Minimal disease activity (MDA) is a validated outcome measure in psoriatic arthritis (PsA) defining a low disease activity state with a cutoff of 5/7. The main aim of the study was to look at the MDA divided into in the seven cutoffs, analyzing the more frequently achieved domains. The relationship between MDA, PASS, PsAID, DAPSA, and the PhGA in all cutoffs was also evaluated.
Cross-sectional analysis on PsA patients satisfying CASPAR criteria. An assessment of disease activity, treatment target, function, and impact of disease was performed. Patients achieving MDA were compared to patients not achieving MDA in order to evaluate the most frequent domain found.
Ninety-three PsA patients were enrolled. MDA was satisfied in 44/93, while in 47 MDA ranged from 1/7 to 4/7. Among the seven domains, Leeds Enthesitis Index (LEI) was the most frequent domain found in all patients. In those not in MDA, BSA ≤ 3 (70%) and swollen joints count ≤ 1 (68%) were also well represented. The domains with a lower percentage of patients not in MDA were HAQ-DI ≤ 0.5 (38.8%), tender joint count ≤ 1 (23%), PtGA ≤ 20 (4.2%) and VAS pain ≤ 15 mm (2%). There was a growing trend, from MDA 1/7 to MDA 7/7 in the percentage of patients in PASS yes, in PsAID ≤ 4, and in DAPSA ≤ 14.
The present study detailed the domains more achieved also in those patients not in MDA showing that “physician-driven” domains are more frequently achieved in our patients.
|PsA is an inflammatory chronic disease with different clinical manifestations.|
|Minimal disease activity (MDA) is an achievable treatment target for PsA patients. However, even when MDA is not achieved, the disease state could be very different when the cut-off of 4 out of 7 criteria is reached, compared to a cut-off of 1 out of 7.|
|Our study demonstrated that some domains are frequently achieved even in patients not in MDA. In particular, swollen joints, enthesitis (by LEI) and BSA≤ 3 are frequently achieved even in those not in MDA.|
|The study showed that “physician-driven” domains are more frequently achieved in all enrolled patients. Moreover, a strong correlation was found with other outcome measures throughout the seven domains.|
Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by a variable clinical course [1, 2]. In the last 10 years, the achievement of clinical remission or low disease activity have been proposed as treatment targets for PsA patients [3, 4]. In particular, minimal disease activity (MDA) is a categorical and validated measure in PsA as treatment response criteria to capture a disease state: patients are in MDA when they satisfy 5/7 of previously published criteria . More recently, a stringent definition of remission (very low disease activity, VLDA), in which all 7/7 criteria had to be satisfied, has been proposed .
MDA has been useful to define the disease state in randomized controlled trials  and in real-world evidence studies [7, 8]. However, even when MDA is not achieved, the disease state could be very different when the cutoff of 4 out of 7 criteria is reached, comparing to a cutoff of 1 out of 7. This could be interesting to be assessed in real life because the achievement of a cutoff of 4/7 criteria has, probably, a different clinical meaning compared to the achievement of only 1/7 criteria.
As potential lack in this field is the assessment of which domains are more frequently achieved in those patients non reaching the MDA 5/7 onwards 7/7. In other words, what are the more frequently missed/achieved domains in patients that do not achieve MDA?
Therefore, the aim of this clinical study was to look at the MDA divided into the seven cutoffs (from 1/7 to 7/7) and analyzing which domains were more frequently achieved, in particular in those not satisfying the MDA, namely from 1/7 to 4/7, in a group of PsA patients, as a “climb” towards MDA. A secondary aim was to assess the relationship between MDA, categorized into seven cutoffs, with the Patient Acceptable Symptoms State (PASS) , the Psoriatic Arthritis Impact of the Disease (PsAID) , the Disease Activity for Psoriatic Arthritis (DAPSA) , and the Physician Global Assessment (PhGA).
