FormalPara Key Summary Points

Why carry out this study?

The Patient Acceptable Symptoms State (PASS) is a dichotomous tool that assesses if a patient with psoriatic arthritis (PsA) accepts her/his disease status by asking them a simple question: “Think about all the ways your PsA has affected you during the last 48 h. If you were to remain in the next few months as you were during the last 48 h, would this be acceptable to you?” A negative answer (“no”) denotes a disease status that is not acceptable to the patient.

The Disease Activity for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Impact of the Disease-12 (PsAID-12) and Health Assessment Questionnaire—Disability Index (HAQ-DI) “acceptance thresholds” have been published, but it is not known if the acceptance thresholds differ between the sexes.

What was learned from the study?

The number of male patients that assessed their disease as being acceptable was higher than the number of females that did so, 70% vs 49.3%. This data support previous studies in which, generally, the male sex more frequently achieved the outcome measures, such as low disease activity, when compared to the female sex.

The DAPSA, PsAID and HAQ-DI thresholds to discriminate a patient with a PASS “yes” from one with a PASS “no” were higher in the female than the male sex. The clinical meaning of these results could be that female patients generally have a greater global disease acceptance inclination compared with male patients.

These results further support the concept that sex differences are present in patients with PsA and that a global PsA evaluation which includes instruments that investigate the patient’s acceptance of their disease status (PASS) should be considered.

Introduction

Psoriatic arthritis (PsA) is a chronic inflammatory disease recognized for its clinical heterogeneity [1]. In fact, to better describe the various phenotypic features, the terms “psoriatic disease” [2] and then “psoriatic syndrome” [3] were proposed. Indeed, PsA is a multidomain disease in which not only the joint but also the skin, bowel and eye can be involved [1]. Moreover, joint involvement was historically divided into five PsA patterns (monoarticular, oligoarticular, polyarticular, axial and interphalangeal distal involvement) [4]. More recently, by using a machine-learning analysis, eight PsA phenotype clusters were described [5]. These clinical findings may lead us to consider patient profiling to be an important aspect in PsA, with the aim being to provide a patient-tailored approach. Another intriguing point that adds clinical heterogeneity to the disease is the awareness of emerging sex differences in PsA burden and treatment response [6, 7]. The disease burden and disease activity seem to be higher in the female sex compared to the male sex [8]. In particular, patient-reported outcomes and tender joint counts were generally higher in the female sex [7]. The differences in PsA between the male and female sexes could be due to various factors, ranging from a different pain processing mechanism [9] to lower treatment efficacy in female patients when compared with male patients, except for Janus kinase inhibitors (JAKi) [7].

Therefore, considering PsA heterogeneity and focusing on the sex differences [7], it would be interesting to explore the thresholds of Disease Activity for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Impact of the Disease-12 (PsAID-12) and the Health Assessment Questionnaire—Disability Index (HAQ-DI) that could discriminate a female or male patient who accepts their disease status from a female or male patient who does not. In fact, aside from the activity, impact and function of the disease, it is paramount to know the patient perspective about the acceptance of the disease. To do so, we adopted a very feasible and validated instrument, namely the Patient Acceptable Symptoms State (PASS), for patients with PsA [10].

PASS is a dichotomous tool that assesses if the patient accepts her/his disease status by asking a simple question: “Think about all the ways your PsA has affected you during the last 48 h. If you were to remain in the next few months as you were during the last 48 h, would this be acceptable to you?” A negative answer (“no”) denotes a disease status that is not acceptable for the patient. Even though DAPSA, PsAID-12, and HAQ-DI “acceptance thresholds” have already been proposed [10, 11], as far as we know, it is still not known if the acceptance thresholds differ between the sexes. Therefore, the aim of the study was to explore any acceptance threshold differences between the male and female sexes in terms of disease activity (DAPSA), impact (PsAID-12) and function (HAQ-DI).

Methods

Patient Selection

This study is a cross-sectional analysis of two longitudinal PsA cohorts from the Rheumatology Unit of the University of Molise (Campobasso) and from the Rheumatology Unit of the University of Tor Vergata (Rome). Patients with a PsA diagnosis (confirmed by a rheumatologist and satisfying the Classification Criteria for Psoriatic Arthritis) who consecutively attended these two outpatient tertiary clinics from January 1, 2022 to December 30, 2022 were considered for the study.

