Predictive Utility of a Short-Term Improvement in Objectively Measured Physical Activity in Rheumatoid Arthritis Patients Initiating Biologics: A Prospective Cohort Study

INTRODUCTION Chronic pain, fatigue, and decreased functional ability are challenging for patients suffering from Rheumatoid Arthritis (RA). Approximately half of this patient population report significant pain, extensive fatigue, and limitation in activities of daily living, including workability, despite comprehensive anti-inflammatory treatment. RA patients have an increased risk of cardiovascular disease similar to diabetes patients, and RA is associated with excess mortality. Physical activity (PA) reduces the cardiovascular risk through various pathways, including the enhanced activity of endothelial nitric oxide synthase, increased blood flow, and improvements in anti-oxidizing mechanisms. The fourth leading risk factor for death globally is physical inactivity, which is responsible for approximately 6% of deaths.

PA has been widely studied in RA, where both self-report questionnaires and performance-based assessments, such as accelerometry, have been applied. The reliability of accelerometry is well established; however, patient reporting of PA is subject to recall bias and biased estimation. Studies have demonstrated only a modest association between self-reported and performance-based measures of PA.

Several accelerometry studies of RA patients have been performed with partially conflicting results. Most studies have proven RA patients to be less physically active than healthy controls, and only a minority of RA patients seem to fulfil the World Health Organization (WHO) recommendations regarding the level of daily physical activity. However, some studies find no differences between RA patients and healthy controls. Several studies have examined differences in PA among RA patients regarding disease activity. They all found PA to be inversely correlated to disease activity or score on the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI). However, most of these studies do not allow inferences about directions of the observed relationships given the study design applied. Only two studies (including n=18 and n = 30, altogether 48 patients) were prospective, leaving this question unanswered.

Rationale and Evidence-Based Research Concomitant fibromyalgia (FM) is a chronic pain syndrome characterized by widespread pain and tenderness, often accompanied by multiple symptoms from various organ systems. FM has been estimated to be present in between 15% and 20% of RA patients. As for RA, PA studies in FM patients assessed by accelerometry have concluded that FM patients are less physically active than healthy controls. Like RA patients, only a minority of FM patients fulfil WHO recommendations regarding daily physical activity, and a former study has shown that RA patients with concomitant FM have higher disease activity (DAS28-CRP) scores than sole RA patients. To our knowledge, no study has examined the impact of concomitant FM in RA patients regarding PA measured by accelerometry and the response to disease-modifying treatment.

Aims and Hypotheses The primary aim of this study is to investigate the prognostic value of immediate change in PA on treatment response among RA patients initiating their first biological treatment (according to Danish national treatment guidelines). The main hypothesis is that treatment response to biological therapy (defined as achieving DAS28-CRP<3.2 after 12-16 weeks, according to Danish national guideline) can be predicted from an initial higher increase in objectively measured PA, measured by accelerometer one week after first biological treatment onset compared to one week before biological treatment onset.