In this cross-sectional analysis of a longitudinal cohort, patients were enrolled at the Rheumatology Unit, Department of Medicine and Health Science-University of Molise. From the June 30, 2019 until December 31, 2019, all PsA patients who were on at least 6-month follow-up treatment with conventional synthetics (cs) and biologic (b) disease-modifying anti-rheumatic drugs (DMARDs) were considered potentially eligible for the study.
Inclusion criteria were:
PsA classified with the ClASsification criteria for Psoriatic ARthritis (CASPAR) criteria ,
Age ≥ 18 years,
AT least 6 months of follow-up at the study visit,
Stable treatment with a csDMARDs or bDMARDs for at least 6 months.
Patients’ data collection included a medical history, physical examination, current use of medications, and laboratory assessment. Demographics and disease characteristics including age, sex, body mass index, and disease duration were taken into account. The clinical assessment encompassed the number of tender and swollen joints (68/66), enthesitis by the Leeds Enthesitis Index (LEI) , and dactylitis. Psoriasis was quantified by the body surface area (BSA) . The Health Assessment Questionnaire-Disability Index (HAQ-DI)  was used to assess function. Patient Global Assessment (PtGA) and pain on Visual Analogic Scale (VAS) were performed by all patients. PhGA of disease activity on a VAS  and C-reactive protein (CRP) were also collected.
MDA, VLDA, DAPSA, PASS, and PsAID
MDA was defined according to Coates et al. . Patients were considered in MDA when they satisfied 5/7 of the following criteria: tender joint count ≤ 1; swollen joint count ≤ 1; BSA ≤ 3; pain on VAS ≤ 15 mm; PtGA ≤ 20 mm; HAQ-DI ≤ 0.5; LEI ≤ 1. VLDA was satisfied when all seven criteria were met .
DAPSA was calculated by adding the number of tender and swollen joints, pain on VAS, PtGA, and CRP (mg/dl) . The PASS is a single question tool to evaluate the level of symptoms at which patients consider themselves well . The PsAID was also assessed .
The study protocol was in compliance with the Declaration of Helsinki; written consent was obtained from each participant. The study was approved by the Institutional Review Board of the University of Molise (protocol no. 0001–09-2017).
Statistical analysis was performed using SPSS (version 27). All demographical and clinical characteristics were summarized by using descriptive statistics. Parametric variables were reported by mean ± standard deviation (SD), and non-parametric ones by median and inter-quartile range (IQR). Categorical data are shown as number and percentage. Spearman’s correlation was used to assess the relationship between MDA divided in the seven cutoffs and DAPSA, PhGA, PsAID. A Spearman’s coefficient rho ≤ 0.2 = very weak, < 0.4 = weak, < 0.6 = moderate, < 0.8 strong and ≤ 1 very strong correlation, respectively. A significance level was accepted at p ≤ 0.05.
Patient characteristics and overall disease activity
In the study period, 93 PsA satisfied the inclusion criteria and were enrolled. Table 1 shows the main clinical characteristics of the enrolled patients. In particular, in Table 1 are reported the different proportions of patients achieving the different MDA cutoffs; 44/93 (47.3%) patients were in MDA.
Analysis of Different Domains
LEI ≤ 1 was the most frequently achieved domain either in the 47 patients not achieving MDA, or in those 44 patients in MDA. On the other hand, pain on VAS ≤ 15 mm was the most frequently missed domain in patients achieving or not MDA. Beyond LEI, the other domains frequently achieved in patients not in MDA were BSA ≤ 3 (70%) and swollen joints count ≤ 1 (68%). On the contrary, the domains with a lower percentage of achievement in patients not in MDA were: HAQ-DI ≤ 0.5 (38.8%), tender joint count ≤ 1 (23%), PtGA ≤ 20 (4.2%), and pain on VAS ≤ 15 mm (2%). All data are shown in Fig. 1. It also shows the “climb” of MDA, divided into the seven cutoffs. There was a growing trend, from MDA 1/7 to MDA 7/7, in the percentage of patients in PASS yes, in PsAID ≤ 4 and in DAPSA ≤ 4 and ≤ 14. In particular, in those MDA 4/7, more than 80% were in PASS yes, 75% in PsAID ≤ 4 and more than 90% in DAPSA ≤ 14.
