Rheumatology News

A Los Angeles County internist will pay nearly $9.5 million to resolve accusations that he submitted false claims to Medicare and California’s Medicaid program.

Part of the payment was a settlement in a civil case in which Minas Kochumian, MD, an internist who ran a solo practice in Northridge, Calif., was accused of submitting claims to Medicare and Medi-Cal for procedures, services, and tests that were never performed. The procedures he falsely billed for included injecting a medication for treating osteoarthritis and osteoporosis, draining tailbone cysts, and removal of various growths.

As part of the settlement, Dr. Kochumian admitted that he intentionally submitted false claims with the intent to deceive the United States and the State of California. The damages and penalties were possible under the federal False Claims Act and the California False Claims Act.

According to the Medical Board of California, Dr. Kochumian’s license is current and set to expire next July.

The allegations against Dr. Kochumian were first brought to the attention of authorities in a whistleblower lawsuit filed by Elize Oganesyan, Dr. Kochumian’s former medical assistant, and Damon Davies, former information technology consultant for the practice. Among her other duties, Ms. Oganesyan was responsible for verifying insurance eligibility and obtaining authorization for drugs, procedures, services, and tests.

The medical assistant first realized that something was amiss when a patient brought her a Medicare Explanation of Benefits document that included charges for an injection the practice had not administered, according to court records. Ms. Oganesyan then realized the clinic was filing claims for other services that were never provided. She stated in the original complaint that the clinic did not even have the necessary equipment for providing some of these tests — skin allergy tests, for example.  

The False Claims Act permits private parties to sue on behalf of the government for false claims for government funds and to receive a share of any recovery. Ms. Oganesyan and Davies will receive more than $1.75 million as their share of the recovery. The whistleblowers’ claims for attorneys’ fees are not resolved by this settlement, according to a statement from the U.S. Attorney’s Office, Eastern District of California.

The $9.5 million payment includes $5.4 million owed by Dr. Kochumian as criminal restitution following his guilty plea to one count of healthcare fraud in a separate criminal case filed in the Central District of California. In addition to the fine, Dr. Kochumian was sentenced to 41 months in prison, according to a statement by California Attorney General Rob Bonta.

“When doctors misuse the state’s Medi-Cal funds, they violate their Hippocratic Oath by harming a program which exists to help California’s Medi-Cal population, including the elderly, the sick, and the vulnerable,” said Mr. Bonta. “Dr. Kochumian’s alleged misconduct violated the trust of the patients in his care, and he selfishly pocketed funds that would otherwise have gone toward critical publicly funded healthcare services.”

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

A Los Angeles County internist will pay nearly $9.5 million to resolve accusations that he submitted false claims to Medicare and California’s Medicaid program.

Part of the payment was a settlement in a civil case in which Minas Kochumian, MD, an internist who ran a solo practice in Northridge, Calif., was accused of submitting claims to Medicare and Medi-Cal for procedures, services, and tests that were never performed. The procedures he falsely billed for included injecting a medication for treating osteoarthritis and osteoporosis, draining tailbone cysts, and removal of various growths.

As part of the settlement, Dr. Kochumian admitted that he intentionally submitted false claims with the intent to deceive the United States and the State of California. The damages and penalties were possible under the federal False Claims Act and the California False Claims Act.

According to the Medical Board of California, Dr. Kochumian’s license is current and set to expire next July.

The allegations against Dr. Kochumian were first brought to the attention of authorities in a whistleblower lawsuit filed by Elize Oganesyan, Dr. Kochumian’s former medical assistant, and Damon Davies, former information technology consultant for the practice. Among her other duties, Ms. Oganesyan was responsible for verifying insurance eligibility and obtaining authorization for drugs, procedures, services, and tests.

The medical assistant first realized that something was amiss when a patient brought her a Medicare Explanation of Benefits document that included charges for an injection the practice had not administered, according to court records. Ms. Oganesyan then realized the clinic was filing claims for other services that were never provided. She stated in the original complaint that the clinic did not even have the necessary equipment for providing some of these tests — skin allergy tests, for example.  

The False Claims Act permits private parties to sue on behalf of the government for false claims for government funds and to receive a share of any recovery. Ms. Oganesyan and Davies will receive more than $1.75 million as their share of the recovery. The whistleblowers’ claims for attorneys’ fees are not resolved by this settlement, according to a statement from the U.S. Attorney’s Office, Eastern District of California.

The $9.5 million payment includes $5.4 million owed by Dr. Kochumian as criminal restitution following his guilty plea to one count of healthcare fraud in a separate criminal case filed in the Central District of California. In addition to the fine, Dr. Kochumian was sentenced to 41 months in prison, according to a statement by California Attorney General Rob Bonta.

“When doctors misuse the state’s Medi-Cal funds, they violate their Hippocratic Oath by harming a program which exists to help California’s Medi-Cal population, including the elderly, the sick, and the vulnerable,” said Mr. Bonta. “Dr. Kochumian’s alleged misconduct violated the trust of the patients in his care, and he selfishly pocketed funds that would otherwise have gone toward critical publicly funded healthcare services.”

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

A Los Angeles County internist will pay nearly $9.5 million to resolve accusations that he submitted false claims to Medicare and California’s Medicaid program.

Part of the payment was a settlement in a civil case in which Minas Kochumian, MD, an internist who ran a solo practice in Northridge, Calif., was accused of submitting claims to Medicare and Medi-Cal for procedures, services, and tests that were never performed. The procedures he falsely billed for included injecting a medication for treating osteoarthritis and osteoporosis, draining tailbone cysts, and removal of various growths.

As part of the settlement, Dr. Kochumian admitted that he intentionally submitted false claims with the intent to deceive the United States and the State of California. The damages and penalties were possible under the federal False Claims Act and the California False Claims Act.

According to the Medical Board of California, Dr. Kochumian’s license is current and set to expire next July.

The allegations against Dr. Kochumian were first brought to the attention of authorities in a whistleblower lawsuit filed by Elize Oganesyan, Dr. Kochumian’s former medical assistant, and Damon Davies, former information technology consultant for the practice. Among her other duties, Ms. Oganesyan was responsible for verifying insurance eligibility and obtaining authorization for drugs, procedures, services, and tests.

The medical assistant first realized that something was amiss when a patient brought her a Medicare Explanation of Benefits document that included charges for an injection the practice had not administered, according to court records. Ms. Oganesyan then realized the clinic was filing claims for other services that were never provided. She stated in the original complaint that the clinic did not even have the necessary equipment for providing some of these tests — skin allergy tests, for example.  

The False Claims Act permits private parties to sue on behalf of the government for false claims for government funds and to receive a share of any recovery. Ms. Oganesyan and Davies will receive more than $1.75 million as their share of the recovery. The whistleblowers’ claims for attorneys’ fees are not resolved by this settlement, according to a statement from the U.S. Attorney’s Office, Eastern District of California.

The $9.5 million payment includes $5.4 million owed by Dr. Kochumian as criminal restitution following his guilty plea to one count of healthcare fraud in a separate criminal case filed in the Central District of California. In addition to the fine, Dr. Kochumian was sentenced to 41 months in prison, according to a statement by California Attorney General Rob Bonta.

“When doctors misuse the state’s Medi-Cal funds, they violate their Hippocratic Oath by harming a program which exists to help California’s Medi-Cal population, including the elderly, the sick, and the vulnerable,” said Mr. Bonta. “Dr. Kochumian’s alleged misconduct violated the trust of the patients in his care, and he selfishly pocketed funds that would otherwise have gone toward critical publicly funded healthcare services.”

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

The U.S. Food and Drug Administration approved baricitinib oral tablets on June 13 as the first systemic treatment for adult patients with severe alopecia areata.

The disorder with the hallmark signs of patchy baldness affects more than 300,000 people in the United States each year. In patients with the autoimmune disorder, the body attacks its own hair follicles and hair falls out, often in clumps. In February, the FDA granted priority review for baricitinib in adults with severe AA.

Baricitinib (Olumiant) is a Janus kinase (JAK) inhibitor, which blocks the activity of one or more enzymes, interfering with the pathway that leads to inflammation.

The FDA reports the most common side effects include upper respiratory tract infections, headache, acne, hyperlipidemia, increase of creatinine phosphokinase, urinary tract infection, elevated liver enzymes, inflammation of hair follicles, fatigue, lower respiratory tract infections, nausea, Candida infections, anemia, neutropenia, abdominal pain, herpes zoster (shingles), and weight gain. The labeling for baricitinib includes a boxed warning for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis.
 

Evidence from two trials led to announcement

The decision came after review of the results from two randomized, double-blind, placebo-controlled trials (BRAVE AA-1 and BRAVE AA-2) with patients who had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool (SALT score) for more than 6 months.

Patients in these trials got either a placebo, 2 mg of baricitinib, or 4 mg of baricitinib every day. The primary endpoint for both trials was the proportion of patients who achieved at least 80% scalp hair coverage at week 36.

In BRAVE AA-1, 22% of the 184 patients who received 2 mg of baricitinib and 35% of the 281 patients who received 4 mg of baricitinib achieved at least 80% scalp hair coverage, compared with 5% of the 189 patients in the placebo group.

In BRAVE AA-2, 17% of the 156 patients who received 2 mg of baricitinib and 32% of the 234 patients who received 4 mg achieved at least 80% scalp hair coverage, compared with 3% of the 156 patients in the placebo group.

The results were reported at the annual meeting of the American Academy of Dermatology meeting in March.

Baricitinib was originally approved in 2018 as a treatment for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF)–blockers. It is also approved for treating COVID-19 in certain hospitalized adults. 

Two other companies, Pfizer and Concert Pharmaceuticals, have JAK inhibitors in late-stage development for AA. The drugs are already on the market for treating rheumatoid arthritis and other autoimmune diseases. FDA approval is important for insurance coverage of the drugs, which have a list price of nearly $2,500 a month, according to The New York Times.

Until now, the only treatments for moderate to severe AA approved by the FDA have been intralesional steroid injections, contact sensitization, and systemic immunosuppressants, but they have demonstrated limited efficacy, are inconvenient for patients to take, and have been unsuitable for use long term.

“Today’s approval will help fulfill a significant unmet need for patients with severe alopecia areata,” Kendall Marcus, MD, director of the Division of Dermatology and Dentistry in the FDA’s Center for Drug Evaluation and Research, said in the press release.

As Medscape reported last month, The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended approval of baricitinib for adults with severe AA.

AA received widespread international attention earlier this year at the Academy Awards ceremony, when actor Will Smith walked from the audience up onto the stage and slapped comedian Chris Rock in the face after he directed a joke at Mr. Smith’s wife, Jada Pinkett Smith, about her shaved head. Mrs. Pinkett Smith has AA and has been public about her struggles with the disease.

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

The U.S. Food and Drug Administration approved baricitinib oral tablets on June 13 as the first systemic treatment for adult patients with severe alopecia areata.

The disorder with the hallmark signs of patchy baldness affects more than 300,000 people in the United States each year. In patients with the autoimmune disorder, the body attacks its own hair follicles and hair falls out, often in clumps. In February, the FDA granted priority review for baricitinib in adults with severe AA.

Baricitinib (Olumiant) is a Janus kinase (JAK) inhibitor, which blocks the activity of one or more enzymes, interfering with the pathway that leads to inflammation.

The FDA reports the most common side effects include upper respiratory tract infections, headache, acne, hyperlipidemia, increase of creatinine phosphokinase, urinary tract infection, elevated liver enzymes, inflammation of hair follicles, fatigue, lower respiratory tract infections, nausea, Candida infections, anemia, neutropenia, abdominal pain, herpes zoster (shingles), and weight gain. The labeling for baricitinib includes a boxed warning for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis.
 

Evidence from two trials led to announcement

The decision came after review of the results from two randomized, double-blind, placebo-controlled trials (BRAVE AA-1 and BRAVE AA-2) with patients who had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool (SALT score) for more than 6 months.

Patients in these trials got either a placebo, 2 mg of baricitinib, or 4 mg of baricitinib every day. The primary endpoint for both trials was the proportion of patients who achieved at least 80% scalp hair coverage at week 36.

In BRAVE AA-1, 22% of the 184 patients who received 2 mg of baricitinib and 35% of the 281 patients who received 4 mg of baricitinib achieved at least 80% scalp hair coverage, compared with 5% of the 189 patients in the placebo group.

In BRAVE AA-2, 17% of the 156 patients who received 2 mg of baricitinib and 32% of the 234 patients who received 4 mg achieved at least 80% scalp hair coverage, compared with 3% of the 156 patients in the placebo group.

The results were reported at the annual meeting of the American Academy of Dermatology meeting in March.

Baricitinib was originally approved in 2018 as a treatment for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF)–blockers. It is also approved for treating COVID-19 in certain hospitalized adults. 

Two other companies, Pfizer and Concert Pharmaceuticals, have JAK inhibitors in late-stage development for AA. The drugs are already on the market for treating rheumatoid arthritis and other autoimmune diseases. FDA approval is important for insurance coverage of the drugs, which have a list price of nearly $2,500 a month, according to The New York Times.

Until now, the only treatments for moderate to severe AA approved by the FDA have been intralesional steroid injections, contact sensitization, and systemic immunosuppressants, but they have demonstrated limited efficacy, are inconvenient for patients to take, and have been unsuitable for use long term.

“Today’s approval will help fulfill a significant unmet need for patients with severe alopecia areata,” Kendall Marcus, MD, director of the Division of Dermatology and Dentistry in the FDA’s Center for Drug Evaluation and Research, said in the press release.

As Medscape reported last month, The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended approval of baricitinib for adults with severe AA.

AA received widespread international attention earlier this year at the Academy Awards ceremony, when actor Will Smith walked from the audience up onto the stage and slapped comedian Chris Rock in the face after he directed a joke at Mr. Smith’s wife, Jada Pinkett Smith, about her shaved head. Mrs. Pinkett Smith has AA and has been public about her struggles with the disease.

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

The U.S. Food and Drug Administration approved baricitinib oral tablets on June 13 as the first systemic treatment for adult patients with severe alopecia areata.

The disorder with the hallmark signs of patchy baldness affects more than 300,000 people in the United States each year. In patients with the autoimmune disorder, the body attacks its own hair follicles and hair falls out, often in clumps. In February, the FDA granted priority review for baricitinib in adults with severe AA.

Baricitinib (Olumiant) is a Janus kinase (JAK) inhibitor, which blocks the activity of one or more enzymes, interfering with the pathway that leads to inflammation.

