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ATX-101: ‘You’re gonna like your new chin’
ISTANBUL – Both clinicians and patients gave favorable marks to a novel injectable pharmacologic treatment for removal of unwanted submental fat – the unsightly double chin – in two phase III randomized trials presented at the annual congress of the European Academy of Dermatology and Venereology.
The investigational chin-fat buster, known as ATX-101, is a proprietary purified synthetic form of deoxycholic acid. Upon injection directly into the submental fat, ATX-101 lyses adipocytes by disrupting their cell membranes.
There is an unmet need for a rigorously studied prescription product for nonsurgical treatment of excess submental fat. Not everyone with a double chin is interested in or a good candidate for the established surgical procedures, observed Dr. Berthold Rzany, a dermatologist at Charité University Hospital, Berlin, who presented a 363-patient, randomized, placebo-controlled phase III trial at the meeting. Participants had to have a body mass index no higher than 30 kg/m2, dissatisfaction with the appearance of their submental area, and a physician rating of moderate to severe submental fat. Three-quarters of the subjects were women, with a mean age of 46 years and a mean BMI of 25.7 kg/m2.
One of the two primary efficacy endpoints required at least a 1-point improvement on the 0- to 4-point Clinician-Reported Submental Fat Rating Scale as assessed 12 weeks after the final treatment. This was achieved in 59% of patients randomized to ATX-101 at a dose of 1mg/cm2 and 65% at 2 mg/cm2, both significantly higher rates than the 23% in placebo-treated controls.
The other primary endpoint required a high level of patient satisfaction with the appearance of their face and chin after treatment as expressed in a Subject Self-Rating Scale score of 4 or more on the 0-6 scale. This endpoint was achieved in 53% of patients treated with ATX-101 at 1 mg/cm2, 66% who received the agent at 2 mg/cm2, and 29% of the placebo group.
ATX-101-treated patients were also significantly more likely to report perceived improvement in the visual and psychological impact of their submental fat. For example, 74% of patients who received ATX-101 at 1 mg/cm2 and 80% at 2 mg/cm2 reported improved definition between their chin and neck, compared with baseline and compared with 28% of placebo-treated controls. In addition, 32% of patients who received the lower dose of ATX-101 and 39% who got the higher dose characterized their submental fat as "a great deal better," compared with baseline, as did a mere 7% of controls.
Also, patients who received ATX-101 reported 12 weeks post treatment that they looked less overweight and were less bothered by and self-conscious about their submental fat, compared with controls.
Treatment-emergent induration, redness, bruising, numbness, and/or swelling variously occurred in one-third to two-thirds of ATX-101 recipients. All of these adverse events were more common than in placebo-treated controls. However, the events were transient and mostly mild or moderate in intensity. The exception was injection site pain, which occurred in roughly 80% of ATX-101-treated patients and was mostly moderate to severe, although it lasted a median of only 1 day, according to Dr. Rzany.
The ATX-101 treatment regimen entails up to 50 2-mL fixed-dose subcutaneous injections 1 cm apart per treatment session. Up to four treatment sessions were permitted, each separated by a minimum of 4 weeks.
In a separate presentation, Dr. Benjamin Ascher reported on 360 randomized patients who participated in the other phase III clinical trial. The two studies had the same design and endpoints.
An improvement of at least 1 point on the Clinician-Reported Submental Fat Rating Scale occurred in 58% of patients randomized to ATX-101 at the 1 mg/cm2 dose, 62% of those who received the higher dose, and 35% on placebo. Moreover, 68% of patients who got ATX-101 at 1 mg/cm2 were satisfied with their resultant appearance as reflected in a Subject Self-Rating Scale score of at least 4. So were 65% of those who received the higher dose and 29% of placebo-treated controls. As in the previously mentioned study, indices of self-image and psychological well being were also improved following the aesthetic therapy. Treatment-related adverse events were mostly transient and mild to moderate in intensity, according to Dr. Ascher, who is in the private practice of aesthetic surgery in Paris.
Both phase III studies were supported by Bayer HealthCare and KYTHERA Biopharmaceuticals. Dr. Rzany and Dr. Ascher serve as advisers to the companies.
ISTANBUL – Both clinicians and patients gave favorable marks to a novel injectable pharmacologic treatment for removal of unwanted submental fat – the unsightly double chin – in two phase III randomized trials presented at the annual congress of the European Academy of Dermatology and Venereology.
The investigational chin-fat buster, known as ATX-101, is a proprietary purified synthetic form of deoxycholic acid. Upon injection directly into the submental fat, ATX-101 lyses adipocytes by disrupting their cell membranes.
There is an unmet need for a rigorously studied prescription product for nonsurgical treatment of excess submental fat. Not everyone with a double chin is interested in or a good candidate for the established surgical procedures, observed Dr. Berthold Rzany, a dermatologist at Charité University Hospital, Berlin, who presented a 363-patient, randomized, placebo-controlled phase III trial at the meeting. Participants had to have a body mass index no higher than 30 kg/m2, dissatisfaction with the appearance of their submental area, and a physician rating of moderate to severe submental fat. Three-quarters of the subjects were women, with a mean age of 46 years and a mean BMI of 25.7 kg/m2.
One of the two primary efficacy endpoints required at least a 1-point improvement on the 0- to 4-point Clinician-Reported Submental Fat Rating Scale as assessed 12 weeks after the final treatment. This was achieved in 59% of patients randomized to ATX-101 at a dose of 1mg/cm2 and 65% at 2 mg/cm2, both significantly higher rates than the 23% in placebo-treated controls.
The other primary endpoint required a high level of patient satisfaction with the appearance of their face and chin after treatment as expressed in a Subject Self-Rating Scale score of 4 or more on the 0-6 scale. This endpoint was achieved in 53% of patients treated with ATX-101 at 1 mg/cm2, 66% who received the agent at 2 mg/cm2, and 29% of the placebo group.
ATX-101-treated patients were also significantly more likely to report perceived improvement in the visual and psychological impact of their submental fat. For example, 74% of patients who received ATX-101 at 1 mg/cm2 and 80% at 2 mg/cm2 reported improved definition between their chin and neck, compared with baseline and compared with 28% of placebo-treated controls. In addition, 32% of patients who received the lower dose of ATX-101 and 39% who got the higher dose characterized their submental fat as "a great deal better," compared with baseline, as did a mere 7% of controls.
Also, patients who received ATX-101 reported 12 weeks post treatment that they looked less overweight and were less bothered by and self-conscious about their submental fat, compared with controls.
Treatment-emergent induration, redness, bruising, numbness, and/or swelling variously occurred in one-third to two-thirds of ATX-101 recipients. All of these adverse events were more common than in placebo-treated controls. However, the events were transient and mostly mild or moderate in intensity. The exception was injection site pain, which occurred in roughly 80% of ATX-101-treated patients and was mostly moderate to severe, although it lasted a median of only 1 day, according to Dr. Rzany.
The ATX-101 treatment regimen entails up to 50 2-mL fixed-dose subcutaneous injections 1 cm apart per treatment session. Up to four treatment sessions were permitted, each separated by a minimum of 4 weeks.
In a separate presentation, Dr. Benjamin Ascher reported on 360 randomized patients who participated in the other phase III clinical trial. The two studies had the same design and endpoints.
An improvement of at least 1 point on the Clinician-Reported Submental Fat Rating Scale occurred in 58% of patients randomized to ATX-101 at the 1 mg/cm2 dose, 62% of those who received the higher dose, and 35% on placebo. Moreover, 68% of patients who got ATX-101 at 1 mg/cm2 were satisfied with their resultant appearance as reflected in a Subject Self-Rating Scale score of at least 4. So were 65% of those who received the higher dose and 29% of placebo-treated controls. As in the previously mentioned study, indices of self-image and psychological well being were also improved following the aesthetic therapy. Treatment-related adverse events were mostly transient and mild to moderate in intensity, according to Dr. Ascher, who is in the private practice of aesthetic surgery in Paris.
Both phase III studies were supported by Bayer HealthCare and KYTHERA Biopharmaceuticals. Dr. Rzany and Dr. Ascher serve as advisers to the companies.
ISTANBUL – Both clinicians and patients gave favorable marks to a novel injectable pharmacologic treatment for removal of unwanted submental fat – the unsightly double chin – in two phase III randomized trials presented at the annual congress of the European Academy of Dermatology and Venereology.
The investigational chin-fat buster, known as ATX-101, is a proprietary purified synthetic form of deoxycholic acid. Upon injection directly into the submental fat, ATX-101 lyses adipocytes by disrupting their cell membranes.
There is an unmet need for a rigorously studied prescription product for nonsurgical treatment of excess submental fat. Not everyone with a double chin is interested in or a good candidate for the established surgical procedures, observed Dr. Berthold Rzany, a dermatologist at Charité University Hospital, Berlin, who presented a 363-patient, randomized, placebo-controlled phase III trial at the meeting. Participants had to have a body mass index no higher than 30 kg/m2, dissatisfaction with the appearance of their submental area, and a physician rating of moderate to severe submental fat. Three-quarters of the subjects were women, with a mean age of 46 years and a mean BMI of 25.7 kg/m2.
One of the two primary efficacy endpoints required at least a 1-point improvement on the 0- to 4-point Clinician-Reported Submental Fat Rating Scale as assessed 12 weeks after the final treatment. This was achieved in 59% of patients randomized to ATX-101 at a dose of 1mg/cm2 and 65% at 2 mg/cm2, both significantly higher rates than the 23% in placebo-treated controls.
The other primary endpoint required a high level of patient satisfaction with the appearance of their face and chin after treatment as expressed in a Subject Self-Rating Scale score of 4 or more on the 0-6 scale. This endpoint was achieved in 53% of patients treated with ATX-101 at 1 mg/cm2, 66% who received the agent at 2 mg/cm2, and 29% of the placebo group.
ATX-101-treated patients were also significantly more likely to report perceived improvement in the visual and psychological impact of their submental fat. For example, 74% of patients who received ATX-101 at 1 mg/cm2 and 80% at 2 mg/cm2 reported improved definition between their chin and neck, compared with baseline and compared with 28% of placebo-treated controls. In addition, 32% of patients who received the lower dose of ATX-101 and 39% who got the higher dose characterized their submental fat as "a great deal better," compared with baseline, as did a mere 7% of controls.
Also, patients who received ATX-101 reported 12 weeks post treatment that they looked less overweight and were less bothered by and self-conscious about their submental fat, compared with controls.
Treatment-emergent induration, redness, bruising, numbness, and/or swelling variously occurred in one-third to two-thirds of ATX-101 recipients. All of these adverse events were more common than in placebo-treated controls. However, the events were transient and mostly mild or moderate in intensity. The exception was injection site pain, which occurred in roughly 80% of ATX-101-treated patients and was mostly moderate to severe, although it lasted a median of only 1 day, according to Dr. Rzany.
The ATX-101 treatment regimen entails up to 50 2-mL fixed-dose subcutaneous injections 1 cm apart per treatment session. Up to four treatment sessions were permitted, each separated by a minimum of 4 weeks.
In a separate presentation, Dr. Benjamin Ascher reported on 360 randomized patients who participated in the other phase III clinical trial. The two studies had the same design and endpoints.
An improvement of at least 1 point on the Clinician-Reported Submental Fat Rating Scale occurred in 58% of patients randomized to ATX-101 at the 1 mg/cm2 dose, 62% of those who received the higher dose, and 35% on placebo. Moreover, 68% of patients who got ATX-101 at 1 mg/cm2 were satisfied with their resultant appearance as reflected in a Subject Self-Rating Scale score of at least 4. So were 65% of those who received the higher dose and 29% of placebo-treated controls. As in the previously mentioned study, indices of self-image and psychological well being were also improved following the aesthetic therapy. Treatment-related adverse events were mostly transient and mild to moderate in intensity, according to Dr. Ascher, who is in the private practice of aesthetic surgery in Paris.
Both phase III studies were supported by Bayer HealthCare and KYTHERA Biopharmaceuticals. Dr. Rzany and Dr. Ascher serve as advisers to the companies.
