Randy Dotinga

SAN DIEGO – Researchers say they’ve developed a novel blood-based assay that can differentiate patients with seropositive or seronegative rheumatoid arthritis from healthy people and those with other inflammatory diseases or osteoarthritis.

While cautioning that the results need to be confirmed, University of Oxford (England) rheumatologist Peter Taylor, PhD, MA, told an audience at the annual meeting of the American College of Rheumatology that the test has an overall mean sensitivity of 90.8% (standard deviation, 0.94%; 95% confidence interval, 83.2%-95.4%) and mean specificity of 96.1% (SD, 0.64%; 95% CI, 92.7%-97.9%). The mean area under the curve (AUC) is 0.991 (SD, 0.001; 95% CI, 97.2%-99.6%).

SAN DIEGO – Researchers say they’ve developed a novel blood-based assay that can differentiate patients with seropositive or seronegative rheumatoid arthritis from healthy people and those with other inflammatory diseases or osteoarthritis.

While cautioning that the results need to be confirmed, University of Oxford (England) rheumatologist Peter Taylor, PhD, MA, told an audience at the annual meeting of the American College of Rheumatology that the test has an overall mean sensitivity of 90.8% (standard deviation, 0.94%; 95% confidence interval, 83.2%-95.4%) and mean specificity of 96.1% (SD, 0.64%; 95% CI, 92.7%-97.9%). The mean area under the curve (AUC) is 0.991 (SD, 0.001; 95% CI, 97.2%-99.6%).

SAN DIEGO – Researchers say they’ve developed a novel blood-based assay that can differentiate patients with seropositive or seronegative rheumatoid arthritis from healthy people and those with other inflammatory diseases or osteoarthritis.

While cautioning that the results need to be confirmed, University of Oxford (England) rheumatologist Peter Taylor, PhD, MA, told an audience at the annual meeting of the American College of Rheumatology that the test has an overall mean sensitivity of 90.8% (standard deviation, 0.94%; 95% confidence interval, 83.2%-95.4%) and mean specificity of 96.1% (SD, 0.64%; 95% CI, 92.7%-97.9%). The mean area under the curve (AUC) is 0.991 (SD, 0.001; 95% CI, 97.2%-99.6%).

SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.

The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.

In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).

In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).

“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.

“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.

As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”

However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
 

PsA trial details

In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.

Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.

“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.

The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.

Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
 

AxSpA trial details

In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.

Participants had a mean age of about 39, and about one-third were female.

Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.

Secondary outcome measures were similar in both groups at week 52.

Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.

In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”

Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.

The FDA made the same dose recommendation for PsA.
 

Study limitations

Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.

“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”

Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.

SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.

The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.

In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).

In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).

“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.

“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.

As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”

However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
 

PsA trial details

In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.

Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.

“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.

The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.

Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
 

AxSpA trial details

In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.

Participants had a mean age of about 39, and about one-third were female.

Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.

Secondary outcome measures were similar in both groups at week 52.

Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.

In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”

Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.

The FDA made the same dose recommendation for PsA.
 

Study limitations

Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.

“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”

Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.

SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.

The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.

In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).

In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).

“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.

“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.

As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”

However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
 

PsA trial details

In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.

Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.

“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.

The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.

Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
 

AxSpA trial details

In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.

Participants had a mean age of about 39, and about one-third were female.

Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.

Secondary outcome measures were similar in both groups at week 52.

Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.

In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”

Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.

The FDA made the same dose recommendation for PsA.
 

Study limitations

Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.

“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”

Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.

An anesthesiologist is suing the Mayo Clinic after it allegedly ordered him to stick to “prescribed messaging” after his outspoken comments about transgender athletes and a federal agency’s sluggishness regarding a COVID-19 treatment.

Michael J. Joyner, MD, claims that the Mayo Clinic violated its own policies by muzzling him, slapping him with an unpaid 1-week suspension, and labeling his comments to the media “unprofessional.”

In his Nov. 13 lawsuit, filed in Minnesota state court, Dr. Joyner asks that a judge order Mayo Clinic to stop its “retaliation and interference” with his “communications about his research.” He that claims the retaliation stems from his 2020 report about a Mayo Clinic business partner’s “attempt to unlawfully access and use protected patient data.”

Medical institutions often refuse to comment on pending litigation. But in a pair of unusual statements, the Mayo Clinic forcefully rebutted Joyner’s claims in some detail: “Dr. Joyner’s lawsuit is yet another manifestation of his refusal to recognize or accept responsibility for his inappropriate behaviors,” it told Becker’s Hospital Review.

In a June letter to colleagues, the institution’s communications head said Dr. Joyner was not punished over his transgender athlete comments but instead because he mistreated coworkers and made “unprofessional” comments to The New York Times.

Dr. Joyner, a prominent physiologist and anesthesiologist who has worked for Mayo Clinic for 36 years, has become a cause célèbre in academic and free-speech circles over the past several months.

Two conversations with journalists appear to be at the heart of the Mayo Clinic’s complaints.

First, a 2022 New York Times article about transgender athletes quoted him about how testosterone dramatically affects performance in males: “There are social aspects to sport, but physiology and biology underpin it. Testosterone is the 800-pound gorilla.”

“The language was at best, insensitive. At worst, transphobic,” an LGBTQ advocate told a TV news station in Rochester, Minn., where the Mayo Clinic is based. The article didn’t elaborate on why the advocate believed the language could be transphobic.

Then, a CNN story in 2023 noted that Dr. Joyner has studied convalescent plasma as a treatment for COVID-19 and quoted him about how the National Institutes of Health declined to take a stand on the use of the therapy: “Joyner said he’s ‘frustrated’ with the NIH’s ‘bureaucratic rope-a-dope,’ calling the agency’s guidelines ‘a wet blanket.’ ”

It is not unusual for medical researchers to comment bluntly to the media about federal agencies.

For example, a 2020 New York Times story that unraveled the Trump Administration’s apparent mischaracterization of Dr. Joyner’s research into convalescent plasma quoted a University of Pittsburgh physician as saying, “For the first time ever, I feel like official people in communications and people at the FDA grossly misrepresented data about a therapy.”

In a March 5 letter, a Mayo Clinic administrator wrote to Dr. Joyner to complain that his comments regarding the NIH were an example of his “problematic” use of “idiomatic language” that “reflects poorly on Mayo Clinic’s brand and reputation.” A paragraph in the letter is redacted in the version posted by the Foundation for Individual Rights and Expression, which supports Dr. Joyner.

The letter adds that Dr. Joyner’s comments to The New York Times “were problematic in the media and the LGBTQI+ community at Mayo Clinic.” The letter, which didn’t elaborate about the blowback, also says that “concerns remain with disrespectful communications with colleagues who describe your tone as unpleasant and having a ‘bullying’ quality to it.”

Kellie Miller, one of Dr. Joyner’s attorneys, noted in a statement that “Dr. Joyner’s personnel file is free of any documentation of Mayo’s ongoing and vague allegations of bullying and unprofessionalism with colleagues.”

The letter also ordered Dr. Joyner to not be rude or criticize the work of others and repair his relationship with Mayo Clinic’s public affairs staff: “This will take individual effort on your part.” It also ordered him to “discuss approved topics only” with reporters, “stick to prescribed messaging,” and not resist if the public affairs department doesn’t let him be interviewed: “Accept ‘no’ for an answer and move forward.”

Medical institutions often monitor how their employees interact with the media in order to control “messaging.” But firm rules at academic medical institutions like the Mayo Clinic may run the risk of running afoul of the tenets of academic freedom.

The institution and its CEO then retaliated by calling his claims “unprofessional,” according to the lawsuit, which provided no further details about the situation.

In a statement, the Mayo Clinic said it “hired an outside attorney to investigate these concerns. The attorney, who is now a federal judge, found there was no retaliation and that Dr. Joyner had engaged in a pattern of asserting inflammatory allegations grounded almost entirely in speculation.”

A petition signed by dozens of professors demands that Mayo Clinic “revoke the penalties and constraints it has imposed on him.”

“Dr. Joyner, a faculty member at a medical school that avows a commitment to academic freedom and to free expression, did not exceed the limits of his expertise in any of his statements to the press that led to these sanctions,” they wrote. “At no time did he claim to be speaking for the Mayo Clinic, and his remarks were well within the mainstream of the range of scientific opinion on topics in which he is expert.”

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

An anesthesiologist is suing the Mayo Clinic after it allegedly ordered him to stick to “prescribed messaging” after his outspoken comments about transgender athletes and a federal agency’s sluggishness regarding a COVID-19 treatment.

Michael J. Joyner, MD, claims that the Mayo Clinic violated its own policies by muzzling him, slapping him with an unpaid 1-week suspension, and labeling his comments to the media “unprofessional.”

In his Nov. 13 lawsuit, filed in Minnesota state court, Dr. Joyner asks that a judge order Mayo Clinic to stop its “retaliation and interference” with his “communications about his research.” He that claims the retaliation stems from his 2020 report about a Mayo Clinic business partner’s “attempt to unlawfully access and use protected patient data.”

Medical institutions often refuse to comment on pending litigation. But in a pair of unusual statements, the Mayo Clinic forcefully rebutted Joyner’s claims in some detail: “Dr. Joyner’s lawsuit is yet another manifestation of his refusal to recognize or accept responsibility for his inappropriate behaviors,” it told Becker’s Hospital Review.

In a June letter to colleagues, the institution’s communications head said Dr. Joyner was not punished over his transgender athlete comments but instead because he mistreated coworkers and made “unprofessional” comments to The New York Times.

Dr. Joyner, a prominent physiologist and anesthesiologist who has worked for Mayo Clinic for 36 years, has become a cause célèbre in academic and free-speech circles over the past several months.

Two conversations with journalists appear to be at the heart of the Mayo Clinic’s complaints.

First, a 2022 New York Times article about transgender athletes quoted him about how testosterone dramatically affects performance in males: “There are social aspects to sport, but physiology and biology underpin it. Testosterone is the 800-pound gorilla.”

“The language was at best, insensitive. At worst, transphobic,” an LGBTQ advocate told a TV news station in Rochester, Minn., where the Mayo Clinic is based. The article didn’t elaborate on why the advocate believed the language could be transphobic.

Then, a CNN story in 2023 noted that Dr. Joyner has studied convalescent plasma as a treatment for COVID-19 and quoted him about how the National Institutes of Health declined to take a stand on the use of the therapy: “Joyner said he’s ‘frustrated’ with the NIH’s ‘bureaucratic rope-a-dope,’ calling the agency’s guidelines ‘a wet blanket.’ ”

It is not unusual for medical researchers to comment bluntly to the media about federal agencies.

For example, a 2020 New York Times story that unraveled the Trump Administration’s apparent mischaracterization of Dr. Joyner’s research into convalescent plasma quoted a University of Pittsburgh physician as saying, “For the first time ever, I feel like official people in communications and people at the FDA grossly misrepresented data about a therapy.”

In a March 5 letter, a Mayo Clinic administrator wrote to Dr. Joyner to complain that his comments regarding the NIH were an example of his “problematic” use of “idiomatic language” that “reflects poorly on Mayo Clinic’s brand and reputation.” A paragraph in the letter is redacted in the version posted by the Foundation for Individual Rights and Expression, which supports Dr. Joyner.

The letter adds that Dr. Joyner’s comments to The New York Times “were problematic in the media and the LGBTQI+ community at Mayo Clinic.” The letter, which didn’t elaborate about the blowback, also says that “concerns remain with disrespectful communications with colleagues who describe your tone as unpleasant and having a ‘bullying’ quality to it.”

