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Rheumatoid arthritis can’t be cured, but it can significantly improve naturally during pregnancy in 50%-75% of women, prior research has established. It may worsen or stay the same during pregnancy in others.

As of yet, there’s no way to tell which experience a woman with RA will have. RA occurs in 1% of adults globally and is three times more likely to occur in women.

However, a novel study of 19 women with RA suggests that blood biomarkers before pregnancy may predict who will get better or worse during pregnancy. If confirmed with larger studies, the discovery could lead to personalizing medication choices for women with RA who are seeking to become pregnant and change prepregnancy counseling for physicians.

Findings from the research, conducted by first author Matthew Wright, MS, of Children’s Hospital Oakland (Calif.) Research Institute and colleagues were published online in Arthritis Research & Therapy.
 

A risky choice for women

Currently, the choice is difficult because stopping medications during pregnancy could cause disease flare and continuing could risk possible harm to the baby as some of the medications have toxic side effects.

Dr. Damini Jawaheer

This is the first study to analyze genetic differences in women with RA who plan to get pregnant, senior author Damini Jawaheer, PhD, research associate professor of medicine in rheumatology at Northwestern University, Chicago, said in an interview.

Identifying women who have the disease and confirming they were planning to get pregnant has been extremely difficult, she noted, especially since the start of their research predated electronic health records (EHRs).

The researchers were able to develop a cohort from work they were already doing with researchers in Denmark, which has a national registry that included both women with RA and women of reproductive age. From there they could contact women about their pregnancy intentions and build the cohort for this study.

Healthy women and women with RA of Danish descent who planned to get pregnant were enrolled and were prospectively followed.
 

Genetic differences at prepregnancy baseline

Researchers analyzed genetic differences through RNA sequencing before pregnancy from 19 women with RA and 13 healthy women.

Of the 19 women with RA, disease activity improved during pregnancy in 14 and worsened in 5.

Before pregnancy, the researchers found, several neutrophil-related genes were significantly overexpressed in women whose RA later improved during pregnancy. Genes related to B cells were highly expressed among women who worsened. Those elevated B-cell–related gene levels were not seen in the group who improved during pregnancy, Dr. Jawaheer added.

“We don’t understand at this point why that is,” she said.

They also compared the blood samples with women in the control group who did not have RA.

“Comparisons to healthy women revealed that the B-cell signature was specific” to women with worsened RA, the authors wrote. “Thus, at the prepregnancy stage, the two groups of RA women differed significantly from each other in terms of B-cell function.”
 

 

 

Information could help to eliminate fear

Dr. Jawaheer said almost all the women in the cohort who have RA said they were afraid to take medications during pregnancy even if the medications they are taking are considered safe.

“If we could reliably predict who’s going to improve, those women would not have to be scared,” she said. They could stop their medications if they know they’re going to improve naturally.

“Women who are predicted to worsen could then work together with their rheumatologist so that they get treatment to prevent them from getting worse,” Dr. Jawaheer said. “Treatment could be focused on that group only.”

Dr. Arthur Kavanaugh

Arthur Kavanaugh, MD, a rheumatologist at University of California San Diego Health and director of the UCSD Center for Innovative Therapy, who was not part of the study, said his patients planning pregnancy struggle with the choices the researchers describe and that investigating potential biomarkers is important.

“Ideally, people would not want to be on anything when they’re pregnant,” he says.

He found the results “intriguing and hypothesis-generating,” but he said the small sample size makes it hard to draw conclusions about the work before it is replicated on a larger scale.

Beth L. Jonas, MD, chief of the division of rheumatology, allergy, and immunology at the University of North Carolina, Chapel Hill, also not a part of the study, said the small study size must be considered, but if the findings are validated in larger studies, the potential is “huge.”

Dr. Beth L. Jonas

She said doctors used to tell their patients years ago that there’s an excellent chance they will be in remission in pregnancy.

Now, she says, “We’ve tempered our advice to say there’s a good chance you’ll still have disease activity during your pregnancy.”

Rheumatologists would be very interested in a predictive biomarker, she said, as would colleagues in obstetrics/gynecology and maternal-fetal medicine physicians who manage high-risk pregnancies and do prepregnancy counseling.

She said she would also like to see these data followed over multiple pregnancies for each woman, noting that some of her patients have seen RA improve in one pregnancy and worsen in another.

A question she has is, “with a single patient with RA, could you measure this multiple times and get different results?”
 

Tackling the unanswered questions

Next, the researchers want to conduct the study with a larger sample in the United States and one that is more diverse than the Danish cohort, which included only White patients. Now, Dr. Jawaheer and her team will have the help of EHRs.

A big part of Dr. Jawaheer’s lab’s focus is to find out why many with RA report “never feeling better” during pregnancy – some even experience remission – and why women who improve during pregnancy report that their disease flares 3-6 months after pregnancy, she said.

Her team is also studying what happens biologically when some women worsen in pregnancy.

Those answers “will give us an indication of what could be a potential drug target,” she said.

The authors and Dr. Kavanaugh and Dr. Jonas reported no relevant financial relationships.