AT THE EADV CONGRESS
Major finding: Patients with excess submental fat who received treatment using a novel subcutaneously injectable agent for the nonsurgical reduction of double chins were significantly more likely to be satisfied with their chin’s appearance afterward than were placebo-treated controls.
Data source: The two studies included a total of 723 patients with moderate to severe excess submental fat.
Disclosures: The studies were funded by Bayer HealthCare and KYTHERA Biopharmaceuticals. The presenters have received research grants from and serve as advisers to the companies.
Knee replacement delayed by hyaluronic acid injections
SAN DIEGO – Viscosupplementation using hyaluronic acid injections delayed total knee replacement for patients with knee osteoarthritis by up to a median 2.6 years in a retrospective observational study.
The study, involving analysis of a large commercial health insurance claims database (Truven MarketScan), included all 16,529 patients with knee osteoarthritis (OA) who made their first visit to a specialist for the condition in 2008-2011 and who eventually went on to total knee replacement surgery.
Among this group were 4,178 knee OA patients who underwent one or more courses of treatment with any of the Food and Drug Administration–approved injectable hyaluronic acid products. A total of 3,647 of these patients were successfully matched to controls with knee OA who had total knee replacement surgery without any prior hyaluronic acid injections, Dr. Roy D. Altman explained at the annual meeting of the American College of Rheumatology.
The matching process relied upon propensity scores based on age, sex, physician specialty, diagnosis at the first specialist visit, and year. Therein lays a significant study limitation: These variables provide only limited ability to adjust for any differences in baseline knee OA severity that might have existed between patients who did or didn’t receive hyaluronic acid injections. Nor can an observational study establish causality, observed Dr. Altman, professor emeritus of medicine at the University of California, Los Angeles.
That being said, the study demonstrated a strong dose-dependent relationship between viscosupplementation and time from first specialist visit to knee replacement surgery, he noted.
Seventy-nine percent of patients who got hyaluronic acid injections received a single course consisting of either one injection or a series of injections, depending upon the specific product. Those patients experienced a median 233-day increase in the time to surgery, compared with matched controls who didn’t get hyaluronic acid injections.
Moreover, the 16% of viscosupplementation recipients who underwent a second round of treatment further delayed their median time from first specialist visit to total knee replacement by an additional 7 months. And that pattern continued in the relatively small numbers of patients who underwent three or more courses of viscosupplementation: Each round of hyaluronic acid injections brought a roughly 7-month further delay in time to surgery, out to a total of 2.6 years.
The study was sponsored by Johnson & Johnson. Dr. Altman reported having no financial conflicts.
SAN DIEGO – Viscosupplementation using hyaluronic acid injections delayed total knee replacement for patients with knee osteoarthritis by up to a median 2.6 years in a retrospective observational study.
The study, involving analysis of a large commercial health insurance claims database (Truven MarketScan), included all 16,529 patients with knee osteoarthritis (OA) who made their first visit to a specialist for the condition in 2008-2011 and who eventually went on to total knee replacement surgery.
Among this group were 4,178 knee OA patients who underwent one or more courses of treatment with any of the Food and Drug Administration–approved injectable hyaluronic acid products. A total of 3,647 of these patients were successfully matched to controls with knee OA who had total knee replacement surgery without any prior hyaluronic acid injections, Dr. Roy D. Altman explained at the annual meeting of the American College of Rheumatology.
The matching process relied upon propensity scores based on age, sex, physician specialty, diagnosis at the first specialist visit, and year. Therein lays a significant study limitation: These variables provide only limited ability to adjust for any differences in baseline knee OA severity that might have existed between patients who did or didn’t receive hyaluronic acid injections. Nor can an observational study establish causality, observed Dr. Altman, professor emeritus of medicine at the University of California, Los Angeles.
That being said, the study demonstrated a strong dose-dependent relationship between viscosupplementation and time from first specialist visit to knee replacement surgery, he noted.
Seventy-nine percent of patients who got hyaluronic acid injections received a single course consisting of either one injection or a series of injections, depending upon the specific product. Those patients experienced a median 233-day increase in the time to surgery, compared with matched controls who didn’t get hyaluronic acid injections.
Moreover, the 16% of viscosupplementation recipients who underwent a second round of treatment further delayed their median time from first specialist visit to total knee replacement by an additional 7 months. And that pattern continued in the relatively small numbers of patients who underwent three or more courses of viscosupplementation: Each round of hyaluronic acid injections brought a roughly 7-month further delay in time to surgery, out to a total of 2.6 years.
The study was sponsored by Johnson & Johnson. Dr. Altman reported having no financial conflicts.
SAN DIEGO – Viscosupplementation using hyaluronic acid injections delayed total knee replacement for patients with knee osteoarthritis by up to a median 2.6 years in a retrospective observational study.
The study, involving analysis of a large commercial health insurance claims database (Truven MarketScan), included all 16,529 patients with knee osteoarthritis (OA) who made their first visit to a specialist for the condition in 2008-2011 and who eventually went on to total knee replacement surgery.
Among this group were 4,178 knee OA patients who underwent one or more courses of treatment with any of the Food and Drug Administration–approved injectable hyaluronic acid products. A total of 3,647 of these patients were successfully matched to controls with knee OA who had total knee replacement surgery without any prior hyaluronic acid injections, Dr. Roy D. Altman explained at the annual meeting of the American College of Rheumatology.
The matching process relied upon propensity scores based on age, sex, physician specialty, diagnosis at the first specialist visit, and year. Therein lays a significant study limitation: These variables provide only limited ability to adjust for any differences in baseline knee OA severity that might have existed between patients who did or didn’t receive hyaluronic acid injections. Nor can an observational study establish causality, observed Dr. Altman, professor emeritus of medicine at the University of California, Los Angeles.
That being said, the study demonstrated a strong dose-dependent relationship between viscosupplementation and time from first specialist visit to knee replacement surgery, he noted.
Seventy-nine percent of patients who got hyaluronic acid injections received a single course consisting of either one injection or a series of injections, depending upon the specific product. Those patients experienced a median 233-day increase in the time to surgery, compared with matched controls who didn’t get hyaluronic acid injections.
Moreover, the 16% of viscosupplementation recipients who underwent a second round of treatment further delayed their median time from first specialist visit to total knee replacement by an additional 7 months. And that pattern continued in the relatively small numbers of patients who underwent three or more courses of viscosupplementation: Each round of hyaluronic acid injections brought a roughly 7-month further delay in time to surgery, out to a total of 2.6 years.
The study was sponsored by Johnson & Johnson. Dr. Altman reported having no financial conflicts.
AT THE ACR ANNUAL MEETING
Major finding: Patients with knee osteoarthritis who eventually underwent total knee replacement had their surgery delayed by a median 233 days if they received one course of viscosupplementation using hyaluronic acid injections. For those who received more than one round of injections, each additional course brought a further average 7-month delay in time to surgery out to 2.6 years.
Data source: Retrospective observational study involving a large commercial health insurance claims database matched 3,647 patients with knee osteoarthritis who underwent total knee replacement after receiving one or more courses of hyaluronic acid injections to an equal number who didn’t get hyaluronic acid injections prior to surgery.
Disclosures: The study was sponsored by Johnson & Johnson. The presenter reported having no financial conflicts.
Knee Osteoarthritis Often Overlooked in the Obese
SAN DIEGO – Knee osteoarthritis is too frequently underdiagnosed and undertreated by primary care physicians and bariatric surgeons in obese patients considering weight loss surgery.
That’s the conclusion Dr. Janice Lin and her coinvestigators at New York University reached based upon their prospective study in which 408 consecutive patients scheduled for bariatric surgery at NYU Langone Medical Center and Bellevue Hospital were screened for this common form of arthritis.
The researchers found that 54% of the obese patients reported significant knee pain. Of these 221 patients, 26 weren’t interested in further evaluation, but 115 were deemed likely to have knee osteoarthritis (OA) on the basis of a brief screen indicating they had knee pain on more than 15 days per month for longer than 1 month, had a visual analog scale (VAS) pain score of at least 30 out of 100, and didn’t have lupus, bilateral knee replacement, crystal disease, psoriasis, or an inflammatory arthritis. These 115 patients formed the study population for this ongoing prospective investigation.
The primary care physicians of only 47% of these 115 patients had evaluated their knee pain. Bariatric surgeons had similarly not addressed the knee pain in about half of cases. Indeed, fewer than one-third of these obese patients with knee pain had been assessed via knee x-rays in accord with guideline-recommended practice.
"In the bariatric population, knee pain is often attributed to mechanical load from obesity without proper evaluation or treatment. Patients are rarely referred to rheumatologists or other appropriate specialists, though they may benefit from such evaluation and management," according to Dr. Lin.
In fact, only 3% of these patients with significant knee pain had been referred to a rheumatologist and 15% to an orthopedic surgeon.
ACR treatment guidelines were for the most part not being followed. Although roughly three-quarters of patients were taking NSAIDs and/or acetaminophen, only 31% of the group had been referred for physical therapy, 14% had received a steroid injection, 11% used a topical NSAID, and 1% had undergone viscosupplementation, recommended as a second-line therapy.
All 115 study participants got a baseline posterior-anterior standing bilateral knee x-ray scored for Kellgren-Lawrence grade. Based on the findings, 19% of patients were determined to not have knee OA, 21% had mild Kellgren-Lawrence grade 1 disease, and the rest had more advanced knee OA.
The group’s mean baseline VAS pain score was 64.5. Their Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) mean pain, stiffness, and function scores were 268, 102, and 938, respectively.
This ongoing study builds upon an earlier retrospective study by Dr. Lin’s coinvestigators at New York University, who reported that 51% of 192 patients who underwent bariatric laparoscopic banding surgery had complete improvement in knee OA pain 19 months later.In the ongoing prospective study, participants will repeat the WOMAC and other validated measures of knee OA pain and function 1, 3, and 6 months after laparascopic banding, sleeve gastrectomy, or gastric bypass. They will also have follow-up knee x-rays. Dr. Lin and her coworkers will be eager to see if any of the three types of bariatric surgery is advantageous in terms of its impact on knee pain, she said.
She reported having no relevant financial conflicts.
SAN DIEGO – Knee osteoarthritis is too frequently underdiagnosed and undertreated by primary care physicians and bariatric surgeons in obese patients considering weight loss surgery.
That’s the conclusion Dr. Janice Lin and her coinvestigators at New York University reached based upon their prospective study in which 408 consecutive patients scheduled for bariatric surgery at NYU Langone Medical Center and Bellevue Hospital were screened for this common form of arthritis.
The researchers found that 54% of the obese patients reported significant knee pain. Of these 221 patients, 26 weren’t interested in further evaluation, but 115 were deemed likely to have knee osteoarthritis (OA) on the basis of a brief screen indicating they had knee pain on more than 15 days per month for longer than 1 month, had a visual analog scale (VAS) pain score of at least 30 out of 100, and didn’t have lupus, bilateral knee replacement, crystal disease, psoriasis, or an inflammatory arthritis. These 115 patients formed the study population for this ongoing prospective investigation.
The primary care physicians of only 47% of these 115 patients had evaluated their knee pain. Bariatric surgeons had similarly not addressed the knee pain in about half of cases. Indeed, fewer than one-third of these obese patients with knee pain had been assessed via knee x-rays in accord with guideline-recommended practice.
"In the bariatric population, knee pain is often attributed to mechanical load from obesity without proper evaluation or treatment. Patients are rarely referred to rheumatologists or other appropriate specialists, though they may benefit from such evaluation and management," according to Dr. Lin.
In fact, only 3% of these patients with significant knee pain had been referred to a rheumatologist and 15% to an orthopedic surgeon.
ACR treatment guidelines were for the most part not being followed. Although roughly three-quarters of patients were taking NSAIDs and/or acetaminophen, only 31% of the group had been referred for physical therapy, 14% had received a steroid injection, 11% used a topical NSAID, and 1% had undergone viscosupplementation, recommended as a second-line therapy.
All 115 study participants got a baseline posterior-anterior standing bilateral knee x-ray scored for Kellgren-Lawrence grade. Based on the findings, 19% of patients were determined to not have knee OA, 21% had mild Kellgren-Lawrence grade 1 disease, and the rest had more advanced knee OA.
