Liver transplants for CRC metastases: Coming into its own?

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Changed
Fri, 04/28/2023 - 15:56

Liver transplant is an effective therapy for patients with primary liver cancer, and outcomes after transplantation are often superior to surgical resection. But the pool of potential patients is increasing, as transplantation is now emerging as an attractive option for select patients with nonresectable colorectal cancer (CRC) liver metastases, as well as those with intrahepatic cholangiocarcinoma (CCA).

Experts in the field highlighted some of the current challenges and opportunities in transplant oncology during a special session at the ASCO Gastrointestinal Cancers Symposium.
 

Transplant is here to stay

To date, the only curative or potentially curative therapy for patients with CRC liver metastases and intrahepatic CCA has been the combination of systemic therapies and R0 resection, said Gonzalo Sapisochin Cantis, MD, associate professor, department of surgery, University of Toronto.

The new idea is that, for patients with unresectable disease, total hepatectomy followed by a liver transplant may be a promising strategy. “This is a very hot topic in transplant oncology,” he said.

Liver transplantation is already established as the best treatment option for patients with primary hepatocellular carcinoma, which has become the main indication for liver transplantation at many centers.

For patients with CRC metastases and intrahepatic CCA, liver transplantation may help cure some patients by extending the conventional margins of surgical oncology, he suggested. “This is basically going to work in patients who have exclusive liver-restricted disease and not in those with metastatic disease. The efficacy is going to be seen by objective and sustained response to some sort of neoadjuvant therapy.”

However, Dr. Sapisochin emphasized liver transplantation is not an option for every patient. “We’re going to have to have clear inclusion and exclusion criteria that need to be defined a priori.”

Intrahepatic CCA has historically been considered a contraindication for liver transplantation. Surgical resection is the preferred first-line treatment and the only one that is potentially curative, he explained. However, most patients are not candidates for surgery, and even if they do have a resection, many of these patients will experience a recurrence, usually in the liver.

There are some studies that support transplantation in this patient population, including one by Dr. Sapisochin and colleagues. That study looked at patients who were transplanted under the assumption that they had hepatocellular carcinoma but were found to actually have intrahepatic CCA. The recurrence rate at 5 years was 18%, and 5-year survival was 65%.

“We were able to show that those patients with small tumors actually can do very well after transplant, with survivals over 70%-80%, which in this population is a very good outcome,” he said.
 

Transplant for CRC metastases

Unresectable liver metastases from colorectal cancer can also be challenging to treat, he said. Surgical resection is the only potential cure with a combination of systemic chemotherapy, but only a minority of patients are candidates for surgery.

Data supporting transplantation for CRC metastases have been emerging. One trial was conducted by researchers in Norway, who developed the Oslo score for risk stratification. “Those with risk factors had worse outcomes, and obviously, having a large tumor diameter, a high CEA (carcinoembryonic antigen), progressing on chemotherapy, or a short interval between the primary resection and the transplant were risk factors for recurrence,” Dr. Sapisochin said.

The 10-year survival among patients with a low Oslo score was 50%. “We’re talking about patients who had no resection possibility and received a transplant after systemic chemotherapy, and they had a 10-year survival of 50%,” he emphasized.

However, Dr. Sapisochin acknowledged the biggest problem transplant surgeons face is that there are not enough donor organs.

One solution is living donor liver transplantation. “Given that this is an unlimited source, you can utilize this as extended criteria and it adds another graft to the system,” he explained.

“We have a protocol for living donor liver transplantations for patients with colorectal liver metastasis,” Dr. Sapisochin said. “We’ve done seven cases so far with pretty good outcomes. One patient, unfortunately, passed away 39 months after transplant with lung metastases, but the rest are alive with no recurrence.”*
 

 

 

More available organs?

R. Mark Ghobrial, MD, PhD, director of the J.C. Walter Jr. Transplant Center at Houston Methodist Hospital, said that, 5 years ago, he was very cautious about liver transplantation for intrahepatic CCA.

He pointed out that, although transplantation for hepatocellular cancer was being done in the 1990s, the results were so poor that a moratorium was placed on the practice. “But now liver transplantation has become the definitive therapy for hepatocellular cancer, and intrahepatic cholangiocarcinoma is going the same way,” he said.

Dr. Ghobrial reiterated that one of the issues in transplantation for oncology patients is the limited supply of available organs, but he believes the landscape for liver transplantation has changed, resulting in more available organs. One factor is that hepatitis C has become curable with the advent of new therapies, and hence, the need for transplantation for patients with this disease has plummeted.

“I’ve done about maybe 800 transplants in the last 5 years. I’ve only transplanted two patients with hepatitis C,” he said. “Now we are doing more transplants for alcoholic liver disease and cancer.”

Improvements in technology are also allowing for more livers to become useable, he pointed out. One example is normothermic machine perfusion, which has entered the clinical arena in the last decade. The technique has shown promising results in improving the quality of marginal organs and increasing the pool of liver grafts.

Another factor that has increased the number of livers available for transplantation is the move to accept organs from circulatory death donors, as well as donations after brain death. “Our transplantation was about 4% of donors after cardiac death, but today this has gone up to almost 16% or 20% of the livers,” Dr. Ghobrial said. “In some centers this has gone up to about 50%.

“Liver transplantation for intrahepatic cholangiocarcinoma and colorectal cancer metastases has come of age for selected patients,” he said.



More caution needed

However, another expert urged some caution, warning that live donation carries risk. Yuman Fong, MD, a surgical oncologist with City of Hope National Medical Center, Duarte, Calif., said that around “1 in 600 live donors die from donation. That is a healthy person dying. This is not a small issue.”

He pointed out that if the criteria for transplant is greatly liberalized, the 5-year survival will not be as high as demonstrated in clinical trials.

Writing about the issue in a recent editorial, Dr. Fong pointed out that cadaveric livers for transplant remain a finite resource and that more than 1,000 patients still die every year on the waiting list for a transplant.

A more reasonable approach would be to advocate for this type of program in regions of the world where cadaveric livers are more plentiful or centers with established living donor transplant programs.

“For us to develop this resource and safeguard patients, family organ donors, and resources, we need to develop what are the best inclusion criteria,” Dr. Fong said. “We have to optimize use of all cadaveric organs and determine if we are willing to transplant borderline organs.”
 

 

 

Ethics of transplanting

Ethicist Arthur L. Caplan, PhD, the Drs. William F. and Virginia Connolly Mitty Professor of Bioethics at New York University, said this is an interesting development in the field of liver transplantation. “There have been attempts in the past, and many did not end well, such as with Steve Jobs. But transplantation is always pushing to expand eligibility, and there has also been much success with that.”

However, Dr. Caplan emphasized the new data are innovative and experimental, which may control how many centers will be able to perform liver transplants in these cancer patient populations. “It has to be data driven as we are dealing with an exceedingly scarce source,” he said. “We know that people can do well, but it adds more stress to the supply of organs, and some patients may not do as well.”

He also emphasized that live donation is not a panacea. “Liver donation from a live donor is not the same as live donation for a kidney. It is much riskier and not that common. So not quite the same.”

The bottom line is that livers for transplantation are a scarce resource and transplant may work well in some cancer patients but not others, he emphasized. “Morally, we want to save lives, but not by adding in people who may not do well. If programs try to stretch the criteria, some may try transplants with more marginal organs.”

Dr. Sapisochin has disclosed relationships with Bayer, Roche, Novartis, Integra, AstraZeneca, Chiesi, Evidera, and Stryker. Dr. Ghobrial reported no relevant financial relationships. Dr. Fong has reported being a scientific consultant for Medtronic and Johnson & Johnson and receiving royalties from Merck and Imugene. Dr. Caplan writes a regular column on ethics for Medscape.

A version of this article first appeared on Medscape.com.

Correction, 4/28/23 - An earlier version of this article misstated when the patient passed away.

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Liver transplant is an effective therapy for patients with primary liver cancer, and outcomes after transplantation are often superior to surgical resection. But the pool of potential patients is increasing, as transplantation is now emerging as an attractive option for select patients with nonresectable colorectal cancer (CRC) liver metastases, as well as those with intrahepatic cholangiocarcinoma (CCA).

Experts in the field highlighted some of the current challenges and opportunities in transplant oncology during a special session at the ASCO Gastrointestinal Cancers Symposium.
 

Transplant is here to stay

To date, the only curative or potentially curative therapy for patients with CRC liver metastases and intrahepatic CCA has been the combination of systemic therapies and R0 resection, said Gonzalo Sapisochin Cantis, MD, associate professor, department of surgery, University of Toronto.

The new idea is that, for patients with unresectable disease, total hepatectomy followed by a liver transplant may be a promising strategy. “This is a very hot topic in transplant oncology,” he said.