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Rheumatoid arthritis can’t be cured, but it can significantly improve naturally during pregnancy in 50%-75% of women, prior research has established. It may worsen or stay the same during pregnancy in others.

As of yet, there’s no way to tell which experience a woman with RA will have. RA occurs in 1% of adults globally and is three times more likely to occur in women.

However, a novel study of 19 women with RA suggests that blood biomarkers before pregnancy may predict who will get better or worse during pregnancy. If confirmed with larger studies, the discovery could lead to personalizing medication choices for women with RA who are seeking to become pregnant and change prepregnancy counseling for physicians.

Findings from the research, conducted by first author Matthew Wright, MS, of Children’s Hospital Oakland (Calif.) Research Institute and colleagues were published online in Arthritis Research & Therapy.
 

A risky choice for women

Currently, the choice is difficult because stopping medications during pregnancy could cause disease flare and continuing could risk possible harm to the baby as some of the medications have toxic side effects.

Dr. Damini Jawaheer

This is the first study to analyze genetic differences in women with RA who plan to get pregnant, senior author Damini Jawaheer, PhD, research associate professor of medicine in rheumatology at Northwestern University, Chicago, said in an interview.

Identifying women who have the disease and confirming they were planning to get pregnant has been extremely difficult, she noted, especially since the start of their research predated electronic health records (EHRs).

The researchers were able to develop a cohort from work they were already doing with researchers in Denmark, which has a national registry that included both women with RA and women of reproductive age. From there they could contact women about their pregnancy intentions and build the cohort for this study.

Healthy women and women with RA of Danish descent who planned to get pregnant were enrolled and were prospectively followed.
 

Genetic differences at prepregnancy baseline

Researchers analyzed genetic differences through RNA sequencing before pregnancy from 19 women with RA and 13 healthy women.

Of the 19 women with RA, disease activity improved during pregnancy in 14 and worsened in 5.

Before pregnancy, the researchers found, several neutrophil-related genes were significantly overexpressed in women whose RA later improved during pregnancy. Genes related to B cells were highly expressed among women who worsened. Those elevated B-cell–related gene levels were not seen in the group who improved during pregnancy, Dr. Jawaheer added.

“We don’t understand at this point why that is,” she said.

They also compared the blood samples with women in the control group who did not have RA.

“Comparisons to healthy women revealed that the B-cell signature was specific” to women with worsened RA, the authors wrote. “Thus, at the prepregnancy stage, the two groups of RA women differed significantly from each other in terms of B-cell function.”
 

 

 

Information could help to eliminate fear

Dr. Jawaheer said almost all the women in the cohort who have RA said they were afraid to take medications during pregnancy even if the medications they are taking are considered safe.

“If we could reliably predict who’s going to improve, those women would not have to be scared,” she said. They could stop their medications if they know they’re going to improve naturally.

“Women who are predicted to worsen could then work together with their rheumatologist so that they get treatment to prevent them from getting worse,” Dr. Jawaheer said. “Treatment could be focused on that group only.”

Dr. Arthur Kavanaugh

Arthur Kavanaugh, MD, a rheumatologist at University of California San Diego Health and director of the UCSD Center for Innovative Therapy, who was not part of the study, said his patients planning pregnancy struggle with the choices the researchers describe and that investigating potential biomarkers is important.

“Ideally, people would not want to be on anything when they’re pregnant,” he says.

He found the results “intriguing and hypothesis-generating,” but he said the small sample size makes it hard to draw conclusions about the work before it is replicated on a larger scale.

Beth L. Jonas, MD, chief of the division of rheumatology, allergy, and immunology at the University of North Carolina, Chapel Hill, also not a part of the study, said the small study size must be considered, but if the findings are validated in larger studies, the potential is “huge.”

Dr. Beth L. Jonas

She said doctors used to tell their patients years ago that there’s an excellent chance they will be in remission in pregnancy.

Now, she says, “We’ve tempered our advice to say there’s a good chance you’ll still have disease activity during your pregnancy.”

Rheumatologists would be very interested in a predictive biomarker, she said, as would colleagues in obstetrics/gynecology and maternal-fetal medicine physicians who manage high-risk pregnancies and do prepregnancy counseling.

She said she would also like to see these data followed over multiple pregnancies for each woman, noting that some of her patients have seen RA improve in one pregnancy and worsen in another.

A question she has is, “with a single patient with RA, could you measure this multiple times and get different results?”
 

Tackling the unanswered questions

Next, the researchers want to conduct the study with a larger sample in the United States and one that is more diverse than the Danish cohort, which included only White patients. Now, Dr. Jawaheer and her team will have the help of EHRs.

A big part of Dr. Jawaheer’s lab’s focus is to find out why many with RA report “never feeling better” during pregnancy – some even experience remission – and why women who improve during pregnancy report that their disease flares 3-6 months after pregnancy, she said.

Her team is also studying what happens biologically when some women worsen in pregnancy.

Those answers “will give us an indication of what could be a potential drug target,” she said.

The authors and Dr. Kavanaugh and Dr. Jonas reported no relevant financial relationships.