The group’s mean baseline VAS pain score was 64.5. Their Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) mean pain, stiffness, and function scores were 268, 102, and 938, respectively.
This ongoing study builds upon an earlier retrospective study by Dr. Lin’s coinvestigators at New York University, who reported that 51% of 192 patients who underwent bariatric laparoscopic banding surgery had complete improvement in knee OA pain 19 months later.In the ongoing prospective study, participants will repeat the WOMAC and other validated measures of knee OA pain and function 1, 3, and 6 months after laparascopic banding, sleeve gastrectomy, or gastric bypass. They will also have follow-up knee x-rays. Dr. Lin and her coworkers will be eager to see if any of the three types of bariatric surgery is advantageous in terms of its impact on knee pain, she said.
She reported having no relevant financial conflicts.
SAN DIEGO – Knee osteoarthritis is too frequently underdiagnosed and undertreated by primary care physicians and bariatric surgeons in obese patients considering weight loss surgery.
That’s the conclusion Dr. Janice Lin and her coinvestigators at New York University reached based upon their prospective study in which 408 consecutive patients scheduled for bariatric surgery at NYU Langone Medical Center and Bellevue Hospital were screened for this common form of arthritis.
The researchers found that 54% of the obese patients reported significant knee pain. Of these 221 patients, 26 weren’t interested in further evaluation, but 115 were deemed likely to have knee osteoarthritis (OA) on the basis of a brief screen indicating they had knee pain on more than 15 days per month for longer than 1 month, had a visual analog scale (VAS) pain score of at least 30 out of 100, and didn’t have lupus, bilateral knee replacement, crystal disease, psoriasis, or an inflammatory arthritis. These 115 patients formed the study population for this ongoing prospective investigation.
The primary care physicians of only 47% of these 115 patients had evaluated their knee pain. Bariatric surgeons had similarly not addressed the knee pain in about half of cases. Indeed, fewer than one-third of these obese patients with knee pain had been assessed via knee x-rays in accord with guideline-recommended practice.
"In the bariatric population, knee pain is often attributed to mechanical load from obesity without proper evaluation or treatment. Patients are rarely referred to rheumatologists or other appropriate specialists, though they may benefit from such evaluation and management," according to Dr. Lin.
In fact, only 3% of these patients with significant knee pain had been referred to a rheumatologist and 15% to an orthopedic surgeon.
ACR treatment guidelines were for the most part not being followed. Although roughly three-quarters of patients were taking NSAIDs and/or acetaminophen, only 31% of the group had been referred for physical therapy, 14% had received a steroid injection, 11% used a topical NSAID, and 1% had undergone viscosupplementation, recommended as a second-line therapy.
All 115 study participants got a baseline posterior-anterior standing bilateral knee x-ray scored for Kellgren-Lawrence grade. Based on the findings, 19% of patients were determined to not have knee OA, 21% had mild Kellgren-Lawrence grade 1 disease, and the rest had more advanced knee OA.
The group’s mean baseline VAS pain score was 64.5. Their Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) mean pain, stiffness, and function scores were 268, 102, and 938, respectively.
This ongoing study builds upon an earlier retrospective study by Dr. Lin’s coinvestigators at New York University, who reported that 51% of 192 patients who underwent bariatric laparoscopic banding surgery had complete improvement in knee OA pain 19 months later.In the ongoing prospective study, participants will repeat the WOMAC and other validated measures of knee OA pain and function 1, 3, and 6 months after laparascopic banding, sleeve gastrectomy, or gastric bypass. They will also have follow-up knee x-rays. Dr. Lin and her coworkers will be eager to see if any of the three types of bariatric surgery is advantageous in terms of its impact on knee pain, she said.
She reported having no relevant financial conflicts.
AT THE ACR ANNUAL MEETING
Knee osteoarthritis often overlooked in the obese
SAN DIEGO – Knee osteoarthritis is too frequently underdiagnosed and undertreated by primary care physicians and bariatric surgeons in obese patients considering weight loss surgery.
That’s the conclusion Dr. Janice Lin and her coinvestigators at New York University reached based upon their prospective study in which 408 consecutive patients scheduled for bariatric surgery at NYU Langone Medical Center and Bellevue Hospital were screened for this common form of arthritis.
The researchers found that 54% of the obese patients reported significant knee pain. Of these 221 patients, 26 weren’t interested in further evaluation, but 115 were deemed likely to have knee osteoarthritis (OA) on the basis of a brief screen indicating they had knee pain on more than 15 days per month for longer than 1 month, had a visual analog scale (VAS) pain score of at least 30 out of 100, and didn’t have lupus, bilateral knee replacement, crystal disease, psoriasis, or an inflammatory arthritis. These 115 patients formed the study population for this ongoing prospective investigation.
The primary care physicians of only 47% of these 115 patients had evaluated their knee pain. Bariatric surgeons had similarly not addressed the knee pain in about half of cases. Indeed, fewer than one-third of these obese patients with knee pain had been assessed via knee x-rays in accord with guideline-recommended practice.
"In the bariatric population, knee pain is often attributed to mechanical load from obesity without proper evaluation or treatment. Patients are rarely referred to rheumatologists or other appropriate specialists, though they may benefit from such evaluation and management," according to Dr. Lin.
In fact, only 3% of these patients with significant knee pain had been referred to a rheumatologist and 15% to an orthopedic surgeon.
ACR treatment guidelines were for the most part not being followed. Although roughly three-quarters of patients were taking NSAIDs and/or acetaminophen, only 31% of the group had been referred for physical therapy, 14% had received a steroid injection, 11% used a topical NSAID, and 1% had undergone viscosupplementation, recommended as a second-line therapy.
All 115 study participants got a baseline posterior-anterior standing bilateral knee x-ray scored for Kellgren-Lawrence grade. Based on the findings, 19% of patients were determined to not have knee OA, 21% had mild Kellgren-Lawrence grade 1 disease, and the rest had more advanced knee OA.
The group’s mean baseline VAS pain score was 64.5. Their Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) mean pain, stiffness, and function scores were 268, 102, and 938, respectively.
This ongoing study builds upon an earlier retrospective study by Dr. Lin’s coinvestigators at New York University, who reported that 51% of 192 patients who underwent bariatric laparoscopic banding surgery had complete improvement in knee OA pain 19 months later.In the ongoing prospective study, participants will repeat the WOMAC and other validated measures of knee OA pain and function 1, 3, and 6 months after laparascopic banding, sleeve gastrectomy, or gastric bypass. They will also have follow-up knee x-rays. Dr. Lin and her coworkers will be eager to see if any of the three types of bariatric surgery is advantageous in terms of its impact on knee pain, she said.
She reported having no relevant financial conflicts.
SAN DIEGO – Knee osteoarthritis is too frequently underdiagnosed and undertreated by primary care physicians and bariatric surgeons in obese patients considering weight loss surgery.
That’s the conclusion Dr. Janice Lin and her coinvestigators at New York University reached based upon their prospective study in which 408 consecutive patients scheduled for bariatric surgery at NYU Langone Medical Center and Bellevue Hospital were screened for this common form of arthritis.
The researchers found that 54% of the obese patients reported significant knee pain. Of these 221 patients, 26 weren’t interested in further evaluation, but 115 were deemed likely to have knee osteoarthritis (OA) on the basis of a brief screen indicating they had knee pain on more than 15 days per month for longer than 1 month, had a visual analog scale (VAS) pain score of at least 30 out of 100, and didn’t have lupus, bilateral knee replacement, crystal disease, psoriasis, or an inflammatory arthritis. These 115 patients formed the study population for this ongoing prospective investigation.
The primary care physicians of only 47% of these 115 patients had evaluated their knee pain. Bariatric surgeons had similarly not addressed the knee pain in about half of cases. Indeed, fewer than one-third of these obese patients with knee pain had been assessed via knee x-rays in accord with guideline-recommended practice.
"In the bariatric population, knee pain is often attributed to mechanical load from obesity without proper evaluation or treatment. Patients are rarely referred to rheumatologists or other appropriate specialists, though they may benefit from such evaluation and management," according to Dr. Lin.
In fact, only 3% of these patients with significant knee pain had been referred to a rheumatologist and 15% to an orthopedic surgeon.
ACR treatment guidelines were for the most part not being followed. Although roughly three-quarters of patients were taking NSAIDs and/or acetaminophen, only 31% of the group had been referred for physical therapy, 14% had received a steroid injection, 11% used a topical NSAID, and 1% had undergone viscosupplementation, recommended as a second-line therapy.
All 115 study participants got a baseline posterior-anterior standing bilateral knee x-ray scored for Kellgren-Lawrence grade. Based on the findings, 19% of patients were determined to not have knee OA, 21% had mild Kellgren-Lawrence grade 1 disease, and the rest had more advanced knee OA.
The group’s mean baseline VAS pain score was 64.5. Their Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) mean pain, stiffness, and function scores were 268, 102, and 938, respectively.
This ongoing study builds upon an earlier retrospective study by Dr. Lin’s coinvestigators at New York University, who reported that 51% of 192 patients who underwent bariatric laparoscopic banding surgery had complete improvement in knee OA pain 19 months later.In the ongoing prospective study, participants will repeat the WOMAC and other validated measures of knee OA pain and function 1, 3, and 6 months after laparascopic banding, sleeve gastrectomy, or gastric bypass. They will also have follow-up knee x-rays. Dr. Lin and her coworkers will be eager to see if any of the three types of bariatric surgery is advantageous in terms of its impact on knee pain, she said.
She reported having no relevant financial conflicts.
SAN DIEGO – Knee osteoarthritis is too frequently underdiagnosed and undertreated by primary care physicians and bariatric surgeons in obese patients considering weight loss surgery.
That’s the conclusion Dr. Janice Lin and her coinvestigators at New York University reached based upon their prospective study in which 408 consecutive patients scheduled for bariatric surgery at NYU Langone Medical Center and Bellevue Hospital were screened for this common form of arthritis.
The researchers found that 54% of the obese patients reported significant knee pain. Of these 221 patients, 26 weren’t interested in further evaluation, but 115 were deemed likely to have knee osteoarthritis (OA) on the basis of a brief screen indicating they had knee pain on more than 15 days per month for longer than 1 month, had a visual analog scale (VAS) pain score of at least 30 out of 100, and didn’t have lupus, bilateral knee replacement, crystal disease, psoriasis, or an inflammatory arthritis. These 115 patients formed the study population for this ongoing prospective investigation.
The primary care physicians of only 47% of these 115 patients had evaluated their knee pain. Bariatric surgeons had similarly not addressed the knee pain in about half of cases. Indeed, fewer than one-third of these obese patients with knee pain had been assessed via knee x-rays in accord with guideline-recommended practice.
"In the bariatric population, knee pain is often attributed to mechanical load from obesity without proper evaluation or treatment. Patients are rarely referred to rheumatologists or other appropriate specialists, though they may benefit from such evaluation and management," according to Dr. Lin.
In fact, only 3% of these patients with significant knee pain had been referred to a rheumatologist and 15% to an orthopedic surgeon.
ACR treatment guidelines were for the most part not being followed. Although roughly three-quarters of patients were taking NSAIDs and/or acetaminophen, only 31% of the group had been referred for physical therapy, 14% had received a steroid injection, 11% used a topical NSAID, and 1% had undergone viscosupplementation, recommended as a second-line therapy.
All 115 study participants got a baseline posterior-anterior standing bilateral knee x-ray scored for Kellgren-Lawrence grade. Based on the findings, 19% of patients were determined to not have knee OA, 21% had mild Kellgren-Lawrence grade 1 disease, and the rest had more advanced knee OA.
The group’s mean baseline VAS pain score was 64.5. Their Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) mean pain, stiffness, and function scores were 268, 102, and 938, respectively.
This ongoing study builds upon an earlier retrospective study by Dr. Lin’s coinvestigators at New York University, who reported that 51% of 192 patients who underwent bariatric laparoscopic banding surgery had complete improvement in knee OA pain 19 months later.In the ongoing prospective study, participants will repeat the WOMAC and other validated measures of knee OA pain and function 1, 3, and 6 months after laparascopic banding, sleeve gastrectomy, or gastric bypass. They will also have follow-up knee x-rays. Dr. Lin and her coworkers will be eager to see if any of the three types of bariatric surgery is advantageous in terms of its impact on knee pain, she said.
