Spondyloarthropathies

As states ban or limit abortion in the wake of the demise of Roe v. Wade, physicians are turning their attention to widely-used drugs that can cause birth defects. At issue: Should these drugs still be prescribed to women of childbearing age if they don’t have the option of terminating their pregnancies?

javi_indy/ Thinkstock

“Doctors are going to understandably be terrified that a patient may become pregnant using a teratogen that they have prescribed,” said University of Pittsburgh rheumatologist Mehret Birru Talabi, MD, PhD, who works in a state where the future of abortion rights is uncertain. “While this was a feared outcome before Roe v. Wade was overturned, abortion provided an escape hatch by which women could avoid having to continue a pregnancy and potentially raise a child with congenital anomalies. I believe that prescribing is going to become much more defensive and conservative. Some clinicians may choose not to prescribe these medications to patients who have childbearing potential, even if they don’t have much risk for pregnancy.”

Other physicians expressed similar concerns in interviews. Duke University, Durham, N.C., rheumatologist Megan E. B. Clowse, MD, MPH, fears that physicians will be wary of prescribing a variety of medications – including new ones for which there are few pregnancy data – if abortion is unavailable. “Women who receive these new or teratogenic medications will likely lose their reproductive autonomy and be forced to choose between having sexual relationships with men, obtaining procedures that make them permanently sterile, or using contraception that may cause intolerable side effects,” she said. “I am very concerned that young women with rheumatic disease will now be left with active disease resulting in joint damage and renal failure.”

Abortion is now banned in at least six states, according to The New York Times. That number may rise to 16 as more restrictions become law. Another five states aren’t expected to ban abortion soon but have implemented gestational age limits on abortion or are expected to adopt them. In another nine states, courts or lawmakers will decide whether abortion remains legal.

Only 20 states and the District of Columbia have firm abortion protections in place.

Numerous drugs are considered teratogens, which means they may cause birth defects. Thalidomide is the most infamous, but there are many more, including several used in rheumatology, dermatology, and gastroenterology. Among the most widely used teratogenic medications are the acne drugs isotretinoin and methotrexate, which are used to treat a variety of conditions, such as cancer, rheumatoid arthritis, and psoriasis.

Dr. Clowse, who helps manage an industry-supported website devoted to reproductive care for women with lupus (www.LupusPregnancy.org), noted that several drugs linked to birth defects and pregnancy loss are commonly prescribed in rheumatology.

“Methotrexate is the most common medication and has been the cornerstone of rheumatoid arthritis [treatment] for at least two decades,” she said. “Mycophenolate is our best medication to treat lupus nephritis, which is inflammation in the kidneys caused by lupus. This is a common complication for young women with lupus, and all of our guideline-recommended treatment regimens include a medication that causes pregnancy loss and birth defects, either mycophenolate or cyclophosphamide.”

Rheumatologists also prescribe a large number of new drugs for which there are few data about pregnancy risks. “It typically takes about two decades to have sufficient data about the safety of our medications,” she said.

Reflecting the sensitivity of the topic, Dr. Clowse made clear that her opinions don’t represent the views of her institution. She works in North Carolina, where the fate of abortion rights is uncertain, according to The New York Times.

What about alternatives? “The short answer is that some of these medications work really well and sometimes much better than the nonteratogenic alternatives,” said Dr. Birru Talabi. “I’m worried about methotrexate. It has been used to induce abortions but is primarily used in the United States as a highly effective treatment for cancer as well as a myriad of rheumatic diseases. If legislators try to restrict access to methotrexate, we may see increasing disability and even death among people who need this medication but cannot access it.”

Rheumatologists aren’t the only physicians who are worrying about the fates of their patients in a new era of abortion restrictions. Gastroenterologist Sunanda Kane, MD, MSPH, of the Mayo Clinic, Rochester, Minn., said several teratogenic medications are used in her field to treat constipation, viral hepatitis, and inflammatory bowel disease.

“When treating women of childbearing age, there are usually alternatives. If we do prescribe a medication with a high teratogenic potential, we counsel and document that we have discussed two forms of birth control to avoid pregnancy. We usually do not prescribe a drug with teratogenic potential with the ‘out’ being an abortion if a pregnancy does occur,” she said. However, “if abortion is not even on the table as an option, we may be much less likely to prescribe these medications. This will be particularly true in patients who clearly do not have the means to travel to have an abortion in any situation.”

Abortion is expected to remain legal in Minnesota, where Dr. Kane practices, but it may be restricted or banned in nearby Wisconsin, depending on the state legislature. None of her patients have had abortions after becoming pregnant while taking the medications, she said, although she “did have a patient who because of her religious faith did not have an abortion after exposure and ended up with a stillbirth.”

The crackdown on abortion won’t just pose risks to patients who take potentially dangerous medications, physicians said. Dr. Kane said pregnancy itself is a significant risk for patients with “very active, uncontrolled gastrointestinal conditions where a pregnancy could be harmful to the mother’s health or result in offspring that are very unhealthy.” These include decompensated cirrhosis, uncontrolled Crohn’s disease or ulcerative colitis, refractory gastroparesis, uncontrolled celiac sprue, and chronic pancreatitis, she said.

“There have been times when after shared decisionmaking, a patient with very active inflammatory bowel disease has decided to terminate the pregnancy because of her own ongoing health issues,” she said. “Not having this option will potentially lead to disastrous results.”

Dr. Clowse, the Duke University rheumatologist, echoed Dr. Kane’s concerns about women who are too sick to bear children. “The removal of abortion rights puts the lives and quality of life for women with rheumatic disease at risk. For patients with lupus and other systemic rheumatic disease, pregnancy can be medically catastrophic, leading to permanent harm and even death to the woman and her offspring. I am worried that women in these conditions will die without lifesaving pregnancy terminations, due to worries about the legal consequences for their physicians.”

The U.S. Supreme Court’s ruling that overturned Roe v. Wade has also raised the prospect that the court could ultimately allow birth control to be restricted or outlawed.

While the ruling states that “nothing in this opinion should be understood to cast doubt on precedents that do not concern abortion,” Justice Clarence Thomas wrote a concurrence in which he said that the court should reconsider a 1960s ruling that forbids the banning of contraceptives. Republicans have dismissed concerns about bans being allowed, although Democrats, including the president and vice president, starkly warn that they could happen.

“If we as providers have to be concerned that there will be an unplanned pregnancy because of the lack of access to contraception,” Dr. Kane said, “this will have significant downstream consequences to the kind of care we can provide and might just drive some providers to not give care to female patients at all given this concern.”

The physicians quoted in this article report no relevant financial relationships.

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

As states ban or limit abortion in the wake of the demise of Roe v. Wade, physicians are turning their attention to widely-used drugs that can cause birth defects. At issue: Should these drugs still be prescribed to women of childbearing age if they don’t have the option of terminating their pregnancies?

javi_indy/ Thinkstock

“Doctors are going to understandably be terrified that a patient may become pregnant using a teratogen that they have prescribed,” said University of Pittsburgh rheumatologist Mehret Birru Talabi, MD, PhD, who works in a state where the future of abortion rights is uncertain. “While this was a feared outcome before Roe v. Wade was overturned, abortion provided an escape hatch by which women could avoid having to continue a pregnancy and potentially raise a child with congenital anomalies. I believe that prescribing is going to become much more defensive and conservative. Some clinicians may choose not to prescribe these medications to patients who have childbearing potential, even if they don’t have much risk for pregnancy.”

Other physicians expressed similar concerns in interviews. Duke University, Durham, N.C., rheumatologist Megan E. B. Clowse, MD, MPH, fears that physicians will be wary of prescribing a variety of medications – including new ones for which there are few pregnancy data – if abortion is unavailable. “Women who receive these new or teratogenic medications will likely lose their reproductive autonomy and be forced to choose between having sexual relationships with men, obtaining procedures that make them permanently sterile, or using contraception that may cause intolerable side effects,” she said. “I am very concerned that young women with rheumatic disease will now be left with active disease resulting in joint damage and renal failure.”

Abortion is now banned in at least six states, according to The New York Times. That number may rise to 16 as more restrictions become law. Another five states aren’t expected to ban abortion soon but have implemented gestational age limits on abortion or are expected to adopt them. In another nine states, courts or lawmakers will decide whether abortion remains legal.

Only 20 states and the District of Columbia have firm abortion protections in place.

Numerous drugs are considered teratogens, which means they may cause birth defects. Thalidomide is the most infamous, but there are many more, including several used in rheumatology, dermatology, and gastroenterology. Among the most widely used teratogenic medications are the acne drugs isotretinoin and methotrexate, which are used to treat a variety of conditions, such as cancer, rheumatoid arthritis, and psoriasis.

Dr. Clowse, who helps manage an industry-supported website devoted to reproductive care for women with lupus (www.LupusPregnancy.org), noted that several drugs linked to birth defects and pregnancy loss are commonly prescribed in rheumatology.

“Methotrexate is the most common medication and has been the cornerstone of rheumatoid arthritis [treatment] for at least two decades,” she said. “Mycophenolate is our best medication to treat lupus nephritis, which is inflammation in the kidneys caused by lupus. This is a common complication for young women with lupus, and all of our guideline-recommended treatment regimens include a medication that causes pregnancy loss and birth defects, either mycophenolate or cyclophosphamide.”

Rheumatologists also prescribe a large number of new drugs for which there are few data about pregnancy risks. “It typically takes about two decades to have sufficient data about the safety of our medications,” she said.

Reflecting the sensitivity of the topic, Dr. Clowse made clear that her opinions don’t represent the views of her institution. She works in North Carolina, where the fate of abortion rights is uncertain, according to The New York Times.

What about alternatives? “The short answer is that some of these medications work really well and sometimes much better than the nonteratogenic alternatives,” said Dr. Birru Talabi. “I’m worried about methotrexate. It has been used to induce abortions but is primarily used in the United States as a highly effective treatment for cancer as well as a myriad of rheumatic diseases. If legislators try to restrict access to methotrexate, we may see increasing disability and even death among people who need this medication but cannot access it.”

Rheumatologists aren’t the only physicians who are worrying about the fates of their patients in a new era of abortion restrictions. Gastroenterologist Sunanda Kane, MD, MSPH, of the Mayo Clinic, Rochester, Minn., said several teratogenic medications are used in her field to treat constipation, viral hepatitis, and inflammatory bowel disease.

“When treating women of childbearing age, there are usually alternatives. If we do prescribe a medication with a high teratogenic potential, we counsel and document that we have discussed two forms of birth control to avoid pregnancy. We usually do not prescribe a drug with teratogenic potential with the ‘out’ being an abortion if a pregnancy does occur,” she said. However, “if abortion is not even on the table as an option, we may be much less likely to prescribe these medications. This will be particularly true in patients who clearly do not have the means to travel to have an abortion in any situation.”

Abortion is expected to remain legal in Minnesota, where Dr. Kane practices, but it may be restricted or banned in nearby Wisconsin, depending on the state legislature. None of her patients have had abortions after becoming pregnant while taking the medications, she said, although she “did have a patient who because of her religious faith did not have an abortion after exposure and ended up with a stillbirth.”

The crackdown on abortion won’t just pose risks to patients who take potentially dangerous medications, physicians said. Dr. Kane said pregnancy itself is a significant risk for patients with “very active, uncontrolled gastrointestinal conditions where a pregnancy could be harmful to the mother’s health or result in offspring that are very unhealthy.” These include decompensated cirrhosis, uncontrolled Crohn’s disease or ulcerative colitis, refractory gastroparesis, uncontrolled celiac sprue, and chronic pancreatitis, she said.

“There have been times when after shared decisionmaking, a patient with very active inflammatory bowel disease has decided to terminate the pregnancy because of her own ongoing health issues,” she said. “Not having this option will potentially lead to disastrous results.”

Dr. Clowse, the Duke University rheumatologist, echoed Dr. Kane’s concerns about women who are too sick to bear children. “The removal of abortion rights puts the lives and quality of life for women with rheumatic disease at risk. For patients with lupus and other systemic rheumatic disease, pregnancy can be medically catastrophic, leading to permanent harm and even death to the woman and her offspring. I am worried that women in these conditions will die without lifesaving pregnancy terminations, due to worries about the legal consequences for their physicians.”

The U.S. Supreme Court’s ruling that overturned Roe v. Wade has also raised the prospect that the court could ultimately allow birth control to be restricted or outlawed.

While the ruling states that “nothing in this opinion should be understood to cast doubt on precedents that do not concern abortion,” Justice Clarence Thomas wrote a concurrence in which he said that the court should reconsider a 1960s ruling that forbids the banning of contraceptives. Republicans have dismissed concerns about bans being allowed, although Democrats, including the president and vice president, starkly warn that they could happen.

“If we as providers have to be concerned that there will be an unplanned pregnancy because of the lack of access to contraception,” Dr. Kane said, “this will have significant downstream consequences to the kind of care we can provide and might just drive some providers to not give care to female patients at all given this concern.”

The physicians quoted in this article report no relevant financial relationships.

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

As states ban or limit abortion in the wake of the demise of Roe v. Wade, physicians are turning their attention to widely-used drugs that can cause birth defects. At issue: Should these drugs still be prescribed to women of childbearing age if they don’t have the option of terminating their pregnancies?

javi_indy/ Thinkstock

“Doctors are going to understandably be terrified that a patient may become pregnant using a teratogen that they have prescribed,” said University of Pittsburgh rheumatologist Mehret Birru Talabi, MD, PhD, who works in a state where the future of abortion rights is uncertain. “While this was a feared outcome before Roe v. Wade was overturned, abortion provided an escape hatch by which women could avoid having to continue a pregnancy and potentially raise a child with congenital anomalies. I believe that prescribing is going to become much more defensive and conservative. Some clinicians may choose not to prescribe these medications to patients who have childbearing potential, even if they don’t have much risk for pregnancy.”

Other physicians expressed similar concerns in interviews. Duke University, Durham, N.C., rheumatologist Megan E. B. Clowse, MD, MPH, fears that physicians will be wary of prescribing a variety of medications – including new ones for which there are few pregnancy data – if abortion is unavailable. “Women who receive these new or teratogenic medications will likely lose their reproductive autonomy and be forced to choose between having sexual relationships with men, obtaining procedures that make them permanently sterile, or using contraception that may cause intolerable side effects,” she said. “I am very concerned that young women with rheumatic disease will now be left with active disease resulting in joint damage and renal failure.”

Abortion is now banned in at least six states, according to The New York Times. That number may rise to 16 as more restrictions become law. Another five states aren’t expected to ban abortion soon but have implemented gestational age limits on abortion or are expected to adopt them. In another nine states, courts or lawmakers will decide whether abortion remains legal.

Only 20 states and the District of Columbia have firm abortion protections in place.

Numerous drugs are considered teratogens, which means they may cause birth defects. Thalidomide is the most infamous, but there are many more, including several used in rheumatology, dermatology, and gastroenterology. Among the most widely used teratogenic medications are the acne drugs isotretinoin and methotrexate, which are used to treat a variety of conditions, such as cancer, rheumatoid arthritis, and psoriasis.

Dr. Clowse, who helps manage an industry-supported website devoted to reproductive care for women with lupus (www.LupusPregnancy.org), noted that several drugs linked to birth defects and pregnancy loss are commonly prescribed in rheumatology.

“Methotrexate is the most common medication and has been the cornerstone of rheumatoid arthritis [treatment] for at least two decades,” she said. “Mycophenolate is our best medication to treat lupus nephritis, which is inflammation in the kidneys caused by lupus. This is a common complication for young women with lupus, and all of our guideline-recommended treatment regimens include a medication that causes pregnancy loss and birth defects, either mycophenolate or cyclophosphamide.”

Rheumatologists also prescribe a large number of new drugs for which there are few data about pregnancy risks. “It typically takes about two decades to have sufficient data about the safety of our medications,” she said.

Reflecting the sensitivity of the topic, Dr. Clowse made clear that her opinions don’t represent the views of her institution. She works in North Carolina, where the fate of abortion rights is uncertain, according to The New York Times.

What about alternatives? “The short answer is that some of these medications work really well and sometimes much better than the nonteratogenic alternatives,” said Dr. Birru Talabi. “I’m worried about methotrexate. It has been used to induce abortions but is primarily used in the United States as a highly effective treatment for cancer as well as a myriad of rheumatic diseases. If legislators try to restrict access to methotrexate, we may see increasing disability and even death among people who need this medication but cannot access it.”

Rheumatologists aren’t the only physicians who are worrying about the fates of their patients in a new era of abortion restrictions. Gastroenterologist Sunanda Kane, MD, MSPH, of the Mayo Clinic, Rochester, Minn., said several teratogenic medications are used in her field to treat constipation, viral hepatitis, and inflammatory bowel disease.

“When treating women of childbearing age, there are usually alternatives. If we do prescribe a medication with a high teratogenic potential, we counsel and document that we have discussed two forms of birth control to avoid pregnancy. We usually do not prescribe a drug with teratogenic potential with the ‘out’ being an abortion if a pregnancy does occur,” she said. However, “if abortion is not even on the table as an option, we may be much less likely to prescribe these medications. This will be particularly true in patients who clearly do not have the means to travel to have an abortion in any situation.”

