Sensitivity of the GEPARD Patient Questionnaire to Identify Psoriatic Arthritis in Patients with Psoriasis in Daily Practice: The GEPARD-Life Study

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1 Original Paper Received: February 8, 2016 Accepted after revision: May 18, 2016 Published online: September 8, 2016 Sensitivity of the GEPARD Patient Questionnaire to Identify Psoriatic Arthritis in Patients with Psoriasis in Daily Practice: The GEPARD-Life Study Peter Härle a Katrin Letschert b Bianca Wittig b Ulrich Mrowietz c a Klinik für Rheumatologie, Klinische Immunologie und Physikalische Therapie, Katholisches Klinikum Mainz, Mainz, b Medical Area Immunology, AbbVie Deutschland GmbH & Co. KG, Wiesbaden, and c Psoriasis Center at the Department of Dermatology, University Medical Center Schleswig-Holstein, Kiel, Germany Key Words Dermatologist Rheumatologist Psoriatic arthritis GEPARD CASPAR Referral Abstract Early detection of psoriatic arthritis (PsA) remains a challenge in clinical practice. Tools such as the German Psoriasis Arthritis Diagnostic (GEPARD) questionnaire have been developed for this purpose. The aim of this study was to determine the performance of the GEPARD questionnaire in the detection of PsA in psoriasis patients following rheumatology evaluation in daily clinical practice in Germany. This was a multicenter study involving 59 dermatology units (university/general hospital/office based), and the GEPARD questionnaire was distributed to psoriasis patients. Patients who had a sum score of 4 positive answers were referred to a rheumatologist for evaluation of PsA. We recruited 1,512 patients, of whom approximately 50% were referred. One third of the referred patients were classified as having PsA after rheumatological assessment. Rates of PsA in university/general hospital settings were higher than those observed in a doctor s office-based setting (43.7 vs. 25.8%). The GEPARD questionnaire demonstrated easy screening of psoriasis patients for PsA S. Karger AG, Basel Introduction Psoriasis is a chronic immune-mediated disease, which occurs in about 2% of the general population in Europe [1]. Following epidemiological studies, the average prevalence of psoriatic arthritis (PsA) among psoriasis patients is 10 30% [2 5]. In approximately 60% of these, disease manifestation of the skin precedes joint inflammation. Taking all cases together, more than 50% of patients with psoriasis experience joint and back pain during their life [6]. Early detection of PsA is very important due to the destructive course of the disease. Around 47% of patients suffering from PsA show irreversible structural joint damage within the first 2 years of the initial manifestations of arthritis [7, 8]. Therefore, it is important to screen patients with psoriasis for the prevalence of inflammatory joint symptoms and start treatment as early as possible in the disease course. Several questionnaires for the detection of PsA have been published but few are used in routine care. In 2010, Härle et al. [9] published the German Psoriasis Arthritis Diagnostic (GEPARD) questionnaire. The questionnaire is filled in by psoriasis patients and can be integrated into karger@karger.com S. Karger AG, Basel /16/ $39.50/0 Prof. Dr. Peter Härle Klinik für Rheumatologie, Klinische Immunologie und Physikalische Therapie Katholisches Klinikum Mainz, An der Goldgrube 11 DE Mainz (Germany) kkmainz.de

2 Fig. 1. Case report form of the GEPARD-Life study. 598 Härle/Letschert/Wittig/Mrowietz

3 Fig. 2. Flowchart of Materials and Methods. psoriasis disease management [10]. The GEPARD questionnaire consists of 13 dichotomous questions related to the peripheral and axial manifestations of PsA. A sum score of 4 positive answers has shown a sensitivity of 89% (95% confidence interval, CI, %) and a specificity of 69.1% (95% CI, %) for the presence of PsA. Patients with a positive result for PsA as determined by the GEPARD questionnaire were examined by rheumatology experts using clinical examination, highresolution ultrasound with power Doppler, magnetic resonance imaging (MRI) of the peripheral and sacroiliac joints, and a 3-phase skeletal scintigraphy. In order to make a final diagnosis of PsA, the Classification Criteria for Psoriatic Arthritis (CASPAR) were used [11]. However, a university hospital as used in the study of 2010 might not reflect the real-life situation and availability of diagnostic methods as in a doctor s office. The time allocated for an individual visit in real-world practice is much shorter, and the diagnostic resources are restricted compared to the academic setting in the initial study from 2010 [9]. The goal of the current examination/study was to show that the German-language GEPARD questionnaire is suitable to detect PsA patients among psoriasis patients at doctor s offices in daily clinical routine, under real-life conditions and to prove its suitability for daily use in Germany. Material and Methods For further details, see the supplementary materials (for all online suppl. material, see (fig. 1, 2 ). Results Study Population and Evaluation Form Starting in February 2010, a total of 1,512 patients with psoriasis were recruited from 59 dermatology outpatient centers (university/general hospital and doctor s offices) GEPARD Questionnaire in Real Life 599