Liver transplantation is already established as the best treatment option for patients with primary hepatocellular carcinoma, which has become the main indication for liver transplantation at many centers.

For patients with CRC metastases and intrahepatic CCA, liver transplantation may help cure some patients by extending the conventional margins of surgical oncology, he suggested. “This is basically going to work in patients who have exclusive liver-restricted disease and not in those with metastatic disease. The efficacy is going to be seen by objective and sustained response to some sort of neoadjuvant therapy.”

However, Dr. Sapisochin emphasized liver transplantation is not an option for every patient. “We’re going to have to have clear inclusion and exclusion criteria that need to be defined a priori.”

Intrahepatic CCA has historically been considered a contraindication for liver transplantation. Surgical resection is the preferred first-line treatment and the only one that is potentially curative, he explained. However, most patients are not candidates for surgery, and even if they do have a resection, many of these patients will experience a recurrence, usually in the liver.

There are some studies that support transplantation in this patient population, including one by Dr. Sapisochin and colleagues. That study looked at patients who were transplanted under the assumption that they had hepatocellular carcinoma but were found to actually have intrahepatic CCA. The recurrence rate at 5 years was 18%, and 5-year survival was 65%.

“We were able to show that those patients with small tumors actually can do very well after transplant, with survivals over 70%-80%, which in this population is a very good outcome,” he said.
 

Transplant for CRC metastases

Unresectable liver metastases from colorectal cancer can also be challenging to treat, he said. Surgical resection is the only potential cure with a combination of systemic chemotherapy, but only a minority of patients are candidates for surgery.

Data supporting transplantation for CRC metastases have been emerging. One trial was conducted by researchers in Norway, who developed the Oslo score for risk stratification. “Those with risk factors had worse outcomes, and obviously, having a large tumor diameter, a high CEA (carcinoembryonic antigen), progressing on chemotherapy, or a short interval between the primary resection and the transplant were risk factors for recurrence,” Dr. Sapisochin said.

The 10-year survival among patients with a low Oslo score was 50%. “We’re talking about patients who had no resection possibility and received a transplant after systemic chemotherapy, and they had a 10-year survival of 50%,” he emphasized.

However, Dr. Sapisochin acknowledged the biggest problem transplant surgeons face is that there are not enough donor organs.

One solution is living donor liver transplantation. “Given that this is an unlimited source, you can utilize this as extended criteria and it adds another graft to the system,” he explained.

“We have a protocol for living donor liver transplantations for patients with colorectal liver metastasis,” Dr. Sapisochin said. “We’ve done seven cases so far with pretty good outcomes. One patient, unfortunately, passed away 39 months after transplant with lung metastases, but the rest are alive with no recurrence.”*
 

 

 

More available organs?

R. Mark Ghobrial, MD, PhD, director of the J.C. Walter Jr. Transplant Center at Houston Methodist Hospital, said that, 5 years ago, he was very cautious about liver transplantation for intrahepatic CCA.

He pointed out that, although transplantation for hepatocellular cancer was being done in the 1990s, the results were so poor that a moratorium was placed on the practice. “But now liver transplantation has become the definitive therapy for hepatocellular cancer, and intrahepatic cholangiocarcinoma is going the same way,” he said.

Dr. Ghobrial reiterated that one of the issues in transplantation for oncology patients is the limited supply of available organs, but he believes the landscape for liver transplantation has changed, resulting in more available organs. One factor is that hepatitis C has become curable with the advent of new therapies, and hence, the need for transplantation for patients with this disease has plummeted.

“I’ve done about maybe 800 transplants in the last 5 years. I’ve only transplanted two patients with hepatitis C,” he said. “Now we are doing more transplants for alcoholic liver disease and cancer.”

Improvements in technology are also allowing for more livers to become useable, he pointed out. One example is normothermic machine perfusion, which has entered the clinical arena in the last decade. The technique has shown promising results in improving the quality of marginal organs and increasing the pool of liver grafts.

Another factor that has increased the number of livers available for transplantation is the move to accept organs from circulatory death donors, as well as donations after brain death. “Our transplantation was about 4% of donors after cardiac death, but today this has gone up to almost 16% or 20% of the livers,” Dr. Ghobrial said. “In some centers this has gone up to about 50%.

“Liver transplantation for intrahepatic cholangiocarcinoma and colorectal cancer metastases has come of age for selected patients,” he said.



More caution needed

However, another expert urged some caution, warning that live donation carries risk. Yuman Fong, MD, a surgical oncologist with City of Hope National Medical Center, Duarte, Calif., said that around “1 in 600 live donors die from donation. That is a healthy person dying. This is not a small issue.”

He pointed out that if the criteria for transplant is greatly liberalized, the 5-year survival will not be as high as demonstrated in clinical trials.

Writing about the issue in a recent editorial, Dr. Fong pointed out that cadaveric livers for transplant remain a finite resource and that more than 1,000 patients still die every year on the waiting list for a transplant.

A more reasonable approach would be to advocate for this type of program in regions of the world where cadaveric livers are more plentiful or centers with established living donor transplant programs.

“For us to develop this resource and safeguard patients, family organ donors, and resources, we need to develop what are the best inclusion criteria,” Dr. Fong said. “We have to optimize use of all cadaveric organs and determine if we are willing to transplant borderline organs.”
 

 

 

Ethics of transplanting

Ethicist Arthur L. Caplan, PhD, the Drs. William F. and Virginia Connolly Mitty Professor of Bioethics at New York University, said this is an interesting development in the field of liver transplantation. “There have been attempts in the past, and many did not end well, such as with Steve Jobs. But transplantation is always pushing to expand eligibility, and there has also been much success with that.”

However, Dr. Caplan emphasized the new data are innovative and experimental, which may control how many centers will be able to perform liver transplants in these cancer patient populations. “It has to be data driven as we are dealing with an exceedingly scarce source,” he said. “We know that people can do well, but it adds more stress to the supply of organs, and some patients may not do as well.”

He also emphasized that live donation is not a panacea. “Liver donation from a live donor is not the same as live donation for a kidney. It is much riskier and not that common. So not quite the same.”

The bottom line is that livers for transplantation are a scarce resource and transplant may work well in some cancer patients but not others, he emphasized. “Morally, we want to save lives, but not by adding in people who may not do well. If programs try to stretch the criteria, some may try transplants with more marginal organs.”

Dr. Sapisochin has disclosed relationships with Bayer, Roche, Novartis, Integra, AstraZeneca, Chiesi, Evidera, and Stryker. Dr. Ghobrial reported no relevant financial relationships. Dr. Fong has reported being a scientific consultant for Medtronic and Johnson & Johnson and receiving royalties from Merck and Imugene. Dr. Caplan writes a regular column on ethics for Medscape.

A version of this article first appeared on Medscape.com.

Correction, 4/28/23 - An earlier version of this article misstated when the patient passed away.

Liver transplant is an effective therapy for patients with primary liver cancer, and outcomes after transplantation are often superior to surgical resection. But the pool of potential patients is increasing, as transplantation is now emerging as an attractive option for select patients with nonresectable colorectal cancer (CRC) liver metastases, as well as those with intrahepatic cholangiocarcinoma (CCA).

Experts in the field highlighted some of the current challenges and opportunities in transplant oncology during a special session at the ASCO Gastrointestinal Cancers Symposium.
 

Transplant is here to stay

To date, the only curative or potentially curative therapy for patients with CRC liver metastases and intrahepatic CCA has been the combination of systemic therapies and R0 resection, said Gonzalo Sapisochin Cantis, MD, associate professor, department of surgery, University of Toronto.

The new idea is that, for patients with unresectable disease, total hepatectomy followed by a liver transplant may be a promising strategy. “This is a very hot topic in transplant oncology,” he said.

Liver transplantation is already established as the best treatment option for patients with primary hepatocellular carcinoma, which has become the main indication for liver transplantation at many centers.

For patients with CRC metastases and intrahepatic CCA, liver transplantation may help cure some patients by extending the conventional margins of surgical oncology, he suggested. “This is basically going to work in patients who have exclusive liver-restricted disease and not in those with metastatic disease. The efficacy is going to be seen by objective and sustained response to some sort of neoadjuvant therapy.”

However, Dr. Sapisochin emphasized liver transplantation is not an option for every patient. “We’re going to have to have clear inclusion and exclusion criteria that need to be defined a priori.”

Intrahepatic CCA has historically been considered a contraindication for liver transplantation. Surgical resection is the preferred first-line treatment and the only one that is potentially curative, he explained. However, most patients are not candidates for surgery, and even if they do have a resection, many of these patients will experience a recurrence, usually in the liver.