The FDA reports the most common side effects include upper respiratory tract infections, headache, acne, hyperlipidemia, increase of creatinine phosphokinase, urinary tract infection, elevated liver enzymes, inflammation of hair follicles, fatigue, lower respiratory tract infections, nausea, Candida infections, anemia, neutropenia, abdominal pain, herpes zoster (shingles), and weight gain. The labeling for baricitinib includes a boxed warning for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis.
 

Evidence from two trials led to announcement

The decision came after review of the results from two randomized, double-blind, placebo-controlled trials (BRAVE AA-1 and BRAVE AA-2) with patients who had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool (SALT score) for more than 6 months.

Patients in these trials got either a placebo, 2 mg of baricitinib, or 4 mg of baricitinib every day. The primary endpoint for both trials was the proportion of patients who achieved at least 80% scalp hair coverage at week 36.

In BRAVE AA-1, 22% of the 184 patients who received 2 mg of baricitinib and 35% of the 281 patients who received 4 mg of baricitinib achieved at least 80% scalp hair coverage, compared with 5% of the 189 patients in the placebo group.

In BRAVE AA-2, 17% of the 156 patients who received 2 mg of baricitinib and 32% of the 234 patients who received 4 mg achieved at least 80% scalp hair coverage, compared with 3% of the 156 patients in the placebo group.

The results were reported at the annual meeting of the American Academy of Dermatology meeting in March.

Baricitinib was originally approved in 2018 as a treatment for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF)–blockers. It is also approved for treating COVID-19 in certain hospitalized adults. 

Two other companies, Pfizer and Concert Pharmaceuticals, have JAK inhibitors in late-stage development for AA. The drugs are already on the market for treating rheumatoid arthritis and other autoimmune diseases. FDA approval is important for insurance coverage of the drugs, which have a list price of nearly $2,500 a month, according to The New York Times.

Until now, the only treatments for moderate to severe AA approved by the FDA have been intralesional steroid injections, contact sensitization, and systemic immunosuppressants, but they have demonstrated limited efficacy, are inconvenient for patients to take, and have been unsuitable for use long term.

“Today’s approval will help fulfill a significant unmet need for patients with severe alopecia areata,” Kendall Marcus, MD, director of the Division of Dermatology and Dentistry in the FDA’s Center for Drug Evaluation and Research, said in the press release.

As Medscape reported last month, The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended approval of baricitinib for adults with severe AA.

AA received widespread international attention earlier this year at the Academy Awards ceremony, when actor Will Smith walked from the audience up onto the stage and slapped comedian Chris Rock in the face after he directed a joke at Mr. Smith’s wife, Jada Pinkett Smith, about her shaved head. Mrs. Pinkett Smith has AA and has been public about her struggles with the disease.

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

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

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

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

IL-17 inhibitor times 2

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

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

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

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

All endpoints met

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

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

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

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

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

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

‘Promising results’

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

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

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

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

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

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

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

IL-17 inhibitor times 2

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

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

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

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

All endpoints met

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

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

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

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

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

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

‘Promising results’

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

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

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

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

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

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

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

IL-17 inhibitor times 2

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

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

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

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

All endpoints met

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

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

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

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

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

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

‘Promising results’

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

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

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

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

When Esther Freeman, MD, PhD, thinks back on what she learned about monkeypox during her training as a dermatologist and an infectious disease epidemiologist, it was widely considered a viral disease with rare outbreaks limited primarily to Central and Western Africa.

“Monkeypox is something we have traditionally only seen very rarely in the U.S.,” Dr. Freeman, director of Global Health Dermatology at Massachusetts General Hospital and Harvard Medical School, Boston, said in an interview. “In the past, outbreaks in the U.S. have been related to international travel or import of exotic pets, which is very different than what we’re seeing as a global community now.”

Courtesy Dr. Ester Freeman

A different clinical presentation

The clinical presentation of monkeypox cases in the current outbreak also differs from that of previous outbreaks. In the past, monkeypox rashes often morphed from a macule to a pustule and commonly affected the face, hands, feet, and trunk, with some patients harboring as many as 200 lesions at once. That pattern still occurs, but increasingly, the presentation is characterized by a more localized spread, especially in the genital region, which Dr. Freeman described as “unusual and not an area we traditionally thought of in the past as a focus for monkeypox.”

Also, affected individuals in the current outbreak may develop fewer lesions, sometimes between 1 and 5 instead of up to 200. “This doesn’t apply to everybody, but it is a bit of a different picture than what we’ve seen in case descriptions and photographs in the past from places like Central Africa,” she said. “What’s being reported out of case clusters from the United Kingdom and Spain is a mix, where some people are having more generalized involvement while others have more localized involvement.” Visual examples of the monkey pox rash can be found in photos from the United Kingdom, the country with the highest number of confirmed cases, on the CDC’s website, and in a report from Spain.

Clusters of monkeypox cases have been reported worldwide in men who have sex with men, “but this is not limited to a particular subgroup of people,” emphasizes Dr. Freeman, who is also a member of the American Academy of Dermatology’s Ad Hoc Task Force to Develop Monkeypox Content, which created an online resource for clinicians. “There are several mechanisms of spread, but direct contact with lesions or infected fluids is one,” she notes.

Moreover, “lesions associated with herpes, syphilis, and molluscum can look similar to a monkeypox lesion. If you have a patient with a new genital lesion and you’re not sure what it is, testing for monkeypox in addition to classic sexually transmitted infections like HSV or syphilis would be reasonable during the current outbreak situation.”

The 2022 monkeypox outbreak may pale in comparison to the spread of COVID-19 in terms of case numbers and societal impact, but dermatologists may be the first point of contact for a person infected with the monkeypox virus. “It’s important for dermatologists to be able to recognize monkeypox, because by recognizing cases, we can stop the outbreak,” Dr. Freeman said. “In theory, an infected person could show up in your clinic, regardless of where you practice in the U.S. But at the same time, it’s important not to panic. This is not COVID-19 all over again; this is different. Yes, it is an outbreak, but we already have a vaccine that works against monkeypox, and while one of the possible modes of transmission for monkeypox is respiratory, it’s much harder to transmit that way than SARS-CoV-2 – it requires closer and longer contact.”

Confirmation of a monkeypox virus infection is based on results of a PCR test based on swabs of a lesion. The AAD task force recommends contacting the local hospital epidemiologist, infection control personnel, and/or state health department about suspected cases, “as different locations will have different regulations on where to send the [PCR] test. If appropriate, the state health department will contact the CDC.”

According to the CDC, current recommendations for personal protective equipment for possible and confirmed monkeypox cases include gown, gloves, a National Institute for Occupational Safety and Health-approved N-95 mask, and eye protection.

 

Topical antiviral an option

If the lesions in a patient with suspected monkeypox have turned into pustules while waiting for the PCR test results, one option is to prescribe 3%-5% topical cidofovir, according to Stephen K. Tyring, MD, PhD, of the departments of dermatology, microbiology & molecular genetics, and internal medicine at the University of Texas Health Science Center, Houston. “That’s the effective antiviral that is most available,” he said. Generic cidofovir is also now available.

Dr. Tyring recommends rapid referral of immunocompromised patients with suspected monkeypox to an infectious disease expert and/or consulting with the CDC. “The pediatric population also seems to be at somewhat more risk, as has been seen in sub-Saharan Africa,” said Dr. Tyring, who is one of the editors of the textbook Tropical Dermatology. “Also, by definition, pregnant women are at more risk because their immune systems aren’t up to par. You also want to make sure that if monkeypox is on a person’s skin that they don’t get it in their eyes, because they could lose their vision.” He added that sub-Saharan Africa has a monkeypox mortality of up to 10%, “which is something we don’t see in the U.S. or Europe. Those of us who grew up in the 20th century got routine smallpox vaccines, and we therefore probably have a degree of immunity to monkeypox. But for the past 40 years or so, unless you are in the military, you are not going to get a routine vaccine to prevent smallpox.”
 

Incubation period, appearance of lesions

Monkeypox has a long incubation period. According to Dr. Freeman, from the point of exposure to the development of symptomatic lesions is typically 7-14 days but can vary from 5-21 days. “It’s important for people to be aware that their exposure may have been in the more distant past, not just a few days ago” she said. “Identifying cases as quickly as possible gives us a window where we can vaccinate close contacts.”

Dr. Freeman and Dr. Tyring reported having no relevant financial disclosures.

CDC guidance on vaccination before and after exposure to monkeypox can be found here . A general Q&A for health care professionals from the CDC can be found here.

When Esther Freeman, MD, PhD, thinks back on what she learned about monkeypox during her training as a dermatologist and an infectious disease epidemiologist, it was widely considered a viral disease with rare outbreaks limited primarily to Central and Western Africa.

“Monkeypox is something we have traditionally only seen very rarely in the U.S.,” Dr. Freeman, director of Global Health Dermatology at Massachusetts General Hospital and Harvard Medical School, Boston, said in an interview. “In the past, outbreaks in the U.S. have been related to international travel or import of exotic pets, which is very different than what we’re seeing as a global community now.”

Courtesy Dr. Ester Freeman

A different clinical presentation

The clinical presentation of monkeypox cases in the current outbreak also differs from that of previous outbreaks. In the past, monkeypox rashes often morphed from a macule to a pustule and commonly affected the face, hands, feet, and trunk, with some patients harboring as many as 200 lesions at once. That pattern still occurs, but increasingly, the presentation is characterized by a more localized spread, especially in the genital region, which Dr. Freeman described as “unusual and not an area we traditionally thought of in the past as a focus for monkeypox.”

Also, affected individuals in the current outbreak may develop fewer lesions, sometimes between 1 and 5 instead of up to 200. “This doesn’t apply to everybody, but it is a bit of a different picture than what we’ve seen in case descriptions and photographs in the past from places like Central Africa,” she said. “What’s being reported out of case clusters from the United Kingdom and Spain is a mix, where some people are having more generalized involvement while others have more localized involvement.” Visual examples of the monkey pox rash can be found in photos from the United Kingdom, the country with the highest number of confirmed cases, on the CDC’s website, and in a report from Spain.

Clusters of monkeypox cases have been reported worldwide in men who have sex with men, “but this is not limited to a particular subgroup of people,” emphasizes Dr. Freeman, who is also a member of the American Academy of Dermatology’s Ad Hoc Task Force to Develop Monkeypox Content, which created an online resource for clinicians. “There are several mechanisms of spread, but direct contact with lesions or infected fluids is one,” she notes.

Moreover, “lesions associated with herpes, syphilis, and molluscum can look similar to a monkeypox lesion. If you have a patient with a new genital lesion and you’re not sure what it is, testing for monkeypox in addition to classic sexually transmitted infections like HSV or syphilis would be reasonable during the current outbreak situation.”

The 2022 monkeypox outbreak may pale in comparison to the spread of COVID-19 in terms of case numbers and societal impact, but dermatologists may be the first point of contact for a person infected with the monkeypox virus. “It’s important for dermatologists to be able to recognize monkeypox, because by recognizing cases, we can stop the outbreak,” Dr. Freeman said. “In theory, an infected person could show up in your clinic, regardless of where you practice in the U.S. But at the same time, it’s important not to panic. This is not COVID-19 all over again; this is different. Yes, it is an outbreak, but we already have a vaccine that works against monkeypox, and while one of the possible modes of transmission for monkeypox is respiratory, it’s much harder to transmit that way than SARS-CoV-2 – it requires closer and longer contact.”

Confirmation of a monkeypox virus infection is based on results of a PCR test based on swabs of a lesion. The AAD task force recommends contacting the local hospital epidemiologist, infection control personnel, and/or state health department about suspected cases, “as different locations will have different regulations on where to send the [PCR] test. If appropriate, the state health department will contact the CDC.”

According to the CDC, current recommendations for personal protective equipment for possible and confirmed monkeypox cases include gown, gloves, a National Institute for Occupational Safety and Health-approved N-95 mask, and eye protection.

 

Topical antiviral an option

If the lesions in a patient with suspected monkeypox have turned into pustules while waiting for the PCR test results, one option is to prescribe 3%-5% topical cidofovir, according to Stephen K. Tyring, MD, PhD, of the departments of dermatology, microbiology & molecular genetics, and internal medicine at the University of Texas Health Science Center, Houston. “That’s the effective antiviral that is most available,” he said. Generic cidofovir is also now available.

Dr. Tyring recommends rapid referral of immunocompromised patients with suspected monkeypox to an infectious disease expert and/or consulting with the CDC. “The pediatric population also seems to be at somewhat more risk, as has been seen in sub-Saharan Africa,” said Dr. Tyring, who is one of the editors of the textbook Tropical Dermatology. “Also, by definition, pregnant women are at more risk because their immune systems aren’t up to par. You also want to make sure that if monkeypox is on a person’s skin that they don’t get it in their eyes, because they could lose their vision.” He added that sub-Saharan Africa has a monkeypox mortality of up to 10%, “which is something we don’t see in the U.S. or Europe. Those of us who grew up in the 20th century got routine smallpox vaccines, and we therefore probably have a degree of immunity to monkeypox. But for the past 40 years or so, unless you are in the military, you are not going to get a routine vaccine to prevent smallpox.”
 

Incubation period, appearance of lesions

Monkeypox has a long incubation period. According to Dr. Freeman, from the point of exposure to the development of symptomatic lesions is typically 7-14 days but can vary from 5-21 days. “It’s important for people to be aware that their exposure may have been in the more distant past, not just a few days ago” she said. “Identifying cases as quickly as possible gives us a window where we can vaccinate close contacts.”

Dr. Freeman and Dr. Tyring reported having no relevant financial disclosures.

CDC guidance on vaccination before and after exposure to monkeypox can be found here . A general Q&A for health care professionals from the CDC can be found here.

When Esther Freeman, MD, PhD, thinks back on what she learned about monkeypox during her training as a dermatologist and an infectious disease epidemiologist, it was widely considered a viral disease with rare outbreaks limited primarily to Central and Western Africa.

“Monkeypox is something we have traditionally only seen very rarely in the U.S.,” Dr. Freeman, director of Global Health Dermatology at Massachusetts General Hospital and Harvard Medical School, Boston, said in an interview. “In the past, outbreaks in the U.S. have been related to international travel or import of exotic pets, which is very different than what we’re seeing as a global community now.”