An inverse correlation (Fig. 2) was found between MDA categories with DAPSA, (rho = − 0.91, p < 0.001), PhGA (rho = − 0.76, p < 0.001) and PsAID (rho = − 0.78, p < 0.001).
To our knowledge, this was the first study to detail the achievement of each single domain included in the MDA and divided by the seven categories. In particular, it seems that some domains are frequently achieved in patients not in MDA, as well as in those in MDA. In fact, in those 47 patients not achieving MDA 5/7, LEI ≤ 1, BSA ≤ 3 and swollen joints count ≤ 1 were satisfied in more than 60%. On the other hand, in the same group of 47 patients, there was a drop of the other domains which were ranging from HAQ-DI ≤ 0.5 in 38% until pain on VAS ≤ 15 mm in 2%. Overall, this study showed that the “objective” or “physician-driven” domains were more frequently reached in all PsA patients enrolled, MDA or not; on the other hand, the most frequently missed domains are those “patient-driven”. Moreover, if we look at those 13 patients in MDA 4/7, 81.8% were in PASS yes, 75% in PsAID ≤ 4 and 92.3% in DAPSA ≤ 14. As a further element to consider, the correlation found between MDA with DAPSA, PhGA, and PsAID might support the view of MDA as an instrument capable of complying with disease activity, physician, and patient’s perspective throughout the seven cutoffs.
However, the achievement of some treatment targets is not always agreed with the patient’s perception of the disease  and this is still an unmet need. In fact, it is possible to observe some residual disease activity in PsA patients and this, possibly, might imply some therapeutic decisions . Furthermore, our study showed that residual activity is detectable in PsA patients even in a condition of MDA showing the importance to know what that remaining activity consists of.
Our study has strengths as well as limitations: the study was performed in a group of patients in a stable treatment and with a cross-sectional design. At the same time, we did not perform any analysis on potential treatment implications in those patients (such as change therapy) due to the study design. However, our study tried to look at the differences in the MDA domains and, as far as we know, this is a novelty in this intriguing topic. Moreover, our patients seem to have a good control of the disease, with most patients having less than three swollen/tender joints and very mild skin involvement. This might explain why skin criteria and enthesis criteria were two of the most frequently fulfilled domains in every category of criteria fulfilled. Other studies partially agree with our results, in particular, Marin J et al. showed that skin was one of the major domains that stopped patients from achieving MDA. In our clinic, patients are followed up regularly and treated to target, and this could explain the results obtained. However, as a possible further explanation is that at least 30% of patients of our group were under IL-12/23, Il-17 inhibitors .
In conclusion, this study detailed which domains are more frequently achieved on MDA divided into the seven cutoffs, underlying that “physician-driven” domains are more frequently achieved in all patients enrolled. Moreover, a strong correlation was found with other outcome measures throughout the seven domains.
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We want to thank the participants in the study.
No funding or sponsorship was received for this study or publication of this article. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
All authors have made substantial contributions to all of these sections: conception and design of the study, acquisition of data, analysis and interpretation of data, drafting the article, revising it critically for important intellectual content and final approval of the version to be submitted.
Ennio Lubrano, Silvia Scriffignano, and Fabio Massimo Perrotta have nothing to disclose.
Compliance with Ethics Guidelines
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. The study was approved by the Institutional Review Board of the University of Molise.
The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.
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Cite this article
Lubrano, E., Scriffignano, S. & Perrotta, F.M. The “Climb” Towards Minimal Disease Activity in Psoriatic Arthritis. Rheumatol Ther 8, 1443–1450 (2021). https://doi.org/10.1007/s40744-021-00343-7
- Psoriatic arthritis
- Minimal disease activity
- Outcome measures