Is Pregnancy Truly the Solution for RA? Save

Pregnancy is perhaps the oldest treatment in rheumatoid arthritis (RA) and has been associated with a natural improvement in disease control in 50-75% of patients. Others, however, are not as successful with unchanged disease activity or worsening of their autoimmune disease. An improved understanding of which patients are likely to do well or flare would help physicians and patients prognosticate, anticipate and better manage medications around pregnancy. On Saturday November 16 at the ACR Convergence, Dr. Damini Jawaheer from Northwestern University will present oral abstract #0872 “Investigating the Natural Improvement of Rheumatoid Arthritis During Pregnancy.”

This study investigates a population of 19 pregnant RA patients and 14 pregnant, healthy controls in Denmark. Blood samples were collected prior to conception and at each trimester and gene expression levels were analyzed with bulk RNA-sequencing. In the 19 women with RA, 14 of 19 (73.7%) had clinical improvement by Clinical Disease Assessment Index (CDAI) score. The remaining 5 of 19 (26.3%) had worsened disease activity.

On genetic analysis, both the “RAworsened” and “RAimproved” groups had differential expression at pre-conception baseline compared to the healthy controls. During the pregnancy, however, the RAimproved patients became more similar to the healthy controls with 86% of the differentially expressed genes no longer noted in the third trimester. In contrast, in RAworsened several genes became newly differentially expressed. This included TUBB2B, a candidate previously noted to be over-expressed in RA synovium. Longitudinally, RAimproved women showed pregnancy-associated expression of genes with neutrophil-related function, with expression increasing by pregnancy trimester. PADI4 was one candidate gene previously implicated in RA, which was noted to increase significantly over the course of pregnancy in patients with worsening RA, but not in those with clinical improvements.

This study is small, yet offers some preliminary data that will guide future research directions. The pregnancy-associated gene expressions help us better understand the physiology driving RA activity, and particularly changes during pregnancy. The study’s abstract does not comment on the role of medication treatment on clinical disease activity or gene expression. Further investigation on this topic can help provide more information on a patient's risks for flares, possible disease monitoring, and implications for treatment during pregnancy.