Kellie Miller, one of Dr. Joyner’s attorneys, noted in a statement that “Dr. Joyner’s personnel file is free of any documentation of Mayo’s ongoing and vague allegations of bullying and unprofessionalism with colleagues.”

The letter also ordered Dr. Joyner to not be rude or criticize the work of others and repair his relationship with Mayo Clinic’s public affairs staff: “This will take individual effort on your part.” It also ordered him to “discuss approved topics only” with reporters, “stick to prescribed messaging,” and not resist if the public affairs department doesn’t let him be interviewed: “Accept ‘no’ for an answer and move forward.”

Medical institutions often monitor how their employees interact with the media in order to control “messaging.” But firm rules at academic medical institutions like the Mayo Clinic may run the risk of running afoul of the tenets of academic freedom.

The institution and its CEO then retaliated by calling his claims “unprofessional,” according to the lawsuit, which provided no further details about the situation.

In a statement, the Mayo Clinic said it “hired an outside attorney to investigate these concerns. The attorney, who is now a federal judge, found there was no retaliation and that Dr. Joyner had engaged in a pattern of asserting inflammatory allegations grounded almost entirely in speculation.”

A petition signed by dozens of professors demands that Mayo Clinic “revoke the penalties and constraints it has imposed on him.”

“Dr. Joyner, a faculty member at a medical school that avows a commitment to academic freedom and to free expression, did not exceed the limits of his expertise in any of his statements to the press that led to these sanctions,” they wrote. “At no time did he claim to be speaking for the Mayo Clinic, and his remarks were well within the mainstream of the range of scientific opinion on topics in which he is expert.”

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

An anesthesiologist is suing the Mayo Clinic after it allegedly ordered him to stick to “prescribed messaging” after his outspoken comments about transgender athletes and a federal agency’s sluggishness regarding a COVID-19 treatment.

Michael J. Joyner, MD, claims that the Mayo Clinic violated its own policies by muzzling him, slapping him with an unpaid 1-week suspension, and labeling his comments to the media “unprofessional.”

In his Nov. 13 lawsuit, filed in Minnesota state court, Dr. Joyner asks that a judge order Mayo Clinic to stop its “retaliation and interference” with his “communications about his research.” He that claims the retaliation stems from his 2020 report about a Mayo Clinic business partner’s “attempt to unlawfully access and use protected patient data.”

Medical institutions often refuse to comment on pending litigation. But in a pair of unusual statements, the Mayo Clinic forcefully rebutted Joyner’s claims in some detail: “Dr. Joyner’s lawsuit is yet another manifestation of his refusal to recognize or accept responsibility for his inappropriate behaviors,” it told Becker’s Hospital Review.

In a June letter to colleagues, the institution’s communications head said Dr. Joyner was not punished over his transgender athlete comments but instead because he mistreated coworkers and made “unprofessional” comments to The New York Times.

Dr. Joyner, a prominent physiologist and anesthesiologist who has worked for Mayo Clinic for 36 years, has become a cause célèbre in academic and free-speech circles over the past several months.

Two conversations with journalists appear to be at the heart of the Mayo Clinic’s complaints.

First, a 2022 New York Times article about transgender athletes quoted him about how testosterone dramatically affects performance in males: “There are social aspects to sport, but physiology and biology underpin it. Testosterone is the 800-pound gorilla.”

“The language was at best, insensitive. At worst, transphobic,” an LGBTQ advocate told a TV news station in Rochester, Minn., where the Mayo Clinic is based. The article didn’t elaborate on why the advocate believed the language could be transphobic.

Then, a CNN story in 2023 noted that Dr. Joyner has studied convalescent plasma as a treatment for COVID-19 and quoted him about how the National Institutes of Health declined to take a stand on the use of the therapy: “Joyner said he’s ‘frustrated’ with the NIH’s ‘bureaucratic rope-a-dope,’ calling the agency’s guidelines ‘a wet blanket.’ ”

It is not unusual for medical researchers to comment bluntly to the media about federal agencies.

For example, a 2020 New York Times story that unraveled the Trump Administration’s apparent mischaracterization of Dr. Joyner’s research into convalescent plasma quoted a University of Pittsburgh physician as saying, “For the first time ever, I feel like official people in communications and people at the FDA grossly misrepresented data about a therapy.”

In a March 5 letter, a Mayo Clinic administrator wrote to Dr. Joyner to complain that his comments regarding the NIH were an example of his “problematic” use of “idiomatic language” that “reflects poorly on Mayo Clinic’s brand and reputation.” A paragraph in the letter is redacted in the version posted by the Foundation for Individual Rights and Expression, which supports Dr. Joyner.

The letter adds that Dr. Joyner’s comments to The New York Times “were problematic in the media and the LGBTQI+ community at Mayo Clinic.” The letter, which didn’t elaborate about the blowback, also says that “concerns remain with disrespectful communications with colleagues who describe your tone as unpleasant and having a ‘bullying’ quality to it.”

Kellie Miller, one of Dr. Joyner’s attorneys, noted in a statement that “Dr. Joyner’s personnel file is free of any documentation of Mayo’s ongoing and vague allegations of bullying and unprofessionalism with colleagues.”

The letter also ordered Dr. Joyner to not be rude or criticize the work of others and repair his relationship with Mayo Clinic’s public affairs staff: “This will take individual effort on your part.” It also ordered him to “discuss approved topics only” with reporters, “stick to prescribed messaging,” and not resist if the public affairs department doesn’t let him be interviewed: “Accept ‘no’ for an answer and move forward.”

Medical institutions often monitor how their employees interact with the media in order to control “messaging.” But firm rules at academic medical institutions like the Mayo Clinic may run the risk of running afoul of the tenets of academic freedom.

The institution and its CEO then retaliated by calling his claims “unprofessional,” according to the lawsuit, which provided no further details about the situation.

In a statement, the Mayo Clinic said it “hired an outside attorney to investigate these concerns. The attorney, who is now a federal judge, found there was no retaliation and that Dr. Joyner had engaged in a pattern of asserting inflammatory allegations grounded almost entirely in speculation.”

A petition signed by dozens of professors demands that Mayo Clinic “revoke the penalties and constraints it has imposed on him.”

“Dr. Joyner, a faculty member at a medical school that avows a commitment to academic freedom and to free expression, did not exceed the limits of his expertise in any of his statements to the press that led to these sanctions,” they wrote. “At no time did he claim to be speaking for the Mayo Clinic, and his remarks were well within the mainstream of the range of scientific opinion on topics in which he is expert.”

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

SAN DIEGO – Even when taken at low doses and over short periods, glucocorticoids (GCs) were linked to a higher risk of major adverse cardiovascular events (MACE) over the long term in a Veterans Affairs population of older, mostly male patients with rheumatoid arthritis, a new retrospective cohort study has found.

The analysis of nearly 19,000 patients, presented by rheumatologist Beth Wallace, MD, MSc, at the annual meeting of the American College of Rheumatology, showed that the level of risk for MACE rose with the dose, duration, and recency of GC use, in which risk increased significantly at prednisone-equivalent doses as low as 5 mg/day, durations as short as 30 days, and with last use as long as 1 year before MACE.

University of Michigan

“Up to half of RA patients in the United States use long-term glucocorticoids despite previous work suggesting they increase MACE in a dose-dependent way,” said Dr. Wallace, assistant professor of medicine at the University of Michigan, Ann Arbor, and a rheumatologist at the VA Ann Arbor Healthcare Center. “Our group previously presented work suggesting that less than 14 days of glucocorticoid use in a 6-month period is associated with a two-thirds increase in odds of MACE over the following 6 months, with 90 days of use associated with more than twofold increase.”

In recent years, researchers such as Dr. Wallace have focused attention on the risks of GCs in RA. The American College of Rheumatology and the European Alliance of Associations for Rheumatology emphasize avoiding long-term use of GCs in RA and keeping doses as small and over the shortest amount of time as possible.

When Dr. Wallace and colleagues looked at the clinical pattern of GC use for patients with RA during the past 2 years, those who took 5 mg, 7.5 mg, and 10 mg daily doses for 30 days and had stopped at least a year before had risk for MACE that rose significantly by 3%, 5%, and 7%, respectively, compared with those who didn’t take GCs in the past 2 years.

While those increases were small, risk for MACE rose even more for those who took the same daily doses for 90 days, increasing 10%, 15%, and 21%, respectively. Researchers linked current ongoing use of GCs for the past 90 days to a 13%, 19%, and 27% higher risk for MACE at those respective doses.

The findings “add to the literature suggesting that there is some risk even with low-dose steroids,” said Michael George, MD, assistant professor of rheumatology and epidemiology at the University of Pennsylvania, Philadelphia, who did not take part in the research but is familiar with the findings.

“We can see that even glucocorticoids taken several years ago may affect cardiovascular risk but that recent use has a bigger effect on risk,” Dr. George said in an interview. “This study also suggests that very low-dose use affects risk.”

For the new study, Dr. Wallace and colleagues examined a Veterans Affairs database and identified 18,882 patients with RA (mean age, 62.5 years; 84% male; 66% GC users) who met the criteria of being > 40 and < 90 years old. The subjects had an initial VA rheumatology visit during 2010-2018 and were excluded if they had a non-RA rheumatologic disorder, prior MACE, or heart failure. MACE was defined as MI, stroke/TIA, cardiac arrest, coronary revascularization, or death from CV cause.

A total of 16% of the cohort had the largest exposure to GCs, defined as use for 90 days or more; 23% had exposure of 14-89 days, and 14% had exposure of 1-13 days.

The median 5-year MACE risk at baseline was 5.3%, and 3,754 patients (19.9%) had high baseline MACE risk. Incident MACE occurred in 4.1% of patients, and the median time to MACE was 2.67 years (interquartile ratio, 1.26-4.45 years).

Covariates included factors such as age, race, sex, body mass index, smoking status, adjusted Elixhauser index, VA risk score for cardiovascular disease, cancer, hospitalization for infection, number of rheumatology clinic visits, and use of lipid-lowering drugs, opioids, methotrexate, biologics, and hydroxychloroquine.

Dr. Wallace noted limitations including the possibility of residual confounding and the influence of background cardiovascular risk. The study didn’t examine the clinical value of taking GCs or compare that to the potential risk. Nor did it examine cost or the risks and benefits of alternative therapeutic options.

A study released earlier this year suggested that patients taking daily prednisolone doses under 5 mg do not have a higher risk of MACE. Previous studies had reached conflicting results.

“Glucocorticoids can provide major benefits to patients, but these benefits must be balanced with the potential risks,” Dr. George said. At low doses, these risks may be small, but they are present. In many cases, escalating DMARD [disease-modifying antirheumatic drug] therapy may be safer than continuing glucocorticoids.”

He added that the risks of GCs may be especially high in older patients and in those who have cardiovascular risk factors: “Often biologics are avoided in these higher-risk patients. But in fact, in many cases biologics may be the safer choice.”

No study funding was reported. Dr. Wallace reported no relevant financial relationships, and some of the other authors reported various ties with industry. Dr. George reported research funding from GlaxoSmithKline and Janssen and consulting fees from AbbVie.

SAN DIEGO – Even when taken at low doses and over short periods, glucocorticoids (GCs) were linked to a higher risk of major adverse cardiovascular events (MACE) over the long term in a Veterans Affairs population of older, mostly male patients with rheumatoid arthritis, a new retrospective cohort study has found.

