Rheumatoid Arthritis (RA) is a common, chronic disease that causes inflammation and often presents with pain in the joints. Untreated, RA can cause severe damage to the joints and their surrounding tissue, and can lead to heart, lung, and nervous system problems. While therapeutic approaches help to improve joint mobility and muscle strength, and improve pain management, RA is not curable. As a chronic disease that generates intense pain, RA has an impact on many aspects of day-to-day life, and often necessitates changes in lifestyle of both patients and their families.
As with any uncurable disease, RA represents a significant unmet medical need, with an estimated prevalence between 0.5 to 1% of the global population. RA clinical research activity is significant, with 3,471 clinical trials registered in ct.gov as of October 10th, 2024. But how are the individual disease manifestations analyzed in these clinical trials? Are we capturing the patient voice sufficiently through standardized measures, to provide pertinent information to guide research and future therapeutic interventions?
Why capture individual disease manifestations of rheumatoid arthritis through Patient Reported Outcomes (PROs)?
The disease symptomatology varies widely between patients, with highly variable levels of pain and inflammation, and a range of body areas affected. As such, characterizing the disease requires collecting a large amount of symptomatology information from a wide range of patients.
- PROs allow symptoms and their impact on day-to-day life to be captured in a way that standard clinical assessment does not permit. As such, PROs provide high value data in RA clinical research.
- PROs also allow mental health signals to be captured, which could also be of high importance in RA clinical research. In other inflammatory disease research, it has been reported that measures of behavior and mental health status can predict future disease activity, as may levels of stress, adequacy of sleep, and availability of coping support mechanisms. These issues are often reported by patients but are not captured by routine clinical measures, and capturing this information contributes to more patient-centered care, an improved patient experience, and potentially better treatments. In one study, researchers found RA to be among the top three reasons that stopped a person from working or limited a person’s ability to work, and reported that 18% of patients said that RA affected their ability to work. This study also found that 21% of patients reported that depression prevented them from working. This supports the importance of measuring mental health consequences, as well as physical symptomatology.
- Capturing PRO data might also add value in economic evaluations of the disease and the assessment of treatment options. As RA is not curable, patients use a range medications to cope with their disease, and recent data show that persons with RA have been estimated to have health care costs 2 to 3 times the rate of individuals without RA. Efforts to develop new, well-targeted treatments will not only contribute to improving the health of RA patients, but will also improve health outcomes and quality of life, and will decrease medical care costs.
As all these aspects are suitable for PRO assessment, adding PRO endpoints in RA clinical research to detect both physical and mental health signals is relevant, and using electronic methods to capture the data is nowadays a well-adopted methodology.
Why combine electronic Patient Reported Outcomes (ePROs) and electronic Clinician Reported Outcomes (eClinROs) for comprehensive rheumatoid arthritis assessment?
Capturing patient insights directly is key, and electronic data collection methods have proven value. However, although necessary, ePRO data are not sufficient to obtain the full picture of disease symptomatology and its impact on quality of life. It is necessary to widen the scope of symptomatology research, and as such, combining ePROs with clinical assessments and eClinRO validated measures will provide a robust combination of data to allow researchers to make scientifically justified conclusions.
It is even more important to combine measures since discrepancies exist between evaluations by patients and clinicians. A study has demonstrated discordance between patient (measured by Patient Global Assessment instrument [PGA]) and physician (measured by Physician Global Assessment scale [PhGA]) and global assessments: while there was a linear correlation between the PGA and PhGA scores, a significant difference in mean score indicates that physicians underestimated disease severity and treatment-related adverse events and their impact on patient-perceived well-being.
Significant efforts have been made in the development and validation of both ePRO and eClinRO instruments, and their use in clinical trial settings has been widely reported in recent decades. With such momentum, what would prevent ePRO and eClinRO endpoints being added in RA clinical trial protocols?
With more than 18 million people affected globally, RA research requires well-designed protocols with fit-for-purpose endpoints. Adding ePRO and eClinRO measures to standard clinical evaluations is the only way to capture inter- and intra-individual variability in symptoms and drive meaningful, patient-centered research. It is only by using adapted measures and collecting high-quality data, that targeted patient-centered research will contribute to better care and work towards a cure for RA patients.