There are some studies that support transplantation in this patient population, including one by Dr. Sapisochin and colleagues. That study looked at patients who were transplanted under the assumption that they had hepatocellular carcinoma but were found to actually have intrahepatic CCA. The recurrence rate at 5 years was 18%, and 5-year survival was 65%.

“We were able to show that those patients with small tumors actually can do very well after transplant, with survivals over 70%-80%, which in this population is a very good outcome,” he said.
 

Transplant for CRC metastases

Unresectable liver metastases from colorectal cancer can also be challenging to treat, he said. Surgical resection is the only potential cure with a combination of systemic chemotherapy, but only a minority of patients are candidates for surgery.

Data supporting transplantation for CRC metastases have been emerging. One trial was conducted by researchers in Norway, who developed the Oslo score for risk stratification. “Those with risk factors had worse outcomes, and obviously, having a large tumor diameter, a high CEA (carcinoembryonic antigen), progressing on chemotherapy, or a short interval between the primary resection and the transplant were risk factors for recurrence,” Dr. Sapisochin said.

The 10-year survival among patients with a low Oslo score was 50%. “We’re talking about patients who had no resection possibility and received a transplant after systemic chemotherapy, and they had a 10-year survival of 50%,” he emphasized.

However, Dr. Sapisochin acknowledged the biggest problem transplant surgeons face is that there are not enough donor organs.

One solution is living donor liver transplantation. “Given that this is an unlimited source, you can utilize this as extended criteria and it adds another graft to the system,” he explained.

“We have a protocol for living donor liver transplantations for patients with colorectal liver metastasis,” Dr. Sapisochin said. “We’ve done seven cases so far with pretty good outcomes. One patient, unfortunately, passed away 39 months after transplant with lung metastases, but the rest are alive with no recurrence.”*
 

 

 

More available organs?

R. Mark Ghobrial, MD, PhD, director of the J.C. Walter Jr. Transplant Center at Houston Methodist Hospital, said that, 5 years ago, he was very cautious about liver transplantation for intrahepatic CCA.

He pointed out that, although transplantation for hepatocellular cancer was being done in the 1990s, the results were so poor that a moratorium was placed on the practice. “But now liver transplantation has become the definitive therapy for hepatocellular cancer, and intrahepatic cholangiocarcinoma is going the same way,” he said.

Dr. Ghobrial reiterated that one of the issues in transplantation for oncology patients is the limited supply of available organs, but he believes the landscape for liver transplantation has changed, resulting in more available organs. One factor is that hepatitis C has become curable with the advent of new therapies, and hence, the need for transplantation for patients with this disease has plummeted.

“I’ve done about maybe 800 transplants in the last 5 years. I’ve only transplanted two patients with hepatitis C,” he said. “Now we are doing more transplants for alcoholic liver disease and cancer.”

Improvements in technology are also allowing for more livers to become useable, he pointed out. One example is normothermic machine perfusion, which has entered the clinical arena in the last decade. The technique has shown promising results in improving the quality of marginal organs and increasing the pool of liver grafts.

Another factor that has increased the number of livers available for transplantation is the move to accept organs from circulatory death donors, as well as donations after brain death. “Our transplantation was about 4% of donors after cardiac death, but today this has gone up to almost 16% or 20% of the livers,” Dr. Ghobrial said. “In some centers this has gone up to about 50%.

“Liver transplantation for intrahepatic cholangiocarcinoma and colorectal cancer metastases has come of age for selected patients,” he said.



More caution needed

However, another expert urged some caution, warning that live donation carries risk. Yuman Fong, MD, a surgical oncologist with City of Hope National Medical Center, Duarte, Calif., said that around “1 in 600 live donors die from donation. That is a healthy person dying. This is not a small issue.”

He pointed out that if the criteria for transplant is greatly liberalized, the 5-year survival will not be as high as demonstrated in clinical trials.

Writing about the issue in a recent editorial, Dr. Fong pointed out that cadaveric livers for transplant remain a finite resource and that more than 1,000 patients still die every year on the waiting list for a transplant.

A more reasonable approach would be to advocate for this type of program in regions of the world where cadaveric livers are more plentiful or centers with established living donor transplant programs.

“For us to develop this resource and safeguard patients, family organ donors, and resources, we need to develop what are the best inclusion criteria,” Dr. Fong said. “We have to optimize use of all cadaveric organs and determine if we are willing to transplant borderline organs.”
 

 

 

Ethics of transplanting

Ethicist Arthur L. Caplan, PhD, the Drs. William F. and Virginia Connolly Mitty Professor of Bioethics at New York University, said this is an interesting development in the field of liver transplantation. “There have been attempts in the past, and many did not end well, such as with Steve Jobs. But transplantation is always pushing to expand eligibility, and there has also been much success with that.”

However, Dr. Caplan emphasized the new data are innovative and experimental, which may control how many centers will be able to perform liver transplants in these cancer patient populations. “It has to be data driven as we are dealing with an exceedingly scarce source,” he said. “We know that people can do well, but it adds more stress to the supply of organs, and some patients may not do as well.”

He also emphasized that live donation is not a panacea. “Liver donation from a live donor is not the same as live donation for a kidney. It is much riskier and not that common. So not quite the same.”

The bottom line is that livers for transplantation are a scarce resource and transplant may work well in some cancer patients but not others, he emphasized. “Morally, we want to save lives, but not by adding in people who may not do well. If programs try to stretch the criteria, some may try transplants with more marginal organs.”

Dr. Sapisochin has disclosed relationships with Bayer, Roche, Novartis, Integra, AstraZeneca, Chiesi, Evidera, and Stryker. Dr. Ghobrial reported no relevant financial relationships. Dr. Fong has reported being a scientific consultant for Medtronic and Johnson & Johnson and receiving royalties from Merck and Imugene. Dr. Caplan writes a regular column on ethics for Medscape.

A version of this article first appeared on Medscape.com.

Correction, 4/28/23 - An earlier version of this article misstated when the patient passed away.

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Liver disease does not worsen IVF outcomes

Article Type
Changed
Fri, 04/28/2023 - 00:35

Having chronic liver disease does not affect outcomes for women who undergo in vitro fertilization (IVF), new research suggests.

The study, published online in the American Journal of Gastroenterology, compared women with and those without chronic liver disease who had normal ovarian reserve and who underwent assisted reproductive technology (ART) treatment in a high-volume fertility practice from 2002 to 2021.

“IVF treatment and pregnancy outcomes were not significantly different compared to controls,” the researchers wrote.

Women with liver disease may experience impaired fertility. For example, women with chronic liver disease, such as hepatitis C virus infection, may have premature ovarian insufficiency, while women with advanced liver disease, cirrhosis, and hepatic decompensation are known to have abnormally low gonadotropin levels.

The prevalence of liver disease in women of reproductive age is rising, leading to “an immediate need for the clinical assessment of reproductive potential in women with chronic liver disease,” the authors wrote.

The literature about ART treatment outcomes for women with liver disease was limited and may not reflect current therapy protocols, researchers found.

“To the best of our knowledge, this study is the largest to date to evaluate IVF efficacy in women with liver disease,” they wrote.
 

Similar outcomes

Researchers identified 295 women with liver disease (mean age, 37.8 ± 5.2 years) who underwent 1,033 contemporary, standard ART treatment cycles. Six patients (2%) had cirrhosis, eight (2.7%) had undergone liver transplantation, and 281 (95.3%) had chronic liver disease, of which viral hepatitis B and C infections were the most prevalent. The final study population consisted of 115 women who underwent 186 IVF cycles, as well as embryo biopsy for genetic testing.

The control group consisted of all the women at the treatment center without liver disease who received contemporary, standard ART treatment because of male factor infertility, which served as an indication that the women had normal ovarian reserve and were considered fertile. These 624 patients underwent 868 IVF cycles with embryo biopsy.

The mean age of the patients with liver disease was significantly higher than that of the control participants. Mean body mass index was also significantly higher for the patients with liver disease, and there were differences in baseline levels of selected hormones, compared with control participants. In addition, among those with liver disease, the number of oocytes retrieved was significantly lower (12.3 ± 7.6 vs. 16.5 ± 8.2; P < .05), as were the number of mature oocytes (9.1 ± 6.2 vs. 12.6 ± 6.7; P < .05), the number of fertilized embryos (7.0 ± 5.2 vs. 9.9 ± 5.9; P < .05), the number of embryos for which biopsy was performed (3.4 ± 2.2 vs. 5.1 ± 3.5; P < .05), and the number of euploid embryos (1.6 ± 1.4 vs. 2.7 ± 2.4; P < .05), compared with control participants.