She reported having no relevant financial conflicts.
AT THE ACR ANNUAL MEETING
Major finding: Significant knee pain in a group of obese patients scheduled for bariatric surgery had previously been evaluated by the patients’ primary care physicians or bariatric surgeons in only about half of cases. Less than one-third had undergone a knee x-ray.
Data source: An ongoing prospective study of 115 bariatric surgery candidates with significant knee pain likely due to knee osteoarthritis.
Disclosures: The presenter of this unfunded study reported having no relevant financial conflicts.
Soda Boosts Rheumatoid Arthritis Risk
SAN DIEGO – Women who regularly drink one or more sugar-sweetened soft drinks per day are at heightened risk of developing seropositive rheumatoid arthritis, according to a massive analysis of combined data from the prospective-cohort Nurses’ Health Study and Nurses’ Health Study II.
During 1.9 million person-years of prospective follow-up in the Nurses' Health Study (NHS) and 1.5 million person-years in NHS II, there were 563 confirmed cases of new-onset seropositive rheumatoid arthritis and 320 cases of seronegative rheumatoid arthritis. The two studies collectively enrolled 238,131 U.S. female registered nurses who periodically filled out validated food frequency questionnaires.
In a multivariate analysis adjusted for numerous potential confounding variables, women who reported drinking an average of one or more non-diet sodas per day had a 71% greater risk of developing seropositive rheumatoid arthritis during follow-up than did those who drank none or less than one per month (P = .005), Yang Hu reported at the annual meeting of the American College of Rheumatology.
It’s noteworthy that the increased risk was present at a cut point of one daily serving, a level of consumption many Americans wouldn’t view as excessive.
The mechanism for the observed association between frequent soft drink consumption and seropositive rheumatoid arthritis remains unclear. The investigators decided to look at sugar-containing soda consumption because it has been shown to be associated with overweight and obesity, type 2 diabetes, and cardiovascular disease. And since obesity has previously been shown to be associated with increased risk of rheumatoid arthritis, the thinking was that obesity might mediate the link between soda consumption and rheumatoid arthritis. Daily soda consumption, however, was independently associated with a 71% increase in risk even after controlling for body mass index in the multivariate analysis, noted Mr. Hu of Brigham and Women’s Hospital, Boston.
Other potential confounders that were adjusted for in the analysis included age, smoking, alcohol consumption, physical activity, reproductive factors, multivitamin use, income level, and diet quality.
The NHS and NHS II studies are funded by the National Institutes of Health. Mr. Hu reported having no financial conflicts of interest, but one of his associates disclosed relationships with several pharmaceutical companies.
*Correction, 11/15/2013: An earlier version of the article misstated the number of nurses involved in the analysis.
SAN DIEGO – Women who regularly drink one or more sugar-sweetened soft drinks per day are at heightened risk of developing seropositive rheumatoid arthritis, according to a massive analysis of combined data from the prospective-cohort Nurses’ Health Study and Nurses’ Health Study II.
During 1.9 million person-years of prospective follow-up in the Nurses' Health Study (NHS) and 1.5 million person-years in NHS II, there were 563 confirmed cases of new-onset seropositive rheumatoid arthritis and 320 cases of seronegative rheumatoid arthritis. The two studies collectively enrolled 238,131 U.S. female registered nurses who periodically filled out validated food frequency questionnaires.
In a multivariate analysis adjusted for numerous potential confounding variables, women who reported drinking an average of one or more non-diet sodas per day had a 71% greater risk of developing seropositive rheumatoid arthritis during follow-up than did those who drank none or less than one per month (P = .005), Yang Hu reported at the annual meeting of the American College of Rheumatology.
It’s noteworthy that the increased risk was present at a cut point of one daily serving, a level of consumption many Americans wouldn’t view as excessive.
The mechanism for the observed association between frequent soft drink consumption and seropositive rheumatoid arthritis remains unclear. The investigators decided to look at sugar-containing soda consumption because it has been shown to be associated with overweight and obesity, type 2 diabetes, and cardiovascular disease. And since obesity has previously been shown to be associated with increased risk of rheumatoid arthritis, the thinking was that obesity might mediate the link between soda consumption and rheumatoid arthritis. Daily soda consumption, however, was independently associated with a 71% increase in risk even after controlling for body mass index in the multivariate analysis, noted Mr. Hu of Brigham and Women’s Hospital, Boston.
Other potential confounders that were adjusted for in the analysis included age, smoking, alcohol consumption, physical activity, reproductive factors, multivitamin use, income level, and diet quality.
The NHS and NHS II studies are funded by the National Institutes of Health. Mr. Hu reported having no financial conflicts of interest, but one of his associates disclosed relationships with several pharmaceutical companies.
*Correction, 11/15/2013: An earlier version of the article misstated the number of nurses involved in the analysis.
SAN DIEGO – Women who regularly drink one or more sugar-sweetened soft drinks per day are at heightened risk of developing seropositive rheumatoid arthritis, according to a massive analysis of combined data from the prospective-cohort Nurses’ Health Study and Nurses’ Health Study II.
During 1.9 million person-years of prospective follow-up in the Nurses' Health Study (NHS) and 1.5 million person-years in NHS II, there were 563 confirmed cases of new-onset seropositive rheumatoid arthritis and 320 cases of seronegative rheumatoid arthritis. The two studies collectively enrolled 238,131 U.S. female registered nurses who periodically filled out validated food frequency questionnaires.
In a multivariate analysis adjusted for numerous potential confounding variables, women who reported drinking an average of one or more non-diet sodas per day had a 71% greater risk of developing seropositive rheumatoid arthritis during follow-up than did those who drank none or less than one per month (P = .005), Yang Hu reported at the annual meeting of the American College of Rheumatology.
It’s noteworthy that the increased risk was present at a cut point of one daily serving, a level of consumption many Americans wouldn’t view as excessive.
The mechanism for the observed association between frequent soft drink consumption and seropositive rheumatoid arthritis remains unclear. The investigators decided to look at sugar-containing soda consumption because it has been shown to be associated with overweight and obesity, type 2 diabetes, and cardiovascular disease. And since obesity has previously been shown to be associated with increased risk of rheumatoid arthritis, the thinking was that obesity might mediate the link between soda consumption and rheumatoid arthritis. Daily soda consumption, however, was independently associated with a 71% increase in risk even after controlling for body mass index in the multivariate analysis, noted Mr. Hu of Brigham and Women’s Hospital, Boston.
Other potential confounders that were adjusted for in the analysis included age, smoking, alcohol consumption, physical activity, reproductive factors, multivitamin use, income level, and diet quality.
The NHS and NHS II studies are funded by the National Institutes of Health. Mr. Hu reported having no financial conflicts of interest, but one of his associates disclosed relationships with several pharmaceutical companies.
*Correction, 11/15/2013: An earlier version of the article misstated the number of nurses involved in the analysis.
AT THE ACR ANNUAL MEETING
Soda pop boosts rheumatoid arthritis risk
SAN DIEGO – Women who regularly drink one or more sugar-sweetened soft drinks per day are at heightened risk of developing seropositive rheumatoid arthritis, according to a massive analysis of combined data from the prospective-cohort Nurses’ Health Study and Nurses’ Health Study II.
During 1.9 million person-years of prospective follow-up in the Nurses' Health Study (NHS) and 1.5 million person-years in NHS II, there were 563 confirmed cases of new-onset seropositive rheumatoid arthritis and 320 cases of seronegative rheumatoid arthritis. The two studies collectively enrolled 238,131 U.S. female registered nurses who periodically filled out validated food frequency questionnaires.
In a multivariate analysis adjusted for numerous potential confounding variables, women who reported drinking an average of one or more non-diet sodas per day had a 71% greater risk of developing seropositive rheumatoid arthritis during follow-up than did those who drank none or less than one per month (P = .005), Yang Hu reported at the annual meeting of the American College of Rheumatology.
It’s noteworthy that the increased risk was present at a cut point of one daily serving, a level of consumption many Americans wouldn’t view as excessive.
The mechanism for the observed association between frequent soft drink consumption and seropositive rheumatoid arthritis remains unclear. The investigators decided to look at sugar-containing soda consumption because it has been shown to be associated with overweight and obesity, type 2 diabetes, and cardiovascular disease. And since obesity has previously been shown to be associated with increased risk of rheumatoid arthritis, the thinking was that obesity might mediate the link between soda consumption and rheumatoid arthritis. Daily soda consumption, however, was independently associated with a 71% increase in risk even after controlling for body mass index in the multivariate analysis, noted Mr. Hu of Brigham and Women’s Hospital, Boston.
Other potential confounders that were adjusted for in the analysis included age, smoking, alcohol consumption, physical activity, reproductive factors, multivitamin use, income level, and diet quality.
The NHS and NHS II studies are funded by the National Institutes of Health. Mr. Hu reported having no financial conflicts of interest, but one of his associates disclosed relationships with several pharmaceutical companies.
*Correction, 11/15/2013: An earlier version of the article misstated the number of nurses involved in the analysis.
SAN DIEGO – Women who regularly drink one or more sugar-sweetened soft drinks per day are at heightened risk of developing seropositive rheumatoid arthritis, according to a massive analysis of combined data from the prospective-cohort Nurses’ Health Study and Nurses’ Health Study II.
During 1.9 million person-years of prospective follow-up in the Nurses' Health Study (NHS) and 1.5 million person-years in NHS II, there were 563 confirmed cases of new-onset seropositive rheumatoid arthritis and 320 cases of seronegative rheumatoid arthritis. The two studies collectively enrolled 238,131 U.S. female registered nurses who periodically filled out validated food frequency questionnaires.
In a multivariate analysis adjusted for numerous potential confounding variables, women who reported drinking an average of one or more non-diet sodas per day had a 71% greater risk of developing seropositive rheumatoid arthritis during follow-up than did those who drank none or less than one per month (P = .005), Yang Hu reported at the annual meeting of the American College of Rheumatology.
It’s noteworthy that the increased risk was present at a cut point of one daily serving, a level of consumption many Americans wouldn’t view as excessive.
The mechanism for the observed association between frequent soft drink consumption and seropositive rheumatoid arthritis remains unclear. The investigators decided to look at sugar-containing soda consumption because it has been shown to be associated with overweight and obesity, type 2 diabetes, and cardiovascular disease. And since obesity has previously been shown to be associated with increased risk of rheumatoid arthritis, the thinking was that obesity might mediate the link between soda consumption and rheumatoid arthritis. Daily soda consumption, however, was independently associated with a 71% increase in risk even after controlling for body mass index in the multivariate analysis, noted Mr. Hu of Brigham and Women’s Hospital, Boston.
Other potential confounders that were adjusted for in the analysis included age, smoking, alcohol consumption, physical activity, reproductive factors, multivitamin use, income level, and diet quality.
The NHS and NHS II studies are funded by the National Institutes of Health. Mr. Hu reported having no financial conflicts of interest, but one of his associates disclosed relationships with several pharmaceutical companies.
*Correction, 11/15/2013: An earlier version of the article misstated the number of nurses involved in the analysis.
SAN DIEGO – Women who regularly drink one or more sugar-sweetened soft drinks per day are at heightened risk of developing seropositive rheumatoid arthritis, according to a massive analysis of combined data from the prospective-cohort Nurses’ Health Study and Nurses’ Health Study II.
During 1.9 million person-years of prospective follow-up in the Nurses' Health Study (NHS) and 1.5 million person-years in NHS II, there were 563 confirmed cases of new-onset seropositive rheumatoid arthritis and 320 cases of seronegative rheumatoid arthritis. The two studies collectively enrolled 238,131 U.S. female registered nurses who periodically filled out validated food frequency questionnaires.
In a multivariate analysis adjusted for numerous potential confounding variables, women who reported drinking an average of one or more non-diet sodas per day had a 71% greater risk of developing seropositive rheumatoid arthritis during follow-up than did those who drank none or less than one per month (P = .005), Yang Hu reported at the annual meeting of the American College of Rheumatology.
It’s noteworthy that the increased risk was present at a cut point of one daily serving, a level of consumption many Americans wouldn’t view as excessive.
