CO:09:6 | Risk of disease flare during pregnancy and postpartum in inflammatory arthritis: association with therapy discontinuation in the prospective P-RHEUM.it study

Dina Zucchi¹, Chiara Tani¹, Francesca Crisafulli², Alessia Gatti², Maria Gerosa³, Cecilia Chighizola³, Melissa Padovan⁴, Salvatore D'Angelo⁵, Florenzo Iannone⁶, Maria Sole Chimenti⁷, Claudia Lomater⁸, Francesca Serale⁹, Veronique Ramoni¹⁰, Oscar Epis¹¹, Bernd Raffeiner¹², Ariela Hoxha¹³, Andrea Doria¹⁴, Leonardo Santo¹⁵, Valentina Canti¹⁶, Francesca Bellisai¹⁷, Giovanna Cuomo¹⁸, on behalf of the P-Rheumit Investigators¹⁹, Greta Carrara²⁰, Cristina Di Nicola²⁰, Davide Rozza²⁰, Carlo Alberto Scirè²⁰, Maria Chiara Gerardi¹¹, Angela Tincani², Laura Andreoli², Marta Mosca¹. | ¹Rheumatology Unit, University of Pisa and Azienda Ospedaliero Universitaria Pisana; ²Rheumatology and Clinical Immunology Unit, ASST Spedali Civili, Brescia; ³Clinical Rheumatology Division, ASST Gaetano Pini-CTO and University of Milano; ⁴Rheumatology Unit, Azienda Ospedaliero-Universitaria S. Anna and University of Ferrara; ⁵Rheumatology Department of Lucania - San Carlo Hospital, Potenza; ⁶Rheumatology Unit, DiMePRE-J, University of Bari; ⁷Department of Systems Medicine, Rheumatology, Allergology and Clinical Immunology, University of Rome-Tor Vergata, Roma; ⁸Torino Academic Rheumatology Center, A.O. Mauriziano di Torino, University of Torino; ⁹Rheumatology Unit, ASL CN1 Cuneo; ¹⁰Internal Medicine Department, ASST Lodi - Ospedale Maggiore di Lodi; ¹¹Division of Rheumatology, Multispecialist Medical Department, Grande Ospedale Metropolitano Niguarda, Milano; ¹²Department of Rheumatology, Central Hospital of Bolzano SABES-ASDAA, Bolzano; ¹³General Medicine and Thrombosis and Hemorrhagic Unit, Department of Medicine, University of Padova; ¹⁴Rheumatology Unit, Department of Medicine, University of Padova; ¹⁵Rheumatology Unit, Mons. Dimiccoli Hospital, Barletta; ¹⁶Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milano; ¹⁷Rheumatology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena; ¹⁸Precision Medicine Department, University of Campania L. Vanvitelli, Napoli; ¹⁹The Italian Society for Rheumatology; ²⁰Epidemiology Research Unit of the Italian Society for Rheumatology, Milano, Italy

Background: There is still a significant unmet need for robust data on pregnancy outcomes in patients with autoimmune rheumatic diseases (ARD), both regarding disease flare and obstetric complications. To address this gap, the Italian Registry of Pregnancies in Rheumatic Diseases (P-RHEUM.it) was designed as a nationwide, web-based longitudinal observational cohort study to collect data about pregnancy in ARD between 2018 and 2023. This analysis focuses on patients with inflammatory arthritis (IA) enrolled in the registry, aiming to describe pregnancy outcomes with special attention to disease flare during pregnancy and postpartum. We also assessed the relationship between treatment discontinuation, treatment at baseline, and flare risk.

Materials and methods: Patients with rheumatoid arthritis (RA), undifferentiated arthritis (UA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), and spondyloarthritis (SpA) were included. Treatment discontinuation is defined as ongoing therapy in the last 12 months, interrupted upon positive pregnancy test. Flare was defined when at least one of the following disease-specific criteria was met: • RA/UA/JIA: a variation of DAS28-CRP between two visits > 1.2, or > 0.6 if DAS28 at previous visit was > 3.2 • PsA: a variation of DAPSA > 4 or > 1.1 between two visits • SpA: variation of ASDAS >= 0.9 The same definitions of flares were applied during the post-partum period up to 6 months after delivery.

Results: A total of 393 patients were included. Cohort characteristics (demographics, disease activity, use or discontinuation of medications during pregnancy) are reported in Table 1 and data on DAS-28, DAPSA and ASDAS during the follow-up in Table 2. During pregnancy, 167/393 patients (42.5%) experienced a flare; in postpartum, 12/248 (4.8%). Flare risk was higher in patients with active disease in the 12 months before pregnancy (p<0.001). Discontinuation of anti-TNF and NSAIDs used in the year before pregnancy was also associated with flare (p<0.001 and p=0.02, respectively). A BMI >30 was linked to increased flare risk (p=0.04), while cDMARD use at baseline and a patient global assessment (PGA) reflecting better health status were protective (p=0.001 and p<0.001). In multivariate analysis, logistic regression was performed: PsA and SpA diagnosis, active disease and anti-TNF discontinuation remained independent predictors (OR 1.02, 95% CI 1.01–1.03, p=0.02; OR 2.19, 95% CI 1.19–4.03, p=0.01). Among patients assessed with DAS28, an increase in disease activity during pregnancy was observed following anti-TNF withdrawal (Figure 1).

Conclusions: These findings highlight the importance of planning pregnancy during periods of well-controlled disease and emphasize the need to educate patients on the safety and importance of continuing pregnancy-compatible therapies. Additionally, close monitoring throughout pregnancy and the postpartum period is crucial.