Monoclonal antibody dispensing during and around pregnancy: a descriptive analysis using electronic health records in Italy

A descriptive analysis of Italian electronic health records from 2012 to 2024 reveals a dramatic increase in monoclonal antibody dispensing for women of reproductive age and a corresponding rise in continued use during pregnancy, suggesting a shift in prescribing practices despite a significant proportion of women still discontinuing treatment upon conception.

The Gist

Imagine your body's immune system is like a highly trained security team. Its job is to spot intruders (viruses and bacteria) and stop them. But sometimes, this team gets confused and starts attacking the building itself (your own organs). This is what happens in autoimmune diseases like rheumatoid arthritis or Crohn's disease.

To fix this, doctors use special "sniper rifles" called Monoclonal Antibodies (mAbs). These are smart drugs that target the specific part of the security team causing the trouble, calming them down without shutting the whole system down.

This study is like a massive, 12-year-long surveillance report from the Lombardy region of Italy. The researchers wanted to answer a very specific question: What happens to these "sniper rifles" when a woman becomes pregnant?

Here is the story of what they found, broken down simply:

1. The "More Guns, More Fire" Trend

In the past (around 2012), very few women of childbearing age were using these special drugs. It was like a rare occurrence. But by 2024, the number of women using them had skyrocketed—increasing by more than 60 times.

• The Analogy: Think of it like a new type of high-tech umbrella. In 2012, almost no one had one. By 2024, almost everyone caught in the rain had one. More women are getting diagnosed with autoimmune issues, and more are getting access to these effective treatments.

2. The Pregnancy "Pause Button"

When a woman gets pregnant, the rules change. The baby is growing inside, and the mother's security team (and the drugs) can accidentally cross the wall into the baby's room.

• The Concern: Doctors were worried these drugs might confuse the baby's developing immune system.
• The Old Rule: For a long time, the advice was: "Stop the drugs as soon as you get pregnant, or at least by the middle of the pregnancy."
• What the Study Saw: The researchers watched the data like a traffic camera. They saw that for many women, the "traffic" of drug dispensing did slow down during pregnancy. About half of the women who were taking these drugs before pregnancy stopped taking them once they were pregnant.
  • The Metaphor: Imagine driving a car (taking the drug). As you approach a school zone (pregnancy), you hit the brakes. Many drivers stopped completely.

3. The "New Rules of the Road"

Here is the most interesting part: The rules are changing.
In the early 2010s, almost everyone hit the brakes hard and stopped the drugs. But in recent years (2021–2024), fewer women are stopping.

• Why? Scientists have learned that some of these "sniper rifles" are actually quite safe for the baby.
• The Star Player: One specific drug, Certolizumab pegol, is like a car with a special "baby-proof" shield. It doesn't cross the wall into the baby's room easily. Because of this, doctors are now saying, "You can keep driving with this one!" The study found that women on this drug were the least likely to stop taking it.

4. The "Switching" and "Restarting"

• Switching: Very few women (only about 3%) tried to swap one drug for another while pregnant. It's rare to change your car engine while driving down the highway.
• Restarting: After the baby is born, about half of the women who had stopped their medication decided to start it again. This is like realizing the rain has started again after the baby is safe, so you grab your umbrella.

5. Who Stops and Who Keeps Going?

The researchers looked at who was more likely to hit the brakes:

• The "Stop" Group: Women who used fertility treatments (like IVF) were slightly more likely to stop the drugs, perhaps because they were extra cautious after working so hard to conceive.
• The "Keep Going" Group: Women who had a history of miscarriage or a very clear, severe autoimmune diagnosis were less likely to stop. They knew the risk of the disease flaring up was too dangerous to gamble with.
• Surprise: It didn't matter much if the woman was rich, poor, young, or old. The decision was mostly about the specific drug and the doctor's advice.

The Big Picture Takeaway

This study is like a long-term weather report. It tells us that:

1. More women are using these powerful drugs.
2. Doctors are becoming less afraid of them during pregnancy.
3. The "Stop immediately" rule is fading away, replaced by a smarter approach: "Keep the treatment going if it's safe and necessary for the mother's health."

The researchers conclude that while we are seeing more women staying on these medications during pregnancy, we need to keep watching closely to make sure both mom and baby stay healthy in the long run. It's a balancing act between keeping the mother's "security team" calm and keeping the baby safe.

Technical Summary

1. Problem Statement

Autoimmune conditions affect 7–13% of women in Europe, often diagnosed during reproductive years. While monoclonal antibodies (mAbs) are increasingly used to manage moderate-to-severe autoimmune diseases, their use during pregnancy presents a clinical dilemma. Due to their IgG structure, most mAbs are actively transported across the placenta from the second trimester, raising concerns about neonatal immune system impacts. Consequently, historical guidelines often advised discontinuing treatment by the second trimester. However, recent evidence suggests that continuing certain mAbs (particularly TNF-inhibitors) may be safer than the risks associated with active disease recurrence.

The Gap: There is a lack of population-wide data describing secular trends in mAb dispensing among women of reproductive age and specific trajectories of use (continuation, discontinuation, switching) during pregnancy. Previous studies were limited by small sample sizes, single-condition focus, or older datasets.

