MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES)

Abstract

Purpose: Our aim was to introduce a simplified MRI instrument, Rapid OsteoArthritis MRI Eligibility Score (ROAMES), for defining structural eligibility of patients for inclusion in disease-modifying osteoarthritis drug trials using a tri-compartmental anatomic approach that enables stratification of knees into different structural phenotypes and includes diagnoses of exclusion. We also aimed to define overlap between phenotypes and determine reliability. Methods: 50 knees from the Foundation for National Institutes of Health Osteoarthritis Biomarkers study, a nested case-control study within the Osteoarthritis Initiative, were selected within pre-defined definitions of phenotypes as either inflammatory, subchondral bone, meniscus/cartilage, atrophic or hypertrophic. A focused scoring instrument was developed covering cartilage, meniscal damage, inflammation and osteophytes. Diagnoses of exclusion were meniscal root tears, osteonecrosis, subchondral insufficiency fracture, tumors, malignant marrow infiltration and acute traumatic changes. Reliability was determined using weighted kappa statistics. Descriptive statistics were used for determining concordance between the a priori phenotypic definition and ROAMES and overlap between phenotypes. Results: ROAMES identified 43 of 50 (86%) pre-defined phenotypes correctly. Of the 50 participants, 27 (54%) had no additional phenotypes other than the pre-defined phenotype. 18 (36%) had one and 5 (10%) had two additional phenotypes. None had three or four additional phenotypes. All features of ROAMES showed almost perfect agreement. One case with osteonecrosis and one with a tumor were detected. Conclusions: ROAMES is able to screen and stratify potentially eligible knees into different structural phenotypes and record relevant diagnoses of exclusion. Reliability of the instrument showed almost perfect agreement.

<p>Development and Prospect of Intra-Articular Injection in the Treatment of Osteoarthritis: A Review</p>

“…To date, the challenges of OA therapy research include complex interactions of various pathological mechanisms, the presence of various phenotypes in the OA pathogenic spectrum and difference in the rate of progression of disease among different populations. 123,124 Especially for the elderly, the safety of drugs is particularly important because of long-term treatment.…”

Effectiveness of drugs with delayed-release structurally modified action depending on the phenotype of osteoarthritis

“…Эти данные свидетельствуют о низкой эффективности данного терапевтического подхода у больных с воспалительным эндотипом заболевания. Полученные результаты можно объяснить прямым влиянием хондроитина и глюкозамина на продукцию провоспалительных цитокинов в тканях суставов [2,11,13,15]. Однако данная когорта больных, как сообщалось ранее, характеризуется относительно низкими параметрами альгофункционального и структурного статуса [14].…”

“…Учитывая несогласованность мнений экспертов и результатов исследований относительно эффективности SYSADOA, особую актуальность приобретает тезис о том, что когорта больных ОА является фенотипически гетерогенной [8,9]. При этом неоднородность когорты больных реализуется на клиническом, молекулярном и структурном уровнях [10,11,12,13]. Понятие о фенотипической неоднородности ОА позволило предположить, что клиническая картина, эффективность того или иного метода лечения определяется особенностями эндотипа заболевания.…”

Setting up distinctive outcome measures for each osteoarthritis phenotype

“…The inclusion of appropriate risk factors or imaging features as valid outcomes into composite indexes may help to identify specific subsets of individuals, such as those who develop certain OA phenotypes or accelerated knee OA. 145 , 146 …”