Rheumatology News

PHILADELPHIA – Prednisone appears to have the edge over colchicine for control of pain in patients with acute calcium pyrophosphate (CPP) crystal arthritis, an intensely painful rheumatic disease primarily affecting older patients.

Among 111 patients with acute CPP crystal arthritis randomized to receive either prednisone or colchicine for control of acute pain in a multicenter study, 2 days of therapy with the oral agents provided equivalent pain relief on the second day, and patients generally tolerated each agent well, reported Tristan Pascart, MD, from the Groupement Hospitalier de l’Institut Catholique de Lille (France).

Neil Osterweil/MDedge News

“Almost three-fourths of patients are considered to be good responders to both drugs on day 3, and, maybe, safety is the key issue distinguishing the two treatments: Colchicine was generally well tolerated, but even with this very short time frame of treatment, one patient out of five had diarrhea, which is more of a concern in this elderly population at risk of dehydration,” he said in an oral abstract session at the annual meeting of the American College of Rheumatology.

In contrast, only about 6% of patients assigned to prednisone had diarrhea, and other adverse events that occurred more frequently with the corticosteroid, including hypertension, hyperglycemia, and insomnia all resolved after the therapy was stopped.
 

Common and acutely painful

Acute CPP crystal arthritis is a common complication that often occurs during hospitalization for primarily nonrheumatologic causes, Dr. Pascart said, and “in the absence of clinical trials, the management relies on expert opinion, which stems from extrapolated data from gap studies” primarily with prednisone or colchicine, Dr. Pascart said.

To fill in the knowledge gap, Dr. Pascart and colleagues conducted the COLCHICORT study to evaluate whether the two drugs were comparable in efficacy and safety for control of acute pain in a vulnerable population.

The multicenter, open-label trial included patients older than age 65 years with an estimated glomerular filtration rate above 30 mL/min per 1.73 m² who presented with acute CPP deposition arthritis with symptoms occurring within the previous 36 hours. CPP arthritis was defined by the identification of CPP crystals on synovial fluid analysis or typical clinical presentation with evidence of chondrocalcinosis on x-rays or ultrasound.

Patients with a history of gout, cognitive decline that could impair pain assessment, or contraindications to either of the study drugs were excluded.

The participants were randomized to receive either colchicine 1.5 mg (1 mg to start, then 0.5 mg one hour later) at baseline and then 1 mg on day 1, or oral prednisone 30 mg at baseline and on day 1. The patients also received 1 g of systemic acetaminophen, and three 50-mg doses of tramadol during the first 24 hours.

Of the 111 patients randomized, 54 were assigned to receive prednisone, and 57 were assigned to receive colchicine. Baseline characteristics were similar between the groups, with a mean age of about 86 years, body mass index of around 25 kg/m², and blood pressure in the range of 130/69 mm Hg.

For nearly half of all patients in study each arm the most painful joint was the knee, followed by wrists and ankles.

There was no difference between the groups in the primary efficacy outcome of a change at 24 hours over baseline in visual analog scale (VAS) (0-100 mm) scores, either in a per-protocol analysis or modified intention-to-treat analysis. The mean change in VAS at 24 hours in the colchicine group was –36.6 mm, compared with –37.7 mm in the prednisone group. The investigators had previously determined that any difference between the two drugs of less than 13 mm on pain VAS at 24 hours would meet the definition for equivalent efficacy.

In both groups, a majority of patients had either an improvement greater than 50% in pain VAS scores and/or a pain VAS score less than 40 mm at both 24 and 48 hours.

At 7 days of follow-up, 21.8% of patients assigned to colchicine had diarrhea, compared with 5.6% of those assigned to prednisone. Adverse events occurring more frequently with prednisone included hyperglycemia, hypertension, and insomnia.

Patients who received colchicine and were also on statins had a trend toward a higher risk for diarrhea, but the study was not adequately powered to detect an association, and the trend was not statistically significant, Dr. Pascart said.

“Taken together, safety issues suggest that prednisone should be considered as the first-line therapy in acute CPP crystal arthritis. Future research is warranted to determine factors increasing the risk of colchicine-induced diarrhea,” he concluded.
 

Both drugs are used

Sara K. Tedeschi, MD, from Brigham & Women’s Hospital in Boston, who attended the session where the data were presented, has a special clinical interest in CPP deposition disease. She applauded Dr. Pascart and colleagues for conducting a rare clinical trial in CPP crystal arthritis.

In an interview, she said that the study suggests “we can keep in mind shorter courses of treatment for acute CPP crystal arthritis; I think that’s one big takeaway from this study.”

Asked whether she would change her practice based on the findings, Dr. Tedeschi replied: “I personally am not sure that I would be moved to use prednisone more than colchicine; I actually take away from this that colchicine is equivalent to prednisone for short-term use for CPP arthritis, but I think it’s also really important to note that this is in the context of quite a lot of acetaminophen and quite a lot of tramadol, and frankly I don’t usually use tramadol with my patients, but I might consider doing that, especially as there were no delirium events in this population.”

Dr. Tedeschi was not involved in the study.

Asked the same question, Michael Toprover, MD, from New York University Langone Medical Center, a moderator of the session who was not involved in the study, said: “I usually use a combination of medications. I generally, in someone who is hospitalized in particular and is in such severe pain, use a combination of colchicine and prednisone, unless I’m worried about infection, in which case I’ll start colchicine until we’ve proven that it’s CPPD, and then I’ll add prednisone.”

The study was funded by PHRC-1 GIRCI Nord Ouest, a clinical research program funded by the Ministry of Health in France. Dr. Pascart, Dr. Tedeschi, and Dr. Toprover all reported having no relevant conflicts of interest.

PHILADELPHIA – Prednisone appears to have the edge over colchicine for control of pain in patients with acute calcium pyrophosphate (CPP) crystal arthritis, an intensely painful rheumatic disease primarily affecting older patients.

Among 111 patients with acute CPP crystal arthritis randomized to receive either prednisone or colchicine for control of acute pain in a multicenter study, 2 days of therapy with the oral agents provided equivalent pain relief on the second day, and patients generally tolerated each agent well, reported Tristan Pascart, MD, from the Groupement Hospitalier de l’Institut Catholique de Lille (France).

Neil Osterweil/MDedge News

“Almost three-fourths of patients are considered to be good responders to both drugs on day 3, and, maybe, safety is the key issue distinguishing the two treatments: Colchicine was generally well tolerated, but even with this very short time frame of treatment, one patient out of five had diarrhea, which is more of a concern in this elderly population at risk of dehydration,” he said in an oral abstract session at the annual meeting of the American College of Rheumatology.

In contrast, only about 6% of patients assigned to prednisone had diarrhea, and other adverse events that occurred more frequently with the corticosteroid, including hypertension, hyperglycemia, and insomnia all resolved after the therapy was stopped.
 

Common and acutely painful

Acute CPP crystal arthritis is a common complication that often occurs during hospitalization for primarily nonrheumatologic causes, Dr. Pascart said, and “in the absence of clinical trials, the management relies on expert opinion, which stems from extrapolated data from gap studies” primarily with prednisone or colchicine, Dr. Pascart said.

To fill in the knowledge gap, Dr. Pascart and colleagues conducted the COLCHICORT study to evaluate whether the two drugs were comparable in efficacy and safety for control of acute pain in a vulnerable population.

The multicenter, open-label trial included patients older than age 65 years with an estimated glomerular filtration rate above 30 mL/min per 1.73 m² who presented with acute CPP deposition arthritis with symptoms occurring within the previous 36 hours. CPP arthritis was defined by the identification of CPP crystals on synovial fluid analysis or typical clinical presentation with evidence of chondrocalcinosis on x-rays or ultrasound.

Patients with a history of gout, cognitive decline that could impair pain assessment, or contraindications to either of the study drugs were excluded.

The participants were randomized to receive either colchicine 1.5 mg (1 mg to start, then 0.5 mg one hour later) at baseline and then 1 mg on day 1, or oral prednisone 30 mg at baseline and on day 1. The patients also received 1 g of systemic acetaminophen, and three 50-mg doses of tramadol during the first 24 hours.

Of the 111 patients randomized, 54 were assigned to receive prednisone, and 57 were assigned to receive colchicine. Baseline characteristics were similar between the groups, with a mean age of about 86 years, body mass index of around 25 kg/m², and blood pressure in the range of 130/69 mm Hg.

For nearly half of all patients in study each arm the most painful joint was the knee, followed by wrists and ankles.

There was no difference between the groups in the primary efficacy outcome of a change at 24 hours over baseline in visual analog scale (VAS) (0-100 mm) scores, either in a per-protocol analysis or modified intention-to-treat analysis. The mean change in VAS at 24 hours in the colchicine group was –36.6 mm, compared with –37.7 mm in the prednisone group. The investigators had previously determined that any difference between the two drugs of less than 13 mm on pain VAS at 24 hours would meet the definition for equivalent efficacy.

In both groups, a majority of patients had either an improvement greater than 50% in pain VAS scores and/or a pain VAS score less than 40 mm at both 24 and 48 hours.

At 7 days of follow-up, 21.8% of patients assigned to colchicine had diarrhea, compared with 5.6% of those assigned to prednisone. Adverse events occurring more frequently with prednisone included hyperglycemia, hypertension, and insomnia.

Patients who received colchicine and were also on statins had a trend toward a higher risk for diarrhea, but the study was not adequately powered to detect an association, and the trend was not statistically significant, Dr. Pascart said.

“Taken together, safety issues suggest that prednisone should be considered as the first-line therapy in acute CPP crystal arthritis. Future research is warranted to determine factors increasing the risk of colchicine-induced diarrhea,” he concluded.
 

Both drugs are used

Sara K. Tedeschi, MD, from Brigham & Women’s Hospital in Boston, who attended the session where the data were presented, has a special clinical interest in CPP deposition disease. She applauded Dr. Pascart and colleagues for conducting a rare clinical trial in CPP crystal arthritis.

In an interview, she said that the study suggests “we can keep in mind shorter courses of treatment for acute CPP crystal arthritis; I think that’s one big takeaway from this study.”

Asked whether she would change her practice based on the findings, Dr. Tedeschi replied: “I personally am not sure that I would be moved to use prednisone more than colchicine; I actually take away from this that colchicine is equivalent to prednisone for short-term use for CPP arthritis, but I think it’s also really important to note that this is in the context of quite a lot of acetaminophen and quite a lot of tramadol, and frankly I don’t usually use tramadol with my patients, but I might consider doing that, especially as there were no delirium events in this population.”

Dr. Tedeschi was not involved in the study.

Asked the same question, Michael Toprover, MD, from New York University Langone Medical Center, a moderator of the session who was not involved in the study, said: “I usually use a combination of medications. I generally, in someone who is hospitalized in particular and is in such severe pain, use a combination of colchicine and prednisone, unless I’m worried about infection, in which case I’ll start colchicine until we’ve proven that it’s CPPD, and then I’ll add prednisone.”

The study was funded by PHRC-1 GIRCI Nord Ouest, a clinical research program funded by the Ministry of Health in France. Dr. Pascart, Dr. Tedeschi, and Dr. Toprover all reported having no relevant conflicts of interest.

PHILADELPHIA – Prednisone appears to have the edge over colchicine for control of pain in patients with acute calcium pyrophosphate (CPP) crystal arthritis, an intensely painful rheumatic disease primarily affecting older patients.

Among 111 patients with acute CPP crystal arthritis randomized to receive either prednisone or colchicine for control of acute pain in a multicenter study, 2 days of therapy with the oral agents provided equivalent pain relief on the second day, and patients generally tolerated each agent well, reported Tristan Pascart, MD, from the Groupement Hospitalier de l’Institut Catholique de Lille (France).

Neil Osterweil/MDedge News

“Almost three-fourths of patients are considered to be good responders to both drugs on day 3, and, maybe, safety is the key issue distinguishing the two treatments: Colchicine was generally well tolerated, but even with this very short time frame of treatment, one patient out of five had diarrhea, which is more of a concern in this elderly population at risk of dehydration,” he said in an oral abstract session at the annual meeting of the American College of Rheumatology.

In contrast, only about 6% of patients assigned to prednisone had diarrhea, and other adverse events that occurred more frequently with the corticosteroid, including hypertension, hyperglycemia, and insomnia all resolved after the therapy was stopped.
 

Common and acutely painful

Acute CPP crystal arthritis is a common complication that often occurs during hospitalization for primarily nonrheumatologic causes, Dr. Pascart said, and “in the absence of clinical trials, the management relies on expert opinion, which stems from extrapolated data from gap studies” primarily with prednisone or colchicine, Dr. Pascart said.

To fill in the knowledge gap, Dr. Pascart and colleagues conducted the COLCHICORT study to evaluate whether the two drugs were comparable in efficacy and safety for control of acute pain in a vulnerable population.

The multicenter, open-label trial included patients older than age 65 years with an estimated glomerular filtration rate above 30 mL/min per 1.73 m² who presented with acute CPP deposition arthritis with symptoms occurring within the previous 36 hours. CPP arthritis was defined by the identification of CPP crystals on synovial fluid analysis or typical clinical presentation with evidence of chondrocalcinosis on x-rays or ultrasound.

Patients with a history of gout, cognitive decline that could impair pain assessment, or contraindications to either of the study drugs were excluded.

The participants were randomized to receive either colchicine 1.5 mg (1 mg to start, then 0.5 mg one hour later) at baseline and then 1 mg on day 1, or oral prednisone 30 mg at baseline and on day 1. The patients also received 1 g of systemic acetaminophen, and three 50-mg doses of tramadol during the first 24 hours.

Of the 111 patients randomized, 54 were assigned to receive prednisone, and 57 were assigned to receive colchicine. Baseline characteristics were similar between the groups, with a mean age of about 86 years, body mass index of around 25 kg/m², and blood pressure in the range of 130/69 mm Hg.

For nearly half of all patients in study each arm the most painful joint was the knee, followed by wrists and ankles.