Rheumatoid arthritis can’t be cured, but it can significantly improve naturally during pregnancy in 50%-75% of women, prior research has established. It may worsen or stay the same during pregnancy in others.

As of yet, there’s no way to tell which experience a woman with RA will have. RA occurs in 1% of adults globally and is three times more likely to occur in women.

However, a novel study of 19 women with RA suggests that blood biomarkers before pregnancy may predict who will get better or worse during pregnancy. If confirmed with larger studies, the discovery could lead to personalizing medication choices for women with RA who are seeking to become pregnant and change prepregnancy counseling for physicians.

Findings from the research, conducted by first author Matthew Wright, MS, of Children’s Hospital Oakland (Calif.) Research Institute and colleagues were published online in Arthritis Research & Therapy.
 

A risky choice for women

Currently, the choice is difficult because stopping medications during pregnancy could cause disease flare and continuing could risk possible harm to the baby as some of the medications have toxic side effects.

Dr. Damini Jawaheer

This is the first study to analyze genetic differences in women with RA who plan to get pregnant, senior author Damini Jawaheer, PhD, research associate professor of medicine in rheumatology at Northwestern University, Chicago, said in an interview.

Identifying women who have the disease and confirming they were planning to get pregnant has been extremely difficult, she noted, especially since the start of their research predated electronic health records (EHRs).

The researchers were able to develop a cohort from work they were already doing with researchers in Denmark, which has a national registry that included both women with RA and women of reproductive age. From there they could contact women about their pregnancy intentions and build the cohort for this study.

Healthy women and women with RA of Danish descent who planned to get pregnant were enrolled and were prospectively followed.
 

Genetic differences at prepregnancy baseline

Researchers analyzed genetic differences through RNA sequencing before pregnancy from 19 women with RA and 13 healthy women.

Of the 19 women with RA, disease activity improved during pregnancy in 14 and worsened in 5.

Before pregnancy, the researchers found, several neutrophil-related genes were significantly overexpressed in women whose RA later improved during pregnancy. Genes related to B cells were highly expressed among women who worsened. Those elevated B-cell–related gene levels were not seen in the group who improved during pregnancy, Dr. Jawaheer added.

“We don’t understand at this point why that is,” she said.

They also compared the blood samples with women in the control group who did not have RA.

“Comparisons to healthy women revealed that the B-cell signature was specific” to women with worsened RA, the authors wrote. “Thus, at the prepregnancy stage, the two groups of RA women differed significantly from each other in terms of B-cell function.”
 

 

 

Information could help to eliminate fear

Dr. Jawaheer said almost all the women in the cohort who have RA said they were afraid to take medications during pregnancy even if the medications they are taking are considered safe.

“If we could reliably predict who’s going to improve, those women would not have to be scared,” she said. They could stop their medications if they know they’re going to improve naturally.

“Women who are predicted to worsen could then work together with their rheumatologist so that they get treatment to prevent them from getting worse,” Dr. Jawaheer said. “Treatment could be focused on that group only.”

Dr. Arthur Kavanaugh

Arthur Kavanaugh, MD, a rheumatologist at University of California San Diego Health and director of the UCSD Center for Innovative Therapy, who was not part of the study, said his patients planning pregnancy struggle with the choices the researchers describe and that investigating potential biomarkers is important.

“Ideally, people would not want to be on anything when they’re pregnant,” he says.

He found the results “intriguing and hypothesis-generating,” but he said the small sample size makes it hard to draw conclusions about the work before it is replicated on a larger scale.

Beth L. Jonas, MD, chief of the division of rheumatology, allergy, and immunology at the University of North Carolina, Chapel Hill, also not a part of the study, said the small study size must be considered, but if the findings are validated in larger studies, the potential is “huge.”

Dr. Beth L. Jonas

She said doctors used to tell their patients years ago that there’s an excellent chance they will be in remission in pregnancy.

Now, she says, “We’ve tempered our advice to say there’s a good chance you’ll still have disease activity during your pregnancy.”

Rheumatologists would be very interested in a predictive biomarker, she said, as would colleagues in obstetrics/gynecology and maternal-fetal medicine physicians who manage high-risk pregnancies and do prepregnancy counseling.

She said she would also like to see these data followed over multiple pregnancies for each woman, noting that some of her patients have seen RA improve in one pregnancy and worsen in another.

A question she has is, “with a single patient with RA, could you measure this multiple times and get different results?”
 

Tackling the unanswered questions

Next, the researchers want to conduct the study with a larger sample in the United States and one that is more diverse than the Danish cohort, which included only White patients. Now, Dr. Jawaheer and her team will have the help of EHRs.

A big part of Dr. Jawaheer’s lab’s focus is to find out why many with RA report “never feeling better” during pregnancy – some even experience remission – and why women who improve during pregnancy report that their disease flares 3-6 months after pregnancy, she said.

Her team is also studying what happens biologically when some women worsen in pregnancy.

Those answers “will give us an indication of what could be a potential drug target,” she said.

The authors and Dr. Kavanaugh and Dr. Jonas reported no relevant financial relationships.

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