OP0210 PREGNANCY OUTCOMES IN RELATION TO DISEASE ACTIVITY AND ANTI-RHEUMATIC TREATMENT STRATEGIES IN WOMEN WITH RHEUMATOID ARTHRITIS – A MATCHED COHORT STUDY FROM SWEDEN AND DENMARK
Authors: K. Hellgren, A. E. Secher, B. Glintborg, A. Lilleoere Rom, B. Gudbjornsson, B. Michelsen, F. Granath, M. L. Hetland
Journal: Annals of the Rheumatic Diseases (2021)

Background: Women with rheumatoid arthritis (RA) are at increased risks of adverse pregnancy outcomes, especially preterm birth (PTB) and small for gestational age (SGA). However, the link between RA disease activity, type and timing of anti-rheumatic treatment, and the risk of these outcomes remains unclear. Objectives: To explore the associations between maternal RA and PTB/SGA in relation to disease activity and use of anti-rheumatic treatment before and during pregnancy. Methods: By linking national medical birth registers to prospective clinical rheumatology registers (CRRs) in Sweden (SRQ) and Denmark (DANBIO), we identified 1739 RA-pregnancies and 17390 control-pregnancies (matched 1:10 on maternal age, birth year, and parity) with delivery 2006-2018. From CRRs and prescribed drug registers, we collected information on RA disease activity (DAS28, CRP and HAQ-score) and anti-rheumatic drugs (biologics, conventional synthetic (cs)DMARDs and oral steroids) nine months before and during pregnancy. Using logistic regression, we estimated adjusted odds ratios (ORs) with 95% confidence intervals (CI) for PTB and SGA in RA-pregnancies vs. control-pregnancies overall, and stratified by disease activity and type of anti-rheumatic treatment before and during pregnancy. Apart from the matching variables we adjusted for body mass index, smoking, educational level and country. Results: Overall, RA-pregnancies were associated with increased ORs of PTB (1.92, 95% CI 1.56-2.35) and SGA (1.93, 95% CI 1.45-2.57). High maternal disease activity during pregnancy strengthened the associations with both PTB and SGA, whereas the ORs approached 1 for low disease activity (control-pregnancies constituting the reference), Table 1. Among RA-pregnancies with available information on DAS28-CRP (n=686, 39%), OR was 2.69 (95% CI 1.37-5.26) for PTB, and 3.39 (95% CI 1.43-8.06) for SGA, comparing DAS28-CRP &gt;=3.2 vs.&lt;3.2 during pregnancy. Stratifying on type of anti-rheumatic treatment did not substantially change the results. Combination therapy with biologics together with oral steroids and/or csDMARDs in the nine months before pregnancy was associated with PTB (ORs spanning 2.57-3.45) and SGA (ORs spanning 2.40-3.81). Table 1. Adjusted odds ratios (ORs)1 for PTB and SGA in RA-pregnancies in relation to disease activity and functional status during pregnancy vs. control pregnancies Preterm birth Small for gestational age 1 Pregnancies, n Events, n (%) Adjusted OR (95% CI) Pregnancies, n Events, n (%) Adjusted OR (95% CI) Control-pregnancies 2 17312 794 (5) 1 (REF) 17184 418 (2) 1(REF) All RA pregnancies 2 1734 144 (8) 1.92 (1.56-2.35 ) 1722 75 (4) 1.93 (1.45-2.57 ) DAS28-CRP 3,4 &lt;3.2 459 26 (6) 1.05 (0.64-1.72) 456 13 (3) 0.96 (0.49-1.91) 3.2-5.1 182 17 (9) 2.40 (1.40-4.11 ) 181 13 (7) 3.13 (1.64-5.97 ) &gt;5.1 43 5 (12) 2.77 (0.86-8.87) 43 4 (9) 4.59 (1.59-13.2 ) No information 1050 96 (9) 2.18 (1.71-2.78 ) 1042 45 (4) 2.06 (1.46-2.90 ) HAQ-score 3 &lt;0.5 338 19 (6) 1.31 (0.79-2.16) 335 8 (2) 0.93 (0.41-2.12) 0.5-0.9 166 15 (9) 2.37 (1.34-4.19 ) 165 5 (3) 1.50 (0.60-3.74) ≥1 196 19 (10) 1.85 (1.06-3.24 ) 195 18 (9) 3.70 (2.05-6.67 ) No information 1034 91 (9) 2.06 (1.60-2.64 ) 1027 44 (4) 1.98 (1.39-2.82 ) CRP, mg/L 3 &lt;10 455 21 (5) 0.91 (0.55-1.51) 452 14 (3) 1.09 (0.57-2.07) 10-29 191 22 (11) 2.58 (1.52-4.38 ) 190 12 (6) 2.68 (1.38-5.22 ) ≥30 57 9 (16) 4.59 (2.28-9.22 ) 57 5 (9) 4.12 (1.68-10.1 ) No information 1031 92 (9) 2.10 (1.64-2.70 ) 1023 44 (4) 2.05 (1.44-2.90 ) 1 Missingness on small for gestational age in 12 RA-pregnancies and 128 control-pregnancies 2 Only among live births, i.e. stillbirths excluded. 3 Maximum value any time during pregnancy 4 Defined as DAS28-CRP without patient’s global health VAS Conclusion: During pregnancy, disease activity rather than treatment, appears to be the most important risk factor for PTB and SGA in RA. The findings highlight the importance of monitoring RA during pregnancy, especially in women receiving extensive anti-rheumatic treatment or with residual disease activity. Acknowledgements: The Nordic clinical rheumatology registers for allowing us to use their clinical data. We also would like to acknowledge the NordForsk and FOREUM, especially the patient representatives of the NordForsk collaboration. Disclosure of Interests: Karin Hellgren Consultant of: UCB, Anne Emilie Secher: None declared, Bente Glintborg Grant/research support from: Pfizer, Biogen and BMS, Ane Lilleoere Rom: None declared, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Brigitte Michelsen Consultant of: Novartis, Grant/research support from: Novartis, Fredrik Granath: None declared, Merete Lund Hetland Speakers bureau: Biogen, Celltrion, Janssen Biologics B.V, MSD, Pfizer, Samsung Biopis, Consultant of: Biogen, Celltrion, Janssen Biologics B.V, MSD, Pfizer, Samsung Biopis, Grant/research support from: AbbVie, Biogen, BMS, Eli Lilly Danmark A/S, Lundbeck Fonden, Pfizer, Roche, Sandoz, Novartis