Among the two groups, there were no statistically significant differences in mature oocyte rate (an indicator of response to controlled ovarian stimulation), fertilization per mature oocyte rate (an indicator of oocyte quality and ability to be fertilized), or embryo ploidy rate (an indicator of genetically normal embryos), as determined by embryo biopsy, the researchers write.

A subanalysis of women who went on to have a single thawed euploid (chromosomally normal) embryo transfer to achieve pregnancy found no statistically significant differences in rates of clinical pregnancy, clinical pregnancy loss, or live births between the liver disease group and the control group.

“Overall, women with chronic liver disease can be counseled that IVF treatment will not significantly differ in response to controlled ovarian stimulation, embryo fertilization rate, or ploidy outcome compared to women without liver disease,” the researchers wrote.
 

 

 

Data for patient counseling

The results could change the current common thinking among clinicians that IVF should not be conducted until liver disease is under optimal control, first author Jessica Lee, BS, a student at Icahn School of Medicine at Mount Sinai, New York, said.

“There was a knowledge gap for studies in the United States, and we hope this study will not only help patients with liver disease but also providers with counseling,” she said.

The findings suggest that “even if you have chronic liver disease and it’s not fully optimized, that should not interfere with pursuing IVF,” said principal investigator Tatyana Kushner, MD, an associate professor of medicine in liver diseases at the Icahn School.

Women with liver disease whose fertility is impaired should receive counseling about fertility preservation options earlier to help access fertility care, the researchers write.

The study’s findings are “encouraging,” said Monika Sarkar, MD, associate professor of medicine in gastroenterology at the University of California, San Francisco.

“With rising numbers of young adults with liver disease, it is encouraging to see dedicated studies that address a topic of importance to our patients – namely, their reproductive health,” she said. “The current study nicely expands beyond previous data to include a control population without liver disease.”
 

Differences in oocyte numbers

Although there were no differences in the success rate of embryo transfer, the researchers did see differences in the number of oocytes. Only 37 mature oocytes made it to transfer in the liver disease group, compared with 609 in the control group, noted Dr. Sarkar, who was not involved with the study.

“The challenge of ART is less at the level of embryo transfer, which is very successful once a euploid embryo is achieved, but rather at the earlier step of retrieval of mature oocytes,” Dr. Sarkar said. “Here, the authors found that patients with liver disease had a significantly lower number of oocytes retrieved, number of mature oocytes, and lower number of fertilized embryos.”

The data suggest that fewer eggs are retrieved per cycle from patients with liver disease, “which ultimately will lower the success per cycle,” Dr. Sarkar said.

“This suggests that referring women with chronic liver disease to ART sooner may help to optimize outcomes,” she added. “Larger data evaluating ability to achieve mature oocytes and subsequent fertilization will also be key for determining whether ART success differs by presence, severity, and type of liver disease.”

As more research on ART outcomes in women with liver disease is conducted, subspecialists in gastrointestinal and liver disease may gain confidence in counseling patients, Dr. Sarkar said.

Ms. Lee, Dr. Kushner, and Dr. Sarkar report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

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Having chronic liver disease does not affect outcomes for women who undergo in vitro fertilization (IVF), new research suggests.

The study, published online in the American Journal of Gastroenterology, compared women with and those without chronic liver disease who had normal ovarian reserve and who underwent assisted reproductive technology (ART) treatment in a high-volume fertility practice from 2002 to 2021.

“IVF treatment and pregnancy outcomes were not significantly different compared to controls,” the researchers wrote.

Women with liver disease may experience impaired fertility. For example, women with chronic liver disease, such as hepatitis C virus infection, may have premature ovarian insufficiency, while women with advanced liver disease, cirrhosis, and hepatic decompensation are known to have abnormally low gonadotropin levels.

The prevalence of liver disease in women of reproductive age is rising, leading to “an immediate need for the clinical assessment of reproductive potential in women with chronic liver disease,” the authors wrote.

The literature about ART treatment outcomes for women with liver disease was limited and may not reflect current therapy protocols, researchers found.

“To the best of our knowledge, this study is the largest to date to evaluate IVF efficacy in women with liver disease,” they wrote.
 

Similar outcomes

Researchers identified 295 women with liver disease (mean age, 37.8 ± 5.2 years) who underwent 1,033 contemporary, standard ART treatment cycles. Six patients (2%) had cirrhosis, eight (2.7%) had undergone liver transplantation, and 281 (95.3%) had chronic liver disease, of which viral hepatitis B and C infections were the most prevalent. The final study population consisted of 115 women who underwent 186 IVF cycles, as well as embryo biopsy for genetic testing.

The control group consisted of all the women at the treatment center without liver disease who received contemporary, standard ART treatment because of male factor infertility, which served as an indication that the women had normal ovarian reserve and were considered fertile. These 624 patients underwent 868 IVF cycles with embryo biopsy.

The mean age of the patients with liver disease was significantly higher than that of the control participants. Mean body mass index was also significantly higher for the patients with liver disease, and there were differences in baseline levels of selected hormones, compared with control participants. In addition, among those with liver disease, the number of oocytes retrieved was significantly lower (12.3 ± 7.6 vs. 16.5 ± 8.2; P < .05), as were the number of mature oocytes (9.1 ± 6.2 vs. 12.6 ± 6.7; P < .05), the number of fertilized embryos (7.0 ± 5.2 vs. 9.9 ± 5.9; P < .05), the number of embryos for which biopsy was performed (3.4 ± 2.2 vs. 5.1 ± 3.5; P < .05), and the number of euploid embryos (1.6 ± 1.4 vs. 2.7 ± 2.4; P < .05), compared with control participants.

Among the two groups, there were no statistically significant differences in mature oocyte rate (an indicator of response to controlled ovarian stimulation), fertilization per mature oocyte rate (an indicator of oocyte quality and ability to be fertilized), or embryo ploidy rate (an indicator of genetically normal embryos), as determined by embryo biopsy, the researchers write.

A subanalysis of women who went on to have a single thawed euploid (chromosomally normal) embryo transfer to achieve pregnancy found no statistically significant differences in rates of clinical pregnancy, clinical pregnancy loss, or live births between the liver disease group and the control group.

“Overall, women with chronic liver disease can be counseled that IVF treatment will not significantly differ in response to controlled ovarian stimulation, embryo fertilization rate, or ploidy outcome compared to women without liver disease,” the researchers wrote.
 

 

 

Data for patient counseling

The results could change the current common thinking among clinicians that IVF should not be conducted until liver disease is under optimal control, first author Jessica Lee, BS, a student at Icahn School of Medicine at Mount Sinai, New York, said.

“There was a knowledge gap for studies in the United States, and we hope this study will not only help patients with liver disease but also providers with counseling,” she said.

The findings suggest that “even if you have chronic liver disease and it’s not fully optimized, that should not interfere with pursuing IVF,” said principal investigator Tatyana Kushner, MD, an associate professor of medicine in liver diseases at the Icahn School.

Women with liver disease whose fertility is impaired should receive counseling about fertility preservation options earlier to help access fertility care, the researchers write.

The study’s findings are “encouraging,” said Monika Sarkar, MD, associate professor of medicine in gastroenterology at the University of California, San Francisco.

“With rising numbers of young adults with liver disease, it is encouraging to see dedicated studies that address a topic of importance to our patients – namely, their reproductive health,” she said. “The current study nicely expands beyond previous data to include a control population without liver disease.”
 

Differences in oocyte numbers

Although there were no differences in the success rate of embryo transfer, the researchers did see differences in the number of oocytes. Only 37 mature oocytes made it to transfer in the liver disease group, compared with 609 in the control group, noted Dr. Sarkar, who was not involved with the study.

“The challenge of ART is less at the level of embryo transfer, which is very successful once a euploid embryo is achieved, but rather at the earlier step of retrieval of mature oocytes,” Dr. Sarkar said. “Here, the authors found that patients with liver disease had a significantly lower number of oocytes retrieved, number of mature oocytes, and lower number of fertilized embryos.”

The data suggest that fewer eggs are retrieved per cycle from patients with liver disease, “which ultimately will lower the success per cycle,” Dr. Sarkar said.

“This suggests that referring women with chronic liver disease to ART sooner may help to optimize outcomes,” she added. “Larger data evaluating ability to achieve mature oocytes and subsequent fertilization will also be key for determining whether ART success differs by presence, severity, and type of liver disease.”

As more research on ART outcomes in women with liver disease is conducted, subspecialists in gastrointestinal and liver disease may gain confidence in counseling patients, Dr. Sarkar said.

Ms. Lee, Dr. Kushner, and Dr. Sarkar report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Having chronic liver disease does not affect outcomes for women who undergo in vitro fertilization (IVF), new research suggests.