Abortion is expected to remain legal in Minnesota, where Dr. Kane practices, but it may be restricted or banned in nearby Wisconsin, depending on the state legislature. None of her patients have had abortions after becoming pregnant while taking the medications, she said, although she “did have a patient who because of her religious faith did not have an abortion after exposure and ended up with a stillbirth.”

The crackdown on abortion won’t just pose risks to patients who take potentially dangerous medications, physicians said. Dr. Kane said pregnancy itself is a significant risk for patients with “very active, uncontrolled gastrointestinal conditions where a pregnancy could be harmful to the mother’s health or result in offspring that are very unhealthy.” These include decompensated cirrhosis, uncontrolled Crohn’s disease or ulcerative colitis, refractory gastroparesis, uncontrolled celiac sprue, and chronic pancreatitis, she said.

“There have been times when after shared decisionmaking, a patient with very active inflammatory bowel disease has decided to terminate the pregnancy because of her own ongoing health issues,” she said. “Not having this option will potentially lead to disastrous results.”

Dr. Clowse, the Duke University rheumatologist, echoed Dr. Kane’s concerns about women who are too sick to bear children. “The removal of abortion rights puts the lives and quality of life for women with rheumatic disease at risk. For patients with lupus and other systemic rheumatic disease, pregnancy can be medically catastrophic, leading to permanent harm and even death to the woman and her offspring. I am worried that women in these conditions will die without lifesaving pregnancy terminations, due to worries about the legal consequences for their physicians.”

The U.S. Supreme Court’s ruling that overturned Roe v. Wade has also raised the prospect that the court could ultimately allow birth control to be restricted or outlawed.

While the ruling states that “nothing in this opinion should be understood to cast doubt on precedents that do not concern abortion,” Justice Clarence Thomas wrote a concurrence in which he said that the court should reconsider a 1960s ruling that forbids the banning of contraceptives. Republicans have dismissed concerns about bans being allowed, although Democrats, including the president and vice president, starkly warn that they could happen.

“If we as providers have to be concerned that there will be an unplanned pregnancy because of the lack of access to contraception,” Dr. Kane said, “this will have significant downstream consequences to the kind of care we can provide and might just drive some providers to not give care to female patients at all given this concern.”

The physicians quoted in this article report no relevant financial relationships.

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

Upadacitinib may soon be used for the treatment of nonradiographic axial spondyloarthritis (nr-axSpA) after the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) gave it its stamp of approval.

AbbVie, the drug’s manufacturer, announced on June 27 that the committee approved the use on June 23. The recommendation to approve market authorization for upadacitinib for nr-axSpA now goes to the European Commission, which is expected to make a decision by the third quarter of 2022.

“The CHMP’s recommendation to approve upadacitinib for patients with nr-axSpA is an important milestone in providing a new treatment option to patients in need,” said Neil Gallagher, MD, vice president of development and chief medical officer of AbbVie. He noted that currently, there are few options to treat symptoms such as inflammation, back pain, and stiffness for these patients.

Officially, the new indication for upadacitinib (Rinvoq) 15 mg once daily is for the treatment of active nr-axSpA in adult patients with objective signs of inflammation, as indicated by elevated C-reactive protein and/or MRI, whose condition has responded inadequately to NSAIDs.

Upadacitinib is a selective Janus kinase (JAK) inhibitor that in human cellular assays preferentially inhibits signaling by JAK1 or JAK1/3.

In the European Union, upadacitinib is currently approved for use in patients with moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and moderate to severe atopic dermatitis. In addition to these indications, it is approved in the United States for ulcerative colitis but not for nr-axSpA.

The committee based its decision on the results of the nr-axSpA study within the SELECT-AXIS-2 trial, recently reported at the European Alliance of Associations for Rheumatology (EULAR) 2022 annual meeting.

The nr-axSpA study met the primary endpoint of a 40% improvement in Assessment of SpondyloArthritis International Society response criteria (ASAS40) and the first 12 of 14 ranked secondary endpoints, according to AbbVie.

The most commonly reported adverse reactions with upadacitinib 15 mg were upper respiratory tract infections, elevated blood creatine phosphokinase levels, elevated alanine transaminase levels, bronchitis, nausea, cough, elevated aspartate transaminase levels, and hypercholesterolemia. These occurred in 2% or more of patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis in clinical trials.

The safety profile of upadacitinib with long-term treatment was generally similar to the safety profile during the placebo-controlled period across indications, AbbVie said.

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

Upadacitinib may soon be used for the treatment of nonradiographic axial spondyloarthritis (nr-axSpA) after the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) gave it its stamp of approval.

AbbVie, the drug’s manufacturer, announced on June 27 that the committee approved the use on June 23. The recommendation to approve market authorization for upadacitinib for nr-axSpA now goes to the European Commission, which is expected to make a decision by the third quarter of 2022.

“The CHMP’s recommendation to approve upadacitinib for patients with nr-axSpA is an important milestone in providing a new treatment option to patients in need,” said Neil Gallagher, MD, vice president of development and chief medical officer of AbbVie. He noted that currently, there are few options to treat symptoms such as inflammation, back pain, and stiffness for these patients.

Officially, the new indication for upadacitinib (Rinvoq) 15 mg once daily is for the treatment of active nr-axSpA in adult patients with objective signs of inflammation, as indicated by elevated C-reactive protein and/or MRI, whose condition has responded inadequately to NSAIDs.

Upadacitinib is a selective Janus kinase (JAK) inhibitor that in human cellular assays preferentially inhibits signaling by JAK1 or JAK1/3.

In the European Union, upadacitinib is currently approved for use in patients with moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and moderate to severe atopic dermatitis. In addition to these indications, it is approved in the United States for ulcerative colitis but not for nr-axSpA.

The committee based its decision on the results of the nr-axSpA study within the SELECT-AXIS-2 trial, recently reported at the European Alliance of Associations for Rheumatology (EULAR) 2022 annual meeting.

The nr-axSpA study met the primary endpoint of a 40% improvement in Assessment of SpondyloArthritis International Society response criteria (ASAS40) and the first 12 of 14 ranked secondary endpoints, according to AbbVie.

The most commonly reported adverse reactions with upadacitinib 15 mg were upper respiratory tract infections, elevated blood creatine phosphokinase levels, elevated alanine transaminase levels, bronchitis, nausea, cough, elevated aspartate transaminase levels, and hypercholesterolemia. These occurred in 2% or more of patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis in clinical trials.

The safety profile of upadacitinib with long-term treatment was generally similar to the safety profile during the placebo-controlled period across indications, AbbVie said.

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

Upadacitinib may soon be used for the treatment of nonradiographic axial spondyloarthritis (nr-axSpA) after the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) gave it its stamp of approval.

AbbVie, the drug’s manufacturer, announced on June 27 that the committee approved the use on June 23. The recommendation to approve market authorization for upadacitinib for nr-axSpA now goes to the European Commission, which is expected to make a decision by the third quarter of 2022.

“The CHMP’s recommendation to approve upadacitinib for patients with nr-axSpA is an important milestone in providing a new treatment option to patients in need,” said Neil Gallagher, MD, vice president of development and chief medical officer of AbbVie. He noted that currently, there are few options to treat symptoms such as inflammation, back pain, and stiffness for these patients.

Officially, the new indication for upadacitinib (Rinvoq) 15 mg once daily is for the treatment of active nr-axSpA in adult patients with objective signs of inflammation, as indicated by elevated C-reactive protein and/or MRI, whose condition has responded inadequately to NSAIDs.

Upadacitinib is a selective Janus kinase (JAK) inhibitor that in human cellular assays preferentially inhibits signaling by JAK1 or JAK1/3.

In the European Union, upadacitinib is currently approved for use in patients with moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and moderate to severe atopic dermatitis. In addition to these indications, it is approved in the United States for ulcerative colitis but not for nr-axSpA.

The committee based its decision on the results of the nr-axSpA study within the SELECT-AXIS-2 trial, recently reported at the European Alliance of Associations for Rheumatology (EULAR) 2022 annual meeting.

The nr-axSpA study met the primary endpoint of a 40% improvement in Assessment of SpondyloArthritis International Society response criteria (ASAS40) and the first 12 of 14 ranked secondary endpoints, according to AbbVie.

The most commonly reported adverse reactions with upadacitinib 15 mg were upper respiratory tract infections, elevated blood creatine phosphokinase levels, elevated alanine transaminase levels, bronchitis, nausea, cough, elevated aspartate transaminase levels, and hypercholesterolemia. These occurred in 2% or more of patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis in clinical trials.

The safety profile of upadacitinib with long-term treatment was generally similar to the safety profile during the placebo-controlled period across indications, AbbVie said.

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

Aiming for a disease activity target while reducing biologic therapy could be a winning approach for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), according to the results of a new study presented at the annual European Congress of Rheumatology.

The findings show that a treat-to-target (T2T) strategy with tapering using a tumor necrosis factor (TNF) inhibitor produces results that are noninferior to a T2T strategy that doesn’t include tapering in these patients.

“Our study has for the first time shown that a treat-to-target tapering strategy is just as good as full-dose continuation, while reducing medication use substantially,” first author Celia Michielsens, MD, a PhD student and researcher at Sint Maartenskliniek in Nijmegen, the Netherlands, said in an interview before her presentation of the study during an oral abstract session at the congress. “Stepwise tapering is also better than fixed-dose reduction or discontinuation, since it is much more individualized.”

The study is now published in Annals of the Rheumatic Diseases.

In the randomized, controlled, open-label, noninferiority study, researchers enrolled patients with PsA or axSpA who were using a TNF inhibitor such as etanercept, adalimumab, or infliximab, and had stable low disease activity for at least 6 months. Patients needed to have a Psoriatic Arthritis Disease Activity Score (PASDAS) of 3.2 or less, or an Ankylosing Spondylitis Disease Activity Score (ASDAS) of at 2.1 or less. In cases of flare, patients were treated with NSAIDs and/or glucorticoids, and if they still had not reached low disease activity after a month, their previous TNF inhibitor dose was reinstated to the last effective interval or dosage, which was maintained throughout the study period. When the patient was already using a full TNF-inhibitor dose or if dose adjustment did not suffice, patients were switched to another biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD).

Participants were randomized, from January 2019 to June 2021, to a tapering or a nontapering T2T strategy in a 2:1 fashion. Then researchers then followed them for 12 months and aimed to determine if the tapering strategy proved noninferior to not tapering within a predefined 20% margin for noninferiority, which Dr. Michielsens said was derived from other studies and what her group determined to be “an acceptable risk.”

Results show strategy is ‘feasible in daily clinical care’

A total of 81 patients – 42 with PsA and 39 with axSpA – were in the group with tapering, and 41 were in the group without tapering: 22 with PsA and 19 with axSpA.

At 12 months, researchers found that 69% of the patients in the group with tapering had low disease activity, measured via the PASDAS and ASDAS, compared with 73% in patients who did not taper. And those in the tapering group saw their medication use dramatically reduced. At the 12-month mark, they were taking just 53% of the defined daily dose for maintenance, compared with 91% of the defined daily dose for the group that didn’t taper.

The researchers were able to successfully taper 72% of the patients in the tapering group, with 28% of them discontinuing their TNF-inhibitor medication entirely. The incidence of flares was 85% in the tapering group and 78% in the nontapering group, a nonsignificant difference (P = .32).

The start of a new medication or an increase in use of an existing medication was more frequent in the tapering group, and significantly so for NSAIDs. An increase in NSAID use was seen in 54% of the tapering group and in just 24% of the nontapering group (P = .002).

Conventional synthetic DMARD use went up in the tapering group, compared with the nontapering group, but this was only among the PsA patients and the change in use was not statistically significant. There were also more frequent increases in glucocorticoid use in the tapering group, compared with the nontapering group, but this was not significant.

Dr. Michielsens said the findings show the value of an individualized approach in treating patients with PsA or axSpA.

“Our study – and those [studies] in rheumatoid arthritis earlier – deliver the highest quality of evidence that disease activity–guided dose personalization can, and in fact should, be used in clinical practice,” she said. “Our pragmatic treat-to-target tapering strategy is feasible in daily clinical care, although treat-to-target using PASDAS and ASDAS needs some implementation. In shared decision-making with patients, a 50% reduction in TNFi use is obtainable, while maintaining low disease activity.”

The increase in the use of NSAIDs is something to be aware of, but it is “not concerning,” Dr. Michielsens added. She pointed out that the NSAID use was typically temporary, used when flares arose, and that the drugs are effective, safe, and inexpensive. She also noted that the use of TNF blockers decreased more than the use of NSAIDs increased.

“This seems a perfectly acceptable trade-off that can be discussed with your patient,” she said.

The 12-month duration of the study is likely long enough to show that the tapering strategy works, Dr. Michielsens said. In rheumatoid arthritis studies, for example, differences in strategies didn’t change after 1 year.

“That said, we are doing an observational extension study to provide more insights in the long-term effects of this treat-to-target strategy,” she said. “At the end of this summer, all patients will have completed their extended follow-up period – a 12-month observational period – so hopefully we can present the results next year at EULAR.”

This study received funding from ReumaNederland. Dr. Michielsens did not have any financial interests to disclose. Two coauthors reported financial relationships with numerous pharmaceutical companies.

Aiming for a disease activity target while reducing biologic therapy could be a winning approach for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), according to the results of a new study presented at the annual European Congress of Rheumatology.

The findings show that a treat-to-target (T2T) strategy with tapering using a tumor necrosis factor (TNF) inhibitor produces results that are noninferior to a T2T strategy that doesn’t include tapering in these patients.

“Our study has for the first time shown that a treat-to-target tapering strategy is just as good as full-dose continuation, while reducing medication use substantially,” first author Celia Michielsens, MD, a PhD student and researcher at Sint Maartenskliniek in Nijmegen, the Netherlands, said in an interview before her presentation of the study during an oral abstract session at the congress. “Stepwise tapering is also better than fixed-dose reduction or discontinuation, since it is much more individualized.”

The study is now published in Annals of the Rheumatic Diseases.

In the randomized, controlled, open-label, noninferiority study, researchers enrolled patients with PsA or axSpA who were using a TNF inhibitor such as etanercept, adalimumab, or infliximab, and had stable low disease activity for at least 6 months. Patients needed to have a Psoriatic Arthritis Disease Activity Score (PASDAS) of 3.2 or less, or an Ankylosing Spondylitis Disease Activity Score (ASDAS) of at 2.1 or less. In cases of flare, patients were treated with NSAIDs and/or glucorticoids, and if they still had not reached low disease activity after a month, their previous TNF inhibitor dose was reinstated to the last effective interval or dosage, which was maintained throughout the study period. When the patient was already using a full TNF-inhibitor dose or if dose adjustment did not suffice, patients were switched to another biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD).

Participants were randomized, from January 2019 to June 2021, to a tapering or a nontapering T2T strategy in a 2:1 fashion. Then researchers then followed them for 12 months and aimed to determine if the tapering strategy proved noninferior to not tapering within a predefined 20% margin for noninferiority, which Dr. Michielsens said was derived from other studies and what her group determined to be “an acceptable risk.”

Results show strategy is ‘feasible in daily clinical care’

A total of 81 patients – 42 with PsA and 39 with axSpA – were in the group with tapering, and 41 were in the group without tapering: 22 with PsA and 19 with axSpA.

At 12 months, researchers found that 69% of the patients in the group with tapering had low disease activity, measured via the PASDAS and ASDAS, compared with 73% in patients who did not taper. And those in the tapering group saw their medication use dramatically reduced. At the 12-month mark, they were taking just 53% of the defined daily dose for maintenance, compared with 91% of the defined daily dose for the group that didn’t taper.

The researchers were able to successfully taper 72% of the patients in the tapering group, with 28% of them discontinuing their TNF-inhibitor medication entirely. The incidence of flares was 85% in the tapering group and 78% in the nontapering group, a nonsignificant difference (P = .32).

The start of a new medication or an increase in use of an existing medication was more frequent in the tapering group, and significantly so for NSAIDs. An increase in NSAID use was seen in 54% of the tapering group and in just 24% of the nontapering group (P = .002).

Conventional synthetic DMARD use went up in the tapering group, compared with the nontapering group, but this was only among the PsA patients and the change in use was not statistically significant. There were also more frequent increases in glucocorticoid use in the tapering group, compared with the nontapering group, but this was not significant.

Dr. Michielsens said the findings show the value of an individualized approach in treating patients with PsA or axSpA.

“Our study – and those [studies] in rheumatoid arthritis earlier – deliver the highest quality of evidence that disease activity–guided dose personalization can, and in fact should, be used in clinical practice,” she said. “Our pragmatic treat-to-target tapering strategy is feasible in daily clinical care, although treat-to-target using PASDAS and ASDAS needs some implementation. In shared decision-making with patients, a 50% reduction in TNFi use is obtainable, while maintaining low disease activity.”