Courtesy Dr. Ester Freeman

A different clinical presentation

The clinical presentation of monkeypox cases in the current outbreak also differs from that of previous outbreaks. In the past, monkeypox rashes often morphed from a macule to a pustule and commonly affected the face, hands, feet, and trunk, with some patients harboring as many as 200 lesions at once. That pattern still occurs, but increasingly, the presentation is characterized by a more localized spread, especially in the genital region, which Dr. Freeman described as “unusual and not an area we traditionally thought of in the past as a focus for monkeypox.”

Also, affected individuals in the current outbreak may develop fewer lesions, sometimes between 1 and 5 instead of up to 200. “This doesn’t apply to everybody, but it is a bit of a different picture than what we’ve seen in case descriptions and photographs in the past from places like Central Africa,” she said. “What’s being reported out of case clusters from the United Kingdom and Spain is a mix, where some people are having more generalized involvement while others have more localized involvement.” Visual examples of the monkey pox rash can be found in photos from the United Kingdom, the country with the highest number of confirmed cases, on the CDC’s website, and in a report from Spain.

Clusters of monkeypox cases have been reported worldwide in men who have sex with men, “but this is not limited to a particular subgroup of people,” emphasizes Dr. Freeman, who is also a member of the American Academy of Dermatology’s Ad Hoc Task Force to Develop Monkeypox Content, which created an online resource for clinicians. “There are several mechanisms of spread, but direct contact with lesions or infected fluids is one,” she notes.

Moreover, “lesions associated with herpes, syphilis, and molluscum can look similar to a monkeypox lesion. If you have a patient with a new genital lesion and you’re not sure what it is, testing for monkeypox in addition to classic sexually transmitted infections like HSV or syphilis would be reasonable during the current outbreak situation.”

The 2022 monkeypox outbreak may pale in comparison to the spread of COVID-19 in terms of case numbers and societal impact, but dermatologists may be the first point of contact for a person infected with the monkeypox virus. “It’s important for dermatologists to be able to recognize monkeypox, because by recognizing cases, we can stop the outbreak,” Dr. Freeman said. “In theory, an infected person could show up in your clinic, regardless of where you practice in the U.S. But at the same time, it’s important not to panic. This is not COVID-19 all over again; this is different. Yes, it is an outbreak, but we already have a vaccine that works against monkeypox, and while one of the possible modes of transmission for monkeypox is respiratory, it’s much harder to transmit that way than SARS-CoV-2 – it requires closer and longer contact.”

Confirmation of a monkeypox virus infection is based on results of a PCR test based on swabs of a lesion. The AAD task force recommends contacting the local hospital epidemiologist, infection control personnel, and/or state health department about suspected cases, “as different locations will have different regulations on where to send the [PCR] test. If appropriate, the state health department will contact the CDC.”

According to the CDC, current recommendations for personal protective equipment for possible and confirmed monkeypox cases include gown, gloves, a National Institute for Occupational Safety and Health-approved N-95 mask, and eye protection.

 

Topical antiviral an option

If the lesions in a patient with suspected monkeypox have turned into pustules while waiting for the PCR test results, one option is to prescribe 3%-5% topical cidofovir, according to Stephen K. Tyring, MD, PhD, of the departments of dermatology, microbiology & molecular genetics, and internal medicine at the University of Texas Health Science Center, Houston. “That’s the effective antiviral that is most available,” he said. Generic cidofovir is also now available.

Dr. Tyring recommends rapid referral of immunocompromised patients with suspected monkeypox to an infectious disease expert and/or consulting with the CDC. “The pediatric population also seems to be at somewhat more risk, as has been seen in sub-Saharan Africa,” said Dr. Tyring, who is one of the editors of the textbook Tropical Dermatology. “Also, by definition, pregnant women are at more risk because their immune systems aren’t up to par. You also want to make sure that if monkeypox is on a person’s skin that they don’t get it in their eyes, because they could lose their vision.” He added that sub-Saharan Africa has a monkeypox mortality of up to 10%, “which is something we don’t see in the U.S. or Europe. Those of us who grew up in the 20th century got routine smallpox vaccines, and we therefore probably have a degree of immunity to monkeypox. But for the past 40 years or so, unless you are in the military, you are not going to get a routine vaccine to prevent smallpox.”
 

Incubation period, appearance of lesions

Monkeypox has a long incubation period. According to Dr. Freeman, from the point of exposure to the development of symptomatic lesions is typically 7-14 days but can vary from 5-21 days. “It’s important for people to be aware that their exposure may have been in the more distant past, not just a few days ago” she said. “Identifying cases as quickly as possible gives us a window where we can vaccinate close contacts.”

Dr. Freeman and Dr. Tyring reported having no relevant financial disclosures.

CDC guidance on vaccination before and after exposure to monkeypox can be found here . A general Q&A for health care professionals from the CDC can be found here.

Angela Intili, MD, an ob.gyn., was used to seeing her medical malpractice insurance premium rise slightly every couple of years. But she was shocked by the drastic rise she recently experienced.

In the last 2 years, Dr. Intili’s premiums shot from $60,000 to $130,000, she said.

“After 30 years of practice, this is the first time I’ve asked myself if I can even afford to continue practicing obstetrics and gynecology,” said Dr. Intili, 62, of Joliet, Ill. “It’s gotten very difficult to make ends meet as far as overhead because of the liability costs. I still love what I’m doing but I don’t know if I can afford to do it anymore.”

Even more frustrating for Dr. Intili was learning that claims in Illinois have sharply declined. From 2016 to 2020, tort filings in Illinois decreased by 43%, according to a state report.

“If claims are going down, I don’t understand why premium payments are going up,” she said.

Physicians across the country are experiencing a similar paradox. Claims are down, yet premiums are rising.

Medscape’s Malpractice Report 2021 found that 42% of primary care physicians were sued in 2020 through mid-2021, down from 52% in 2019. Fifty-six percent of specialists were sued in 2020 through mid-2021 compared with 62% in 2019, the report found. The pandemic was undoubtedly behind the decrease in suits, according to legal experts.

Yet, physicians paid higher premiums in 2021 and are on track for increases again in 2022, according to data and analysts.

According to Conning, direct premiums written for physicians increased 7.0% in 2021 (from $5.01 billion to $5.36 billion). Conning, an investment management firm that serves the insurance industry, analyzes annual financial reports filed by insurers to state insurance departments. The Medical Liability Monitor’s 2021 report found that premiums for internists, surgeons, and ob.gyns. in states without Patient Compensation Funds rose by an average of 2% in 2021.

The disparities raise questions about why physicians are paying higher premiums when having fewer claims is likely saving insurers’ money. Shouldn’t physicians’ rates reflect the reduction in claims?
 

Cases plummet during pandemic

During the pandemic, the volume of new medical malpractice claims dwindled to nearly nothing, said Michael Matray, editor of the Medical Liability Monitor, a national publication that analyzes medical liability insurance premiums.

“The court system closed for a while,” he said. “No elective procedures were being done in 2020 and the early parts of 2021. If you have no treatment, you have no malpractice, so of course, claims frequency tumbled down to a trickle.”

The number of large awards also decreased during the pandemic, noted Bill Burns, a director of insurance research at Conning.

“For claims that were already in the system, many of them could not be resolved because of the court closures, inability to take statements and depositions, etc.,” he said. “This resulted in a drop in verdicts.”

In 2021, there were 16 medical malpractice verdicts of $10 million or more in the United States, according to TransRe, an international reinsurance company that tracks large verdicts. In 2020, there were six verdicts of $10 million or more, TransRe research found. This is down from 52 verdicts of $10 million or more in 2019 and 46 verdicts of $10 million or more in 2018.

But although the pandemic lowered claims and decreased the number of payouts, one important aspect was untouched by the COVID era, said Richard E. Anderson, MD, chairman and CEO for The Doctors Company, a national medical liability insurer, and TDC Group.

“It’s a fair question: If claims are down, why are premiums continuing to go up?” Dr. Anderson said. “The answer is severity.”
 

High-dollar verdicts pave expensive path

The upward trend in severity has continued for about 6 years and has not slowed, Dr. Anderson said. Severity refers to high-dollar verdicts and settlements.

“We’re seeing record-high verdicts all over the country,” he said. “We used to have maps that showed the top 10 medical malpractice verdicts or awards, and they would be clustered where you’d expect them to be, New York, Florida, Illinois, and so forth. Now, if you look at those top 10 verdicts, they could be anywhere in the country.”

In Minnesota for instance, a jury awarded a record $111 million in damages to a college student in May after finding a hospital and an orthopedic surgeon negligent in treating his broken leg. In April, a Kansas City jury awarded a family $25 million after finding that an ob.gyn. and hospital failed to properly treat a mother in labor, causing brain damage to her infant.  

Such record payouts factor into premium costs, said Ned Rand Jr., CEO for ProAssurance, a national medical liability insurer. Though only a minority of claims reach that level, when a high award occurs, it puts pressure on the ultimate cost to resolve claims, he said. The frequency of claims filed is also expected to soon rebound, he noted.

“As we price the product sitting here today, we have to factor both of those in,” Mr. Rand said. “That’s why we, as an industry, continue to see, by and large, rates going up. And we fell behind. Some of this severity, in particular, as an industry, we weren’t pricing fully for, so we’ve been playing catch-up.”

High-dollar awards – also called nuclear verdicts – set the arena for future settlements in similar cases, Dr. Anderson added.

“If it was an orthopedic case for instance, and there was a similar injury in another case, that’s the trial lawyers’ starting point for the award,” he said. “Now, they’re not going to get it, but it distorts the negotiations. As we have more and more nuclear verdicts, it becomes harder to settle claims for reasonable amounts.”
 

What does 2022 have in store?

Analysts say the backlog of malpractice claims in the court system could prove calamitous for premiums and the liability landscape.

Courts are slogging through the pileup caused by the pandemic, but it’s estimated that there is still about a one-third larger case backlog than normal, according to Mr. Matray.

Such delayed claims may end up costing more because of social inflation, said Mr. Burns.

“People look at the world differently than they did 2 years ago,” he said. “A jury may have awarded $5 million for a claim a few years ago. But then the pandemic hits, and we have the George Floyd incident, and we have people out of work and a shortage in baby formula. Yet, companies are still making a lot of money and many insurance companies are turning record profits. Today, that jury may look at a sympathetic malpractice victim and award $10 million for the same claim.”

Concerns also exist about a potential surge of new malpractice claims. Mr. Rand compares the possible wave to a large bubble.

“I liken it to a cartoon, when one character grabs the hose and a big bubble forms as the water builds up,” he said. “Then the character releases, and water comes flooding out. As an industry, we wait, wondering: Is there going to be this flood of claims as the court systems reopen and the statute of limitations approach around some of these claims? That’s an ongoing concern.”

As for impending premiums, physicians can expect rises in 2022 and again in 2023, according to Chris Wojciechowski, a partner at TigerRisk Partners, a reinsurance broker.

“In general, there is a lot of uncertainty around the state of the economy, the tort environment, litigation post COVID, and overall volatility across the capital markets,” he said. “Furthermore, thanks to social and financial inflation, the potential for very severe verdicts has increased dramatically, and as courthouses reopen, the trends are not looking favorable. While many of the physician carriers have strong balance sheets, they can’t lose money on an underwriting basis forever.”

For Dr. Intili, the Illinois ob.gyn., news of another impending increase in 2022 is distressing. She expects another 10%-20% rise in 2022, she said. If she were younger and earlier in her career, she might’ve considered moving, she said, but her family lives in Illinois and she cares for her older parents.

“I’m not ready to retire,” Dr. Intili said. “I’m looking into options, possibly becoming a hospitalist or doing locum tenens work. I’ve been a solo practitioner for 27 years and I love the autonomy. But these high premiums are making it almost impossible to continue.”

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

Angela Intili, MD, an ob.gyn., was used to seeing her medical malpractice insurance premium rise slightly every couple of years. But she was shocked by the drastic rise she recently experienced.

In the last 2 years, Dr. Intili’s premiums shot from $60,000 to $130,000, she said.

“After 30 years of practice, this is the first time I’ve asked myself if I can even afford to continue practicing obstetrics and gynecology,” said Dr. Intili, 62, of Joliet, Ill. “It’s gotten very difficult to make ends meet as far as overhead because of the liability costs. I still love what I’m doing but I don’t know if I can afford to do it anymore.”

Even more frustrating for Dr. Intili was learning that claims in Illinois have sharply declined. From 2016 to 2020, tort filings in Illinois decreased by 43%, according to a state report.

“If claims are going down, I don’t understand why premium payments are going up,” she said.

Physicians across the country are experiencing a similar paradox. Claims are down, yet premiums are rising.

Medscape’s Malpractice Report 2021 found that 42% of primary care physicians were sued in 2020 through mid-2021, down from 52% in 2019. Fifty-six percent of specialists were sued in 2020 through mid-2021 compared with 62% in 2019, the report found. The pandemic was undoubtedly behind the decrease in suits, according to legal experts.

Yet, physicians paid higher premiums in 2021 and are on track for increases again in 2022, according to data and analysts.

According to Conning, direct premiums written for physicians increased 7.0% in 2021 (from $5.01 billion to $5.36 billion). Conning, an investment management firm that serves the insurance industry, analyzes annual financial reports filed by insurers to state insurance departments. The Medical Liability Monitor’s 2021 report found that premiums for internists, surgeons, and ob.gyns. in states without Patient Compensation Funds rose by an average of 2% in 2021.

The disparities raise questions about why physicians are paying higher premiums when having fewer claims is likely saving insurers’ money. Shouldn’t physicians’ rates reflect the reduction in claims?
 

Cases plummet during pandemic

During the pandemic, the volume of new medical malpractice claims dwindled to nearly nothing, said Michael Matray, editor of the Medical Liability Monitor, a national publication that analyzes medical liability insurance premiums.

“The court system closed for a while,” he said. “No elective procedures were being done in 2020 and the early parts of 2021. If you have no treatment, you have no malpractice, so of course, claims frequency tumbled down to a trickle.”

The number of large awards also decreased during the pandemic, noted Bill Burns, a director of insurance research at Conning.

“For claims that were already in the system, many of them could not be resolved because of the court closures, inability to take statements and depositions, etc.,” he said. “This resulted in a drop in verdicts.”

In 2021, there were 16 medical malpractice verdicts of $10 million or more in the United States, according to TransRe, an international reinsurance company that tracks large verdicts. In 2020, there were six verdicts of $10 million or more, TransRe research found. This is down from 52 verdicts of $10 million or more in 2019 and 46 verdicts of $10 million or more in 2018.