The analysis of nearly 19,000 patients, presented by rheumatologist Beth Wallace, MD, MSc, at the annual meeting of the American College of Rheumatology, showed that the level of risk for MACE rose with the dose, duration, and recency of GC use, in which risk increased significantly at prednisone-equivalent doses as low as 5 mg/day, durations as short as 30 days, and with last use as long as 1 year before MACE.

University of Michigan

“Up to half of RA patients in the United States use long-term glucocorticoids despite previous work suggesting they increase MACE in a dose-dependent way,” said Dr. Wallace, assistant professor of medicine at the University of Michigan, Ann Arbor, and a rheumatologist at the VA Ann Arbor Healthcare Center. “Our group previously presented work suggesting that less than 14 days of glucocorticoid use in a 6-month period is associated with a two-thirds increase in odds of MACE over the following 6 months, with 90 days of use associated with more than twofold increase.”

In recent years, researchers such as Dr. Wallace have focused attention on the risks of GCs in RA. The American College of Rheumatology and the European Alliance of Associations for Rheumatology emphasize avoiding long-term use of GCs in RA and keeping doses as small and over the shortest amount of time as possible.

When Dr. Wallace and colleagues looked at the clinical pattern of GC use for patients with RA during the past 2 years, those who took 5 mg, 7.5 mg, and 10 mg daily doses for 30 days and had stopped at least a year before had risk for MACE that rose significantly by 3%, 5%, and 7%, respectively, compared with those who didn’t take GCs in the past 2 years.

While those increases were small, risk for MACE rose even more for those who took the same daily doses for 90 days, increasing 10%, 15%, and 21%, respectively. Researchers linked current ongoing use of GCs for the past 90 days to a 13%, 19%, and 27% higher risk for MACE at those respective doses.

The findings “add to the literature suggesting that there is some risk even with low-dose steroids,” said Michael George, MD, assistant professor of rheumatology and epidemiology at the University of Pennsylvania, Philadelphia, who did not take part in the research but is familiar with the findings.

“We can see that even glucocorticoids taken several years ago may affect cardiovascular risk but that recent use has a bigger effect on risk,” Dr. George said in an interview. “This study also suggests that very low-dose use affects risk.”

For the new study, Dr. Wallace and colleagues examined a Veterans Affairs database and identified 18,882 patients with RA (mean age, 62.5 years; 84% male; 66% GC users) who met the criteria of being > 40 and < 90 years old. The subjects had an initial VA rheumatology visit during 2010-2018 and were excluded if they had a non-RA rheumatologic disorder, prior MACE, or heart failure. MACE was defined as MI, stroke/TIA, cardiac arrest, coronary revascularization, or death from CV cause.

A total of 16% of the cohort had the largest exposure to GCs, defined as use for 90 days or more; 23% had exposure of 14-89 days, and 14% had exposure of 1-13 days.

The median 5-year MACE risk at baseline was 5.3%, and 3,754 patients (19.9%) had high baseline MACE risk. Incident MACE occurred in 4.1% of patients, and the median time to MACE was 2.67 years (interquartile ratio, 1.26-4.45 years).

Covariates included factors such as age, race, sex, body mass index, smoking status, adjusted Elixhauser index, VA risk score for cardiovascular disease, cancer, hospitalization for infection, number of rheumatology clinic visits, and use of lipid-lowering drugs, opioids, methotrexate, biologics, and hydroxychloroquine.

Dr. Wallace noted limitations including the possibility of residual confounding and the influence of background cardiovascular risk. The study didn’t examine the clinical value of taking GCs or compare that to the potential risk. Nor did it examine cost or the risks and benefits of alternative therapeutic options.

A study released earlier this year suggested that patients taking daily prednisolone doses under 5 mg do not have a higher risk of MACE. Previous studies had reached conflicting results.

“Glucocorticoids can provide major benefits to patients, but these benefits must be balanced with the potential risks,” Dr. George said. At low doses, these risks may be small, but they are present. In many cases, escalating DMARD [disease-modifying antirheumatic drug] therapy may be safer than continuing glucocorticoids.”

He added that the risks of GCs may be especially high in older patients and in those who have cardiovascular risk factors: “Often biologics are avoided in these higher-risk patients. But in fact, in many cases biologics may be the safer choice.”

No study funding was reported. Dr. Wallace reported no relevant financial relationships, and some of the other authors reported various ties with industry. Dr. George reported research funding from GlaxoSmithKline and Janssen and consulting fees from AbbVie.

SAN DIEGO – Even when taken at low doses and over short periods, glucocorticoids (GCs) were linked to a higher risk of major adverse cardiovascular events (MACE) over the long term in a Veterans Affairs population of older, mostly male patients with rheumatoid arthritis, a new retrospective cohort study has found.

The analysis of nearly 19,000 patients, presented by rheumatologist Beth Wallace, MD, MSc, at the annual meeting of the American College of Rheumatology, showed that the level of risk for MACE rose with the dose, duration, and recency of GC use, in which risk increased significantly at prednisone-equivalent doses as low as 5 mg/day, durations as short as 30 days, and with last use as long as 1 year before MACE.

University of Michigan

“Up to half of RA patients in the United States use long-term glucocorticoids despite previous work suggesting they increase MACE in a dose-dependent way,” said Dr. Wallace, assistant professor of medicine at the University of Michigan, Ann Arbor, and a rheumatologist at the VA Ann Arbor Healthcare Center. “Our group previously presented work suggesting that less than 14 days of glucocorticoid use in a 6-month period is associated with a two-thirds increase in odds of MACE over the following 6 months, with 90 days of use associated with more than twofold increase.”

In recent years, researchers such as Dr. Wallace have focused attention on the risks of GCs in RA. The American College of Rheumatology and the European Alliance of Associations for Rheumatology emphasize avoiding long-term use of GCs in RA and keeping doses as small and over the shortest amount of time as possible.

When Dr. Wallace and colleagues looked at the clinical pattern of GC use for patients with RA during the past 2 years, those who took 5 mg, 7.5 mg, and 10 mg daily doses for 30 days and had stopped at least a year before had risk for MACE that rose significantly by 3%, 5%, and 7%, respectively, compared with those who didn’t take GCs in the past 2 years.

While those increases were small, risk for MACE rose even more for those who took the same daily doses for 90 days, increasing 10%, 15%, and 21%, respectively. Researchers linked current ongoing use of GCs for the past 90 days to a 13%, 19%, and 27% higher risk for MACE at those respective doses.

The findings “add to the literature suggesting that there is some risk even with low-dose steroids,” said Michael George, MD, assistant professor of rheumatology and epidemiology at the University of Pennsylvania, Philadelphia, who did not take part in the research but is familiar with the findings.

“We can see that even glucocorticoids taken several years ago may affect cardiovascular risk but that recent use has a bigger effect on risk,” Dr. George said in an interview. “This study also suggests that very low-dose use affects risk.”

For the new study, Dr. Wallace and colleagues examined a Veterans Affairs database and identified 18,882 patients with RA (mean age, 62.5 years; 84% male; 66% GC users) who met the criteria of being > 40 and < 90 years old. The subjects had an initial VA rheumatology visit during 2010-2018 and were excluded if they had a non-RA rheumatologic disorder, prior MACE, or heart failure. MACE was defined as MI, stroke/TIA, cardiac arrest, coronary revascularization, or death from CV cause.

A total of 16% of the cohort had the largest exposure to GCs, defined as use for 90 days or more; 23% had exposure of 14-89 days, and 14% had exposure of 1-13 days.

The median 5-year MACE risk at baseline was 5.3%, and 3,754 patients (19.9%) had high baseline MACE risk. Incident MACE occurred in 4.1% of patients, and the median time to MACE was 2.67 years (interquartile ratio, 1.26-4.45 years).

Covariates included factors such as age, race, sex, body mass index, smoking status, adjusted Elixhauser index, VA risk score for cardiovascular disease, cancer, hospitalization for infection, number of rheumatology clinic visits, and use of lipid-lowering drugs, opioids, methotrexate, biologics, and hydroxychloroquine.

Dr. Wallace noted limitations including the possibility of residual confounding and the influence of background cardiovascular risk. The study didn’t examine the clinical value of taking GCs or compare that to the potential risk. Nor did it examine cost or the risks and benefits of alternative therapeutic options.

A study released earlier this year suggested that patients taking daily prednisolone doses under 5 mg do not have a higher risk of MACE. Previous studies had reached conflicting results.

“Glucocorticoids can provide major benefits to patients, but these benefits must be balanced with the potential risks,” Dr. George said. At low doses, these risks may be small, but they are present. In many cases, escalating DMARD [disease-modifying antirheumatic drug] therapy may be safer than continuing glucocorticoids.”

He added that the risks of GCs may be especially high in older patients and in those who have cardiovascular risk factors: “Often biologics are avoided in these higher-risk patients. But in fact, in many cases biologics may be the safer choice.”

No study funding was reported. Dr. Wallace reported no relevant financial relationships, and some of the other authors reported various ties with industry. Dr. George reported research funding from GlaxoSmithKline and Janssen and consulting fees from AbbVie.

SAN DIEGO – Patients with early oligoarticular psoriatic arthritis (PsA) who took apremilast (Otezla) had more than double the response rate of placebo-treated patients by 16 weeks in a double-blind and randomized phase 4 study.

Oligoarticular PsA can significantly affect quality of life even though few joints are affected, and there’s a lack of relevant clinical data to guide treatment, said rheumatologist Philip J. Mease, MD, of the University of Washington and Swedish Medical Center, Seattle, who reported the results in a presentation at the annual meeting of the American College of Rheumatology.

The findings of the study, called FOREMOST, support the use of the drug in mild PsA, Alexis Ogdie, MD, director of the Penn Psoriatic Arthritis Clinic and the Penn Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, Philadelphia, said in an interview. Dr. Ogdie, who was not involved with the research, noted that rheumatologists commonly prescribe apremilast for mild PsA, although previous research has focused on severe PsA cases.

By 16 weeks, 33.9% of 203 who received apremilast and 16% of 105 who received placebo (difference, 18.5%; 95% confidence interval, 8.9-28.1; P = .0008) met the trial’s primary outcome, a modified version of minimal disease activity score (MDA-Joints), which required attainment of 1 or fewer swollen and/or tender joints plus three of five additional criteria (psoriasis body surface area of 3% or less, a patient pain visual analog scale assessment of 15 mm or less out of 0-100 mm, a patient global assessment of 20 mm or less out of 0-100 mm, a Health Assessment Questionnaire-Disability Index score of 0.5 or less, and a Leeds Enthesitis Index score of 1 or less). The primary analysis was conducted only in joints affected at baseline.

The researchers recruited patients with 2-4 swollen and/or tender joints out of a total of 66-68 joints assessed; most patients (87%) randomized in the study had 4 or fewer active joints at baseline. The patients had a mean age of 50.9. The mean duration of PsA was 9.9 months, and 39.9% of patients were taking a conventional disease-modifying antirheumatic drug.

In a clinically important outcome, the percentage who had a patient-reported pain response improvement defined as “significant” reached 31.4% with placebo, compared with 48.8% for apremilast (difference, 17.7%; 95% CI, 6.0-29.4; P = .0044), and the percentage who reached a patient-reported pain response defined as “major” totaled 19.1% for placebo vs. 41.3% for apremilast (difference, 22.3%; 95% CI, 11.7-32.9; P = .002).

