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T2T approach in women with RA associated with increased fertility

Presented by
Prof. Radboud Dolhain, Erasmus University Medical Center, the Netherlands
Conference
ACR 2024
Doi
https://doi.org/10.55788/5932c2d0
A Dutch study found that adopting a treat-to-target (T2T) strategy focused on achieving remission significantly improved fertility in women with rheumatoid arthritis (RA), bringing it closer to that of the general population. No direct relation was found between TNF inhibitor use and fertility.

Around three-quarters of RA patients are women, and clinical onset often occurs during their childbearing years. However, RA may lower the chance of pregnancy, as infertility rates (defined as the inability to conceive within 1 year of unprotected intercourse) are up to 42% in women with RA compared with 10–15% in the general population [1]. RA-related factors associated with fertility were previously studied in the Pregnancy-induced Amelioration of RA (PARA) cohort [2]. These factors include age, nulliparity, disease activity, use of NSAIDs, and use of prednisone (>7.5 mg/day).

The results of the PARA study prompted the initiation of a new cohort, namely the Preconception Counseling in Active RA (PreCARA). The PreCARA study went on to show that in women who wish to conceive, a T2T approach aiming at remission but avoiding NSAIDs and high-dose prednisone is feasible [3]. To achieve this, sulfasalazine and hydroxychloroquine were prescribed, plus, if needed, a TNF inhibitor or low-dose prednisone.

The Dutch group, led by Prof. Radboud Dolhain (Erasmus University Medical Center, the Netherlands), evaluated whether a T2T strategy in the PreCARA cohort (2012–2023) was associated with a shorter time to pregnancy than in the historical reference cohort of the PARA study (2002–2010) [4].

The PreCARA and PARA cohorts had 215 and 245 participants, respectively. Prof. Dolhain noted that disease activity in the first trimester was significantly lower in the PreCARA cohort (DAS28 of 2.03 vs 3.48; P<0.01). In the PreCARA cohort, medication use was much more common, including the use of TNF inhibitors (53% vs 4%; P<0.01).

The median time to pregnancy in the PreCARA cohort was 84 days (range 0–298) in participants who got pregnant, compared with 196 days (77–464) in the PARA study (P<0.01). In the PreCARA cohort, 23% was not pregnant within 1 year; in the PARA cohort, this was 42% (P<0.01). A Kaplan-Meier survival curve depicting pregnancy within 5 years also showed a statistically significant difference in favour of the PreCARA cohort, with differences being much greater in the first 3 years (see Figure).

Figure: Time to pregnancy in the PreCARA (T2T) and PARA (historical controls) cohort: Kaplan-Meier curve for being pregnant within 5 years [4]



Factors associated with pregnancy in the PreCARA cohort included maternal age per year (HR 0.95) and nulliparity (HR 0.69). These findings suggest that the T2T approach could significantly improve fertility management in women with RA.

  1. De Man YA, et al. Arthritis Rheum. 2008;59(9):1241-8.
  2. Brouwer J, et al. Ann Rheum Dis. 2015;74(10):1836-41.
  3. Smeele HTW, et al. Ann Rheum Dis. 2021;80(7):859-64.
  4. Quaak CH, et al. Improved fertility in women with rheumatoid arthritis and a wish to conceive when treated according to a treat-to-target approach aimed at remission. Abstract 1647, ACR Convergence 2024, 14–19 November, Washington DC, USA.

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