The increase in the use of NSAIDs is something to be aware of, but it is “not concerning,” Dr. Michielsens added. She pointed out that the NSAID use was typically temporary, used when flares arose, and that the drugs are effective, safe, and inexpensive. She also noted that the use of TNF blockers decreased more than the use of NSAIDs increased.

“This seems a perfectly acceptable trade-off that can be discussed with your patient,” she said.

The 12-month duration of the study is likely long enough to show that the tapering strategy works, Dr. Michielsens said. In rheumatoid arthritis studies, for example, differences in strategies didn’t change after 1 year.

“That said, we are doing an observational extension study to provide more insights in the long-term effects of this treat-to-target strategy,” she said. “At the end of this summer, all patients will have completed their extended follow-up period – a 12-month observational period – so hopefully we can present the results next year at EULAR.”

This study received funding from ReumaNederland. Dr. Michielsens did not have any financial interests to disclose. Two coauthors reported financial relationships with numerous pharmaceutical companies.

Aiming for a disease activity target while reducing biologic therapy could be a winning approach for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), according to the results of a new study presented at the annual European Congress of Rheumatology.

The findings show that a treat-to-target (T2T) strategy with tapering using a tumor necrosis factor (TNF) inhibitor produces results that are noninferior to a T2T strategy that doesn’t include tapering in these patients.

“Our study has for the first time shown that a treat-to-target tapering strategy is just as good as full-dose continuation, while reducing medication use substantially,” first author Celia Michielsens, MD, a PhD student and researcher at Sint Maartenskliniek in Nijmegen, the Netherlands, said in an interview before her presentation of the study during an oral abstract session at the congress. “Stepwise tapering is also better than fixed-dose reduction or discontinuation, since it is much more individualized.”

The study is now published in Annals of the Rheumatic Diseases.

In the randomized, controlled, open-label, noninferiority study, researchers enrolled patients with PsA or axSpA who were using a TNF inhibitor such as etanercept, adalimumab, or infliximab, and had stable low disease activity for at least 6 months. Patients needed to have a Psoriatic Arthritis Disease Activity Score (PASDAS) of 3.2 or less, or an Ankylosing Spondylitis Disease Activity Score (ASDAS) of at 2.1 or less. In cases of flare, patients were treated with NSAIDs and/or glucorticoids, and if they still had not reached low disease activity after a month, their previous TNF inhibitor dose was reinstated to the last effective interval or dosage, which was maintained throughout the study period. When the patient was already using a full TNF-inhibitor dose or if dose adjustment did not suffice, patients were switched to another biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD).

Participants were randomized, from January 2019 to June 2021, to a tapering or a nontapering T2T strategy in a 2:1 fashion. Then researchers then followed them for 12 months and aimed to determine if the tapering strategy proved noninferior to not tapering within a predefined 20% margin for noninferiority, which Dr. Michielsens said was derived from other studies and what her group determined to be “an acceptable risk.”

Results show strategy is ‘feasible in daily clinical care’

A total of 81 patients – 42 with PsA and 39 with axSpA – were in the group with tapering, and 41 were in the group without tapering: 22 with PsA and 19 with axSpA.

At 12 months, researchers found that 69% of the patients in the group with tapering had low disease activity, measured via the PASDAS and ASDAS, compared with 73% in patients who did not taper. And those in the tapering group saw their medication use dramatically reduced. At the 12-month mark, they were taking just 53% of the defined daily dose for maintenance, compared with 91% of the defined daily dose for the group that didn’t taper.

The researchers were able to successfully taper 72% of the patients in the tapering group, with 28% of them discontinuing their TNF-inhibitor medication entirely. The incidence of flares was 85% in the tapering group and 78% in the nontapering group, a nonsignificant difference (P = .32).

The start of a new medication or an increase in use of an existing medication was more frequent in the tapering group, and significantly so for NSAIDs. An increase in NSAID use was seen in 54% of the tapering group and in just 24% of the nontapering group (P = .002).

Conventional synthetic DMARD use went up in the tapering group, compared with the nontapering group, but this was only among the PsA patients and the change in use was not statistically significant. There were also more frequent increases in glucocorticoid use in the tapering group, compared with the nontapering group, but this was not significant.

Dr. Michielsens said the findings show the value of an individualized approach in treating patients with PsA or axSpA.

“Our study – and those [studies] in rheumatoid arthritis earlier – deliver the highest quality of evidence that disease activity–guided dose personalization can, and in fact should, be used in clinical practice,” she said. “Our pragmatic treat-to-target tapering strategy is feasible in daily clinical care, although treat-to-target using PASDAS and ASDAS needs some implementation. In shared decision-making with patients, a 50% reduction in TNFi use is obtainable, while maintaining low disease activity.”

The increase in the use of NSAIDs is something to be aware of, but it is “not concerning,” Dr. Michielsens added. She pointed out that the NSAID use was typically temporary, used when flares arose, and that the drugs are effective, safe, and inexpensive. She also noted that the use of TNF blockers decreased more than the use of NSAIDs increased.

“This seems a perfectly acceptable trade-off that can be discussed with your patient,” she said.

The 12-month duration of the study is likely long enough to show that the tapering strategy works, Dr. Michielsens said. In rheumatoid arthritis studies, for example, differences in strategies didn’t change after 1 year.

“That said, we are doing an observational extension study to provide more insights in the long-term effects of this treat-to-target strategy,” she said. “At the end of this summer, all patients will have completed their extended follow-up period – a 12-month observational period – so hopefully we can present the results next year at EULAR.”

This study received funding from ReumaNederland. Dr. Michielsens did not have any financial interests to disclose. Two coauthors reported financial relationships with numerous pharmaceutical companies.

MRI criteria used to diagnose axial spondyloarthritis (axSpA) may require gender-specific revision, according to research conducted at Charité Universitätsmedizin Berlin.

Although established MRI markers were detected in both sexes, their prevalence was substantially different in some cases – ankylosis and fat metaplasia were more prevalent in male than female patients, for example, while sclerosis was far more common in females.

“There’s increasing evidence in the literature and awareness in clinical practice that there are some sex differences in the clinical presentation of axSpA,” said radiologist Sevtap Tugce Ulas, MD, at the annual European Congress of Rheumatology.

She presented the first results of a study examining the diagnostic performance of MRI findings for men and women. “Men have a high risk of structural damage, while women are more likely to be affected by peripheral manifestations with a higher risk for pain, stiffness, and fatigue.”

Joint biomechanics are different in men and women, she pointed out, which might explain some of the disparities. She observed that diagnostic delay – a known problem in axSpA – was “significantly longer” in female patients.

Dr. Ulas and colleagues conducted a post hoc analysis of participants in six prospective axSpA cohorts. From a total of more than 1,100 participants, the researchers identified 684 who had both a clinical diagnosis and complete imaging data available for evaluation. The study population included 379 men and women with and 305 men and women without axSpA.

The mean age overall in all groups was 37 years, with axSpA patients more likely than controls to have elevated C-reactive protein levels; levels were also higher in men with axSpA, compared with in women with axSpA.

Men with axSpA also were more likely than women to be HLA-B27 positive (91% vs. 79%), but there were similar mean Bath Ankylosing Spondylitis Disease Activity Index scores recorded (4.4 vs. 4.6) among the subjects with axSpA.

Two experienced radiologists, blinded to the clinical diagnosis, scored the MRI images independently of each other, looking for the presence of ankylosis; erosions; sclerosis; fat metaplasia; and bone marrow edema in the ventral, mid, and dorsal regions of the sacroiliac joints. Any disagreement between the two reviewers was assessed by a third, more experienced radiologist.

Clear differences in MRI markers

“If you look in detail, we found no major sex-specific differences for erosion and bone marrow edema,” Dr. Ulas reported.

The situation was quite different for other MRI parameters examined. Indeed, more men than women had evidence of ankylosis (24.3% vs. 7.4%) and fat metaplasia (58.8% vs. 42.6%). Conversely, women were more likely than men to have evidence of sclerosis (75.0% vs. 57.6%).

“To make the performance more easily comparable, we calculated a diagnostic odds ratio, which is simply positive likelihood ratio divided by negative likelihood ratio,” Dr. Ulas said.

Doing this showed that the presence of ankylosis had “an almost 10 times stronger performance in men,” with a DOR of 40.1 versus 4.7 for women.

“Interestingly, this was not only caused by low prevalence in females, but also by high rates of false positives,” she said.

DOR for the other parameters in men and women were 18.6 and 6.3 for fat metaplasia, 2.5 and 3.0 for sclerosis, 17.6 and 11.1 for joint erosion, and 2.5 and 3.7 for bone edema.

Overall, diagnostic accuracy was improved only when middle and dorsal lesions were considered.
 

‘Remarkably different’ results

“By definition, these patients have the same disease,” said Hendrik Schulze-Koops, MD, of Ludwig Maximilian University of Munich (Germany).

EULAR

Yet these are “remarkably different” findings, Dr. Schulze-Koops said during a closing highlights session of the congress.

Current imaging practices don’t differentiate between the sexes but perhaps they might need to, he said, because these data suggest “female patients have a different MRI pattern from what we learn from the textbooks.

“[The investigators] say diagnostic performance of established imaging markers on MRI is significantly lower in female axSpA patients, and we should consider this when we are in the situation where we question the disease.”

Marta Mosca, MD, PhD, of the University of Pisa (Italy) and who cochaired the session in which Dr. Ulas had presented the findings commented: “I think is very interesting. We always talk about gender differences in treatment and in the assessment.”

However, Dr. Mosca asked if there were plans to study other patient cohorts, notably those not just referred by a rheumatologist, as that was “a big limitation.”

Dr. Ulas replied: “I think we need follow-up studies to investigate this problem, because we know that there are differences in the clinical presentation and also in the imaging, and this is an important point.”

Of course, there are other limitations, Dr. Ulas said, such as the sole use of conventional T1-weighted spin echo sequences. Although often routinely used in clinical practice, this imaging technique can lead to overestimation of structural damage. Moreover, “subtle differences might have been missed” in bone marrow edema because it wasn’t included in the semiquantitative scoring system used.

“Most importantly, the MRI images under investigation were also used in the diagnostic process, which carries the risk of circular reasoning,” Dr. Ulas said.

However, there are clearly some differences in imaging appearance between men and women, and “we show a significantly lower performance of many typical MRI findings in women,” Dr. Ulas said. “We hope that these findings might spark a critical discussion on the appropriateness of sex-blind classification criteria for axSpA, and hopefully, eventually lead to refined criteria for both sexes.”

Dr. Ulas had no conflicts of interest to disclose. Dr. Schulze-Koops and Dr. Mosca were not involved in the study and had no relevant disclosures.

MRI criteria used to diagnose axial spondyloarthritis (axSpA) may require gender-specific revision, according to research conducted at Charité Universitätsmedizin Berlin.

Although established MRI markers were detected in both sexes, their prevalence was substantially different in some cases – ankylosis and fat metaplasia were more prevalent in male than female patients, for example, while sclerosis was far more common in females.

“There’s increasing evidence in the literature and awareness in clinical practice that there are some sex differences in the clinical presentation of axSpA,” said radiologist Sevtap Tugce Ulas, MD, at the annual European Congress of Rheumatology.

She presented the first results of a study examining the diagnostic performance of MRI findings for men and women. “Men have a high risk of structural damage, while women are more likely to be affected by peripheral manifestations with a higher risk for pain, stiffness, and fatigue.”

Joint biomechanics are different in men and women, she pointed out, which might explain some of the disparities. She observed that diagnostic delay – a known problem in axSpA – was “significantly longer” in female patients.

Dr. Ulas and colleagues conducted a post hoc analysis of participants in six prospective axSpA cohorts. From a total of more than 1,100 participants, the researchers identified 684 who had both a clinical diagnosis and complete imaging data available for evaluation. The study population included 379 men and women with and 305 men and women without axSpA.

The mean age overall in all groups was 37 years, with axSpA patients more likely than controls to have elevated C-reactive protein levels; levels were also higher in men with axSpA, compared with in women with axSpA.

Men with axSpA also were more likely than women to be HLA-B27 positive (91% vs. 79%), but there were similar mean Bath Ankylosing Spondylitis Disease Activity Index scores recorded (4.4 vs. 4.6) among the subjects with axSpA.

Two experienced radiologists, blinded to the clinical diagnosis, scored the MRI images independently of each other, looking for the presence of ankylosis; erosions; sclerosis; fat metaplasia; and bone marrow edema in the ventral, mid, and dorsal regions of the sacroiliac joints. Any disagreement between the two reviewers was assessed by a third, more experienced radiologist.

Clear differences in MRI markers

“If you look in detail, we found no major sex-specific differences for erosion and bone marrow edema,” Dr. Ulas reported.

The situation was quite different for other MRI parameters examined. Indeed, more men than women had evidence of ankylosis (24.3% vs. 7.4%) and fat metaplasia (58.8% vs. 42.6%). Conversely, women were more likely than men to have evidence of sclerosis (75.0% vs. 57.6%).

“To make the performance more easily comparable, we calculated a diagnostic odds ratio, which is simply positive likelihood ratio divided by negative likelihood ratio,” Dr. Ulas said.

Doing this showed that the presence of ankylosis had “an almost 10 times stronger performance in men,” with a DOR of 40.1 versus 4.7 for women.

“Interestingly, this was not only caused by low prevalence in females, but also by high rates of false positives,” she said.

DOR for the other parameters in men and women were 18.6 and 6.3 for fat metaplasia, 2.5 and 3.0 for sclerosis, 17.6 and 11.1 for joint erosion, and 2.5 and 3.7 for bone edema.

Overall, diagnostic accuracy was improved only when middle and dorsal lesions were considered.
 

‘Remarkably different’ results

“By definition, these patients have the same disease,” said Hendrik Schulze-Koops, MD, of Ludwig Maximilian University of Munich (Germany).

EULAR

Yet these are “remarkably different” findings, Dr. Schulze-Koops said during a closing highlights session of the congress.

Current imaging practices don’t differentiate between the sexes but perhaps they might need to, he said, because these data suggest “female patients have a different MRI pattern from what we learn from the textbooks.

“[The investigators] say diagnostic performance of established imaging markers on MRI is significantly lower in female axSpA patients, and we should consider this when we are in the situation where we question the disease.”

Marta Mosca, MD, PhD, of the University of Pisa (Italy) and who cochaired the session in which Dr. Ulas had presented the findings commented: “I think is very interesting. We always talk about gender differences in treatment and in the assessment.”

However, Dr. Mosca asked if there were plans to study other patient cohorts, notably those not just referred by a rheumatologist, as that was “a big limitation.”

Dr. Ulas replied: “I think we need follow-up studies to investigate this problem, because we know that there are differences in the clinical presentation and also in the imaging, and this is an important point.”

Of course, there are other limitations, Dr. Ulas said, such as the sole use of conventional T1-weighted spin echo sequences. Although often routinely used in clinical practice, this imaging technique can lead to overestimation of structural damage. Moreover, “subtle differences might have been missed” in bone marrow edema because it wasn’t included in the semiquantitative scoring system used.

“Most importantly, the MRI images under investigation were also used in the diagnostic process, which carries the risk of circular reasoning,” Dr. Ulas said.

However, there are clearly some differences in imaging appearance between men and women, and “we show a significantly lower performance of many typical MRI findings in women,” Dr. Ulas said. “We hope that these findings might spark a critical discussion on the appropriateness of sex-blind classification criteria for axSpA, and hopefully, eventually lead to refined criteria for both sexes.”

Dr. Ulas had no conflicts of interest to disclose. Dr. Schulze-Koops and Dr. Mosca were not involved in the study and had no relevant disclosures.

MRI criteria used to diagnose axial spondyloarthritis (axSpA) may require gender-specific revision, according to research conducted at Charité Universitätsmedizin Berlin.

Although established MRI markers were detected in both sexes, their prevalence was substantially different in some cases – ankylosis and fat metaplasia were more prevalent in male than female patients, for example, while sclerosis was far more common in females.

“There’s increasing evidence in the literature and awareness in clinical practice that there are some sex differences in the clinical presentation of axSpA,” said radiologist Sevtap Tugce Ulas, MD, at the annual European Congress of Rheumatology.

She presented the first results of a study examining the diagnostic performance of MRI findings for men and women. “Men have a high risk of structural damage, while women are more likely to be affected by peripheral manifestations with a higher risk for pain, stiffness, and fatigue.”

Joint biomechanics are different in men and women, she pointed out, which might explain some of the disparities. She observed that diagnostic delay – a known problem in axSpA – was “significantly longer” in female patients.

Dr. Ulas and colleagues conducted a post hoc analysis of participants in six prospective axSpA cohorts. From a total of more than 1,100 participants, the researchers identified 684 who had both a clinical diagnosis and complete imaging data available for evaluation. The study population included 379 men and women with and 305 men and women without axSpA.

The mean age overall in all groups was 37 years, with axSpA patients more likely than controls to have elevated C-reactive protein levels; levels were also higher in men with axSpA, compared with in women with axSpA.