4 Fig. 3. Flow of patients in the GEPARD- Life study. throughout Germany. Patients with a GEPARD questionnaire with 4 yes answers were further evaluated for PsA. The flow of patients through the study is shown in figure 3. Patient Characteristics Table 1 shows the demographics and disease characteristics of the study population. There were no statistical differences between the total study population, the 600 Härle/Letschert/Wittig/Mrowietz

5 Table 1. Characteristics of patients who answered yes to 4 questions in the GEPARD questionnaire a All patients (n = 1,512) All patients University hospital General hospital Doctor s office Unknown Patients Number 1, Mean age ± SD, years 49.4 ± ± ± ± ± 16.8 Female, % Male, % Mean duration of psoriasis ± SD, years 17.1 ± ± ± ± ± 11.0 Mean PASI ± SD 8.89 ± ± ± ± ± 8.00 Location of psoriasis manifestation, % Scalp Anal cleft Nails Scalp + anal cleft Scalp + nails Anal cleft + nails Scalp + anal cleft + nails Not assessed Duration of symptoms, % >1 week >1 month >3 months >6 months >1 year >3 years >5 years Unknown Recruiting institution, % University/hospital 39.8 Doctor s office 55.4 Unknown 4.8 population available for analysis and patients excluded (details given in fig. 3 ) from the analysis because of formal errors. Prevalence, Clinical Appearance, and Location of Treatments of Patients with PsA This study is a noninterventional documentation: Post hoc analyses were performed according to study center qualification. The frequency of patients in the dermatology setting with 4 yes answers in the GEPARD questionnaire was 52.9% (800/1,512 patients). After elimination of incomplete data sets, 1,002 of the 1,512 patients were eligible for further final analysis ( fig. 3 ; tables 1 and 2 ). Patients with a positive GEPARD questionnaire were referred to follow-up with a rheumatologist. Finally, 517 of 1,002 patients (51.6%) had a full rheumatology workup and were eligible for analysis. The prevalence of PsA according to the CASPAR classification criteria was 33.8% (175 of 517 GEPARD-positive patients evaluated); 342 of 517 had negative CASPAR classification criteria. In the university/general hospital settings, 43.7% of patients (104/238) were GEPARD positive and had a score of 3 points on CASPAR, meaning that these patients were considered to have PsA. Conversely, only 25.8% of patients (68/264) met the same criteria in the doctor s office-based setting. This was the case in 134 patients in university/general hospital setting and 196 patients treated in doctors offices. In 15 patients, the study center was not specified. Interestingly, the rheumatologist s assessment was different at the university/general hospital compared to the doctor s office ( table 3 ): according to their clinical judgment, 29% of patients with pso- GEPARD Questionnaire in Real Life 601

6 Table 1 (continued) b Patients with complete data sets (n = 1,002) Complete data sets University hospital General hospital Doctor s office Unknown Patients Number 1, Mean age ± SD, years 49.2 ± ± ± ± ± 16.9 Female, % Male, % Mean duration of psoriasis ± SD, years 16.9 ± ± ± ± ± 10.8 Mean PASI ± SD 9.29 ± ± ± ± ± 10.0 Location of psoriasis manifestation, % Scalp Anal cleft Nails Scalp + anal cleft Scalp + nails Anal cleft + nails Scalp + anal cleft + nails No comment Duration of symptoms, % >1 week >1 month >3 months >6 months >1 year >3 years >5 years Unknown Recruiting institution, % University/general hospital 39.8 Doctor s office 54.2 Unknown 6.0 Table 2. Patients classified for PsA using CASPAR 3 and GEPARD 4 Patients (n = 517) University/ general hospital (n = 238) Doctor s office (n = 264) Unknown (hospital or doctor s office) (n = 15) Active 104 (43.7) 68 (25.8) 3 (20.0) Not active 134 (56.3) 196 (74.2) 12 (80.0) Results are numbers, with percentages in parentheses. riasis and a positive GEPARD questionnaire (69/238) in the university/general hospital setting were judged as not having active PsA; 47 of them were CASPAR positive. In the medical office, 50 patients were judged as not having active PsA (29 were CASPAR positive, 21 CASPAR negative). Comparable results were obtained in the offices. Here, 19% of patients (50/264) were judged as not having active PsA clinically despite positive CASPAR criteria, and 58% of these patients (29/50) were classified as meeting the CASPAR criteria. Discussion Despite the development and validation of several questionnaires for early identification of psoriasis patients with PsA, there is still need of a tool that can be used in everyday dermatological practice. In 2010, we published a patient screening questionnaire (GEPARD) for the evaluation of PsA in a popula- 602 Härle/Letschert/Wittig/Mrowietz