The mechanism for the observed association between frequent soft drink consumption and seropositive rheumatoid arthritis remains unclear. The investigators decided to look at sugar-containing soda consumption because it has been shown to be associated with overweight and obesity, type 2 diabetes, and cardiovascular disease. And since obesity has previously been shown to be associated with increased risk of rheumatoid arthritis, the thinking was that obesity might mediate the link between soda consumption and rheumatoid arthritis. Daily soda consumption, however, was independently associated with a 71% increase in risk even after controlling for body mass index in the multivariate analysis, noted Mr. Hu of Brigham and Women’s Hospital, Boston.
Other potential confounders that were adjusted for in the analysis included age, smoking, alcohol consumption, physical activity, reproductive factors, multivitamin use, income level, and diet quality.
The NHS and NHS II studies are funded by the National Institutes of Health. Mr. Hu reported having no financial conflicts of interest, but one of his associates disclosed relationships with several pharmaceutical companies.
*Correction, 11/15/2013: An earlier version of the article misstated the number of nurses involved in the analysis.
AT THE ACR ANNUAL MEETING
Major finding: Women who reported drinking an average of one or more sugar-containing soft drinks per day had a highly significant 71% increased risk of developing seropositive rheumatoid arthritis during prospective follow-up than those who drank none or less than one serving per month.
Data source: This was an analysis of 238,131 American female nurses* prospectively followed for 3.4 million person-years in the Nurses’ Health Study and Nurses’ Health Study II.
Disclosures: The studies were funded by the National Institutes of Health. Mr. Hu reported having no financial conflicts.
Novel predictor of poor outcomes in lupus pregnancies
SAN DIEGO – Alteration in the balance of placentally secreted angiogenic factors early in pregnancy provides a potent new predictor of subsequent preeclampsia and other poor outcomes in pregnant women with systemic lupus erythematosus and/or antiphospholipid antibody syndrome.
Patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibody syndrome (APS) who had an elevated ratio of a splice variant of vascular endothelial growth factor R1 called sFLT1 to placental growth factor (PlGF) when measured at 16-19 weeks’ gestation were at 13.8-fold increased relative risk of preeclampsia before 34 weeks, compared with patients with an sFLT1/PlGF ratio below that cut-point in the large, multicenter, observational PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and SLE) study, Dr. Jane E. Salmon reported at the annual meeting of the American College of Rheumatology.
"Nearly half of the patients with an SFLT1/PlGF ratio greater than 3.45 when measured at 16-19 weeks’ gestation will develop early preeclampsia. On the other hand, a low ratio, as well as low levels of sFLT1 or high levels of PlGF, can reassure physicians and patients that preterm preeclampsia is unlikely: a 3% chance," said Dr. Salmon, professor of medicine and of ob.gyn. at Cornell University and a rheumatologist at the Hospital for Special Surgery, both in New York.
Pregnancy in patients with lupus is associated with obstetric complications placing both mother and fetus at great risk. Yet, until now it hasn’t been possible to predict which patients will have poor outcomes.
The key to identifying those at high risk lies in a recognition that preeclampsia and other poor outcomes are dramatic manifestations of placental insufficiency, which actually begins, initially silently, early in pregnancy. The maternal hypertension, proteinuria, thrombocytopenia, and other end-organ manifestations of preeclampsia are caused by maternal endothelial dysfunction mediated by placental secretion of antiangiogenic factors. Angiogenic growth factors, such as PIGF and vascular endothelial growth factor (VEGF), are essential to a healthy endothelium. But placentally secreted sFLT1 binds to these two angiogenic growth factors, rendering them unavailable to the endothelium, she explained.
Overexpression of sFLT1 in multiple animal models results in hypertension and proteinuria, the hallmarks of preeclampsia. Moreover, cancer patients treated with VEGF inhibitors often develop these two conditions. Based in part on these observations, Dr. Salmon and her coinvestigators turned to the PROMISSE study to test their hypothesis that elevated levels of antiangiogenic factors early in pregnancy predict poor outcomes in patients with SLE and/or APS. The prospective study involved 503 pregnant women with SLE and/or APS and 204 healthy controls, all with monthly blood draws starting before 12 weeks’ gestation.
The composite outcome of preeclampsia, small for gestational age, indicated preterm delivery, and other adverse events occurred in 37% of SLE patients who also had APS. The rate was 16% in patients with SLE alone, 26% in those with APS alone, and 3% in controls.
Subjects with SLE and/or APS who developed preeclampsia and other pregnancy complications displayed significantly higher levels of sFLT1 beginning at 12 weeks and sustained through 31 weeks’ gestation, compared with those with normal pregnancies. Moreover, PlGF levels were significantly lower during weeks 16-31 in the patients with pregnancy complications. The investigators determined that the best predictor of pregnancy complications was the ratio of antiangiogenic sFLT1 to angiogenic PlGF. And the optimal cut-point was 3.45.
Audience members said that while a predictive test for preeclampsia is most welcome, the fact remains that physicians don’t have a lot to offer in terms of prevention or treatment of this feared pregnancy complication. Dr. Salmon responded that the SFLT1/PlGF ratio can be used to risk-stratify pregnant lupus patients for future interventional trials with new drugs looking at new pathways. Already, for example, other investigators have reported some success using a strategy targeting sFLT1 itself. In a small study, they found that women with severe preeclampsia who had their blood run through a heparin column that binds and removes sFLT1 were able to maintain their pregnancies for up to 2 weeks.
"It’s a tiny, open-label trial involving a device, but I think that will move forward," she predicted.
The PROMISSE study was funded by the National Institutes of Health, the Alliance for Lupus Research, and the Mary Kirkland Center for Lupus Research at the Hospital for Special Surgery. Dr. Salmon reported having received research grants from and/or serving as a consultant to Alexion, Novartis, and Roche.
SLE, APS, vascular endothelial growth factor R1, sFLT1, placental growth factor, PlGF, preeclampsia, PROMISSE study, Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and SLE study, Dr. Jane E. Salmon, annual meeting of the American College of Rheumatology, early preeclampsia,
SAN DIEGO – Alteration in the balance of placentally secreted angiogenic factors early in pregnancy provides a potent new predictor of subsequent preeclampsia and other poor outcomes in pregnant women with systemic lupus erythematosus and/or antiphospholipid antibody syndrome.
Patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibody syndrome (APS) who had an elevated ratio of a splice variant of vascular endothelial growth factor R1 called sFLT1 to placental growth factor (PlGF) when measured at 16-19 weeks’ gestation were at 13.8-fold increased relative risk of preeclampsia before 34 weeks, compared with patients with an sFLT1/PlGF ratio below that cut-point in the large, multicenter, observational PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and SLE) study, Dr. Jane E. Salmon reported at the annual meeting of the American College of Rheumatology.
"Nearly half of the patients with an SFLT1/PlGF ratio greater than 3.45 when measured at 16-19 weeks’ gestation will develop early preeclampsia. On the other hand, a low ratio, as well as low levels of sFLT1 or high levels of PlGF, can reassure physicians and patients that preterm preeclampsia is unlikely: a 3% chance," said Dr. Salmon, professor of medicine and of ob.gyn. at Cornell University and a rheumatologist at the Hospital for Special Surgery, both in New York.
Pregnancy in patients with lupus is associated with obstetric complications placing both mother and fetus at great risk. Yet, until now it hasn’t been possible to predict which patients will have poor outcomes.
The key to identifying those at high risk lies in a recognition that preeclampsia and other poor outcomes are dramatic manifestations of placental insufficiency, which actually begins, initially silently, early in pregnancy. The maternal hypertension, proteinuria, thrombocytopenia, and other end-organ manifestations of preeclampsia are caused by maternal endothelial dysfunction mediated by placental secretion of antiangiogenic factors. Angiogenic growth factors, such as PIGF and vascular endothelial growth factor (VEGF), are essential to a healthy endothelium. But placentally secreted sFLT1 binds to these two angiogenic growth factors, rendering them unavailable to the endothelium, she explained.
Overexpression of sFLT1 in multiple animal models results in hypertension and proteinuria, the hallmarks of preeclampsia. Moreover, cancer patients treated with VEGF inhibitors often develop these two conditions. Based in part on these observations, Dr. Salmon and her coinvestigators turned to the PROMISSE study to test their hypothesis that elevated levels of antiangiogenic factors early in pregnancy predict poor outcomes in patients with SLE and/or APS. The prospective study involved 503 pregnant women with SLE and/or APS and 204 healthy controls, all with monthly blood draws starting before 12 weeks’ gestation.
The composite outcome of preeclampsia, small for gestational age, indicated preterm delivery, and other adverse events occurred in 37% of SLE patients who also had APS. The rate was 16% in patients with SLE alone, 26% in those with APS alone, and 3% in controls.
Subjects with SLE and/or APS who developed preeclampsia and other pregnancy complications displayed significantly higher levels of sFLT1 beginning at 12 weeks and sustained through 31 weeks’ gestation, compared with those with normal pregnancies. Moreover, PlGF levels were significantly lower during weeks 16-31 in the patients with pregnancy complications. The investigators determined that the best predictor of pregnancy complications was the ratio of antiangiogenic sFLT1 to angiogenic PlGF. And the optimal cut-point was 3.45.
Audience members said that while a predictive test for preeclampsia is most welcome, the fact remains that physicians don’t have a lot to offer in terms of prevention or treatment of this feared pregnancy complication. Dr. Salmon responded that the SFLT1/PlGF ratio can be used to risk-stratify pregnant lupus patients for future interventional trials with new drugs looking at new pathways. Already, for example, other investigators have reported some success using a strategy targeting sFLT1 itself. In a small study, they found that women with severe preeclampsia who had their blood run through a heparin column that binds and removes sFLT1 were able to maintain their pregnancies for up to 2 weeks.
"It’s a tiny, open-label trial involving a device, but I think that will move forward," she predicted.
The PROMISSE study was funded by the National Institutes of Health, the Alliance for Lupus Research, and the Mary Kirkland Center for Lupus Research at the Hospital for Special Surgery. Dr. Salmon reported having received research grants from and/or serving as a consultant to Alexion, Novartis, and Roche.
SAN DIEGO – Alteration in the balance of placentally secreted angiogenic factors early in pregnancy provides a potent new predictor of subsequent preeclampsia and other poor outcomes in pregnant women with systemic lupus erythematosus and/or antiphospholipid antibody syndrome.
Patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibody syndrome (APS) who had an elevated ratio of a splice variant of vascular endothelial growth factor R1 called sFLT1 to placental growth factor (PlGF) when measured at 16-19 weeks’ gestation were at 13.8-fold increased relative risk of preeclampsia before 34 weeks, compared with patients with an sFLT1/PlGF ratio below that cut-point in the large, multicenter, observational PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and SLE) study, Dr. Jane E. Salmon reported at the annual meeting of the American College of Rheumatology.
"Nearly half of the patients with an SFLT1/PlGF ratio greater than 3.45 when measured at 16-19 weeks’ gestation will develop early preeclampsia. On the other hand, a low ratio, as well as low levels of sFLT1 or high levels of PlGF, can reassure physicians and patients that preterm preeclampsia is unlikely: a 3% chance," said Dr. Salmon, professor of medicine and of ob.gyn. at Cornell University and a rheumatologist at the Hospital for Special Surgery, both in New York.
Pregnancy in patients with lupus is associated with obstetric complications placing both mother and fetus at great risk. Yet, until now it hasn’t been possible to predict which patients will have poor outcomes.
The key to identifying those at high risk lies in a recognition that preeclampsia and other poor outcomes are dramatic manifestations of placental insufficiency, which actually begins, initially silently, early in pregnancy. The maternal hypertension, proteinuria, thrombocytopenia, and other end-organ manifestations of preeclampsia are caused by maternal endothelial dysfunction mediated by placental secretion of antiangiogenic factors. Angiogenic growth factors, such as PIGF and vascular endothelial growth factor (VEGF), are essential to a healthy endothelium. But placentally secreted sFLT1 binds to these two angiogenic growth factors, rendering them unavailable to the endothelium, she explained.