But although the pandemic lowered claims and decreased the number of payouts, one important aspect was untouched by the COVID era, said Richard E. Anderson, MD, chairman and CEO for The Doctors Company, a national medical liability insurer, and TDC Group.

“It’s a fair question: If claims are down, why are premiums continuing to go up?” Dr. Anderson said. “The answer is severity.”
 

High-dollar verdicts pave expensive path

The upward trend in severity has continued for about 6 years and has not slowed, Dr. Anderson said. Severity refers to high-dollar verdicts and settlements.

“We’re seeing record-high verdicts all over the country,” he said. “We used to have maps that showed the top 10 medical malpractice verdicts or awards, and they would be clustered where you’d expect them to be, New York, Florida, Illinois, and so forth. Now, if you look at those top 10 verdicts, they could be anywhere in the country.”

In Minnesota for instance, a jury awarded a record $111 million in damages to a college student in May after finding a hospital and an orthopedic surgeon negligent in treating his broken leg. In April, a Kansas City jury awarded a family $25 million after finding that an ob.gyn. and hospital failed to properly treat a mother in labor, causing brain damage to her infant.  

Such record payouts factor into premium costs, said Ned Rand Jr., CEO for ProAssurance, a national medical liability insurer. Though only a minority of claims reach that level, when a high award occurs, it puts pressure on the ultimate cost to resolve claims, he said. The frequency of claims filed is also expected to soon rebound, he noted.

“As we price the product sitting here today, we have to factor both of those in,” Mr. Rand said. “That’s why we, as an industry, continue to see, by and large, rates going up. And we fell behind. Some of this severity, in particular, as an industry, we weren’t pricing fully for, so we’ve been playing catch-up.”

High-dollar awards – also called nuclear verdicts – set the arena for future settlements in similar cases, Dr. Anderson added.

“If it was an orthopedic case for instance, and there was a similar injury in another case, that’s the trial lawyers’ starting point for the award,” he said. “Now, they’re not going to get it, but it distorts the negotiations. As we have more and more nuclear verdicts, it becomes harder to settle claims for reasonable amounts.”
 

What does 2022 have in store?

Analysts say the backlog of malpractice claims in the court system could prove calamitous for premiums and the liability landscape.

Courts are slogging through the pileup caused by the pandemic, but it’s estimated that there is still about a one-third larger case backlog than normal, according to Mr. Matray.

Such delayed claims may end up costing more because of social inflation, said Mr. Burns.

“People look at the world differently than they did 2 years ago,” he said. “A jury may have awarded $5 million for a claim a few years ago. But then the pandemic hits, and we have the George Floyd incident, and we have people out of work and a shortage in baby formula. Yet, companies are still making a lot of money and many insurance companies are turning record profits. Today, that jury may look at a sympathetic malpractice victim and award $10 million for the same claim.”

Concerns also exist about a potential surge of new malpractice claims. Mr. Rand compares the possible wave to a large bubble.

“I liken it to a cartoon, when one character grabs the hose and a big bubble forms as the water builds up,” he said. “Then the character releases, and water comes flooding out. As an industry, we wait, wondering: Is there going to be this flood of claims as the court systems reopen and the statute of limitations approach around some of these claims? That’s an ongoing concern.”

As for impending premiums, physicians can expect rises in 2022 and again in 2023, according to Chris Wojciechowski, a partner at TigerRisk Partners, a reinsurance broker.

“In general, there is a lot of uncertainty around the state of the economy, the tort environment, litigation post COVID, and overall volatility across the capital markets,” he said. “Furthermore, thanks to social and financial inflation, the potential for very severe verdicts has increased dramatically, and as courthouses reopen, the trends are not looking favorable. While many of the physician carriers have strong balance sheets, they can’t lose money on an underwriting basis forever.”

For Dr. Intili, the Illinois ob.gyn., news of another impending increase in 2022 is distressing. She expects another 10%-20% rise in 2022, she said. If she were younger and earlier in her career, she might’ve considered moving, she said, but her family lives in Illinois and she cares for her older parents.

“I’m not ready to retire,” Dr. Intili said. “I’m looking into options, possibly becoming a hospitalist or doing locum tenens work. I’ve been a solo practitioner for 27 years and I love the autonomy. But these high premiums are making it almost impossible to continue.”

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

Angela Intili, MD, an ob.gyn., was used to seeing her medical malpractice insurance premium rise slightly every couple of years. But she was shocked by the drastic rise she recently experienced.

In the last 2 years, Dr. Intili’s premiums shot from $60,000 to $130,000, she said.

“After 30 years of practice, this is the first time I’ve asked myself if I can even afford to continue practicing obstetrics and gynecology,” said Dr. Intili, 62, of Joliet, Ill. “It’s gotten very difficult to make ends meet as far as overhead because of the liability costs. I still love what I’m doing but I don’t know if I can afford to do it anymore.”

Even more frustrating for Dr. Intili was learning that claims in Illinois have sharply declined. From 2016 to 2020, tort filings in Illinois decreased by 43%, according to a state report.

“If claims are going down, I don’t understand why premium payments are going up,” she said.

Physicians across the country are experiencing a similar paradox. Claims are down, yet premiums are rising.

Medscape’s Malpractice Report 2021 found that 42% of primary care physicians were sued in 2020 through mid-2021, down from 52% in 2019. Fifty-six percent of specialists were sued in 2020 through mid-2021 compared with 62% in 2019, the report found. The pandemic was undoubtedly behind the decrease in suits, according to legal experts.

Yet, physicians paid higher premiums in 2021 and are on track for increases again in 2022, according to data and analysts.

According to Conning, direct premiums written for physicians increased 7.0% in 2021 (from $5.01 billion to $5.36 billion). Conning, an investment management firm that serves the insurance industry, analyzes annual financial reports filed by insurers to state insurance departments. The Medical Liability Monitor’s 2021 report found that premiums for internists, surgeons, and ob.gyns. in states without Patient Compensation Funds rose by an average of 2% in 2021.

The disparities raise questions about why physicians are paying higher premiums when having fewer claims is likely saving insurers’ money. Shouldn’t physicians’ rates reflect the reduction in claims?
 

Cases plummet during pandemic

During the pandemic, the volume of new medical malpractice claims dwindled to nearly nothing, said Michael Matray, editor of the Medical Liability Monitor, a national publication that analyzes medical liability insurance premiums.

“The court system closed for a while,” he said. “No elective procedures were being done in 2020 and the early parts of 2021. If you have no treatment, you have no malpractice, so of course, claims frequency tumbled down to a trickle.”

The number of large awards also decreased during the pandemic, noted Bill Burns, a director of insurance research at Conning.

“For claims that were already in the system, many of them could not be resolved because of the court closures, inability to take statements and depositions, etc.,” he said. “This resulted in a drop in verdicts.”

In 2021, there were 16 medical malpractice verdicts of $10 million or more in the United States, according to TransRe, an international reinsurance company that tracks large verdicts. In 2020, there were six verdicts of $10 million or more, TransRe research found. This is down from 52 verdicts of $10 million or more in 2019 and 46 verdicts of $10 million or more in 2018.

But although the pandemic lowered claims and decreased the number of payouts, one important aspect was untouched by the COVID era, said Richard E. Anderson, MD, chairman and CEO for The Doctors Company, a national medical liability insurer, and TDC Group.

“It’s a fair question: If claims are down, why are premiums continuing to go up?” Dr. Anderson said. “The answer is severity.”
 

High-dollar verdicts pave expensive path

The upward trend in severity has continued for about 6 years and has not slowed, Dr. Anderson said. Severity refers to high-dollar verdicts and settlements.

“We’re seeing record-high verdicts all over the country,” he said. “We used to have maps that showed the top 10 medical malpractice verdicts or awards, and they would be clustered where you’d expect them to be, New York, Florida, Illinois, and so forth. Now, if you look at those top 10 verdicts, they could be anywhere in the country.”

In Minnesota for instance, a jury awarded a record $111 million in damages to a college student in May after finding a hospital and an orthopedic surgeon negligent in treating his broken leg. In April, a Kansas City jury awarded a family $25 million after finding that an ob.gyn. and hospital failed to properly treat a mother in labor, causing brain damage to her infant.  

Such record payouts factor into premium costs, said Ned Rand Jr., CEO for ProAssurance, a national medical liability insurer. Though only a minority of claims reach that level, when a high award occurs, it puts pressure on the ultimate cost to resolve claims, he said. The frequency of claims filed is also expected to soon rebound, he noted.

“As we price the product sitting here today, we have to factor both of those in,” Mr. Rand said. “That’s why we, as an industry, continue to see, by and large, rates going up. And we fell behind. Some of this severity, in particular, as an industry, we weren’t pricing fully for, so we’ve been playing catch-up.”

High-dollar awards – also called nuclear verdicts – set the arena for future settlements in similar cases, Dr. Anderson added.

“If it was an orthopedic case for instance, and there was a similar injury in another case, that’s the trial lawyers’ starting point for the award,” he said. “Now, they’re not going to get it, but it distorts the negotiations. As we have more and more nuclear verdicts, it becomes harder to settle claims for reasonable amounts.”
 

What does 2022 have in store?

Analysts say the backlog of malpractice claims in the court system could prove calamitous for premiums and the liability landscape.

Courts are slogging through the pileup caused by the pandemic, but it’s estimated that there is still about a one-third larger case backlog than normal, according to Mr. Matray.

Such delayed claims may end up costing more because of social inflation, said Mr. Burns.

“People look at the world differently than they did 2 years ago,” he said. “A jury may have awarded $5 million for a claim a few years ago. But then the pandemic hits, and we have the George Floyd incident, and we have people out of work and a shortage in baby formula. Yet, companies are still making a lot of money and many insurance companies are turning record profits. Today, that jury may look at a sympathetic malpractice victim and award $10 million for the same claim.”

Concerns also exist about a potential surge of new malpractice claims. Mr. Rand compares the possible wave to a large bubble.

“I liken it to a cartoon, when one character grabs the hose and a big bubble forms as the water builds up,” he said. “Then the character releases, and water comes flooding out. As an industry, we wait, wondering: Is there going to be this flood of claims as the court systems reopen and the statute of limitations approach around some of these claims? That’s an ongoing concern.”

As for impending premiums, physicians can expect rises in 2022 and again in 2023, according to Chris Wojciechowski, a partner at TigerRisk Partners, a reinsurance broker.

“In general, there is a lot of uncertainty around the state of the economy, the tort environment, litigation post COVID, and overall volatility across the capital markets,” he said. “Furthermore, thanks to social and financial inflation, the potential for very severe verdicts has increased dramatically, and as courthouses reopen, the trends are not looking favorable. While many of the physician carriers have strong balance sheets, they can’t lose money on an underwriting basis forever.”

For Dr. Intili, the Illinois ob.gyn., news of another impending increase in 2022 is distressing. She expects another 10%-20% rise in 2022, she said. If she were younger and earlier in her career, she might’ve considered moving, she said, but her family lives in Illinois and she cares for her older parents.

“I’m not ready to retire,” Dr. Intili said. “I’m looking into options, possibly becoming a hospitalist or doing locum tenens work. I’ve been a solo practitioner for 27 years and I love the autonomy. But these high premiums are making it almost impossible to continue.”

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

Deucravacitinib and orelabrutinib – two novel oral drugs under investigation for the treatment of systemic lupus erythematosus (SLE) – have performed well in early clinical trials reported as late-breaking abstracts at the annual European Congress of Rheumatology.

In the phase 2 PAISLEY study, up to 58% of patients treated with deucravacitinib versus 34% of placebo-treated patients met the primary study endpoint of an SLE Responder Index-4 (SRI-4) after 38 weeks of treatment. Deucravacitinib also “achieved or meaningfully improved” all of the secondary endpoints set out in the 363-patient trial and was reported to have a safety and tolerability profile that was generally similar to placebo.

“Deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials,” said Eric F. Morand, MD, PhD, a clinical rheumatologist and head of the School of Clinical Sciences at Monash University in Melbourne.

In a separate, ongoing phase 1b/2a study designed to evaluate orelabrutinib as a potential treatment for SLE, no safety concerns were seen with the investigational drug, along with “trending efficacy,” that supports “further studies in larger and longer-term trials,” according to the study’s investigators.

“What sets these two new drugs apart from currently available targeted therapies are their mode of action,” said Md Yuzaiful Md Yusof, MBChB, PhD, who was not involved in either study.

“The results from the PAISLEY study are promising, and it’s good to see the patients recruited were of diverse ethnicity [50%–60% were White],” added Dr. Md Yusof, a senior research fellow within the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine and a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust.

He noted that the placebo rate was also low: “This could be contributed to by keeping the background prednisolone dose low, which is often a challenge in designing SLE trials.”
 

Deucravacitinib – the distant cousin of the JAK family?

“Deucravacitinib is a compound you might not have heard of before,” Dr. Morand said.

“It’s an inhibitor of a kinase called TYK2, which, broadly speaking, is a member of JAK [Janus kinase] family,” he explained in an interview. TYK2 regulates signal transduction downstream of receptors for interleukin (IL)-23 and IL-12 pathways and the type I interferon family.

“It’s a very finite set of cytokine signals” that are being blocked with deucravacitinib, he said, adding that this means it’s more directly targeting SLE pathogenic mechanisms than perhaps other JAK inhibitor compounds.

“It also means that it shouldn’t have some of the downsides of the other JAK inhibitors,” Dr. Morand said, “such as hematopoietic side effects, including cytopenias.”
 

The phase 2 PAISLEY study

This study involved 363 patients with moderate to severe, active SLE were recruited and randomized to receive placebo (n = 90) or one of three doses of deucravacitinib: 3 mg twice daily (n = 91), 6 mg twice daily (n = 93), or 12 mg once daily (n = 89). Most patients were also taking multiple background therapies, but this was similar across the four treatment arms.

The SRI-4 primary endpoint after 38 weeks of treatment was met by 34.4% of patients who received placebo, but 58.2% of those treated with deucravacitinib 3 mg twice daily (P = .0006 versus placebo), 49.5% (P = .021) of those treated with 6 mg twice daily, and 44.9% (P = .078) treated with 12 mg once daily.

“All secondary outcome measures were achieved or meaningfully improved at week 48, including SRI-4, BICLA [British Isles Lupus Assessment Group-based Composite Lupus Assessment], low-level disease activity state [LLDAS], reduction in skin disease and reduction in arthritis,” Dr. Morand said.