2. Methodology

• Study Design: A descriptive study analyzing electronic health records (EHR).
• Setting & Data Source: Lombardy, Italy (population ~10 million), utilizing linked regional healthcare databases.
• Study Period: January 1, 2012, to December 31, 2024.
• Study Population:
  • Cohort: 3,049,175 women of reproductive age (14–49 years) resident in Lombardy.
  • Pregnancies: 859,699 pregnancies reaching ≥20 weeks gestation.
  • Exposure Definition: Dispensing of 23 specific mAbs used for seven key autoimmune conditions (e.g., IBD, Rheumatoid Arthritis, Psoriasis, MS, SLE, Myasthenia Gravis).
• Exposure Periods: Defined based on estimated conception dates:
  • 1 year pre-conception.
  • Trimesters 1, 2, and 3.
  • 1 year post-partum.
• Key Metrics:
  • Prevalence of dispensing over time (secular trends).
  • Longitudinal trajectories (continuation vs. discontinuation).
  • Discontinuation: Defined as a dispensation in the pre-pregnancy period followed by a gap in dispensing before the third trimester.
  • Switching: Changing mAbs between periods.
  • Resumption: Re-initiating treatment post-partum.
• Statistical Analysis:
  • Calculation of prevalence with 95% Confidence Intervals (CIs).
  • Logistic regression to identify factors associated with discontinuation (adjusting for calendar year), including maternal demographics, socioeconomic status, and clinical history.
  • Robust standard errors were used to account for multiple pregnancies per woman.

3. Key Contributions

• First Population-Wide Analysis: This is the first study to describe secular trends in mAb dispensing across all women of reproductive age and all pregnancies in a large population (3M+ women) over a 12-year period.
• Granular Trajectory Analysis: It provides detailed data on the timing of discontinuation, switching, and resumption, moving beyond simple "use vs. non-use" metrics.
• Drug-Specific Insights: It differentiates trends across specific mAbs (e.g., Adalimumab, Certolizumab pegol, Natalizumab), highlighting how guidelines and safety data influence specific drug choices during pregnancy.
• Contemporary Data: The dataset extends to 2024, capturing the most recent shifts in clinical practice and guideline updates (e.g., EULAR and ECCO recommendations).

4. Key Results

• Secular Trends:
  • Overall Increase: mAb dispensing prevalence among women of reproductive age increased significantly from 0.049% (2012) to 0.40% (2024).
  • Pregnancy Increase: Prevalence of dispensing during pregnancy increased >60-fold, from 0.0041% (2012) to 0.27% (2024).
  • Dominant Drugs: In 2024, Certolizumab pegol was the most dispensed mAb during pregnancy (0.095%), followed by Adalimumab (0.064%) and Natalizumab (rapidly increasing to 0.037%).
• Dispensing Trajectories:
  • Decline During Pregnancy: Prevalence decreased from 0.080% pre-pregnancy to 0.051% by the third trimester.
  • Discontinuation: Among pre-existing users (n=722), 53.3% discontinued treatment before or during pregnancy.
  • Timing of Discontinuation: The most common time for stopping was the second trimester (37.7%), followed by the third (27.5%).
  • Continuation Trends: The rate of continuation increased over time, rising from 18.2% (2012–2014) to 58.3% (2021–2024).
  • Switching: Rare (3.3% of pre-existing users).
  • Resumption: 55.8% of those who discontinued resumed mAb treatment within one year post-partum.
• Factors Associated with Discontinuation:
  • Drug Type: Users of Certolizumab pegol and multiple drugs were significantly less likely to discontinue. Conversely, users of Secukinumab, Ustekinumab, and "other" mAbs were more likely to discontinue.
  • Clinical History: A recorded autoimmune condition diagnosis was associated with lower odds of discontinuation (OR=0.62).
  • Conception Method: Pregnancies conceived via Assisted Reproductive Technology (ART) had higher odds of discontinuation (OR=1.92).
  • Demographics: Maternal age, education, country of birth, and employment status showed no significant association with discontinuation.

5. Significance and Implications

• Guideline Alignment: The observed decrease in discontinuation rates over time and the specific preference for Certolizumab pegol (which lacks the Fc region required for active placental transfer) align with recent updates in European clinical guidelines (EULAR, ECCO) that support continuing treatment for active disease.
• Safety Signal: The data suggests a shift in clinical practice where the risk of active autoimmune disease is increasingly weighed against theoretical drug risks, leading to higher continuation rates.
• Post-Partum Care: The increase in dispensing post-partum highlights the need for monitoring disease flares after delivery, a known risk period for conditions like Rheumatoid Arthritis and MS.
• Future Research: The study underscores the need for outcome studies (maternal and fetal) specifically for newer and less commonly used mAbs, as safety data remains sparse for some agents.
• Limitations: The study relies on dispensing records (not actual consumption) and lacks primary care data on disease severity, which is a key driver for clinical decisions. It also excludes pregnancies ending before 20 weeks.

In conclusion, this study provides critical evidence that mAb use during pregnancy in Italy is rising and becoming more sustained, reflecting an evolution in clinical management toward maintaining disease control rather than routine discontinuation.