Overexpression of sFLT1 in multiple animal models results in hypertension and proteinuria, the hallmarks of preeclampsia. Moreover, cancer patients treated with VEGF inhibitors often develop these two conditions. Based in part on these observations, Dr. Salmon and her coinvestigators turned to the PROMISSE study to test their hypothesis that elevated levels of antiangiogenic factors early in pregnancy predict poor outcomes in patients with SLE and/or APS. The prospective study involved 503 pregnant women with SLE and/or APS and 204 healthy controls, all with monthly blood draws starting before 12 weeks’ gestation.
The composite outcome of preeclampsia, small for gestational age, indicated preterm delivery, and other adverse events occurred in 37% of SLE patients who also had APS. The rate was 16% in patients with SLE alone, 26% in those with APS alone, and 3% in controls.
Subjects with SLE and/or APS who developed preeclampsia and other pregnancy complications displayed significantly higher levels of sFLT1 beginning at 12 weeks and sustained through 31 weeks’ gestation, compared with those with normal pregnancies. Moreover, PlGF levels were significantly lower during weeks 16-31 in the patients with pregnancy complications. The investigators determined that the best predictor of pregnancy complications was the ratio of antiangiogenic sFLT1 to angiogenic PlGF. And the optimal cut-point was 3.45.
Audience members said that while a predictive test for preeclampsia is most welcome, the fact remains that physicians don’t have a lot to offer in terms of prevention or treatment of this feared pregnancy complication. Dr. Salmon responded that the SFLT1/PlGF ratio can be used to risk-stratify pregnant lupus patients for future interventional trials with new drugs looking at new pathways. Already, for example, other investigators have reported some success using a strategy targeting sFLT1 itself. In a small study, they found that women with severe preeclampsia who had their blood run through a heparin column that binds and removes sFLT1 were able to maintain their pregnancies for up to 2 weeks.
"It’s a tiny, open-label trial involving a device, but I think that will move forward," she predicted.
The PROMISSE study was funded by the National Institutes of Health, the Alliance for Lupus Research, and the Mary Kirkland Center for Lupus Research at the Hospital for Special Surgery. Dr. Salmon reported having received research grants from and/or serving as a consultant to Alexion, Novartis, and Roche.
SLE, APS, vascular endothelial growth factor R1, sFLT1, placental growth factor, PlGF, preeclampsia, PROMISSE study, Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and SLE study, Dr. Jane E. Salmon, annual meeting of the American College of Rheumatology, early preeclampsia,
SLE, APS, vascular endothelial growth factor R1, sFLT1, placental growth factor, PlGF, preeclampsia, PROMISSE study, Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and SLE study, Dr. Jane E. Salmon, annual meeting of the American College of Rheumatology, early preeclampsia,
AT THE ACR ANNUAL MEETING
Major finding: Pregnant patients with SLE and/or APS had nearly a 14-fold increased risk of developing preeclampsia before 34 weeks’ gestation when they displayed an abnormal ratio of two key placentally derived angiogenic factors at 16-19 weeks’ gestation.
Data source: This analysis included 503 pregnant women with SLE and/or APS and 204 pregnant controls participating in the prospective, observational, multicenter PROMISSE study.
Disclosures: The study was funded by the National Institutes of Health, the Alliance for Lupus Research, and the Mary Kirkland Center for Lupus Research at the Hospital for Special Surgery. The presenter reported no relevant financial interests.
Pregabalin improves fibromyalgia pain with comorbid depression
SAN DIEGO – Pregabalin significantly improved fibromyalgia pain even in patients who were being treated for comorbid depression in a double-blind, crossover clinical trial.
The clinical relevance of this new finding lies in the fact that up to 70% of fibromyalgia patients have a lifetime history of depression, and about 25% are on antidepressant medication when they present for treatment of fibromyalgia. Yet all the studies that led to Food and Drug Administration approval of pregabalin (Lyrica) for treatment of fibromyalgia pain required that participants not be on antidepressant medication. Thus, there has been no information as to the effectiveness and safety of pregabalin in fibromyalgia patients on concomitant antidepressants for comorbid depression, Dr. Lesley M. Arnold explained at the annual meeting of the American College of Rheumatology.
She presented a 14-week, randomized, double-blind, multicenter study involving 197 patients who met the 1990 American College of Rheumatology criteria for fibromyalgia. All participants also carried a diagnosis of major depression, depression NOS (not otherwise specified), or dysthymia for which they were taking a stable dose of a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).
This was a typical population of fibromyalgia patients: 93% were women, 94% white, with a mean age of 50 years. Their on-treatment depression was mild as evidenced by a baseline mean Hospital Anxiety and Depression Scale–Depression score of 8.0. They were randomized to 6 weeks of placebo or pregabalin started at 150 mg/day dosed twice daily and optimized over the first 3 weeks to either 300 or 450 mg/day as per the product labeling. Three-quarters of patients reached 450 mg/day. After the first 6 weeks of treatment, a 2-week washout period followed, then a switch to the alternate regimen for another 6 weeks.
The primary endpoint was change in mean self-reported pain score based on the average of daily pain scores for the previous 7 days. From a mean baseline pain score of 6.7 on a 0-10 scale, the score dropped to 4.84 on pregabalin, a significantly greater improvement than the 5.45 with placebo. The response to pregabalin was rapid: The improvement in pain scores became significant within the first week and was maintained to the study’s end, reported Dr. Arnold, professor of psychiatry and behavioral neuroscience and director of the Women’s Health Research Program at the University of Cincinnati.
Most patients would find this roughly 28% reduction in pain with pregabalin to be clinically meaningful, she added. In addition, secondary endpoints in the study now being analyzed address improvement in function and global quality of life. Those results will be available within several months.
Pregabalin has a well-established safety profile. No surprises were noted when the drug was used with concomitant antidepressants. The most frequently reported adverse events were dizziness in 28% of patients and sleepiness in 20%. Discontinuation because of adverse events occurred in 6.1% of patients on pregabalin and 3.4% on placebo.
Elsewhere at the ACR meeting, Dr. Arnold presented the results of a phase III, randomized trial in which a novel, investigational, once-daily, controlled-release formulation of pregabalin outperformed placebo in 441 fibromyalgia patients.
Both studies were funded by Pfizer. Dr. Arnold reported receiving research grants from and serving as a consultant to the company.
SAN DIEGO – Pregabalin significantly improved fibromyalgia pain even in patients who were being treated for comorbid depression in a double-blind, crossover clinical trial.
The clinical relevance of this new finding lies in the fact that up to 70% of fibromyalgia patients have a lifetime history of depression, and about 25% are on antidepressant medication when they present for treatment of fibromyalgia. Yet all the studies that led to Food and Drug Administration approval of pregabalin (Lyrica) for treatment of fibromyalgia pain required that participants not be on antidepressant medication. Thus, there has been no information as to the effectiveness and safety of pregabalin in fibromyalgia patients on concomitant antidepressants for comorbid depression, Dr. Lesley M. Arnold explained at the annual meeting of the American College of Rheumatology.
She presented a 14-week, randomized, double-blind, multicenter study involving 197 patients who met the 1990 American College of Rheumatology criteria for fibromyalgia. All participants also carried a diagnosis of major depression, depression NOS (not otherwise specified), or dysthymia for which they were taking a stable dose of a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).
This was a typical population of fibromyalgia patients: 93% were women, 94% white, with a mean age of 50 years. Their on-treatment depression was mild as evidenced by a baseline mean Hospital Anxiety and Depression Scale–Depression score of 8.0. They were randomized to 6 weeks of placebo or pregabalin started at 150 mg/day dosed twice daily and optimized over the first 3 weeks to either 300 or 450 mg/day as per the product labeling. Three-quarters of patients reached 450 mg/day. After the first 6 weeks of treatment, a 2-week washout period followed, then a switch to the alternate regimen for another 6 weeks.
The primary endpoint was change in mean self-reported pain score based on the average of daily pain scores for the previous 7 days. From a mean baseline pain score of 6.7 on a 0-10 scale, the score dropped to 4.84 on pregabalin, a significantly greater improvement than the 5.45 with placebo. The response to pregabalin was rapid: The improvement in pain scores became significant within the first week and was maintained to the study’s end, reported Dr. Arnold, professor of psychiatry and behavioral neuroscience and director of the Women’s Health Research Program at the University of Cincinnati.
Most patients would find this roughly 28% reduction in pain with pregabalin to be clinically meaningful, she added. In addition, secondary endpoints in the study now being analyzed address improvement in function and global quality of life. Those results will be available within several months.
Pregabalin has a well-established safety profile. No surprises were noted when the drug was used with concomitant antidepressants. The most frequently reported adverse events were dizziness in 28% of patients and sleepiness in 20%. Discontinuation because of adverse events occurred in 6.1% of patients on pregabalin and 3.4% on placebo.
Elsewhere at the ACR meeting, Dr. Arnold presented the results of a phase III, randomized trial in which a novel, investigational, once-daily, controlled-release formulation of pregabalin outperformed placebo in 441 fibromyalgia patients.
Both studies were funded by Pfizer. Dr. Arnold reported receiving research grants from and serving as a consultant to the company.
SAN DIEGO – Pregabalin significantly improved fibromyalgia pain even in patients who were being treated for comorbid depression in a double-blind, crossover clinical trial.
The clinical relevance of this new finding lies in the fact that up to 70% of fibromyalgia patients have a lifetime history of depression, and about 25% are on antidepressant medication when they present for treatment of fibromyalgia. Yet all the studies that led to Food and Drug Administration approval of pregabalin (Lyrica) for treatment of fibromyalgia pain required that participants not be on antidepressant medication. Thus, there has been no information as to the effectiveness and safety of pregabalin in fibromyalgia patients on concomitant antidepressants for comorbid depression, Dr. Lesley M. Arnold explained at the annual meeting of the American College of Rheumatology.
She presented a 14-week, randomized, double-blind, multicenter study involving 197 patients who met the 1990 American College of Rheumatology criteria for fibromyalgia. All participants also carried a diagnosis of major depression, depression NOS (not otherwise specified), or dysthymia for which they were taking a stable dose of a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).
This was a typical population of fibromyalgia patients: 93% were women, 94% white, with a mean age of 50 years. Their on-treatment depression was mild as evidenced by a baseline mean Hospital Anxiety and Depression Scale–Depression score of 8.0. They were randomized to 6 weeks of placebo or pregabalin started at 150 mg/day dosed twice daily and optimized over the first 3 weeks to either 300 or 450 mg/day as per the product labeling. Three-quarters of patients reached 450 mg/day. After the first 6 weeks of treatment, a 2-week washout period followed, then a switch to the alternate regimen for another 6 weeks.
The primary endpoint was change in mean self-reported pain score based on the average of daily pain scores for the previous 7 days. From a mean baseline pain score of 6.7 on a 0-10 scale, the score dropped to 4.84 on pregabalin, a significantly greater improvement than the 5.45 with placebo. The response to pregabalin was rapid: The improvement in pain scores became significant within the first week and was maintained to the study’s end, reported Dr. Arnold, professor of psychiatry and behavioral neuroscience and director of the Women’s Health Research Program at the University of Cincinnati.
Most patients would find this roughly 28% reduction in pain with pregabalin to be clinically meaningful, she added. In addition, secondary endpoints in the study now being analyzed address improvement in function and global quality of life. Those results will be available within several months.
Pregabalin has a well-established safety profile. No surprises were noted when the drug was used with concomitant antidepressants. The most frequently reported adverse events were dizziness in 28% of patients and sleepiness in 20%. Discontinuation because of adverse events occurred in 6.1% of patients on pregabalin and 3.4% on placebo.
Elsewhere at the ACR meeting, Dr. Arnold presented the results of a phase III, randomized trial in which a novel, investigational, once-daily, controlled-release formulation of pregabalin outperformed placebo in 441 fibromyalgia patients.
Both studies were funded by Pfizer. Dr. Arnold reported receiving research grants from and serving as a consultant to the company.
AT THE ACR ANNUAL MEETING
Major finding: Pregabalin resulted in an improvement in mean pain scores from 6.7 at baseline to 4.84 in fibromyalgia patients on antidepressant medication for comorbid depression.
Data source: A 14-week, randomized, double-blind, prospective, multicenter, placebo-controlled crossover study involving 197 fibromyalgia patients on antidepressant medication for comorbid depression.