There was no difference between the groups in the primary efficacy outcome of a change at 24 hours over baseline in visual analog scale (VAS) (0-100 mm) scores, either in a per-protocol analysis or modified intention-to-treat analysis. The mean change in VAS at 24 hours in the colchicine group was –36.6 mm, compared with –37.7 mm in the prednisone group. The investigators had previously determined that any difference between the two drugs of less than 13 mm on pain VAS at 24 hours would meet the definition for equivalent efficacy.

In both groups, a majority of patients had either an improvement greater than 50% in pain VAS scores and/or a pain VAS score less than 40 mm at both 24 and 48 hours.

At 7 days of follow-up, 21.8% of patients assigned to colchicine had diarrhea, compared with 5.6% of those assigned to prednisone. Adverse events occurring more frequently with prednisone included hyperglycemia, hypertension, and insomnia.

Patients who received colchicine and were also on statins had a trend toward a higher risk for diarrhea, but the study was not adequately powered to detect an association, and the trend was not statistically significant, Dr. Pascart said.

“Taken together, safety issues suggest that prednisone should be considered as the first-line therapy in acute CPP crystal arthritis. Future research is warranted to determine factors increasing the risk of colchicine-induced diarrhea,” he concluded.
 

Both drugs are used

Sara K. Tedeschi, MD, from Brigham & Women’s Hospital in Boston, who attended the session where the data were presented, has a special clinical interest in CPP deposition disease. She applauded Dr. Pascart and colleagues for conducting a rare clinical trial in CPP crystal arthritis.

In an interview, she said that the study suggests “we can keep in mind shorter courses of treatment for acute CPP crystal arthritis; I think that’s one big takeaway from this study.”

Asked whether she would change her practice based on the findings, Dr. Tedeschi replied: “I personally am not sure that I would be moved to use prednisone more than colchicine; I actually take away from this that colchicine is equivalent to prednisone for short-term use for CPP arthritis, but I think it’s also really important to note that this is in the context of quite a lot of acetaminophen and quite a lot of tramadol, and frankly I don’t usually use tramadol with my patients, but I might consider doing that, especially as there were no delirium events in this population.”

Dr. Tedeschi was not involved in the study.

Asked the same question, Michael Toprover, MD, from New York University Langone Medical Center, a moderator of the session who was not involved in the study, said: “I usually use a combination of medications. I generally, in someone who is hospitalized in particular and is in such severe pain, use a combination of colchicine and prednisone, unless I’m worried about infection, in which case I’ll start colchicine until we’ve proven that it’s CPPD, and then I’ll add prednisone.”

The study was funded by PHRC-1 GIRCI Nord Ouest, a clinical research program funded by the Ministry of Health in France. Dr. Pascart, Dr. Tedeschi, and Dr. Toprover all reported having no relevant conflicts of interest.

PHILADELPHIA – Women with spondyloarthritis (SpA) who are desiring pregnancy may want to consider decreasing use or discontinuing use (with supervision) of nonsteroidal anti-inflammatory drugs before conception, new data suggest.

Researchers have found a connection between NSAID use and age and a significantly longer time to conception among women with spondyloarthritis. Sabrina Hamroun, MMed, with the rheumatology department at the University Hospital Cochin, Paris, presented the findings during a press conference at the annual meeting of the American College of Rheumatology.

Subfertility group took an average of 16 months to get pregnant

Subfertility was observed in 40 (45.4%) of the women, with an average time to conception of 16.1 months. A woman was considered subfertile if her time to conception was more than 12 months or if she did not become pregnant.

The average preconception Bath Ankylosing Spondylitis Disease Activity Index score was 2.9 (+/- 2.1), the authors noted. The average age of the participants was 32 years.

Twenty-three patients were treated with NSAIDs, eight with corticosteroids, 12 with conventional synthetic disease-modifying antirheumatic drugs, and 61 with biologics.

Researchers adjusted for factors including age, body mass index, disease duration and severity, smoking, form of SpA (axial, peripheral, or both), and medication in the preconception period.

They found significant associations between longer time to conception and age (hazard ratio, 1.22; 95% confidence interval, 1.08-1.40; P < .001), and a much higher hazard ratio with the use of NSAIDs during preconception (HR, 3.01; 95% CI, 2.15-3.85; P = .01).

Some data unavailable

Ms. Hamroun acknowledged that no data were available on the frequency of sexual intercourse or quality of life, factors that could affect time to conception. Women were asked when they discontinued contraceptive use and actively began trying to become pregnant.

She stated that information on the dose of NSAIDs used by the patients was incomplete, noting, “We were therefore unable to adjust the results of our statistical analyses on the dose used by patients.”

Additionally, because the study participants were patients at tertiary centers in France and had more severe disease, the results may not be generalizable to all women of childbearing age. Patients with less severe SpA are often managed in outpatient settings in France, she said.

When asked about alternatives to NSAIDs, Ms. Hamroun said that anti–tumor necrosis factor agents with low placental passage may be a good alternative “if a woman with long-standing difficulties to conceive needs a regular use of NSAIDs to control disease activity, in the absence of any other cause of subfertility.”

The patient’s age must also be considered, she noted.

“A therapeutic switch may be favored in a woman over 35 years of age, for example, whose fertility is already impaired by age,” Ms. Hamroun said.

As for the mechanism that might explain the effects of NSAIDs on conception, Ms. Hamroun said that prostaglandins are essential to ovulation and embryo implantation and explained that NSAIDs may work against ovulation and result in poor implantation (miscarriage) by blocking prostaglandins.

She pointed out that her results are in line with the ACR’s recommendation to discontinue NSAID use during the preconception period in women with SpA who are having difficulty conceiving.
 

Control before conception is important

Sinead Maguire, MD, a clinical and research fellow in the Spondylitis Program at Toronto (Ont.) Western Hospital who was not part of the study, said the study highlights the importance of optimizing disease control before conception.

“There are a number of things rheumatologists can do to support our SpA patients when they are trying to conceive,” she told this news organization. “One of the most important issues to address is ensuring their SpA is in remission and continues to remain so. For that reason, if a woman is requiring regular NSAIDs for symptom control, the results of this study might encourage me to consider a biologic agent sooner to ensure remission.”

She urged women who want to become pregnant to discuss medications with their rheumatologist before trying to conceive.

“It is very exciting to see studies such as this so that rheumatologists can provide answers to our patients’ questions with evidence-based advice,” she said.

Ms. Hamroun and several coauthors had no disclosures. Other coauthors disclosed relationships with companies including Merck/MSD, Novartis, Janssen, AbbVie/Abbott, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Galapagos, Eli Lilly, Novartis, and/or UCB. Dr. Maguire reports no relevant financial relationships.

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

PHILADELPHIA – Women with spondyloarthritis (SpA) who are desiring pregnancy may want to consider decreasing use or discontinuing use (with supervision) of nonsteroidal anti-inflammatory drugs before conception, new data suggest.

Researchers have found a connection between NSAID use and age and a significantly longer time to conception among women with spondyloarthritis. Sabrina Hamroun, MMed, with the rheumatology department at the University Hospital Cochin, Paris, presented the findings during a press conference at the annual meeting of the American College of Rheumatology.

Subfertility group took an average of 16 months to get pregnant

Subfertility was observed in 40 (45.4%) of the women, with an average time to conception of 16.1 months. A woman was considered subfertile if her time to conception was more than 12 months or if she did not become pregnant.

The average preconception Bath Ankylosing Spondylitis Disease Activity Index score was 2.9 (+/- 2.1), the authors noted. The average age of the participants was 32 years.

Twenty-three patients were treated with NSAIDs, eight with corticosteroids, 12 with conventional synthetic disease-modifying antirheumatic drugs, and 61 with biologics.

Researchers adjusted for factors including age, body mass index, disease duration and severity, smoking, form of SpA (axial, peripheral, or both), and medication in the preconception period.

They found significant associations between longer time to conception and age (hazard ratio, 1.22; 95% confidence interval, 1.08-1.40; P < .001), and a much higher hazard ratio with the use of NSAIDs during preconception (HR, 3.01; 95% CI, 2.15-3.85; P = .01).

Some data unavailable

Ms. Hamroun acknowledged that no data were available on the frequency of sexual intercourse or quality of life, factors that could affect time to conception. Women were asked when they discontinued contraceptive use and actively began trying to become pregnant.

She stated that information on the dose of NSAIDs used by the patients was incomplete, noting, “We were therefore unable to adjust the results of our statistical analyses on the dose used by patients.”

Additionally, because the study participants were patients at tertiary centers in France and had more severe disease, the results may not be generalizable to all women of childbearing age. Patients with less severe SpA are often managed in outpatient settings in France, she said.

When asked about alternatives to NSAIDs, Ms. Hamroun said that anti–tumor necrosis factor agents with low placental passage may be a good alternative “if a woman with long-standing difficulties to conceive needs a regular use of NSAIDs to control disease activity, in the absence of any other cause of subfertility.”

The patient’s age must also be considered, she noted.

“A therapeutic switch may be favored in a woman over 35 years of age, for example, whose fertility is already impaired by age,” Ms. Hamroun said.

As for the mechanism that might explain the effects of NSAIDs on conception, Ms. Hamroun said that prostaglandins are essential to ovulation and embryo implantation and explained that NSAIDs may work against ovulation and result in poor implantation (miscarriage) by blocking prostaglandins.

She pointed out that her results are in line with the ACR’s recommendation to discontinue NSAID use during the preconception period in women with SpA who are having difficulty conceiving.
 

Control before conception is important

Sinead Maguire, MD, a clinical and research fellow in the Spondylitis Program at Toronto (Ont.) Western Hospital who was not part of the study, said the study highlights the importance of optimizing disease control before conception.

“There are a number of things rheumatologists can do to support our SpA patients when they are trying to conceive,” she told this news organization. “One of the most important issues to address is ensuring their SpA is in remission and continues to remain so. For that reason, if a woman is requiring regular NSAIDs for symptom control, the results of this study might encourage me to consider a biologic agent sooner to ensure remission.”

She urged women who want to become pregnant to discuss medications with their rheumatologist before trying to conceive.

“It is very exciting to see studies such as this so that rheumatologists can provide answers to our patients’ questions with evidence-based advice,” she said.

Ms. Hamroun and several coauthors had no disclosures. Other coauthors disclosed relationships with companies including Merck/MSD, Novartis, Janssen, AbbVie/Abbott, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Galapagos, Eli Lilly, Novartis, and/or UCB. Dr. Maguire reports no relevant financial relationships.

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

PHILADELPHIA – Women with spondyloarthritis (SpA) who are desiring pregnancy may want to consider decreasing use or discontinuing use (with supervision) of nonsteroidal anti-inflammatory drugs before conception, new data suggest.

Researchers have found a connection between NSAID use and age and a significantly longer time to conception among women with spondyloarthritis. Sabrina Hamroun, MMed, with the rheumatology department at the University Hospital Cochin, Paris, presented the findings during a press conference at the annual meeting of the American College of Rheumatology.

Subfertility group took an average of 16 months to get pregnant

Subfertility was observed in 40 (45.4%) of the women, with an average time to conception of 16.1 months. A woman was considered subfertile if her time to conception was more than 12 months or if she did not become pregnant.

The average preconception Bath Ankylosing Spondylitis Disease Activity Index score was 2.9 (+/- 2.1), the authors noted. The average age of the participants was 32 years.

Twenty-three patients were treated with NSAIDs, eight with corticosteroids, 12 with conventional synthetic disease-modifying antirheumatic drugs, and 61 with biologics.

Researchers adjusted for factors including age, body mass index, disease duration and severity, smoking, form of SpA (axial, peripheral, or both), and medication in the preconception period.

They found significant associations between longer time to conception and age (hazard ratio, 1.22; 95% confidence interval, 1.08-1.40; P < .001), and a much higher hazard ratio with the use of NSAIDs during preconception (HR, 3.01; 95% CI, 2.15-3.85; P = .01).

Some data unavailable

Ms. Hamroun acknowledged that no data were available on the frequency of sexual intercourse or quality of life, factors that could affect time to conception. Women were asked when they discontinued contraceptive use and actively began trying to become pregnant.

She stated that information on the dose of NSAIDs used by the patients was incomplete, noting, “We were therefore unable to adjust the results of our statistical analyses on the dose used by patients.”

Additionally, because the study participants were patients at tertiary centers in France and had more severe disease, the results may not be generalizable to all women of childbearing age. Patients with less severe SpA are often managed in outpatient settings in France, she said.

When asked about alternatives to NSAIDs, Ms. Hamroun said that anti–tumor necrosis factor agents with low placental passage may be a good alternative “if a woman with long-standing difficulties to conceive needs a regular use of NSAIDs to control disease activity, in the absence of any other cause of subfertility.”

The patient’s age must also be considered, she noted.

“A therapeutic switch may be favored in a woman over 35 years of age, for example, whose fertility is already impaired by age,” Ms. Hamroun said.

As for the mechanism that might explain the effects of NSAIDs on conception, Ms. Hamroun said that prostaglandins are essential to ovulation and embryo implantation and explained that NSAIDs may work against ovulation and result in poor implantation (miscarriage) by blocking prostaglandins.

She pointed out that her results are in line with the ACR’s recommendation to discontinue NSAID use during the preconception period in women with SpA who are having difficulty conceiving.
 

Control before conception is important

Sinead Maguire, MD, a clinical and research fellow in the Spondylitis Program at Toronto (Ont.) Western Hospital who was not part of the study, said the study highlights the importance of optimizing disease control before conception.

“There are a number of things rheumatologists can do to support our SpA patients when they are trying to conceive,” she told this news organization. “One of the most important issues to address is ensuring their SpA is in remission and continues to remain so. For that reason, if a woman is requiring regular NSAIDs for symptom control, the results of this study might encourage me to consider a biologic agent sooner to ensure remission.”

She urged women who want to become pregnant to discuss medications with their rheumatologist before trying to conceive.

“It is very exciting to see studies such as this so that rheumatologists can provide answers to our patients’ questions with evidence-based advice,” she said.

Ms. Hamroun and several coauthors had no disclosures. Other coauthors disclosed relationships with companies including Merck/MSD, Novartis, Janssen, AbbVie/Abbott, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Galapagos, Eli Lilly, Novartis, and/or UCB. Dr. Maguire reports no relevant financial relationships.