Data Collection

For each patient, a detailed medical history was collected and a clinical evaluation was performed. Sex, age, weight, height, body mass index (BMI), smoking habit and PsA disease duration were collected. Moreover, clinical characteristics such as the presence of psoriasis and the body surface area (BSA) were assessed. During the clinical assessment, the number of tender (out of 68) and swollen (out of 66) joints (TJC and SJC, respectively) was recorded. To measure clinical enthesitis, the Leeds Enthesitis Index was calculated, and dactylitis was assessed as present, past or never. During the visit, each patient filled in the Patient Global Assessment (PtGA) based on the Visual Analogue Scale (VAS) (0–10), the pain VAS (0–10), the PsAID-12 and the HAQ-DI, and the Physician Global Assessment was performed by the physician [12]. Disease activity was expressed via DAPSA. Laboratory parameters such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also collected. Comorbidities and current rheumatological treatment were recorded.

For each patient, the PASS was recorded upon asking, “Think about all the ways your PsA has affected you during the last 48 h. If you were to remain in the next few months as you were during the last 48 h, would this be acceptable to you?” A positive answer (“yes”) denoted that the disease status was acceptable to the patient, while a negative answer denoted that the disease status was not acceptable. The study protocol was carried out 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. 0001-017-2021).

Statistical Analysis

Statistical analysis was performed using IBM SPSS software (version 27). All demographic and clinical characteristics were summarized using descriptive statistics and split according to sex (male or female). Normally distributed variables were reported as mean ± standard deviation (SD), and non-normally distributed variables were reported as median and interquartile range (IQR). Categorical data are shown as the number and the percentage of valid data. Patients reporting missing data were not included in the analysis.

To identify the DAPSA, PsAID and HAQ-DI thresholds that differentiated patients who reported a PASS “yes” (acceptance of the disease) from those who reported a PASS “no” (non-acceptance of the disease), we used the receiver operating characteristic (ROC) curve, assessing the area under the curve (AUC) and the specificity and sensitivity values for both the female and male sexes. Moreover, Cohen’s kappa test was used to determine the agreement of a PASS “yes” with DAPSA ≤ 14 (low disease activity), PsAID ≤ 4 (low impact of the disease) and HAQ-DI ≤ 0.5 (good function): this analysis was carried out separately for male and female patients to explore any differences in the agreement. The results for Cohen’s kappa were interpreted as follows: 0, no agreement; > 0 and ≤ 0.20, slight agreement; > 0.20 and ≤ 0.40, fair agreement; > 0.40 and ≤ 0.60, moderate agreement; > 0.60 and ≤ 0.80, good agreement; > 0.80 and ≤ 1.00, almost perfect agreement. Moreover, the relationship between PASS and fibromyalgia was assessed in both male and female patients by using Fisher’s exact test.

Results

Three hundred ten patients were enrolled in the study, of whom 48.7% (151) were female and 51.3% (159) were male. DAPSA, HAQ-DI and PsAID had significantly higher values in female patients (Table 1).

Table 1 Demographic, physical and clinical characteristics and the comorbidities of all studied patients split by sex
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Among female patients, 68/138 (49.3%) reported a PASS “yes,” while 103/147 (70%) male patients assessed their symptom state as being acceptable.

When the ROC curves were generated, we found that a DAPSA score of 11.7 best differentiated male patients with PsA who reported a PASS “yes” from those who reported a PASS “no,” with an AUC of 0.87 (95% CI 0.80–0.94, specificity = 81%, sensitivity = 81%) (Fig. 1). Instead, a DAPSA score of 13.3 best differentiated female patients who reported a PASS “yes” from those who reported a PASS “no,” with an AUC of 0.95 (95% CI 0.91–0.99, specificity = 94%, sensitivity = 88%) (Fig. 1).

