Comparative Effectiveness of Targeted Therapy in RA Patients

Comparative Effectiveness of Biologic Disease-modifying Antirheumatic Drugs and Small Molecular Inhibitors in Patients With Moderate to Severe RA: Prospective Observational Study

The objective of a multicenter prospective observational study is to compare effectiveness and safety of biologic disease-modifying antirheumatic drugs and small molecular inhibitors in patients with moderately to severely active rheumatoid arthritis patients who have had an inadequate response or intolerace to methotrexate.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Adalimuab, Etanercept, Tocilizumab, or Abatacept; Drug: Tofacitinib or Baricitinib

Detailed Description

This study is a multicenter prospective observational study to show non-inferiority of clinical efficacy for small molecular inhibitors after 48 week of treatment to biologic disease modifying anti-rheumatic drugs (bDMARDs) in patients having moderately to severely active RA and who have been intolerant to conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) including methotrexate.

Primary end point is a percentage of participants of achieving low disease activity according to Disease Activity Score in 28 joints-Erythrocyte Sedientation Rate (DAS28-ESR) at weeks 24. A total of 506 RA patients will be included, and allocated in ratio of 1:1 to bDMARD group and small molecule inhibitor group. Group allocation is determined by shared-decision making, so that the number of participants could be re-assessed according to recruitment status of participatns.

• Study Type: Observational
• Enrollment (Anticipated): 506

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 04763
    • Recruiting
    • Hanyang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Korean RA patients who start biologic disease modifying anti-rheumatic drugs (bDMARDs) or small molecule inhibitors with moderately to severely active RA who have had an inadequate response or intolerance to methotrexate and naive to any bDMARDs or small molecule inhibitors.

Description

Inclusion Criteria:

Patients are included in this study if they are:

• 19 years or olders
• Patients who satisfy the 1987 American College of Rheumatology (ACR) or 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA
• Patients having moderately to severely active RA who are intolerant to csDMARDs including methotrexate and those who have never been exposed to bDMARDs or small molecular inhibitors before
• Patients who provide written consent to participate in this study

Exclusion Criteria:

• Patients who are contraindicated to bDMARDs or small molecule inhibitor
• Patients who have plans for pregnancy or elective surgery
• Patients who had ever diagnosed with any malignancy or are treated for malginancy
• Patients who cannot voluntarily provie a written consent to participate in this study
• Patients who did not provide a written consent to participate in this study