Men with axSpA also were more likely than women to be HLA-B27 positive (91% vs. 79%), but there were similar mean Bath Ankylosing Spondylitis Disease Activity Index scores recorded (4.4 vs. 4.6) among the subjects with axSpA.

Two experienced radiologists, blinded to the clinical diagnosis, scored the MRI images independently of each other, looking for the presence of ankylosis; erosions; sclerosis; fat metaplasia; and bone marrow edema in the ventral, mid, and dorsal regions of the sacroiliac joints. Any disagreement between the two reviewers was assessed by a third, more experienced radiologist.

Clear differences in MRI markers

“If you look in detail, we found no major sex-specific differences for erosion and bone marrow edema,” Dr. Ulas reported.

The situation was quite different for other MRI parameters examined. Indeed, more men than women had evidence of ankylosis (24.3% vs. 7.4%) and fat metaplasia (58.8% vs. 42.6%). Conversely, women were more likely than men to have evidence of sclerosis (75.0% vs. 57.6%).

“To make the performance more easily comparable, we calculated a diagnostic odds ratio, which is simply positive likelihood ratio divided by negative likelihood ratio,” Dr. Ulas said.

Doing this showed that the presence of ankylosis had “an almost 10 times stronger performance in men,” with a DOR of 40.1 versus 4.7 for women.

“Interestingly, this was not only caused by low prevalence in females, but also by high rates of false positives,” she said.

DOR for the other parameters in men and women were 18.6 and 6.3 for fat metaplasia, 2.5 and 3.0 for sclerosis, 17.6 and 11.1 for joint erosion, and 2.5 and 3.7 for bone edema.

Overall, diagnostic accuracy was improved only when middle and dorsal lesions were considered.
 

‘Remarkably different’ results

“By definition, these patients have the same disease,” said Hendrik Schulze-Koops, MD, of Ludwig Maximilian University of Munich (Germany).

EULAR

Yet these are “remarkably different” findings, Dr. Schulze-Koops said during a closing highlights session of the congress.

Current imaging practices don’t differentiate between the sexes but perhaps they might need to, he said, because these data suggest “female patients have a different MRI pattern from what we learn from the textbooks.

“[The investigators] say diagnostic performance of established imaging markers on MRI is significantly lower in female axSpA patients, and we should consider this when we are in the situation where we question the disease.”

Marta Mosca, MD, PhD, of the University of Pisa (Italy) and who cochaired the session in which Dr. Ulas had presented the findings commented: “I think is very interesting. We always talk about gender differences in treatment and in the assessment.”

However, Dr. Mosca asked if there were plans to study other patient cohorts, notably those not just referred by a rheumatologist, as that was “a big limitation.”

Dr. Ulas replied: “I think we need follow-up studies to investigate this problem, because we know that there are differences in the clinical presentation and also in the imaging, and this is an important point.”

Of course, there are other limitations, Dr. Ulas said, such as the sole use of conventional T1-weighted spin echo sequences. Although often routinely used in clinical practice, this imaging technique can lead to overestimation of structural damage. Moreover, “subtle differences might have been missed” in bone marrow edema because it wasn’t included in the semiquantitative scoring system used.

“Most importantly, the MRI images under investigation were also used in the diagnostic process, which carries the risk of circular reasoning,” Dr. Ulas said.

However, there are clearly some differences in imaging appearance between men and women, and “we show a significantly lower performance of many typical MRI findings in women,” Dr. Ulas said. “We hope that these findings might spark a critical discussion on the appropriateness of sex-blind classification criteria for axSpA, and hopefully, eventually lead to refined criteria for both sexes.”

Dr. Ulas had no conflicts of interest to disclose. Dr. Schulze-Koops and Dr. Mosca were not involved in the study and had no relevant disclosures.

COPENHAGEN – Use of the dual interleukin (IL)–17 inhibitor bimekizumab (Bimzelx) was associated with rapid reductions in signs and symptoms of radiographic axial spondyloarthritis, reported investigators in the BE MOBILE 2 phase 3 trial.

At least half of all patients achieved an Ankylosing Spondylitis Disease Activity Score (ASDAS) of less than 2.1 by week 24 of treatment with bimekizumab, and there were marked reductions in objective signs of inflammation, reported Désiréé van der Heijde, MD, PhD, of Leiden (Netherlands) University Medical Center.

“The safety we have seen in this trial was consistent with what we have seen [with bimekizumab] in other trials and other diseases,” she said at the annual European Congress of Rheumatology.
 

IL-17 inhibitor times 2

Bimekizumab is a monoclonal immunoglobulin 1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.

In the BE MOBILE 2 trial, investigators enrolled patients aged 18 years and older who had ankylosing spondylitis, who met modified New York criteria, who had active disease at screening and at baseline, as defined by having a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 4 or more and spinal pain of 4 or more on a scale of 0-10, and whose disease failed to respond to two different NSAIDs or who were either intolerant of or had contraindications to NSAIDs.

The patients were randomly assigned on a 2:1 basis to receive either bimekizumab 160 mg every 4 weeks (221 patients) or placebo (111 patients) for 16 weeks. All patients were switched over at 16 weeks to bimekizumab maintenance for up to 1 year of total treatment.

Dr. Van der Heijde reported 24-week data from the trial, including data from 8 weeks of additional follow-up.
 

All endpoints met

The trial met its primary endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 16. There was a 44.8% improvement with bimekizumab, compared with 22.6% with placebo (P < .001).

All secondary endpoints also favored the bimekizumab arm, including ASAS 40 among patients who had not previously received a tumor necrosis factor (TNF)–alpha inhibitor, ASAS 20, BASDAI functional index, ankylosing spondylitis quality-of-life index, and others.

Responses to bimekizumab were consistent across subpopulations of patients with or without prior TNF-alpha inhibitor exposure, Dr. van der Heidje said.

In addition, use of bimekizumab was associated with a significant improvement from baseline, compared with placebo, in objective measures of inflammation, including MRI spine Berlin score at week 16 (mean, –2.3 vs. 0; P < .001), Spondylitis Research Consortium of Canada (SPARCC) MRI sacroiliac joint score at week 16 (mean, –5.6 vs. 1.1), and high-sensitivity C-reactive protein at week 16 (mean, 2.4 vs. 6.3 mg/L; P < .001).

The most frequent treatment-related adverse events were nasopharyngitis, diarrhea, and oral candidiasis, all of which were more common in the bimekizumab arm, as well as headache, the incidence of which was similar between the arms.

Overall, 6.4% of patients taking bimekizumab had fungal infections, compared with none in the placebo group. The infections were mild or moderate, localized, and mucocutaneous in nature. Only two patients discontinued the drug because of fungal infections: one for oral candidiasis, and one for esophageal candidiasis.

‘Promising results’

Fabian Proft, MD, head of the clinical trials unit at Charité University Hospital in Berlin, who was not involved in the study, told this news organization that the data looked very good.

“These are the first phase 3 data on dual inhibition of IL-17A and F with bimekizumab in axial spondyloarthritis, and the data are really promising,” he said. “For nonradiographic disease, the data also look very promising, and when we’re looking into the future, it might be a therapeutic option for us as treating rheumatologists.”

The study was funded by UCB Pharma. Dr. van der Heijde has received consulting fees from the company and others. Dr. Proft has consulted for and has been on the speaker’s bureau for UCB and other pharmaceutical companies.

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

COPENHAGEN – Use of the dual interleukin (IL)–17 inhibitor bimekizumab (Bimzelx) was associated with rapid reductions in signs and symptoms of radiographic axial spondyloarthritis, reported investigators in the BE MOBILE 2 phase 3 trial.

At least half of all patients achieved an Ankylosing Spondylitis Disease Activity Score (ASDAS) of less than 2.1 by week 24 of treatment with bimekizumab, and there were marked reductions in objective signs of inflammation, reported Désiréé van der Heijde, MD, PhD, of Leiden (Netherlands) University Medical Center.

“The safety we have seen in this trial was consistent with what we have seen [with bimekizumab] in other trials and other diseases,” she said at the annual European Congress of Rheumatology.
 

IL-17 inhibitor times 2

Bimekizumab is a monoclonal immunoglobulin 1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.

In the BE MOBILE 2 trial, investigators enrolled patients aged 18 years and older who had ankylosing spondylitis, who met modified New York criteria, who had active disease at screening and at baseline, as defined by having a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 4 or more and spinal pain of 4 or more on a scale of 0-10, and whose disease failed to respond to two different NSAIDs or who were either intolerant of or had contraindications to NSAIDs.

The patients were randomly assigned on a 2:1 basis to receive either bimekizumab 160 mg every 4 weeks (221 patients) or placebo (111 patients) for 16 weeks. All patients were switched over at 16 weeks to bimekizumab maintenance for up to 1 year of total treatment.

Dr. Van der Heijde reported 24-week data from the trial, including data from 8 weeks of additional follow-up.
 

All endpoints met

The trial met its primary endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 16. There was a 44.8% improvement with bimekizumab, compared with 22.6% with placebo (P < .001).

All secondary endpoints also favored the bimekizumab arm, including ASAS 40 among patients who had not previously received a tumor necrosis factor (TNF)–alpha inhibitor, ASAS 20, BASDAI functional index, ankylosing spondylitis quality-of-life index, and others.

Responses to bimekizumab were consistent across subpopulations of patients with or without prior TNF-alpha inhibitor exposure, Dr. van der Heidje said.

In addition, use of bimekizumab was associated with a significant improvement from baseline, compared with placebo, in objective measures of inflammation, including MRI spine Berlin score at week 16 (mean, –2.3 vs. 0; P < .001), Spondylitis Research Consortium of Canada (SPARCC) MRI sacroiliac joint score at week 16 (mean, –5.6 vs. 1.1), and high-sensitivity C-reactive protein at week 16 (mean, 2.4 vs. 6.3 mg/L; P < .001).

The most frequent treatment-related adverse events were nasopharyngitis, diarrhea, and oral candidiasis, all of which were more common in the bimekizumab arm, as well as headache, the incidence of which was similar between the arms.

Overall, 6.4% of patients taking bimekizumab had fungal infections, compared with none in the placebo group. The infections were mild or moderate, localized, and mucocutaneous in nature. Only two patients discontinued the drug because of fungal infections: one for oral candidiasis, and one for esophageal candidiasis.

‘Promising results’

Fabian Proft, MD, head of the clinical trials unit at Charité University Hospital in Berlin, who was not involved in the study, told this news organization that the data looked very good.

“These are the first phase 3 data on dual inhibition of IL-17A and F with bimekizumab in axial spondyloarthritis, and the data are really promising,” he said. “For nonradiographic disease, the data also look very promising, and when we’re looking into the future, it might be a therapeutic option for us as treating rheumatologists.”

The study was funded by UCB Pharma. Dr. van der Heijde has received consulting fees from the company and others. Dr. Proft has consulted for and has been on the speaker’s bureau for UCB and other pharmaceutical companies.

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

COPENHAGEN – Use of the dual interleukin (IL)–17 inhibitor bimekizumab (Bimzelx) was associated with rapid reductions in signs and symptoms of radiographic axial spondyloarthritis, reported investigators in the BE MOBILE 2 phase 3 trial.

At least half of all patients achieved an Ankylosing Spondylitis Disease Activity Score (ASDAS) of less than 2.1 by week 24 of treatment with bimekizumab, and there were marked reductions in objective signs of inflammation, reported Désiréé van der Heijde, MD, PhD, of Leiden (Netherlands) University Medical Center.

“The safety we have seen in this trial was consistent with what we have seen [with bimekizumab] in other trials and other diseases,” she said at the annual European Congress of Rheumatology.
 

IL-17 inhibitor times 2

Bimekizumab is a monoclonal immunoglobulin 1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.

In the BE MOBILE 2 trial, investigators enrolled patients aged 18 years and older who had ankylosing spondylitis, who met modified New York criteria, who had active disease at screening and at baseline, as defined by having a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 4 or more and spinal pain of 4 or more on a scale of 0-10, and whose disease failed to respond to two different NSAIDs or who were either intolerant of or had contraindications to NSAIDs.

The patients were randomly assigned on a 2:1 basis to receive either bimekizumab 160 mg every 4 weeks (221 patients) or placebo (111 patients) for 16 weeks. All patients were switched over at 16 weeks to bimekizumab maintenance for up to 1 year of total treatment.

Dr. Van der Heijde reported 24-week data from the trial, including data from 8 weeks of additional follow-up.
 

All endpoints met

The trial met its primary endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 16. There was a 44.8% improvement with bimekizumab, compared with 22.6% with placebo (P < .001).

All secondary endpoints also favored the bimekizumab arm, including ASAS 40 among patients who had not previously received a tumor necrosis factor (TNF)–alpha inhibitor, ASAS 20, BASDAI functional index, ankylosing spondylitis quality-of-life index, and others.

Responses to bimekizumab were consistent across subpopulations of patients with or without prior TNF-alpha inhibitor exposure, Dr. van der Heidje said.

In addition, use of bimekizumab was associated with a significant improvement from baseline, compared with placebo, in objective measures of inflammation, including MRI spine Berlin score at week 16 (mean, –2.3 vs. 0; P < .001), Spondylitis Research Consortium of Canada (SPARCC) MRI sacroiliac joint score at week 16 (mean, –5.6 vs. 1.1), and high-sensitivity C-reactive protein at week 16 (mean, 2.4 vs. 6.3 mg/L; P < .001).

The most frequent treatment-related adverse events were nasopharyngitis, diarrhea, and oral candidiasis, all of which were more common in the bimekizumab arm, as well as headache, the incidence of which was similar between the arms.

Overall, 6.4% of patients taking bimekizumab had fungal infections, compared with none in the placebo group. The infections were mild or moderate, localized, and mucocutaneous in nature. Only two patients discontinued the drug because of fungal infections: one for oral candidiasis, and one for esophageal candidiasis.

‘Promising results’

Fabian Proft, MD, head of the clinical trials unit at Charité University Hospital in Berlin, who was not involved in the study, told this news organization that the data looked very good.

“These are the first phase 3 data on dual inhibition of IL-17A and F with bimekizumab in axial spondyloarthritis, and the data are really promising,” he said. “For nonradiographic disease, the data also look very promising, and when we’re looking into the future, it might be a therapeutic option for us as treating rheumatologists.”

The study was funded by UCB Pharma. Dr. van der Heijde has received consulting fees from the company and others. Dr. Proft has consulted for and has been on the speaker’s bureau for UCB and other pharmaceutical companies.

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

COPENHAGEN – European recommendations and overarching principles for the management of patients with axial spondyloarthritis (axSpA) have remained largely unchanged since 2016 – with a few notable but very important exceptions.

The 2022 updated recommendations include a new point regarding which biologic agents to use for patients with recurrent uveitis, active inflammatory bowel disease (IBD), or significant psoriasis, as well as new advice to reevaluate the diagnosis and consider the presence of comorbidities if the disease doesn’t respond to current therapies, reported Sofia Ramiro, MD, PhD, from Leiden (Netherlands) University Medical Center.

She summarized the 2022 updates at the annual European Congress of Rheumatology on behalf of colleagues in the ASAS (Assessment of SpondyloArthritis International Society)/EULAR committee.

Among other significant updates are a recommendation for managing patients with persistently high disease activity despite conventional therapy, and a recommendation as to what to do when a first biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) fails, Dr. Ramiro said at the meeting.

“Although we have more changes in the pharmacological part, I would like to emphasize the importance of nonpharmacological treatment in axial SpA,” she said.

Overarching principles

The members of the committee that created the recommendations were in complete agreement that axSpA, as they state in the overarching principles, “is a potentially severe disease with diverse manifestations, usually requiring multidisciplinary management coordinated by the rheumatologist.”

They also universally acknowledged that “the primary goal of treating the patient with axSpA is to maximize health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, preservation/normalization of function, and social participation.”

The overarching principles include the aforementioned emphasis on both pharmacologic and nonpharmacologic management, shared decision-making between patients and rheumatologists, and awareness of the potential financial toxicities and societal problems that patients face.

A closer look: New recommendations

As noted before, there are two new recommendations since the 2016 iteration.

Recommendation No. 10 states, “If there is a history of recurrent uveitis or active IBD, preference should be given to a monoclonal antibody against TNF-alpha [tumor necrosis factor–alpha]. For patients with significant psoriasis, an IL-17 [interleukin-17] inhibitor may be preferred.”

This recommendation stipulates that it refers only to IL-17A inhibitors.

The other new recommendation, No. 11, seems like plain common sense. It states, “Absence of response to treatment should trigger reevaluation of the diagnosis and consideration of the presence of comorbidities.”

Revised recommendations

The two significantly revised recommendations deal with drug therapy.

Recommendation No. 9 holds that for patients with persistently high disease activity despite conventional therapy, a TNF inhibitor, including the pegylated humanized antigen-binding fragment certolizumab pegol (Cimzia), an IL-17 inhibitor, or Janus kinase (JAK) inhibitor, should be considered.