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

PHILADELPHIA – Combining the immunomodulatory agent mycophenolate with the antifibrotic pirfenidone led to more rapid improvement and showed a trend to be more effective than mycophenolate mofetil alone for treating the signs and symptoms of scleroderma-related interstitial lung disease, but the combination therapy came with an increase in side effects, according to results from the Scleroderma Lung Study III.

Dinesh Khanna, MBBS, MSc, of the University of Michigan, Ann Arbor, presented the results at the annual meeting of the American College of Rheumatology. He noted some problems with the study – namely its small size, enrolling only 51 patients, about one-third of its original goal. But he also said it showed a potential signal for efficacy and that the study itself could serve as a “template” for future studies of combination mycophenolate mofetil (MMF) plus pirfenidone therapy for scleroderma-related interstitial lung disease (SSc-ILD).

“The pirfenidone patients had quite a bit more GI side effects and photosensitivity, and those are known side effects,” Dr. Khanna said in an interview. “So the combination therapy had more side effects but trends to higher efficacy.”

The design of SLS-III, a phase 2 clinical trial, was a challenge, Dr. Khanna explained. The goal was to enroll 150 SSc-ILD patients who hadn’t had any previous treatment for their disease. Finding those patients proved difficult. “In fact, if you look at the recent history, 70% of the patients with early diffuse scleroderma are on MMF,” he said in his presentation. Compounding low study enrollment was the intervening COVID-19 pandemic, he added.
 

Testing a faster-acting combination

Nonetheless, the trial managed to enroll 27 patients in the combination therapy group and 24 in the MMF-plus-placebo group and compared their outcomes over 18 months. Study dosing was 1,500 mg MMF twice daily and pirfenidone 801 mg three times daily, titrated to the tolerable dose.

Despite the study’s being underpowered, Dr. Khanna said, it still reported some notable outcomes that merit further investigation. “I think what was intriguing in the study was the long-term benefit in the patient-reported outcomes and the structural changes,” he said in the interview.

Among those notable outcomes was a clinically significant change in forced vital capacity (FVC) percentage for the combination vs. the placebo groups: 2.24% vs. 2.09%. He also noted that the combination group saw a somewhat more robust improvement in FVC at six months: 2.59% (± 0.98%) vs. 0.92% (± 1.1%) in the placebo group.

The combination group showed greater improvements in high-resolution computed tomography-evaluated lung involvement and lung fibrosis and patient-reported outcomes, including a statistically significant 3.67-point greater improvement in PROMIS-29 physical function score (4.42 vs. 0.75).

The patients on combination therapy had higher rates of serious adverse events (SAEs), and seven discontinued one or both study drugs early, all in the combined arm. Four combination therapy patients had six SAEs, compared to two placebo patients with three SAEs. In the combination group, SAEs included chest pain, herpes zoster ophthalmicus, nodular basal cell cancer, marginal zone B cell lymphoma, renal crisis, and dyspnea. SAEs in the placebo group were colitis, COVID-19 and hypoxic respiratory failure.

Study design challenges

Nonetheless, Dr. Khanna said the SLS-III data are consistent with the SLS-II findings, with mean improvements in FVC of 2.24% and 2.1%, respectively.

“The next study may be able to replicate what we tried to do, keeping in mind that there are really no MMF-naive patients who are walking around,” Dr. Khanna said. “So the challenge is about the feasibility of recruiting within a trial vs. trying to show a statistical difference between the drug and placebo.”

This study could serve as a foundation for future studies of MMF in patients with SSc-ILD, Robert Spiera, MD, of the Hospital for Special Surgery in New York, said in an interview. “There are lessons to be learned both from the study but also from prior studies looking at MMF use in the background in patients treated with other drugs in clinical trials,” he said.

Dr. Spiera noted that the study had other challenges besides the difficulty in recruiting patients who hadn’t been on MMF therapy. “A great challenge is that the benefit with regard to the impact on the lungs from MMF seems most prominent in the first 6 months to a year to even 2 years that somebody is on the drug,” he said.

The other challenge with this study is that a large proportion of patients had limited systemic disease and relatively lower levels of skin disease compared with other studies of patients on MMF, Dr. Spiera said.

“The optimal treatment of scleroderma-associated lung disease remains a very important and not-adequately met need,” he said. “Particularly, we’re looking for drugs that are tolerable in a patient population that are very prone to GI side effects in general. This study and others have taught us a lot about trial design, and I think more globally this will allow us to move this field forward.”

Dr. Khanna disclosed relationships with Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Horizon Therapeutics USA, Janssen Global Services, Prometheus Biosciences, Mitsubishi Tanabe Pharma Corp., Genentech/Roche, Theraly, and Pfizer. Genentech provided funding for the study and pirfenidone and placebo drugs at no cost.

Dr. Spiera disclosed relationships with GlaxoSmithKline, Boehringer-Ingelheim, Corbus Pharmaceutical, InflaRx, AbbVie/Abbott, Sanofi, Novartis, Chemocentryx, Roche and Vera.

PHILADELPHIA – Combining the immunomodulatory agent mycophenolate with the antifibrotic pirfenidone led to more rapid improvement and showed a trend to be more effective than mycophenolate mofetil alone for treating the signs and symptoms of scleroderma-related interstitial lung disease, but the combination therapy came with an increase in side effects, according to results from the Scleroderma Lung Study III.

Dinesh Khanna, MBBS, MSc, of the University of Michigan, Ann Arbor, presented the results at the annual meeting of the American College of Rheumatology. He noted some problems with the study – namely its small size, enrolling only 51 patients, about one-third of its original goal. But he also said it showed a potential signal for efficacy and that the study itself could serve as a “template” for future studies of combination mycophenolate mofetil (MMF) plus pirfenidone therapy for scleroderma-related interstitial lung disease (SSc-ILD).

“The pirfenidone patients had quite a bit more GI side effects and photosensitivity, and those are known side effects,” Dr. Khanna said in an interview. “So the combination therapy had more side effects but trends to higher efficacy.”

The design of SLS-III, a phase 2 clinical trial, was a challenge, Dr. Khanna explained. The goal was to enroll 150 SSc-ILD patients who hadn’t had any previous treatment for their disease. Finding those patients proved difficult. “In fact, if you look at the recent history, 70% of the patients with early diffuse scleroderma are on MMF,” he said in his presentation. Compounding low study enrollment was the intervening COVID-19 pandemic, he added.
 

Testing a faster-acting combination

Nonetheless, the trial managed to enroll 27 patients in the combination therapy group and 24 in the MMF-plus-placebo group and compared their outcomes over 18 months. Study dosing was 1,500 mg MMF twice daily and pirfenidone 801 mg three times daily, titrated to the tolerable dose.

Despite the study’s being underpowered, Dr. Khanna said, it still reported some notable outcomes that merit further investigation. “I think what was intriguing in the study was the long-term benefit in the patient-reported outcomes and the structural changes,” he said in the interview.

Among those notable outcomes was a clinically significant change in forced vital capacity (FVC) percentage for the combination vs. the placebo groups: 2.24% vs. 2.09%. He also noted that the combination group saw a somewhat more robust improvement in FVC at six months: 2.59% (± 0.98%) vs. 0.92% (± 1.1%) in the placebo group.

The combination group showed greater improvements in high-resolution computed tomography-evaluated lung involvement and lung fibrosis and patient-reported outcomes, including a statistically significant 3.67-point greater improvement in PROMIS-29 physical function score (4.42 vs. 0.75).

The patients on combination therapy had higher rates of serious adverse events (SAEs), and seven discontinued one or both study drugs early, all in the combined arm. Four combination therapy patients had six SAEs, compared to two placebo patients with three SAEs. In the combination group, SAEs included chest pain, herpes zoster ophthalmicus, nodular basal cell cancer, marginal zone B cell lymphoma, renal crisis, and dyspnea. SAEs in the placebo group were colitis, COVID-19 and hypoxic respiratory failure.

Study design challenges

Nonetheless, Dr. Khanna said the SLS-III data are consistent with the SLS-II findings, with mean improvements in FVC of 2.24% and 2.1%, respectively.

“The next study may be able to replicate what we tried to do, keeping in mind that there are really no MMF-naive patients who are walking around,” Dr. Khanna said. “So the challenge is about the feasibility of recruiting within a trial vs. trying to show a statistical difference between the drug and placebo.”

This study could serve as a foundation for future studies of MMF in patients with SSc-ILD, Robert Spiera, MD, of the Hospital for Special Surgery in New York, said in an interview. “There are lessons to be learned both from the study but also from prior studies looking at MMF use in the background in patients treated with other drugs in clinical trials,” he said.

Dr. Spiera noted that the study had other challenges besides the difficulty in recruiting patients who hadn’t been on MMF therapy. “A great challenge is that the benefit with regard to the impact on the lungs from MMF seems most prominent in the first 6 months to a year to even 2 years that somebody is on the drug,” he said.

The other challenge with this study is that a large proportion of patients had limited systemic disease and relatively lower levels of skin disease compared with other studies of patients on MMF, Dr. Spiera said.

“The optimal treatment of scleroderma-associated lung disease remains a very important and not-adequately met need,” he said. “Particularly, we’re looking for drugs that are tolerable in a patient population that are very prone to GI side effects in general. This study and others have taught us a lot about trial design, and I think more globally this will allow us to move this field forward.”

Dr. Khanna disclosed relationships with Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Horizon Therapeutics USA, Janssen Global Services, Prometheus Biosciences, Mitsubishi Tanabe Pharma Corp., Genentech/Roche, Theraly, and Pfizer. Genentech provided funding for the study and pirfenidone and placebo drugs at no cost.

Dr. Spiera disclosed relationships with GlaxoSmithKline, Boehringer-Ingelheim, Corbus Pharmaceutical, InflaRx, AbbVie/Abbott, Sanofi, Novartis, Chemocentryx, Roche and Vera.

PHILADELPHIA – Combining the immunomodulatory agent mycophenolate with the antifibrotic pirfenidone led to more rapid improvement and showed a trend to be more effective than mycophenolate mofetil alone for treating the signs and symptoms of scleroderma-related interstitial lung disease, but the combination therapy came with an increase in side effects, according to results from the Scleroderma Lung Study III.

Dinesh Khanna, MBBS, MSc, of the University of Michigan, Ann Arbor, presented the results at the annual meeting of the American College of Rheumatology. He noted some problems with the study – namely its small size, enrolling only 51 patients, about one-third of its original goal. But he also said it showed a potential signal for efficacy and that the study itself could serve as a “template” for future studies of combination mycophenolate mofetil (MMF) plus pirfenidone therapy for scleroderma-related interstitial lung disease (SSc-ILD).

“The pirfenidone patients had quite a bit more GI side effects and photosensitivity, and those are known side effects,” Dr. Khanna said in an interview. “So the combination therapy had more side effects but trends to higher efficacy.”

The design of SLS-III, a phase 2 clinical trial, was a challenge, Dr. Khanna explained. The goal was to enroll 150 SSc-ILD patients who hadn’t had any previous treatment for their disease. Finding those patients proved difficult. “In fact, if you look at the recent history, 70% of the patients with early diffuse scleroderma are on MMF,” he said in his presentation. Compounding low study enrollment was the intervening COVID-19 pandemic, he added.
 

Testing a faster-acting combination

Nonetheless, the trial managed to enroll 27 patients in the combination therapy group and 24 in the MMF-plus-placebo group and compared their outcomes over 18 months. Study dosing was 1,500 mg MMF twice daily and pirfenidone 801 mg three times daily, titrated to the tolerable dose.

Despite the study’s being underpowered, Dr. Khanna said, it still reported some notable outcomes that merit further investigation. “I think what was intriguing in the study was the long-term benefit in the patient-reported outcomes and the structural changes,” he said in the interview.

Among those notable outcomes was a clinically significant change in forced vital capacity (FVC) percentage for the combination vs. the placebo groups: 2.24% vs. 2.09%. He also noted that the combination group saw a somewhat more robust improvement in FVC at six months: 2.59% (± 0.98%) vs. 0.92% (± 1.1%) in the placebo group.

The combination group showed greater improvements in high-resolution computed tomography-evaluated lung involvement and lung fibrosis and patient-reported outcomes, including a statistically significant 3.67-point greater improvement in PROMIS-29 physical function score (4.42 vs. 0.75).

The patients on combination therapy had higher rates of serious adverse events (SAEs), and seven discontinued one or both study drugs early, all in the combined arm. Four combination therapy patients had six SAEs, compared to two placebo patients with three SAEs. In the combination group, SAEs included chest pain, herpes zoster ophthalmicus, nodular basal cell cancer, marginal zone B cell lymphoma, renal crisis, and dyspnea. SAEs in the placebo group were colitis, COVID-19 and hypoxic respiratory failure.

Study design challenges

Nonetheless, Dr. Khanna said the SLS-III data are consistent with the SLS-II findings, with mean improvements in FVC of 2.24% and 2.1%, respectively.

“The next study may be able to replicate what we tried to do, keeping in mind that there are really no MMF-naive patients who are walking around,” Dr. Khanna said. “So the challenge is about the feasibility of recruiting within a trial vs. trying to show a statistical difference between the drug and placebo.”

This study could serve as a foundation for future studies of MMF in patients with SSc-ILD, Robert Spiera, MD, of the Hospital for Special Surgery in New York, said in an interview. “There are lessons to be learned both from the study but also from prior studies looking at MMF use in the background in patients treated with other drugs in clinical trials,” he said.

Dr. Spiera noted that the study had other challenges besides the difficulty in recruiting patients who hadn’t been on MMF therapy. “A great challenge is that the benefit with regard to the impact on the lungs from MMF seems most prominent in the first 6 months to a year to even 2 years that somebody is on the drug,” he said.

The other challenge with this study is that a large proportion of patients had limited systemic disease and relatively lower levels of skin disease compared with other studies of patients on MMF, Dr. Spiera said.