In addition, early biomarker results showed reductions in double-stranded DNA titers and increases in serum C4 complement with deucravacitinib across the duration of the study.

In discussion, Dr. Morand was asked about the seemingly negative or inverse dose response seen in the trial, with the best results seen with the 3-mg twice daily dose, then lower effects seen with two higher doses.

“Our analysis is that it’s not an inverse dose response, but rather a flat dose response above the 3-mg [twice daily] dose,” he said, noting that there was a higher dropout rate because of adverse effects in the 12-mg once daily group and those participants were recorded as nonresponders.

“We think what we’ve seen here is that 3 mg twice daily is a sufficient dose and there was no additional therapeutic gain above that.”

Rates of adverse events (AEs), serious AEs, and AEs of interest were overall fairly similar between deucravacitinib and placebo groups. The most common side effects seen with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. Skin reactions, such as acne, rash, and pruritis, among others, were more common in deucravacitinib- than in placebo-treated patients.

Importantly, Dr. Morand noted that there were no major cardiac events or thrombotic events and no deaths seen in the study. There was no signal for an increase in serious or opportunistic infections, including herpes zoster. There was no effect on common laboratory parameters.

“These are very encouraging results for patients with SLE,” Albert Roy, executive director of Lupus Therapeutics, said in a press release issued by the Lupus Research Alliance.

“We are honored to have played a role in this exciting work by helping to conduct this clinical trial through our Lupus Clinical Investigators Network of renowned North American academic centers.”

In an interview, he added: “We’re cautiously optimistic. Hopefully, if it continues to progress through phase 3, it’ll be the first oral agent that would be approved for lupus, notwithstanding prednisone and Plaquenil [hydroxychloroquine], back in the 50s.”

Orelabrutinib phase 2 study in SLE

Another approach to oral route of administration under investigation in SLE is the use of orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) that was approved in China in December 2020 for the treatment of certain lymphomas and leukemias.

The rationale for testing it in SLE comes from two preclinical studies that had suggested a possible benefit in reducing disease activity, explained Zhanguo Li, MD, PhD, professor at Peking University People’s Hospital in Beijing. He presented the results of an ongoing randomized, double-blind, placebo-controlled, phase Ib/IIa dose-finding study comparing three different doses of orelabrutinib (50, 80, and 100 mg, once daily) to placebo.

As in the deucravacitinib trial, the SRI-4 was used to assess the potential efficacy of orelabrutinib, although in a much smaller patient population (n = 92) and at a shorter time point (12 weeks). Results showed an 11%-20% difference between the percentage of patients who met SRI-4 response criteria with orelabrutinib and those on placebo, at a respective 46.5%, 53.3%, 56.3% and 35.7%.

SLE Disease Activity Index (SLEDAI) scores showed a similar benefit of orelabrutinib over placebo, with 54%-63% and 30% of patients, respectively, achieving a score of 8 or more.

Adverse event rates were similar to those of placebo with most events being of mild or moderate nature. Three patients treated with orelabrutinib experienced serious adverse events, of which one was grade 3, but there were no reported deaths.

Pharmacokinetic and pharmacodynamic data showed a dose effect, and nearly complete occupancy of BTK was achieved at all dose levels for 24 hours, consistent with once-daily dosing.

“BTK plays an important role in B-cell regulation, thus B-cell and myeloid-cell blockade through BTK inhibition is an interesting potential new target for SLE,” Dr. Md Yusof said.

“Data from this early dose-ranging trial is encouraging. No major safety signal apart from mild reduction in lymphocyte and white cell counts,” he added.

“There are still plenty of challenges ahead for this drug’s development, particularly as none of the BTK inhibitors have yet to succeed in phase 3 trials in rheumatic and musculoskeletal diseases,” Dr. Md Yusof said.

Early days for both agents

While both seem currently promising, it’s very early days for deucravacitinib and orelabrutinib as possible new agents for SLE.

Aside from SLE, deucravacitinib is being tested across multiple immune-mediated diseases. This includes psoriasis, where two phase 3 trials – POETYK PSO-1 and POETYK PSO-2 – have already been completed, and psoriatic arthritis, where a phase 2 trial has been reported; all with positive results.

Phase 3 testing of deucravacitinib will go ahead and recruitment may start toward the end of this year, but it’ll take years to complete the studies, Dr. Morand said. Even if the trials prove positive, neither agent is going to be available for clinical use for several years.

A case in point is anifrolumab (Saphnelo), which Dr. Morand was involved in assessing. Despite gaining approval in the United States and across much of the world, the drug still going through reimbursement processes.

“The trial data, and lots of post hoc analysis, show clearly that it’s a major step forward in treating lupus,” he said in an interview, but “access is limited in most places, so hands-on experience with that new treatment is still limited for most clinicians.”

As for all the other new targeted approaches under investigation, “although there’s a lot of trial activity, there’s still a couple of years away before any of the current trials deliver new treatment. That’s if they provide positive findings. Indeed, there have been numerous agents that have shown promise at phase 2 but then fall at the final phase 3 hurdle, including baricitinib, which Dr. Morand reported on in a separate poster presentation.

Phase 3 data proved disappointing: “Results are not sufficiently positive for that to go forward,” he said, adding that “transitioning from a successful phase 2 to a successful phase 3 is challenging, and many products have failed.”

Dr. Morand added: “It’s a very exciting time to be in lupus research, and there’s a lot of optimism about the future. But when I go back to my clinic tomorrow, I treat my patients exactly the same as I did last week and last year.”

It’s yet to be seen if deucravacitinib will fulfill its early promise, but it’s off to an impressive start. A positive for patients is that it’s an oral drug, with the potential to improve access to treatment across the world where getting infusions may be an issue.

“These are some of the most exciting data that I’ve seen at the phase 2 level in terms of effect size across all the readouts that are used,” Dr. Morand said. “There’s no guesswork here; it worked across all the measures. That’s very reassuring.”

The PAISLEY study was sponsored by Bristol-Myers Squibb. Dr. Morand has acted as a consultant to the company and received research support for the conduct of the trial. He disclosed acting as a consultant or receiving research funding from AbbVie, Amgen, AstraZeneca, Biogen, Eli Lilly, EMD Serono, Janssen, Genentech, Servier, Novartis, and UCB. Mr. Roy is the executive director of Lupus Therapeutics, which manages the Lupus Clinical Investigators Network based in North America. Lupus Therapeutics is the clinical trials arm of the Lupus Research Alliance, a nongovernmental, nonprofit funder of lupus research worldwide. The orelabrutinib study was sponsored by InnoCare Pharma. Dr. Li is the principal investigator for the trial but had no conflicts of interest to declare. Dr. Md Yusof disclosed receiving consultancy fees from Aurinia Pharmaceuticals.

Deucravacitinib and orelabrutinib – two novel oral drugs under investigation for the treatment of systemic lupus erythematosus (SLE) – have performed well in early clinical trials reported as late-breaking abstracts at the annual European Congress of Rheumatology.

In the phase 2 PAISLEY study, up to 58% of patients treated with deucravacitinib versus 34% of placebo-treated patients met the primary study endpoint of an SLE Responder Index-4 (SRI-4) after 38 weeks of treatment. Deucravacitinib also “achieved or meaningfully improved” all of the secondary endpoints set out in the 363-patient trial and was reported to have a safety and tolerability profile that was generally similar to placebo.

“Deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials,” said Eric F. Morand, MD, PhD, a clinical rheumatologist and head of the School of Clinical Sciences at Monash University in Melbourne.

In a separate, ongoing phase 1b/2a study designed to evaluate orelabrutinib as a potential treatment for SLE, no safety concerns were seen with the investigational drug, along with “trending efficacy,” that supports “further studies in larger and longer-term trials,” according to the study’s investigators.

“What sets these two new drugs apart from currently available targeted therapies are their mode of action,” said Md Yuzaiful Md Yusof, MBChB, PhD, who was not involved in either study.

“The results from the PAISLEY study are promising, and it’s good to see the patients recruited were of diverse ethnicity [50%–60% were White],” added Dr. Md Yusof, a senior research fellow within the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine and a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust.

He noted that the placebo rate was also low: “This could be contributed to by keeping the background prednisolone dose low, which is often a challenge in designing SLE trials.”
 

Deucravacitinib – the distant cousin of the JAK family?

“Deucravacitinib is a compound you might not have heard of before,” Dr. Morand said.

“It’s an inhibitor of a kinase called TYK2, which, broadly speaking, is a member of JAK [Janus kinase] family,” he explained in an interview. TYK2 regulates signal transduction downstream of receptors for interleukin (IL)-23 and IL-12 pathways and the type I interferon family.

“It’s a very finite set of cytokine signals” that are being blocked with deucravacitinib, he said, adding that this means it’s more directly targeting SLE pathogenic mechanisms than perhaps other JAK inhibitor compounds.

“It also means that it shouldn’t have some of the downsides of the other JAK inhibitors,” Dr. Morand said, “such as hematopoietic side effects, including cytopenias.”
 

The phase 2 PAISLEY study

This study involved 363 patients with moderate to severe, active SLE were recruited and randomized to receive placebo (n = 90) or one of three doses of deucravacitinib: 3 mg twice daily (n = 91), 6 mg twice daily (n = 93), or 12 mg once daily (n = 89). Most patients were also taking multiple background therapies, but this was similar across the four treatment arms.

The SRI-4 primary endpoint after 38 weeks of treatment was met by 34.4% of patients who received placebo, but 58.2% of those treated with deucravacitinib 3 mg twice daily (P = .0006 versus placebo), 49.5% (P = .021) of those treated with 6 mg twice daily, and 44.9% (P = .078) treated with 12 mg once daily.

“All secondary outcome measures were achieved or meaningfully improved at week 48, including SRI-4, BICLA [British Isles Lupus Assessment Group-based Composite Lupus Assessment], low-level disease activity state [LLDAS], reduction in skin disease and reduction in arthritis,” Dr. Morand said.

In addition, early biomarker results showed reductions in double-stranded DNA titers and increases in serum C4 complement with deucravacitinib across the duration of the study.

In discussion, Dr. Morand was asked about the seemingly negative or inverse dose response seen in the trial, with the best results seen with the 3-mg twice daily dose, then lower effects seen with two higher doses.

“Our analysis is that it’s not an inverse dose response, but rather a flat dose response above the 3-mg [twice daily] dose,” he said, noting that there was a higher dropout rate because of adverse effects in the 12-mg once daily group and those participants were recorded as nonresponders.

“We think what we’ve seen here is that 3 mg twice daily is a sufficient dose and there was no additional therapeutic gain above that.”

Rates of adverse events (AEs), serious AEs, and AEs of interest were overall fairly similar between deucravacitinib and placebo groups. The most common side effects seen with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. Skin reactions, such as acne, rash, and pruritis, among others, were more common in deucravacitinib- than in placebo-treated patients.

Importantly, Dr. Morand noted that there were no major cardiac events or thrombotic events and no deaths seen in the study. There was no signal for an increase in serious or opportunistic infections, including herpes zoster. There was no effect on common laboratory parameters.

“These are very encouraging results for patients with SLE,” Albert Roy, executive director of Lupus Therapeutics, said in a press release issued by the Lupus Research Alliance.

“We are honored to have played a role in this exciting work by helping to conduct this clinical trial through our Lupus Clinical Investigators Network of renowned North American academic centers.”

In an interview, he added: “We’re cautiously optimistic. Hopefully, if it continues to progress through phase 3, it’ll be the first oral agent that would be approved for lupus, notwithstanding prednisone and Plaquenil [hydroxychloroquine], back in the 50s.”

Orelabrutinib phase 2 study in SLE

Another approach to oral route of administration under investigation in SLE is the use of orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) that was approved in China in December 2020 for the treatment of certain lymphomas and leukemias.

The rationale for testing it in SLE comes from two preclinical studies that had suggested a possible benefit in reducing disease activity, explained Zhanguo Li, MD, PhD, professor at Peking University People’s Hospital in Beijing. He presented the results of an ongoing randomized, double-blind, placebo-controlled, phase Ib/IIa dose-finding study comparing three different doses of orelabrutinib (50, 80, and 100 mg, once daily) to placebo.

As in the deucravacitinib trial, the SRI-4 was used to assess the potential efficacy of orelabrutinib, although in a much smaller patient population (n = 92) and at a shorter time point (12 weeks). Results showed an 11%-20% difference between the percentage of patients who met SRI-4 response criteria with orelabrutinib and those on placebo, at a respective 46.5%, 53.3%, 56.3% and 35.7%.

SLE Disease Activity Index (SLEDAI) scores showed a similar benefit of orelabrutinib over placebo, with 54%-63% and 30% of patients, respectively, achieving a score of 8 or more.

Adverse event rates were similar to those of placebo with most events being of mild or moderate nature. Three patients treated with orelabrutinib experienced serious adverse events, of which one was grade 3, but there were no reported deaths.

Pharmacokinetic and pharmacodynamic data showed a dose effect, and nearly complete occupancy of BTK was achieved at all dose levels for 24 hours, consistent with once-daily dosing.

“BTK plays an important role in B-cell regulation, thus B-cell and myeloid-cell blockade through BTK inhibition is an interesting potential new target for SLE,” Dr. Md Yusof said.

“Data from this early dose-ranging trial is encouraging. No major safety signal apart from mild reduction in lymphocyte and white cell counts,” he added.

“There are still plenty of challenges ahead for this drug’s development, particularly as none of the BTK inhibitors have yet to succeed in phase 3 trials in rheumatic and musculoskeletal diseases,” Dr. Md Yusof said.

Early days for both agents

While both seem currently promising, it’s very early days for deucravacitinib and orelabrutinib as possible new agents for SLE.

Aside from SLE, deucravacitinib is being tested across multiple immune-mediated diseases. This includes psoriasis, where two phase 3 trials – POETYK PSO-1 and POETYK PSO-2 – have already been completed, and psoriatic arthritis, where a phase 2 trial has been reported; all with positive results.

Phase 3 testing of deucravacitinib will go ahead and recruitment may start toward the end of this year, but it’ll take years to complete the studies, Dr. Morand said. Even if the trials prove positive, neither agent is going to be available for clinical use for several years.

A case in point is anifrolumab (Saphnelo), which Dr. Morand was involved in assessing. Despite gaining approval in the United States and across much of the world, the drug still going through reimbursement processes.