Recommendation No. 12 states that if the first biologic or targeted synthetic DMARD fails, switching to another biologic DMARD (TNF inhibitor or IL-17 inhibitor) or JAK inhibitor should be considered.

Transatlantic similarities, differences

Lianne Gensler, MD, a rheumatologist and professor of medicine at the University of California, San Francisco, who served on the committee that developed the 2019 American College of Rheumatology guidelines for the treatment of ankylosing spondylitis and nonradiographic axSpA, said that, while there are similarities between some of the recommendations promulgated on each side of the Atlantic, there are significant differences and even opposing viewpoints.

A primary difference between the two is the methodology used to arrive at the recommendations in the first place, she said in an interview with this news organization.

“ACR uses a very robust approach to guideline development, where each question is addressed by a ‘PICO’ ” population, intervention, control, and outcomes – and that’s good if you have good evidence, but sometimes – often, in fact – we don’t have strong evidence that would lead everyone to choose the same approach every time, and that’s true especially in inflammatory arthritis, where there’s a lot of shared decision-making, so many of the recommendations out of ACR are conditional,” she said.

In contrast, the ASAS/EULAR recommendations are based largely on broader levels of evidence and on consensus. In developing the European recommendations, the authors were able to take into account drugs that were newly approved since the 2019 ACR guidelines were issued, she noted.

Although many of the broader recommendations are similar, they diverge when it comes to specific issues, such as whether to treat to target.

“ACR guidelines say, ‘Do not treat to target.’ EULAR guidelines say it’s okay to treat to target. ACR guidelines made that decision because at that time, there was no treat-to-target data,” Dr, Gensler said.

“I think, as rheumatologists, we always want to aim for a goal in a patient, so it’s not unreasonable, but I think we shouldn’t attach too much to a number,” she said.

Another difference is that the ACR guidelines recommend against switching to a biosimilar agent when a patient’s condition is stable with the originator biologic.

Dr. Gensler said that she particularly appreciated the new EULAR recommendation (No. 11) to reconsider the diagnosis for patients for whom therapies have failed.

“The sense that nonresponse means ongoing disease activity and therefore drug escalation or change needs to happen is not always the right answer,” she said.

The process for developing the recommendations was supported by EULAR. Dr. Ramiro has received research grants and consulting and/or speaking fees from AbbVie, Eli Lilly, Galapagos, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. Dr. Gensler has received research grant support from Novartis, Pfizer, and UCB and has consulting relationships with AbbVie, Gilead, Janssen, MoonLake, Novartis, and Pfizer.

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

COPENHAGEN – European recommendations and overarching principles for the management of patients with axial spondyloarthritis (axSpA) have remained largely unchanged since 2016 – with a few notable but very important exceptions.

The 2022 updated recommendations include a new point regarding which biologic agents to use for patients with recurrent uveitis, active inflammatory bowel disease (IBD), or significant psoriasis, as well as new advice to reevaluate the diagnosis and consider the presence of comorbidities if the disease doesn’t respond to current therapies, reported Sofia Ramiro, MD, PhD, from Leiden (Netherlands) University Medical Center.

She summarized the 2022 updates at the annual European Congress of Rheumatology on behalf of colleagues in the ASAS (Assessment of SpondyloArthritis International Society)/EULAR committee.

Among other significant updates are a recommendation for managing patients with persistently high disease activity despite conventional therapy, and a recommendation as to what to do when a first biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) fails, Dr. Ramiro said at the meeting.

“Although we have more changes in the pharmacological part, I would like to emphasize the importance of nonpharmacological treatment in axial SpA,” she said.

Overarching principles

The members of the committee that created the recommendations were in complete agreement that axSpA, as they state in the overarching principles, “is a potentially severe disease with diverse manifestations, usually requiring multidisciplinary management coordinated by the rheumatologist.”

They also universally acknowledged that “the primary goal of treating the patient with axSpA is to maximize health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, preservation/normalization of function, and social participation.”

The overarching principles include the aforementioned emphasis on both pharmacologic and nonpharmacologic management, shared decision-making between patients and rheumatologists, and awareness of the potential financial toxicities and societal problems that patients face.

A closer look: New recommendations

As noted before, there are two new recommendations since the 2016 iteration.

Recommendation No. 10 states, “If there is a history of recurrent uveitis or active IBD, preference should be given to a monoclonal antibody against TNF-alpha [tumor necrosis factor–alpha]. For patients with significant psoriasis, an IL-17 [interleukin-17] inhibitor may be preferred.”

This recommendation stipulates that it refers only to IL-17A inhibitors.

The other new recommendation, No. 11, seems like plain common sense. It states, “Absence of response to treatment should trigger reevaluation of the diagnosis and consideration of the presence of comorbidities.”

Revised recommendations

The two significantly revised recommendations deal with drug therapy.

Recommendation No. 9 holds that for patients with persistently high disease activity despite conventional therapy, a TNF inhibitor, including the pegylated humanized antigen-binding fragment certolizumab pegol (Cimzia), an IL-17 inhibitor, or Janus kinase (JAK) inhibitor, should be considered.

Recommendation No. 12 states that if the first biologic or targeted synthetic DMARD fails, switching to another biologic DMARD (TNF inhibitor or IL-17 inhibitor) or JAK inhibitor should be considered.

Transatlantic similarities, differences

Lianne Gensler, MD, a rheumatologist and professor of medicine at the University of California, San Francisco, who served on the committee that developed the 2019 American College of Rheumatology guidelines for the treatment of ankylosing spondylitis and nonradiographic axSpA, said that, while there are similarities between some of the recommendations promulgated on each side of the Atlantic, there are significant differences and even opposing viewpoints.

A primary difference between the two is the methodology used to arrive at the recommendations in the first place, she said in an interview with this news organization.

“ACR uses a very robust approach to guideline development, where each question is addressed by a ‘PICO’ ” population, intervention, control, and outcomes – and that’s good if you have good evidence, but sometimes – often, in fact – we don’t have strong evidence that would lead everyone to choose the same approach every time, and that’s true especially in inflammatory arthritis, where there’s a lot of shared decision-making, so many of the recommendations out of ACR are conditional,” she said.

In contrast, the ASAS/EULAR recommendations are based largely on broader levels of evidence and on consensus. In developing the European recommendations, the authors were able to take into account drugs that were newly approved since the 2019 ACR guidelines were issued, she noted.

Although many of the broader recommendations are similar, they diverge when it comes to specific issues, such as whether to treat to target.

“ACR guidelines say, ‘Do not treat to target.’ EULAR guidelines say it’s okay to treat to target. ACR guidelines made that decision because at that time, there was no treat-to-target data,” Dr, Gensler said.

“I think, as rheumatologists, we always want to aim for a goal in a patient, so it’s not unreasonable, but I think we shouldn’t attach too much to a number,” she said.

Another difference is that the ACR guidelines recommend against switching to a biosimilar agent when a patient’s condition is stable with the originator biologic.

Dr. Gensler said that she particularly appreciated the new EULAR recommendation (No. 11) to reconsider the diagnosis for patients for whom therapies have failed.

“The sense that nonresponse means ongoing disease activity and therefore drug escalation or change needs to happen is not always the right answer,” she said.

The process for developing the recommendations was supported by EULAR. Dr. Ramiro has received research grants and consulting and/or speaking fees from AbbVie, Eli Lilly, Galapagos, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. Dr. Gensler has received research grant support from Novartis, Pfizer, and UCB and has consulting relationships with AbbVie, Gilead, Janssen, MoonLake, Novartis, and Pfizer.

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

COPENHAGEN – European recommendations and overarching principles for the management of patients with axial spondyloarthritis (axSpA) have remained largely unchanged since 2016 – with a few notable but very important exceptions.

The 2022 updated recommendations include a new point regarding which biologic agents to use for patients with recurrent uveitis, active inflammatory bowel disease (IBD), or significant psoriasis, as well as new advice to reevaluate the diagnosis and consider the presence of comorbidities if the disease doesn’t respond to current therapies, reported Sofia Ramiro, MD, PhD, from Leiden (Netherlands) University Medical Center.

She summarized the 2022 updates at the annual European Congress of Rheumatology on behalf of colleagues in the ASAS (Assessment of SpondyloArthritis International Society)/EULAR committee.

Among other significant updates are a recommendation for managing patients with persistently high disease activity despite conventional therapy, and a recommendation as to what to do when a first biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) fails, Dr. Ramiro said at the meeting.

“Although we have more changes in the pharmacological part, I would like to emphasize the importance of nonpharmacological treatment in axial SpA,” she said.

Overarching principles

The members of the committee that created the recommendations were in complete agreement that axSpA, as they state in the overarching principles, “is a potentially severe disease with diverse manifestations, usually requiring multidisciplinary management coordinated by the rheumatologist.”

They also universally acknowledged that “the primary goal of treating the patient with axSpA is to maximize health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, preservation/normalization of function, and social participation.”

The overarching principles include the aforementioned emphasis on both pharmacologic and nonpharmacologic management, shared decision-making between patients and rheumatologists, and awareness of the potential financial toxicities and societal problems that patients face.

A closer look: New recommendations

As noted before, there are two new recommendations since the 2016 iteration.

Recommendation No. 10 states, “If there is a history of recurrent uveitis or active IBD, preference should be given to a monoclonal antibody against TNF-alpha [tumor necrosis factor–alpha]. For patients with significant psoriasis, an IL-17 [interleukin-17] inhibitor may be preferred.”

This recommendation stipulates that it refers only to IL-17A inhibitors.

The other new recommendation, No. 11, seems like plain common sense. It states, “Absence of response to treatment should trigger reevaluation of the diagnosis and consideration of the presence of comorbidities.”

Revised recommendations

The two significantly revised recommendations deal with drug therapy.

Recommendation No. 9 holds that for patients with persistently high disease activity despite conventional therapy, a TNF inhibitor, including the pegylated humanized antigen-binding fragment certolizumab pegol (Cimzia), an IL-17 inhibitor, or Janus kinase (JAK) inhibitor, should be considered.

Recommendation No. 12 states that if the first biologic or targeted synthetic DMARD fails, switching to another biologic DMARD (TNF inhibitor or IL-17 inhibitor) or JAK inhibitor should be considered.

Transatlantic similarities, differences

Lianne Gensler, MD, a rheumatologist and professor of medicine at the University of California, San Francisco, who served on the committee that developed the 2019 American College of Rheumatology guidelines for the treatment of ankylosing spondylitis and nonradiographic axSpA, said that, while there are similarities between some of the recommendations promulgated on each side of the Atlantic, there are significant differences and even opposing viewpoints.

A primary difference between the two is the methodology used to arrive at the recommendations in the first place, she said in an interview with this news organization.

“ACR uses a very robust approach to guideline development, where each question is addressed by a ‘PICO’ ” population, intervention, control, and outcomes – and that’s good if you have good evidence, but sometimes – often, in fact – we don’t have strong evidence that would lead everyone to choose the same approach every time, and that’s true especially in inflammatory arthritis, where there’s a lot of shared decision-making, so many of the recommendations out of ACR are conditional,” she said.

In contrast, the ASAS/EULAR recommendations are based largely on broader levels of evidence and on consensus. In developing the European recommendations, the authors were able to take into account drugs that were newly approved since the 2019 ACR guidelines were issued, she noted.

Although many of the broader recommendations are similar, they diverge when it comes to specific issues, such as whether to treat to target.

“ACR guidelines say, ‘Do not treat to target.’ EULAR guidelines say it’s okay to treat to target. ACR guidelines made that decision because at that time, there was no treat-to-target data,” Dr, Gensler said.

“I think, as rheumatologists, we always want to aim for a goal in a patient, so it’s not unreasonable, but I think we shouldn’t attach too much to a number,” she said.

Another difference is that the ACR guidelines recommend against switching to a biosimilar agent when a patient’s condition is stable with the originator biologic.

Dr. Gensler said that she particularly appreciated the new EULAR recommendation (No. 11) to reconsider the diagnosis for patients for whom therapies have failed.

“The sense that nonresponse means ongoing disease activity and therefore drug escalation or change needs to happen is not always the right answer,” she said.

The process for developing the recommendations was supported by EULAR. Dr. Ramiro has received research grants and consulting and/or speaking fees from AbbVie, Eli Lilly, Galapagos, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. Dr. Gensler has received research grant support from Novartis, Pfizer, and UCB and has consulting relationships with AbbVie, Gilead, Janssen, MoonLake, Novartis, and Pfizer.

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

COPENHAGEN – The Janus kinase (JAK) inhibitor upadacitinib (Rinvoq, AbbVie) was associated with significant improvements in disease activity, pain, function, and quality of life, compared with placebo, in patients with nonradiographic axial spondyloarthritis (nr-axSpA), results of the first efficacy analysis of the phase 3, randomized SELECT-AXIS-2 trial showed.

The trial met its primary endpoint of an improvement of Assessment of SpondyloArthritis International Society 40% (ASAS 40) response criteria in the prespecified efficacy analysis at week 14, reported Filip Van den Bosch, MD, PhD, Ghent (Belgium) University.

In all, 45% of patients randomized to receive upadacitinib achieved an ASAS 40, compared with 23% of those assigned to placebo (P < .001).

“This is the first study showing efficacy and showing that the JAK inhibitor upadacitinib might be a therapeutic option in patients with active, nonradiographic spondyloarthritis,” Van den Bosch said at the annual European Congress of Rheumatology.

Although JAK inhibitors have previously been shown to be efficacious and safe for the treatment of ankylosing spondylitis, the SELECT-AXIS-2 trial is the first to evaluate a JAK inhibitor in nonradiographic axSpA, he added.
 

Study details

Patients 18 years and older with rheumatologist-diagnosed nr-axSpA were eligible for the study if they also met 2009 ASAS classification criteria for axSpA but not the radiologic criterion of modified New York criteria; had objective signs of active inflammation consistent with axSpA on MRI of the sacroiliac joints and/or high-sensitivity C-reactive protein above the upper limit of normal (2.87 mg/L) at screening; and had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and patient-assessment of total back pain scores of 4 or greater based on a 0-10 numeric rating scale at study entry.

Patients were screened with MRI imaging of the spine and x-rays of the sacroiliac joints and spine, and then randomized to receive either placebo (157 patients) or upadacitinib 15 mg daily (158 patients) for 52 weeks. At the end of 52 weeks, all patients on upadacitinib will continue on the drug at the same dose level, and those assigned to placebo will be switched over to 15 mg upadacitinib daily maintenance.

As well as meeting the primary endpoint at week 14, response rates with the JAK inhibitor were higher at all time points over this initial time period, Dr. Van den Bosch noted.
 

Most targets hit

Of 14 multiplicity-controlled secondary endpoints, 12 were statistically better with upadacitinib, including change from baseline in patient’s assessment of total back pain, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Disease Activity Score, Low Disease Activity, Ankylosing Spondylitis Quality of Life, and MRI Spondyloarthritis Research Consortium of Canada score for sacroiliac joints.

Only the BASDAI and Maastricht Ankylosing Spondylitis Enthesitis Score were not significantly better with the JAK inhibitor.

The safety of upadacitinib in this setting was consistent with its known safety profile, Dr. Van den Bosch said.

Approximately half of all patients in each trial arm had an adverse event. Serious adverse events were reported in four patients assigned to upadacitinib versus two on placebo, and serious adverse events requiring drug discontinuation occurred in two and four patients, respectively.
 

‘Important’ data

Fabian Proft, MD, head of the clinical trials unit at Charite University Hospital, Berlin, who was not involved in the study, said in an interview that the findings were not surprising.

“We know the efficacy of upadacitinib already in radiographic axial spondyloarthritis, and from all the other drugs that we also know that are effective in radiographic axial spondyloarthritis that are similarly effective in nonradiographic disease,” he said.

“I think it is really important because it is the first data on JAK inhibition also in non-radiographic axial spondyloarthritis – an important step,” said Dr. Proft, who was comoderator of the oral abstract session where Van den Bosch reported the data.

The trial was supported by AbbVie. Dr. Van den Bosch disclosed speaker and consulting fees from AbbVie and others. Dr. Proft disclosed speaker and consulting fees from AbbVie as well.

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

COPENHAGEN – The Janus kinase (JAK) inhibitor upadacitinib (Rinvoq, AbbVie) was associated with significant improvements in disease activity, pain, function, and quality of life, compared with placebo, in patients with nonradiographic axial spondyloarthritis (nr-axSpA), results of the first efficacy analysis of the phase 3, randomized SELECT-AXIS-2 trial showed.

The trial met its primary endpoint of an improvement of Assessment of SpondyloArthritis International Society 40% (ASAS 40) response criteria in the prespecified efficacy analysis at week 14, reported Filip Van den Bosch, MD, PhD, Ghent (Belgium) University.

In all, 45% of patients randomized to receive upadacitinib achieved an ASAS 40, compared with 23% of those assigned to placebo (P < .001).

“This is the first study showing efficacy and showing that the JAK inhibitor upadacitinib might be a therapeutic option in patients with active, nonradiographic spondyloarthritis,” Van den Bosch said at the annual European Congress of Rheumatology.