7 Table 3. Patients (numbers with percentages) with or without PsA and CASPAR score 3 or 3 analyzed by practice setting Patients Total CASPAR 3 CASPAR <3 University/general hospital (43.7) 134 (56.3) Active PsA 59 (24.8) 52 (88.1) 7 (11.9) No active PsA 69 (29.0) 47 (68.1) 22 (31.9) Not available 110 (46.2) 5 (4.55) 105 (95.5) Office based (25.8) 196 (74.2) Active PsA 45 (17.0) 37 (82.2) 8 (17.8) No active PsA 50 (19.0) 29 (58.0) 21 (42.0) Not available 169 (64.0) 2 (1.18) 167 (98.8) tion of patients with psoriasis. These patients completed the questionnaire and were evaluated and classified according to the CASPAR criteria for PsA. Validation of the GEPARD questionnaire was performed in an academic hospital, including a comprehensive clinical and diagnostic workup. Patients with psoriasis were carefully examined by a clinician and by imaging techniques such as ultrasound, MRI, and scintigraphy for inflammatory articular manifestations (arthritis, enthesitis, and spondylitis). This resulted in a high sensitivity and specificity of the patient-focused GEPARD questionnaire with a sum score of 4 yes answers on the 13-item questionnaire. In daily routine practice, the screening of patients with psoriasis is often hampered, mainly due to time constraints, the lack of reimbursement of ultrasound of the joints, and limited access to diagnostic methods (MRI, scintigraphy) to detect early inflammatory disease. In this study, our aim was to investigate real-world ( GEPARD-Life ) screening of patients with psoriasis in office-based dermatology with the GEPARD patient questionnaire and, in the case of patients with a positive GEPARD sum score of 4, the evaluation of inflammatory manifestations (arthritis, enthesitis, spondylitis) through rheumatologists. Recently, Henes et al. [12] published a study where they were using the GEPARD questionnaire in psoriasis patients. GEPARD-positive patients were further examined in one reference center of rheumatology to diagnose and confirm PsA. 50.5% of the psoriasis patients were GEPARD positive (at least 4 positive answers). Patients with positive answers to question 7 ( Have you ever been diagnosed with arthritis? ) (82/412 patients) and 4 positive GEPARD answers were investigated with respect to their joint disease. Overall, in 30.2% of patients, PsA was diagnosed or confirmed by the rheumatologist, not least based on imaging methods. In our study, collaboration by dermatologists and rheumatologists was performed as in daily business. The cutoff value of 4 questions was used to simplify the procedures for daily practice as much as possible. Here, in dermatology settings, 1,512 consecutive psoriasis patients were screened using the GEPARD questionnaire. 1,002 patients had complete dermatology data; thereof 517 patients with positive GEPARD scores could be included into the final analysis. According to the CASPAR classification criteria applied to patients with a positive GEPARD, 175/517 patients were classified as having PsA. This reflects 17.5% of the psoriasis patients analyzed (175/1,002). In the GEPARD validation study [9], 43 of 54 (79.6%) patients had a positive GEPARD score and a positive CASPAR classification. In the study by Härle et al. [9], ultrasound, scintigraphy and MRI were applied to detect signs of arthritis, enthesitis or spondylitis in patients with psoriasis. Taken together, the data clearly demonstrate the value of GEPARD to preselect risk patients if the final diagnosis is confirmed on the basis of rheumatologists experience and imaging methods. Interestingly, in our study the rate of patients with a positive GEPARD score who were also tested positive for CASPAR criteria in a university/general hospital setting (59.4%) was higher as compared to patients diagnosed at a doctor s office (38.8%). Since imaging was not mandatory in the CRF, detailed data on the use of diagnostic methods were not provided. This might explain a higher rate of PsA diagnosis in hospitals with a higher use of ultrasound or MRI. Taking together the results of office and university/ general hospital in this study, 175 of 517 patients were GEPARD positive and had positive CASPAR criteria (33.8%). The final diagnosis of rheumatologists, however, was lower with 21.1% (104/517). In relation to all exam- GEPARD Questionnaire in Real Life 603