The study, published online in the American Journal of Gastroenterology, compared women with and those without chronic liver disease who had normal ovarian reserve and who underwent assisted reproductive technology (ART) treatment in a high-volume fertility practice from 2002 to 2021.

“IVF treatment and pregnancy outcomes were not significantly different compared to controls,” the researchers wrote.

Women with liver disease may experience impaired fertility. For example, women with chronic liver disease, such as hepatitis C virus infection, may have premature ovarian insufficiency, while women with advanced liver disease, cirrhosis, and hepatic decompensation are known to have abnormally low gonadotropin levels.

The prevalence of liver disease in women of reproductive age is rising, leading to “an immediate need for the clinical assessment of reproductive potential in women with chronic liver disease,” the authors wrote.

The literature about ART treatment outcomes for women with liver disease was limited and may not reflect current therapy protocols, researchers found.

“To the best of our knowledge, this study is the largest to date to evaluate IVF efficacy in women with liver disease,” they wrote.
 

Similar outcomes

Researchers identified 295 women with liver disease (mean age, 37.8 ± 5.2 years) who underwent 1,033 contemporary, standard ART treatment cycles. Six patients (2%) had cirrhosis, eight (2.7%) had undergone liver transplantation, and 281 (95.3%) had chronic liver disease, of which viral hepatitis B and C infections were the most prevalent. The final study population consisted of 115 women who underwent 186 IVF cycles, as well as embryo biopsy for genetic testing.

The control group consisted of all the women at the treatment center without liver disease who received contemporary, standard ART treatment because of male factor infertility, which served as an indication that the women had normal ovarian reserve and were considered fertile. These 624 patients underwent 868 IVF cycles with embryo biopsy.

The mean age of the patients with liver disease was significantly higher than that of the control participants. Mean body mass index was also significantly higher for the patients with liver disease, and there were differences in baseline levels of selected hormones, compared with control participants. In addition, among those with liver disease, the number of oocytes retrieved was significantly lower (12.3 ± 7.6 vs. 16.5 ± 8.2; P < .05), as were the number of mature oocytes (9.1 ± 6.2 vs. 12.6 ± 6.7; P < .05), the number of fertilized embryos (7.0 ± 5.2 vs. 9.9 ± 5.9; P < .05), the number of embryos for which biopsy was performed (3.4 ± 2.2 vs. 5.1 ± 3.5; P < .05), and the number of euploid embryos (1.6 ± 1.4 vs. 2.7 ± 2.4; P < .05), compared with control participants.

Among the two groups, there were no statistically significant differences in mature oocyte rate (an indicator of response to controlled ovarian stimulation), fertilization per mature oocyte rate (an indicator of oocyte quality and ability to be fertilized), or embryo ploidy rate (an indicator of genetically normal embryos), as determined by embryo biopsy, the researchers write.

A subanalysis of women who went on to have a single thawed euploid (chromosomally normal) embryo transfer to achieve pregnancy found no statistically significant differences in rates of clinical pregnancy, clinical pregnancy loss, or live births between the liver disease group and the control group.

“Overall, women with chronic liver disease can be counseled that IVF treatment will not significantly differ in response to controlled ovarian stimulation, embryo fertilization rate, or ploidy outcome compared to women without liver disease,” the researchers wrote.
 

 

 

Data for patient counseling

The results could change the current common thinking among clinicians that IVF should not be conducted until liver disease is under optimal control, first author Jessica Lee, BS, a student at Icahn School of Medicine at Mount Sinai, New York, said.

“There was a knowledge gap for studies in the United States, and we hope this study will not only help patients with liver disease but also providers with counseling,” she said.

The findings suggest that “even if you have chronic liver disease and it’s not fully optimized, that should not interfere with pursuing IVF,” said principal investigator Tatyana Kushner, MD, an associate professor of medicine in liver diseases at the Icahn School.

Women with liver disease whose fertility is impaired should receive counseling about fertility preservation options earlier to help access fertility care, the researchers write.

The study’s findings are “encouraging,” said Monika Sarkar, MD, associate professor of medicine in gastroenterology at the University of California, San Francisco.

“With rising numbers of young adults with liver disease, it is encouraging to see dedicated studies that address a topic of importance to our patients – namely, their reproductive health,” she said. “The current study nicely expands beyond previous data to include a control population without liver disease.”
 

Differences in oocyte numbers

Although there were no differences in the success rate of embryo transfer, the researchers did see differences in the number of oocytes. Only 37 mature oocytes made it to transfer in the liver disease group, compared with 609 in the control group, noted Dr. Sarkar, who was not involved with the study.

“The challenge of ART is less at the level of embryo transfer, which is very successful once a euploid embryo is achieved, but rather at the earlier step of retrieval of mature oocytes,” Dr. Sarkar said. “Here, the authors found that patients with liver disease had a significantly lower number of oocytes retrieved, number of mature oocytes, and lower number of fertilized embryos.”

The data suggest that fewer eggs are retrieved per cycle from patients with liver disease, “which ultimately will lower the success per cycle,” Dr. Sarkar said.

“This suggests that referring women with chronic liver disease to ART sooner may help to optimize outcomes,” she added. “Larger data evaluating ability to achieve mature oocytes and subsequent fertilization will also be key for determining whether ART success differs by presence, severity, and type of liver disease.”

As more research on ART outcomes in women with liver disease is conducted, subspecialists in gastrointestinal and liver disease may gain confidence in counseling patients, Dr. Sarkar said.

Ms. Lee, Dr. Kushner, and Dr. Sarkar report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

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FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY

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RA causally associated with ischemic heart disease and myocardial infarction

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Key clinical point: Rheumatoid arthritis (RA) is associated with a significant increase in the risk for ischemic heart disease (IHD) and myocardial infarction (MI), and managing RA activity may reduce the risk for cardiovascular diseases.

 

Major finding: RA is significantly associated with an increased risk for IHD (odds ratio [OR] 1.0006; P  =  .001551915) and MI (OR 1.0458; P  =  .001636), but not arrhythmia and atrial fibrillation.

 

Study details: Findings are from a two-sample Mendelian randomization study including patients and matched control individuals for RA (n = 14,361 and n = 43,923, respectively), MI (n = 12,801 and n = 187,840, respectively), IHD (n = 5861 and n = 457,149, respectively), atrial fibrillation (n = 60,620 and n = 970,216, respectively), and arrhythmia (n = 2545 and n = 460,388, respectively).

 

Disclosures: This study was supported by the Young Talent Development Plan of Changzhou Health Commission, China, and other sources. The authors declared no conflicts of interest.

 

Source: Wang M et al. Relationship between rheumatoid arthritis and cardiovascular comorbidity, causation or co-occurrence: A Mendelian randomization study. Front Cardiovasc Med. 2023;10:1099861 (Mar 17). Doi: 10.3389/fcvm.2023.1099861

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Key clinical point: Rheumatoid arthritis (RA) is associated with a significant increase in the risk for ischemic heart disease (IHD) and myocardial infarction (MI), and managing RA activity may reduce the risk for cardiovascular diseases.

 

Major finding: RA is significantly associated with an increased risk for IHD (odds ratio [OR] 1.0006; P  =  .001551915) and MI (OR 1.0458; P  =  .001636), but not arrhythmia and atrial fibrillation.

 

Study details: Findings are from a two-sample Mendelian randomization study including patients and matched control individuals for RA (n = 14,361 and n = 43,923, respectively), MI (n = 12,801 and n = 187,840, respectively), IHD (n = 5861 and n = 457,149, respectively), atrial fibrillation (n = 60,620 and n = 970,216, respectively), and arrhythmia (n = 2545 and n = 460,388, respectively).

 

Disclosures: This study was supported by the Young Talent Development Plan of Changzhou Health Commission, China, and other sources. The authors declared no conflicts of interest.

 

Source: Wang M et al. Relationship between rheumatoid arthritis and cardiovascular comorbidity, causation or co-occurrence: A Mendelian randomization study. Front Cardiovasc Med. 2023;10:1099861 (Mar 17). Doi: 10.3389/fcvm.2023.1099861

Key clinical point: Rheumatoid arthritis (RA) is associated with a significant increase in the risk for ischemic heart disease (IHD) and myocardial infarction (MI), and managing RA activity may reduce the risk for cardiovascular diseases.

 

Major finding: RA is significantly associated with an increased risk for IHD (odds ratio [OR] 1.0006; P  =  .001551915) and MI (OR 1.0458; P  =  .001636), but not arrhythmia and atrial fibrillation.

