Jelena Vojinovic1, Angela Tincani2, Alberto Sulli3, Stefano Soldano3, Laura Andreoli4, Francesca Dall'Ara4, Ruxandra Ionescu5, Katarina Simic Pasalic6, Inete Balcune7, Ivan Ferraz-Amaro8, Małgorzata Tlustochowicz9, Irena Butrimiene10, Egle Punceviciene11, Natalia Toroptsova12, Simeon Grazio13, Jadranka Morovic-Vergles14, Pavol Masaryk15, Kati Otsa16, Miguel Bernardes17, Vladimira Boyadzhieva18, Fausto Salaffi19, Maurizio Cutolo20. 1. Clinical Centre, Medical Faculty, University of Nis, Bul Zorana Djindjica 81 Nis, Serbia. Electronic address: vojinovic.jelena@gmail.com. 2. Rheumatology and Clinical Immunology Unit, ASST Spedali Civili of Brescia and Dpt. of Clinical and Experimental Science, University of Brescia, Italy. Electronic address: tincani@med.unibs.it. 3. Research Laboratory and Academic Division of Rheumatology, Department of Internal Medicine, University of Genova, IRCCS San Martino-Clinical, Viale Benedetto VX/6, 16132 Genova, Italy. 4. Rheumatology and Clinical Immunology Unit, ASST Spedali Civili of Brescia and Dpt. of Clinical and Experimental Science, University of Brescia, Italy. 5. Spitalul Sf. Maria, Clinica Medicina Interna Reumatologie, Bulevard Ion Mihalache 37-39, sector 1, Bucarest, Romania. Electronic address: ruxandraionescu1@gmail.com. 6. Institute of Rheumatology, Resavska 69, Belgrade, Serbia. Electronic address: simicpasalickatarina@gmail.com. 7. Division of Rheumatology, Paula Stradina Clinical Hospital, Pilsonu 13, Nr. 26, corpuss 10, LV-1001 Riga, Latvia. Electronic address: ine@no.lv. 8. Hospital Universitario de Canarias, Servicio de Reumatología, Planta 5, Ofra s/n La Cuesta, 38320 Santa Cruz de Tenerife, Spain. Electronic address: iferrazamaro@hotmail.com. 9. Rheumatology Institute, Military Medical Institute, Ul. Szaserów 128, 04-141 Warszawa, Poland. Electronic address: m.tlustochowicz@gmail.com. 10. Clinic of Rheumatology, Orthopedics Traumatology and Plastic Surgery, Vilnius University, Santariskiu Str. 2, LT-08406 Vilnius, Lithuania. 11. Clinic of Rheumatology, Orthopedics Traumatology and Plastic Surgery, Vilnius University, Santariskiu Str. 2, LT-08406 Vilnius, Lithuania. Electronic address: epunceviciene@gmail.com. 12. Scientific Research Institute of Rheumatology "V.A.Nasonova", Kashirskoye shosse 34A, 115522 Moscow, Russia. Electronic address: epid@irramn.ru. 13. Department of Rheumatology, Sisters of Mercy Clinical Hospital Centre University, Physical and Rehabilitation Medicine Vinogradska 29, 10000 Zagreb, Croatia. Electronic address: simeon.grazio@zg.t-com.hr. 14. Department for Clinical Immunology and Rheumatology, Clinical Hospital Dubrava, School of Medicine, University of Zagreb, Croatia. Electronic address: jmorovic@kbd.hr. 15. National Institute of Rheumatic Diseases, Nábrezie I. Krasku 4, 921 01 Piestany, Slovakia. Electronic address: pavol.masaryk@nurch.sk. 16. Department of Rheumatology, Tallinn Central Hospital, Pärnu mnt 104, 11312 Tallinn, Estonia. Electronic address: katii.otse@itk.ee. 17. Rheumatology Department, São João Hospital Center, Faculty of Medicine, University of Porto, Rua Dr Plácido da Costa, 4200-450 Porto, Portugal. Electronic address: mbernardes09@gmail.com. 18. UMHAT "St. Iv. Rilski" Clinic of Rheumatology, Medical University Sofia, Urvich str, fl 1, 1612 Sofia, Bulgaria. Electronic address: vladimira.boyadzhieva@gmail.com. 19. Department of Rheumatology, Università Politecnica delle Marche, Ancona, Italy. Electronic address: fausto.salaffi@gmail.com. 20. Research Laboratory and Academic Division of Rheumatology, Department of Internal Medicine, University of Genova, IRCCS San Martino-Clinical, Viale Benedetto VX/6, 16132 Genova, Italy. Electronic address: mcutolo@unige.it.