Disclosures: The study was sponsored by Pfizer. The presenter has received research grants from and serves as a consultant to the company.
Novel PDT method proves superior for difficult AKs
ISTANBUL – A novel form of photodynamic therapy achieved a much higher cure rate than did conventional PDT, based on a randomized controlled trial of organ transplant recipients with numerous actinic keratoses.
The novel approach combines pretreatment with ablative fractional laser resurfacing followed immediately by application of a photosensitizing agent and natural light exposure. In addition to its efficacy, the novel PDT approach was painless. Conventional PDT can be particularly painful for organ transplant recipients as they tend to have particularly thick and widespread lesions located at pain-sensitive sites including the underarms, dorsal hands, and face, Dr. Merete Haedersdal reported at the annual congress of the European Academy of Dermatology and Venereology.
"From a clinical point of view, we are struggling with these patients. ... Now we can individualize PDT. We already have a wonderful conventional PDT, but now we’re better off with these combined techniques, especially when we are going to treat larger areas as in this high-risk group of patients," said Dr. Haedersdal, professor of dermatology at the University of Copenhagen.
As a result of their long-term immunosuppressive therapy, organ transplant recipients have a 100-fold higher risk than the general population for squamous cell carcinoma. Further, their skin tumors grow aggressively; 6%-8% of organ transplant recipients die due to nonmelanoma skin cancers.
The novel PDT approach begins with ablative fractional laser resurfacing to create tiny holes in the skin, allowing increased uptake of the photosensitizer. Dr. Haedersdal and her coworkers used methyl aminolevulinate 16% cream, applied immediately after laser treatment. It takes 30 minutes to start the biochemical process of protoporphyrin-9 production, and the patient then goes outside for a full 2 hours of natural light exposure. This photoactivation period averaged 62,583 lux in the study. The patient then covers the treated area or stays inside for the rest of the day.
Dr. Haedersdal reported on 16 patients with a total of 542 actinic keratoses (AKs) on the scalp, chest, and extremities. The patients had received a donor organ a median of 14 years earlier. In each patient, four symmetrical skin areas within the same anatomic region were mapped out and randomized to receive a single treatment with either the novel laser-assisted daylight PDT, conventional PDT with a red light–emitting diode light source, PDT with daylight rather than the LED light source, or ablative fractional laser therapy alone.
The primary endpoint was the cure rate, or complete lesion response of all AKs at 3 months post treatment. The cure rate was 74% in the laser-assisted daylight PDT group compared with 50% with daylight PDT, 48% with conventional PDT, and 0 with laser-only treatment. When the analysis was restricted to the thicker, grade II and III AKs, the cure rate was 67% with the novel therapy, 50% with conventional PDT, 40% with daylight PDT, and 0 with laser-only treatment.
Median pain scores on a 0-10 visual analog scale were 0 for the areas treated with laser-assisted daylight PDT, laser only, and daylight PDT compared with 4.5 for the portion of skin targeted with conventional PDT. The key to pain-free PDT, according to Dr. Haedersdal, is to do the laser resurfacing at a very low fluence, allowing for continuous daylight photobleaching. The fractional laser therapy is delivered at a total of 5.6 mJ using 4.6 mJ per pulse, 1.15 W, a 50-microsecond pulse duration, 500 Hz, and 2.4% density using a 2,940-nm erbium laser. The laser holes are drilled into the epidermal layer, but not below the basement membrane.
Crusting and erythema developed in all PDT-treated patients but were slightly more intense in the areas treated with laser-assisted PDT. One patient in the laser-assisted PDT group had transient hypopigmentation.
Based on blinded assessments at 3 months, the laser-assisted daylight PDT areas displayed significantly greater skin smoothening and rejuvenation with less dyschromia than the other treatment zones. Cosmesis was rated "excellent" in the laser-treated zones of 10 out of 16 patients, a much higher rate than seen in the other treatment areas.
Dr. Haedersdal reported having received research grants from roughly half a dozen medical device and pharmaceutical companies.
ISTANBUL – A novel form of photodynamic therapy achieved a much higher cure rate than did conventional PDT, based on a randomized controlled trial of organ transplant recipients with numerous actinic keratoses.
The novel approach combines pretreatment with ablative fractional laser resurfacing followed immediately by application of a photosensitizing agent and natural light exposure. In addition to its efficacy, the novel PDT approach was painless. Conventional PDT can be particularly painful for organ transplant recipients as they tend to have particularly thick and widespread lesions located at pain-sensitive sites including the underarms, dorsal hands, and face, Dr. Merete Haedersdal reported at the annual congress of the European Academy of Dermatology and Venereology.
"From a clinical point of view, we are struggling with these patients. ... Now we can individualize PDT. We already have a wonderful conventional PDT, but now we’re better off with these combined techniques, especially when we are going to treat larger areas as in this high-risk group of patients," said Dr. Haedersdal, professor of dermatology at the University of Copenhagen.
As a result of their long-term immunosuppressive therapy, organ transplant recipients have a 100-fold higher risk than the general population for squamous cell carcinoma. Further, their skin tumors grow aggressively; 6%-8% of organ transplant recipients die due to nonmelanoma skin cancers.
The novel PDT approach begins with ablative fractional laser resurfacing to create tiny holes in the skin, allowing increased uptake of the photosensitizer. Dr. Haedersdal and her coworkers used methyl aminolevulinate 16% cream, applied immediately after laser treatment. It takes 30 minutes to start the biochemical process of protoporphyrin-9 production, and the patient then goes outside for a full 2 hours of natural light exposure. This photoactivation period averaged 62,583 lux in the study. The patient then covers the treated area or stays inside for the rest of the day.
Dr. Haedersdal reported on 16 patients with a total of 542 actinic keratoses (AKs) on the scalp, chest, and extremities. The patients had received a donor organ a median of 14 years earlier. In each patient, four symmetrical skin areas within the same anatomic region were mapped out and randomized to receive a single treatment with either the novel laser-assisted daylight PDT, conventional PDT with a red light–emitting diode light source, PDT with daylight rather than the LED light source, or ablative fractional laser therapy alone.
The primary endpoint was the cure rate, or complete lesion response of all AKs at 3 months post treatment. The cure rate was 74% in the laser-assisted daylight PDT group compared with 50% with daylight PDT, 48% with conventional PDT, and 0 with laser-only treatment. When the analysis was restricted to the thicker, grade II and III AKs, the cure rate was 67% with the novel therapy, 50% with conventional PDT, 40% with daylight PDT, and 0 with laser-only treatment.
Median pain scores on a 0-10 visual analog scale were 0 for the areas treated with laser-assisted daylight PDT, laser only, and daylight PDT compared with 4.5 for the portion of skin targeted with conventional PDT. The key to pain-free PDT, according to Dr. Haedersdal, is to do the laser resurfacing at a very low fluence, allowing for continuous daylight photobleaching. The fractional laser therapy is delivered at a total of 5.6 mJ using 4.6 mJ per pulse, 1.15 W, a 50-microsecond pulse duration, 500 Hz, and 2.4% density using a 2,940-nm erbium laser. The laser holes are drilled into the epidermal layer, but not below the basement membrane.
Crusting and erythema developed in all PDT-treated patients but were slightly more intense in the areas treated with laser-assisted PDT. One patient in the laser-assisted PDT group had transient hypopigmentation.
Based on blinded assessments at 3 months, the laser-assisted daylight PDT areas displayed significantly greater skin smoothening and rejuvenation with less dyschromia than the other treatment zones. Cosmesis was rated "excellent" in the laser-treated zones of 10 out of 16 patients, a much higher rate than seen in the other treatment areas.
Dr. Haedersdal reported having received research grants from roughly half a dozen medical device and pharmaceutical companies.
ISTANBUL – A novel form of photodynamic therapy achieved a much higher cure rate than did conventional PDT, based on a randomized controlled trial of organ transplant recipients with numerous actinic keratoses.
The novel approach combines pretreatment with ablative fractional laser resurfacing followed immediately by application of a photosensitizing agent and natural light exposure. In addition to its efficacy, the novel PDT approach was painless. Conventional PDT can be particularly painful for organ transplant recipients as they tend to have particularly thick and widespread lesions located at pain-sensitive sites including the underarms, dorsal hands, and face, Dr. Merete Haedersdal reported at the annual congress of the European Academy of Dermatology and Venereology.
"From a clinical point of view, we are struggling with these patients. ... Now we can individualize PDT. We already have a wonderful conventional PDT, but now we’re better off with these combined techniques, especially when we are going to treat larger areas as in this high-risk group of patients," said Dr. Haedersdal, professor of dermatology at the University of Copenhagen.
As a result of their long-term immunosuppressive therapy, organ transplant recipients have a 100-fold higher risk than the general population for squamous cell carcinoma. Further, their skin tumors grow aggressively; 6%-8% of organ transplant recipients die due to nonmelanoma skin cancers.
The novel PDT approach begins with ablative fractional laser resurfacing to create tiny holes in the skin, allowing increased uptake of the photosensitizer. Dr. Haedersdal and her coworkers used methyl aminolevulinate 16% cream, applied immediately after laser treatment. It takes 30 minutes to start the biochemical process of protoporphyrin-9 production, and the patient then goes outside for a full 2 hours of natural light exposure. This photoactivation period averaged 62,583 lux in the study. The patient then covers the treated area or stays inside for the rest of the day.
Dr. Haedersdal reported on 16 patients with a total of 542 actinic keratoses (AKs) on the scalp, chest, and extremities. The patients had received a donor organ a median of 14 years earlier. In each patient, four symmetrical skin areas within the same anatomic region were mapped out and randomized to receive a single treatment with either the novel laser-assisted daylight PDT, conventional PDT with a red light–emitting diode light source, PDT with daylight rather than the LED light source, or ablative fractional laser therapy alone.
The primary endpoint was the cure rate, or complete lesion response of all AKs at 3 months post treatment. The cure rate was 74% in the laser-assisted daylight PDT group compared with 50% with daylight PDT, 48% with conventional PDT, and 0 with laser-only treatment. When the analysis was restricted to the thicker, grade II and III AKs, the cure rate was 67% with the novel therapy, 50% with conventional PDT, 40% with daylight PDT, and 0 with laser-only treatment.
Median pain scores on a 0-10 visual analog scale were 0 for the areas treated with laser-assisted daylight PDT, laser only, and daylight PDT compared with 4.5 for the portion of skin targeted with conventional PDT. The key to pain-free PDT, according to Dr. Haedersdal, is to do the laser resurfacing at a very low fluence, allowing for continuous daylight photobleaching. The fractional laser therapy is delivered at a total of 5.6 mJ using 4.6 mJ per pulse, 1.15 W, a 50-microsecond pulse duration, 500 Hz, and 2.4% density using a 2,940-nm erbium laser. The laser holes are drilled into the epidermal layer, but not below the basement membrane.
Crusting and erythema developed in all PDT-treated patients but were slightly more intense in the areas treated with laser-assisted PDT. One patient in the laser-assisted PDT group had transient hypopigmentation.
Based on blinded assessments at 3 months, the laser-assisted daylight PDT areas displayed significantly greater skin smoothening and rejuvenation with less dyschromia than the other treatment zones. Cosmesis was rated "excellent" in the laser-treated zones of 10 out of 16 patients, a much higher rate than seen in the other treatment areas.
Dr. Haedersdal reported having received research grants from roughly half a dozen medical device and pharmaceutical companies.
AT THE EADV CONGRESS
Major finding: Three months post treatment, the actinic keratosis cure rate was 74% in organ transplant recipients who underwent a novel form of ablative fractional resurfacing–assisted photodynamic therapy with daylight as a photoactivator, compared with 48% with conventional PDT.
Data source: A randomized trial including 16 organ transplant recipients with a total of 542 actinic keratoses.
Disclosures: This study was funded by a Danish research foundation. The presenter has received research grants from half a dozen medical device and pharmaceutical companies.
Early aggressive therapy in JIA brings prolonged disease inactivation
SAN DIEGO – Starting aggressive multidrug therapy within the first several months after children were diagnosed with severe polyarticular juvenile idiopathic arthritis resulted in a "phenomenal" rate of clinical inactive disease, which occurred faster and was sustained longer than with high-dose methotrexate monotherapy in a randomized, double-blind, multicenter clinical trial.