“The optimal treatment of scleroderma-associated lung disease remains a very important and not-adequately met need,” he said. “Particularly, we’re looking for drugs that are tolerable in a patient population that are very prone to GI side effects in general. This study and others have taught us a lot about trial design, and I think more globally this will allow us to move this field forward.”

Dr. Khanna disclosed relationships with Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Horizon Therapeutics USA, Janssen Global Services, Prometheus Biosciences, Mitsubishi Tanabe Pharma Corp., Genentech/Roche, Theraly, and Pfizer. Genentech provided funding for the study and pirfenidone and placebo drugs at no cost.

Dr. Spiera disclosed relationships with GlaxoSmithKline, Boehringer-Ingelheim, Corbus Pharmaceutical, InflaRx, AbbVie/Abbott, Sanofi, Novartis, Chemocentryx, Roche and Vera.

In my last column, I discussed blogging as a great way to capture the attention of anyone interested in your practice, especially prospective patients. If you are already blogging – or would like to consider a less crowded and competitive activity – podcasting might be the answer. At this writing (November 2022), more than 600 million blogs are online, compared with about 2 million podcasts, and relatively few of them are run by physicians. With podcasts, you have a better chance of standing out in a crowded online world.

Starting a podcast is not difficult, but there are several steps you need to go through before launching one.

As with blogging, start by outlining a long-range plan. Your general topic will probably be your specialty, but you will need to narrow your focus to a few specific subjects, such as the problems you see most often, or a subspecialty that you concentrate on. You can always expand your topic later, as you get more popular. Choose a name for your podcast, and purchase a domain name that accurately describes it.

You will also need to choose a hosting service. Numerous inexpensive hosting platforms are available, and a simple Google search will find them for you. Many of them provide free learning materials, helpful creative tools, and customer support to get you through the confusing technical aspects. They can also help you choose a music introduction (to add a bit of polish), and help you piece together your audio segments. Buzzsprout, RSS.com, and Podbean get good reviews on many sites. (As always, I have no financial interest in any company or service mentioned herein.)

Hosting services can assist you in creating a template – a framework that you can reuse each time you record an episode – containing your intro and exit music, tracks for your conversations, etc. This will make your podcasts instantly recognizable each time your listeners tune in.

Many podcasting experts recommend recruiting a co-host. This can be an associate within your practice, a friend who practices elsewhere, or perhaps a resident in an academic setting. You will be able to spread the workload of creating, editing, and promoting. Plus, it is much easier to generate interesting content when two people are having a conversation, rather than one person lecturing from a prepared script. You might also consider having multiple co-hosts, either to expand episodes into group discussions, or to take turns working with you in covering different subjects.

How long you make your podcast is entirely up to you. Some consultants recommend specific time frames, such as 5 minutes (because that’s an average attention span), or 28 minutes (because that’s the average driving commute time). There are short podcasts and long ones; whatever works for you is fine, as long as you don’t drift off the topic. Furthermore, no one says they must all be the same length; when you are finished talking, you are done. And no one says you must stick with one subject throughout. Combining several short segments might hold more listeners’ interest and will make it easier to share small clips on social media.

Content guidelines are similar to those for blogs. Give people content that will be of interest or benefit to them. Talk about subjects – medical and otherwise – that are relevant to your practice or are prominent in the news.

As with blogs, try to avoid polarizing political discussions, and while it’s fine to discuss treatments and procedures that you offer, aggressive solicitation tends to make viewers look elsewhere. Keep any medical advice in general terms; don’t portray any specific patients as examples.

When your podcast is ready, your hosting platform will show you how to submit it to iTunes, and how to submit your podcast RSS feed to other podcast directories. As you upload new episodes, your host will automatically update your RSS feed, so that any directory you are listed on will receive the new episode.

Once you are uploaded, you can use your host’s social sharing tools to spread the word. As with blogs, use social media, such as your practice’s Facebook page, to push podcast updates into patients’ feeds and track relevant Twitter hashtags to find online communities that might be interested in your subject matter. You should also find your episode embed code (which your host will have) and place it in a prominent place on your website so patients can listen directly from there.

Transcriptions are another excellent promotional tool. Search engines will “read” your podcasts and list them in searches. Some podcast hosts will do transcribing for a fee, but there are independent transcription services as well.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

In my last column, I discussed blogging as a great way to capture the attention of anyone interested in your practice, especially prospective patients. If you are already blogging – or would like to consider a less crowded and competitive activity – podcasting might be the answer. At this writing (November 2022), more than 600 million blogs are online, compared with about 2 million podcasts, and relatively few of them are run by physicians. With podcasts, you have a better chance of standing out in a crowded online world.

Starting a podcast is not difficult, but there are several steps you need to go through before launching one.

As with blogging, start by outlining a long-range plan. Your general topic will probably be your specialty, but you will need to narrow your focus to a few specific subjects, such as the problems you see most often, or a subspecialty that you concentrate on. You can always expand your topic later, as you get more popular. Choose a name for your podcast, and purchase a domain name that accurately describes it.

You will also need to choose a hosting service. Numerous inexpensive hosting platforms are available, and a simple Google search will find them for you. Many of them provide free learning materials, helpful creative tools, and customer support to get you through the confusing technical aspects. They can also help you choose a music introduction (to add a bit of polish), and help you piece together your audio segments. Buzzsprout, RSS.com, and Podbean get good reviews on many sites. (As always, I have no financial interest in any company or service mentioned herein.)

Hosting services can assist you in creating a template – a framework that you can reuse each time you record an episode – containing your intro and exit music, tracks for your conversations, etc. This will make your podcasts instantly recognizable each time your listeners tune in.

Many podcasting experts recommend recruiting a co-host. This can be an associate within your practice, a friend who practices elsewhere, or perhaps a resident in an academic setting. You will be able to spread the workload of creating, editing, and promoting. Plus, it is much easier to generate interesting content when two people are having a conversation, rather than one person lecturing from a prepared script. You might also consider having multiple co-hosts, either to expand episodes into group discussions, or to take turns working with you in covering different subjects.

How long you make your podcast is entirely up to you. Some consultants recommend specific time frames, such as 5 minutes (because that’s an average attention span), or 28 minutes (because that’s the average driving commute time). There are short podcasts and long ones; whatever works for you is fine, as long as you don’t drift off the topic. Furthermore, no one says they must all be the same length; when you are finished talking, you are done. And no one says you must stick with one subject throughout. Combining several short segments might hold more listeners’ interest and will make it easier to share small clips on social media.

Content guidelines are similar to those for blogs. Give people content that will be of interest or benefit to them. Talk about subjects – medical and otherwise – that are relevant to your practice or are prominent in the news.

As with blogs, try to avoid polarizing political discussions, and while it’s fine to discuss treatments and procedures that you offer, aggressive solicitation tends to make viewers look elsewhere. Keep any medical advice in general terms; don’t portray any specific patients as examples.

When your podcast is ready, your hosting platform will show you how to submit it to iTunes, and how to submit your podcast RSS feed to other podcast directories. As you upload new episodes, your host will automatically update your RSS feed, so that any directory you are listed on will receive the new episode.

Once you are uploaded, you can use your host’s social sharing tools to spread the word. As with blogs, use social media, such as your practice’s Facebook page, to push podcast updates into patients’ feeds and track relevant Twitter hashtags to find online communities that might be interested in your subject matter. You should also find your episode embed code (which your host will have) and place it in a prominent place on your website so patients can listen directly from there.

Transcriptions are another excellent promotional tool. Search engines will “read” your podcasts and list them in searches. Some podcast hosts will do transcribing for a fee, but there are independent transcription services as well.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

In my last column, I discussed blogging as a great way to capture the attention of anyone interested in your practice, especially prospective patients. If you are already blogging – or would like to consider a less crowded and competitive activity – podcasting might be the answer. At this writing (November 2022), more than 600 million blogs are online, compared with about 2 million podcasts, and relatively few of them are run by physicians. With podcasts, you have a better chance of standing out in a crowded online world.

Starting a podcast is not difficult, but there are several steps you need to go through before launching one.

As with blogging, start by outlining a long-range plan. Your general topic will probably be your specialty, but you will need to narrow your focus to a few specific subjects, such as the problems you see most often, or a subspecialty that you concentrate on. You can always expand your topic later, as you get more popular. Choose a name for your podcast, and purchase a domain name that accurately describes it.

You will also need to choose a hosting service. Numerous inexpensive hosting platforms are available, and a simple Google search will find them for you. Many of them provide free learning materials, helpful creative tools, and customer support to get you through the confusing technical aspects. They can also help you choose a music introduction (to add a bit of polish), and help you piece together your audio segments. Buzzsprout, RSS.com, and Podbean get good reviews on many sites. (As always, I have no financial interest in any company or service mentioned herein.)

Hosting services can assist you in creating a template – a framework that you can reuse each time you record an episode – containing your intro and exit music, tracks for your conversations, etc. This will make your podcasts instantly recognizable each time your listeners tune in.

Many podcasting experts recommend recruiting a co-host. This can be an associate within your practice, a friend who practices elsewhere, or perhaps a resident in an academic setting. You will be able to spread the workload of creating, editing, and promoting. Plus, it is much easier to generate interesting content when two people are having a conversation, rather than one person lecturing from a prepared script. You might also consider having multiple co-hosts, either to expand episodes into group discussions, or to take turns working with you in covering different subjects.

How long you make your podcast is entirely up to you. Some consultants recommend specific time frames, such as 5 minutes (because that’s an average attention span), or 28 minutes (because that’s the average driving commute time). There are short podcasts and long ones; whatever works for you is fine, as long as you don’t drift off the topic. Furthermore, no one says they must all be the same length; when you are finished talking, you are done. And no one says you must stick with one subject throughout. Combining several short segments might hold more listeners’ interest and will make it easier to share small clips on social media.

Content guidelines are similar to those for blogs. Give people content that will be of interest or benefit to them. Talk about subjects – medical and otherwise – that are relevant to your practice or are prominent in the news.

As with blogs, try to avoid polarizing political discussions, and while it’s fine to discuss treatments and procedures that you offer, aggressive solicitation tends to make viewers look elsewhere. Keep any medical advice in general terms; don’t portray any specific patients as examples.

When your podcast is ready, your hosting platform will show you how to submit it to iTunes, and how to submit your podcast RSS feed to other podcast directories. As you upload new episodes, your host will automatically update your RSS feed, so that any directory you are listed on will receive the new episode.

Once you are uploaded, you can use your host’s social sharing tools to spread the word. As with blogs, use social media, such as your practice’s Facebook page, to push podcast updates into patients’ feeds and track relevant Twitter hashtags to find online communities that might be interested in your subject matter. You should also find your episode embed code (which your host will have) and place it in a prominent place on your website so patients can listen directly from there.

Transcriptions are another excellent promotional tool. Search engines will “read” your podcasts and list them in searches. Some podcast hosts will do transcribing for a fee, but there are independent transcription services as well.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

PHILADELPHIA – Aggressive therapy using conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in combination with biologic agents early, soon after a child is diagnosed with polyarticular juvenile idiopathic arthritis (pJIA), enabled more patients to achieve clinical remission and longer times in inactive disease than more conventional therapeutic approaches, 3-year results of prospective, observational study demonstrated.

The results of The Childhood Arthritis and Rheumatology Research Alliance STOP-JIA study, which Yukiko Kimura, MD, presented at the annual meeting of the American College of Rheumatology, showed early combination therapy had benefits, compared with other treatment strategies that were more evident at 3 years than at 1 year of study.

“The STOP-JIA study showed that, after 3 years, patients who started a biologic early on in combination with methotrexate spent more time in inactive disease and achieved clinical remission more often when compared to those started on traditional step-up therapy,” Dr. Kimura, chief of pediatric rheumatology at Hackensack (N.J.) Meridian Health and professor of pediatrics at the Hackensack Meridian School of Medicine, said at a press conference. “This study shows that the treatment of poly-JIA patients receive initially very early on in their disease matters even 3 years after that treatment was started.”

The study compared three CARRA consensus treatment plans (CTP) for untreated pediatric pJIA patients: step-up (SU) – starting conventional synthetic DMARD therapy and adding a biologic if needed after 3 or more months; early-combination (EC) therapy – starting synthetic and biologic DMARDs together; and biologic first (BF) therapy – starting biologic DMARD monotherapy.

Dr. Kimura explained the rationale for the study. “Since biologic treatments were introduced more than 20 years ago, the prognosis for JIA significantly improved. These very effective medicines often work wonders, quickly reducing pain and inflammation in joint disease activity,” she said in the press conference. “What is not known, however, is when is the best time to start these very effective treatments.”

The most common approach is to start with a synthetic DMARD, typically methotrexate, and wait before starting a biologic, Dr. Kimura said.

“But even though methotrexate can work very well by itself, it does not work for every patient, and we don’t know whether waiting months for it to work and then starting a biologic might potentially lessen their effectiveness,” Dr. Kimura added. “We don’t know if there’s a window of opportunity that’s lost while waiting to see whether methotrexate will work.”

The study originally enrolled 400 patients, 297 of whom completed the 3-year visit – 190 in SU, 76 in EC and 31 in BF. At 12 months, the study found no statistically significant difference in clinically inactive disease (CID) between the groups, Dr. Kimura said.

Even at the 3-year visit, the percentage of patients in CID off glucocorticoids and clinical Juvenile Arthritis Disease Activity Score based on 10 joints inactive disease (cJADAS 10 ID) did not differ among the three groups, Dr. Kimura said in presenting the results. “But,” she added, “greater proportions of early-combination CTP group were able to achieve clinical remissions and spend more time with inactive disease in both CID and cJADAS 10.”

A closer look at the outcomes showed some separation between early-combination therapy and the other two treatment plans. The incidence of clinical remission (at any time point over 36 months) was 67.1% in the EC group vs. 49.1% and 47.3%, respectively, in the BF and SU groups, Dr. Kimura said. “The difference between the early-combination and step-up groups was highly significant [P = .007],” she added.