Although JAK inhibitors have previously been shown to be efficacious and safe for the treatment of ankylosing spondylitis, the SELECT-AXIS-2 trial is the first to evaluate a JAK inhibitor in nonradiographic axSpA, he added.
 

Study details

Patients 18 years and older with rheumatologist-diagnosed nr-axSpA were eligible for the study if they also met 2009 ASAS classification criteria for axSpA but not the radiologic criterion of modified New York criteria; had objective signs of active inflammation consistent with axSpA on MRI of the sacroiliac joints and/or high-sensitivity C-reactive protein above the upper limit of normal (2.87 mg/L) at screening; and had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and patient-assessment of total back pain scores of 4 or greater based on a 0-10 numeric rating scale at study entry.

Patients were screened with MRI imaging of the spine and x-rays of the sacroiliac joints and spine, and then randomized to receive either placebo (157 patients) or upadacitinib 15 mg daily (158 patients) for 52 weeks. At the end of 52 weeks, all patients on upadacitinib will continue on the drug at the same dose level, and those assigned to placebo will be switched over to 15 mg upadacitinib daily maintenance.

As well as meeting the primary endpoint at week 14, response rates with the JAK inhibitor were higher at all time points over this initial time period, Dr. Van den Bosch noted.
 

Most targets hit

Of 14 multiplicity-controlled secondary endpoints, 12 were statistically better with upadacitinib, including change from baseline in patient’s assessment of total back pain, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Disease Activity Score, Low Disease Activity, Ankylosing Spondylitis Quality of Life, and MRI Spondyloarthritis Research Consortium of Canada score for sacroiliac joints.

Only the BASDAI and Maastricht Ankylosing Spondylitis Enthesitis Score were not significantly better with the JAK inhibitor.

The safety of upadacitinib in this setting was consistent with its known safety profile, Dr. Van den Bosch said.

Approximately half of all patients in each trial arm had an adverse event. Serious adverse events were reported in four patients assigned to upadacitinib versus two on placebo, and serious adverse events requiring drug discontinuation occurred in two and four patients, respectively.
 

‘Important’ data

Fabian Proft, MD, head of the clinical trials unit at Charite University Hospital, Berlin, who was not involved in the study, said in an interview that the findings were not surprising.

“We know the efficacy of upadacitinib already in radiographic axial spondyloarthritis, and from all the other drugs that we also know that are effective in radiographic axial spondyloarthritis that are similarly effective in nonradiographic disease,” he said.

“I think it is really important because it is the first data on JAK inhibition also in non-radiographic axial spondyloarthritis – an important step,” said Dr. Proft, who was comoderator of the oral abstract session where Van den Bosch reported the data.

The trial was supported by AbbVie. Dr. Van den Bosch disclosed speaker and consulting fees from AbbVie and others. Dr. Proft disclosed speaker and consulting fees from AbbVie as well.

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

COPENHAGEN – The Janus kinase (JAK) inhibitor upadacitinib (Rinvoq, AbbVie) was associated with significant improvements in disease activity, pain, function, and quality of life, compared with placebo, in patients with nonradiographic axial spondyloarthritis (nr-axSpA), results of the first efficacy analysis of the phase 3, randomized SELECT-AXIS-2 trial showed.

The trial met its primary endpoint of an improvement of Assessment of SpondyloArthritis International Society 40% (ASAS 40) response criteria in the prespecified efficacy analysis at week 14, reported Filip Van den Bosch, MD, PhD, Ghent (Belgium) University.

In all, 45% of patients randomized to receive upadacitinib achieved an ASAS 40, compared with 23% of those assigned to placebo (P < .001).

“This is the first study showing efficacy and showing that the JAK inhibitor upadacitinib might be a therapeutic option in patients with active, nonradiographic spondyloarthritis,” Van den Bosch said at the annual European Congress of Rheumatology.

Although JAK inhibitors have previously been shown to be efficacious and safe for the treatment of ankylosing spondylitis, the SELECT-AXIS-2 trial is the first to evaluate a JAK inhibitor in nonradiographic axSpA, he added.
 

Study details

Patients 18 years and older with rheumatologist-diagnosed nr-axSpA were eligible for the study if they also met 2009 ASAS classification criteria for axSpA but not the radiologic criterion of modified New York criteria; had objective signs of active inflammation consistent with axSpA on MRI of the sacroiliac joints and/or high-sensitivity C-reactive protein above the upper limit of normal (2.87 mg/L) at screening; and had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and patient-assessment of total back pain scores of 4 or greater based on a 0-10 numeric rating scale at study entry.

Patients were screened with MRI imaging of the spine and x-rays of the sacroiliac joints and spine, and then randomized to receive either placebo (157 patients) or upadacitinib 15 mg daily (158 patients) for 52 weeks. At the end of 52 weeks, all patients on upadacitinib will continue on the drug at the same dose level, and those assigned to placebo will be switched over to 15 mg upadacitinib daily maintenance.

As well as meeting the primary endpoint at week 14, response rates with the JAK inhibitor were higher at all time points over this initial time period, Dr. Van den Bosch noted.
 

Most targets hit

Of 14 multiplicity-controlled secondary endpoints, 12 were statistically better with upadacitinib, including change from baseline in patient’s assessment of total back pain, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Disease Activity Score, Low Disease Activity, Ankylosing Spondylitis Quality of Life, and MRI Spondyloarthritis Research Consortium of Canada score for sacroiliac joints.

Only the BASDAI and Maastricht Ankylosing Spondylitis Enthesitis Score were not significantly better with the JAK inhibitor.

The safety of upadacitinib in this setting was consistent with its known safety profile, Dr. Van den Bosch said.

Approximately half of all patients in each trial arm had an adverse event. Serious adverse events were reported in four patients assigned to upadacitinib versus two on placebo, and serious adverse events requiring drug discontinuation occurred in two and four patients, respectively.
 

‘Important’ data

Fabian Proft, MD, head of the clinical trials unit at Charite University Hospital, Berlin, who was not involved in the study, said in an interview that the findings were not surprising.

“We know the efficacy of upadacitinib already in radiographic axial spondyloarthritis, and from all the other drugs that we also know that are effective in radiographic axial spondyloarthritis that are similarly effective in nonradiographic disease,” he said.

“I think it is really important because it is the first data on JAK inhibition also in non-radiographic axial spondyloarthritis – an important step,” said Dr. Proft, who was comoderator of the oral abstract session where Van den Bosch reported the data.

The trial was supported by AbbVie. Dr. Van den Bosch disclosed speaker and consulting fees from AbbVie and others. Dr. Proft disclosed speaker and consulting fees from AbbVie as well.

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

Obstetrician Beverly Gray, MD, is already seeing the effects of the Roe v. Wade abortion debate in her North Carolina practice.

The state allows abortion but requires that women get counseling with a qualified health professional 72 hours before the procedure. “Aside from that, we still have patients asking for more efficacious contraceptive methods just in case,” said Dr. Gray, residency director and division director for women’s community and population health and associate professor for obstetrics and gynecology at Duke University, Durham, N.C.

Patients and staff in her clinic have also been approaching her about tubal ligation. “They’re asking about additional birth control methods because they’re concerned about what’s going to happen” with the challenge to the historic Roe v. Wade decision in the Supreme Court and subsequent actions in the states to restrict or ban abortion, she said.

This has implications not just for abortion but for medications known to affect pregnancy. “What I’m really worried about is physicians will be withholding medicine because they’re concerned about teratogenic effects,” said Dr. Gray.

With more states issuing restrictions on abortion, doctors are worried that patients needing certain drugs to maintain their lupus flares, cancer, or other diseases may decide not to take them in the event they accidentally become pregnant. If the drug is known to affect the fetus, the fear is a patient who lives in a state with abortion restrictions will no longer have the option to terminate a pregnancy.

zoranm/Getty Images

The U.S. landscape on abortion restrictions

A leaked draft of a U.S. Supreme Court opinion on Mississippi’s 15-week abortion ban has sent the medical community into a tailspin. The case, Dobbs v. Jackson Women’s Health Organization, challenges the 1973 Roe v. Wade decision that affirms the constitutional right to abortion. It’s anticipated the high court will decide on the case in June.

Although the upcoming decision is subject to change, the draft indicated the high court would uphold the Mississippi ban. This would essentially overturn the 1973 ruling. An earlier Supreme Court decision allowing a Texas law banning abortion at 6 weeks suggests the court may already be heading in this direction. At the state level, legislatures have been moving on divergent paths – some taking steps to preserve abortion rights, others initiating restrictions.

More than 100 abortion restrictions in 19 states took effect in 2021, according to the Guttmacher Institute, which tracks such metrics. In 2022, “two key themes are anti-abortion policymakers’ continued pursuit of various types of abortion bans and restrictions on medication abortion,” the institute reported.

Forty-six states and the District of Columbia have introduced 2,025 restrictions or proactive measures on sexual and reproductive health and rights so far this year. The latest tally from Guttmacher, updated in late May, revealed that 11 states so far have enacted 42 abortion restrictions. A total of 6 states (Arizona, Florida, Idaho, Kentucky, Oklahoma, and Wyoming) have issued nine bans on abortion.

Comparatively, 11 states have enacted 19 protective abortion measures.

Twenty-two states have introduced 117 restrictions on medication abortions, which account for 54% of U.S. abortions. This includes seven measures that would ban medication abortion outright, according to Guttmacher. Kentucky and South Dakota collectively have enacted 14 restrictions on medication abortion, as well as provisions that ban mailing of abortion pills.
 

Chilling effect on prescribing

Some physicians anticipate that drugs such as the “morning-after” pill (levonorgestrel) will become less available as restrictions go into effect, since these are medications designed to prevent pregnancy.*

However, the ongoing effort to put a lid on abortion measures has prompted concerns about a trickle-down effect on other medications that are otherwise life-changing or lifesaving to patients but pose a risk to the fetus.

Several drugs are well documented to affect fetal growth and development of the fetus, ranging from mild, transitory effects to severe, permanent birth defects, said Ronald G. Grifka, MD, chief medical officer of University of Michigan Health-West and clinical professor of pediatrics at the University of Michigan Medical School, Ann Arbor. “As new medications are developed, we will need heightened attention to make sure they are safe for the fetus,” he added.

Christina Chambers

The iPLEDGE factor

Some rheumatology drugs like lenalidomide (Revlimid) require a valid negative pregnancy test in a lab every month. Similarly, the iPLEDGE Risk Evaluation and Mitigation Strategy seeks to reduce the teratogenicity of isotretinoin by requiring two types of birth control and regular pregnancy tests by users.

For isotretinoin specifically, abortion restrictions “could lead to increased adherence to pregnancy prevention measures which are already stringent in iPLEDGE. But on the other hand, it could lead to reduced willingness of physicians to prescribe or patients to take the medication,” said Dr. Chambers.

With programs like iPLEDGE in effect, the rate of pregnancies and abortions that occur in dermatology are relatively low, said Jenny Murase, MD, associate clinical professor of dermatology at the University of California, San Francisco.

Fewer women in clinical trials?

Abortion restrictions could possibly discourage women of reproductive age to participate in a clinical trial for a new medication, said Dr. Chambers.

A female patient with a chronic disease who’s randomized to receive a new medication may be required to use certain types of birth control because of unknown potential adverse effects the drug may have on the fetus. But in some cases, accidental pregnancies happen.

The participant in the trial may say, “I don’t know enough about the safety of this drug in pregnancy, and I’ve already taken it. I want to terminate the pregnancy,” said Dr. Chambers. Thinking ahead, a woman may decide not to do the trial to avoid the risk of getting pregnant and not having the option to terminate the pregnancy.

This could apply to new drugs such as antiviral treatments, or medications for severe chronic disease that typically have no clinical trial data in pregnancy prior to initial release into the market.

Women may start taking the drug without thinking about getting pregnant, then realize there are no safety data and become concerned about its effects on a future pregnancy.

The question is: Will abortion restrictions have a chilling effect on these new drugs as well? Patients and their doctors may decide not to try it until more data are available. “I can see where abortion restrictions would change the risk or benefit calculation in thinking about what you do or don’t prescribe or take during reproductive age,” said Dr. Chambers.
 

The upside of restrictions?

If there’s a positive side to these developments with abortion bans, it may encourage women taking new medications or joining clinical trials to think even more carefully about adherence to effective contraception, said Dr. Chambers.

Some methods are more effective than others, she emphasized. “When you have an unplanned pregnancy, it could mean that the method you used wasn’t optimal or you weren’t using it as recommended.” A goal moving forward is to encourage more thoughtful use of highly effective contraceptives, thus reducing the number of unplanned pregnancies, she added.

If patients are taking methotrexate, “the time to think about pregnancy is before getting pregnant so you can switch to a drug that’s compatible with pregnancy,” she said.

This whole thought process regarding pregnancy planning could work toward useful health goals, said Dr. Chambers. “Nobody thinks termination is the preferred method, but planning ahead should involve a discussion of what works best for the patient.”

Patients do have other choices, said Dr. Grifka. “Fortunately, there are many commonly prescribed medications which cross the placenta and have no ill effects on the fetus.”

Talking to patients about choices

Dr. Clowse, who spends a lot of time training rheumatologists, encourages them to have conversations with patients about pregnancy planning. It’s a lot to manage, getting the right drug to a female patient with chronic illness, especially in this current climate of abortion upheaval, she noted.

Her approach is to have an open and honest conversation with patients about their concerns and fears, what the realities are, and what the potential future options are for certain rheumatology drugs in the United States.

Some women who see what’s happening across the country may become so risk averse that they may choose to die rather than take a lifesaving drug that poses certain risks under new restrictions.

“I think that’s tragic,” said Dr. Clowse.

To help their patients, Dr. Gray believes physicians across specialties should better educate themselves about physiology in pregnancy and how to counsel patients on the impact of not taking medications in pregnancy.

In her view, it’s almost coercive to say to a patient, “You really need to have effective contraception if I’m going to give you this lifesaving or quality-of-life-improving medication.”

When confronting such scenarios, Dr. Gray doesn’t think physicians need to change how they counsel patients about contraception. “I don’t think we should be putting pressure on patients to consider other permanent methods just because there’s a lack of abortion options.”

Patients will eventually make those decisions for themselves, she said. “They’re going to want a more efficacious method because they’re worried about not having access to abortion if they get pregnant.”

Dr. Gray reports being a site principal investigator for a phase 3 trial for VeraCept IUD, funded by Sebela Pharmaceuticals. Dr. Clowse reports receiving research funding and doing consulting for GlaxoSmithKline.

*Correction, 6/2/2022: A previous version of this article misstated the intended use of drugs such as the “morning-after” pill (levonorgestrel). They are taken to prevent unintended pregnancy.

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

Obstetrician Beverly Gray, MD, is already seeing the effects of the Roe v. Wade abortion debate in her North Carolina practice.

The state allows abortion but requires that women get counseling with a qualified health professional 72 hours before the procedure. “Aside from that, we still have patients asking for more efficacious contraceptive methods just in case,” said Dr. Gray, residency director and division director for women’s community and population health and associate professor for obstetrics and gynecology at Duke University, Durham, N.C.

Patients and staff in her clinic have also been approaching her about tubal ligation. “They’re asking about additional birth control methods because they’re concerned about what’s going to happen” with the challenge to the historic Roe v. Wade decision in the Supreme Court and subsequent actions in the states to restrict or ban abortion, she said.

This has implications not just for abortion but for medications known to affect pregnancy. “What I’m really worried about is physicians will be withholding medicine because they’re concerned about teratogenic effects,” said Dr. Gray.

With more states issuing restrictions on abortion, doctors are worried that patients needing certain drugs to maintain their lupus flares, cancer, or other diseases may decide not to take them in the event they accidentally become pregnant. If the drug is known to affect the fetus, the fear is a patient who lives in a state with abortion restrictions will no longer have the option to terminate a pregnancy.

zoranm/Getty Images

The U.S. landscape on abortion restrictions

A leaked draft of a U.S. Supreme Court opinion on Mississippi’s 15-week abortion ban has sent the medical community into a tailspin. The case, Dobbs v. Jackson Women’s Health Organization, challenges the 1973 Roe v. Wade decision that affirms the constitutional right to abortion. It’s anticipated the high court will decide on the case in June.

Although the upcoming decision is subject to change, the draft indicated the high court would uphold the Mississippi ban. This would essentially overturn the 1973 ruling. An earlier Supreme Court decision allowing a Texas law banning abortion at 6 weeks suggests the court may already be heading in this direction. At the state level, legislatures have been moving on divergent paths – some taking steps to preserve abortion rights, others initiating restrictions.

More than 100 abortion restrictions in 19 states took effect in 2021, according to the Guttmacher Institute, which tracks such metrics. In 2022, “two key themes are anti-abortion policymakers’ continued pursuit of various types of abortion bans and restrictions on medication abortion,” the institute reported.

Forty-six states and the District of Columbia have introduced 2,025 restrictions or proactive measures on sexual and reproductive health and rights so far this year. The latest tally from Guttmacher, updated in late May, revealed that 11 states so far have enacted 42 abortion restrictions. A total of 6 states (Arizona, Florida, Idaho, Kentucky, Oklahoma, and Wyoming) have issued nine bans on abortion.