 

Study details: Findings are from a two-sample Mendelian randomization study including patients and matched control individuals for RA (n = 14,361 and n = 43,923, respectively), MI (n = 12,801 and n = 187,840, respectively), IHD (n = 5861 and n = 457,149, respectively), atrial fibrillation (n = 60,620 and n = 970,216, respectively), and arrhythmia (n = 2545 and n = 460,388, respectively).

 

Disclosures: This study was supported by the Young Talent Development Plan of Changzhou Health Commission, China, and other sources. The authors declared no conflicts of interest.

 

Source: Wang M et al. Relationship between rheumatoid arthritis and cardiovascular comorbidity, causation or co-occurrence: A Mendelian randomization study. Front Cardiovasc Med. 2023;10:1099861 (Mar 17). Doi: 10.3389/fcvm.2023.1099861

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Mortality risk accrues with time after diagnosis of RA

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Key clinical point: Mortality risk varied with time and increased only during the second not the first decade after the diagnosis of rheumatoid arthritis (RA), with respiratory diseases potentially surpassing cardiovascular diseases as major attributable factors.

 

Major finding: Increase in mortality was observed at 20 years (standardized mortality ratio [SMR] 1.49; P < .001) but not during the first 10 years (P  =  .44) after RA diagnosis, with pneumonia (cause-specific SMR 5.22; 95% CI 2.26-10.29) and interstitial lung disease (cause-specific SMR 7.64; 95% CI 2.98-14.69) being major contributors.

 

Study details: Findings are from an analysis of 1895 patients with RA from the Australian Rheumatology Association Database (ARAD) registry who received biologic, targeted synthetic, or conventional synthetic disease-modifying antirheumatic drugs.

 

Disclosures: ARAD received support through the Australian Rheumatology Association from various sources. Three authors declared receiving grants, funding, or honoraria from different sources unrelated to this study.

 

Source: Black RJ et al. Mortality estimates and excess mortality in rheumatoid arthritis. Rheumatology (Oxford). 2023 (Mar 15). Doi: 10.1093/rheumatology/kead106

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Key clinical point: Mortality risk varied with time and increased only during the second not the first decade after the diagnosis of rheumatoid arthritis (RA), with respiratory diseases potentially surpassing cardiovascular diseases as major attributable factors.

 

Major finding: Increase in mortality was observed at 20 years (standardized mortality ratio [SMR] 1.49; P < .001) but not during the first 10 years (P  =  .44) after RA diagnosis, with pneumonia (cause-specific SMR 5.22; 95% CI 2.26-10.29) and interstitial lung disease (cause-specific SMR 7.64; 95% CI 2.98-14.69) being major contributors.

 

Study details: Findings are from an analysis of 1895 patients with RA from the Australian Rheumatology Association Database (ARAD) registry who received biologic, targeted synthetic, or conventional synthetic disease-modifying antirheumatic drugs.

 

Disclosures: ARAD received support through the Australian Rheumatology Association from various sources. Three authors declared receiving grants, funding, or honoraria from different sources unrelated to this study.

 

Source: Black RJ et al. Mortality estimates and excess mortality in rheumatoid arthritis. Rheumatology (Oxford). 2023 (Mar 15). Doi: 10.1093/rheumatology/kead106

Key clinical point: Mortality risk varied with time and increased only during the second not the first decade after the diagnosis of rheumatoid arthritis (RA), with respiratory diseases potentially surpassing cardiovascular diseases as major attributable factors.

 

Major finding: Increase in mortality was observed at 20 years (standardized mortality ratio [SMR] 1.49; P < .001) but not during the first 10 years (P  =  .44) after RA diagnosis, with pneumonia (cause-specific SMR 5.22; 95% CI 2.26-10.29) and interstitial lung disease (cause-specific SMR 7.64; 95% CI 2.98-14.69) being major contributors.

 

Study details: Findings are from an analysis of 1895 patients with RA from the Australian Rheumatology Association Database (ARAD) registry who received biologic, targeted synthetic, or conventional synthetic disease-modifying antirheumatic drugs.

 

Disclosures: ARAD received support through the Australian Rheumatology Association from various sources. Three authors declared receiving grants, funding, or honoraria from different sources unrelated to this study.

 

Source: Black RJ et al. Mortality estimates and excess mortality in rheumatoid arthritis. Rheumatology (Oxford). 2023 (Mar 15). Doi: 10.1093/rheumatology/kead106

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RA raises risk for bronchial asthma and asthma-related comorbidities

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Key clinical point: Rheumatoid arthritis (RA) was significantly associated with an increased risk for bronchial asthma, allergic rhinitis, and sinusitis, and a notable interrelation was observed between the presence of asthma and obesity in patients with RA.

 

Major finding: Presence of RA significantly increased the risk for asthma (odds ratio [OR] 2.32; 95% CI 1.51-3.57), allergic rhinitis (OR 1.51; 95% CI 1.08-2.10), and sinusitis (OR 1.64; 95% CI 1.08-2.50) in the whole cohort and the prevalence of obesity in patients with asthma (64.0% vs 40.2%; P  =  .034).

 

Study details: This population-based cross-sectional study included 14,272 participants, of which 334 had RA.

 

Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korean Government. The authors declared no conflicts of interest.

 

Source: Kim JG et al. Association of rheumatoid arthritis with bronchial asthma and asthma-related comorbidities: A population-based national surveillance study. Front Med (Lausanne). 2023;10:1006290 (Mar 10). Doi: 10.3389/fmed.2023.1006290

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Key clinical point: Rheumatoid arthritis (RA) was significantly associated with an increased risk for bronchial asthma, allergic rhinitis, and sinusitis, and a notable interrelation was observed between the presence of asthma and obesity in patients with RA.

 

Major finding: Presence of RA significantly increased the risk for asthma (odds ratio [OR] 2.32; 95% CI 1.51-3.57), allergic rhinitis (OR 1.51; 95% CI 1.08-2.10), and sinusitis (OR 1.64; 95% CI 1.08-2.50) in the whole cohort and the prevalence of obesity in patients with asthma (64.0% vs 40.2%; P  =  .034).

 

Study details: This population-based cross-sectional study included 14,272 participants, of which 334 had RA.

 

Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korean Government. The authors declared no conflicts of interest.

 

Source: Kim JG et al. Association of rheumatoid arthritis with bronchial asthma and asthma-related comorbidities: A population-based national surveillance study. Front Med (Lausanne). 2023;10:1006290 (Mar 10). Doi: 10.3389/fmed.2023.1006290

Key clinical point: Rheumatoid arthritis (RA) was significantly associated with an increased risk for bronchial asthma, allergic rhinitis, and sinusitis, and a notable interrelation was observed between the presence of asthma and obesity in patients with RA.

 

Major finding: Presence of RA significantly increased the risk for asthma (odds ratio [OR] 2.32; 95% CI 1.51-3.57), allergic rhinitis (OR 1.51; 95% CI 1.08-2.10), and sinusitis (OR 1.64; 95% CI 1.08-2.50) in the whole cohort and the prevalence of obesity in patients with asthma (64.0% vs 40.2%; P  =  .034).

 

Study details: This population-based cross-sectional study included 14,272 participants, of which 334 had RA.

 

Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korean Government. The authors declared no conflicts of interest.

 

Source: Kim JG et al. Association of rheumatoid arthritis with bronchial asthma and asthma-related comorbidities: A population-based national surveillance study. Front Med (Lausanne). 2023;10:1006290 (Mar 10). Doi: 10.3389/fmed.2023.1006290

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Meta-analysis reveals superior efficacy and safety outcomes with abatacept in RA

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Key clinical point: Abatacept with or without conventional synthetic disease-modifying antirheumatic drugs (csDMARD) demonstrated better efficacy and favorable safety outcomes compared with placebo, csDMARD, or other biologic DMARD (bDMARD) in patients with rheumatoid arthritis (RA).

 

Major finding: Patients treated with abatacept with or without csDMARD vs placebo, csDMARD, or other bDMARD were more likely to achieve American College of Rheumatology (ACR) 20 (relative risk [RR] 1.57; 95% CI 1.27-1.93), ACR50 (RR 1.84; 95% CI 1.38-2.44), and ACR70 (RR 2.36; 95% CI 1.60-3.47) responses, as well as were less likely to experience adverse events (RR 0.93; 95% CI 0.84-1.03).

 

Study details: Findings are from a systematic review and meta-analysis of 13 randomized controlled trials including 5978 patients with RA who were randomly assigned to receive abatacept alone, abatacept with csDMARD, placebo, csDMARD, or other bDMARD.

 

Disclosures: This study was supported by the National Key R&D Program of China. The authors did not report conflicts of interest.

