NCT06016517

Application of the Personalized N-of-1 Trial Design in Patients With Rheumatoid Arthritis

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 18 (estimated)
• Sponsor: Tufts Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this N-of-1 study is to learn about treatment for individual patients who have rheumatoid arthritis (RA,) for which many treatments are available. The treatments are different in how they work, the way they are given, side- effects, and cost. While treatment guidelines are available, finding the best treatment order of treatments is often based on physician choice. The main question this study aims to answer are: * What are the effects of different treatments on RA symptoms and condition for each individual patient * What is the effectiveness of different treatments across all patients enrolled in the N-of-1 study Participants will be enrolled and randomized to a sequence of three U.S. Food and Drug Administration (FDA) approved RA medications: 1. etanercept, 2. adalimumab, 3. upadacitinib 4. tocilizumab. Participants will be asked to complete questionnaires about their condition and quality of life fortnightly, monthly and/or quarterly (either in clinic or remotely) and report their level of pain on alternate days (remotely).

Detailed description

Rheumatoid arthritis (RA) is a chronic, slowly progressive condition for which numerous treatment options are available. The therapies vary in mechanism of action, mode of administration, side- effect (adverse event) profile, and cost. While consensus treatment guidelines are available, identifying an optimal treatment sequence is often based on clinician choice with treatment changes based on tolerability and short- term outcome. The N-of-1 trial will evaluate individual participant and aggregate data. Individual participants will be enrolled and randomized to a sequence of three U.S. Food and Drug Administration (FDA)-approved therapeutic agents etanercept, adalimumab, upadacitinib and tocilizumab. The N-of-1- RA protocol describes patient allocation into a series of individual comparisons. • Patients with newly diagnosed rheumatoid arthritis following initial treatment with methotrexate (MTX). Participants will be allocated to: * MTX responder * MTX non- responder or partial responder Eligible participants will either continue MTX or discontinue MTX, based on response to initial therapy and tolerance. Participants identified for subsequent biologic therapy will enter the biologic therapy phase of the study; with MTX either continued or not continued. This phase consists of a sequence of 4 therapeutic intervention regimens, each lasting 12-weeks. The treatment conditions are as follows: A. Tumor Necrosis Factor (TNF) Inhibitor biologic: etanercept 50 mg subcutaneously weekly. B: TNF- inhibitor biologic: Adalimumab 40 mg subcutaneously every 2 weeks. C. Janus Kinase (JAK) Inhibitor: Upadacitinib 15 mg orally once daily. D. Interleukin 6 (IL-6) Inhibitor: Tocilizumab 162 mg administered SQ every 2 weeks (if there is an inadequate response to prior three biologics). Primary Objective (individual N-of-1 trial): To generate randomized evidence about the effects of therapeutic agents on RA symptoms and disease activity to inform decision about best treatment at the end of the trial period for each participant. Secondary Objective (aggregation of the series of N-of-1 trials): To evaluate the average relative effectiveness of therapeutic agents across all participants and explore heterogeneity of treatment effects. For the aggregated series of N-of-1 trial, we will use the following hierarchy of endpoints. Primary Endpoint: • DAS28 (CRP and ESR) Secondary Endpoints: * American College of Rheumatology 20% (ACR20), 50% (ACR50) and 70% (ACR70) response * Routine Assessment of Patient Index Data (RAPID3) score based on participants' report of overall assessment of the disease, the level of pain, and the amount of physical disability * Short Form 12-Item Health Survey (SF-12) measuring the impact of disease on overall quality of life during the prior 4 weeks (physical function, pain, general and mental health, vitality, social function, physical and emotional health) * Report of worst pain and effect of pain on function (0-10) every other day * Treatment Burden Questionnaire (TBQ) administered at the end of each treatment condition Safety Endpoint(s): • Number (and proportion) of patients reporting treatment emergent adverse events (TEAEs) (by MedDRA system organ class and preferred term) For each individual N-of-1 trial, we will use the endpoints listed above, but without any pre-specified hierarchy, assuming that each patient will identify endpoints most important to them.

Conditions

• Arthritis, Rheumatoid

Interventions

Type	Name	Description
DRUG	Etanercept	50 mg subcutaneously weekly
DRUG	Adalimumab	40 mg subcutaneously every 2 weeks
DRUG	Upadacitinib	15 mg orally once daily with subcutaneous placebo injection every 2 weeks
DRUG	Tocilizumab	162 mg administered SQ every 2 weeks

Timeline

• Start date: 2026-05-01
• Primary completion: 2027-12-15
• Completion: 2028-12-01
• First posted: 2023-08-29
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States