In this post hoc analysis of the MAAPs study we verified that a high percentage (54.7%) of patients with established PsA undergoing systemic therapies reached a low disease impact according to the PsAID questionnaire. However, joint or skin remission, defined by the evaluating physician, was not consistent with an acceptable symptomatic status. The agreement between other disease outcomes, such as the MDA response, or the HAQ, was fair or moderate, with respect to the PASS state. However, the best concordance rate between this status and a clinical outcome was found with cDAPSA remission (k: 0.58, p < 0.0001). On the other hand, the presence of DIP joint involvement, a higher CRP value at study visit, or a family history of PsA, diminished the odds of having reached a low impact of disease according to the PsAID.
In recent years, the rheumatology community has witnessed an intense search for sensitive and valid instruments that capture those clinical aspects related to disease activity, as well as those linked to the response to the scheduled treatments; along with other instruments, more focused on the experiences and perceptions lived by PsA patients [3–6, 15]. Despite this intense search, there is a remarkable mismatch between the results derived from the instruments for measuring disease activity (e.g., DAPSA), or those that assess the treatment objectives (e.g., MDA), and the PROMs (e.g., pain, fatigue, PsAID). Our results do not escape this decoupling, and in fact, the worst agreement was between the definition of remission by clinicians, and the PASS state according to the PsAID questionnaire. On the contrary, the best agreement was seen between cDAPSA remission and PASS. In this sense, our findings are quite consistent with those of the recently published ReFlap (Remission/Flare in PsA) study [16]. In ReFlap, adults with physician-confirmed PsA and > 2 years of disease duration in 14 countries were included. Remission was defined as very low disease activity (VLDA), DAPSA ≤ 4, and physician-perceived and patient-perceived remission. In this study, DAPSA-based remission/low disease activity (LDA) performed better than VLDA/MDA to detect patient defined remission or remission/LDA. Further, physician-perceived remission/LDA using a single question was frequent (67.6%) but performed poorly against other definitions [16].
Which are the drivers of this discordance between patient-perceived remission, or low impact of disease, and physician-defined remission?. Discordance between patients and physicians may vary according to levels of disease activity. Possibly, in high disease activity, both patient and physician global assessments (PGA/ PhGA) will be unsatisfactory, whereas in LDA, patient and physician expectations may differ more frequently. In a recent study that included 460 patients (40.4% undergoing treatment with biologic agents), discordance defined by |PGA − PhGA| ≥3 of 10, concerned 134 patients (29.1%), and 115 patients (85.8% of the patients with discordance) had PGA > PhGA. Higher fatigue, lower self-perceived coping, and impaired social participation, were independently associated with a higher difference PGA − PhGA [10]. Authors concluded that factors associated with discordance were psychological rather than physical domains of health. In our study, the most active components of the MDA response in subjects with high disease impact were pain, PGA, and HAQ ≥ 0.5. This may reflect that pain (regardless of inflammatory activity), and physical dysfunction, are the main drivers of a state of high disease impact in these patients.
This mismatch between the visions of doctors and patients is not a minor matter [17]. In another recent study, it was found that one third of patients in a clinically acceptable condition according to the evaluating physician, did not reach the MDA response, so that if a treat to target strategy had been applied, these patients should have received a therapeutic intensification [18]. Therefore, we need to balance the information from conventional activity measures, with those reflecting patient´s perceptions, in order to make clinical and therapeutic decision making that conform to current disease management recommendations [19].
The nail plates and DIP joints are closely connected through a network of entheses, so that inflammation at these anchor points is the common immune connector to both domains of psoriatic disease [20]. Although the involvement of DIP joints is a well-known feature of PsA, little is known about the effect of this manifestation on QoL, the impact of the disease, or the achievement of treatment goals. A very recent study, showed that DIP disease decreased the odds of having reached the MDA response [21]. In our study, we have found a negative association between this manifestation and the PASS state; however, we did not detect any link between this trait and the MDA response. We can speculate on the fact that perhaps some of these patients could actually have DIP osteoarthritis (OA), which is usually associated with OA at other locations, resulting in a worse functional status. However, one of the exclusion criteria of this study was the presence of a suspected or confirmed hand OA.
We also found that a positive PsA family history decreased the chances of reaching a state of low disease impact. In a classic study, HLA antigens B27, when DR7 was present, and DQw3, when DR7 was absent, predicted disease progression across all transitions, while HLA-B39 was associated with progression in early disease [22]. Disease progression, understood as progression of structural damage, is the main factor associated with a high HAQ (one of the most active components in our patients with high disease impact) [23]. This may allow us to speculate with some genetic background driving the factors associated to the perception of disease impact. However, the concept of disease impact is multifactorial, so this assumption does not go beyond being a mere hypothesis that requires adequately designed studies.
A recent subanalysis of the ReFlap study showed that high life impact (PsAID ≥ 4) was associated with female gender, enthesitis, tender joints, and comorbidities [24]. Although in our study more men reached an MDA status, none of the factors found in the aforementioned Reflap study was associated with a high impact of disease in our population. Even more, some comorbidities (obesity, CHD) were positively associated with a low impact of disease in our series. Although obesity, and other elements of the metabolic syndrome, has been associated with worse QoL and worse therapeutic response in PsA, not all studies point in that direction [25, 26].
Our study has the limitations of any cross-sectional study. It is therefore, an observation at a specific timepoint of a disease, such as PsA, which tends to a high phenotypic variability over time. In addition, the instrument chosen to measure disease activity (e.g., DAPSA) does not include important aspects of the disease (axial involvement, skin, enthesitis). On the other hand, the PsAID questionnaire surely captures many patient´s perceptions, which go far beyond what can be included in a therapeutic objective such as MDA. Therefore, mismatch between these instruments is not unexpected.