SLIDESHOW Rheumatoid Arthritis: Examining Patient-Reported Outcomes
What Are Patient-Reported Outcomes?
Patient-Reported Outcomes (PROs) are symptoms patients with rheumatoid arthritis (RA) observe during the natural history of their disease. They provide clinicians with the patient’s perspective on her wellbeing. There is consensus on the importance of patient-reported pain, physical function, and global assessment of disease activity in assessing patients for treatment response.<sup>3</sup> Many experts also consider fatigue and the duration of morning stiffness to be important PROs, but more data are needed to correlate these measures with outcomes. Other PROs with potential significance in assessing outcomes include flare, work participation or productivity, sleep quality, emotional distress, and coping.<sup>2,3</sup> The use of PROs to assess disease activity allows patients with RA to take an active role in their treatment and contribute to RA research. Several challenges exist when incorporating PROs into practice, including variability in which PROs an instrument assesses and the heterogeneous nature of RA. <i>Photo Credit: Dr P. Marazzi/Science Source</i>
How Do PROs Correspond With Clinical Outcomes?
Observational studies of patients with RA have shown that change in PROs like patient global disease assessment, pain, function, and fatigue correspond with objective measures of disease activity. In an observational trial of patients with RA treated with adalimumab, 68% of patients with objective improvement in disease activity after 1 year of treatment had significant improvement in pain, 39% had significant improvement in fatigue, and 42% had significant improvement in function. Only 23% of patients with an objective therapeutic response had no significant change in any PRO assessed. Conversely, in the cohort of patients who did not have objective improvement, rates of significant improvement for pain, fatigue, and function were 29%, 15%, and 17%, respectively.<sup>4</sup> Other studies have found that in addition to providing an accurate measure of treatment response, PROs are good predictors of long-term outcomes.<sup>4</sup>
What Do Clinical Trials Tell Us About PROs?
Clinical trials show that PROs are sensitive enough to differentiate between active treatment and placebo and they correspond with standard LDA assessments.<sup>2,4,5</sup> A trial that compared tofacitinib with methotrexate found at least 70% of patients with clinically significant improvements in Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), or ACR70 remission scores also had significant improvement in physical function and pain.<sup>5</sup> In another trial, which combined a tumor necrosis factor inhibitor with methotrexate, data showed moderate to high concordance between the SDAI, CDAI, and PROs.<sup>6</sup> Instruments like the SDAI and CDAI, which use a composite of swollen and tender joints and patient and physician global assessment to measure LDA, appear to weigh joint counts heavier than PROs.<sup>2</sup> As a result, investigators are considering a broader range of PROs to help understand heterogeneous treatment responses and identify outcomes that are most important to patients.
Do PROs Correspond With Imaging Outcomes?
Over the years, many studies have identified an association between radiologic damage and physical function as measured by the health assessment questionnaire-disability index (HAQ-DI).<sup>7</sup> More recently, a post hoc analysis from the GO-BEFORE trial of golimumab (ClinicalTrials.gov Identifier NCT00264537) evaluated the relationship between magnetic resonance imaging (MRI) findings and PROs.<sup>8</sup> More synovitis, osteitis, and bone erosion on MRI corresponded with increased HAQ-DI scores, pain, and patient global assessment scores. Patients who had improvement in synovitis and bone erosion on MRI after 1 year of therapy also had improvement in PROs. All PROs worsened in patients with lesser degrees of improvement or progression of erosion on MRI after 1 year. Progression on x-ray did not correlate with worse PROs. Longer trials that measured MRI changes versus PROs would be useful. <i>Photo Credit: SPL/Science Source</i>
Discordance Between Patient and Physician Assessments
In approximately one-third of cases, patient and physician global assessments of disease activity are discordant.<sup>9</sup> Studies suggest that physicians typically rate disease activity lower than patients with RA. Reasons are unclear, although it may partly be because physicians are more concerned with joint swelling and tenderness or laboratory values, whereas patients are more concerned with pain and functional impairment. The PRESERVE clinical trial of etanercept found 32% of patients and physicians had discordant global assessment scores at baseline.<sup>9</sup> Patients with more serve disease were more likely to have discordant scores. After 36 weeks of therapy, discordance decreased to 27%. Data also showed 42% of patients had discordance between objective measures of disease activity and their global assessment of disease activity. Considering a broader range of PROs may improve clinicians’ understanding of treatment response.
What Are Some Challenges in Measuring PROs?
