“Treat to target” has become one of the most important buzz phrases in rheumatology today, particularly for rheumatoid arthritis (RA). The treat-to-target movement was based, at least in part, on data supporting tight control of other chronic diseases such as diabetes mellitus (DM) and hypertension (HTN) on improved long-term outcomes with reduction in end-organ damage. Indeed, one of the 10 recommendations for treat to target states, “The desired treatment target should be maintained throughout the remaining course of the disease.”1 Unfortunately, this goal does not always seem to apply to a growing population of RA patients—women who are or desire to become pregnant. It is precisely because of the introduction of successful treatment options for RA and the growing potential for remission that many women of childbearing age now feel healthy enough to consider childbearing and childrearing. However, there remains a reluctance to control disease activity during pregnancy for fear of adverse effects of drug exposure on the fetus. It is likely that, as rheumatologists trained in the prebiologic era, we have had relatively little experience with treating pregnant women in the past, and therefore have some discomfort with this topic.
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October 2012What the Current Data Show
For many decades, data on RA disease activity during pregnancy supported the notion that the great majority of patients experienced improvement or even remission of active disease during pregnancy, with improvements noted early in gestation and continuing through delivery.2 There was little corresponding study of the effects of RA upon pregnancy outcome. However, more recent data have cast some doubt on the magnitude of disease quiescence during pregnancy and the notion that fetal outcomes are unrelated to maternal disease activity. Prospective observational studies performed within the last decade using standardized measures of disease activities have begun to quantify the extent of disease burden during pregnancy. These have shown, in general, that there continues to be a good proportion of RA patients who experience improvements in disease activity during pregnancy.
However, in contrast to earlier reports, these data demonstrate that fewer than half of patients with moderate disease at conception experience a moderate or good response according to European League Against Rheumatism criteria by the third trimester, leaving the remaining women with a Disease Assessment Score–28 of >3.2 (intermediate and severe disease activity) during pregnancy.3 In the nonpregnant patient, this would be considered a failure. One could argue that pregnancy is an exception to the treat-to-target goals for two reasons: 1) this is a short period of time in a woman’s lifetime of RA; and 2) past data suggested no adverse pregnancy outcomes, therefore the risks of active disease to the fetus are too low to consider potential teratogenic risk of medication exposure.
Certainly, a full-term pregnancy is only 40 weeks long, which is a relatively short period in a lifetime of RA. Medications are often withdrawn in anticipation of a pregnancy months before conception and are not restarted until after the completion of breastfeeding. Considering that many women desire more than one child, and newer data suggest that women with RA have increased difficulties conceiving, the total “active reproductive” period of time for a given woman is likely several years at least.4 Prospective observational studies and clinical trial data clearly demonstrate that active disease is associated with progression of erosions even within 12 months.5 Therefore, over a woman’s reproductive life, periodic undertreated disease during preconception, conception, and pregnancy may result in increased morbidity and damage accrual. Many self-sacrificing mothers may argue that the increased maternal disease burden is worth subsequent protection of the unborn child from medication exposure.