 

Source: Ahamada MM and Wu X. Analysis of efficacy and safety of abatacept for rheumatoid arthritis: Systematic review and meta-analysis. Clin Exp Rheumatol. 2023 (Mar 7). Doi: 10.55563/clinexprheumatol/2xjg0d

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Key clinical point: Abatacept with or without conventional synthetic disease-modifying antirheumatic drugs (csDMARD) demonstrated better efficacy and favorable safety outcomes compared with placebo, csDMARD, or other biologic DMARD (bDMARD) in patients with rheumatoid arthritis (RA).

 

Major finding: Patients treated with abatacept with or without csDMARD vs placebo, csDMARD, or other bDMARD were more likely to achieve American College of Rheumatology (ACR) 20 (relative risk [RR] 1.57; 95% CI 1.27-1.93), ACR50 (RR 1.84; 95% CI 1.38-2.44), and ACR70 (RR 2.36; 95% CI 1.60-3.47) responses, as well as were less likely to experience adverse events (RR 0.93; 95% CI 0.84-1.03).

 

Study details: Findings are from a systematic review and meta-analysis of 13 randomized controlled trials including 5978 patients with RA who were randomly assigned to receive abatacept alone, abatacept with csDMARD, placebo, csDMARD, or other bDMARD.

 

Disclosures: This study was supported by the National Key R&D Program of China. The authors did not report conflicts of interest.

 

Source: Ahamada MM and Wu X. Analysis of efficacy and safety of abatacept for rheumatoid arthritis: Systematic review and meta-analysis. Clin Exp Rheumatol. 2023 (Mar 7). Doi: 10.55563/clinexprheumatol/2xjg0d

Key clinical point: Abatacept with or without conventional synthetic disease-modifying antirheumatic drugs (csDMARD) demonstrated better efficacy and favorable safety outcomes compared with placebo, csDMARD, or other biologic DMARD (bDMARD) in patients with rheumatoid arthritis (RA).

 

Major finding: Patients treated with abatacept with or without csDMARD vs placebo, csDMARD, or other bDMARD were more likely to achieve American College of Rheumatology (ACR) 20 (relative risk [RR] 1.57; 95% CI 1.27-1.93), ACR50 (RR 1.84; 95% CI 1.38-2.44), and ACR70 (RR 2.36; 95% CI 1.60-3.47) responses, as well as were less likely to experience adverse events (RR 0.93; 95% CI 0.84-1.03).

 

Study details: Findings are from a systematic review and meta-analysis of 13 randomized controlled trials including 5978 patients with RA who were randomly assigned to receive abatacept alone, abatacept with csDMARD, placebo, csDMARD, or other bDMARD.

 

Disclosures: This study was supported by the National Key R&D Program of China. The authors did not report conflicts of interest.

 

Source: Ahamada MM and Wu X. Analysis of efficacy and safety of abatacept for rheumatoid arthritis: Systematic review and meta-analysis. Clin Exp Rheumatol. 2023 (Mar 7). Doi: 10.55563/clinexprheumatol/2xjg0d

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Factors to guide individualized benefit-risk assessment and decision-making with tofacitinib in RA

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Key clinical point: Factors like age ≥65 years or current or former smoking accounted for excess risk with tofacitinib vs tumor necrosis factor inhibitor (TNFi) use in patients with rheumatoid arthritis (RA).

 

Major finding: Tofacitinib vs TNFi significantly increased the risk for malignancies (hazard ratio [HR] 1.55; 95% CI 1.05-2.30), venous thromboembolism (HR 5.19; 95% CI 1.86-14.46), and all-cause death (HR 2.24; 95% CI 1.20-4.19) among patients who were ≥65 years old or ever smokers, but not among those aged <65 years and never smokers.

 

Study details: Findings are from a post hoc analysis of the ORAL Surveillance trial including patients with RA (n = 4362) treated with tofacitinib or TNFi and an exploratory analysis of RA, PsA, and ulcerative colitis (UC) development programs including tofacitinib-exposed patients with RA (n = 7964), psoriatic arthritis (n = 783), and UC (n = 1157).

 

Disclosures: This study was sponsored by Pfizer Inc. Six authors declared being employees and stockholders of Pfizer. Two authors declared receiving speaking, consulting, or lecture fees or research grants from Pfizer and other sources.

 

Source: Kristensen LE et al. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: An analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 (Mar 17). Doi: 10.1136/ard-2022-223715

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Key clinical point: Factors like age ≥65 years or current or former smoking accounted for excess risk with tofacitinib vs tumor necrosis factor inhibitor (TNFi) use in patients with rheumatoid arthritis (RA).

 

Major finding: Tofacitinib vs TNFi significantly increased the risk for malignancies (hazard ratio [HR] 1.55; 95% CI 1.05-2.30), venous thromboembolism (HR 5.19; 95% CI 1.86-14.46), and all-cause death (HR 2.24; 95% CI 1.20-4.19) among patients who were ≥65 years old or ever smokers, but not among those aged <65 years and never smokers.

 

Study details: Findings are from a post hoc analysis of the ORAL Surveillance trial including patients with RA (n = 4362) treated with tofacitinib or TNFi and an exploratory analysis of RA, PsA, and ulcerative colitis (UC) development programs including tofacitinib-exposed patients with RA (n = 7964), psoriatic arthritis (n = 783), and UC (n = 1157).

 

Disclosures: This study was sponsored by Pfizer Inc. Six authors declared being employees and stockholders of Pfizer. Two authors declared receiving speaking, consulting, or lecture fees or research grants from Pfizer and other sources.

 

Source: Kristensen LE et al. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: An analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 (Mar 17). Doi: 10.1136/ard-2022-223715

Key clinical point: Factors like age ≥65 years or current or former smoking accounted for excess risk with tofacitinib vs tumor necrosis factor inhibitor (TNFi) use in patients with rheumatoid arthritis (RA).

 

Major finding: Tofacitinib vs TNFi significantly increased the risk for malignancies (hazard ratio [HR] 1.55; 95% CI 1.05-2.30), venous thromboembolism (HR 5.19; 95% CI 1.86-14.46), and all-cause death (HR 2.24; 95% CI 1.20-4.19) among patients who were ≥65 years old or ever smokers, but not among those aged <65 years and never smokers.

 

Study details: Findings are from a post hoc analysis of the ORAL Surveillance trial including patients with RA (n = 4362) treated with tofacitinib or TNFi and an exploratory analysis of RA, PsA, and ulcerative colitis (UC) development programs including tofacitinib-exposed patients with RA (n = 7964), psoriatic arthritis (n = 783), and UC (n = 1157).

 

Disclosures: This study was sponsored by Pfizer Inc. Six authors declared being employees and stockholders of Pfizer. Two authors declared receiving speaking, consulting, or lecture fees or research grants from Pfizer and other sources.

 

Source: Kristensen LE et al. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: An analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 (Mar 17). Doi: 10.1136/ard-2022-223715

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RA onset after initiating bDMARD raises risk for severe infections

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Key clinical point: Risk for severe infections significantly increased in patients who were newly diagnosed with rheumatoid arthritis (RA) after initiating biologic disease-modifying antirheumatic drugs (bDMARD).

 

Major finding: Over a period of 8 years, severe infection rates significantly increased in patients who were newly diagnosed with RA after initiating bDMARD (adjusted difference between pre- and post-bDMARD rates [Δ] 1.85; P  =  .001), whereas no significant change was observed in control individuals from the general population (Δ 0.12; P  =  .29).

 

Study details: Findings are from a population-based retrospective cohort study including 60,226 patients with newly diagnosed RA and 588,499 age- and sex-matched control individuals without any inflammatory arthritis from the general population who initiated bDMARD.

 

Disclosures: This study was supported by the Canadian Institute of Health Research and other sources. The authors declared no conflicts of interest.

 

Source: Zhou VY et al. Risk of severe infections after the introduction of biologic DMARDs in people with newly diagnosed rheumatoid arthritis: A population-based interrupted time-series analysis. Rheumatology (Oxford). 2023 (Apr 4). Doi: 10.1093/rheumatology/kead158

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Key clinical point: Risk for severe infections significantly increased in patients who were newly diagnosed with rheumatoid arthritis (RA) after initiating biologic disease-modifying antirheumatic drugs (bDMARD).

 

Major finding: Over a period of 8 years, severe infection rates significantly increased in patients who were newly diagnosed with RA after initiating bDMARD (adjusted difference between pre- and post-bDMARD rates [Δ] 1.85; P  =  .001), whereas no significant change was observed in control individuals from the general population (Δ 0.12; P  =  .29).

 

Study details: Findings are from a population-based retrospective cohort study including 60,226 patients with newly diagnosed RA and 588,499 age- and sex-matched control individuals without any inflammatory arthritis from the general population who initiated bDMARD.

