Efficacy and cost-effectiveness of Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis: protocol for a randomised placebo-controlled trial (the SCUlpTOR trial).

INTRODUCTION: Knee osteoarthritis (KOA) is a highly prevalent disabling joint disease. Intra-articular stem cell therapy is increasingly being used for treating KOA with little high-quality evidence to support its use. The aim of this study is to investigate the efficacy, safety and cost-effectiveness of allogeneic mesenchymal stem cells (Cymerus MSCs) for treating symptomatic tibiofemoral KOA and improving knee structure over 24 months. METHODS AND ANALYSIS: The Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis study is a phase III, multi-centre, parallel, superiority, randomised, double-blind, placebo-controlled trial, which will be conducted in Sydney and Hobart, Australia. 440 participants (220 per arm) aged over 40 years with painful KOA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) with medial minimum joint space width between 1 and 4 mm in the study knee will be recruited from the community and randomly allocated to receive either intra-articular MSCs or saline at baseline, week 3 and week 52. The coprimary outcomes will be the proportion of participants achieving patient-acceptable symptom state for knee pain at 24 months and quantitative central medial femorotibial compartment cartilage thickness change from baseline to 24 months. Main secondary outcomes include change in knee pain, Patient Global Assessment, physical function, quality of life and other structural changes. Additional data for cost-effectiveness analysis will also be recorded. Adverse events will be monitored throughout the study. The primary analysis will be conducted using modified intention-to-treat. ETHICS AND DISSEMINATION: This protocol has been approved by The University of Sydney (USYD) Human Research Ethics Committee (HREC) #: 2020/119 and The University of Tasmania (UTAS) HREC #: H0021868. All participants will be required to provide informed consent. Dissemination will occur through conferences, social media, and scientific publications. TRIAL REGISTRATION NUMBERS: Australian New Zealand Clinical Trials Registry (ACTRN12620000870954); U1111-1234-4897.

Endorsement of the domains of knee and hip osteoarthritis (OA) flare: A report from the OMERACT 2020 inaugural virtual consensus vote from the flares in OA working group.

OBJECTIVE: Towards developing an instrument to measure knee and hip osteoarthritis (KHOA) flare, the Outcome Measures in Rheumatology (OMERACT) Flares in OA Working Group first sought to identify and define relevant domains of flare in KHOA. METHODS: Guided by OMERACT Filter 2.1, candidate domains were identified from data generated in interviews, in English or French, with persons with KHOA and health professionals (HPs) who treat OA. The first and second rounds of an online Delphi process with patients and HPs, including researchers, selected relevant domains. The third round provided agreement on the selected domains and their definitions. At the virtual OMERACT 2020 workshop, the proposed domains and their definitions were discussed in facilitated breakout groups with patients and HPs. Participants then voted, with consensus set at ≥70%. RESULTS: Qualitative interviews characterizing OA flare were completed with 29 persons with KHOA and 16 HPs. Content was analyzed and grouped into nine clusters. These candidate domains were included in two Delphi rounds, completed by 91 patients and 165 HPs then 50 patients and 116 HPs, per round, respectively. This resulted in selecting five relevant domains. A final Delphi round, completed by 38 patients and 89 HPs, provided agreement on these domains and their definitions. The OMERACT virtual vote included 27 patients and 106 HPs. The domains and their definitions were endorsed with ≥98% agreement. Domains include: Pain, Swelling, Stiffness, Psychological aspects, and Impact of symptoms, all defined "during flare". CONCLUSION: Using OMERACT methodology, we have developed five domains of KHOA flare that were highly endorsed by patients and HPs.

National osteoarthritis strategy brief report: Advanced care.