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
RA patients who start bDMARD; The efficacy and safety of targeted therapy will be evaluated in RA patients who are treated with a biologic disease modifying antirheumatic drug (bDMARD) including Adalimuab, Etanercept, Tocilizumab or Abatacept after shared-decision making.	Drug: Adalimuab, Etanercept, Tocilizumab, or Abatacept; A specific targeted therapy wil be decided by shared-decision making, a bidirectional process in which clinicians and patients make decisions based on clinical evidence that balances risks and expected outcomes with patient preferences and values.; Other Names: Humira, Enbrel, Etoloche, Eucept, Actemra, or Orencia
RA patients who start small molecule inhibitor; The efficacy and safety of targeted therapy will be evaluated in RA patients who are treated with a small molecular inhibitor including Tofacitinib or Baricitinib after shared-decision making.	Drug: Tofacitinib or Baricitinib; A specific targeted therapy wil be decided by shared-decision making, a bidirectional process in which clinicians and patients make decisions based on clinical evidence that balances risks and expected outcomes with patient preferences and values.; Other Names: Xeljanz or Olumiant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants achieving low disease activity according to Disease Activity Score 28 joints-Erythrocyte sedimentation (DAS28-ESR)	Disease Activity Score 28 joints-Erythrocyte sedimentation (DAS28-ESR) below 3.2 indicates low disease activity of RA.	At weeks 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Health Assessment Questionnaire (HAQ)	The HAQ-DI is a patient-reported assessment of physical function that includes 20 items in eight categories representing a comprehensive set of functional activities, including dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Patients are asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst), with a higher score representing a high-dependency disability.	At weeks 12, 24, and 48
Changes in EuroQol-5 dimension (EQ-5D)	The EQ-5D is a generic instrument for measuring health-related quality of life. The EQ-5D-5L essentially consists of two parts: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). Patients are asked about their ability to complete specific tasks today using the following dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4) and extreme problems (5). EQ-5D-5L health states can be summarised using the 5-digit code, after that, it is represented by a single summary number (index scores). Health state index scores generally range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health), with higher scores indicating higher health utility.	At weeks 12, 24, and 48
Changes in EuroQol visual analogue scale (EQ VAS)	The EQ-5D is a generic instrument for measuring health-related quality of life. The EQ-5D-5L essentially consists of two parts: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The second part of the questionnaire consists of a visual analogue scale (VAS) on which the patient rates his/her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health).	At weeks 12, 24, and 48
Percentage of participants achieving low disease activity according to Disease Activity Score 28 joints-Erythrocyte sedimentation rate (DAS28-ESR)	Disease Activity Score 28 joints-Erythrocyte sedimentation (DAS28-ESR) below 3.2 indicates low disease activity of RA.	At weeks 12 and 48
Percentage of participants achieving remission according to Disease Activity Score 28 joints-Erythrocyte sedimentation rate (DAS28-ESR)	Disease Activity Score 28 joints-Erythrocyte sedimentation (DAS28-ESR) below 2.6 indicates remission of RA.	At weeks 12, 24, and 48
Percentage of participants with European League Against Rheumatism (EULAR) Response according to Disease Activity Score 28 joints-Erythrocyte sedimentation rate (DAS28-ESR)	The European League Against Rheumatism (EULAR) response criteria classify patients as good, moderate, or nonresponders, using the individual amount of change in DAS28 and the level of DAS reached (low, moderate, or high); good responders were patients with an improvement of >1.2 and a present score of ≤3.2; moderate responders were patients with an improvement of >0.6 to ≤1.2 and a present score of ≤5.1, or an improvement of >1.2 and a present score of >3.2; non-responders were any patients with an improvement of ≤0.6, or patients with an improvement of >0.6 to 1.2 and a present score of >5.1	At weeks 12, 24, and 48
Percentage of participants having radiologic progression in RA (if possible)	Percentage of participants having radiologic progression in rheumatoid arthritis (if possible)	At weeks 48
Percentage of participants having changes in ultrasonographic findings of RA (if possible)	Percentage of participants having changes in ultrasonographic findings of rheumatoid arthritis (if possible)	At weeks 48
Biomarkers predictive of treatment response of RA (if possible)	We would like to discover serum biomarkers predicting 24-week treatment response in each targeted therapy for RA patients. Serum samples will be collected before target therapies (at 0 week) and grouped according to the treatment response after 24 weeks. The putative biomarkers predicting treatment response will be screened using proteomics method and validated via ELISA.	At weeks 24
Incidence of adverse events (AEs) or serious adverse events (SAEs) of targeted therapy (if possible)	Incidence of adverse events (AEs) or serious adverse events (SAEs) of targeted therapy (if possible)	At weeks 48
Compliance with targeted therapy defined by Patient-reported adherence and Modified Morisky scale (if possible)	This 6-item questionnaire measures two domains of adherence; knowledge and motivation. Patients are categorized as having 'high' or 'low' knowledge and motivation based on their yes or no response to each of the six questions of the Modified Morisky Scale. Each 'no' response to each question results in +1 (except question 5, in which a 'yes' response would result in +1) and 'yes' responses to each question result in +0 (except question 5, where a 'no' response would result in +0). Scores for the 6-item of Modified Morisky Scale can range from 0 to 6, with higher scores indicating better adherence.	At weeks 48

Collaborators and Investigators

• Sponsor: Hanyang University
• Collaborators: Ministry of Health, Republic of Korea
• Investigators: Principal Investigator: Yoon-Kyoung Sung, MD, PhD, MPH, Hanyang University

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2020
• Primary Completion (Anticipated): August 19, 2023
• Study Completion (Anticipated): August 19, 2024

Study Registration Dates

• First Submitted: June 7, 2020
• First Submitted That Met QC Criteria: June 23, 2020
• First Posted (Actual): June 26, 2020

Study Record Updates

• Last Update Posted (Actual): June 26, 2020
• Last Update Submitted That Met QC Criteria: June 23, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Arthritis; Joint Diseases; Musculoskeletal Diseases; Arthritis, Rheumatoid
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Arthritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Protein Kinase Inhibitors; Immune Checkpoint Inhibitors; Etanercept; Abatacept; Tofacitinib
• Other Study ID Numbers: HUHRD-SPE-20-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No