 

Disclosures: This study was supported by the Canadian Institute of Health Research and other sources. The authors declared no conflicts of interest.

 

Source: Zhou VY et al. Risk of severe infections after the introduction of biologic DMARDs in people with newly diagnosed rheumatoid arthritis: A population-based interrupted time-series analysis. Rheumatology (Oxford). 2023 (Apr 4). Doi: 10.1093/rheumatology/kead158

Key clinical point: Risk for severe infections significantly increased in patients who were newly diagnosed with rheumatoid arthritis (RA) after initiating biologic disease-modifying antirheumatic drugs (bDMARD).

 

Major finding: Over a period of 8 years, severe infection rates significantly increased in patients who were newly diagnosed with RA after initiating bDMARD (adjusted difference between pre- and post-bDMARD rates [Δ] 1.85; P  =  .001), whereas no significant change was observed in control individuals from the general population (Δ 0.12; P  =  .29).

 

Study details: Findings are from a population-based retrospective cohort study including 60,226 patients with newly diagnosed RA and 588,499 age- and sex-matched control individuals without any inflammatory arthritis from the general population who initiated bDMARD.

 

Disclosures: This study was supported by the Canadian Institute of Health Research and other sources. The authors declared no conflicts of interest.

 

Source: Zhou VY et al. Risk of severe infections after the introduction of biologic DMARDs in people with newly diagnosed rheumatoid arthritis: A population-based interrupted time-series analysis. Rheumatology (Oxford). 2023 (Apr 4). Doi: 10.1093/rheumatology/kead158

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Tofacitinib associated with reduced risk of developing ILD in patients with RA

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Key clinical point: Patients with rheumatoid arthritis (RA) treated with tofacitinib had a 69% lower risk of developing interstitial lung disease (ILD) than those treated with adalimumab.

 

Major finding: Compared with adalimumab, tofacitinib resulted in the lowest incidence of ILD (incidence rate ratio 0.43; 95% CI 0.18-1.05), followed by abatacept, tocilizumab, and rituximab. Tofacitinib was associated with a significant 69% reduced risk of developing ILD compared with adalimumab (adjusted hazard ratio 0.31; P  =  .009).

 

Study details: Findings are from a retrospective cohort study including 28,559 patients with RA without preexisting ILD who were newly administered adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib, of which 276 patients were diagnosed with incident ILD.

 

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors did not report conflicts of interest.

 

Source: Baker MC et al. Incidence of interstitial lung disease in patients with rheumatoid arthritis treated with biologic and targeted synthetic disease-modifying antirheumatic drugs. JAMA Netw Open. 2023;6(3):e233640 (Mar 20). Doi: 10.1001/jamanetworkopen.2023.3640

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Key clinical point: Patients with rheumatoid arthritis (RA) treated with tofacitinib had a 69% lower risk of developing interstitial lung disease (ILD) than those treated with adalimumab.

 

Major finding: Compared with adalimumab, tofacitinib resulted in the lowest incidence of ILD (incidence rate ratio 0.43; 95% CI 0.18-1.05), followed by abatacept, tocilizumab, and rituximab. Tofacitinib was associated with a significant 69% reduced risk of developing ILD compared with adalimumab (adjusted hazard ratio 0.31; P  =  .009).

 

Study details: Findings are from a retrospective cohort study including 28,559 patients with RA without preexisting ILD who were newly administered adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib, of which 276 patients were diagnosed with incident ILD.

 

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors did not report conflicts of interest.

 

Source: Baker MC et al. Incidence of interstitial lung disease in patients with rheumatoid arthritis treated with biologic and targeted synthetic disease-modifying antirheumatic drugs. JAMA Netw Open. 2023;6(3):e233640 (Mar 20). Doi: 10.1001/jamanetworkopen.2023.3640

Key clinical point: Patients with rheumatoid arthritis (RA) treated with tofacitinib had a 69% lower risk of developing interstitial lung disease (ILD) than those treated with adalimumab.

 

Major finding: Compared with adalimumab, tofacitinib resulted in the lowest incidence of ILD (incidence rate ratio 0.43; 95% CI 0.18-1.05), followed by abatacept, tocilizumab, and rituximab. Tofacitinib was associated with a significant 69% reduced risk of developing ILD compared with adalimumab (adjusted hazard ratio 0.31; P  =  .009).

 

Study details: Findings are from a retrospective cohort study including 28,559 patients with RA without preexisting ILD who were newly administered adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib, of which 276 patients were diagnosed with incident ILD.

 

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors did not report conflicts of interest.

 

Source: Baker MC et al. Incidence of interstitial lung disease in patients with rheumatoid arthritis treated with biologic and targeted synthetic disease-modifying antirheumatic drugs. JAMA Netw Open. 2023;6(3):e233640 (Mar 20). Doi: 10.1001/jamanetworkopen.2023.3640

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Discontinuing half-dose csDMARD feasible in some patients with RA in remission

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Key clinical point: Continuation of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) was not superior to withdrawal in patients with rheumatoid arthritis (RA) in sustained remission with half-dose csDMARD, suggesting withdrawal of half-dose csDMARD is feasible in some patients.

 

Major finding: Although discontinuing vs continuing half-dose csDMARD led to a numerically higher risk for flares within 12 months (risk difference 21.5%; 95% CI −3.4% to 49.7%), more patients discontinuing vs continuing half-dose csDMARD showed no radiographic joint damage progression (risk difference 13.9%; 95% CI −10.6% to 38.3%) and regained Disease Activity Score-based remission (80.0% [95% CI 44.4%-97.5%] vs 66.7% [95% CI 9.5%-99.2%]) at the first visit after flare.

 

Study details: This open-label trial, a part of the ARCTIC REWIND project, included 56 patients with RA who were in sustained remission for ≥12 months with half-dose csDMARD and were randomly assigned to discontinue or continue half-dose csDMARD.

 

Disclosures: This study was funded by the Research Council of Norway and other sources. Several authors declared receiving research grants or personal fees from various sources.

 

Source: Lillegraven S et al. Discontinuation of conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and excellent disease control. JAMA. 2023;329(12):1024-1026 (Mar 28). Doi: 10.1001/jama.2023.0492

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Key clinical point: Continuation of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) was not superior to withdrawal in patients with rheumatoid arthritis (RA) in sustained remission with half-dose csDMARD, suggesting withdrawal of half-dose csDMARD is feasible in some patients.

 

Major finding: Although discontinuing vs continuing half-dose csDMARD led to a numerically higher risk for flares within 12 months (risk difference 21.5%; 95% CI −3.4% to 49.7%), more patients discontinuing vs continuing half-dose csDMARD showed no radiographic joint damage progression (risk difference 13.9%; 95% CI −10.6% to 38.3%) and regained Disease Activity Score-based remission (80.0% [95% CI 44.4%-97.5%] vs 66.7% [95% CI 9.5%-99.2%]) at the first visit after flare.

 

Study details: This open-label trial, a part of the ARCTIC REWIND project, included 56 patients with RA who were in sustained remission for ≥12 months with half-dose csDMARD and were randomly assigned to discontinue or continue half-dose csDMARD.

 

Disclosures: This study was funded by the Research Council of Norway and other sources. Several authors declared receiving research grants or personal fees from various sources.

 

Source: Lillegraven S et al. Discontinuation of conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and excellent disease control. JAMA. 2023;329(12):1024-1026 (Mar 28). Doi: 10.1001/jama.2023.0492

Key clinical point: Continuation of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) was not superior to withdrawal in patients with rheumatoid arthritis (RA) in sustained remission with half-dose csDMARD, suggesting withdrawal of half-dose csDMARD is feasible in some patients.

 

Major finding: Although discontinuing vs continuing half-dose csDMARD led to a numerically higher risk for flares within 12 months (risk difference 21.5%; 95% CI −3.4% to 49.7%), more patients discontinuing vs continuing half-dose csDMARD showed no radiographic joint damage progression (risk difference 13.9%; 95% CI −10.6% to 38.3%) and regained Disease Activity Score-based remission (80.0% [95% CI 44.4%-97.5%] vs 66.7% [95% CI 9.5%-99.2%]) at the first visit after flare.

 

Study details: This open-label trial, a part of the ARCTIC REWIND project, included 56 patients with RA who were in sustained remission for ≥12 months with half-dose csDMARD and were randomly assigned to discontinue or continue half-dose csDMARD.

 

Disclosures: This study was funded by the Research Council of Norway and other sources. Several authors declared receiving research grants or personal fees from various sources.

 

Source: Lillegraven S et al. Discontinuation of conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and excellent disease control. JAMA. 2023;329(12):1024-1026 (Mar 28). Doi: 10.1001/jama.2023.0492

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