“The trial data, and lots of post hoc analysis, show clearly that it’s a major step forward in treating lupus,” he said in an interview, but “access is limited in most places, so hands-on experience with that new treatment is still limited for most clinicians.”

As for all the other new targeted approaches under investigation, “although there’s a lot of trial activity, there’s still a couple of years away before any of the current trials deliver new treatment. That’s if they provide positive findings. Indeed, there have been numerous agents that have shown promise at phase 2 but then fall at the final phase 3 hurdle, including baricitinib, which Dr. Morand reported on in a separate poster presentation.

Phase 3 data proved disappointing: “Results are not sufficiently positive for that to go forward,” he said, adding that “transitioning from a successful phase 2 to a successful phase 3 is challenging, and many products have failed.”

Dr. Morand added: “It’s a very exciting time to be in lupus research, and there’s a lot of optimism about the future. But when I go back to my clinic tomorrow, I treat my patients exactly the same as I did last week and last year.”

It’s yet to be seen if deucravacitinib will fulfill its early promise, but it’s off to an impressive start. A positive for patients is that it’s an oral drug, with the potential to improve access to treatment across the world where getting infusions may be an issue.

“These are some of the most exciting data that I’ve seen at the phase 2 level in terms of effect size across all the readouts that are used,” Dr. Morand said. “There’s no guesswork here; it worked across all the measures. That’s very reassuring.”

The PAISLEY study was sponsored by Bristol-Myers Squibb. Dr. Morand has acted as a consultant to the company and received research support for the conduct of the trial. He disclosed acting as a consultant or receiving research funding from AbbVie, Amgen, AstraZeneca, Biogen, Eli Lilly, EMD Serono, Janssen, Genentech, Servier, Novartis, and UCB. Mr. Roy is the executive director of Lupus Therapeutics, which manages the Lupus Clinical Investigators Network based in North America. Lupus Therapeutics is the clinical trials arm of the Lupus Research Alliance, a nongovernmental, nonprofit funder of lupus research worldwide. The orelabrutinib study was sponsored by InnoCare Pharma. Dr. Li is the principal investigator for the trial but had no conflicts of interest to declare. Dr. Md Yusof disclosed receiving consultancy fees from Aurinia Pharmaceuticals.

Deucravacitinib and orelabrutinib – two novel oral drugs under investigation for the treatment of systemic lupus erythematosus (SLE) – have performed well in early clinical trials reported as late-breaking abstracts at the annual European Congress of Rheumatology.

In the phase 2 PAISLEY study, up to 58% of patients treated with deucravacitinib versus 34% of placebo-treated patients met the primary study endpoint of an SLE Responder Index-4 (SRI-4) after 38 weeks of treatment. Deucravacitinib also “achieved or meaningfully improved” all of the secondary endpoints set out in the 363-patient trial and was reported to have a safety and tolerability profile that was generally similar to placebo.

“Deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials,” said Eric F. Morand, MD, PhD, a clinical rheumatologist and head of the School of Clinical Sciences at Monash University in Melbourne.

In a separate, ongoing phase 1b/2a study designed to evaluate orelabrutinib as a potential treatment for SLE, no safety concerns were seen with the investigational drug, along with “trending efficacy,” that supports “further studies in larger and longer-term trials,” according to the study’s investigators.

“What sets these two new drugs apart from currently available targeted therapies are their mode of action,” said Md Yuzaiful Md Yusof, MBChB, PhD, who was not involved in either study.

“The results from the PAISLEY study are promising, and it’s good to see the patients recruited were of diverse ethnicity [50%–60% were White],” added Dr. Md Yusof, a senior research fellow within the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine and a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust.

He noted that the placebo rate was also low: “This could be contributed to by keeping the background prednisolone dose low, which is often a challenge in designing SLE trials.”
 

Deucravacitinib – the distant cousin of the JAK family?

“Deucravacitinib is a compound you might not have heard of before,” Dr. Morand said.

“It’s an inhibitor of a kinase called TYK2, which, broadly speaking, is a member of JAK [Janus kinase] family,” he explained in an interview. TYK2 regulates signal transduction downstream of receptors for interleukin (IL)-23 and IL-12 pathways and the type I interferon family.

“It’s a very finite set of cytokine signals” that are being blocked with deucravacitinib, he said, adding that this means it’s more directly targeting SLE pathogenic mechanisms than perhaps other JAK inhibitor compounds.

“It also means that it shouldn’t have some of the downsides of the other JAK inhibitors,” Dr. Morand said, “such as hematopoietic side effects, including cytopenias.”
 

The phase 2 PAISLEY study

This study involved 363 patients with moderate to severe, active SLE were recruited and randomized to receive placebo (n = 90) or one of three doses of deucravacitinib: 3 mg twice daily (n = 91), 6 mg twice daily (n = 93), or 12 mg once daily (n = 89). Most patients were also taking multiple background therapies, but this was similar across the four treatment arms.

The SRI-4 primary endpoint after 38 weeks of treatment was met by 34.4% of patients who received placebo, but 58.2% of those treated with deucravacitinib 3 mg twice daily (P = .0006 versus placebo), 49.5% (P = .021) of those treated with 6 mg twice daily, and 44.9% (P = .078) treated with 12 mg once daily.

“All secondary outcome measures were achieved or meaningfully improved at week 48, including SRI-4, BICLA [British Isles Lupus Assessment Group-based Composite Lupus Assessment], low-level disease activity state [LLDAS], reduction in skin disease and reduction in arthritis,” Dr. Morand said.

In addition, early biomarker results showed reductions in double-stranded DNA titers and increases in serum C4 complement with deucravacitinib across the duration of the study.

In discussion, Dr. Morand was asked about the seemingly negative or inverse dose response seen in the trial, with the best results seen with the 3-mg twice daily dose, then lower effects seen with two higher doses.

“Our analysis is that it’s not an inverse dose response, but rather a flat dose response above the 3-mg [twice daily] dose,” he said, noting that there was a higher dropout rate because of adverse effects in the 12-mg once daily group and those participants were recorded as nonresponders.

“We think what we’ve seen here is that 3 mg twice daily is a sufficient dose and there was no additional therapeutic gain above that.”

Rates of adverse events (AEs), serious AEs, and AEs of interest were overall fairly similar between deucravacitinib and placebo groups. The most common side effects seen with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. Skin reactions, such as acne, rash, and pruritis, among others, were more common in deucravacitinib- than in placebo-treated patients.

Importantly, Dr. Morand noted that there were no major cardiac events or thrombotic events and no deaths seen in the study. There was no signal for an increase in serious or opportunistic infections, including herpes zoster. There was no effect on common laboratory parameters.

“These are very encouraging results for patients with SLE,” Albert Roy, executive director of Lupus Therapeutics, said in a press release issued by the Lupus Research Alliance.

“We are honored to have played a role in this exciting work by helping to conduct this clinical trial through our Lupus Clinical Investigators Network of renowned North American academic centers.”

In an interview, he added: “We’re cautiously optimistic. Hopefully, if it continues to progress through phase 3, it’ll be the first oral agent that would be approved for lupus, notwithstanding prednisone and Plaquenil [hydroxychloroquine], back in the 50s.”

Orelabrutinib phase 2 study in SLE

Another approach to oral route of administration under investigation in SLE is the use of orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) that was approved in China in December 2020 for the treatment of certain lymphomas and leukemias.

The rationale for testing it in SLE comes from two preclinical studies that had suggested a possible benefit in reducing disease activity, explained Zhanguo Li, MD, PhD, professor at Peking University People’s Hospital in Beijing. He presented the results of an ongoing randomized, double-blind, placebo-controlled, phase Ib/IIa dose-finding study comparing three different doses of orelabrutinib (50, 80, and 100 mg, once daily) to placebo.

As in the deucravacitinib trial, the SRI-4 was used to assess the potential efficacy of orelabrutinib, although in a much smaller patient population (n = 92) and at a shorter time point (12 weeks). Results showed an 11%-20% difference between the percentage of patients who met SRI-4 response criteria with orelabrutinib and those on placebo, at a respective 46.5%, 53.3%, 56.3% and 35.7%.

SLE Disease Activity Index (SLEDAI) scores showed a similar benefit of orelabrutinib over placebo, with 54%-63% and 30% of patients, respectively, achieving a score of 8 or more.

Adverse event rates were similar to those of placebo with most events being of mild or moderate nature. Three patients treated with orelabrutinib experienced serious adverse events, of which one was grade 3, but there were no reported deaths.

Pharmacokinetic and pharmacodynamic data showed a dose effect, and nearly complete occupancy of BTK was achieved at all dose levels for 24 hours, consistent with once-daily dosing.

“BTK plays an important role in B-cell regulation, thus B-cell and myeloid-cell blockade through BTK inhibition is an interesting potential new target for SLE,” Dr. Md Yusof said.

“Data from this early dose-ranging trial is encouraging. No major safety signal apart from mild reduction in lymphocyte and white cell counts,” he added.

“There are still plenty of challenges ahead for this drug’s development, particularly as none of the BTK inhibitors have yet to succeed in phase 3 trials in rheumatic and musculoskeletal diseases,” Dr. Md Yusof said.

Early days for both agents

While both seem currently promising, it’s very early days for deucravacitinib and orelabrutinib as possible new agents for SLE.

Aside from SLE, deucravacitinib is being tested across multiple immune-mediated diseases. This includes psoriasis, where two phase 3 trials – POETYK PSO-1 and POETYK PSO-2 – have already been completed, and psoriatic arthritis, where a phase 2 trial has been reported; all with positive results.

Phase 3 testing of deucravacitinib will go ahead and recruitment may start toward the end of this year, but it’ll take years to complete the studies, Dr. Morand said. Even if the trials prove positive, neither agent is going to be available for clinical use for several years.

A case in point is anifrolumab (Saphnelo), which Dr. Morand was involved in assessing. Despite gaining approval in the United States and across much of the world, the drug still going through reimbursement processes.

“The trial data, and lots of post hoc analysis, show clearly that it’s a major step forward in treating lupus,” he said in an interview, but “access is limited in most places, so hands-on experience with that new treatment is still limited for most clinicians.”

As for all the other new targeted approaches under investigation, “although there’s a lot of trial activity, there’s still a couple of years away before any of the current trials deliver new treatment. That’s if they provide positive findings. Indeed, there have been numerous agents that have shown promise at phase 2 but then fall at the final phase 3 hurdle, including baricitinib, which Dr. Morand reported on in a separate poster presentation.

Phase 3 data proved disappointing: “Results are not sufficiently positive for that to go forward,” he said, adding that “transitioning from a successful phase 2 to a successful phase 3 is challenging, and many products have failed.”

Dr. Morand added: “It’s a very exciting time to be in lupus research, and there’s a lot of optimism about the future. But when I go back to my clinic tomorrow, I treat my patients exactly the same as I did last week and last year.”

It’s yet to be seen if deucravacitinib will fulfill its early promise, but it’s off to an impressive start. A positive for patients is that it’s an oral drug, with the potential to improve access to treatment across the world where getting infusions may be an issue.

“These are some of the most exciting data that I’ve seen at the phase 2 level in terms of effect size across all the readouts that are used,” Dr. Morand said. “There’s no guesswork here; it worked across all the measures. That’s very reassuring.”

The PAISLEY study was sponsored by Bristol-Myers Squibb. Dr. Morand has acted as a consultant to the company and received research support for the conduct of the trial. He disclosed acting as a consultant or receiving research funding from AbbVie, Amgen, AstraZeneca, Biogen, Eli Lilly, EMD Serono, Janssen, Genentech, Servier, Novartis, and UCB. Mr. Roy is the executive director of Lupus Therapeutics, which manages the Lupus Clinical Investigators Network based in North America. Lupus Therapeutics is the clinical trials arm of the Lupus Research Alliance, a nongovernmental, nonprofit funder of lupus research worldwide. The orelabrutinib study was sponsored by InnoCare Pharma. Dr. Li is the principal investigator for the trial but had no conflicts of interest to declare. Dr. Md Yusof disclosed receiving consultancy fees from Aurinia Pharmaceuticals.

Living the dream, diagnosing the nightmare

Does a bad dream mean you should be consulting your doctor about an impending neurologic disease? Maybe.

New research published in eClinicalMedicine suggests that, for some people, bad dreams and nightmares have been associated with developing Parkinson’s disease later in life. Dr. Abidemi I. Otaiku of the University of Birmingham (England) analyzed data from a cohort study involving 3,818 older men, of whom 2.3% were diagnosed with Parkinson’s during the 12 years of follow-up.

©Wavebreakmedia Ltd/Thinkstock

Dr. Otaiku found those with frequent nightmares – at least once per week – were twice as likely to develop Parkinson’s than were those without, with most of the diagnoses coming in the first 5 years.

Although more research needs to be done, “identifying the significance of bad dreams and nightmares could indicate that individuals who experience changes to their dreams in older age – without any obvious trigger – should seek medical advice,” he said in a Eurekalert statement.

Dr. Otaiku pointed out that studying dreams can tell us a lot about how our brains work and are structured. By using electroencephalography, Dr. Otaiku plans to look into the biological reasons for why we dream the way we do.

So could it be that those killer clowns are actually giving you a heads up on your health?
 

Maybe next time try a paper route

There’s just no winning with teenagers sometimes. You tell them to go outside, they’ll sit in the dark playing video games all night. You tell them to get better grades, they’ll skip school. You tell them to get a hobby, they’ll scam the German government for millions of euros.

The COVID-19 pandemic has been tricky for governments to manage. Massive amounts of infrastructure needed to be set up, and that means corners got cut. Germany was no exception in this regard; the government entrusted the Kassenärztlichen Vereinigung, a doctor’s association, with overseeing COVID testing and payment at private test centers. To make things a bit easier, all they required private test centers to provide to receive reimbursement was an invoice.

AvailableLight/Getty Images

This is where our 17-year-old from Freiburg comes in. In a spark of entrepreneurial genius, he decided to falsify documents and create an entirely fictional COVID test center. The KV approved it, and between March and July of 2021, he sent in thousands of fake invoices. Over that 4-month period, he submitted 500,000 invoices and received 5.7 million euros as compensation. That’s a few thousand tests per day, which was absolutely absurd, but he avoided scrutiny for months.