RA is a heterogeneous disease, which is why PROs are so important for assessing disease activity. One patient may have several swollen joints but report less pain than a patient with no swollen joints.<sup>2</sup> A major challenge in assessing PROs is understanding how comorbidities or other health problems unrelated to RA might affect patient assessments of pain, fatigue, and function.<sup>3</sup> For example, in a patient with fibromyalgia, is the pain attributable to RA or to fibromyalgia? Depression, present in up to 40% of RA patients, is also associated with worse PROs.<sup>10</sup> One study showed patients with depression were significantly more likely to have higher scores for pain and fatigue. In the study, limited English proficiency and less advantageous sociodemographic variables also corresponded with worse PROs.<sup>10</sup> For patients with limited health literacy, the patient global assessment is complex and confusing.<sup>11</sup> Instruments are needed that have been validated in patients with limited health literacy or English proficiency.
How Are PROs Measured?
No standardization exists for the use of PRO instruments in clinical practice, and several are used, which measure different outcomes. Most instruments evaluate pain, patient global assessment, and fatigue using a visual analog scale (VAS).<sup>5</sup> A systematic review of the literature for articles on PRO instruments in RA published in the past 20 years identified the following instruments as the strongest and most thoroughly validated:<sup>12</sup> • Patient-derived Disease Activity Score with 28-joint counts (Pt-DAS28) • Rheumatoid Arthritis Disease Activity Index (RADAI) • RADAI-5 • Routine Assessment of Patient Index Data (RAPID)-5 Rheumatologists are increasingly expected to track PROs in clinical care. More guidance is needed on how to select an instrument for assessing PROs and how to apply the information obtained.<sup>3</sup>
New PRO Instruments
New instruments to measure PROs are involving RA patients in the development process. The Patient Uncertainty Questionnaire-Rheumatology (PUQ-R) is a PRO instrument designed with input from and validated in patients with lupus or RA.<sup>13</sup> It includes 5 domains of uncertainty, which the authors say has important implications for patient care. PUQ-R domains corresponded with results from non-RA-specific instruments that measure uncertainty. However, it will need to be evaluated in relation to disease activity instruments before being used to assess treatment response. The Dutch Rheumatoid Arthritis Impact of Disease (RAID) is another recently validated instrument created with patient input.<sup>14</sup> The researchers conducted focus groups among a group of RA patients from 10 countries. It includes 5 domains: emotional well-being, pain, performing daily activities, fatigue, and coping. The authors identified translation issues as an important challenge in developing new PRO instruments.
What About PROs in Juvenile Idiopathic Arthritis?
PROs are also important for assessing disease activity in juveniles with juvenile idiopathic arthritis (JIA).<sup>15</sup> Pediatric patients with JIA are affected by the same symptoms as adults with RA. However, the symptoms may have a greater effect on their physical and social development. Measuring PROs in children can be challenging, and studies have identified high levels of discordance between how parents, patients, and physicians perceive patient well-being.<sup>15</sup> Including PROs in clinical trials of pediatric patients with JIA offers a valuable opportunity to assess the relationship between PROs and long-term outcomes and behaviors. Validated instruments are available to measure PROs in children of various ages.
How Can Patients Track Symptoms?
Smart phone apps are available that patients can use to track their RA symptoms between visits to the clinic: • MyRA • Rheumatoid Arthritis Track + React • RA Helper • RheumaTrack A tracker is also available through the Arthritis Power initiative (arthritispower.creakyjoints.org). The app is part of a research initiative into PROs sponsored by CreakyJoints. Although patients will not receive feedback on what they report, they will have a daily record of their PROs that they can share with their physician, and they will be contributing to knowledge about PROs and treatment response. Collecting information about a broad range of PROs has the potential to lead to more patient-centered care and better treatments.
The goal of the treat-to-target approach used in rheumatoid arthritis (RA) is to help patients achieve remission or a state of low-disease activity (LDA).1 Although current methods for assessing response depend heavily on objective measures such as joint counts, imaging, and laboratory tests, patient-reported outcomes (PROs) are critical for assessing treatment response. Studies have found strong correlations between PROs and disease activity, and clinical trials of novel RA drugs are increasingly incorporating PROs as endpoints.2
However, considerable variation exists as to which PROs are used and how they are measured. More data are needed to identify truly meaningful PROs and validate PRO instruments across various patient populations.2 Validation of a PRO instrument as an effective independent tool for measuring disease activity and treatment response may one day allow decreased reliance on expensive or time-consuming assessments, such as magnetic resonance imaging (MRI) or joint counts.
This slideshow originally appeared here.
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