The Effect of Guided Care With Vectra Compared to Treatment as Usual in Patients With Rheumatoid Arthritis

S

Sequenom

Status

Enrolling

Conditions

Rheumatoid Arthritis (RA)

Treatments

Diagnostic Test: Vectra

Study type

Observational

Funder types

Industry

Identifiers

NCT03631225
133-CL-01

Details and patient eligibility

About

The goal of treating patients diagnosed with rheumatoid arthritis (RA) is to achieve remission or low disease activity and thereby prevent joint damage, loss of physical function, and disability. Optimal management requires regular assessment of disease activity, with treatment changes made as needed for optimal efficacy. Vectra is a blood serum test that looks at 12 biomarkers and produces a score on a scale of 1 to 100. The Vectra score has been shown to be the strongest predictor of risk for progression of disease. There is opportunity to gain more information about the utility of Vectra in a real-world clinical setting. This study will, therefore, evaluate the utility of Vectra for guiding treatment decisions and improving RA-related outcomes in comparison with usual care, which will not include Vectra testing. This study will enable a direct evaluation of the clinical benefit associated with using Vectra to guide treatment decisions in patients with RA.

Full description

Disease activity in RA can be assessed by physical examination, patient-reported outcomes (PROs) or laboratory tests. Joints counts and PROs are partly or entirely subjective. Their ability to support clinical assessment is limited in certain settings, including for RA patients with common comorbidities, such fibromyalgia, obesity, or depression, or with clinically uncertain inflammatory burden. It can be difficult to assess the origin of ongoing pain in such patients using clinical assessment alone. The two blood tests routinely used to assess RA disease activity, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are objective but are in the normal range in more than half of RA patients with active disease, which reduces their negative predictive value and greatly limits their utility. These clinical and laboratory measures are variously combined in composite scores of RA disease activity, such as the 28-joint count Disease Activity Score (DAS28) or the Clinical Disease Activity Index (CDAI) which are not widely used in the US outside of clinical trials because complete, formal joint counts are time-consuming and composite scores pose logistic challenges in a busy clinic setting. Radiographic progression (RP) is a validated endpoint accepted by the FDA for clinical trials that reflects RA-related damage to joints. It is associated with long-term disability. Optimal care requires that the risk of progression be reduced. Quantitative scoring of RP is performed only for clinical trials and is not used for assessing RP risk in clinical practice. Rheumatologists are generally not trained to score radiographs and they are very time-consuming to score, typically taking 20 or more minutes per patient for a skilled reader. However, they are a valuable scientific endpoint in that they serve as a valid proxy for long term damage and associated RA-related disability. Conventional clinical and laboratory-based measures of RA disease activity are weak predictors of RP, including among patients in clinical remission, where progression can still occur. Thus, an objective, convenient measure that reflects pathologically meaningful disease activity and predicts risk for progression is needed for optimal management of RA. The multi-biomarker disease activity (MBDA) test, Vectra®, is an objective tool that combines serum concentrations of 12 biomarkers in a validated algorithm to produce a score on a scale of 1 to 100. The MBDA test was subsequently adjusted to account for the effects of age, sex, and leptin (a surrogate for adiposity) in patients with rheumatoid arthritis (RA). The Vectra score has been shown to be the strongest predictor of risk for RP, compared with conventional disease activity measures, including DAS28-CRP, CRP and the swollen joint count. In multivariate analyses, it was the only disease activity measure to independently predict RP. High Vectra scores (>44) are associated with greatest risk for progression and low and moderate scores with very low risk. Across multiple studies, Vectra has a negative predictive value for progression of 93-97%, and in a meta-analysis, the relative risk for progression with a high Vectra score (5.1) is substantially greater than with a high DAS28-CRP (1.4) or high CRP (1.6). The predictive value of Vectra exists even when the Vectra score and clinical measures are discordant, which means that patients with high DAS28-CRP have little risk for RP when Vectra score is low and, conversely, patients with low DAS28-CRP have high risk for RP when Vectra score is high. Thus, reducing high Vectra scores should be a primary goal of therapy, regardless of the level of clinical disease activity, and using Vectra scores to guide therapy should be an effective way to prevent radiographic progression. A recent prospective study of daily and diurnal variation in Vectra score established that the minimally important difference (MID) in Vectra score - i.e., the magnitude of change in Vectra score that is needed to be confident that it reflects real biologic change and is not due only to random variation - is greater than or equal to 8 Vectra units. Accordingly, a threshold of 8 can be used in guidances for using Vectra to evaluate treatment response. The primary objective is to compare the clinical response from baseline to 12 months among patients with RA receiving Vectra-Guided care versus those receiving usual care. The secondary objectives of this study are to: Evaluate the rate of radiographic progression from baseline to year 1 among patients with RA whose care is guided by Vectra relative to those receiving usual care. Evaluate changes in Vectra score from baseline to 6 months and baseline to year 1 among patients with RA whose care is guided by Vectra DA relative to those receiving usual care. Evaluate clinical response from baseline to 1 year among patients with RA receiving Vectra-guided care relative to those receiving usual care.

Enrollment

1,500 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • ≥ 18 years old at screening visit
  • Diagnosed with RA according to 1987 or 2010 criteria of the American College of Rheumatology
  • At the time of the pre-baseline visit, patient has a CDAI score of >10
  • Currently taking one or more non-biologic or biologic DMARD at screening and for at least the 3 months prior to screening
  • Visit at time of screening scheduled as part of routine care
  • Subject and/or physician willing to consider treatment change at screening
  • No expectation of imminent treatment change at screening or baseline visit

Exclusion criteria

  • Currently taking an anti-IL-6R drug (tocilizumab, sarilumab)
  • Any contraindication, administrative barrier, or financial limitation (e.g. no insurance coverage) that makes it impossible for subject to receive at least one new biologic or JAKi therapy for RA
  • Active infection
  • History of malignancy within the past 5 years or any evidence of persistent malignancy, except fully excised basal cell or squamous cell carcinomas of the skin, or cervical carcinoma in situ that has been treated or excised in a curative procedure
  • Current enrollment in another clinical trial
  • Any condition or circumstance that makes it likely the patient will not be able to complete the trial

Trial design

1,500 participants in 2 patient groups

Guided-Care Arm
Description:
Physicians will use the reported Vectra score to guide treatment decisions
Treatment:
Diagnostic Test: Vectra
Usual Care Arm
Description:
Physicians will treat patient per standard of care without the use of the Vectra score

Trial contacts and locations

30

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Central trial contact

Ana Gugila; Graham McLennan

Data sourced from clinicaltrials.gov

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