EC also had an edge in the percentage of time patients spent in CID (over 36 months): 39.2% versus 32% and 27.4%, respectively, in the BF and SU groups (P = .006 for EV vs. SU), as well as cJADAS 10 ID (50.6% in EC group vs. 42.8% and 37.5%, respectively in the BF and SU groups; P = .005 for EC vs. SU).

Dr. Kimura said that the STOP JIA trial will continue with longer-term analysis and ongoing monitoring of study patients through the CARRA registry. “These longer-term analyses and readouts will be important because even though the results at 12 months didn’t seem as definitive, it seems the longer we go, the more impact we see of the treatments that were started early on in this disease.”

The findings from this study are “significantly important,” Nina T. Washington, MD, MPH, a pediatric rheumatologist at the University of New Mexico Hospital, Albuquerque, and the Mary Bridge Children’s Hospital in Tacoma, Wash., said in an interview. “At least for the past decade we’ve really been advocating towards earlier and aggressive therapy, and that’s what this study shows: the sooner you can treat this disease, the sooner you can attack those joints that are inflamed, the better outcome you give the patient.”

The study also confirms that pediatric rheumatologists are not overtreating patients with pJIA, she added.

“In a sense we’re actually treating and preventing and if you have a child that has arthritis, it’s okay to treat that child,” Dr. Washington said. “For me that’s the most reassuring thing: that I’m not necessarily going overboard. If I have a child with polyarticular JIA and they have multiple inflamed joints and I have the evidence as they’re sitting in front of me, and I treat them. I’m going to give them the best outcome.”

The Patient Centered Outcomes Research Institute provided study funding. Dr. Kimura is chair of the CARRA JIA disease research committee and cochair of the CARRA Registry and Research Oversight Committee. She disclosed a financial relationship with Genentech. Dr. Washington has no relevant relationships to disclose.
 

PHILADELPHIA – Aggressive therapy using conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in combination with biologic agents early, soon after a child is diagnosed with polyarticular juvenile idiopathic arthritis (pJIA), enabled more patients to achieve clinical remission and longer times in inactive disease than more conventional therapeutic approaches, 3-year results of prospective, observational study demonstrated.

The results of The Childhood Arthritis and Rheumatology Research Alliance STOP-JIA study, which Yukiko Kimura, MD, presented at the annual meeting of the American College of Rheumatology, showed early combination therapy had benefits, compared with other treatment strategies that were more evident at 3 years than at 1 year of study.

“The STOP-JIA study showed that, after 3 years, patients who started a biologic early on in combination with methotrexate spent more time in inactive disease and achieved clinical remission more often when compared to those started on traditional step-up therapy,” Dr. Kimura, chief of pediatric rheumatology at Hackensack (N.J.) Meridian Health and professor of pediatrics at the Hackensack Meridian School of Medicine, said at a press conference. “This study shows that the treatment of poly-JIA patients receive initially very early on in their disease matters even 3 years after that treatment was started.”

The study compared three CARRA consensus treatment plans (CTP) for untreated pediatric pJIA patients: step-up (SU) – starting conventional synthetic DMARD therapy and adding a biologic if needed after 3 or more months; early-combination (EC) therapy – starting synthetic and biologic DMARDs together; and biologic first (BF) therapy – starting biologic DMARD monotherapy.

Dr. Kimura explained the rationale for the study. “Since biologic treatments were introduced more than 20 years ago, the prognosis for JIA significantly improved. These very effective medicines often work wonders, quickly reducing pain and inflammation in joint disease activity,” she said in the press conference. “What is not known, however, is when is the best time to start these very effective treatments.”

The most common approach is to start with a synthetic DMARD, typically methotrexate, and wait before starting a biologic, Dr. Kimura said.

“But even though methotrexate can work very well by itself, it does not work for every patient, and we don’t know whether waiting months for it to work and then starting a biologic might potentially lessen their effectiveness,” Dr. Kimura added. “We don’t know if there’s a window of opportunity that’s lost while waiting to see whether methotrexate will work.”

The study originally enrolled 400 patients, 297 of whom completed the 3-year visit – 190 in SU, 76 in EC and 31 in BF. At 12 months, the study found no statistically significant difference in clinically inactive disease (CID) between the groups, Dr. Kimura said.

Even at the 3-year visit, the percentage of patients in CID off glucocorticoids and clinical Juvenile Arthritis Disease Activity Score based on 10 joints inactive disease (cJADAS 10 ID) did not differ among the three groups, Dr. Kimura said in presenting the results. “But,” she added, “greater proportions of early-combination CTP group were able to achieve clinical remissions and spend more time with inactive disease in both CID and cJADAS 10.”

A closer look at the outcomes showed some separation between early-combination therapy and the other two treatment plans. The incidence of clinical remission (at any time point over 36 months) was 67.1% in the EC group vs. 49.1% and 47.3%, respectively, in the BF and SU groups, Dr. Kimura said. “The difference between the early-combination and step-up groups was highly significant [P = .007],” she added.

EC also had an edge in the percentage of time patients spent in CID (over 36 months): 39.2% versus 32% and 27.4%, respectively, in the BF and SU groups (P = .006 for EV vs. SU), as well as cJADAS 10 ID (50.6% in EC group vs. 42.8% and 37.5%, respectively in the BF and SU groups; P = .005 for EC vs. SU).

Dr. Kimura said that the STOP JIA trial will continue with longer-term analysis and ongoing monitoring of study patients through the CARRA registry. “These longer-term analyses and readouts will be important because even though the results at 12 months didn’t seem as definitive, it seems the longer we go, the more impact we see of the treatments that were started early on in this disease.”

The findings from this study are “significantly important,” Nina T. Washington, MD, MPH, a pediatric rheumatologist at the University of New Mexico Hospital, Albuquerque, and the Mary Bridge Children’s Hospital in Tacoma, Wash., said in an interview. “At least for the past decade we’ve really been advocating towards earlier and aggressive therapy, and that’s what this study shows: the sooner you can treat this disease, the sooner you can attack those joints that are inflamed, the better outcome you give the patient.”

The study also confirms that pediatric rheumatologists are not overtreating patients with pJIA, she added.

“In a sense we’re actually treating and preventing and if you have a child that has arthritis, it’s okay to treat that child,” Dr. Washington said. “For me that’s the most reassuring thing: that I’m not necessarily going overboard. If I have a child with polyarticular JIA and they have multiple inflamed joints and I have the evidence as they’re sitting in front of me, and I treat them. I’m going to give them the best outcome.”

The Patient Centered Outcomes Research Institute provided study funding. Dr. Kimura is chair of the CARRA JIA disease research committee and cochair of the CARRA Registry and Research Oversight Committee. She disclosed a financial relationship with Genentech. Dr. Washington has no relevant relationships to disclose.
 

PHILADELPHIA – Aggressive therapy using conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in combination with biologic agents early, soon after a child is diagnosed with polyarticular juvenile idiopathic arthritis (pJIA), enabled more patients to achieve clinical remission and longer times in inactive disease than more conventional therapeutic approaches, 3-year results of prospective, observational study demonstrated.

The results of The Childhood Arthritis and Rheumatology Research Alliance STOP-JIA study, which Yukiko Kimura, MD, presented at the annual meeting of the American College of Rheumatology, showed early combination therapy had benefits, compared with other treatment strategies that were more evident at 3 years than at 1 year of study.

“The STOP-JIA study showed that, after 3 years, patients who started a biologic early on in combination with methotrexate spent more time in inactive disease and achieved clinical remission more often when compared to those started on traditional step-up therapy,” Dr. Kimura, chief of pediatric rheumatology at Hackensack (N.J.) Meridian Health and professor of pediatrics at the Hackensack Meridian School of Medicine, said at a press conference. “This study shows that the treatment of poly-JIA patients receive initially very early on in their disease matters even 3 years after that treatment was started.”

The study compared three CARRA consensus treatment plans (CTP) for untreated pediatric pJIA patients: step-up (SU) – starting conventional synthetic DMARD therapy and adding a biologic if needed after 3 or more months; early-combination (EC) therapy – starting synthetic and biologic DMARDs together; and biologic first (BF) therapy – starting biologic DMARD monotherapy.

Dr. Kimura explained the rationale for the study. “Since biologic treatments were introduced more than 20 years ago, the prognosis for JIA significantly improved. These very effective medicines often work wonders, quickly reducing pain and inflammation in joint disease activity,” she said in the press conference. “What is not known, however, is when is the best time to start these very effective treatments.”

The most common approach is to start with a synthetic DMARD, typically methotrexate, and wait before starting a biologic, Dr. Kimura said.

“But even though methotrexate can work very well by itself, it does not work for every patient, and we don’t know whether waiting months for it to work and then starting a biologic might potentially lessen their effectiveness,” Dr. Kimura added. “We don’t know if there’s a window of opportunity that’s lost while waiting to see whether methotrexate will work.”

The study originally enrolled 400 patients, 297 of whom completed the 3-year visit – 190 in SU, 76 in EC and 31 in BF. At 12 months, the study found no statistically significant difference in clinically inactive disease (CID) between the groups, Dr. Kimura said.

Even at the 3-year visit, the percentage of patients in CID off glucocorticoids and clinical Juvenile Arthritis Disease Activity Score based on 10 joints inactive disease (cJADAS 10 ID) did not differ among the three groups, Dr. Kimura said in presenting the results. “But,” she added, “greater proportions of early-combination CTP group were able to achieve clinical remissions and spend more time with inactive disease in both CID and cJADAS 10.”

A closer look at the outcomes showed some separation between early-combination therapy and the other two treatment plans. The incidence of clinical remission (at any time point over 36 months) was 67.1% in the EC group vs. 49.1% and 47.3%, respectively, in the BF and SU groups, Dr. Kimura said. “The difference between the early-combination and step-up groups was highly significant [P = .007],” she added.

EC also had an edge in the percentage of time patients spent in CID (over 36 months): 39.2% versus 32% and 27.4%, respectively, in the BF and SU groups (P = .006 for EV vs. SU), as well as cJADAS 10 ID (50.6% in EC group vs. 42.8% and 37.5%, respectively in the BF and SU groups; P = .005 for EC vs. SU).

Dr. Kimura said that the STOP JIA trial will continue with longer-term analysis and ongoing monitoring of study patients through the CARRA registry. “These longer-term analyses and readouts will be important because even though the results at 12 months didn’t seem as definitive, it seems the longer we go, the more impact we see of the treatments that were started early on in this disease.”

The findings from this study are “significantly important,” Nina T. Washington, MD, MPH, a pediatric rheumatologist at the University of New Mexico Hospital, Albuquerque, and the Mary Bridge Children’s Hospital in Tacoma, Wash., said in an interview. “At least for the past decade we’ve really been advocating towards earlier and aggressive therapy, and that’s what this study shows: the sooner you can treat this disease, the sooner you can attack those joints that are inflamed, the better outcome you give the patient.”

The study also confirms that pediatric rheumatologists are not overtreating patients with pJIA, she added.

“In a sense we’re actually treating and preventing and if you have a child that has arthritis, it’s okay to treat that child,” Dr. Washington said. “For me that’s the most reassuring thing: that I’m not necessarily going overboard. If I have a child with polyarticular JIA and they have multiple inflamed joints and I have the evidence as they’re sitting in front of me, and I treat them. I’m going to give them the best outcome.”

The Patient Centered Outcomes Research Institute provided study funding. Dr. Kimura is chair of the CARRA JIA disease research committee and cochair of the CARRA Registry and Research Oversight Committee. She disclosed a financial relationship with Genentech. Dr. Washington has no relevant relationships to disclose.
 

PHILADELPHIA – Patients with systemic lupus erythematosus treated with lower doses of hydroxychloroquine (HCQ) had an increased risk for hospitalization for flares, according to study results presented during a press conference at the annual meeting of the American College of Rheumatology.

Doses decreased with changing guidelines

Guidelines over the years have recommended decreasing doses of HCQ. In 2011, ophthalmology guidelines recommended limiting HCQ dosing to 6.5 mg/kg per day or less of ideal body weight to reduce the chance of retinopathy. For many patients, this required a dose lower than 400 mg/day, an amount frequently used to treat lupus.

In 2016, updated guidelines further lowered the dosage of HCQ, recommending 5 mg/kg or less of patient’s actual body weight.

The effects that lower dosing has had on SLE-associated hospitalizations was unknown, which inspired Dr. Nestor’s research.

The team conducted a case-crossover study within the Mass General Brigham SLE cohort.

Hospitalizations studied over a decade

Dr. Nestor and colleagues identified patients with SLE (via electronic health records) who had at least one visit for SLE and were prescribed HCQ between January 2011 and December 2021, the period over which the recommendations were made.

They identified patients who had been hospitalized during that decade with SLE as the primary discharge diagnosis.

Patients were excluded if they had non-SLE indications, such as kidney transplant or infection without a concomitant SLE flare.

Of 2,971 patients with SLE who used HCQ, 576 had at least one hospitalization with primary discharge diagnosis of SLE.

Of these, 108 were hospitalized for an SLE flare and had used HCQ prior to that hospitalization and had at least one control period with HCQ use during the study period.

All of the patients in the study had to have a case period and a control period, Dr. Nestor explained. The case period was 6 months on HCQ ending in hospitalization for lupus and the control period was 6 months on HCQ that did not end in hospitalization for lupus.
 

Significantly increased hospitalizations

Low-dose HCQ by weight-based dose (≤ 5 vs. > 5 mg/kg per day) and by non–weight-based dose (< 400 vs. 400 mg per day) were both associated with significantly increased hospitalizations for SLE (adjusted odds ratio, 4.41; 95% confidence interval, 1.50-12.98; and AOR, 3.48; 95% CI, 1.33-9.13, respectively).

The average age of the hospitalized group was 36 years. Most patients (92%) were female, 43.5% were White, and 32.4% were Black.

In calling for reassessment of the dosing, Dr. Nestor said, “We are protecting our patients against a very long-term side effect of hydroxychloroquine retinopathy. [It] typically takes 10-20 years to develop in our patients. But by doing that, we’re missing many of the short-term benefits from hydroxychloroquine in our patients, leading to more lupus flares, which leads to more end-organ damage.”