BACKGROUND: Osteoarthritis (OA) is one of the most common chronic joint diseases and a leading cause of pain and disability in Australia. A National Osteoarthritis Strategy (the Strategy) was developed to outline a national plan to achieve optimal health outcomes for people at risk of, or with, OA. OBJECTIVE: This article focuses on the theme of advanced care of patients with OA within the Strategy. DISCUSSION: The Strategy was developed in consultation with a leadership group, thematic working groups, an implementation advisory committee, multisectoral stakeholders and the public. This Strategy identified three priorities in advanced care for osteoarthritis. In brief, these include surgical decision making, referral for evidence-informed non-surgical alternatives and surgical services. A set of goals within these priority areas and strategies was also proposed by the working group in consultation with stakeholders nationwide. Peak arthritis bodies and major healthcare professional associations currently endorse the Strategy.

Developing a Preliminary Definition and Domains of Flare in Knee and Hip Osteoarthritis (OA): Consensus Building of the Flare-in-OA OMERACT Group.

Flare in knee and hip osteoarthritis (OA) is more than just an exacerbation of pain. Unstructured, semistructured, and focus group interviews followed by Delphi surveys with patients and health professionals (HP) generated candidate domains of an OA flare. Content analysis of interviews with 29 patients and 16 HP extracted 180 statements, which were grouped into 9 clusters. Delphi consensus with 50 patients (Australia, Canada, and France) and 116 HP (17 countries on 4 continents) identified 5 flare domains: pain, swelling, stiffness, psychological aspects, and effect of symptoms. Elements for a preliminary definition of an OA flare are proposed. Registered at clinicaltrials.gov NCT02892058.

Uptake of the OMERACT-OARSI Hip and Knee Osteoarthritis Core Outcome Set: Review of Randomized Controlled Trials from 1997 to 2017.

OBJECTIVE: To assess the uptake of the OMERACT-OARSI (Outcome Measures in Rheumatology- Osteoarthritis Research Society International) core outcome set (COS) domains in hip and/or knee osteoarthritis (OA) trials. METHODS: There were 382 trials of hip and/or knee OA identified from the ClinicalTrial.gov registry from 1997 to 2017. Frequency of COS adoption was assessed by year and per 5-yearly phases. RESULTS: COS adoption decreased from 61% between 1997 and 2001 to 38% between 2012 and 2016. Pain (95%) and physical function (86%) were most consistently adopted. Patient's global assessment (48%) was the principal missing domain. CONCLUSION: Limited adoption of the COS domains indicates that further consideration to improve uptake is required.

The OMERACT-OARSI Core Domain Set for Measurement in Clinical Trials of Hip and/or Knee Osteoarthritis.

OBJECTIVE: To update the 1997 OMERACT-OARSI (Outcome Measures in Rheumatology-Osteoarthritis Research Society International) core domain set for clinical trials in hip and/or knee osteoarthritis (OA). METHODS: An initial review of the COMET database of core outcome sets (COS) was undertaken to identify all domains reported in previous COS including individuals with hip and/or knee OA. These were presented during 5 patient and health professionals/researcher meetings in 3 continents (Europe, Australasia, North America). A 3-round international Delphi survey was then undertaken among patients, healthcare professionals, researchers, and industry representatives to gain consensus on key domains to be included in a core domain set for hip and/or knee OA. Findings were presented and discussed in small groups at OMERACT 2018, where consensus was obtained in the final plenary. RESULTS: Four previous COS were identified. Using these, and the patient and health professionals/researcher meetings, 50 potential domains formed the Delphi survey. There were 426 individuals from 25 different countries who contributed to the Delphi exercise. OMERACT 2018 delegates (n = 129) voted on candidate domains. Six domains gained agreement as mandatory to be measured and reported in all hip and/or knee OA clinical trials: pain, physical function, quality of life, and patient's global assessment of the target joint, in addition to the mandated core domain of adverse events including mortality. Joint structure was agreed as mandatory in specific circumstances, i.e., depending on the intervention. CONCLUSION: The updated core domain set for hip and/or knee OA has been agreed upon. Work will commence to determine which outcome measurement instrument should be recommended to cover each core domain.