Abstract
OBJECTIVE: To collect data on vitamin D (25(OH)D) serum levels in a large number of rheumatoid arthritis (RA) patients from different European countries, to investigate their relation with disease activity, disability, quality of life, and possibly to construct a new Patient Reported Outcome (PRO) questionnaire in order to self-estimate if they are at risk for vitamin D insufficiency/deficiency-related clinical implications (D-PRO). METHODS: This was a European League Against Rheumatism (EULAR) supported cross-sectional study (project No CLI064) which involved 625 RA patients (mean age 55±11years, mean disease duration 11±9years), 276 age and sex matched healthy subjects, and rheumatologists working in academic institutions or hospital centres, as well as PARE organizations (patient representatives) from 13 European countries. Serum samples for 25(OH)D level measurement were collected during winter time and analyzed in a central laboratory using chemiluminescence immunoassay (DiaSorin). Patient past medical history was recorded. RA patients were provided with three questionnaires: the Rheumatoid Arthritis Impact Diseases score (RAID), the Health Assessment Questionnaire (HAQ), and the new D-PRO questionnaire at the time of 25(OH)D serum sampling. D-PRO questionnaire consisted of three domains, Symptom Risk Score (SRS), Habitus Risk Score (HRS) and Global Risk Score (SRS+HRS=GRS), constructed with items possibly related to vitamin D deficiency. D-PRO was correlated with both clinical and PRO scores. DAS28-CRP was also evaluated. Statistical analysis was performed by non parametric tests. RESULTS: Mean serum concentration of 25(OH)D in RA patients (17.62±9.76ng/ml) was found significantly lower if compared to the levels obtained in matched controls (18.95±9.45ng/ml) (p=0.01), with statistically significant differences among several European countries. Negative correlations were found between 25(OH)D serum levels and DAS28-CRP (p<0.001), RAID (p=0.05) and HAQ (p=0.04) scores in the RA patients group. Negative correlations were also found in the cohort of enrolled RA patients between 25(OH)D serum concentrations and SRS (p=0.04), HRS (p=0.02) and GRS (p=0.02) domains of the D-PRO questionnaire. CONCLUSIONS: This first multicentre European survey add new evidences that vitamin D insufficiency/deficiency is frequent in RA patients with statistically significant differences among several countries. Vitamin D serum concentrations seem to correlate negatively and significantly with the D-PRO Global Risk Score, clinimetric indexes for quality of life, disease activity and disability in present cohort of RA European patients.
OBJECTIVE: To collect data on vitamin D (25(OH)D) serum levels in a large number of rheumatoid arthritis (RA) patients from different European countries, to investigate their relation with disease activity, disability, quality of life, and possibly to construct a new Patient Reported Outcome (PRO) questionnaire in order to self-estimate if they are at risk for vitamin Dinsufficiency/deficiency-related clinical implications (D-PRO). METHODS: This was a European League Against Rheumatism (EULAR) supported cross-sectional study (project No CLI064) which involved 625 RApatients (mean age 55±11years, mean disease duration 11±9years), 276 age and sex matched healthy subjects, and rheumatologists working in academic institutions or hospital centres, as well as PARE organizations (patient representatives) from 13 European countries. Serum samples for 25(OH)D level measurement were collected during winter time and analyzed in a central laboratory using chemiluminescence immunoassay (DiaSorin). Patient past medical history was recorded. RApatients were provided with three questionnaires: the Rheumatoid Arthritis Impact Diseases score (RAID), the Health Assessment Questionnaire (HAQ), and the new D-PRO questionnaire at the time of 25(OH)D serum sampling. D-PRO questionnaire consisted of three domains, Symptom Risk Score (SRS), Habitus Risk Score (HRS) and Global Risk Score (SRS+HRS=GRS), constructed with items possibly related to vitamin D deficiency. D-PRO was correlated with both clinical and PRO scores. DAS28-CRP was also evaluated. Statistical analysis was performed by non parametric tests. RESULTS: Mean serum concentration of 25(OH)D in RApatients (17.62±9.76ng/ml) was found significantly lower if compared to the levels obtained in matched controls (18.95±9.45ng/ml) (p=0.01), with statistically significant differences among several European countries. Negative correlations were found between 25(OH)D serum levels and DAS28-CRP (p<0.001), RAID (p=0.05) and HAQ (p=0.04) scores in the RApatients group. Negative correlations were also found in the cohort of enrolled RApatients between 25(OH)D serum concentrations and SRS (p=0.04), HRS (p=0.02) and GRS (p=0.02) domains of the D-PRO questionnaire. CONCLUSIONS: This first multicentre European survey add new evidences that vitamin Dinsufficiency/deficiency is frequent in RApatients with statistically significant differences among several countries. Vitamin D serum concentrations seem to correlate negatively and significantly with the D-PRO Global Risk Score, clinimetric indexes for quality of life, disease activity and disability in present cohort of RA European patients.