NCT03813771

Targeted Treatment Early With Etanercept + Methotrexate vs.T2T Care for DMARD-naïve Early RA Patients Based on naïve T-cell Stratification

Targeted Treatment Early With Etanercept Plus Methotrexate Versus T2T Care for DMARD-naïve Early RA Patients. A Prospective, Longitudinal Cohort Study With Embedded Pilot Randomised Controlled Trial to Assess Treatment Rationalisation Based on naïve T-cell Stratification.

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 106 (estimated)
• Sponsor: University of Leeds · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The main aim of the study is to determine the clinical utility of naive T-cell stratification for rationalising treatment with methotrexate (MTX), for DMARD-naive early RA patients. Thus, it aims to determine whether TNFi therapy (Benepali) instituted as first-line therapy in DMARD-naive early RA patients with poor T-cell prognostication confers better outcomes (clinical, structural and immunological). Hence, this would enable early targeted treatment for those with a poorer prognosis based on their immunological status.

Detailed description

The current optimal therapeutic approach in early RA is to start MTX to target inflammation and induce remission.Prediction of MTX therapy response remains a key clinical need to enable the identification of patients who would benefit from an alternative, more aggressive treatment strategy. Multiple predictors of remission with MTX have been reported over the years but none have entered routine clinical practice. We previously reported that T-cell phenotyping at baseline could predict remission in DMARD-naïve early RA treated with MTX. Reduced naïve CD4+ T-cell frequency was the most predictive factor, using both a pilot and a replication cohort.These data confirmed the potential value of using naïve CD4+ T-cells as a biomarker of MTX induced remission in early RA. The clinical utility of measuring T-cell subsets is therefore strongly indicated by these data and suggests that measurement of T- cell subsets can be used to rationalise the use of MTX as first-line therapy.Predicting response to MTX has important clinical value to identify patients who will do well on MTX but furthermore for directing those who will have a sub-optimal response to MTX to receive alternative therapy without any harmful delay and in line with the treat to target principle. The current study aims to confirm/validate the clinical value of T-cell subset quantification for the prediction of MTX response in early RA, by stratified interventions based on baseline naïve CD4+ T-cell status. This is a Single centre, phase IV, open-label, prospective, longitudinal cohort study with an embedded pilot randomised controlled trial that aims to assess whether MTX can be rationalised as a first-line treatment for DMARD-naïve early RA patients, according to baseline naïve CD4+ T-cell stratification. Patients with newly diagnosed RA satisfying the inclusion criteria will be recruited from our early arthritis clinic. Eligible patients will be provided with written information on the study and will be given a minimum of 24 hours to read this information prior to being contacted by a research nurse (within one week). If interested they will be invited to a screening appointment within four weeks to confirm eligibility, obtain written consent and to collect the necessary clinical and laboratory data as per the study schedule. Following the screening visit, patients will attend a baseline assessment within four weeks. Patients will be stratified based on their naïve CD4+ T-cell frequency (normal or abnormal based on our pre-defined cut-off values according to age and sex-matched controls). Patients with a normal T-cell frequency (Arm A) will commence MTX 15mg/week PO (+HCQ 400mg od) as per standard T2T practice. Follow-up (4, 12 and 24 weeks), dose escalation of MTX and treatment of flare will also be conducted in line with T2T care. Patients with an abnormal T-cell frequency will be randomized 1:1 into 2 groups using randomly permuted block sizes and also followed up as per T2T care: The first group (Arm B) will receive MTX 15mg/week PO (+HCQ 400mg od) The second group (Arm C) will receive MTX 15mg/week PO (+HCQ 400mg od) in combination with 50 mg subcutaneous Benepali® administered weekly. Patients will be followed up for a period of 24 weeks and will undergo clinical, immunological and imaging assessments as stated in the study schedule. Following completion of the study, patients will either be followed up in our established inflammatory arthritis or biologics clinic. Patients in group C will discontinue their Benepali®. This study will take place at the rheumatology out-patient department in Chapel Allerton Hospital, Leeds.

Conditions

• Rheumatoid Arthritis

Interventions

Type	Name	Description
DRUG	Benepali	Benepali will be adminstered subcutaneously at a dose of 50mg weekly and discontinued at the primary endpoint (24 weeks).
DRUG	Sulfasalazine	Sulfasalazine will be added at follow up visits (T2T care) if the subject fails to achieve low disease activity,administered orally at a dose of 1g twice daily.
DRUG	Methotrexate	Methotrexate will be administered orally at a starting dose of 15mg weekly. It may be increased in line with T2T care (to a maximum of 25mg) over the 24 weeks.
DRUG	Hydroxychloroquine	Hydroxychloroquine will be added at follow up visits (T2T care) if the subject fails to achieve low diseaseactivity, administered at a dose of 200mg daily.

Timeline

• Start date: 2019-03-01
• Primary completion: 2023-02-01
• Completion: 2023-02-01
• First posted: 2019-01-23
• Last updated: 2019-01-23

Locations

1 site across 1 country: United Kingdom