Comparatively, 11 states have enacted 19 protective abortion measures.

Twenty-two states have introduced 117 restrictions on medication abortions, which account for 54% of U.S. abortions. This includes seven measures that would ban medication abortion outright, according to Guttmacher. Kentucky and South Dakota collectively have enacted 14 restrictions on medication abortion, as well as provisions that ban mailing of abortion pills.
 

Chilling effect on prescribing

Some physicians anticipate that drugs such as the “morning-after” pill (levonorgestrel) will become less available as restrictions go into effect, since these are medications designed to prevent pregnancy.*

However, the ongoing effort to put a lid on abortion measures has prompted concerns about a trickle-down effect on other medications that are otherwise life-changing or lifesaving to patients but pose a risk to the fetus.

Several drugs are well documented to affect fetal growth and development of the fetus, ranging from mild, transitory effects to severe, permanent birth defects, said Ronald G. Grifka, MD, chief medical officer of University of Michigan Health-West and clinical professor of pediatrics at the University of Michigan Medical School, Ann Arbor. “As new medications are developed, we will need heightened attention to make sure they are safe for the fetus,” he added.

Christina Chambers

The iPLEDGE factor

Some rheumatology drugs like lenalidomide (Revlimid) require a valid negative pregnancy test in a lab every month. Similarly, the iPLEDGE Risk Evaluation and Mitigation Strategy seeks to reduce the teratogenicity of isotretinoin by requiring two types of birth control and regular pregnancy tests by users.

For isotretinoin specifically, abortion restrictions “could lead to increased adherence to pregnancy prevention measures which are already stringent in iPLEDGE. But on the other hand, it could lead to reduced willingness of physicians to prescribe or patients to take the medication,” said Dr. Chambers.

With programs like iPLEDGE in effect, the rate of pregnancies and abortions that occur in dermatology are relatively low, said Jenny Murase, MD, associate clinical professor of dermatology at the University of California, San Francisco.

Fewer women in clinical trials?

Abortion restrictions could possibly discourage women of reproductive age to participate in a clinical trial for a new medication, said Dr. Chambers.

A female patient with a chronic disease who’s randomized to receive a new medication may be required to use certain types of birth control because of unknown potential adverse effects the drug may have on the fetus. But in some cases, accidental pregnancies happen.

The participant in the trial may say, “I don’t know enough about the safety of this drug in pregnancy, and I’ve already taken it. I want to terminate the pregnancy,” said Dr. Chambers. Thinking ahead, a woman may decide not to do the trial to avoid the risk of getting pregnant and not having the option to terminate the pregnancy.

This could apply to new drugs such as antiviral treatments, or medications for severe chronic disease that typically have no clinical trial data in pregnancy prior to initial release into the market.

Women may start taking the drug without thinking about getting pregnant, then realize there are no safety data and become concerned about its effects on a future pregnancy.

The question is: Will abortion restrictions have a chilling effect on these new drugs as well? Patients and their doctors may decide not to try it until more data are available. “I can see where abortion restrictions would change the risk or benefit calculation in thinking about what you do or don’t prescribe or take during reproductive age,” said Dr. Chambers.
 

The upside of restrictions?

If there’s a positive side to these developments with abortion bans, it may encourage women taking new medications or joining clinical trials to think even more carefully about adherence to effective contraception, said Dr. Chambers.

Some methods are more effective than others, she emphasized. “When you have an unplanned pregnancy, it could mean that the method you used wasn’t optimal or you weren’t using it as recommended.” A goal moving forward is to encourage more thoughtful use of highly effective contraceptives, thus reducing the number of unplanned pregnancies, she added.

If patients are taking methotrexate, “the time to think about pregnancy is before getting pregnant so you can switch to a drug that’s compatible with pregnancy,” she said.

This whole thought process regarding pregnancy planning could work toward useful health goals, said Dr. Chambers. “Nobody thinks termination is the preferred method, but planning ahead should involve a discussion of what works best for the patient.”

Patients do have other choices, said Dr. Grifka. “Fortunately, there are many commonly prescribed medications which cross the placenta and have no ill effects on the fetus.”

Talking to patients about choices

Dr. Clowse, who spends a lot of time training rheumatologists, encourages them to have conversations with patients about pregnancy planning. It’s a lot to manage, getting the right drug to a female patient with chronic illness, especially in this current climate of abortion upheaval, she noted.

Her approach is to have an open and honest conversation with patients about their concerns and fears, what the realities are, and what the potential future options are for certain rheumatology drugs in the United States.

Some women who see what’s happening across the country may become so risk averse that they may choose to die rather than take a lifesaving drug that poses certain risks under new restrictions.

“I think that’s tragic,” said Dr. Clowse.

To help their patients, Dr. Gray believes physicians across specialties should better educate themselves about physiology in pregnancy and how to counsel patients on the impact of not taking medications in pregnancy.

In her view, it’s almost coercive to say to a patient, “You really need to have effective contraception if I’m going to give you this lifesaving or quality-of-life-improving medication.”

When confronting such scenarios, Dr. Gray doesn’t think physicians need to change how they counsel patients about contraception. “I don’t think we should be putting pressure on patients to consider other permanent methods just because there’s a lack of abortion options.”

Patients will eventually make those decisions for themselves, she said. “They’re going to want a more efficacious method because they’re worried about not having access to abortion if they get pregnant.”

Dr. Gray reports being a site principal investigator for a phase 3 trial for VeraCept IUD, funded by Sebela Pharmaceuticals. Dr. Clowse reports receiving research funding and doing consulting for GlaxoSmithKline.

*Correction, 6/2/2022: A previous version of this article misstated the intended use of drugs such as the “morning-after” pill (levonorgestrel). They are taken to prevent unintended pregnancy.

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

Obstetrician Beverly Gray, MD, is already seeing the effects of the Roe v. Wade abortion debate in her North Carolina practice.

The state allows abortion but requires that women get counseling with a qualified health professional 72 hours before the procedure. “Aside from that, we still have patients asking for more efficacious contraceptive methods just in case,” said Dr. Gray, residency director and division director for women’s community and population health and associate professor for obstetrics and gynecology at Duke University, Durham, N.C.

Patients and staff in her clinic have also been approaching her about tubal ligation. “They’re asking about additional birth control methods because they’re concerned about what’s going to happen” with the challenge to the historic Roe v. Wade decision in the Supreme Court and subsequent actions in the states to restrict or ban abortion, she said.

This has implications not just for abortion but for medications known to affect pregnancy. “What I’m really worried about is physicians will be withholding medicine because they’re concerned about teratogenic effects,” said Dr. Gray.

With more states issuing restrictions on abortion, doctors are worried that patients needing certain drugs to maintain their lupus flares, cancer, or other diseases may decide not to take them in the event they accidentally become pregnant. If the drug is known to affect the fetus, the fear is a patient who lives in a state with abortion restrictions will no longer have the option to terminate a pregnancy.

zoranm/Getty Images

The U.S. landscape on abortion restrictions

A leaked draft of a U.S. Supreme Court opinion on Mississippi’s 15-week abortion ban has sent the medical community into a tailspin. The case, Dobbs v. Jackson Women’s Health Organization, challenges the 1973 Roe v. Wade decision that affirms the constitutional right to abortion. It’s anticipated the high court will decide on the case in June.

Although the upcoming decision is subject to change, the draft indicated the high court would uphold the Mississippi ban. This would essentially overturn the 1973 ruling. An earlier Supreme Court decision allowing a Texas law banning abortion at 6 weeks suggests the court may already be heading in this direction. At the state level, legislatures have been moving on divergent paths – some taking steps to preserve abortion rights, others initiating restrictions.

More than 100 abortion restrictions in 19 states took effect in 2021, according to the Guttmacher Institute, which tracks such metrics. In 2022, “two key themes are anti-abortion policymakers’ continued pursuit of various types of abortion bans and restrictions on medication abortion,” the institute reported.

Forty-six states and the District of Columbia have introduced 2,025 restrictions or proactive measures on sexual and reproductive health and rights so far this year. The latest tally from Guttmacher, updated in late May, revealed that 11 states so far have enacted 42 abortion restrictions. A total of 6 states (Arizona, Florida, Idaho, Kentucky, Oklahoma, and Wyoming) have issued nine bans on abortion.

Comparatively, 11 states have enacted 19 protective abortion measures.

Twenty-two states have introduced 117 restrictions on medication abortions, which account for 54% of U.S. abortions. This includes seven measures that would ban medication abortion outright, according to Guttmacher. Kentucky and South Dakota collectively have enacted 14 restrictions on medication abortion, as well as provisions that ban mailing of abortion pills.
 

Chilling effect on prescribing

Some physicians anticipate that drugs such as the “morning-after” pill (levonorgestrel) will become less available as restrictions go into effect, since these are medications designed to prevent pregnancy.*

However, the ongoing effort to put a lid on abortion measures has prompted concerns about a trickle-down effect on other medications that are otherwise life-changing or lifesaving to patients but pose a risk to the fetus.

Several drugs are well documented to affect fetal growth and development of the fetus, ranging from mild, transitory effects to severe, permanent birth defects, said Ronald G. Grifka, MD, chief medical officer of University of Michigan Health-West and clinical professor of pediatrics at the University of Michigan Medical School, Ann Arbor. “As new medications are developed, we will need heightened attention to make sure they are safe for the fetus,” he added.

Christina Chambers

The iPLEDGE factor

Some rheumatology drugs like lenalidomide (Revlimid) require a valid negative pregnancy test in a lab every month. Similarly, the iPLEDGE Risk Evaluation and Mitigation Strategy seeks to reduce the teratogenicity of isotretinoin by requiring two types of birth control and regular pregnancy tests by users.

For isotretinoin specifically, abortion restrictions “could lead to increased adherence to pregnancy prevention measures which are already stringent in iPLEDGE. But on the other hand, it could lead to reduced willingness of physicians to prescribe or patients to take the medication,” said Dr. Chambers.

With programs like iPLEDGE in effect, the rate of pregnancies and abortions that occur in dermatology are relatively low, said Jenny Murase, MD, associate clinical professor of dermatology at the University of California, San Francisco.

Fewer women in clinical trials?

Abortion restrictions could possibly discourage women of reproductive age to participate in a clinical trial for a new medication, said Dr. Chambers.

A female patient with a chronic disease who’s randomized to receive a new medication may be required to use certain types of birth control because of unknown potential adverse effects the drug may have on the fetus. But in some cases, accidental pregnancies happen.

The participant in the trial may say, “I don’t know enough about the safety of this drug in pregnancy, and I’ve already taken it. I want to terminate the pregnancy,” said Dr. Chambers. Thinking ahead, a woman may decide not to do the trial to avoid the risk of getting pregnant and not having the option to terminate the pregnancy.

This could apply to new drugs such as antiviral treatments, or medications for severe chronic disease that typically have no clinical trial data in pregnancy prior to initial release into the market.

Women may start taking the drug without thinking about getting pregnant, then realize there are no safety data and become concerned about its effects on a future pregnancy.

The question is: Will abortion restrictions have a chilling effect on these new drugs as well? Patients and their doctors may decide not to try it until more data are available. “I can see where abortion restrictions would change the risk or benefit calculation in thinking about what you do or don’t prescribe or take during reproductive age,” said Dr. Chambers.
 

The upside of restrictions?

If there’s a positive side to these developments with abortion bans, it may encourage women taking new medications or joining clinical trials to think even more carefully about adherence to effective contraception, said Dr. Chambers.

Some methods are more effective than others, she emphasized. “When you have an unplanned pregnancy, it could mean that the method you used wasn’t optimal or you weren’t using it as recommended.” A goal moving forward is to encourage more thoughtful use of highly effective contraceptives, thus reducing the number of unplanned pregnancies, she added.

If patients are taking methotrexate, “the time to think about pregnancy is before getting pregnant so you can switch to a drug that’s compatible with pregnancy,” she said.

This whole thought process regarding pregnancy planning could work toward useful health goals, said Dr. Chambers. “Nobody thinks termination is the preferred method, but planning ahead should involve a discussion of what works best for the patient.”

Patients do have other choices, said Dr. Grifka. “Fortunately, there are many commonly prescribed medications which cross the placenta and have no ill effects on the fetus.”

Talking to patients about choices

Dr. Clowse, who spends a lot of time training rheumatologists, encourages them to have conversations with patients about pregnancy planning. It’s a lot to manage, getting the right drug to a female patient with chronic illness, especially in this current climate of abortion upheaval, she noted.

Her approach is to have an open and honest conversation with patients about their concerns and fears, what the realities are, and what the potential future options are for certain rheumatology drugs in the United States.

Some women who see what’s happening across the country may become so risk averse that they may choose to die rather than take a lifesaving drug that poses certain risks under new restrictions.

“I think that’s tragic,” said Dr. Clowse.

To help their patients, Dr. Gray believes physicians across specialties should better educate themselves about physiology in pregnancy and how to counsel patients on the impact of not taking medications in pregnancy.

In her view, it’s almost coercive to say to a patient, “You really need to have effective contraception if I’m going to give you this lifesaving or quality-of-life-improving medication.”

When confronting such scenarios, Dr. Gray doesn’t think physicians need to change how they counsel patients about contraception. “I don’t think we should be putting pressure on patients to consider other permanent methods just because there’s a lack of abortion options.”

Patients will eventually make those decisions for themselves, she said. “They’re going to want a more efficacious method because they’re worried about not having access to abortion if they get pregnant.”

Dr. Gray reports being a site principal investigator for a phase 3 trial for VeraCept IUD, funded by Sebela Pharmaceuticals. Dr. Clowse reports receiving research funding and doing consulting for GlaxoSmithKline.

*Correction, 6/2/2022: A previous version of this article misstated the intended use of drugs such as the “morning-after” pill (levonorgestrel). They are taken to prevent unintended pregnancy.

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

Being identified as someone that was advised to stay at home and shield, or keep away from face-to-face interactions with others, during the COVID-19 pandemic was indicative of an increased risk for dying from COVID-19 within 28 days of infection, a U.K. study of inflammatory arthritis patients versus the general population suggests.

In fact, shielding status was the highest ranked of all the risk factors identified for early mortality from COVID-19, with a hazard ratio of 1.52 (95% confidence interval, 1.40-1.64) comparing people with and without inflammatory arthritis (IA) who had tested positive.

The list of risk factors associated with higher mortality in the IA patients versus the general population also included diabetes (HR, 1.38), smoking (HR, 1.27), hypertension (HR, 1.19), glucocorticoid use (HR, 1.17), and cancer (HR, 1.10), as well as increasing age (HR, 1.08) and body mass index (HR, 1.01).

Also important was the person’s prior hospitalization history, with those needing in-hospital care in the year running up to their admission for COVID-19 associated with a 34% higher risk for death, and being hospitalized previously with a serious infection was associated with a 20% higher risk.

This has more to do people’s overall vulnerability than their IA, suggested the team behind the findings, who also found that the risk of catching COVID-19 was significantly lower among patients with IA than the general population (3.5% vs. 6%), presumably because of shielding.

Examining the risks for COVID-19 in real-life practice

“COVID-19 has caused over 10 million deaths,” Roxanne Cooksey, PhD, said at the annual meeting of the British Society for Rheumatology. “It’s greatly affected vulnerable individuals, which includes individuals with IA, this is due to their compromised immune system and increased risk of infection and the medications that they take to manage their conditions.

“Previous studies have had mixed results about whether people with IA have an increased risk of poor outcome,” added Dr. Cooksey, who is a postdoctoral researcher in the division of infection and immunity at Cardiff (Wales) University.

“So, our research question looks to investigate inflammatory arthritis – that’s rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis – to see whether the conditions themselves or indeed their medications predispose individuals to an increased risk of contracting COVID or even more adverse outcomes.”

Dr. Cooksey and colleagues looked specifically at COVID-19 infection rates and outcomes in adults living in Wales during the first year of the pandemic (March 2020 to May 2021). As such they used routinely collected, anonymized health data from the SAIL Databank and performed a retrospective, population-based cohort study. In total, there were 1,966 people with inflammatory arthritis identified as having COVID-19 and 166,602 people without IA but who had COVID-19 in the study population.

As might be expected, people with inflammatory arthritis who tested positive for COVID-19 were older than those testing positive in the general population, at a mean of 62 years versus 46 years. They were also more likely to have been advised to shield (49.4% versus 4.6%), which in the United Kingdom constituted of receiving a letter telling them about the importance of social distancing, wearing a mask when out in public, and quarantining themselves at home whenever possible.

The main outcomes were hospitalizations and mortality within 28 days of COVID-19 infection. Considering the overall inflammatory arthritis population, rates of both outcomes were higher versus the general population. And when the researchers analyzed the risks according to the type of inflammatory arthritis, the associations were not statistically significant in a multivariable analysis for people with any of the inflammatory arthritis diagnoses: rheumatoid arthritis (n = 1,283), psoriatic arthritis (n = 514), or ankylosing spondylitis (n = 246). Some patients had more than one inflammatory arthritis diagnosis.
 