She said patients taking HCQ for lupus are asked to see an ophthalmologist once a year to monitor for the side effect, adding that rheumatologists and ophthalmologists could work together to adjust the guidelines.

Dr. Nestor suggested it’s possible that patients need higher doses of HCQ earlier in their disease and lower doses later. “Perhaps it’s just the patients who are particularly active who need the higher doses,” she said.

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

PHILADELPHIA – Patients with systemic lupus erythematosus treated with lower doses of hydroxychloroquine (HCQ) had an increased risk for hospitalization for flares, according to study results presented during a press conference at the annual meeting of the American College of Rheumatology.

Doses decreased with changing guidelines

Guidelines over the years have recommended decreasing doses of HCQ. In 2011, ophthalmology guidelines recommended limiting HCQ dosing to 6.5 mg/kg per day or less of ideal body weight to reduce the chance of retinopathy. For many patients, this required a dose lower than 400 mg/day, an amount frequently used to treat lupus.

In 2016, updated guidelines further lowered the dosage of HCQ, recommending 5 mg/kg or less of patient’s actual body weight.

The effects that lower dosing has had on SLE-associated hospitalizations was unknown, which inspired Dr. Nestor’s research.

The team conducted a case-crossover study within the Mass General Brigham SLE cohort.

Hospitalizations studied over a decade

Dr. Nestor and colleagues identified patients with SLE (via electronic health records) who had at least one visit for SLE and were prescribed HCQ between January 2011 and December 2021, the period over which the recommendations were made.

They identified patients who had been hospitalized during that decade with SLE as the primary discharge diagnosis.

Patients were excluded if they had non-SLE indications, such as kidney transplant or infection without a concomitant SLE flare.

Of 2,971 patients with SLE who used HCQ, 576 had at least one hospitalization with primary discharge diagnosis of SLE.

Of these, 108 were hospitalized for an SLE flare and had used HCQ prior to that hospitalization and had at least one control period with HCQ use during the study period.

All of the patients in the study had to have a case period and a control period, Dr. Nestor explained. The case period was 6 months on HCQ ending in hospitalization for lupus and the control period was 6 months on HCQ that did not end in hospitalization for lupus.
 

Significantly increased hospitalizations

Low-dose HCQ by weight-based dose (≤ 5 vs. > 5 mg/kg per day) and by non–weight-based dose (< 400 vs. 400 mg per day) were both associated with significantly increased hospitalizations for SLE (adjusted odds ratio, 4.41; 95% confidence interval, 1.50-12.98; and AOR, 3.48; 95% CI, 1.33-9.13, respectively).

The average age of the hospitalized group was 36 years. Most patients (92%) were female, 43.5% were White, and 32.4% were Black.

In calling for reassessment of the dosing, Dr. Nestor said, “We are protecting our patients against a very long-term side effect of hydroxychloroquine retinopathy. [It] typically takes 10-20 years to develop in our patients. But by doing that, we’re missing many of the short-term benefits from hydroxychloroquine in our patients, leading to more lupus flares, which leads to more end-organ damage.”

She said patients taking HCQ for lupus are asked to see an ophthalmologist once a year to monitor for the side effect, adding that rheumatologists and ophthalmologists could work together to adjust the guidelines.

Dr. Nestor suggested it’s possible that patients need higher doses of HCQ earlier in their disease and lower doses later. “Perhaps it’s just the patients who are particularly active who need the higher doses,” she said.

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

PHILADELPHIA – Patients with systemic lupus erythematosus treated with lower doses of hydroxychloroquine (HCQ) had an increased risk for hospitalization for flares, according to study results presented during a press conference at the annual meeting of the American College of Rheumatology.

Doses decreased with changing guidelines

Guidelines over the years have recommended decreasing doses of HCQ. In 2011, ophthalmology guidelines recommended limiting HCQ dosing to 6.5 mg/kg per day or less of ideal body weight to reduce the chance of retinopathy. For many patients, this required a dose lower than 400 mg/day, an amount frequently used to treat lupus.

In 2016, updated guidelines further lowered the dosage of HCQ, recommending 5 mg/kg or less of patient’s actual body weight.

The effects that lower dosing has had on SLE-associated hospitalizations was unknown, which inspired Dr. Nestor’s research.

The team conducted a case-crossover study within the Mass General Brigham SLE cohort.

Hospitalizations studied over a decade

Dr. Nestor and colleagues identified patients with SLE (via electronic health records) who had at least one visit for SLE and were prescribed HCQ between January 2011 and December 2021, the period over which the recommendations were made.

They identified patients who had been hospitalized during that decade with SLE as the primary discharge diagnosis.

Patients were excluded if they had non-SLE indications, such as kidney transplant or infection without a concomitant SLE flare.

Of 2,971 patients with SLE who used HCQ, 576 had at least one hospitalization with primary discharge diagnosis of SLE.

Of these, 108 were hospitalized for an SLE flare and had used HCQ prior to that hospitalization and had at least one control period with HCQ use during the study period.

All of the patients in the study had to have a case period and a control period, Dr. Nestor explained. The case period was 6 months on HCQ ending in hospitalization for lupus and the control period was 6 months on HCQ that did not end in hospitalization for lupus.
 

Significantly increased hospitalizations

Low-dose HCQ by weight-based dose (≤ 5 vs. > 5 mg/kg per day) and by non–weight-based dose (< 400 vs. 400 mg per day) were both associated with significantly increased hospitalizations for SLE (adjusted odds ratio, 4.41; 95% confidence interval, 1.50-12.98; and AOR, 3.48; 95% CI, 1.33-9.13, respectively).

The average age of the hospitalized group was 36 years. Most patients (92%) were female, 43.5% were White, and 32.4% were Black.

In calling for reassessment of the dosing, Dr. Nestor said, “We are protecting our patients against a very long-term side effect of hydroxychloroquine retinopathy. [It] typically takes 10-20 years to develop in our patients. But by doing that, we’re missing many of the short-term benefits from hydroxychloroquine in our patients, leading to more lupus flares, which leads to more end-organ damage.”

She said patients taking HCQ for lupus are asked to see an ophthalmologist once a year to monitor for the side effect, adding that rheumatologists and ophthalmologists could work together to adjust the guidelines.

Dr. Nestor suggested it’s possible that patients need higher doses of HCQ earlier in their disease and lower doses later. “Perhaps it’s just the patients who are particularly active who need the higher doses,” she said.

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

Adults who underwent either total ankle replacement or ankle fusion for end-stage ankle osteoarthritis showed similar clinical scores and adverse event numbers, in a randomized controlled trial of approximately 300 patients.

Ankle osteoarthritis remains a cause of severe pain and disability. Patients are treated nonoperatively if possible, but surgery is often needed for individuals with end-stage disease, wrote Andrew Goldberg, MBBS, of University College London and colleagues in the Annals of Internal Medicine.

“Most patients with ankle arthritis respond to nonoperative treatments, such as weight loss, activity modification, support braces, and analgesia, [but] once the disease has progressed to end-stage osteoarthritis, the main surgical treatments are total ankle re-placement or ankle arthrodesis,” Dr. Goldberg said, in an interview.

In the new study, patients were randomized to receive either a total ankle replacement (TAR) or ankle fusion (AF).

“We showed that, in both treatment groups the clinical scores improved hugely, by more than three times the minimal clinically important difference,” Dr. Goldberg said in an interview.

“Although the ankle replacement arm improved, on average, by more than an extra 4 points over ankle fusion, this was not considered clinically or statistically significant,” he said.

The study is the first randomized trial to show high-quality and robust results, he noted, and findings support data from previous studies.

“Although both TAR and ankle fusion have been shown to be effective, they are very different treatments, with one fusing the bones so that there is no ankle joint movement, and the other replacing the joint with the aim of retaining ankle joint movement. It is difficult for a patient to know which treatment is more suitable for them, with most seeking guidance from their surgeon,” he said.

Generating high-quality evidence

The study, a randomized, multicenter, open-label trial known as TARVA (Total Ankle Replacement Versus Ankle Arthrodesis), aimed to compare the clinical effectiveness of the two existing publicly funded U.K. treatment options, the authors wrote.

Patients were recruited at 17 U.K. centers between March 6, 2015, and Jan. 10, 2019. The study enrolled 303 adults aged 50-85 years with end-stage ankle osteoarthritis. The mean age of the participants was 68 years; 71% were men. A total of 137 TAR patients and 144 ankle fusion patients completed their surgeries with clinical scores available for analysis. Baseline characteristics were mainly similar between the groups.

Blinding was not possible because of the nature of the procedures, but the surgeons who screened the patients were not aware of the randomization allocations, the researchers noted. A total of 33 surgeons participated in the trial, with a median number of seven patients per surgeon during the study period.

For TAR, U.K. surgeons use both two-component, fixed-bearing and three-component, mobile-bearing implants, the authors write. Ankle fusion was done using the surgeon’s usual technique of either arthroscopic-assisted or open ankle fusion.

The primary outcome was the change in the Manchester–Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores from baseline to 52 weeks after surgery. The MOXFQ-W/S uses a scale of 0-100, with lower scores representing better outcomes. Secondary outcomes included change in the MOXFQ-W/S scores at 26 weeks after surgery, as well as measures of patient quality of life.

No statistically significant difference

Overall, the mean MOXFQ-W/S scores improved significantly from baseline to 52 weeks for both groups, with average improvements of 49.9 in the TAR group and 44.4 points in the AF group. The average scores at 52 weeks were 31.4 in the TAR group and 36.8 in the AF group.

The adjusted difference in score change from baseline was –5.56, showing a slightly greater degree of improvement with TAR, but this difference was not clinically or statistically significant, the researchers noted.

Adverse event numbers were similar for both procedures, with 54% of TAR patients and 53% of AF patients experiencing at least 1 adverse event during the study period. Of those, 18% of TAR patients and 24% of AF patients experienced at least 1 serious adverse event.

However, the TAR patients experienced a higher rate of wound healing complications and nerve injuries, while thromboembolism was higher in the AF patients, the researchers noted.

A prespecified subgroup analysis of patients with osteoarthritis in adjacent joints suggested a greater improvement in TAR, compared with AF, a difference that increased when fixed-bearing TAR was compared with AF, the authors wrote.

“This reinforces previous reports that suggest that the presence of adjacent joint arthritis may be an indication for ankle replacement over AF,” the authors wrote in their discussion.

“Many of these patients did not have any symptoms in the adjacent joints,” they noted.

“The presence of adjacent joint arthritis, meaning the wear and tear of the joints around the ankle joint, seemed to favor ankle replacement,” Dr. Goldberg said. Approximately 30 joints in the foot continue to move after the ankle is fused, and if these adjacent joints are not healthy before surgery [as was the case in 42% of the study patients], the results of fusion were less successful, he explained.

A post hoc analysis between TAR subtypes showed that patients who had fixed-bearing TAR had significantly greater improvements, compared with AF patients, but this difference was not observed in patients who had mobile-bearing TAR, the researchers noted.

Dr. Goldberg said it was surprising “that, in a separate analysis, we found that the fixed-bearing ankle replacement patients [who accounted for half of the implants used] improved by a much greater difference when compared to ankle fusion.”

The study findings were limited by several factors including the short follow-up and study design that allowed surgeons to choose any implant and technique, the researchers noted.

Other limitations include a lack of data on cost-effectiveness and the impact of comorbidities on outcomes, they wrote. However, the study is the first completed multicenter randomized controlled trial to compare TAR and AF procedures for end-stage ankle osteoarthritis and shows that both yield similar clinical improvements, they concluded.

Data can inform treatment discussion

The take-home messages for clinicians are that both ankle replacement and ankle fusion are effective treatments that improve patients’ quality of life, and it is important to establish the health of adjacent joints before making treatment recommendations, Dr. Goldberg said.

“Careful counseling on the relative risks of each procedure should be part of the informed consent process,” he added. Ideally, all patients seeking surgical care for ankle arthritis should have a choice between ankle replacement and ankle fusion, but sometimes there is inequity of provision of the two treatments, he noted.

“We now encourage all surgeons to work in ankle arthritis networks so that every patient, no matter where they live, can have choice about the best treatment for them,” he said.

Researchers met the challenge of surgical RCT

Randomized trials of surgical interventions are challenging to conduct, and therefore limited, wrote Bruce Sangeorzan, MD, of the University of Washington, Seattle, and colleagues in an accompanying editorial. However, the new study was strengthened by the inclusion of 17 centers for heterogeneity of implant type and surgeon experience level, the editorialists said in the Annals of Internal Medicine.

The study is especially important, because ankle arthritis treatment is very understudied, compared with hip and knee arthritis, but it has a similar impact on activity, editorial coauthor Dr. Sangeorzan said in an interview.

“Randomized controlled trials are the gold standard for comparing medical therapies,” he said, “but they are very difficult to do in surgical treatments, particularly when the two treatments can be differentiated, in this case by movement of the ankle.”

In addition, there is a strong placebo effect attached to interventions, Dr. Sangeorzan noted. “Determining best-case treatment relies on prospective research, preferably randomized. Since both ankle fusion and ankle replacement are effective therapies, a prospective randomized trial is the best way to help make treatment decisions,” he said.

The current study findings are not surprising, but they are preliminary, and 1 year of follow-up is not enough to determine effectiveness, Dr. Sangeorzan emphasized. However, “the authors have done the hard work of randomizing the patients and collecting the data, and the patients can now be followed for a longer time,” he said.

“In addition, the trial was designed with multiple secondary outcome measures, so the data can be matched up with larger trials that were not randomized to identify key elements of success for each procedure,” he noted.

The key message for clinicians is that ankle arthritis has a significant impact on patients’ lives, but there are two effective treatments that can reduce the impact of the disease, said Dr. Sangeorzan. “The data suggest that there are differences in implant design and differences in comorbidities that should influence decision-making,” he added.

Additional research is needed in the form of a longer study duration with larger cohorts, said Dr. Sangeorzan. In particular, researchers need to determine what comorbidities might drive patients to one type of care vs. another, he said. “The suggestion that [patients receiving implants with two motion segments have better outcomes than those receiving implants with a one-motion segment] also deserves further study,” he added.