In an exploratory analysis of all joints, the percentages meeting MDA-Joints criteria for response were 7.9% with placebo and 21.3% with apremilast (difference, 13.6%; 95% CI, 5.9-21.4; P = .0028. Focusing on this exploratory analysis, Dr. Ogdie noted that examination of all joints is “more consistent” with the understanding of disease activity than only looking at the initial joints that had disease activity.

A post-hoc analysis among subjects with 2-4 affected joints found rates similar to the primary endpoint analysis: MDA-Joints response rates were reached by 34.4% of those who took apremilast and by 17.2% of those who took placebo.

When asked about the relatively low response rate for apremilast, Dr. Ogdie said the drug is “a really mild medication, which is why it belongs in the mild disease population. That’s balanced by the fact that it has a pretty good safety profile,” especially compared with the alternative of methotrexate, she said.

Almost all patients can tolerate apremilast, she said, although they may experience nausea or diarrhea. (The study found that adverse events were as expected for apremilast, and the drug was well tolerated.) Blood labs aren’t necessary, she added, as they are in patients taking methotrexate.

As for cost, apremilast is a highly expensive drug, especially when compared to methotrexate, which costs pennies per tablet at some pharmacies. Amgen, the manufacturer of apremilast, lists the price as $4,600 a month. Still, insurers generally cover apremilast, Dr. Ogdie said.

The study was sponsored by Amgen. Dr. Mease reported financial relationships with many pharmaceutical companies, including Amgen. Many other coauthors reported financial relationships with Amgen and other pharmaceutical companies or were employees of Amgen. Dr. Ogdie reported having multiple consulting relationships with pharmaceutical companies, including Amgen, and receiving grant funding from multiple companies as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Psoriasis Foundation, Rheumatology Research Foundation, and Forward Databank.

SAN DIEGO – Patients with early oligoarticular psoriatic arthritis (PsA) who took apremilast (Otezla) had more than double the response rate of placebo-treated patients by 16 weeks in a double-blind and randomized phase 4 study.

Oligoarticular PsA can significantly affect quality of life even though few joints are affected, and there’s a lack of relevant clinical data to guide treatment, said rheumatologist Philip J. Mease, MD, of the University of Washington and Swedish Medical Center, Seattle, who reported the results in a presentation at the annual meeting of the American College of Rheumatology.

The findings of the study, called FOREMOST, support the use of the drug in mild PsA, Alexis Ogdie, MD, director of the Penn Psoriatic Arthritis Clinic and the Penn Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, Philadelphia, said in an interview. Dr. Ogdie, who was not involved with the research, noted that rheumatologists commonly prescribe apremilast for mild PsA, although previous research has focused on severe PsA cases.

By 16 weeks, 33.9% of 203 who received apremilast and 16% of 105 who received placebo (difference, 18.5%; 95% confidence interval, 8.9-28.1; P = .0008) met the trial’s primary outcome, a modified version of minimal disease activity score (MDA-Joints), which required attainment of 1 or fewer swollen and/or tender joints plus three of five additional criteria (psoriasis body surface area of 3% or less, a patient pain visual analog scale assessment of 15 mm or less out of 0-100 mm, a patient global assessment of 20 mm or less out of 0-100 mm, a Health Assessment Questionnaire-Disability Index score of 0.5 or less, and a Leeds Enthesitis Index score of 1 or less). The primary analysis was conducted only in joints affected at baseline.

The researchers recruited patients with 2-4 swollen and/or tender joints out of a total of 66-68 joints assessed; most patients (87%) randomized in the study had 4 or fewer active joints at baseline. The patients had a mean age of 50.9. The mean duration of PsA was 9.9 months, and 39.9% of patients were taking a conventional disease-modifying antirheumatic drug.

In a clinically important outcome, the percentage who had a patient-reported pain response improvement defined as “significant” reached 31.4% with placebo, compared with 48.8% for apremilast (difference, 17.7%; 95% CI, 6.0-29.4; P = .0044), and the percentage who reached a patient-reported pain response defined as “major” totaled 19.1% for placebo vs. 41.3% for apremilast (difference, 22.3%; 95% CI, 11.7-32.9; P = .002).

In an exploratory analysis of all joints, the percentages meeting MDA-Joints criteria for response were 7.9% with placebo and 21.3% with apremilast (difference, 13.6%; 95% CI, 5.9-21.4; P = .0028. Focusing on this exploratory analysis, Dr. Ogdie noted that examination of all joints is “more consistent” with the understanding of disease activity than only looking at the initial joints that had disease activity.

A post-hoc analysis among subjects with 2-4 affected joints found rates similar to the primary endpoint analysis: MDA-Joints response rates were reached by 34.4% of those who took apremilast and by 17.2% of those who took placebo.

When asked about the relatively low response rate for apremilast, Dr. Ogdie said the drug is “a really mild medication, which is why it belongs in the mild disease population. That’s balanced by the fact that it has a pretty good safety profile,” especially compared with the alternative of methotrexate, she said.

Almost all patients can tolerate apremilast, she said, although they may experience nausea or diarrhea. (The study found that adverse events were as expected for apremilast, and the drug was well tolerated.) Blood labs aren’t necessary, she added, as they are in patients taking methotrexate.

As for cost, apremilast is a highly expensive drug, especially when compared to methotrexate, which costs pennies per tablet at some pharmacies. Amgen, the manufacturer of apremilast, lists the price as $4,600 a month. Still, insurers generally cover apremilast, Dr. Ogdie said.

The study was sponsored by Amgen. Dr. Mease reported financial relationships with many pharmaceutical companies, including Amgen. Many other coauthors reported financial relationships with Amgen and other pharmaceutical companies or were employees of Amgen. Dr. Ogdie reported having multiple consulting relationships with pharmaceutical companies, including Amgen, and receiving grant funding from multiple companies as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Psoriasis Foundation, Rheumatology Research Foundation, and Forward Databank.

SAN DIEGO – Patients with early oligoarticular psoriatic arthritis (PsA) who took apremilast (Otezla) had more than double the response rate of placebo-treated patients by 16 weeks in a double-blind and randomized phase 4 study.

Oligoarticular PsA can significantly affect quality of life even though few joints are affected, and there’s a lack of relevant clinical data to guide treatment, said rheumatologist Philip J. Mease, MD, of the University of Washington and Swedish Medical Center, Seattle, who reported the results in a presentation at the annual meeting of the American College of Rheumatology.

The findings of the study, called FOREMOST, support the use of the drug in mild PsA, Alexis Ogdie, MD, director of the Penn Psoriatic Arthritis Clinic and the Penn Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, Philadelphia, said in an interview. Dr. Ogdie, who was not involved with the research, noted that rheumatologists commonly prescribe apremilast for mild PsA, although previous research has focused on severe PsA cases.

By 16 weeks, 33.9% of 203 who received apremilast and 16% of 105 who received placebo (difference, 18.5%; 95% confidence interval, 8.9-28.1; P = .0008) met the trial’s primary outcome, a modified version of minimal disease activity score (MDA-Joints), which required attainment of 1 or fewer swollen and/or tender joints plus three of five additional criteria (psoriasis body surface area of 3% or less, a patient pain visual analog scale assessment of 15 mm or less out of 0-100 mm, a patient global assessment of 20 mm or less out of 0-100 mm, a Health Assessment Questionnaire-Disability Index score of 0.5 or less, and a Leeds Enthesitis Index score of 1 or less). The primary analysis was conducted only in joints affected at baseline.

The researchers recruited patients with 2-4 swollen and/or tender joints out of a total of 66-68 joints assessed; most patients (87%) randomized in the study had 4 or fewer active joints at baseline. The patients had a mean age of 50.9. The mean duration of PsA was 9.9 months, and 39.9% of patients were taking a conventional disease-modifying antirheumatic drug.

In a clinically important outcome, the percentage who had a patient-reported pain response improvement defined as “significant” reached 31.4% with placebo, compared with 48.8% for apremilast (difference, 17.7%; 95% CI, 6.0-29.4; P = .0044), and the percentage who reached a patient-reported pain response defined as “major” totaled 19.1% for placebo vs. 41.3% for apremilast (difference, 22.3%; 95% CI, 11.7-32.9; P = .002).

In an exploratory analysis of all joints, the percentages meeting MDA-Joints criteria for response were 7.9% with placebo and 21.3% with apremilast (difference, 13.6%; 95% CI, 5.9-21.4; P = .0028. Focusing on this exploratory analysis, Dr. Ogdie noted that examination of all joints is “more consistent” with the understanding of disease activity than only looking at the initial joints that had disease activity.

A post-hoc analysis among subjects with 2-4 affected joints found rates similar to the primary endpoint analysis: MDA-Joints response rates were reached by 34.4% of those who took apremilast and by 17.2% of those who took placebo.

When asked about the relatively low response rate for apremilast, Dr. Ogdie said the drug is “a really mild medication, which is why it belongs in the mild disease population. That’s balanced by the fact that it has a pretty good safety profile,” especially compared with the alternative of methotrexate, she said.

Almost all patients can tolerate apremilast, she said, although they may experience nausea or diarrhea. (The study found that adverse events were as expected for apremilast, and the drug was well tolerated.) Blood labs aren’t necessary, she added, as they are in patients taking methotrexate.

As for cost, apremilast is a highly expensive drug, especially when compared to methotrexate, which costs pennies per tablet at some pharmacies. Amgen, the manufacturer of apremilast, lists the price as $4,600 a month. Still, insurers generally cover apremilast, Dr. Ogdie said.

The study was sponsored by Amgen. Dr. Mease reported financial relationships with many pharmaceutical companies, including Amgen. Many other coauthors reported financial relationships with Amgen and other pharmaceutical companies or were employees of Amgen. Dr. Ogdie reported having multiple consulting relationships with pharmaceutical companies, including Amgen, and receiving grant funding from multiple companies as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Psoriasis Foundation, Rheumatology Research Foundation, and Forward Databank.

SAN DIEGO – The Food and Drug Administration has launched Project Optimus to dramatically overhaul how oncology therapies are developed in clinical trials, with investigational blood cancer drugs taking center stage in this effort.

The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.

Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”

The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.

In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
 

Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?

Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.

Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?

Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.

Q: What is FDA’s goal for Project Optimus?

Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.

Q: What kind of resistance is the FDA getting from drug companies?

Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.

Q: How will all this affect drug development?

Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.

Q: Could this reduce the number of investigational drugs?

Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.

Q: What do you think the future holds?

Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.

SAN DIEGO – The Food and Drug Administration has launched Project Optimus to dramatically overhaul how oncology therapies are developed in clinical trials, with investigational blood cancer drugs taking center stage in this effort.

The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.

Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”

The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.

In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
 

Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?

Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.

Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?

Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.

Q: What is FDA’s goal for Project Optimus?

Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.

Q: What kind of resistance is the FDA getting from drug companies?

Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.

Q: How will all this affect drug development?

Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.

Q: Could this reduce the number of investigational drugs?

Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.

Q: What do you think the future holds?

Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.

SAN DIEGO – The Food and Drug Administration has launched Project Optimus to dramatically overhaul how oncology therapies are developed in clinical trials, with investigational blood cancer drugs taking center stage in this effort.

The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.

Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”

The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.

In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
 

Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?

Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.

Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?

Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.

Q: What is FDA’s goal for Project Optimus?

Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.

Q: What kind of resistance is the FDA getting from drug companies?

Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.

Q: How will all this affect drug development?

Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.

Q: Could this reduce the number of investigational drugs?

Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.

Q: What do you think the future holds?

Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.

SAN DIEGO – A real-world analysis linked the PEXIVAS reduced-dose glucocorticoid (GC) regimen to a higher likelihood of a group of poor outcomes such as death in patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).

The retrospective observational study, presented at the annual meeting of the American College of Rheumatology, aimed to see whether results from the landmark PEXIVAS trial would hold up in a real-world analysis given some important limitations of the PEXIVAS’s primary outcome and its relative lack of balance in choice of induction agents.

First author of the new study, Sophie Nagle, MD, of Cochin Hospital in Paris, and colleagues in the French Vasculitis Study Group noted that PEXIVAS “demonstrated noninferiority of reduced-dose GC regimen compared to standard dose for the incidence of death or end-stage kidney disease (ESKD), with a significant reduction in serious infections at 1 year. However, the primary endpoint did not include disease progression or relapse, the majority of patients received cyclophosphamide as induction therapy, and subgroup analysis showed a trend towards an increased risk of death or ESKD in [rituximab]-treated patients.”

The new findings “give us pause about using low-dose glucocorticoid regimens” and suggest that rheumatologists might be a little more conservative about their use than randomized controlled trials such as PEXIVAS might suggest, said Vanderbilt University vasculitis specialist Kevin W. Byram, MD, who’s familiar with the findings but did not take part in the study.

Dr. Nagle reported that among 234 patients with either GPA or MPA, 33.3% of 126 who received a reduced-dose GC regimen experienced one of the 12-month composite primary outcome’s events of death, disease relapse, ESKD, or disease progression before remission that required treatment modification, compared with 18.5% of 108 who received the standard GC regimen (P = .016).

In a propensity score analysis, the higher risk of poor outcomes in the reduced-dose group remained (hazard ratio, 1.57; 95% confidence interval, 0.93-2.64). A multivariate analysis also identified a higher risk for the composite primary outcome in the reduced-dose group (HR, 1.72; 95% CI, 1.08-2.74), although there was no association with an increased risk of death or ESKD.

The PEXIVAS study, published in 2020, supported lower GC doses in antineutrophil cytoplasmic antibody–associated vasculitis, potentially revolutionizing treatment. “Historically, we have used high doses of glucocorticoids on slower tapers to treat this disease, which itself is a strategy that leads to potential complications,” Dr. Byram said. “PEXIVAS suggested we could potentially use less glucocorticoids in these patients.”

For the retrospective, multicenter study, researchers tracked patients from 2018 to 2022, all aged 15 and above. They included 93 with MPA and 141 with GPA. Nearly half were female, and they had a mean age of 61 years. The patients had severe flare-ups treated with rituximab or cyclophosphamide induction and reduced-dose or standard GC regimen.

The standard care and reduced-dose groups were similar, Dr. Nagle said, although the standard group had significantly more patients with GPA (71% vs. 29% with MPA) than did the low-dose group (51% with GPA, 49% with MPA).

The researchers reported that in a reduced-dose subgroup, patients with creatinine levels above 300 micromol/L were more likely to meet the primary endpoint (relative risk, 2.14; 95% CI, 1.14-4.03). Those treated with the reduced-dose GC regimen were also more likely to reach the primary endpoint (HR, 1.61; 95% CI, 0.94-2.77) and die or develop ESKD (HR, 2.42; 95% CI, 1.04-5.66).

However, adverse events at 12 months were similar in both groups: The authors noted that those who received the reduced-dose GC regimen didn’t have higher risk of death, ESKD, or severe infections.

The authors highlighted that “increased vigilance is required when using the reduced-dose GC regimen especially in two subgroups of patients due to the risk of failure: Patients receiving rituximab as induction therapy [and] patients with severe initial kidney disease (serum creatinine > 300 micromol/L).”

The study authors note several limitations: The study is retrospective, and the standard dose group is heterogeneous.

“This study raises the idea that we need to be careful in using low-dose glucocorticoid regimens, but not avoid them all together,” Dr. Byram said. “The finding that those with worse kidney function fared worse lines up with my clinical experiences. There are clearly populations with this disease that could benefit from more steroid, and it tends to be the ones that are sicker at presentation, particularly those requiring ICU-level care.”

He advised colleagues to “not be dogmatic and use strict low-dose regimens ‘just because.’ ”

No study funding was reported. Dr. Nagle reported having no relevant financial relationships, and disclosures for other authors were not reported. Dr. Byram reports serving on the Vasculitis Foundation board of directors.

SAN DIEGO – A real-world analysis linked the PEXIVAS reduced-dose glucocorticoid (GC) regimen to a higher likelihood of a group of poor outcomes such as death in patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).

The retrospective observational study, presented at the annual meeting of the American College of Rheumatology, aimed to see whether results from the landmark PEXIVAS trial would hold up in a real-world analysis given some important limitations of the PEXIVAS’s primary outcome and its relative lack of balance in choice of induction agents.

First author of the new study, Sophie Nagle, MD, of Cochin Hospital in Paris, and colleagues in the French Vasculitis Study Group noted that PEXIVAS “demonstrated noninferiority of reduced-dose GC regimen compared to standard dose for the incidence of death or end-stage kidney disease (ESKD), with a significant reduction in serious infections at 1 year. However, the primary endpoint did not include disease progression or relapse, the majority of patients received cyclophosphamide as induction therapy, and subgroup analysis showed a trend towards an increased risk of death or ESKD in [rituximab]-treated patients.”

The new findings “give us pause about using low-dose glucocorticoid regimens” and suggest that rheumatologists might be a little more conservative about their use than randomized controlled trials such as PEXIVAS might suggest, said Vanderbilt University vasculitis specialist Kevin W. Byram, MD, who’s familiar with the findings but did not take part in the study.

Dr. Nagle reported that among 234 patients with either GPA or MPA, 33.3% of 126 who received a reduced-dose GC regimen experienced one of the 12-month composite primary outcome’s events of death, disease relapse, ESKD, or disease progression before remission that required treatment modification, compared with 18.5% of 108 who received the standard GC regimen (P = .016).

In a propensity score analysis, the higher risk of poor outcomes in the reduced-dose group remained (hazard ratio, 1.57; 95% confidence interval, 0.93-2.64). A multivariate analysis also identified a higher risk for the composite primary outcome in the reduced-dose group (HR, 1.72; 95% CI, 1.08-2.74), although there was no association with an increased risk of death or ESKD.

The PEXIVAS study, published in 2020, supported lower GC doses in antineutrophil cytoplasmic antibody–associated vasculitis, potentially revolutionizing treatment. “Historically, we have used high doses of glucocorticoids on slower tapers to treat this disease, which itself is a strategy that leads to potential complications,” Dr. Byram said. “PEXIVAS suggested we could potentially use less glucocorticoids in these patients.”

For the retrospective, multicenter study, researchers tracked patients from 2018 to 2022, all aged 15 and above. They included 93 with MPA and 141 with GPA. Nearly half were female, and they had a mean age of 61 years. The patients had severe flare-ups treated with rituximab or cyclophosphamide induction and reduced-dose or standard GC regimen.

The standard care and reduced-dose groups were similar, Dr. Nagle said, although the standard group had significantly more patients with GPA (71% vs. 29% with MPA) than did the low-dose group (51% with GPA, 49% with MPA).

The researchers reported that in a reduced-dose subgroup, patients with creatinine levels above 300 micromol/L were more likely to meet the primary endpoint (relative risk, 2.14; 95% CI, 1.14-4.03). Those treated with the reduced-dose GC regimen were also more likely to reach the primary endpoint (HR, 1.61; 95% CI, 0.94-2.77) and die or develop ESKD (HR, 2.42; 95% CI, 1.04-5.66).

However, adverse events at 12 months were similar in both groups: The authors noted that those who received the reduced-dose GC regimen didn’t have higher risk of death, ESKD, or severe infections.

The authors highlighted that “increased vigilance is required when using the reduced-dose GC regimen especially in two subgroups of patients due to the risk of failure: Patients receiving rituximab as induction therapy [and] patients with severe initial kidney disease (serum creatinine > 300 micromol/L).”

The study authors note several limitations: The study is retrospective, and the standard dose group is heterogeneous.

“This study raises the idea that we need to be careful in using low-dose glucocorticoid regimens, but not avoid them all together,” Dr. Byram said. “The finding that those with worse kidney function fared worse lines up with my clinical experiences. There are clearly populations with this disease that could benefit from more steroid, and it tends to be the ones that are sicker at presentation, particularly those requiring ICU-level care.”

He advised colleagues to “not be dogmatic and use strict low-dose regimens ‘just because.’ ”

No study funding was reported. Dr. Nagle reported having no relevant financial relationships, and disclosures for other authors were not reported. Dr. Byram reports serving on the Vasculitis Foundation board of directors.

SAN DIEGO – A real-world analysis linked the PEXIVAS reduced-dose glucocorticoid (GC) regimen to a higher likelihood of a group of poor outcomes such as death in patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).

The retrospective observational study, presented at the annual meeting of the American College of Rheumatology, aimed to see whether results from the landmark PEXIVAS trial would hold up in a real-world analysis given some important limitations of the PEXIVAS’s primary outcome and its relative lack of balance in choice of induction agents.

First author of the new study, Sophie Nagle, MD, of Cochin Hospital in Paris, and colleagues in the French Vasculitis Study Group noted that PEXIVAS “demonstrated noninferiority of reduced-dose GC regimen compared to standard dose for the incidence of death or end-stage kidney disease (ESKD), with a significant reduction in serious infections at 1 year. However, the primary endpoint did not include disease progression or relapse, the majority of patients received cyclophosphamide as induction therapy, and subgroup analysis showed a trend towards an increased risk of death or ESKD in [rituximab]-treated patients.”

The new findings “give us pause about using low-dose glucocorticoid regimens” and suggest that rheumatologists might be a little more conservative about their use than randomized controlled trials such as PEXIVAS might suggest, said Vanderbilt University vasculitis specialist Kevin W. Byram, MD, who’s familiar with the findings but did not take part in the study.

Dr. Nagle reported that among 234 patients with either GPA or MPA, 33.3% of 126 who received a reduced-dose GC regimen experienced one of the 12-month composite primary outcome’s events of death, disease relapse, ESKD, or disease progression before remission that required treatment modification, compared with 18.5% of 108 who received the standard GC regimen (P = .016).

In a propensity score analysis, the higher risk of poor outcomes in the reduced-dose group remained (hazard ratio, 1.57; 95% confidence interval, 0.93-2.64). A multivariate analysis also identified a higher risk for the composite primary outcome in the reduced-dose group (HR, 1.72; 95% CI, 1.08-2.74), although there was no association with an increased risk of death or ESKD.

The PEXIVAS study, published in 2020, supported lower GC doses in antineutrophil cytoplasmic antibody–associated vasculitis, potentially revolutionizing treatment. “Historically, we have used high doses of glucocorticoids on slower tapers to treat this disease, which itself is a strategy that leads to potential complications,” Dr. Byram said. “PEXIVAS suggested we could potentially use less glucocorticoids in these patients.”

For the retrospective, multicenter study, researchers tracked patients from 2018 to 2022, all aged 15 and above. They included 93 with MPA and 141 with GPA. Nearly half were female, and they had a mean age of 61 years. The patients had severe flare-ups treated with rituximab or cyclophosphamide induction and reduced-dose or standard GC regimen.