In the end, it wasn’t even the KV that noticed the fraud, but the bank. A bank employee noticed millions flowing into the account of a teenager and suspected money laundering, alerting the government. Fortunately for our young friend, since he was under 18 when he hatched his scheme, he was tried as a minor, avoiding jail time. His ill-gotten gains were confiscated, he has to pay a relatively minimal fine, and he will be on probation for 1 year. And presumably, he’ll be on the receiving end of the grounding of a lifetime.
 

You look like I need more sleep

Like most people, not getting our beauty sleep can make us look tired and feel less attractive, but a new study from Sweden shows that the sleep deprived also are more likely to find others less attractive. That’s probably not a good finding for singles who often go out trying to meet someone after a long day of work.

PRImageFactory/iStock/Getty Images

For the study, 45 young men and women were required to spend one night with no sleep and then another night with the possibility of 8 hours of sleep. The following mornings, eye-tracking technology was used as they looked at images of happy, angry, fearful, and neutral faces. The subjects then rated the faces for attractiveness, trustworthiness, and healthiness.

“The finding that sleep-deprived subjects in our experiment rated angry faces as less trustworthy and healthy-looking and neutral and fearful faces as less attractive indicates that sleep loss is associated with more negative social impressions of others,” senior author Christian Benedict of Uppsala University said in a statement.

When we are sleep deprived, the researchers added, we might not stop to really look at someone else, which has a negative impact on how we perceive people because we are not focusing on what their facial expressions are really telling us.

We already knew that not sleeping well has many negative effects on us, but now – thank you very much, science – we have something else to think about. Better hope your crush at work gets enough sleep so you’ll be accurately noticed.
 

The expanding-hole illusion of science

Time for a LOTME-style reality check: I think, therefore I am.

So far, so good. Next step: I think, therefore I am. I think.

Works for us. Now for the biggie: I think I am seeing the black hole in the middle of this image expanding.

Laeng, Nabil, and Kitaoka

Does that work for you? Do you perceive the black hole as expanding? If you do, then you fit in with the 86% of subjects in a recent study who perceived the same thing.

Lead author Bruno Laeng of the University of Oslo explained the effect in a statement from Frontiers Science News. “The circular smear or shadow gradient of the central black hole evokes a marked impression of optic flow, as if the observer were heading forward into a hole or tunnel. ... The pupil reacts to how we perceive light – even if this ‘light’ is imaginary like in the illusion – and not just to the amount of light energy that actually enters the eye.”

The illusion is so good at deceiving the brain “that it even prompts a dilation reflex of the pupils to let in more light, just as would happen if we were really moving into a dark area,” the investigators said.

Of the 50 men and women who had their eye movements measured while looking at the illusion, only 14% didn’t perceive the illusion when the hole was black. When the hole was a color, that figure went up to 20%. There also was a strong dilation reflex with black holes, but colored holes caused the subjects’ pupils to constrict, they noted.

Dr. Laeng and his associates can’t explain why some people don’t see the movement, but they did offer this: “Pupils’ dilation or contraction reflex is not a closed-loop mechanism, like a photocell opening a door, impervious to any other information than the actual amount of light stimulating the photoreceptor. Rather, the eye adjusts to perceived and even imagined light, not simply to physical energy.”

And now, back to our reality check: We think we perceive the light of a cheeseburger, therefore it’s time for lunch.

Living the dream, diagnosing the nightmare

Does a bad dream mean you should be consulting your doctor about an impending neurologic disease? Maybe.

New research published in eClinicalMedicine suggests that, for some people, bad dreams and nightmares have been associated with developing Parkinson’s disease later in life. Dr. Abidemi I. Otaiku of the University of Birmingham (England) analyzed data from a cohort study involving 3,818 older men, of whom 2.3% were diagnosed with Parkinson’s during the 12 years of follow-up.

©Wavebreakmedia Ltd/Thinkstock

Dr. Otaiku found those with frequent nightmares – at least once per week – were twice as likely to develop Parkinson’s than were those without, with most of the diagnoses coming in the first 5 years.

Although more research needs to be done, “identifying the significance of bad dreams and nightmares could indicate that individuals who experience changes to their dreams in older age – without any obvious trigger – should seek medical advice,” he said in a Eurekalert statement.

Dr. Otaiku pointed out that studying dreams can tell us a lot about how our brains work and are structured. By using electroencephalography, Dr. Otaiku plans to look into the biological reasons for why we dream the way we do.

So could it be that those killer clowns are actually giving you a heads up on your health?
 

Maybe next time try a paper route

There’s just no winning with teenagers sometimes. You tell them to go outside, they’ll sit in the dark playing video games all night. You tell them to get better grades, they’ll skip school. You tell them to get a hobby, they’ll scam the German government for millions of euros.

The COVID-19 pandemic has been tricky for governments to manage. Massive amounts of infrastructure needed to be set up, and that means corners got cut. Germany was no exception in this regard; the government entrusted the Kassenärztlichen Vereinigung, a doctor’s association, with overseeing COVID testing and payment at private test centers. To make things a bit easier, all they required private test centers to provide to receive reimbursement was an invoice.

AvailableLight/Getty Images

This is where our 17-year-old from Freiburg comes in. In a spark of entrepreneurial genius, he decided to falsify documents and create an entirely fictional COVID test center. The KV approved it, and between March and July of 2021, he sent in thousands of fake invoices. Over that 4-month period, he submitted 500,000 invoices and received 5.7 million euros as compensation. That’s a few thousand tests per day, which was absolutely absurd, but he avoided scrutiny for months.

In the end, it wasn’t even the KV that noticed the fraud, but the bank. A bank employee noticed millions flowing into the account of a teenager and suspected money laundering, alerting the government. Fortunately for our young friend, since he was under 18 when he hatched his scheme, he was tried as a minor, avoiding jail time. His ill-gotten gains were confiscated, he has to pay a relatively minimal fine, and he will be on probation for 1 year. And presumably, he’ll be on the receiving end of the grounding of a lifetime.
 

You look like I need more sleep

Like most people, not getting our beauty sleep can make us look tired and feel less attractive, but a new study from Sweden shows that the sleep deprived also are more likely to find others less attractive. That’s probably not a good finding for singles who often go out trying to meet someone after a long day of work.

PRImageFactory/iStock/Getty Images

For the study, 45 young men and women were required to spend one night with no sleep and then another night with the possibility of 8 hours of sleep. The following mornings, eye-tracking technology was used as they looked at images of happy, angry, fearful, and neutral faces. The subjects then rated the faces for attractiveness, trustworthiness, and healthiness.

“The finding that sleep-deprived subjects in our experiment rated angry faces as less trustworthy and healthy-looking and neutral and fearful faces as less attractive indicates that sleep loss is associated with more negative social impressions of others,” senior author Christian Benedict of Uppsala University said in a statement.

When we are sleep deprived, the researchers added, we might not stop to really look at someone else, which has a negative impact on how we perceive people because we are not focusing on what their facial expressions are really telling us.

We already knew that not sleeping well has many negative effects on us, but now – thank you very much, science – we have something else to think about. Better hope your crush at work gets enough sleep so you’ll be accurately noticed.
 

The expanding-hole illusion of science

Time for a LOTME-style reality check: I think, therefore I am.

So far, so good. Next step: I think, therefore I am. I think.

Works for us. Now for the biggie: I think I am seeing the black hole in the middle of this image expanding.

Laeng, Nabil, and Kitaoka

Does that work for you? Do you perceive the black hole as expanding? If you do, then you fit in with the 86% of subjects in a recent study who perceived the same thing.

Lead author Bruno Laeng of the University of Oslo explained the effect in a statement from Frontiers Science News. “The circular smear or shadow gradient of the central black hole evokes a marked impression of optic flow, as if the observer were heading forward into a hole or tunnel. ... The pupil reacts to how we perceive light – even if this ‘light’ is imaginary like in the illusion – and not just to the amount of light energy that actually enters the eye.”

The illusion is so good at deceiving the brain “that it even prompts a dilation reflex of the pupils to let in more light, just as would happen if we were really moving into a dark area,” the investigators said.

Of the 50 men and women who had their eye movements measured while looking at the illusion, only 14% didn’t perceive the illusion when the hole was black. When the hole was a color, that figure went up to 20%. There also was a strong dilation reflex with black holes, but colored holes caused the subjects’ pupils to constrict, they noted.

Dr. Laeng and his associates can’t explain why some people don’t see the movement, but they did offer this: “Pupils’ dilation or contraction reflex is not a closed-loop mechanism, like a photocell opening a door, impervious to any other information than the actual amount of light stimulating the photoreceptor. Rather, the eye adjusts to perceived and even imagined light, not simply to physical energy.”

And now, back to our reality check: We think we perceive the light of a cheeseburger, therefore it’s time for lunch.

Living the dream, diagnosing the nightmare

Does a bad dream mean you should be consulting your doctor about an impending neurologic disease? Maybe.

New research published in eClinicalMedicine suggests that, for some people, bad dreams and nightmares have been associated with developing Parkinson’s disease later in life. Dr. Abidemi I. Otaiku of the University of Birmingham (England) analyzed data from a cohort study involving 3,818 older men, of whom 2.3% were diagnosed with Parkinson’s during the 12 years of follow-up.

©Wavebreakmedia Ltd/Thinkstock

Dr. Otaiku found those with frequent nightmares – at least once per week – were twice as likely to develop Parkinson’s than were those without, with most of the diagnoses coming in the first 5 years.

Although more research needs to be done, “identifying the significance of bad dreams and nightmares could indicate that individuals who experience changes to their dreams in older age – without any obvious trigger – should seek medical advice,” he said in a Eurekalert statement.

Dr. Otaiku pointed out that studying dreams can tell us a lot about how our brains work and are structured. By using electroencephalography, Dr. Otaiku plans to look into the biological reasons for why we dream the way we do.

So could it be that those killer clowns are actually giving you a heads up on your health?
 

Maybe next time try a paper route

There’s just no winning with teenagers sometimes. You tell them to go outside, they’ll sit in the dark playing video games all night. You tell them to get better grades, they’ll skip school. You tell them to get a hobby, they’ll scam the German government for millions of euros.

The COVID-19 pandemic has been tricky for governments to manage. Massive amounts of infrastructure needed to be set up, and that means corners got cut. Germany was no exception in this regard; the government entrusted the Kassenärztlichen Vereinigung, a doctor’s association, with overseeing COVID testing and payment at private test centers. To make things a bit easier, all they required private test centers to provide to receive reimbursement was an invoice.

AvailableLight/Getty Images

This is where our 17-year-old from Freiburg comes in. In a spark of entrepreneurial genius, he decided to falsify documents and create an entirely fictional COVID test center. The KV approved it, and between March and July of 2021, he sent in thousands of fake invoices. Over that 4-month period, he submitted 500,000 invoices and received 5.7 million euros as compensation. That’s a few thousand tests per day, which was absolutely absurd, but he avoided scrutiny for months.

In the end, it wasn’t even the KV that noticed the fraud, but the bank. A bank employee noticed millions flowing into the account of a teenager and suspected money laundering, alerting the government. Fortunately for our young friend, since he was under 18 when he hatched his scheme, he was tried as a minor, avoiding jail time. His ill-gotten gains were confiscated, he has to pay a relatively minimal fine, and he will be on probation for 1 year. And presumably, he’ll be on the receiving end of the grounding of a lifetime.
 

You look like I need more sleep

Like most people, not getting our beauty sleep can make us look tired and feel less attractive, but a new study from Sweden shows that the sleep deprived also are more likely to find others less attractive. That’s probably not a good finding for singles who often go out trying to meet someone after a long day of work.

PRImageFactory/iStock/Getty Images

For the study, 45 young men and women were required to spend one night with no sleep and then another night with the possibility of 8 hours of sleep. The following mornings, eye-tracking technology was used as they looked at images of happy, angry, fearful, and neutral faces. The subjects then rated the faces for attractiveness, trustworthiness, and healthiness.

“The finding that sleep-deprived subjects in our experiment rated angry faces as less trustworthy and healthy-looking and neutral and fearful faces as less attractive indicates that sleep loss is associated with more negative social impressions of others,” senior author Christian Benedict of Uppsala University said in a statement.

When we are sleep deprived, the researchers added, we might not stop to really look at someone else, which has a negative impact on how we perceive people because we are not focusing on what their facial expressions are really telling us.

We already knew that not sleeping well has many negative effects on us, but now – thank you very much, science – we have something else to think about. Better hope your crush at work gets enough sleep so you’ll be accurately noticed.
 

The expanding-hole illusion of science

Time for a LOTME-style reality check: I think, therefore I am.

So far, so good. Next step: I think, therefore I am. I think.

Works for us. Now for the biggie: I think I am seeing the black hole in the middle of this image expanding.

Laeng, Nabil, and Kitaoka

Does that work for you? Do you perceive the black hole as expanding? If you do, then you fit in with the 86% of subjects in a recent study who perceived the same thing.

Lead author Bruno Laeng of the University of Oslo explained the effect in a statement from Frontiers Science News. “The circular smear or shadow gradient of the central black hole evokes a marked impression of optic flow, as if the observer were heading forward into a hole or tunnel. ... The pupil reacts to how we perceive light – even if this ‘light’ is imaginary like in the illusion – and not just to the amount of light energy that actually enters the eye.”

The illusion is so good at deceiving the brain “that it even prompts a dilation reflex of the pupils to let in more light, just as would happen if we were really moving into a dark area,” the investigators said.

Of the 50 men and women who had their eye movements measured while looking at the illusion, only 14% didn’t perceive the illusion when the hole was black. When the hole was a color, that figure went up to 20%. There also was a strong dilation reflex with black holes, but colored holes caused the subjects’ pupils to constrict, they noted.

Dr. Laeng and his associates can’t explain why some people don’t see the movement, but they did offer this: “Pupils’ dilation or contraction reflex is not a closed-loop mechanism, like a photocell opening a door, impervious to any other information than the actual amount of light stimulating the photoreceptor. Rather, the eye adjusts to perceived and even imagined light, not simply to physical energy.”

And now, back to our reality check: We think we perceive the light of a cheeseburger, therefore it’s time for lunch.

COPENHAGEN – Discontinuing maintenance immunosuppressive therapy (IST) in patients with proliferative lupus nephritis in remission proved less effective than continuing it in terms of the rates of renal relapse and severe systemic lupus erythematosus (SLE) flare, results from the WIN-Lupus trial show.

Lead researcher Noemie Jourde-Chiche, MD, assistant professor at Aix-Marseille (France) University, presented the results at the annual European Congress of Rheumatology.