The research was supported by the UK National Institute for Health and Care Research Health Technology Assessment Programme. The trial was sponsored by University College London. Dr. Goldberg disclosed grant support from NIHR HTA, as well as financial relationships with companies including Stryker, Paragon 28, and stock options with Standing CT Company, Elstree Waterfront Outpatients, and X Bolt Orthopedics.

The editorialists had no financial conflicts to disclose.

Adults who underwent either total ankle replacement or ankle fusion for end-stage ankle osteoarthritis showed similar clinical scores and adverse event numbers, in a randomized controlled trial of approximately 300 patients.

Ankle osteoarthritis remains a cause of severe pain and disability. Patients are treated nonoperatively if possible, but surgery is often needed for individuals with end-stage disease, wrote Andrew Goldberg, MBBS, of University College London and colleagues in the Annals of Internal Medicine.

“Most patients with ankle arthritis respond to nonoperative treatments, such as weight loss, activity modification, support braces, and analgesia, [but] once the disease has progressed to end-stage osteoarthritis, the main surgical treatments are total ankle re-placement or ankle arthrodesis,” Dr. Goldberg said, in an interview.

In the new study, patients were randomized to receive either a total ankle replacement (TAR) or ankle fusion (AF).

“We showed that, in both treatment groups the clinical scores improved hugely, by more than three times the minimal clinically important difference,” Dr. Goldberg said in an interview.

“Although the ankle replacement arm improved, on average, by more than an extra 4 points over ankle fusion, this was not considered clinically or statistically significant,” he said.

The study is the first randomized trial to show high-quality and robust results, he noted, and findings support data from previous studies.

“Although both TAR and ankle fusion have been shown to be effective, they are very different treatments, with one fusing the bones so that there is no ankle joint movement, and the other replacing the joint with the aim of retaining ankle joint movement. It is difficult for a patient to know which treatment is more suitable for them, with most seeking guidance from their surgeon,” he said.

Generating high-quality evidence

The study, a randomized, multicenter, open-label trial known as TARVA (Total Ankle Replacement Versus Ankle Arthrodesis), aimed to compare the clinical effectiveness of the two existing publicly funded U.K. treatment options, the authors wrote.

Patients were recruited at 17 U.K. centers between March 6, 2015, and Jan. 10, 2019. The study enrolled 303 adults aged 50-85 years with end-stage ankle osteoarthritis. The mean age of the participants was 68 years; 71% were men. A total of 137 TAR patients and 144 ankle fusion patients completed their surgeries with clinical scores available for analysis. Baseline characteristics were mainly similar between the groups.

Blinding was not possible because of the nature of the procedures, but the surgeons who screened the patients were not aware of the randomization allocations, the researchers noted. A total of 33 surgeons participated in the trial, with a median number of seven patients per surgeon during the study period.

For TAR, U.K. surgeons use both two-component, fixed-bearing and three-component, mobile-bearing implants, the authors write. Ankle fusion was done using the surgeon’s usual technique of either arthroscopic-assisted or open ankle fusion.

The primary outcome was the change in the Manchester–Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores from baseline to 52 weeks after surgery. The MOXFQ-W/S uses a scale of 0-100, with lower scores representing better outcomes. Secondary outcomes included change in the MOXFQ-W/S scores at 26 weeks after surgery, as well as measures of patient quality of life.

No statistically significant difference

Overall, the mean MOXFQ-W/S scores improved significantly from baseline to 52 weeks for both groups, with average improvements of 49.9 in the TAR group and 44.4 points in the AF group. The average scores at 52 weeks were 31.4 in the TAR group and 36.8 in the AF group.

The adjusted difference in score change from baseline was –5.56, showing a slightly greater degree of improvement with TAR, but this difference was not clinically or statistically significant, the researchers noted.

Adverse event numbers were similar for both procedures, with 54% of TAR patients and 53% of AF patients experiencing at least 1 adverse event during the study period. Of those, 18% of TAR patients and 24% of AF patients experienced at least 1 serious adverse event.

However, the TAR patients experienced a higher rate of wound healing complications and nerve injuries, while thromboembolism was higher in the AF patients, the researchers noted.

A prespecified subgroup analysis of patients with osteoarthritis in adjacent joints suggested a greater improvement in TAR, compared with AF, a difference that increased when fixed-bearing TAR was compared with AF, the authors wrote.

“This reinforces previous reports that suggest that the presence of adjacent joint arthritis may be an indication for ankle replacement over AF,” the authors wrote in their discussion.

“Many of these patients did not have any symptoms in the adjacent joints,” they noted.

“The presence of adjacent joint arthritis, meaning the wear and tear of the joints around the ankle joint, seemed to favor ankle replacement,” Dr. Goldberg said. Approximately 30 joints in the foot continue to move after the ankle is fused, and if these adjacent joints are not healthy before surgery [as was the case in 42% of the study patients], the results of fusion were less successful, he explained.

A post hoc analysis between TAR subtypes showed that patients who had fixed-bearing TAR had significantly greater improvements, compared with AF patients, but this difference was not observed in patients who had mobile-bearing TAR, the researchers noted.

Dr. Goldberg said it was surprising “that, in a separate analysis, we found that the fixed-bearing ankle replacement patients [who accounted for half of the implants used] improved by a much greater difference when compared to ankle fusion.”

The study findings were limited by several factors including the short follow-up and study design that allowed surgeons to choose any implant and technique, the researchers noted.

Other limitations include a lack of data on cost-effectiveness and the impact of comorbidities on outcomes, they wrote. However, the study is the first completed multicenter randomized controlled trial to compare TAR and AF procedures for end-stage ankle osteoarthritis and shows that both yield similar clinical improvements, they concluded.

Data can inform treatment discussion

The take-home messages for clinicians are that both ankle replacement and ankle fusion are effective treatments that improve patients’ quality of life, and it is important to establish the health of adjacent joints before making treatment recommendations, Dr. Goldberg said.

“Careful counseling on the relative risks of each procedure should be part of the informed consent process,” he added. Ideally, all patients seeking surgical care for ankle arthritis should have a choice between ankle replacement and ankle fusion, but sometimes there is inequity of provision of the two treatments, he noted.

“We now encourage all surgeons to work in ankle arthritis networks so that every patient, no matter where they live, can have choice about the best treatment for them,” he said.

Researchers met the challenge of surgical RCT

Randomized trials of surgical interventions are challenging to conduct, and therefore limited, wrote Bruce Sangeorzan, MD, of the University of Washington, Seattle, and colleagues in an accompanying editorial. However, the new study was strengthened by the inclusion of 17 centers for heterogeneity of implant type and surgeon experience level, the editorialists said in the Annals of Internal Medicine.

The study is especially important, because ankle arthritis treatment is very understudied, compared with hip and knee arthritis, but it has a similar impact on activity, editorial coauthor Dr. Sangeorzan said in an interview.

“Randomized controlled trials are the gold standard for comparing medical therapies,” he said, “but they are very difficult to do in surgical treatments, particularly when the two treatments can be differentiated, in this case by movement of the ankle.”

In addition, there is a strong placebo effect attached to interventions, Dr. Sangeorzan noted. “Determining best-case treatment relies on prospective research, preferably randomized. Since both ankle fusion and ankle replacement are effective therapies, a prospective randomized trial is the best way to help make treatment decisions,” he said.

The current study findings are not surprising, but they are preliminary, and 1 year of follow-up is not enough to determine effectiveness, Dr. Sangeorzan emphasized. However, “the authors have done the hard work of randomizing the patients and collecting the data, and the patients can now be followed for a longer time,” he said.

“In addition, the trial was designed with multiple secondary outcome measures, so the data can be matched up with larger trials that were not randomized to identify key elements of success for each procedure,” he noted.

The key message for clinicians is that ankle arthritis has a significant impact on patients’ lives, but there are two effective treatments that can reduce the impact of the disease, said Dr. Sangeorzan. “The data suggest that there are differences in implant design and differences in comorbidities that should influence decision-making,” he added.

Additional research is needed in the form of a longer study duration with larger cohorts, said Dr. Sangeorzan. In particular, researchers need to determine what comorbidities might drive patients to one type of care vs. another, he said. “The suggestion that [patients receiving implants with two motion segments have better outcomes than those receiving implants with a one-motion segment] also deserves further study,” he added.

The research was supported by the UK National Institute for Health and Care Research Health Technology Assessment Programme. The trial was sponsored by University College London. Dr. Goldberg disclosed grant support from NIHR HTA, as well as financial relationships with companies including Stryker, Paragon 28, and stock options with Standing CT Company, Elstree Waterfront Outpatients, and X Bolt Orthopedics.

The editorialists had no financial conflicts to disclose.

Adults who underwent either total ankle replacement or ankle fusion for end-stage ankle osteoarthritis showed similar clinical scores and adverse event numbers, in a randomized controlled trial of approximately 300 patients.

Ankle osteoarthritis remains a cause of severe pain and disability. Patients are treated nonoperatively if possible, but surgery is often needed for individuals with end-stage disease, wrote Andrew Goldberg, MBBS, of University College London and colleagues in the Annals of Internal Medicine.

“Most patients with ankle arthritis respond to nonoperative treatments, such as weight loss, activity modification, support braces, and analgesia, [but] once the disease has progressed to end-stage osteoarthritis, the main surgical treatments are total ankle re-placement or ankle arthrodesis,” Dr. Goldberg said, in an interview.

In the new study, patients were randomized to receive either a total ankle replacement (TAR) or ankle fusion (AF).

“We showed that, in both treatment groups the clinical scores improved hugely, by more than three times the minimal clinically important difference,” Dr. Goldberg said in an interview.

“Although the ankle replacement arm improved, on average, by more than an extra 4 points over ankle fusion, this was not considered clinically or statistically significant,” he said.

The study is the first randomized trial to show high-quality and robust results, he noted, and findings support data from previous studies.

“Although both TAR and ankle fusion have been shown to be effective, they are very different treatments, with one fusing the bones so that there is no ankle joint movement, and the other replacing the joint with the aim of retaining ankle joint movement. It is difficult for a patient to know which treatment is more suitable for them, with most seeking guidance from their surgeon,” he said.

Generating high-quality evidence

The study, a randomized, multicenter, open-label trial known as TARVA (Total Ankle Replacement Versus Ankle Arthrodesis), aimed to compare the clinical effectiveness of the two existing publicly funded U.K. treatment options, the authors wrote.

Patients were recruited at 17 U.K. centers between March 6, 2015, and Jan. 10, 2019. The study enrolled 303 adults aged 50-85 years with end-stage ankle osteoarthritis. The mean age of the participants was 68 years; 71% were men. A total of 137 TAR patients and 144 ankle fusion patients completed their surgeries with clinical scores available for analysis. Baseline characteristics were mainly similar between the groups.

Blinding was not possible because of the nature of the procedures, but the surgeons who screened the patients were not aware of the randomization allocations, the researchers noted. A total of 33 surgeons participated in the trial, with a median number of seven patients per surgeon during the study period.

For TAR, U.K. surgeons use both two-component, fixed-bearing and three-component, mobile-bearing implants, the authors write. Ankle fusion was done using the surgeon’s usual technique of either arthroscopic-assisted or open ankle fusion.

The primary outcome was the change in the Manchester–Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores from baseline to 52 weeks after surgery. The MOXFQ-W/S uses a scale of 0-100, with lower scores representing better outcomes. Secondary outcomes included change in the MOXFQ-W/S scores at 26 weeks after surgery, as well as measures of patient quality of life.

No statistically significant difference

Overall, the mean MOXFQ-W/S scores improved significantly from baseline to 52 weeks for both groups, with average improvements of 49.9 in the TAR group and 44.4 points in the AF group. The average scores at 52 weeks were 31.4 in the TAR group and 36.8 in the AF group.

The adjusted difference in score change from baseline was –5.56, showing a slightly greater degree of improvement with TAR, but this difference was not clinically or statistically significant, the researchers noted.

Adverse event numbers were similar for both procedures, with 54% of TAR patients and 53% of AF patients experiencing at least 1 adverse event during the study period. Of those, 18% of TAR patients and 24% of AF patients experienced at least 1 serious adverse event.

However, the TAR patients experienced a higher rate of wound healing complications and nerve injuries, while thromboembolism was higher in the AF patients, the researchers noted.

A prespecified subgroup analysis of patients with osteoarthritis in adjacent joints suggested a greater improvement in TAR, compared with AF, a difference that increased when fixed-bearing TAR was compared with AF, the authors wrote.

“This reinforces previous reports that suggest that the presence of adjacent joint arthritis may be an indication for ankle replacement over AF,” the authors wrote in their discussion.

“Many of these patients did not have any symptoms in the adjacent joints,” they noted.

“The presence of adjacent joint arthritis, meaning the wear and tear of the joints around the ankle joint, seemed to favor ankle replacement,” Dr. Goldberg said. Approximately 30 joints in the foot continue to move after the ankle is fused, and if these adjacent joints are not healthy before surgery [as was the case in 42% of the study patients], the results of fusion were less successful, he explained.

A post hoc analysis between TAR subtypes showed that patients who had fixed-bearing TAR had significantly greater improvements, compared with AF patients, but this difference was not observed in patients who had mobile-bearing TAR, the researchers noted.

Dr. Goldberg said it was surprising “that, in a separate analysis, we found that the fixed-bearing ankle replacement patients [who accounted for half of the implants used] improved by a much greater difference when compared to ankle fusion.”

The study findings were limited by several factors including the short follow-up and study design that allowed surgeons to choose any implant and technique, the researchers noted.

Other limitations include a lack of data on cost-effectiveness and the impact of comorbidities on outcomes, they wrote. However, the study is the first completed multicenter randomized controlled trial to compare TAR and AF procedures for end-stage ankle osteoarthritis and shows that both yield similar clinical improvements, they concluded.

Data can inform treatment discussion

The take-home messages for clinicians are that both ankle replacement and ankle fusion are effective treatments that improve patients’ quality of life, and it is important to establish the health of adjacent joints before making treatment recommendations, Dr. Goldberg said.