The standard care and reduced-dose groups were similar, Dr. Nagle said, although the standard group had significantly more patients with GPA (71% vs. 29% with MPA) than did the low-dose group (51% with GPA, 49% with MPA).

The researchers reported that in a reduced-dose subgroup, patients with creatinine levels above 300 micromol/L were more likely to meet the primary endpoint (relative risk, 2.14; 95% CI, 1.14-4.03). Those treated with the reduced-dose GC regimen were also more likely to reach the primary endpoint (HR, 1.61; 95% CI, 0.94-2.77) and die or develop ESKD (HR, 2.42; 95% CI, 1.04-5.66).

However, adverse events at 12 months were similar in both groups: The authors noted that those who received the reduced-dose GC regimen didn’t have higher risk of death, ESKD, or severe infections.

The authors highlighted that “increased vigilance is required when using the reduced-dose GC regimen especially in two subgroups of patients due to the risk of failure: Patients receiving rituximab as induction therapy [and] patients with severe initial kidney disease (serum creatinine > 300 micromol/L).”

The study authors note several limitations: The study is retrospective, and the standard dose group is heterogeneous.

“This study raises the idea that we need to be careful in using low-dose glucocorticoid regimens, but not avoid them all together,” Dr. Byram said. “The finding that those with worse kidney function fared worse lines up with my clinical experiences. There are clearly populations with this disease that could benefit from more steroid, and it tends to be the ones that are sicker at presentation, particularly those requiring ICU-level care.”

He advised colleagues to “not be dogmatic and use strict low-dose regimens ‘just because.’ ”

No study funding was reported. Dr. Nagle reported having no relevant financial relationships, and disclosures for other authors were not reported. Dr. Byram reports serving on the Vasculitis Foundation board of directors.

LA JOLLA, CALIF. – Twelve years ago, an international task force of the European Alliance of Associations for Rheumatology (EULAR) released recommendations regarding nomenclature in calcium pyrophosphate deposition disease (CPPD), aiming to standardize the way the condition is described. “Pseudogout” was out, and “acute CPP crystal arthritis” was in, and a confusing array of multi-named phenotypes gained specific labels.

Since 2011, the nomenclature guidelines have been cited hundreds of times, but a new report finds that the medical literature mostly hasn’t followed the recommendations. The findings were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN), which is taking another stab at overhauling CPPD nomenclature.

“The objective is to uniform and standardize the labels of the disease, the disease elements, and the clinical states,” rheumatologist Charlotte Jauffret, MD, of the Catholic University of Lille (France), said in a presentation. CPPD is a widely underdiagnosed disease that’s worth the same efforts to standardize nomenclature as occurred in gout, she said.

As Dr. Jauffret explained, CPPD has a diversity of phenotypes in asymptomatic, acute, and chronic forms that pose challenges to diagnosis. “The same terms are used to depict different concepts, and some disease elements are depicted through different names,” she said.

Among other suggestions, the 2011 EULAR recommendations suggested that rheumatologists use the terms chronic CPP crystal inflammatory arthritis instead of “pseudo-rheumatoid arthritis,” osteoarthritis with CPPD, instead of “pseudo-osteoarthritis,” and severe joint degeneration instead of “pseudo-neuropathic joint disease.”

Later reports noted that terms such as CPPD and chondrocalcinosis are still wrongly used interchangeably and called for an international consensus on nomenclature, Dr. Jauffret said.

For the new report, Dr. Jauffret and colleagues examined 985 articles from 2000-2022. The guidelines were often not followed even after the release of the recommendations.

For example, 49% of relevant papers used the label “pseudogout” before 2011, and 43% did afterward. A total of 34% of relevant papers described CPPD as chondrocalcinosis prior to 2011, and 22% did afterward.

G-CAN’s next steps are to reach consensus on terminology through online and in-person meetings in 2024, Dr. Jauffret said.
 

Use of correct gout nomenclature labels improved

In a related presentation, rheumatologist Ellen Prendergast, MBChB, of Dunedin Hospital in New Zealand, reported the results of a newly published review of gout studies before and after G-CAN released consensus recommendations for gout nomenclature in 2019. “There has been improvement in the agreed labels in some areas, but there remains quite significant variability,” she said.

The review examined American College of Rheumatology and EULAR annual meeting abstracts: 596 from 2016-2017 and 392 from 2020-2021. Dr. Prendergast said researchers focused on abstracts instead of published studies in order to gain the most up-to-date understanding of nomenclature.

“Use of the agreed labels ‘urate’ and ‘gout flare’ increased between the two periods. There were 219 of 383 (57.2%) abstracts with the agreed label ‘urate’ in 2016-2017, compared with 164 of 232 (70.7%) in 2020-2021 (P = .001),” the researchers reported. “There were 60 of 175 (34.3%) abstracts with the agreed label ‘gout flare’ in 2016-2017, compared with 57 of 109 (52.3%) in 2020-2021 (P = .003).”

And the use of the term “chronic gout,” which the guidelines recommend against, fell from 29 of 596 (4.9%) abstracts in 2016-2017 to 8 of 392 (2.0%) abstracts in 2020-2021 (P = .02).

One author of the gout nomenclature study reports various consulting fees, speaker fees, or grants outside the submitted work. The other authors of the two studies report no disclosures.

LA JOLLA, CALIF. – Twelve years ago, an international task force of the European Alliance of Associations for Rheumatology (EULAR) released recommendations regarding nomenclature in calcium pyrophosphate deposition disease (CPPD), aiming to standardize the way the condition is described. “Pseudogout” was out, and “acute CPP crystal arthritis” was in, and a confusing array of multi-named phenotypes gained specific labels.

Since 2011, the nomenclature guidelines have been cited hundreds of times, but a new report finds that the medical literature mostly hasn’t followed the recommendations. The findings were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN), which is taking another stab at overhauling CPPD nomenclature.

“The objective is to uniform and standardize the labels of the disease, the disease elements, and the clinical states,” rheumatologist Charlotte Jauffret, MD, of the Catholic University of Lille (France), said in a presentation. CPPD is a widely underdiagnosed disease that’s worth the same efforts to standardize nomenclature as occurred in gout, she said.

As Dr. Jauffret explained, CPPD has a diversity of phenotypes in asymptomatic, acute, and chronic forms that pose challenges to diagnosis. “The same terms are used to depict different concepts, and some disease elements are depicted through different names,” she said.

Among other suggestions, the 2011 EULAR recommendations suggested that rheumatologists use the terms chronic CPP crystal inflammatory arthritis instead of “pseudo-rheumatoid arthritis,” osteoarthritis with CPPD, instead of “pseudo-osteoarthritis,” and severe joint degeneration instead of “pseudo-neuropathic joint disease.”

Later reports noted that terms such as CPPD and chondrocalcinosis are still wrongly used interchangeably and called for an international consensus on nomenclature, Dr. Jauffret said.

For the new report, Dr. Jauffret and colleagues examined 985 articles from 2000-2022. The guidelines were often not followed even after the release of the recommendations.

For example, 49% of relevant papers used the label “pseudogout” before 2011, and 43% did afterward. A total of 34% of relevant papers described CPPD as chondrocalcinosis prior to 2011, and 22% did afterward.

G-CAN’s next steps are to reach consensus on terminology through online and in-person meetings in 2024, Dr. Jauffret said.
 

Use of correct gout nomenclature labels improved

In a related presentation, rheumatologist Ellen Prendergast, MBChB, of Dunedin Hospital in New Zealand, reported the results of a newly published review of gout studies before and after G-CAN released consensus recommendations for gout nomenclature in 2019. “There has been improvement in the agreed labels in some areas, but there remains quite significant variability,” she said.

The review examined American College of Rheumatology and EULAR annual meeting abstracts: 596 from 2016-2017 and 392 from 2020-2021. Dr. Prendergast said researchers focused on abstracts instead of published studies in order to gain the most up-to-date understanding of nomenclature.

“Use of the agreed labels ‘urate’ and ‘gout flare’ increased between the two periods. There were 219 of 383 (57.2%) abstracts with the agreed label ‘urate’ in 2016-2017, compared with 164 of 232 (70.7%) in 2020-2021 (P = .001),” the researchers reported. “There were 60 of 175 (34.3%) abstracts with the agreed label ‘gout flare’ in 2016-2017, compared with 57 of 109 (52.3%) in 2020-2021 (P = .003).”

And the use of the term “chronic gout,” which the guidelines recommend against, fell from 29 of 596 (4.9%) abstracts in 2016-2017 to 8 of 392 (2.0%) abstracts in 2020-2021 (P = .02).

One author of the gout nomenclature study reports various consulting fees, speaker fees, or grants outside the submitted work. The other authors of the two studies report no disclosures.

LA JOLLA, CALIF. – Twelve years ago, an international task force of the European Alliance of Associations for Rheumatology (EULAR) released recommendations regarding nomenclature in calcium pyrophosphate deposition disease (CPPD), aiming to standardize the way the condition is described. “Pseudogout” was out, and “acute CPP crystal arthritis” was in, and a confusing array of multi-named phenotypes gained specific labels.

Since 2011, the nomenclature guidelines have been cited hundreds of times, but a new report finds that the medical literature mostly hasn’t followed the recommendations. The findings were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN), which is taking another stab at overhauling CPPD nomenclature.

“The objective is to uniform and standardize the labels of the disease, the disease elements, and the clinical states,” rheumatologist Charlotte Jauffret, MD, of the Catholic University of Lille (France), said in a presentation. CPPD is a widely underdiagnosed disease that’s worth the same efforts to standardize nomenclature as occurred in gout, she said.

As Dr. Jauffret explained, CPPD has a diversity of phenotypes in asymptomatic, acute, and chronic forms that pose challenges to diagnosis. “The same terms are used to depict different concepts, and some disease elements are depicted through different names,” she said.

Among other suggestions, the 2011 EULAR recommendations suggested that rheumatologists use the terms chronic CPP crystal inflammatory arthritis instead of “pseudo-rheumatoid arthritis,” osteoarthritis with CPPD, instead of “pseudo-osteoarthritis,” and severe joint degeneration instead of “pseudo-neuropathic joint disease.”

Later reports noted that terms such as CPPD and chondrocalcinosis are still wrongly used interchangeably and called for an international consensus on nomenclature, Dr. Jauffret said.

For the new report, Dr. Jauffret and colleagues examined 985 articles from 2000-2022. The guidelines were often not followed even after the release of the recommendations.

For example, 49% of relevant papers used the label “pseudogout” before 2011, and 43% did afterward. A total of 34% of relevant papers described CPPD as chondrocalcinosis prior to 2011, and 22% did afterward.

G-CAN’s next steps are to reach consensus on terminology through online and in-person meetings in 2024, Dr. Jauffret said.
 

Use of correct gout nomenclature labels improved

In a related presentation, rheumatologist Ellen Prendergast, MBChB, of Dunedin Hospital in New Zealand, reported the results of a newly published review of gout studies before and after G-CAN released consensus recommendations for gout nomenclature in 2019. “There has been improvement in the agreed labels in some areas, but there remains quite significant variability,” she said.

The review examined American College of Rheumatology and EULAR annual meeting abstracts: 596 from 2016-2017 and 392 from 2020-2021. Dr. Prendergast said researchers focused on abstracts instead of published studies in order to gain the most up-to-date understanding of nomenclature.

