One of OrACORe’s founding studies is the MeTeOR (Meniscal Tear in Osteoarthritis Research) trial, which was conceptualized in 2002, enrolled its first participant in 2008, and recently obtained funding to perform a final 12-year follow-up visit. MeTeOR is a randomized controlled trial designed to compare outcomes of arthroscopic partial meniscectomy (APM) and nonoperative physical therapy in persons with knee osteoarthritis and meniscal tear. We spoke with Drs. Jeffrey Katz, MD, MSc, Elena Losina, PhD, and Morgan Jones, MD, MPH, to discuss the history of the project and their expectations for the upcoming follow-up study. In this installment, we review the history of the MeTeOR Trial, and in a subsequent blog entry we will discuss the upcoming follow-up study.
MeTeOR was designed to answer a central question: is arthroscopic partial meniscectomy preferable to physical therapy as treatment for meniscal tear? To the nearly 10 million people in the US with symptomatic knee osteoarthritis (OA) and meniscal tear and their physicians, the answer is of real consequence.
The MeTeOR investigation was informed and inspired by a 2002 paper published in the New England Journal of Medicine (Moseley et al. 2002). In this study, patients with knee osteoarthritis (OA) were randomly assigned to receive one of three treatments: arthroscopic knee debridement, lavage surgery, or placebo surgery. After two years of follow-up, the authors found that self-reported pain and function outcomes were similar across all three groups. The observation that a commonly performed surgery was no more effective than placebo upended the common understanding at the time of the utility of knee arthroscopy for OA.
These findings piqued the interest of Dr. Katz, who discussed them with his colleagues Dr. Nizar Mahomed, MD, of University of Toronto, and Dr. Losina. “We were thinking that [the 2002 study] didn’t address the population in whom arthroscopy is done most often — people with OA and meniscal tear,” Dr. Katz said. “There was a general sense after the Moseley study that arthroscopy is probably not effective for OA but may be effective [in patients] with OA and meniscal tear. When physicians evaluated patients with OA, they would try to ascertain whether the patient also had a meniscal tear. If so, surgery could be considered. We wondered if surgery was effective in this scenario.”
This line of thinking inspired the MeTeOR study, which was designed by Dr. Katz as the Principal Investigator and Dr. Losina as the lead methodologist. “[The methodology] was complicated because [MeTeOR] doesn’t quite fit into the typical framework of placebo-controlled trials,” Dr. Losina said. “In trials with surgical and non-surgical treatment arms, it is challenging to create a control group where the participants do not know which treatment arm they aree randomized to.” Grant writing and submissions to the National Institute of Health (NIH) continued through 2006 before funding was secured in 2007.
MeTeOR recruitment began in 2008 across five sites: Brigham and Women’s Hospital, The Hospital for Special Surgery (New York, NY), Cleveland Clinic (Cleveland, OH), Vanderbilt Medical Center (Nashville, TN), and Mayo Clinic (Rochester, MN). With funds from the American Recovery and Reinvestment Act of 2009, two clinical sites were added – Rush University (Chicago, IL) and Washington University (St. Louis, MO). This additional funding also enabled the team to obtain follow-up MRIs at 18 months.
Over a three-year period, MeTeOR randomized 351 participants to receive either APM or physical therapy. The investigators found that at six months post-randomization, both the operative and nonoperative groups reported similar levels of improvement in pain and functional status. Primary results from the first year of follow up were published in the New England Journal of Medicine in 2013.
Still, the investigators wanted to understand the longer-term (up to five years) ramifications of APM in relation to non-surgical treatments in these subjects. Additional funding was secured in 2013 with the goal to evaluate “whether any of the clinical changes we observed early on post-randomization were sustained or changed over time, and whether one or the other treatment arm — we suspected the surgical arm — might show more deterioration in their MRI at five years,” Dr. Katz said. Analyses on the five-year structural outcomes using longitudinal MRI data from the MeTeOR cohort are currently underway.
While MeTeOR investigators have published several papers in recent years, one of the most notable examined the outcomes of participants who were originally assigned to the non-surgical arm but later opted to have APM. “Crossover between groups is always a concern,” Dr. Losina said. “Randomized participants who are not satisfied with the non-surgical arm can cross over and receive surgery. We tried to encourage our clinical team and study participants to hold on for 12 weeks, but it is challenging to keep randomized subjects within their study arm.”
It turned out that these crossover participants reported similar pain and function outcomes after surgery to those who underwent surgery at baseline. According to Dr. Katz, “that finding supported the clinical strategy of treating non-operatively first, as subjects who underwent PT generally did very well. Those who did not improve and [later] opted for surgery experienced good surgical outcomes; we did not observe any real penalty for waiting.”
Dr. Jones, Co-Investigator at the Cleveland Clinic MeTeOR site, is one of the original MeTeOR investigators and enrolling surgeons. Dr. Jones remarked that MeTeOR findings have allowed him to “give people information about what to expect if they choose different treatments. I see a lot of patients with meniscus tear and osteoarthritis. Before MeTeOR, there were a lot of people who wanted to have their tear fixed surgically, but now we can give them good solid evidence that if they try physical therapy first, they can still have just as good of an outcome after surgery.”
Further analyses of MRI data from the 18-month and five-year follow-up studies revealed that the operative group experienced more deterioration in the joint, defined as a loss of cartilage and an increase in osteophyte formation, than the non-operative group. The surgically treated subjects also underwent a total knee replacement at a higher proportion than subjects treated with physical therapy only. Dr. Losina noted that one of the more important questions that remain involves the long-term implications of the imaging findings. “If surgery offers faster symptom relief in the short-term but ultimately leads to faster progression in the longer term, is it an important piece of information to consider when discussing the surgical and non-surgical options with patients?”
We will pick up the story in the next installment of this blog, where we’ll discuss the recently funded 12-year follow up of the MeTeOR cohort.