“Careful counseling on the relative risks of each procedure should be part of the informed consent process,” he added. Ideally, all patients seeking surgical care for ankle arthritis should have a choice between ankle replacement and ankle fusion, but sometimes there is inequity of provision of the two treatments, he noted.

“We now encourage all surgeons to work in ankle arthritis networks so that every patient, no matter where they live, can have choice about the best treatment for them,” he said.

Researchers met the challenge of surgical RCT

Randomized trials of surgical interventions are challenging to conduct, and therefore limited, wrote Bruce Sangeorzan, MD, of the University of Washington, Seattle, and colleagues in an accompanying editorial. However, the new study was strengthened by the inclusion of 17 centers for heterogeneity of implant type and surgeon experience level, the editorialists said in the Annals of Internal Medicine.

The study is especially important, because ankle arthritis treatment is very understudied, compared with hip and knee arthritis, but it has a similar impact on activity, editorial coauthor Dr. Sangeorzan said in an interview.

“Randomized controlled trials are the gold standard for comparing medical therapies,” he said, “but they are very difficult to do in surgical treatments, particularly when the two treatments can be differentiated, in this case by movement of the ankle.”

In addition, there is a strong placebo effect attached to interventions, Dr. Sangeorzan noted. “Determining best-case treatment relies on prospective research, preferably randomized. Since both ankle fusion and ankle replacement are effective therapies, a prospective randomized trial is the best way to help make treatment decisions,” he said.

The current study findings are not surprising, but they are preliminary, and 1 year of follow-up is not enough to determine effectiveness, Dr. Sangeorzan emphasized. However, “the authors have done the hard work of randomizing the patients and collecting the data, and the patients can now be followed for a longer time,” he said.

“In addition, the trial was designed with multiple secondary outcome measures, so the data can be matched up with larger trials that were not randomized to identify key elements of success for each procedure,” he noted.

The key message for clinicians is that ankle arthritis has a significant impact on patients’ lives, but there are two effective treatments that can reduce the impact of the disease, said Dr. Sangeorzan. “The data suggest that there are differences in implant design and differences in comorbidities that should influence decision-making,” he added.

Additional research is needed in the form of a longer study duration with larger cohorts, said Dr. Sangeorzan. In particular, researchers need to determine what comorbidities might drive patients to one type of care vs. another, he said. “The suggestion that [patients receiving implants with two motion segments have better outcomes than those receiving implants with a one-motion segment] also deserves further study,” he added.

The research was supported by the UK National Institute for Health and Care Research Health Technology Assessment Programme. The trial was sponsored by University College London. Dr. Goldberg disclosed grant support from NIHR HTA, as well as financial relationships with companies including Stryker, Paragon 28, and stock options with Standing CT Company, Elstree Waterfront Outpatients, and X Bolt Orthopedics.

The editorialists had no financial conflicts to disclose.

Getting COVID-19 a second time doubles a person’s chance of dying and triples the likelihood of being hospitalized in the next 6 months, a new study found.

Vaccination and booster status did not improve survival or hospitalization rates among people who were infected more than once.

“Reinfection with COVID-19 increases the risk of both acute outcomes and long COVID,” study author Ziyad Al-Aly, MD, told Reuters. “This was evident in unvaccinated, vaccinated and boosted people.”

The study was published in the journal Nature Medicine.

Researchers analyzed U.S. Department of Veterans Affairs data, including 443,588 people with a first infection of SARS-CoV-2, 40,947 people who were infected two or more times, and 5.3 million people who had not been infected with coronavirus, whose data served as the control group.

“During the past few months, there’s been an air of invincibility among people who have had COVID-19 or their vaccinations and boosters, and especially among people who have had an infection and also received vaccines; some people started to [refer] to these individuals as having a sort of superimmunity to the virus,” Dr. Al-Aly said in a press release from Washington University in St. Louis. “Without ambiguity, our research showed that getting an infection a second, third or fourth time contributes to additional health risks in the acute phase, meaning the first 30 days after infection, and in the months beyond, meaning the long COVID phase.”

Being infected with COVID-19 more than once also dramatically increased the risk of developing lung problems, heart conditions, or brain conditions. The heightened risks persisted for 6 months.

Researchers said a limitation of their study was that data primarily came from White males.

An expert not involved in the study told Reuters that the Veterans Affairs population does not reflect the general population. Patients at VA health facilities are generally older with more than normal health complications, said John Moore, PhD, a professor of microbiology and immunology at Weill Cornell Medicine, New York.

Dr. Al-Aly encouraged people to be vigilant as they plan for the holiday season, Reuters reported.

“We had started seeing a lot of patients coming to the clinic with an air of invincibility,” he told Reuters. “They wondered, ‘Does getting a reinfection really matter?’ The answer is yes, it absolutely does.”

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

Getting COVID-19 a second time doubles a person’s chance of dying and triples the likelihood of being hospitalized in the next 6 months, a new study found.

Vaccination and booster status did not improve survival or hospitalization rates among people who were infected more than once.

“Reinfection with COVID-19 increases the risk of both acute outcomes and long COVID,” study author Ziyad Al-Aly, MD, told Reuters. “This was evident in unvaccinated, vaccinated and boosted people.”

The study was published in the journal Nature Medicine.

Researchers analyzed U.S. Department of Veterans Affairs data, including 443,588 people with a first infection of SARS-CoV-2, 40,947 people who were infected two or more times, and 5.3 million people who had not been infected with coronavirus, whose data served as the control group.

“During the past few months, there’s been an air of invincibility among people who have had COVID-19 or their vaccinations and boosters, and especially among people who have had an infection and also received vaccines; some people started to [refer] to these individuals as having a sort of superimmunity to the virus,” Dr. Al-Aly said in a press release from Washington University in St. Louis. “Without ambiguity, our research showed that getting an infection a second, third or fourth time contributes to additional health risks in the acute phase, meaning the first 30 days after infection, and in the months beyond, meaning the long COVID phase.”

Being infected with COVID-19 more than once also dramatically increased the risk of developing lung problems, heart conditions, or brain conditions. The heightened risks persisted for 6 months.

Researchers said a limitation of their study was that data primarily came from White males.

An expert not involved in the study told Reuters that the Veterans Affairs population does not reflect the general population. Patients at VA health facilities are generally older with more than normal health complications, said John Moore, PhD, a professor of microbiology and immunology at Weill Cornell Medicine, New York.

Dr. Al-Aly encouraged people to be vigilant as they plan for the holiday season, Reuters reported.

“We had started seeing a lot of patients coming to the clinic with an air of invincibility,” he told Reuters. “They wondered, ‘Does getting a reinfection really matter?’ The answer is yes, it absolutely does.”

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

Getting COVID-19 a second time doubles a person’s chance of dying and triples the likelihood of being hospitalized in the next 6 months, a new study found.

Vaccination and booster status did not improve survival or hospitalization rates among people who were infected more than once.

“Reinfection with COVID-19 increases the risk of both acute outcomes and long COVID,” study author Ziyad Al-Aly, MD, told Reuters. “This was evident in unvaccinated, vaccinated and boosted people.”

The study was published in the journal Nature Medicine.

Researchers analyzed U.S. Department of Veterans Affairs data, including 443,588 people with a first infection of SARS-CoV-2, 40,947 people who were infected two or more times, and 5.3 million people who had not been infected with coronavirus, whose data served as the control group.

“During the past few months, there’s been an air of invincibility among people who have had COVID-19 or their vaccinations and boosters, and especially among people who have had an infection and also received vaccines; some people started to [refer] to these individuals as having a sort of superimmunity to the virus,” Dr. Al-Aly said in a press release from Washington University in St. Louis. “Without ambiguity, our research showed that getting an infection a second, third or fourth time contributes to additional health risks in the acute phase, meaning the first 30 days after infection, and in the months beyond, meaning the long COVID phase.”

Being infected with COVID-19 more than once also dramatically increased the risk of developing lung problems, heart conditions, or brain conditions. The heightened risks persisted for 6 months.

Researchers said a limitation of their study was that data primarily came from White males.

An expert not involved in the study told Reuters that the Veterans Affairs population does not reflect the general population. Patients at VA health facilities are generally older with more than normal health complications, said John Moore, PhD, a professor of microbiology and immunology at Weill Cornell Medicine, New York.

Dr. Al-Aly encouraged people to be vigilant as they plan for the holiday season, Reuters reported.

“We had started seeing a lot of patients coming to the clinic with an air of invincibility,” he told Reuters. “They wondered, ‘Does getting a reinfection really matter?’ The answer is yes, it absolutely does.”

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

PHILADELPHIA – Oral remibrutinib was well tolerated and had a good safety profile over 24 weeks among patients with moderate to severe Sjögren syndrome (SS), according to new phase 2 data presented at the annual meeting of the American College of Rheumatology.

Thomas Dörner, MD, with the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin, presented the data from the double-blind, randomized, placebo-controlled, proof-of-concept study.

The authors said the results of the study suggest that remibrutinib, a highly specific inhibitor of Bruton tyrosine kinase, has the potential to become the first effective oral disease-modifying therapy for SS.

The 73 participants in the study had moderate to severe SS. The baseline EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score was at least 5, EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) was at least 5, and anti-Ro/SSA antibody positivity was 3 months or less before screening. The patients’ unstimulated whole salivary flow rate was > 0 mL/min.

Overall, 73 patients (71 women) were randomly assigned to receive either remibrutinib 100 mg twice a day (n = 24), remibrutinib 100 mg four times a day (n = 25), or placebo (n = 24) between August 2019 and May 2021.

Remibrutinib met the primary endpoint and resulted in a statistically significant improvement in ESSDAI score for both regimens combined compared with placebo at week 24 (ESSDAI, –2.86).
 

Patient-reported outcomes similar to placebo

Patient-reported outcomes, including scores on ESSPRI, Functional Assessment of Chronic Illness Therapy–Fatigue, and EuroQol-5 Dimension, were similar in the treatment groups and the placebo group.

“All of the patients, including the placebo patients, improved over the time of the study,” Dr. Dörner said.

The average age of the patients was 51.8 years (range, 18-75 years). Groups were generally balanced with regard to demographic qualities and disease severity at baseline, and the patients represented the SS population well, Dr. Dörner said.

No severe adverse events were reported. Infections were the most frequently reported adverse events, and the rates were similar with the study drug and placebo. No notable liver abnormalities were reported in any of the groups.

Chrisanna Dobrowolski, MD, assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York, told this news organization, “Preliminary results are promising, but they failed to show improvements in patient-reported quality-of-life measures.

“Having statistical improvements in disease activity measures without clinically meaningful improvement in patient quality of life may limit the value of this treatment,” she said.

Dr. Dobrowolski added that the follow-up period of 6 months is short, and larger studies over a longer period are needed to better assess the effect on patients’ quality of life.

“Regardless, this is the first oral medication which has shown disease-modifying potential for the glandular symptoms of SS and is an exciting new avenue of investigation to be further explored,” she said.

Patients with SS 15 to 20 times more likely to develop B-cell lymphoma as a life-threatening complication. SS is a systemic autoimmune disease characterized by B-cell hyperactivation, lymphoid infiltration, progressive destruction of exocrine glands, and various complications outside the glands, the study authors wrote in the abstract.
 

Nearly 4 million in U.S. live with the disease

Nearly 4 million people in the United States live with the disease. Common symptoms include light sensitivity, dry eye, dry mouth, fatigue, and joint pain.

SS can be difficult to diagnose because the symptoms vary from person to person and can be confused with those caused by other diseases.

Ardy Fenando, MD, a rheumatology fellow with the University of Kansas Medical Center, said in an interview, “We need more therapies for Sjögren’s. Heterogeneity complicates the way we set the primary endpoints. Therefore, we haven’t had a proven treatment for Sjögren’s. This is supported by previous RCTs [randomized controlled trials] that failed to meet the primary end points.”

Dr. Dörner has relationships with AbbVie, Eli Lilly, Roche/Genentech, Janssen, Novartis, Bristol-Myers Squibb), and UCB. Other authors have various relationships with industry. Dr. Fenando and Dr. Dobrowolski have disclosed no relevant financial relationships.

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

PHILADELPHIA – Oral remibrutinib was well tolerated and had a good safety profile over 24 weeks among patients with moderate to severe Sjögren syndrome (SS), according to new phase 2 data presented at the annual meeting of the American College of Rheumatology.

Thomas Dörner, MD, with the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin, presented the data from the double-blind, randomized, placebo-controlled, proof-of-concept study.

The authors said the results of the study suggest that remibrutinib, a highly specific inhibitor of Bruton tyrosine kinase, has the potential to become the first effective oral disease-modifying therapy for SS.

The 73 participants in the study had moderate to severe SS. The baseline EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score was at least 5, EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) was at least 5, and anti-Ro/SSA antibody positivity was 3 months or less before screening. The patients’ unstimulated whole salivary flow rate was > 0 mL/min.

Overall, 73 patients (71 women) were randomly assigned to receive either remibrutinib 100 mg twice a day (n = 24), remibrutinib 100 mg four times a day (n = 25), or placebo (n = 24) between August 2019 and May 2021.

Remibrutinib met the primary endpoint and resulted in a statistically significant improvement in ESSDAI score for both regimens combined compared with placebo at week 24 (ESSDAI, –2.86).
 

Patient-reported outcomes similar to placebo

Patient-reported outcomes, including scores on ESSPRI, Functional Assessment of Chronic Illness Therapy–Fatigue, and EuroQol-5 Dimension, were similar in the treatment groups and the placebo group.

“All of the patients, including the placebo patients, improved over the time of the study,” Dr. Dörner said.

The average age of the patients was 51.8 years (range, 18-75 years). Groups were generally balanced with regard to demographic qualities and disease severity at baseline, and the patients represented the SS population well, Dr. Dörner said.

No severe adverse events were reported. Infections were the most frequently reported adverse events, and the rates were similar with the study drug and placebo. No notable liver abnormalities were reported in any of the groups.

Chrisanna Dobrowolski, MD, assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York, told this news organization, “Preliminary results are promising, but they failed to show improvements in patient-reported quality-of-life measures.