Vibeke Strand, MD: Assessing Correlations of Patient-Reported Outcomes in Rheumatoid Arthritis

Rheumatology Network sat down with Vibeke Strand, MD, to explore her upcoming ACR presentation, “Assessing the Relationship of Patient Global Assessment of Disease Activity and Health Related Quality of Life by SF-36 with Other Patient-Reported Outcomes in Rheumatoid Arthritis: Post Hoc Analyses of Data from Phase 3 Trials of Baricitinib.” Strand is an adjunct clinical professor in the Division of Immunology and Rheumatology at Stanford University School of Medicine.

In these post-hoc analyses of randomized controlled trial (RCT), of baricitinib (BARI), investigators analyzed improvements in patient-reported outcomes (PROs) in patients with rheumatoid arthritis. They determined the importance of PROs on the Patient Global Assessment of Disease Activity (PtGA) and health-related quality of life (HRQoL), as well as if this differed in patients with either good disease control, those who had not achieved low disease activity, and those in remission.

“Baricitinib treatment resulted in statistically significant clinically meaningful changes in PROs versus a placebo in 3 different patient populations: RA-BEGIN focused on early disease, the naïve population, RA-BEAM patients had an inadequate response to disease-modifying antirheumatic drugs (DMARD-IR) and those in RA-BEAM were biologic DMARD-IR,” explained Strand.

Rheumatology Network: Can you tell me a bit more about the study design?

Vibeke Strand, MD: The difference between RA-BEAM and RA-BEACON is that BEAM was looking at BARI 4 and BARI 4 + methotrexate. There is also a placebo group in both BEAM and BEACON, and an adalimumab comparison in BEAM. In the early RA group, it's just methotrexate, no placebo, versus the 2 doses of baricitinib. But what this is really about is the PROs and what the studies are trying to do is tell us how important these PROs are.

Investigators were trying to figure out the most influential PROs that determined PtGA and how the short form 36 (SF-36) HRQoL instrument, which is generic, but very sensitive, discriminative, and well validated in RA, affects scores So here, they're just looking at the components summary scores, both physical (PCS) and mental (MCS). As improvements get bigger, you can really see patients know that they're getting better.

RN: What is the clinical significance of these results?

VS: It isn't just that pain determines patient global fatigue and HRQoL, different aspects also contribute to this. And essentially, the only way to really look at all this is to look across all of them, as opposed to just picking HRQoL, or pain, or fatigue. But also, we must remember that PtGA is defined as all of the ways your disease affects you and how you are doing today. It's meant to be a question about how you think your disease activity is, based on both the questions we've asked you, such as physical function, pain, etc, but also the questions we haven't asked you. In essence, it's supposed to be the most accurate assessment of how a patient's doing.

It’s important to collect information from multiple PROs in RCTs, and in clinical practice, because RA affects so many different aspects of your life.

RN: What first interested your team in determining the relationship between the PtGA and the HRQoL with other PROs within this patient population?

VS: We’ve been doing these types of analyses in RA now for a long time. And what was good here was that we were looking at across the 3 trials with baricitinib, not just 1 population.

RN: What were the results of this study?

Not only are we going to look at the relationship between these different PROs on PtGA and the HRQoL by the PCS and MCS, but we also determined whether this is different in patients in low disease activity.

So, as you might expect, as has already been published, pain is strongly correlated with PtGA. It has been well recognized as an important influencing factor. But pain was also negatively correlated with PCS improvements on a level of about a moderate correlation and the MCS, which are looking at emotional and mental health, had a negative, but low, correlation.

When you include Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), it's moderately positively correlated with the HRQoL and it's actually the most important influencing factor for MCS scores, including emotional, social functioning, mental health, and vitality. And together, the FACIT-F and the PtGA were moderately negatively correlated, because when PtGA gets better and is going down, FACIT and SF-36 scores go up. I like PROs that show you improvements because you can graph them for patients and doctors.

Morning stiffness is important, but it's very weakly correlated with all of these other outcomes, because morning stiffness often doesn't get better. We did a long-term study several years ago and found out that patients with morning stiffness maintain that morning stiffness. They don't improve, even when they've changed therapy. And so, if you get a new onset of it, it usually means you're flaring.

In summary, these correlations were the same whether patients had gone into remission, had stayed in low disease activity, or hadn't done either.

“These results confirm prior findings, such as high correlations of pain with PtGA. We, however, observed that the relationships between other PROs with PtGA, PCS, or MCS scores were stable across time points over the first 6 months of treatment in differing patient populations, ranging from early to later disease. PtGA, PCS, and MCS scores were each associated with different PROs, indicating the importance of collecting multiple PROs in RCTs and real-world clinical practice,” investigators concluded.