“Use of the agreed labels ‘urate’ and ‘gout flare’ increased between the two periods. There were 219 of 383 (57.2%) abstracts with the agreed label ‘urate’ in 2016-2017, compared with 164 of 232 (70.7%) in 2020-2021 (P = .001),” the researchers reported. “There were 60 of 175 (34.3%) abstracts with the agreed label ‘gout flare’ in 2016-2017, compared with 57 of 109 (52.3%) in 2020-2021 (P = .003).”

And the use of the term “chronic gout,” which the guidelines recommend against, fell from 29 of 596 (4.9%) abstracts in 2016-2017 to 8 of 392 (2.0%) abstracts in 2020-2021 (P = .02).

One author of the gout nomenclature study reports various consulting fees, speaker fees, or grants outside the submitted work. The other authors of the two studies report no disclosures.

LA JOLLA, Calif. – A new analysis suggests that it may not be necessary to delay urate-lowering therapy (ULT) in gout flares, and a study warns of the potential heightened risk of peripheral arterial disease (PAD) in gout.

The reports were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

The urate-lowering report, a systematic review and meta-analysis, suggests that the use of ULT during a gout flare “does not affect flare severity nor the duration of the flare or risk of recurrence in the subsequent month,” lead author Vicky Tai, MBChB, of the University of Auckland (New Zealand), said in a presentation.

She noted that there’s ongoing debate about whether ULT should be delayed until a week or two after gout flares subside to avoid their return. “This is reflected in guidelines on gout management, which have provided inconsistent recommendations on the issue,” Dr. Tai said.

As she noted, the American College of Rheumatology’s 2020 gout guidelines conditionally recommended starting ULT during gout flares – and not afterward – if it’s indicated. (The guidelines also conditionally recommend against ULT in a first gout flare, however, with a few exceptions.)

The British Society for Rheumatology’s 2017 gout guidelines suggested waiting until flares have settled down and “the patient was no longer in pain,” although ULT may be started in patients with frequent attacks. The European Alliance of Associations for Rheumatology’s gout guidelines from 2016 didn’t address timing, Dr. Tai said.

For the new analysis, Dr. Tai and colleagues examined six randomized studies from the United States (two), China (two), Taiwan (one), and Thailand (one) that examined the use of allopurinol (three studies), febuxostat (two studies), and probenecid (one). The studies, dated from 2012 to 2023, randomized 226 subjects with gout to early initiation of ULT vs. 219 who received placebo or delayed ULT. Subjects were tracked for a median of 28 days (15 days to 12 weeks).

Three of the studies were deemed to have high risk of bias.

There were no differences in patient-rated pain scores at various time points, duration of gout flares (examined in three studies), or recurrence of gout flares (examined in four studies).

“Other outcomes of interest, including long-term adherence, time to achieve target serum urate, and patient satisfaction with treatment, were not examined,” Dr. Tai said. “Adverse events were similar between groups.”

She cautioned that the sample sizes are small, and the findings may not be applicable to patients with tophaceous gout or comorbid renal disease.

A similar meta-analysis published in 2022 examined five studies (including three of those in the new analysis); among the five was one study from 1987 that examined azapropazone and indomethacin plus allopurinol. The review found “that initiation of ULT during an acute gout flare did not prolong the duration of acute flares.”
 

Risk for PAD

In the other study, researchers raised an alarm after finding a high rate of PAD in patients with gout regardless of whether they also had diabetes, which is a known risk factor for PAD. “Our data suggest that gout is an underrecognized risk factor for PAD and indicates the importance of assessing for PAD in gout patients,” lead author Nicole Leung, MD, of NYU Langone Health, said in a presentation.

According to Dr. Leung, there’s little known about links between PAD and gout, although she highlighted a 2018 study that found that patients with obstructive coronary artery disease were more likely to have poor outcomes if they also developed gout after catheterization. She highlighted a 2022 study that found higher rates of lower-extremity amputations in patients with gout independent of cardiovascular disease and diabetes. However, she noted that a link to PAD is unclear, and the study found a link between gout and amputations that was independent of PAD.

Patients with gout, she added, are not routinely screened for PAD.

For the new retrospective, cross-sectional analysis, Dr. Leung and colleagues examined Veterans Administration data from 2014 to 2018 for 7.2 million patients. The population was largely male.

Of those, 140,862 (2.52%) – the control group – had no gout or diabetes. In comparison, 11,449 (5.56%) of 205,904 with gout but not diabetes had PAD, for a rate 2.2 times greater than the control group). PAD occurred in 101,582 (8.70%) of 1,168,138 with diabetes but not gout, giving a rate 3.2 times greater than the control group. The rate was highest among people with both gout and diabetes, at 9.97% (9,905 of 99,377), which is about four times greater than the control group.

The link between gout and PAD remained after adjustment for creatinine levels, age, gender, and body mass index. Diabetes was linked to a higher risk for PAD than was gout, and the effect of both conditions combined was “less than additive.” This “may suggest an overlap and pathophysiology between the two,” she said.

Disclosure information was not provided. The Rheumatology Research Foundation funded the PAD study; funding information for the ULT/gout flare analysis was not provided.

LA JOLLA, Calif. – A new analysis suggests that it may not be necessary to delay urate-lowering therapy (ULT) in gout flares, and a study warns of the potential heightened risk of peripheral arterial disease (PAD) in gout.

The reports were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

The urate-lowering report, a systematic review and meta-analysis, suggests that the use of ULT during a gout flare “does not affect flare severity nor the duration of the flare or risk of recurrence in the subsequent month,” lead author Vicky Tai, MBChB, of the University of Auckland (New Zealand), said in a presentation.

She noted that there’s ongoing debate about whether ULT should be delayed until a week or two after gout flares subside to avoid their return. “This is reflected in guidelines on gout management, which have provided inconsistent recommendations on the issue,” Dr. Tai said.

As she noted, the American College of Rheumatology’s 2020 gout guidelines conditionally recommended starting ULT during gout flares – and not afterward – if it’s indicated. (The guidelines also conditionally recommend against ULT in a first gout flare, however, with a few exceptions.)

The British Society for Rheumatology’s 2017 gout guidelines suggested waiting until flares have settled down and “the patient was no longer in pain,” although ULT may be started in patients with frequent attacks. The European Alliance of Associations for Rheumatology’s gout guidelines from 2016 didn’t address timing, Dr. Tai said.

For the new analysis, Dr. Tai and colleagues examined six randomized studies from the United States (two), China (two), Taiwan (one), and Thailand (one) that examined the use of allopurinol (three studies), febuxostat (two studies), and probenecid (one). The studies, dated from 2012 to 2023, randomized 226 subjects with gout to early initiation of ULT vs. 219 who received placebo or delayed ULT. Subjects were tracked for a median of 28 days (15 days to 12 weeks).

Three of the studies were deemed to have high risk of bias.

There were no differences in patient-rated pain scores at various time points, duration of gout flares (examined in three studies), or recurrence of gout flares (examined in four studies).

“Other outcomes of interest, including long-term adherence, time to achieve target serum urate, and patient satisfaction with treatment, were not examined,” Dr. Tai said. “Adverse events were similar between groups.”

She cautioned that the sample sizes are small, and the findings may not be applicable to patients with tophaceous gout or comorbid renal disease.

A similar meta-analysis published in 2022 examined five studies (including three of those in the new analysis); among the five was one study from 1987 that examined azapropazone and indomethacin plus allopurinol. The review found “that initiation of ULT during an acute gout flare did not prolong the duration of acute flares.”
 

Risk for PAD

In the other study, researchers raised an alarm after finding a high rate of PAD in patients with gout regardless of whether they also had diabetes, which is a known risk factor for PAD. “Our data suggest that gout is an underrecognized risk factor for PAD and indicates the importance of assessing for PAD in gout patients,” lead author Nicole Leung, MD, of NYU Langone Health, said in a presentation.

According to Dr. Leung, there’s little known about links between PAD and gout, although she highlighted a 2018 study that found that patients with obstructive coronary artery disease were more likely to have poor outcomes if they also developed gout after catheterization. She highlighted a 2022 study that found higher rates of lower-extremity amputations in patients with gout independent of cardiovascular disease and diabetes. However, she noted that a link to PAD is unclear, and the study found a link between gout and amputations that was independent of PAD.

Patients with gout, she added, are not routinely screened for PAD.

For the new retrospective, cross-sectional analysis, Dr. Leung and colleagues examined Veterans Administration data from 2014 to 2018 for 7.2 million patients. The population was largely male.

Of those, 140,862 (2.52%) – the control group – had no gout or diabetes. In comparison, 11,449 (5.56%) of 205,904 with gout but not diabetes had PAD, for a rate 2.2 times greater than the control group). PAD occurred in 101,582 (8.70%) of 1,168,138 with diabetes but not gout, giving a rate 3.2 times greater than the control group. The rate was highest among people with both gout and diabetes, at 9.97% (9,905 of 99,377), which is about four times greater than the control group.

The link between gout and PAD remained after adjustment for creatinine levels, age, gender, and body mass index. Diabetes was linked to a higher risk for PAD than was gout, and the effect of both conditions combined was “less than additive.” This “may suggest an overlap and pathophysiology between the two,” she said.

Disclosure information was not provided. The Rheumatology Research Foundation funded the PAD study; funding information for the ULT/gout flare analysis was not provided.

LA JOLLA, Calif. – A new analysis suggests that it may not be necessary to delay urate-lowering therapy (ULT) in gout flares, and a study warns of the potential heightened risk of peripheral arterial disease (PAD) in gout.

The reports were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

The urate-lowering report, a systematic review and meta-analysis, suggests that the use of ULT during a gout flare “does not affect flare severity nor the duration of the flare or risk of recurrence in the subsequent month,” lead author Vicky Tai, MBChB, of the University of Auckland (New Zealand), said in a presentation.

She noted that there’s ongoing debate about whether ULT should be delayed until a week or two after gout flares subside to avoid their return. “This is reflected in guidelines on gout management, which have provided inconsistent recommendations on the issue,” Dr. Tai said.

As she noted, the American College of Rheumatology’s 2020 gout guidelines conditionally recommended starting ULT during gout flares – and not afterward – if it’s indicated. (The guidelines also conditionally recommend against ULT in a first gout flare, however, with a few exceptions.)

The British Society for Rheumatology’s 2017 gout guidelines suggested waiting until flares have settled down and “the patient was no longer in pain,” although ULT may be started in patients with frequent attacks. The European Alliance of Associations for Rheumatology’s gout guidelines from 2016 didn’t address timing, Dr. Tai said.

For the new analysis, Dr. Tai and colleagues examined six randomized studies from the United States (two), China (two), Taiwan (one), and Thailand (one) that examined the use of allopurinol (three studies), febuxostat (two studies), and probenecid (one). The studies, dated from 2012 to 2023, randomized 226 subjects with gout to early initiation of ULT vs. 219 who received placebo or delayed ULT. Subjects were tracked for a median of 28 days (15 days to 12 weeks).

Three of the studies were deemed to have high risk of bias.

There were no differences in patient-rated pain scores at various time points, duration of gout flares (examined in three studies), or recurrence of gout flares (examined in four studies).

“Other outcomes of interest, including long-term adherence, time to achieve target serum urate, and patient satisfaction with treatment, were not examined,” Dr. Tai said. “Adverse events were similar between groups.”

She cautioned that the sample sizes are small, and the findings may not be applicable to patients with tophaceous gout or comorbid renal disease.

A similar meta-analysis published in 2022 examined five studies (including three of those in the new analysis); among the five was one study from 1987 that examined azapropazone and indomethacin plus allopurinol. The review found “that initiation of ULT during an acute gout flare did not prolong the duration of acute flares.”
 

