Manuel Bécède1, Farideh Alasti2, Irina Gessl3, Lukas Haupt4, Andreas Kerschbaumer5, Uriel Landesmann6, Michaela Loiskandl7, Gabriela M Supp8, Josef S Smolen9, Daniel Aletaha10. 1. Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria. Electronic address: manuel.becede@meduniwien.ac.at. 2. Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria. Electronic address: farideh.alasti@meduniwien.ac.at. 3. Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria. Electronic address: irina.gessl@meduniwien.ac.at. 4. Second Department of Medicine, Hietzing Hospital, Vienna, Austria. Electronic address: lukas.haupt@wienkav.at. 5. Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria. Electronic address: andreas.kerschbaumer@meduniwien.ac.at. 6. Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria. Electronic address: uriel.landesmann@meduniwien.ac.at. 7. Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria. Electronic address: michaela.loiskandl@meduniwien.ac.at. 8. Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria. Electronic address: gabriela.supp@meduniwien.ac.at. 9. Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Second Department of Medicine, Hietzing Hospital, Vienna, Austria. Electronic address: josef.smolen@wienkav.at. 10. Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria. Electronic address: daniel.aletaha@meduniwien.ac.at.
Abstract
BACKGROUND: Despite modern therapeutics and treatment strategies, a subset of rheumatoid arthritis (RA) patients remains insufficiently responsive to multiple therapies. Here, we identify predictors of such refractory RA ("reRA"). METHODS: Patients from a longitudinal academic clinical database with reRA (defined as failing to reach the treatment target of at least low disease activity with ≥3 DMARD courses, including ≥1 biological, over a total of ≥18 months) were compared to patients who did respond within the first two treatments (treatment amenable RA, "taRA"). We performed logistic regression analysis to identify risk factors for refractory disease, and several sensitivity analyses concerning different potential definitions for reRA to confirm the robustness of the results; key findings were also validated in an independent community cohort. RESULTS: We enrolled 412 patients, of whom 70 were reRA and 102 taRA; 240 patients fulfilled neither definition. ReRA patients were more frequently female (92.9 vs. 70.6%, p < 0.001), younger (44.37 vs. 51.14 years, p = 0.002), and had higher CDAI levels at first presentation (26.06 vs. 15.39, p < 0.001). Treatment delay was significantly longer for reRA than for taRA (3.17 vs. 1.45 years, p = 0.001). In multivariable analyses, treatment delay, female gender and higher disease activity remained as independent predictors of refractory disease. Based on the identified predictors, we developed a matrix model for risk of future reRA. CONCLUSIONS: Our data identified delay to initial treatment, female gender and higher disease activity as important predictors of a later refractory course of RA. Delay of treatment initiation is the single most important modifiable risk factor of refractory disease.
BACKGROUND: Despite modern therapeutics and treatment strategies, a subset of rheumatoid arthritis (RA) patients remains insufficiently responsive to multiple therapies. Here, we identify predictors of such refractory RA ("reRA"). METHODS:Patients from a longitudinal academic clinical database with reRA (defined as failing to reach the treatment target of at least low disease activity with ≥3 DMARD courses, including ≥1 biological, over a total of ≥18 months) were compared to patients who did respond within the first two treatments (treatment amenable RA, "taRA"). We performed logistic regression analysis to identify risk factors for refractory disease, and several sensitivity analyses concerning different potential definitions for reRA to confirm the robustness of the results; key findings were also validated in an independent community cohort. RESULTS: We enrolled 412 patients, of whom 70 were reRA and 102 taRA; 240 patients fulfilled neither definition. ReRA patients were more frequently female (92.9 vs. 70.6%, p < 0.001), younger (44.37 vs. 51.14 years, p = 0.002), and had higher CDAI levels at first presentation (26.06 vs. 15.39, p < 0.001). Treatment delay was significantly longer for reRA than for taRA (3.17 vs. 1.45 years, p = 0.001). In multivariable analyses, treatment delay, female gender and higher disease activity remained as independent predictors of refractory disease. Based on the identified predictors, we developed a matrix model for risk of future reRA. CONCLUSIONS: Our data identified delay to initial treatment, female gender and higher disease activity as important predictors of a later refractory course of RA. Delay of treatment initiation is the single most important modifiable risk factor of refractory disease.
Authors: Ingiäld Hafström; Sofia Ajeganova; Maria LE Andersson; Sidona-Valentina Bala; Stefan Bergman; Ann Bremander; Kristina Forslind; Karina Malm; Björn Svensson Journal: Open Access Rheumatol Date: 2019-09-09
Authors: Kevin L Winthrop; Michael E Weinblatt; Joan Bathon; Gerd R Burmester; Philip J Mease; Leslie Crofford; Vivian Bykerk; Maxime Dougados; James Todd Rosenbaum; Xavier Mariette; Joachim Sieper; Fritz Melchers; Bruce N Cronstein; Ferry C Breedveld; Joachim Kalden; Josef S Smolen; Daniel Furst Journal: Ann Rheum Dis Date: 2019-10-29 Impact factor: 19.103
Authors: Désirée van der Heijde; Jacob M van Laar; György Nagy; Nadia Mt Roodenrijs; Paco Mj Welsing; Melinda Kedves; Attila Hamar; Marlies C van der Goes; Alison Kent; Margot Bakkers; Etienne Blaas; Ladislav Senolt; Zoltan Szekanecz; Ernest Choy; Maxime Dougados; Johannes Wg Jacobs; Rinie Geenen; Hans Wj Bijlsma; Angela Zink; Daniel Aletaha; Leonard Schoneveld; Piet van Riel; Loriane Gutermann; Yeliz Prior; Elena Nikiphorou; Gianfranco Ferraccioli; Georg Schett; Kimme L Hyrich; Ulf Mueller-Ladner; Maya H Buch; Iain B McInnes Journal: Ann Rheum Dis Date: 2020-10-01 Impact factor: 19.103