8 ined psoriasis patients in this study (n = 1,002), this reflects a prevalence of 10.4%. Reich et al. [13] examined 1,511 psoriasis patients in a German center and identified 20.6% as PsA patients. In the literature, the worldwide prevalence of PsA in patients with psoriasis varies between 10 and 30% [2 5]. The rate of 17.5% positive CASPAR-classified PsA in psoriasis patients with 10.4% with active PsA in this study fits this range. Clinical examination alone is known to underestimate joint inflammation and damage, and the use of ultrasound confers additional diagnostic value [14 17]. In 2011, De Simone et al. [14] showed that the use of additional testing for structural abnormalities by simple X-ray and correlation with ultrasound is a valuable tool for detecting bone, synovial, and tendon abnormalities which is time-consuming and costly for screening and therefore not used in daily practice. In GEPARD-Life, after additional diagnosis for inflammatory manifestations in the university/general hospital setting, 68.1% of patients with nonactive PsA were identified as meeting CASPAR criteria, in contrast to only 58.0% of patients in the doctor s office-based setting. One may speculate that ultrasound reimbursed by German health insurances is used less frequently in doctor s offices than in a university/general hospital setting. In the last few years, several studies were performed to either test the different existing questionnaires to quantify the prevalence of PsA among psoriasis patients. The CONTEST study [18, 19] compared PASE [20], ToPas [21] and PEST [22] with the EARP questionnaire [23]. The most important result is that all of the used questionnaires have a very low specificity and acceptable sensitivity values [21]. This is in line with the results of our questionnaire where more than 50% of all patients had a positive GEPARD questionnaire. Another study showed that the detection of PsA by these questionnaires is possible in 43 45% of the examined psoriasis patients [24]. The same group [25] published data from the multinational PREPARE study, which revealed that the use of laboratory data for diagnosis, i.e. erythrocyte sedimentation rate, had only marginal influence on diagnosis, while clinical examination alone seemed to be sufficient: From 949 psoriasis patients, 285 were diagnosed with PsA during clinical examination, with only 1.2% of patients detected on the basis of additional laboratory data. These findings underline the impact of our results: complicated and time-consuming efforts are not necessary for the preselection of PsA patients. However, it is crucial to evaluate these patients further using ultrasound or MRI in order to determine disease activity, extent and sites of inflammation that are not easily accessible, such as the spine or entheses. In summary, the GEPARD-Life study showed that 33.8% of the patients with psoriasis who answered yes to 4 questions on the GEPARD patient questionnaire could be classified as having PsA according to the CASPAR criteria. Recent publications support the assumption that even clinically mild disease manifestations may still lead to progressive joint destruction [26]. The GEPARD-Life study is the first which demonstrates the value of the GEPARD questionnaire in everyday dermatological and rheumatological practice. A positive GEPARD score indicates further imaging and diagnostic tools for PsA evaluation. Acknowledgment The authors would like to thank Imma Fischer (Tübingen, Germany) for statistical analyses of the data. AbbVie funded the study and the analysis, and approved the manuscript for submission. Statement of Ethics The local ethical committees in Germany approved the study. Disclosure Statement P.H. has been paid consulting or speakers fees by AbbVie, Pfizer, Roche, Merck Sharp & Dohme, Chugai, UCB, and Janssen Biotech Inc. K.L. and B.W. are employees of AbbVie GmbH & Co. KG, Germany. U.M. has been an advisor and/or received speakers honoraria and/or received grants and/or participated in clinical trials of the following companies: AbbVie, Almirall-Hermal, Amgen, BASF, Biogen Idec, Celgene, Centocor, Eli Lilly, Forward Pharma, Galderma, Janssen, Leo Pharma, Medac, MSD, Miltenyi Biotech, Novartis, Pfizer, Teva, VBL, and Xenoport. References 1 Nevitt GJ, Hutchinson PE: Psoriasis in the community: prevalence, severity and patients beliefs and attitudes towards the disease. Br J Dermatol 1996; 135: Helliwell PS, Taylor WJ: Classification and diagnostic criteria for psoriatic arthritis. Ann Rheum Dis 2005; 64(suppl 2):ii3 ii8. 3 Sadek HA, Abdel-Nasser AM, El-Amawy TA, Hassan SZ: Rheumatic manifestations of psoriasis. Clin Rheumatol 2007; 26: Härle/Letschert/Wittig/Mrowietz

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