"This is a groundbreaking study. This is the first-ever study in children that has used clinical inactive disease as the primary endpoint. And it showed that clinical inactive disease – or remission, if you’d like – is achievable if you treat early and aggressively," declared Dr. Carol A. Wallace, professor of pediatrics at the University of Washington, Seattle, and rheumatology division chief at Seattle Children’s Hospital.
At the annual meeting of the American College of Rheumatology, she presented a new secondary analysis from the previously reported landmark Trial of Early Aggressive Therapy in Polyarticular Juvenile Idiopathic Arthritis (TREAT-JIA), in which 85 patients diagnosed a median of 4.2 months prior to enrollment were randomized double-blind to one of two treatment arms: combination therapy with subcutaneous methotrexate at 0.5 mg/kg per week, etanercept at 0.8 mg/kg per week, plus prednisolone at 0.5 mg/kg per day tapered to zero by 17 weeks; or subcutaneous methotrexate dosed identically plus double placebos (Arthritis Rheum. 2012;64:2012-21).
The group on multidrug therapy spent a median of 42% of days during the 12-month study in a state of clinical inactive disease, compared with 24% for patients who started on methotrexate alone. And those figures don’t convey the full impact of combination therapy. Seventeen of the 28 patients in the methotrexate monotherapy group who achieved clinical inactive disease did so only after undergoing a protocol-mandated switch to open-label combination therapy because they failed to receive an ACR 70 response within the first 4 months, yet in the intent-to-treat analysis those 17 patients were counted in the methotrexate-alone group.
The term "clinical inactive disease" is defined stringently in pediatric rheumatology, Dr. Wallace explained. It requires that a patient must have zero joints with active arthritis, no elevation in ESR, no uveitis, a Physician Global Assessment score of 0 on a 0-10 scale, and no fever, rash, hepatosplenomegaly, or lymphadenopathy.
The fact that 68% of study patients achieved clinical inactive disease at some point is particularly impressive in light of their high burden of disease, Dr. Wallace observed. Their baseline Physician Global Assessment score was 7, and nearly 40% of subjects were rheumatoid factor positive.
A major goal in the secondary analysis was to identify predictors of a favorable treatment response. The investigators found two. One was time to treatment. It was a linear relationship: The earlier the treatment began, the more time patients spent in a state of clinical inactive disease. Those who started treatment having a disease duration of 3 months or less had clinical inactive disease at a median of 40% of clinic visits, regardless of treatment arm, while patients who began therapy with a disease duration of more than 3 months had clinical inactive disease at only 11% of visits.
The other predictor of a favorable response was achieving an ACR 70 response at 4 months, regardless of the treatment regimen employed. Among 49 patients who did so, 86% attained clinical inactive disease during the 12-month study, compared with a 44% rate among those who did not achieve the early ACR 70. Nine patients in the multidrug therapy arm and three on methotrexate monotherapy achieved a complete remission, defined as 6 months of continuous clinical inactive disease; all 12 of these patients had an ACR 70 response at 4 months.
Side effects in the two treatment groups were similarly uncommon.
The investigators are now attempting to learn whether the immune system of successfully treated children with juvenile idiopathic arthritis eventually returns to normal, making it safe to discontinue medications. The final word isn’t in yet, but Dr. Wallace is doubtful.
"At least 50% of children do flare when their medications are stopped, and they don’t always achieve the same level of disease response the second time around," said the pediatric rheumatologist.
The TREAT-JIA trial was funded by the National Institute of Allergy and Infectious Diseases and the Howe Endowment for Juvenile Idiopathic Arthritis Research. Dr. Wallace reported having no financial conflicts.
SAN DIEGO – Starting aggressive multidrug therapy within the first several months after children were diagnosed with severe polyarticular juvenile idiopathic arthritis resulted in a "phenomenal" rate of clinical inactive disease, which occurred faster and was sustained longer than with high-dose methotrexate monotherapy in a randomized, double-blind, multicenter clinical trial.
"This is a groundbreaking study. This is the first-ever study in children that has used clinical inactive disease as the primary endpoint. And it showed that clinical inactive disease – or remission, if you’d like – is achievable if you treat early and aggressively," declared Dr. Carol A. Wallace, professor of pediatrics at the University of Washington, Seattle, and rheumatology division chief at Seattle Children’s Hospital.
At the annual meeting of the American College of Rheumatology, she presented a new secondary analysis from the previously reported landmark Trial of Early Aggressive Therapy in Polyarticular Juvenile Idiopathic Arthritis (TREAT-JIA), in which 85 patients diagnosed a median of 4.2 months prior to enrollment were randomized double-blind to one of two treatment arms: combination therapy with subcutaneous methotrexate at 0.5 mg/kg per week, etanercept at 0.8 mg/kg per week, plus prednisolone at 0.5 mg/kg per day tapered to zero by 17 weeks; or subcutaneous methotrexate dosed identically plus double placebos (Arthritis Rheum. 2012;64:2012-21).
The group on multidrug therapy spent a median of 42% of days during the 12-month study in a state of clinical inactive disease, compared with 24% for patients who started on methotrexate alone. And those figures don’t convey the full impact of combination therapy. Seventeen of the 28 patients in the methotrexate monotherapy group who achieved clinical inactive disease did so only after undergoing a protocol-mandated switch to open-label combination therapy because they failed to receive an ACR 70 response within the first 4 months, yet in the intent-to-treat analysis those 17 patients were counted in the methotrexate-alone group.
The term "clinical inactive disease" is defined stringently in pediatric rheumatology, Dr. Wallace explained. It requires that a patient must have zero joints with active arthritis, no elevation in ESR, no uveitis, a Physician Global Assessment score of 0 on a 0-10 scale, and no fever, rash, hepatosplenomegaly, or lymphadenopathy.
The fact that 68% of study patients achieved clinical inactive disease at some point is particularly impressive in light of their high burden of disease, Dr. Wallace observed. Their baseline Physician Global Assessment score was 7, and nearly 40% of subjects were rheumatoid factor positive.
A major goal in the secondary analysis was to identify predictors of a favorable treatment response. The investigators found two. One was time to treatment. It was a linear relationship: The earlier the treatment began, the more time patients spent in a state of clinical inactive disease. Those who started treatment having a disease duration of 3 months or less had clinical inactive disease at a median of 40% of clinic visits, regardless of treatment arm, while patients who began therapy with a disease duration of more than 3 months had clinical inactive disease at only 11% of visits.
The other predictor of a favorable response was achieving an ACR 70 response at 4 months, regardless of the treatment regimen employed. Among 49 patients who did so, 86% attained clinical inactive disease during the 12-month study, compared with a 44% rate among those who did not achieve the early ACR 70. Nine patients in the multidrug therapy arm and three on methotrexate monotherapy achieved a complete remission, defined as 6 months of continuous clinical inactive disease; all 12 of these patients had an ACR 70 response at 4 months.
Side effects in the two treatment groups were similarly uncommon.
The investigators are now attempting to learn whether the immune system of successfully treated children with juvenile idiopathic arthritis eventually returns to normal, making it safe to discontinue medications. The final word isn’t in yet, but Dr. Wallace is doubtful.
"At least 50% of children do flare when their medications are stopped, and they don’t always achieve the same level of disease response the second time around," said the pediatric rheumatologist.
The TREAT-JIA trial was funded by the National Institute of Allergy and Infectious Diseases and the Howe Endowment for Juvenile Idiopathic Arthritis Research. Dr. Wallace reported having no financial conflicts.
SAN DIEGO – Starting aggressive multidrug therapy within the first several months after children were diagnosed with severe polyarticular juvenile idiopathic arthritis resulted in a "phenomenal" rate of clinical inactive disease, which occurred faster and was sustained longer than with high-dose methotrexate monotherapy in a randomized, double-blind, multicenter clinical trial.
"This is a groundbreaking study. This is the first-ever study in children that has used clinical inactive disease as the primary endpoint. And it showed that clinical inactive disease – or remission, if you’d like – is achievable if you treat early and aggressively," declared Dr. Carol A. Wallace, professor of pediatrics at the University of Washington, Seattle, and rheumatology division chief at Seattle Children’s Hospital.
At the annual meeting of the American College of Rheumatology, she presented a new secondary analysis from the previously reported landmark Trial of Early Aggressive Therapy in Polyarticular Juvenile Idiopathic Arthritis (TREAT-JIA), in which 85 patients diagnosed a median of 4.2 months prior to enrollment were randomized double-blind to one of two treatment arms: combination therapy with subcutaneous methotrexate at 0.5 mg/kg per week, etanercept at 0.8 mg/kg per week, plus prednisolone at 0.5 mg/kg per day tapered to zero by 17 weeks; or subcutaneous methotrexate dosed identically plus double placebos (Arthritis Rheum. 2012;64:2012-21).
The group on multidrug therapy spent a median of 42% of days during the 12-month study in a state of clinical inactive disease, compared with 24% for patients who started on methotrexate alone. And those figures don’t convey the full impact of combination therapy. Seventeen of the 28 patients in the methotrexate monotherapy group who achieved clinical inactive disease did so only after undergoing a protocol-mandated switch to open-label combination therapy because they failed to receive an ACR 70 response within the first 4 months, yet in the intent-to-treat analysis those 17 patients were counted in the methotrexate-alone group.
The term "clinical inactive disease" is defined stringently in pediatric rheumatology, Dr. Wallace explained. It requires that a patient must have zero joints with active arthritis, no elevation in ESR, no uveitis, a Physician Global Assessment score of 0 on a 0-10 scale, and no fever, rash, hepatosplenomegaly, or lymphadenopathy.
The fact that 68% of study patients achieved clinical inactive disease at some point is particularly impressive in light of their high burden of disease, Dr. Wallace observed. Their baseline Physician Global Assessment score was 7, and nearly 40% of subjects were rheumatoid factor positive.
A major goal in the secondary analysis was to identify predictors of a favorable treatment response. The investigators found two. One was time to treatment. It was a linear relationship: The earlier the treatment began, the more time patients spent in a state of clinical inactive disease. Those who started treatment having a disease duration of 3 months or less had clinical inactive disease at a median of 40% of clinic visits, regardless of treatment arm, while patients who began therapy with a disease duration of more than 3 months had clinical inactive disease at only 11% of visits.
The other predictor of a favorable response was achieving an ACR 70 response at 4 months, regardless of the treatment regimen employed. Among 49 patients who did so, 86% attained clinical inactive disease during the 12-month study, compared with a 44% rate among those who did not achieve the early ACR 70. Nine patients in the multidrug therapy arm and three on methotrexate monotherapy achieved a complete remission, defined as 6 months of continuous clinical inactive disease; all 12 of these patients had an ACR 70 response at 4 months.
Side effects in the two treatment groups were similarly uncommon.
The investigators are now attempting to learn whether the immune system of successfully treated children with juvenile idiopathic arthritis eventually returns to normal, making it safe to discontinue medications. The final word isn’t in yet, but Dr. Wallace is doubtful.
"At least 50% of children do flare when their medications are stopped, and they don’t always achieve the same level of disease response the second time around," said the pediatric rheumatologist.
The TREAT-JIA trial was funded by the National Institute of Allergy and Infectious Diseases and the Howe Endowment for Juvenile Idiopathic Arthritis Research. Dr. Wallace reported having no financial conflicts.
AT THE ACR ANNUAL MEETING
Major finding: Children with polyarticular juvenile idiopathic arthritis who started on the combination of methotrexate, etanercept, and prednisolone within the first few months after diagnosis spent a median of 42% of a 12-month study in a state of clinical inactive disease, whereas for those assigned to methotrexate alone, the corresponding figure was 24%.
Data source: A randomized, double-blind, placebo-controlled, 15-center clinical trial involving 85 patients with polyarticular juvenile idiopathic arthritis of a median 4.2 months duration prior to enrollment.
Disclosures: The National Institute of Allergy and Infectious Diseases and the Howe Endowment for Juvenile Idiopathic Arthritis funded the study. Dr. Wallace reported having no financial conflicts.