What does this all mean?

Dr. Cooksey conceded that there were lots of limitations to the data collected – from misclassification bias to data possibly not have been recorded completely or missing because of the disruption to health care services during the early stages of the pandemic. Patients may have been told to shield but not actually shielded, she observed, and maybe because a lack of testing COVID-19 cases were missed or people could have been asymptomatic or unable to be tested.

“The study supports the role of shielding in inflammatory arthritis,” Dr. Cooksey said, particularly in those with RA and the risk factors associated with an increased risk in death. However, that may not mean the entire population, she suggested, saying that “refining the criteria for shielding will help mitigate the negative effects of the entire IA population.”

Senior team member Ernest Choy, MD, added his thoughts, saying that, rather than giving generic shielding recommendations to all IA patients, not everyone has the same risk, so maybe not everyone needs to shield to the same level.

“Psoriatic arthritis patients and ankylosing spondylitis patients are younger, so they really don’t have as high a risk like patients with rheumatoid arthritis,” he said.

Dr. Choy, who is professor of rheumatology at the Cardiff Institute of Infection & Immunity, commented that it was not surprising to find that a prior serious infection was a risk for COVID-19 mortality. This risk factor was examined because of the known association between biologic use and the risk for serious infection.

Moreover, he said that, “if you have a serious comorbidity that requires you to get admitted to hospital, that is a reflection of your vulnerability.”

Dr. Cooksey and Dr. Choy had no relevant conflicts of interest to disclose.

Being identified as someone that was advised to stay at home and shield, or keep away from face-to-face interactions with others, during the COVID-19 pandemic was indicative of an increased risk for dying from COVID-19 within 28 days of infection, a U.K. study of inflammatory arthritis patients versus the general population suggests.

In fact, shielding status was the highest ranked of all the risk factors identified for early mortality from COVID-19, with a hazard ratio of 1.52 (95% confidence interval, 1.40-1.64) comparing people with and without inflammatory arthritis (IA) who had tested positive.

The list of risk factors associated with higher mortality in the IA patients versus the general population also included diabetes (HR, 1.38), smoking (HR, 1.27), hypertension (HR, 1.19), glucocorticoid use (HR, 1.17), and cancer (HR, 1.10), as well as increasing age (HR, 1.08) and body mass index (HR, 1.01).

Also important was the person’s prior hospitalization history, with those needing in-hospital care in the year running up to their admission for COVID-19 associated with a 34% higher risk for death, and being hospitalized previously with a serious infection was associated with a 20% higher risk.

This has more to do people’s overall vulnerability than their IA, suggested the team behind the findings, who also found that the risk of catching COVID-19 was significantly lower among patients with IA than the general population (3.5% vs. 6%), presumably because of shielding.

Examining the risks for COVID-19 in real-life practice

“COVID-19 has caused over 10 million deaths,” Roxanne Cooksey, PhD, said at the annual meeting of the British Society for Rheumatology. “It’s greatly affected vulnerable individuals, which includes individuals with IA, this is due to their compromised immune system and increased risk of infection and the medications that they take to manage their conditions.

“Previous studies have had mixed results about whether people with IA have an increased risk of poor outcome,” added Dr. Cooksey, who is a postdoctoral researcher in the division of infection and immunity at Cardiff (Wales) University.

“So, our research question looks to investigate inflammatory arthritis – that’s rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis – to see whether the conditions themselves or indeed their medications predispose individuals to an increased risk of contracting COVID or even more adverse outcomes.”

Dr. Cooksey and colleagues looked specifically at COVID-19 infection rates and outcomes in adults living in Wales during the first year of the pandemic (March 2020 to May 2021). As such they used routinely collected, anonymized health data from the SAIL Databank and performed a retrospective, population-based cohort study. In total, there were 1,966 people with inflammatory arthritis identified as having COVID-19 and 166,602 people without IA but who had COVID-19 in the study population.

As might be expected, people with inflammatory arthritis who tested positive for COVID-19 were older than those testing positive in the general population, at a mean of 62 years versus 46 years. They were also more likely to have been advised to shield (49.4% versus 4.6%), which in the United Kingdom constituted of receiving a letter telling them about the importance of social distancing, wearing a mask when out in public, and quarantining themselves at home whenever possible.

The main outcomes were hospitalizations and mortality within 28 days of COVID-19 infection. Considering the overall inflammatory arthritis population, rates of both outcomes were higher versus the general population. And when the researchers analyzed the risks according to the type of inflammatory arthritis, the associations were not statistically significant in a multivariable analysis for people with any of the inflammatory arthritis diagnoses: rheumatoid arthritis (n = 1,283), psoriatic arthritis (n = 514), or ankylosing spondylitis (n = 246). Some patients had more than one inflammatory arthritis diagnosis.
 

What does this all mean?

Dr. Cooksey conceded that there were lots of limitations to the data collected – from misclassification bias to data possibly not have been recorded completely or missing because of the disruption to health care services during the early stages of the pandemic. Patients may have been told to shield but not actually shielded, she observed, and maybe because a lack of testing COVID-19 cases were missed or people could have been asymptomatic or unable to be tested.

“The study supports the role of shielding in inflammatory arthritis,” Dr. Cooksey said, particularly in those with RA and the risk factors associated with an increased risk in death. However, that may not mean the entire population, she suggested, saying that “refining the criteria for shielding will help mitigate the negative effects of the entire IA population.”

Senior team member Ernest Choy, MD, added his thoughts, saying that, rather than giving generic shielding recommendations to all IA patients, not everyone has the same risk, so maybe not everyone needs to shield to the same level.

“Psoriatic arthritis patients and ankylosing spondylitis patients are younger, so they really don’t have as high a risk like patients with rheumatoid arthritis,” he said.

Dr. Choy, who is professor of rheumatology at the Cardiff Institute of Infection & Immunity, commented that it was not surprising to find that a prior serious infection was a risk for COVID-19 mortality. This risk factor was examined because of the known association between biologic use and the risk for serious infection.

Moreover, he said that, “if you have a serious comorbidity that requires you to get admitted to hospital, that is a reflection of your vulnerability.”

Dr. Cooksey and Dr. Choy had no relevant conflicts of interest to disclose.

Being identified as someone that was advised to stay at home and shield, or keep away from face-to-face interactions with others, during the COVID-19 pandemic was indicative of an increased risk for dying from COVID-19 within 28 days of infection, a U.K. study of inflammatory arthritis patients versus the general population suggests.

In fact, shielding status was the highest ranked of all the risk factors identified for early mortality from COVID-19, with a hazard ratio of 1.52 (95% confidence interval, 1.40-1.64) comparing people with and without inflammatory arthritis (IA) who had tested positive.

The list of risk factors associated with higher mortality in the IA patients versus the general population also included diabetes (HR, 1.38), smoking (HR, 1.27), hypertension (HR, 1.19), glucocorticoid use (HR, 1.17), and cancer (HR, 1.10), as well as increasing age (HR, 1.08) and body mass index (HR, 1.01).

Also important was the person’s prior hospitalization history, with those needing in-hospital care in the year running up to their admission for COVID-19 associated with a 34% higher risk for death, and being hospitalized previously with a serious infection was associated with a 20% higher risk.

This has more to do people’s overall vulnerability than their IA, suggested the team behind the findings, who also found that the risk of catching COVID-19 was significantly lower among patients with IA than the general population (3.5% vs. 6%), presumably because of shielding.

Examining the risks for COVID-19 in real-life practice

“COVID-19 has caused over 10 million deaths,” Roxanne Cooksey, PhD, said at the annual meeting of the British Society for Rheumatology. “It’s greatly affected vulnerable individuals, which includes individuals with IA, this is due to their compromised immune system and increased risk of infection and the medications that they take to manage their conditions.

“Previous studies have had mixed results about whether people with IA have an increased risk of poor outcome,” added Dr. Cooksey, who is a postdoctoral researcher in the division of infection and immunity at Cardiff (Wales) University.

“So, our research question looks to investigate inflammatory arthritis – that’s rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis – to see whether the conditions themselves or indeed their medications predispose individuals to an increased risk of contracting COVID or even more adverse outcomes.”

Dr. Cooksey and colleagues looked specifically at COVID-19 infection rates and outcomes in adults living in Wales during the first year of the pandemic (March 2020 to May 2021). As such they used routinely collected, anonymized health data from the SAIL Databank and performed a retrospective, population-based cohort study. In total, there were 1,966 people with inflammatory arthritis identified as having COVID-19 and 166,602 people without IA but who had COVID-19 in the study population.

As might be expected, people with inflammatory arthritis who tested positive for COVID-19 were older than those testing positive in the general population, at a mean of 62 years versus 46 years. They were also more likely to have been advised to shield (49.4% versus 4.6%), which in the United Kingdom constituted of receiving a letter telling them about the importance of social distancing, wearing a mask when out in public, and quarantining themselves at home whenever possible.

The main outcomes were hospitalizations and mortality within 28 days of COVID-19 infection. Considering the overall inflammatory arthritis population, rates of both outcomes were higher versus the general population. And when the researchers analyzed the risks according to the type of inflammatory arthritis, the associations were not statistically significant in a multivariable analysis for people with any of the inflammatory arthritis diagnoses: rheumatoid arthritis (n = 1,283), psoriatic arthritis (n = 514), or ankylosing spondylitis (n = 246). Some patients had more than one inflammatory arthritis diagnosis.
 

What does this all mean?

Dr. Cooksey conceded that there were lots of limitations to the data collected – from misclassification bias to data possibly not have been recorded completely or missing because of the disruption to health care services during the early stages of the pandemic. Patients may have been told to shield but not actually shielded, she observed, and maybe because a lack of testing COVID-19 cases were missed or people could have been asymptomatic or unable to be tested.

“The study supports the role of shielding in inflammatory arthritis,” Dr. Cooksey said, particularly in those with RA and the risk factors associated with an increased risk in death. However, that may not mean the entire population, she suggested, saying that “refining the criteria for shielding will help mitigate the negative effects of the entire IA population.”

Senior team member Ernest Choy, MD, added his thoughts, saying that, rather than giving generic shielding recommendations to all IA patients, not everyone has the same risk, so maybe not everyone needs to shield to the same level.

“Psoriatic arthritis patients and ankylosing spondylitis patients are younger, so they really don’t have as high a risk like patients with rheumatoid arthritis,” he said.

Dr. Choy, who is professor of rheumatology at the Cardiff Institute of Infection & Immunity, commented that it was not surprising to find that a prior serious infection was a risk for COVID-19 mortality. This risk factor was examined because of the known association between biologic use and the risk for serious infection.

Moreover, he said that, “if you have a serious comorbidity that requires you to get admitted to hospital, that is a reflection of your vulnerability.”

Dr. Cooksey and Dr. Choy had no relevant conflicts of interest to disclose.

The Food and Drug Administration has approved upadacitinib (Rinvoq) as an oral treatment for active ankylosing spondylitis in adults, its manufacturer AbbVie announced April 29.

Upadacitinib, a selective and reversible Janus kinase inhibitor, is the second drug in its class to be FDA approved for ankylosing spondylitis, after tofacitinib (Xeljanz) in December.

Upadacitinib is now indicated for patients with active ankylosing spondylitis (AS) who have had an insufficient response or intolerance with one or more tumor necrosis factor (TNF) blockers. Upadacitinib is already approved by the FDA for adults with active psoriatic arthritis, moderately to severely active rheumatoid arthritis, and moderately to severely active ulcerative colitis who have had an insufficient response or intolerance with one or more TNF inhibitors. It also has been approved for adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis.

The European Medicines Agency gave marketing approval for upadacitinib in adults with active AS in January 2021.

Two main clinical studies form the basis for the FDA’s approval decision. The phase 3 SELECT-AXIS 2 clinical trial involved patients with an inadequate response or intolerance to one or two biologic disease-modifying antirheumatic drugs (bDMARDs). A total of 44.5% patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of at least 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40) at 14 weeks, compared against 18.2% with placebo.

The second study, the phase 2/3 SELECT-AXIS 1 clinical trial, tested upadacitinib in patients who had never taken bDMARDs and had an inadequate response or intolerance to at least two NSAIDs. In this study, significantly more patients randomly assigned to 15 mg upadacitinib achieved ASAS 40 at 14 weeks, compared with placebo (51% vs. 26%).

Patients randomly assigned to upadacitinib also showed significant improvements in signs and symptoms of AS, as well as improvements in physical function and disease activity, compared with placebo, after 14 weeks. The safety profile for patients with AS treated with upadacitinib was similar to that seen in studies of patients with rheumatoid arthritis or psoriatic arthritis. Potential severe side effects include increased risk for death in patients aged 50 years and older with at least one cardiovascular risk factor; increased risk of serious infections, such as tuberculosis; and increased risk of certain cancers, according to the company statement.

Read the complete prescribing information here.

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

The Food and Drug Administration has approved upadacitinib (Rinvoq) as an oral treatment for active ankylosing spondylitis in adults, its manufacturer AbbVie announced April 29.

Upadacitinib, a selective and reversible Janus kinase inhibitor, is the second drug in its class to be FDA approved for ankylosing spondylitis, after tofacitinib (Xeljanz) in December.

Upadacitinib is now indicated for patients with active ankylosing spondylitis (AS) who have had an insufficient response or intolerance with one or more tumor necrosis factor (TNF) blockers. Upadacitinib is already approved by the FDA for adults with active psoriatic arthritis, moderately to severely active rheumatoid arthritis, and moderately to severely active ulcerative colitis who have had an insufficient response or intolerance with one or more TNF inhibitors. It also has been approved for adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis.

The European Medicines Agency gave marketing approval for upadacitinib in adults with active AS in January 2021.

Two main clinical studies form the basis for the FDA’s approval decision. The phase 3 SELECT-AXIS 2 clinical trial involved patients with an inadequate response or intolerance to one or two biologic disease-modifying antirheumatic drugs (bDMARDs). A total of 44.5% patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of at least 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40) at 14 weeks, compared against 18.2% with placebo.

The second study, the phase 2/3 SELECT-AXIS 1 clinical trial, tested upadacitinib in patients who had never taken bDMARDs and had an inadequate response or intolerance to at least two NSAIDs. In this study, significantly more patients randomly assigned to 15 mg upadacitinib achieved ASAS 40 at 14 weeks, compared with placebo (51% vs. 26%).

Patients randomly assigned to upadacitinib also showed significant improvements in signs and symptoms of AS, as well as improvements in physical function and disease activity, compared with placebo, after 14 weeks. The safety profile for patients with AS treated with upadacitinib was similar to that seen in studies of patients with rheumatoid arthritis or psoriatic arthritis. Potential severe side effects include increased risk for death in patients aged 50 years and older with at least one cardiovascular risk factor; increased risk of serious infections, such as tuberculosis; and increased risk of certain cancers, according to the company statement.

Read the complete prescribing information here.

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

The Food and Drug Administration has approved upadacitinib (Rinvoq) as an oral treatment for active ankylosing spondylitis in adults, its manufacturer AbbVie announced April 29.

Upadacitinib, a selective and reversible Janus kinase inhibitor, is the second drug in its class to be FDA approved for ankylosing spondylitis, after tofacitinib (Xeljanz) in December.

Upadacitinib is now indicated for patients with active ankylosing spondylitis (AS) who have had an insufficient response or intolerance with one or more tumor necrosis factor (TNF) blockers. Upadacitinib is already approved by the FDA for adults with active psoriatic arthritis, moderately to severely active rheumatoid arthritis, and moderately to severely active ulcerative colitis who have had an insufficient response or intolerance with one or more TNF inhibitors. It also has been approved for adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis.

The European Medicines Agency gave marketing approval for upadacitinib in adults with active AS in January 2021.

Two main clinical studies form the basis for the FDA’s approval decision. The phase 3 SELECT-AXIS 2 clinical trial involved patients with an inadequate response or intolerance to one or two biologic disease-modifying antirheumatic drugs (bDMARDs). A total of 44.5% patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of at least 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40) at 14 weeks, compared against 18.2% with placebo.

The second study, the phase 2/3 SELECT-AXIS 1 clinical trial, tested upadacitinib in patients who had never taken bDMARDs and had an inadequate response or intolerance to at least two NSAIDs. In this study, significantly more patients randomly assigned to 15 mg upadacitinib achieved ASAS 40 at 14 weeks, compared with placebo (51% vs. 26%).

Patients randomly assigned to upadacitinib also showed significant improvements in signs and symptoms of AS, as well as improvements in physical function and disease activity, compared with placebo, after 14 weeks. The safety profile for patients with AS treated with upadacitinib was similar to that seen in studies of patients with rheumatoid arthritis or psoriatic arthritis. Potential severe side effects include increased risk for death in patients aged 50 years and older with at least one cardiovascular risk factor; increased risk of serious infections, such as tuberculosis; and increased risk of certain cancers, according to the company statement.

Read the complete prescribing information here.

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