within the study period (requiring omission of study medication > 28 days). 5. The presence of other comorbidities, which the physician deems as significant to interfere with evaluation (musculoskeletal condition such as osteoarthritis & fibromyalgia). 6. Diagnosis of another inflammatory arthritis or conective tissue disease e.g. psoriatic arthritis or Ankylosing spondylitis, primary Sjogren’s syndrome, systemic sclerosis, systemic lupus erythematosus, polymyositis. 7. Patients with any ongoing or active infection or any major episode of severe infection requiring hospitalization or treatment with IV antibiotics within the preceding 4 weeks of screening and/or orally administered antibiotics in the preceding 2 weeks of screening. 8. Any contraindication to conventional DMARD’s and anti-TNF therapy 9. In receipt of a live vaccination within 4 weeks prior to screening 10.Patients with abnormal liver function at the time of screening or abnormal blood tests as shown by: o Aminotransferase (AST)/alanine aminotransferase (ALT) >3x upper limit of normal (ULN), OR Bilirubin >51µmol/L o Serum Creatinine >175 mmol/L, eGFR below 30ml/L/min/1.73m2 o Neutrophils <2000 x 10*6/L o Platelets <125 x 109/L o Haemoglobin <90 g/L for males and <85 g/L for females

Design outcomes

Secondary

Measure	Time frame
Timepoint(s) of evaluation of this end point: As outlined above; Secondary end point(s): • The difference in the proportions of patients in clinical remission (DAS28 =2.6) after 12 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies • The difference in the proportions of patients in clinical remission (DAS28 =2.6) at 12 weeks and 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care (Arm B) vs. etanercept + methotrexate (Arm C) • The differences in the medians of patient-reported outcome measures (EMS, VAS scales, HAQ-DI) after 12 weeks & 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies • The differences in the medians of patient-reported outcome measures (EMS, VAS scales, HAQ-DI) after 12 weeks & 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care(Arm B) vs. etanercept + methotrexate (Arm C) • The difference in the proportions of patients in imaging remission (PD=0) after 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) or abnormal (Arm B) naïve CD4+T-cell frequencies • The difference in the proportions of patients in imaging remission (PD = 0) 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care (Arm B) vs. etanercept + methotrexate (Arm C) • The difference in the proportion of patients with normal naïve CD4+ T-cells at 24 weeks (24 weeks)for patients with abnormal baseline naïve CD4+ T-cells receiving methotrexatewith T2T care (Arm B) vs. etanercept + methotrexate (Arm C) • The difference in the proportions of patients achieving sustained	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: As outlined above; Secondary end point(s): • The difference in the proportions of patients in clinical remission (DAS28 =2.6) after 12 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies • The difference in the proportions of patients in clinical remission (DAS28 =2.6) at 12 weeks and 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care (Arm B) vs. etanercept + methotrexate (Arm C) • The differences in the medians of patient-reported outcome measures (EMS, VAS scales, HAQ-DI) after 12 weeks & 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies • The differences in the medians of patient-reported outcome measures (EMS, VAS scales, HAQ-DI) after 12 weeks & 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care(Arm B) vs. etanercept + methotrexate (Arm C) • The difference in the proportions of patients in imaging remission (PD=0) after 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) or abnormal (Arm B) naïve CD4+T-cell frequencies • The difference in the proportions of patients in imaging remission (PD = 0) 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care (Arm B) vs. etanercept + methotrexate (Arm C) • The difference in the proportion of patients with normal naïve CD4+ T-cells at 24 weeks (24 weeks)for patients with abnormal baseline naïve CD4+ T-cells receiving methotrexatewith T2T care (Arm B) vs. etanercept + methotrexate (Arm C) • The difference in the proportions of patients achieving sustained

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Primary

Measure	Time frame
Timepoint(s) of evaluation of this end point: 24 weeks;Primary end point(s): The difference in the proportions of patients in clinical remission (DAS28 =2.6) at 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies. ; Main Objective: Overall Aim: To determine whether a patient's baseline naive T-cell frequency can guide treatment decisions for treatment-naive early RA patients. Specifically, can we rationalise the use of MTX and offer more targeted treatment for patients with a poor prognosis based on their naive T-cells? Primary Objective: To determine whether the proportion of patients achieving clinical remission after first-line treatment with methotrexate and standard treat to target care differs according to naive CD4+ T-cell frequency (normal/abnormal) at baseline. ; Secondary Objective: 1. To determine the proportion of patients that achieve clinical remission for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving etanercept + methotrexate compared to methotrexate with T2T care. 2. To determine whether the proportion of patients that achieve ultrasound remission (absence of inflammation on ultrasound) with first-line treatment with MTX and T2T care differs according to naïve T-cell frequency (normal/abnormal) at baseline. 3. To determine the proportion of patients that achieve ultrasound remission for patients with abnormal baseline naïve T-cell frequencies receiving etanercept + MTX compared to MTX with T2T care. 4. To determine the proportion of patients who normalize their T-cell frequency for patients with abnormal baseline naïve T-cells receiving MTX with T2T care or etanercept + MTX. 5. To determine whether patient reported outcomes differ between patients with normal or abnormal baseline naive T-cells.	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: 24 weeks;Primary end point(s): The difference in the proportions of patients in clinical remission (DAS28 =2.6) at 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies. ; Main Objective: Overall Aim: To determine whether a patient's baseline naive T-cell frequency can guide treatment decisions for treatment-naive early RA patients. Specifically, can we rationalise the use of MTX and offer more targeted treatment for patients with a poor prognosis based on their naive T-cells? Primary Objective: To determine whether the proportion of patients achieving clinical remission after first-line treatment with methotrexate and standard treat to target care differs according to naive CD4+ T-cell frequency (normal/abnormal) at baseline. ; Secondary Objective: 1. To determine the proportion of patients that achieve clinical remission for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving etanercept + methotrexate compared to methotrexate with T2T care. 2. To determine whether the proportion of patients that achieve ultrasound remission (absence of inflammation on ultrasound) with first-line treatment with MTX and T2T care differs according to naïve T-cell frequency (normal/abnormal) at baseline. 3. To determine the proportion of patients that achieve ultrasound remission for patients with abnormal baseline naïve T-cell frequencies receiving etanercept + MTX compared to MTX with T2T care. 4. To determine the proportion of patients who normalize their T-cell frequency for patients with abnormal baseline naïve T-cells receiving MTX with T2T care or etanercept + MTX. 5. To determine whether patient reported outcomes differ between patients with normal or abnormal baseline naive T-cells.

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Countries

United Kingdom

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026