The randomized, controlled trial aimed to determine the optimal duration of maintenance IST for proliferative lupus nephritis, by asking whether discontinuation of such therapy after 2-3 years was noninferior to IST continuation for 2 more years.

“This is the first randomized IST trial in proliferative lupus nephritis,” Dr. Jourde-Chiche reported. “We found that noninferiority of IST discontinuation was not demonstrated, and those who discontinued had a higher risk of SLE flares, but the majority of patients who discontinued did not experience flare.”

Regarding the incidence of renal relapse, no statistically significant difference was found between patients who continued versus those who discontinued IST.

Rheumatologist Christophe Richez, MD, of the Groupe Hospitalier Pellegrin-CHU de Bordeaux (France) welcomed the trial. “The work does not find a significant difference but suggests that with more power, the difference would have been significant,” he said in an interview.

He added that a significant number of patients refused to enter the study for several reasons, including scheduling a pregnancy and fear of relapse after stopping the treatment. “This in itself shows that we need this type of study to know if we can stop the treatment to plan a pregnancy or if a relay treatment is necessary. These data also mean we can now better inform our patients about the benefit-risk [profile] of continuing treatment or not.”

Dr. Richez, who was not involved in the trial, noted that the data provide information that strongly suggest more research is needed to better determine which patients are at risk of relapse, and consequently, for which patients is discontinuation possible. “There’s also a need for further analysis of tolerance to the immunosuppressive drugs according to the strategy.”

Finally, he referred to the issue around therapeutic adherence that is often faced with management of lupus. “The data from this study will allow us to better explain to patients the need to continue or discontinue their treatments, including hydroxychloroquine, and also the possibility of decreasing the immunosuppressive drugs to half-dose.”

Maintenance therapy in lupus nephritis: To continue or not?

Conducted in 28 French centers, participants had class III or IV lupus nephritis with active lesions and had previously received induction IST of cyclophosphamide or mycophenolate mofetil with hydroxychloroquine and glucocorticoids. Maintenance IST was azathioprine or mycophenolate mofetil, hydroxychloroquine, and possibly low-dose glucocorticoids (below 10 mg/day).

A total of 96 patients were randomized into two groups: continuation of maintenance therapy (azathioprine or mycophenolate mofetil for 2-3 more years, hydroxychloroquine, and possibly low-dose glucocorticoids (below 10 mg/day), or discontinuation of maintenance therapy (azathioprine or mycophenolate mofetil) over 3 months.

Both study arms were similar with a mean age of 36-37 years, and 82%-86% of patients were female, 59%-67% were White. They had a mean disease duration of 7-9 years, and 72%-80% had experienced their first flare of proliferative nephritis. A total of 54%-65% had received cyclophosphamide induction therapy, and 75%-81% were on mycophenolate mofetil maintenance therapy that had been ongoing for a mean of 2.8 years. Tests of patients’ kidney function revealed a mean serum creatinine of 67-72 micromol/L and estimated glomerular filtration rate (eGFR) of 94-101 mL/min per 1.73 m². The mean SLE Disease Activity Index score was around 2.

Follow-up visits were conducted every 3 months for 2 years, and the trial had a primary end point of renal relapse rate at 24 months (confirmed by kidney biopsy), while secondary endpoints included rate of severe SLE flares, survival without renal relapse, or severe flare and adverse events, among others.

Patients were excluded if they were not taking hydroxychloroquine, had extrarenal SLE, an eGFR less than 30 mL/min per 1.73 m² or stage VI disease. After some participants did not finish the trial because of pregnancy, wish for pregnancy, or adverse events, data from a total of 40 in the IST continuation group and 44 in the discontinuation group were analyzed.
 

Noninferiority of discontinuation versus continuation not shown

A total of 12.5% in the continuation arm experienced renal relapse over 24 months, compared with 27.3% in the discontinuation arm (P = .079).

“The endpoint of noninferiority of discontinuation of immunosuppressive therapy was not shown, but no statistically significant difference was found between groups for renal relapse,” Dr. Jourde-Chiche said.

Severe SLE flares (renal or extrarenal) occurred significantly less often over 24 months in the continuation arm at 12.5% versus 31.8% in the discontinuation arm (P = .034).

However, Dr. Jourde-Chiche pointed out that “the majority of patients who discontinued treatment did not experience a flare.”

No differences were seen between groups with respect to any secondary endpoints. “Fortunately, no patients died or reached end-stage renal disease, and overall, the adverse events did not differ between groups,” she reported.

The study identified several risk factors for renal relapse, among which were low complement component 3 and higher baseline urinary protein to creatinine ratio.
 

Longer immunosuppressive therapy prediscontinuation leads to better results

Gabriella Moroni, MD, of the nephrology unit at Ospedale Maggiore Policlinico, Milan, authored a review of studies that attempted to interrupt glucocorticoids and other immunosuppressive agents in lupus nephritis and in SLE. Her review concluded that “the available data suggest that therapy withdrawal is feasible at least in patients enjoying a complete clinical remission after a prolonged therapy.”

Asked to comment on the French study, Dr. Moroni said the trial was very welcome. “In our long-term experience, we have stopped IST in 73 patients with lupus nephritis, followed for a mean of 23 years. Of these, 32 never reassumed therapy and 20 had at least one flare.”

Dr. Moroni noted that those participants who did not experience flares had significantly longer IST and longer remission before discontinuation and took hydroxychloroquine more frequently.

“We feel that, to prevent severe flares, firstly, lupus nephritis should be in complete remission for at least 3 years, and secondly, patients should have received IST for at least 5 years before discontinuation; immunosuppressive drugs should be tapered off very slowly and after strict clinical surveillance, and finally, hydroxychloroquine can prevent extrarenal flares.

Dr. Jourde-Chiche reported serving on a speakers bureau for Vifor Pharma and receiving grant/research support from Fresenius Medical Care. Some coauthors reported financial ties to many pharmaceutical companies. Dr. Richez said he has received fees for lectures or boards from GlaxoSmithKline, AstraZeneca, and Novartis. Dr. Moroni had no relevant disclosures.

COPENHAGEN – Discontinuing maintenance immunosuppressive therapy (IST) in patients with proliferative lupus nephritis in remission proved less effective than continuing it in terms of the rates of renal relapse and severe systemic lupus erythematosus (SLE) flare, results from the WIN-Lupus trial show.

Lead researcher Noemie Jourde-Chiche, MD, assistant professor at Aix-Marseille (France) University, presented the results at the annual European Congress of Rheumatology.

The randomized, controlled trial aimed to determine the optimal duration of maintenance IST for proliferative lupus nephritis, by asking whether discontinuation of such therapy after 2-3 years was noninferior to IST continuation for 2 more years.

“This is the first randomized IST trial in proliferative lupus nephritis,” Dr. Jourde-Chiche reported. “We found that noninferiority of IST discontinuation was not demonstrated, and those who discontinued had a higher risk of SLE flares, but the majority of patients who discontinued did not experience flare.”

Regarding the incidence of renal relapse, no statistically significant difference was found between patients who continued versus those who discontinued IST.

Rheumatologist Christophe Richez, MD, of the Groupe Hospitalier Pellegrin-CHU de Bordeaux (France) welcomed the trial. “The work does not find a significant difference but suggests that with more power, the difference would have been significant,” he said in an interview.

He added that a significant number of patients refused to enter the study for several reasons, including scheduling a pregnancy and fear of relapse after stopping the treatment. “This in itself shows that we need this type of study to know if we can stop the treatment to plan a pregnancy or if a relay treatment is necessary. These data also mean we can now better inform our patients about the benefit-risk [profile] of continuing treatment or not.”

Dr. Richez, who was not involved in the trial, noted that the data provide information that strongly suggest more research is needed to better determine which patients are at risk of relapse, and consequently, for which patients is discontinuation possible. “There’s also a need for further analysis of tolerance to the immunosuppressive drugs according to the strategy.”

Finally, he referred to the issue around therapeutic adherence that is often faced with management of lupus. “The data from this study will allow us to better explain to patients the need to continue or discontinue their treatments, including hydroxychloroquine, and also the possibility of decreasing the immunosuppressive drugs to half-dose.”

Maintenance therapy in lupus nephritis: To continue or not?

Conducted in 28 French centers, participants had class III or IV lupus nephritis with active lesions and had previously received induction IST of cyclophosphamide or mycophenolate mofetil with hydroxychloroquine and glucocorticoids. Maintenance IST was azathioprine or mycophenolate mofetil, hydroxychloroquine, and possibly low-dose glucocorticoids (below 10 mg/day).

A total of 96 patients were randomized into two groups: continuation of maintenance therapy (azathioprine or mycophenolate mofetil for 2-3 more years, hydroxychloroquine, and possibly low-dose glucocorticoids (below 10 mg/day), or discontinuation of maintenance therapy (azathioprine or mycophenolate mofetil) over 3 months.

Both study arms were similar with a mean age of 36-37 years, and 82%-86% of patients were female, 59%-67% were White. They had a mean disease duration of 7-9 years, and 72%-80% had experienced their first flare of proliferative nephritis. A total of 54%-65% had received cyclophosphamide induction therapy, and 75%-81% were on mycophenolate mofetil maintenance therapy that had been ongoing for a mean of 2.8 years. Tests of patients’ kidney function revealed a mean serum creatinine of 67-72 micromol/L and estimated glomerular filtration rate (eGFR) of 94-101 mL/min per 1.73 m². The mean SLE Disease Activity Index score was around 2.

Follow-up visits were conducted every 3 months for 2 years, and the trial had a primary end point of renal relapse rate at 24 months (confirmed by kidney biopsy), while secondary endpoints included rate of severe SLE flares, survival without renal relapse, or severe flare and adverse events, among others.

Patients were excluded if they were not taking hydroxychloroquine, had extrarenal SLE, an eGFR less than 30 mL/min per 1.73 m² or stage VI disease. After some participants did not finish the trial because of pregnancy, wish for pregnancy, or adverse events, data from a total of 40 in the IST continuation group and 44 in the discontinuation group were analyzed.
 

Noninferiority of discontinuation versus continuation not shown

A total of 12.5% in the continuation arm experienced renal relapse over 24 months, compared with 27.3% in the discontinuation arm (P = .079).

“The endpoint of noninferiority of discontinuation of immunosuppressive therapy was not shown, but no statistically significant difference was found between groups for renal relapse,” Dr. Jourde-Chiche said.

Severe SLE flares (renal or extrarenal) occurred significantly less often over 24 months in the continuation arm at 12.5% versus 31.8% in the discontinuation arm (P = .034).

However, Dr. Jourde-Chiche pointed out that “the majority of patients who discontinued treatment did not experience a flare.”

No differences were seen between groups with respect to any secondary endpoints. “Fortunately, no patients died or reached end-stage renal disease, and overall, the adverse events did not differ between groups,” she reported.

The study identified several risk factors for renal relapse, among which were low complement component 3 and higher baseline urinary protein to creatinine ratio.
 

Longer immunosuppressive therapy prediscontinuation leads to better results

Gabriella Moroni, MD, of the nephrology unit at Ospedale Maggiore Policlinico, Milan, authored a review of studies that attempted to interrupt glucocorticoids and other immunosuppressive agents in lupus nephritis and in SLE. Her review concluded that “the available data suggest that therapy withdrawal is feasible at least in patients enjoying a complete clinical remission after a prolonged therapy.”

Asked to comment on the French study, Dr. Moroni said the trial was very welcome. “In our long-term experience, we have stopped IST in 73 patients with lupus nephritis, followed for a mean of 23 years. Of these, 32 never reassumed therapy and 20 had at least one flare.”

Dr. Moroni noted that those participants who did not experience flares had significantly longer IST and longer remission before discontinuation and took hydroxychloroquine more frequently.

“We feel that, to prevent severe flares, firstly, lupus nephritis should be in complete remission for at least 3 years, and secondly, patients should have received IST for at least 5 years before discontinuation; immunosuppressive drugs should be tapered off very slowly and after strict clinical surveillance, and finally, hydroxychloroquine can prevent extrarenal flares.

Dr. Jourde-Chiche reported serving on a speakers bureau for Vifor Pharma and receiving grant/research support from Fresenius Medical Care. Some coauthors reported financial ties to many pharmaceutical companies. Dr. Richez said he has received fees for lectures or boards from GlaxoSmithKline, AstraZeneca, and Novartis. Dr. Moroni had no relevant disclosures.

COPENHAGEN – Discontinuing maintenance immunosuppressive therapy (IST) in patients with proliferative lupus nephritis in remission proved less effective than continuing it in terms of the rates of renal relapse and severe systemic lupus erythematosus (SLE) flare, results from the WIN-Lupus trial show.

Lead researcher Noemie Jourde-Chiche, MD, assistant professor at Aix-Marseille (France) University, presented the results at the annual European Congress of Rheumatology.

The randomized, controlled trial aimed to determine the optimal duration of maintenance IST for proliferative lupus nephritis, by asking whether discontinuation of such therapy after 2-3 years was noninferior to IST continuation for 2 more years.

“This is the first randomized IST trial in proliferative lupus nephritis,” Dr. Jourde-Chiche reported. “We found that noninferiority of IST discontinuation was not demonstrated, and those who discontinued had a higher risk of SLE flares, but the majority of patients who discontinued did not experience flare.”

Regarding the incidence of renal relapse, no statistically significant difference was found between patients who continued versus those who discontinued IST.

Rheumatologist Christophe Richez, MD, of the Groupe Hospitalier Pellegrin-CHU de Bordeaux (France) welcomed the trial. “The work does not find a significant difference but suggests that with more power, the difference would have been significant,” he said in an interview.

He added that a significant number of patients refused to enter the study for several reasons, including scheduling a pregnancy and fear of relapse after stopping the treatment. “This in itself shows that we need this type of study to know if we can stop the treatment to plan a pregnancy or if a relay treatment is necessary. These data also mean we can now better inform our patients about the benefit-risk [profile] of continuing treatment or not.”

Dr. Richez, who was not involved in the trial, noted that the data provide information that strongly suggest more research is needed to better determine which patients are at risk of relapse, and consequently, for which patients is discontinuation possible. “There’s also a need for further analysis of tolerance to the immunosuppressive drugs according to the strategy.”

Finally, he referred to the issue around therapeutic adherence that is often faced with management of lupus. “The data from this study will allow us to better explain to patients the need to continue or discontinue their treatments, including hydroxychloroquine, and also the possibility of decreasing the immunosuppressive drugs to half-dose.”