Phenotypic Variability and Disparities in Treatment and Outcomes of Childhood Arthritis Throughout the World: Results from the EPOCA Study

Background: The characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate prevalence of disease categories, treatment modalities and disease status across different geographic areas. Methods: International paediatric rheumatologists were asked to enrol a consecutive sample of children with juvenile idiopathic arthritis. Each patient underwent retrospective and cross-sectional assessments, including parent-reported outcomes. Level of disease activity and damage were correlated with wealth of the country, expressed as gross domestic product per capita. Findings: Between 2011 and 2016, 9,081 patients were enrolled at 130 centres in 49 countries, grouped in 8 geographic areas. A wide difference in the prevalence of disease categories across areas was seen, with systemic arthritis and oligoarthritis being relatively more common in Southeast Asia (33%) and Southern Europe (56·7%), respectively, and rheumatoid-factor negative polyarthritis and enthesitis related arthritis being relatively more frequent in North America (31·5%) and Southeast Asia (29·8%), respectively. Prevalence of uveitis was highest in Northern Europe and Southern Europe (19·2% and 19%, respectively) and lowest in Latin America (6·5%), Africa & Middle East (6·1%), and Southeast Asia (5·1%). Median age at disease onset was lower in Southern Europe (3·5 years) than in other regions (4·7-7·4 years). Biologic disease-modifying anti-rheumatic drugs (DMARDs) were prescribed more frequently in Western countries (30·5-46%) than in other geographic settings (21·1- 25·1%). Patients living in lower-income countries had greater disease activity and damage than patients cared for in wealthier countries. Damage was associated with referral delay. Interpretation: Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographic areas. The greater disease burden in lower-resource settings highlights the need for public health efforts aimed to improve equity in access to effective treatments and structure and process of care. Funding Statement: IRCCS Istituto Giannina Gaslini, Genoa, Italy. Declaration of Interests: Dr. Bovis reports personal fees from Biogen, Novartis, outside the submitted work. Dr. Foell reports grants from Novartis, Pfizer; personal fees from Novartis, Pfizer, Sobi, Chugai-Roche, during the conduct of the study. Dr. Shafaie reports grants from IRCCS Istituto Giannina Gaslini, during the conduct of the study. Dr. Lazar reports grants from IRCCS Istituto Giannina Gaslini, during the conduct of the study; non- financial support from Abbvie; personal fees from ROCHE, outside the submitted work. Dr. Lovell reports other funding from Astra-Zeneca Pharm, Wyeth Pharm, Amgen, Abbott, Pfizer, Hoffman-La Roche, Novartis, UBC, Takeda, Janssen, GSK, Boehringer Ingelheim, Celgene, Novartis, Roche, Bristol Myers Squibb, Abbvie, Pfizer, Roche, Forest Research, outside the submitted work. Dr. Martini reports grants from Abbvie, Boehringer, Novartis, R-Pharm, BMS, Hoffman-La Roche, Janssen, Novartis, Pfizer, Sobi, outside the submitted work; personal fees from Abbvie, Astrazeneca, Novartis, Pfizer, Roche, R-Pharm, Sanofi, UCB, outside the submitted work. Dr. Ravelli reports personal fees from AbbVie, BMS, Pfizer, Hoffman LaRoche, Novartis, Centocor, Francesco Angelini and Reckitt Benckiser, outside the submitted work. Dr. Ruperto reports personal fees from Abbott, AbbVie, Amgen, Biogenidec, Astellas, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer, BMS, CD-Pharma,Celgene, CrescendoBio, EMD Serono, Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Rewind Arms, R-Pharma, Sanofi Aventis, Servier, Sinergie, Takeda, Vertex, UCB Biosciences GmbH, outside the submitted work; grants from Abbott, BMS, Francesco Angelini, GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma, Wyeth, outside the submitted work. Dr. Trachana reports personal fees from IRCCS Istituto Giannina Gaslini, during the conduct of the study; personal fees from Novartis, Pfizer, IRCCS Istituto Giannina Gaslini, outside the submitted work. Dr. Aggarwal, Dr. Al-Mayouf, Dr. Alongi, Dr. Consolaro, Dr. de Inocencio, Dr. Demirkaya, Dr. Flato, Dr. Garay, Dr. Giancane, Dr. Miettunen, Dr. Mihaylova, Dr. Montobbio, Dr. Nielsen, Dr. Orban, Dr. Pistorio, Dr. Rumba-Rozenfelde, Dr. Saad-Magalhaes, Dr. Susic, Dr. van Dijkhuizen and Dr. Wulffraat have nothing to disclose. Ethics Approval Statement: All participating centres obtained the approval of the study protocol by their local Ethics Committee, according to national laws. The parents or guardians of all patients and healthy children provided written informed consent to participation in the study.