Title: Acute flares and flare phenotypes in knee osteoarthritis: an observational case-crossover study to improve recognition and advice for prevention and management
Funder: Health Education England

Abstract: Osteoarthritis, most commonly affecting the knee joints, is a leading cause of persistent pain and years lived with disability in populations worldwide. Each year in the UK one million people consult their general practitioner under a diagosis of osteoarthritis, a minority of all those living with the problem. Direct costs attributed to osteoarthritis account for 1.0-2.5% of gross domestic product, mainly due to costs relating to total joint arthroplasty. Although osteoarthritis is most commonly perceived as a slowly progressive disease, the rate of progression differs between individuals and the nature and severity of symptoms vary within individuals over time. My proposal focuses on research that will aid patients and healthcare practitioners in the prevention and management of acute, often unpredictable, flare-ups of severe pain. 'Acute-on-chronic' episodes are a well-recognised feature of many long-term conditions (e.g. chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, gout) but are only now being seen as important in the course of osteoarthritis. From qualitative studies we know that these acute flares can be distressing and disabling, can precipitate increases in analgesia and primary healthcare consultation, and may disrupt long-term behaviour change recommended for osteoarthritis (e.g. maintaining a healthy weight and regular physical activity). Beyond this, however, very little is known of the nature, occurrence, and determinants of acute flares in osteoarthritis from quantitative studies.Building on developmental studies and with input from national and international collaborators, I will conduct a case-crossover study design and novel web-based data collection platform with the following specific objectives: to estimate the time course of acute flares in knee osteoarthritis with respect to symptoms, activities, and role interference, in order to provide better information to patients and practitioners on the likely short-term prognosisto describe the extent to which acute flares are anticipated by patients, and to identify the most common and consistently associated proximate causes (triggers'), in order to help make acute flares more predictable and therefore potentially preventableto determine whether characteristics of the patient and his/her problem can identify individuals who are susceptible to flares (frequent flare phenotypes'), in order to target flare management and preventive advice in practice 565 people aged 40 years with a recent primary care consultation diagnosis of knee osteoarthritis will be recruited from the registers of up to 17 general practices. After a baseline survey, participants will be followed for up to a year through a combination of scheduled, monthly follow-up ('control windows') and event-driven measurement at the time of an acute flare ('case windows'). Data collection on a range of physical and psychological exposures in both case and control windows will be used to identify triggers for acute flares. The significant and unique feature is the emphasis on using a within-person design to understand pain variability and acute flares and their prevention and management. This study will fill an important gap within the current UK-based national policy and dissemination strategy for osteoarthritis management. Benefit to patients and the NHS will be realised within 5 years of completion, focussed on the following: providing clinicians in routine consultation with key questions to help identify patients having, or at most risk, of frequent flare-ups providing patients with a self-management advice booklet about common triggers for flares together with early flare-up self-recognition and modification strategies suggesting how the timing and delivery of generic National Institute for Health and Care Excellence guideline recommendations for osteoarthritis can be tailored and targeted to patients experiencing frequent flares phenotypes providing a frequent-flarer phenotype' case definition for application in future biomarker and intervention studies

Lay abstract: AimThis study is about acute episodes (known as flare-ups or flares) of painful knee osteoarthritis. We are trying to find out: when and why people have flare-ups why some people have more flare-ups than others the different types of flare-ups that people get (flare phenotypes'). We hope our findings will help to reduce the impact of painful flare-ups on peoples' lives and develop specific treatments for people who need them most.Background Over 8 million people in the UK have seen their doctor about osteoarthritis. It is the main cause of long-term physical disability in later life, but its effects are also seen in middle age. Joint pain, stiffness and other related symptoms can interfere with sleep, mood, and a wide range of daily activities. This makes it difficult for people to keep doing the things they need and want to do.People generally think of osteoarthritis as aches and pains in joints that gradually get worse over the years. But many patients tell us they get acute flare-ups that are difficult to cope with, particularly when they are severe and unpredictable. These acute flare-ups can cause people to seek help from healthcare professionals. They can also disrupt healthy routines, like keeping physically active and losing weight, that play a role in slowing the progression of osteoarthritis.The National Institute for Health and Care Excellence recommends that basic treatments such as written information and advice on exercises and physical activity should be offered to all people with painful osteoarthritis. However, there is little evidence on which to base advice to patients on how to predict and manage sudden and unusual flare-ups of pain.Design and methods We will use a study design method known as a case-crossover study' to identify what triggers flare-ups and other features of flare-ups specific to each individual. A case- crossover' study involves comparing what people usually do with what happens just before they had a flare-up. It is used to work out why people with knee aches and pains cross over' into an acute flare-up. By recruiting people through their doctor, we will: ask 565 participants with painful knee osteoarthritis to answer questions about what they have been doing over a seven-day period; we will do this once a month for a year collect additional information about participants' daily activities for the previous seven days if they have experienced a flare-up of their knee osteoarthritis compare what participants have been doing on the days when their knee pain is good, with days just before their knee pain flares up. This will help understand how flare- ups may relate to the activities people do and how these might be changed to prevent or lessen the severity of flare-ups in the future.It is important that information about flare-ups can be collected as soon as they happen. So, participants will be asked to provide information via the internet using an on-line questionnaire.Patient and public involvement As part of an advisory group, 16 patients with knee osteoarthritis have helped develop the study. The internet website and study questions are being designed and tested with the patient advisory group. This will make sure that questions are easy to answer and that the internet website is user-friendly and works on computers and smart phones and similar devices.The patient advisory group will also help to: develop information for the website to help keep participants interested in the study produce training information for primary healthcare professionals using the study results make a patient self-management booklet using the study results. Dissemination Study results will be presented to other researchers at conferences, published in journals, and disseminated through osteoarthritis charities and health professionals' training. Plans to share findings with the general public will be developed with the patient advisory group. By working with primary healthcare providers and patients, it is anticipated that the findings of this research study will improve patient care in the following ways: by providing patients with information on the most common triggers for flares, and what things to watch for in the early stages of a flare-up that may predict how long it will last by providing primary healthcare professionals with simple questions to identify patients who are getting flare-ups by providing policymakers with evidence to make a new recommendation for managing acute flare-ups that can be included in clinical guidelines so that the right care and personalised treatment advice are provided to the right patient at the right time.

Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: MUSCULOSKELETAL