Fig. 1
figure 1

ROC curves showing the thresholds for DAPSA, PsAID and HAQ. DAPSA Disease Activity for Psoriatic Arthritis, HAQ Health Assessment Questionnaire—Disability Index, PsAID Psoriatic Arthritis Impact of the Disease, ROC receiver operating characteristic

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Similarly, the PsAID threshold that distinguished an acceptable patient condition from a non-acceptable one was higher in female than in male patients: a value of 3.85 best differentiated female patients who reported a PASS “yes” from those who reported a PASS “no” (AUC of 0.85; 95% CI 0.78–0.92, specificity = 66%, sensitivity = 95%), whereas a PsAID value of 1.85 (AUC of 0.81; 95% CI 0.72–0.87, specificity = 76%, sensitivity = 68%) (Fig. 1) differentiated a PASS “yes” and a PASS “no” for male patients.

Finally, a HAQ-DI score of 0.625 best differentiated male patients who reported a PASS “yes” from those who reported a PASS “no” (AUC of 0.73; 95% CI 0.64–0.82, specificity = 68%, sensitivity of 74%), and a HAQ-DI score of 0.750 best differentiated female patients who reported a PASS “yes” from those who reported a PASS “no” (AUC = 0.81; 95% CI 0.73–0.88, specificity = 81%, sensitivity = 69%) (Fig. 1).

The agreement between a PASS “yes” and low disease activity according to DAPSA (≤ 14) was different in the male and female sexes: there was moderate agreement in male patients (kappa = 0.56) and good agreement in female patients (kappa = 0.80). The agreement (kappa value) between a PASS “yes” and a low impact of the disease according to PsAID (≤ 4) and between a PASS “yes” and HAQ-DI ≤ 0.500 was higher in the female sex, with a moderate agreement value (Table 2).

Table 2 Cohen’s K agreement (CI 95%) between a PASS “yes” and disease activity by DAPSA, impact by PsAID and function by HAQ-DI
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Interestingly, the presence of fibromyalgia (in this group of patients) was not a discriminating factor that differentiated patients with a PASS “no” from those with a PASS “yes” for either male or female patients (Table 3).

Table 3 Comparison between patients with and without fibromyalgia by PASS result (“yes” or “no”) and by sex (using Fisher’s exact test)
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Discussion

In the present study, we analyzed the differences between male and female patients with PsA in terms of their acceptance of the disease. The number of male patients that assessed their disease as acceptable was higher than the number of females who did: 70% vs 49.3%. These data support previous studies in which, generally, the male sex achieved outcome measures such as low disease activity more frequently when compared to the female sex [6,7,8]. In fact, female patients showed higher values of DAPSA, but the DAPSA threshold to discriminate a patient with a PASS “yes” from one with a PASS “no” was higher in the female sex when compared to the male sex; the same results were found for PsAID and for HAQ-DI. Therefore, the clinical meaning of these results could be that a female patient generally has a greater global disease acceptance inclination, even though their disease activity, patient-reported outcome and quality of life are worse. As in previous studies on other chronic pain syndromes, it seems that, when confronted by pain, women will “accept and move,” while men will “feel blue” [12]. These results may further imply that a global PsA evaluation that includes instruments that investigate the patient’s acceptance of their disease status should be considered [13]. As recently shown [7], the sex-related differences in the clinical outcomes of patients with PsA seem to be related to a different response to advanced therapies; it would be interesting to differentiate the PASS statuses of males and females in a larger group of patients based on the pharmacological treatment class.

Moreover, a PASS “yes” showed good agreement with low disease activity according to DAPSA in female patients, indicating that PASS can be deemed a good instrument to detect low disease activity in the female sex. In other words, considering that many metric instruments to detect the disease activity in patients with PsA have been developed and validated [14], PASS could be a simple tool to confirm good disease control from the patient perspective.

Given the nature of this study, it has some strengths and some limitations. As far as we know, this is the first study evaluating the PASS state in patients with PsA differentiated by sex; this could be useful in routine clinical practice. On the other hand, longitudinal data are needed to confirm these preliminary results, and it would be advisable to perform the same study in a different group of patients with PsA (i.e., with different geographic and demographic characteristics) to confirm these thresholds, since the acceptance thresholds may not be applicable to all PsA patient populations. Finally, a dependence on patient self-reports, which may be subject to subjective bias, and a potential overlap between PsA symptoms and other inadequately controlled conditions like fibromyalgia should be taken into account.

Conclusion

In conclusion, although female patients generally have a higher disease activity than male patients, they accept their disease status at higher values of DAPSA, PsAID and HAQ-DI. Finally, this study further supports the concept that sex differences are present in patients with PsA.