Risk for PAD

In the other study, researchers raised an alarm after finding a high rate of PAD in patients with gout regardless of whether they also had diabetes, which is a known risk factor for PAD. “Our data suggest that gout is an underrecognized risk factor for PAD and indicates the importance of assessing for PAD in gout patients,” lead author Nicole Leung, MD, of NYU Langone Health, said in a presentation.

According to Dr. Leung, there’s little known about links between PAD and gout, although she highlighted a 2018 study that found that patients with obstructive coronary artery disease were more likely to have poor outcomes if they also developed gout after catheterization. She highlighted a 2022 study that found higher rates of lower-extremity amputations in patients with gout independent of cardiovascular disease and diabetes. However, she noted that a link to PAD is unclear, and the study found a link between gout and amputations that was independent of PAD.

Patients with gout, she added, are not routinely screened for PAD.

For the new retrospective, cross-sectional analysis, Dr. Leung and colleagues examined Veterans Administration data from 2014 to 2018 for 7.2 million patients. The population was largely male.

Of those, 140,862 (2.52%) – the control group – had no gout or diabetes. In comparison, 11,449 (5.56%) of 205,904 with gout but not diabetes had PAD, for a rate 2.2 times greater than the control group). PAD occurred in 101,582 (8.70%) of 1,168,138 with diabetes but not gout, giving a rate 3.2 times greater than the control group. The rate was highest among people with both gout and diabetes, at 9.97% (9,905 of 99,377), which is about four times greater than the control group.

The link between gout and PAD remained after adjustment for creatinine levels, age, gender, and body mass index. Diabetes was linked to a higher risk for PAD than was gout, and the effect of both conditions combined was “less than additive.” This “may suggest an overlap and pathophysiology between the two,” she said.

Disclosure information was not provided. The Rheumatology Research Foundation funded the PAD study; funding information for the ULT/gout flare analysis was not provided.

SAN DIEGO – Scientists are seeing positive early results from treating relapsed/refractory T-cell blood cancers with un–gene-edited chimeric antigen receptor (CAR) T-cell therapy, a translational immunologist told colleagues at the annual meeting of the Society for Immunotherapy of Cancer. Some patients have had durable complete remission.

As Baylor College of Medicine’s Max Mamonkin, PhD, noted in a presentation, patients with conditions such as T-cell lymphoma and T-cell acute lymphoblastic leukemia (ALL) have limited treatment options and grim prognoses. “This is an area with huge unmet need,” he said. “They don’t have options that patients with B-cell malignancies have, like [CAR T-cell therapy] and bispecifics.”

One big challenge is that CAR-targeted antigens in T-cell blood cancers are shared by both normal and malignant T-cells, he said. That poses a risk during therapy that the engineered cells will target each other with “disastrous consequences.”

Research by his team and others have shown that gene editing can help the cells to stop engaging in “fratricide,” Dr. Mamonkin said.

The problem is “it’s much easier to do gene editing on the bench and much harder to translate it into the clinic,” especially in light of limitations posed by the Food and Drug administration, he said. “We started to think about alternative methods to get this approach to the clinic.”

One strategy is to use pharmacologic inhibition via the Bruton’s tyrosine kinase inhibitors ibrutinib and dasatinib to mute the tendency of CAR T toward self-destruction. When tested in mice, “the unedited cells not just persisted, they expanded with sustained anti-leukemic activity and significantly prolonged their lives even more than the knock-out [gene-edited] cells.”

The research has now moved to human subjects. In 2021, researchers at Texas Children’s Hospital and Houston Methodist Hospital launched a clinical trial to test CD7 CAR T-cell therapy with CD28 in 21 patients with CD7-positive T-cell lymphoma. The initial part of the transplant-enabling CRIMSON-NE study is expected to be completed by mid-2024, and patients will be followed for 15 years.

Early results show that CD7 CAR T-cells have persisted in the blood of patients over weeks and months, Dr. Mamonkin said. In eight patients, “we’re seeing good evidence of activity,” with two patients reaching complete remissions.

The findings suggest that CD7 can be targeted in T-cell malignancies, he said. What about CD5? A similar study known as MAGENTA is testing CD5 CAR T-cell therapy with CD28 in T-cell leukemia and lymphoma in 42 patients. The phase 1 trial began in 2017. It’s expected to be completed by 2024 and to track patients for 15 years.

Results so far have been positive with complete remission achieved in three of nine patients with T-cell lymphoma; two remained in remission for more than 4 years.

Results in T-cell ALL improved after researchers adjusted the manufacturing of the cells. As for durability in these patients, “we try to bridge them to transplantation as soon as possible.”

As for side effects overall, there wasn’t much immune effector cell-associated neurotoxicity syndrome, and the CD7 approach seems to be more inflammatory, he said.

The presentation didn’t address the potential cost of the therapies. CAR T-cell therapy can cost between $500,000 and $1 million. Medicare covers it, but Medicaid may not depending on the state, and insurers may refuse to pay for it.

Dr. Mamonkin disclosed ties with Allogene, Amgen, Fate, Galapagos, March Bio, and NKILT.

SAN DIEGO – Scientists are seeing positive early results from treating relapsed/refractory T-cell blood cancers with un–gene-edited chimeric antigen receptor (CAR) T-cell therapy, a translational immunologist told colleagues at the annual meeting of the Society for Immunotherapy of Cancer. Some patients have had durable complete remission.

As Baylor College of Medicine’s Max Mamonkin, PhD, noted in a presentation, patients with conditions such as T-cell lymphoma and T-cell acute lymphoblastic leukemia (ALL) have limited treatment options and grim prognoses. “This is an area with huge unmet need,” he said. “They don’t have options that patients with B-cell malignancies have, like [CAR T-cell therapy] and bispecifics.”

One big challenge is that CAR-targeted antigens in T-cell blood cancers are shared by both normal and malignant T-cells, he said. That poses a risk during therapy that the engineered cells will target each other with “disastrous consequences.”

Research by his team and others have shown that gene editing can help the cells to stop engaging in “fratricide,” Dr. Mamonkin said.

The problem is “it’s much easier to do gene editing on the bench and much harder to translate it into the clinic,” especially in light of limitations posed by the Food and Drug administration, he said. “We started to think about alternative methods to get this approach to the clinic.”

One strategy is to use pharmacologic inhibition via the Bruton’s tyrosine kinase inhibitors ibrutinib and dasatinib to mute the tendency of CAR T toward self-destruction. When tested in mice, “the unedited cells not just persisted, they expanded with sustained anti-leukemic activity and significantly prolonged their lives even more than the knock-out [gene-edited] cells.”

The research has now moved to human subjects. In 2021, researchers at Texas Children’s Hospital and Houston Methodist Hospital launched a clinical trial to test CD7 CAR T-cell therapy with CD28 in 21 patients with CD7-positive T-cell lymphoma. The initial part of the transplant-enabling CRIMSON-NE study is expected to be completed by mid-2024, and patients will be followed for 15 years.

Early results show that CD7 CAR T-cells have persisted in the blood of patients over weeks and months, Dr. Mamonkin said. In eight patients, “we’re seeing good evidence of activity,” with two patients reaching complete remissions.

The findings suggest that CD7 can be targeted in T-cell malignancies, he said. What about CD5? A similar study known as MAGENTA is testing CD5 CAR T-cell therapy with CD28 in T-cell leukemia and lymphoma in 42 patients. The phase 1 trial began in 2017. It’s expected to be completed by 2024 and to track patients for 15 years.

Results so far have been positive with complete remission achieved in three of nine patients with T-cell lymphoma; two remained in remission for more than 4 years.

Results in T-cell ALL improved after researchers adjusted the manufacturing of the cells. As for durability in these patients, “we try to bridge them to transplantation as soon as possible.”

As for side effects overall, there wasn’t much immune effector cell-associated neurotoxicity syndrome, and the CD7 approach seems to be more inflammatory, he said.

The presentation didn’t address the potential cost of the therapies. CAR T-cell therapy can cost between $500,000 and $1 million. Medicare covers it, but Medicaid may not depending on the state, and insurers may refuse to pay for it.

Dr. Mamonkin disclosed ties with Allogene, Amgen, Fate, Galapagos, March Bio, and NKILT.

SAN DIEGO – Scientists are seeing positive early results from treating relapsed/refractory T-cell blood cancers with un–gene-edited chimeric antigen receptor (CAR) T-cell therapy, a translational immunologist told colleagues at the annual meeting of the Society for Immunotherapy of Cancer. Some patients have had durable complete remission.

As Baylor College of Medicine’s Max Mamonkin, PhD, noted in a presentation, patients with conditions such as T-cell lymphoma and T-cell acute lymphoblastic leukemia (ALL) have limited treatment options and grim prognoses. “This is an area with huge unmet need,” he said. “They don’t have options that patients with B-cell malignancies have, like [CAR T-cell therapy] and bispecifics.”

One big challenge is that CAR-targeted antigens in T-cell blood cancers are shared by both normal and malignant T-cells, he said. That poses a risk during therapy that the engineered cells will target each other with “disastrous consequences.”

Research by his team and others have shown that gene editing can help the cells to stop engaging in “fratricide,” Dr. Mamonkin said.

The problem is “it’s much easier to do gene editing on the bench and much harder to translate it into the clinic,” especially in light of limitations posed by the Food and Drug administration, he said. “We started to think about alternative methods to get this approach to the clinic.”

One strategy is to use pharmacologic inhibition via the Bruton’s tyrosine kinase inhibitors ibrutinib and dasatinib to mute the tendency of CAR T toward self-destruction. When tested in mice, “the unedited cells not just persisted, they expanded with sustained anti-leukemic activity and significantly prolonged their lives even more than the knock-out [gene-edited] cells.”

The research has now moved to human subjects. In 2021, researchers at Texas Children’s Hospital and Houston Methodist Hospital launched a clinical trial to test CD7 CAR T-cell therapy with CD28 in 21 patients with CD7-positive T-cell lymphoma. The initial part of the transplant-enabling CRIMSON-NE study is expected to be completed by mid-2024, and patients will be followed for 15 years.

Early results show that CD7 CAR T-cells have persisted in the blood of patients over weeks and months, Dr. Mamonkin said. In eight patients, “we’re seeing good evidence of activity,” with two patients reaching complete remissions.

The findings suggest that CD7 can be targeted in T-cell malignancies, he said. What about CD5? A similar study known as MAGENTA is testing CD5 CAR T-cell therapy with CD28 in T-cell leukemia and lymphoma in 42 patients. The phase 1 trial began in 2017. It’s expected to be completed by 2024 and to track patients for 15 years.

Results so far have been positive with complete remission achieved in three of nine patients with T-cell lymphoma; two remained in remission for more than 4 years.

Results in T-cell ALL improved after researchers adjusted the manufacturing of the cells. As for durability in these patients, “we try to bridge them to transplantation as soon as possible.”

As for side effects overall, there wasn’t much immune effector cell-associated neurotoxicity syndrome, and the CD7 approach seems to be more inflammatory, he said.

The presentation didn’t address the potential cost of the therapies. CAR T-cell therapy can cost between $500,000 and $1 million. Medicare covers it, but Medicaid may not depending on the state, and insurers may refuse to pay for it.

Dr. Mamonkin disclosed ties with Allogene, Amgen, Fate, Galapagos, March Bio, and NKILT.