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American College of Rheumatology (ACR): Annual Scientific Meeting
Walking program eased chemo-related joint pain
SAN DIEGO – A 6-week, low-impact walking program relieved joint pain and stiffness and increased the number of minutes per week walking among elderly breast cancer survivors on aromatase inhibitors.
"A breast cancer diagnosis can be an ‘a-ha’ moment for women," Kirsten A. Nyrop, Ph.D, said during a press briefing at the annual meeting of the American College of Rheumatology. "Some of the women with whom we spoke said: ‘My cardiologist told me to walk and my general practitioner told me to walk, but when my oncologist asked me to walk, I started walking.’ "
Dr. Nyrop, of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, and her associates studied 20 patients who were taking an aromatase inhibitor for stage I-III breast cancer and had self-reported joint pain. The walking program they used was the Arthritis Foundation’s Walk With Ease. The program recommends that participants walk 30 minutes per day at least 5 days per week.
"We wanted to be certain we were reaching these women with a message that would resonate with them and a program that they felt was safe, something that they could comfortably do," Dr. Nyrop said.
The researchers administered visual analog scales (VAS) for joint pain, stiffness, and fatigue, as well as Arthritic Self-Efficacy (ASE) scales for joint and pain symptoms. The mean age of study participants was 71 years, 85% were white, and their mean body mass index was 29 kg/m2.
After 6 weeks in the walking program, researchers noticed improvements from baseline in the VAS pain score (effect size = 0.15) and VAS fatigue score (effect size = 0.22); changes in the VAS stiffness score approached statistical significance (effect size = 0.56). "That’s promising," Dr. Nyrop said. Scores on the ASE scales also improved from baseline for pain and fatigue, but the changes did not reach significance.
Significant increases in walking were observed from baseline in terms of the number of times per week walked (mean increase of 1.9 times; effect size = 0.68), number of minutes per walk (mean increase of 8.3 minutes; effect size = 0.48), and total number of minutes walked per week (mean increase of 62.6 minutes; effect size = 0.53).
One study participant wrote: "I absolutely feel the connection between aromatase inhibitors and exercise. On days I don’t walk, I am stiff, but if I walk, I am not stiff. Keep moving; it really helps."
A larger, follow-up study with a randomized controlled design is underway with funding by the National Cancer Institute.
The study was funded by the University of North Carolina Institute on Aging. Dr. Nyrop said that she had no relevant financial conflicts to disclose.
SAN DIEGO – A 6-week, low-impact walking program relieved joint pain and stiffness and increased the number of minutes per week walking among elderly breast cancer survivors on aromatase inhibitors.
"A breast cancer diagnosis can be an ‘a-ha’ moment for women," Kirsten A. Nyrop, Ph.D, said during a press briefing at the annual meeting of the American College of Rheumatology. "Some of the women with whom we spoke said: ‘My cardiologist told me to walk and my general practitioner told me to walk, but when my oncologist asked me to walk, I started walking.’ "
Dr. Nyrop, of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, and her associates studied 20 patients who were taking an aromatase inhibitor for stage I-III breast cancer and had self-reported joint pain. The walking program they used was the Arthritis Foundation’s Walk With Ease. The program recommends that participants walk 30 minutes per day at least 5 days per week.
"We wanted to be certain we were reaching these women with a message that would resonate with them and a program that they felt was safe, something that they could comfortably do," Dr. Nyrop said.
The researchers administered visual analog scales (VAS) for joint pain, stiffness, and fatigue, as well as Arthritic Self-Efficacy (ASE) scales for joint and pain symptoms. The mean age of study participants was 71 years, 85% were white, and their mean body mass index was 29 kg/m2.
After 6 weeks in the walking program, researchers noticed improvements from baseline in the VAS pain score (effect size = 0.15) and VAS fatigue score (effect size = 0.22); changes in the VAS stiffness score approached statistical significance (effect size = 0.56). "That’s promising," Dr. Nyrop said. Scores on the ASE scales also improved from baseline for pain and fatigue, but the changes did not reach significance.
Significant increases in walking were observed from baseline in terms of the number of times per week walked (mean increase of 1.9 times; effect size = 0.68), number of minutes per walk (mean increase of 8.3 minutes; effect size = 0.48), and total number of minutes walked per week (mean increase of 62.6 minutes; effect size = 0.53).
One study participant wrote: "I absolutely feel the connection between aromatase inhibitors and exercise. On days I don’t walk, I am stiff, but if I walk, I am not stiff. Keep moving; it really helps."
A larger, follow-up study with a randomized controlled design is underway with funding by the National Cancer Institute.
The study was funded by the University of North Carolina Institute on Aging. Dr. Nyrop said that she had no relevant financial conflicts to disclose.
SAN DIEGO – A 6-week, low-impact walking program relieved joint pain and stiffness and increased the number of minutes per week walking among elderly breast cancer survivors on aromatase inhibitors.
"A breast cancer diagnosis can be an ‘a-ha’ moment for women," Kirsten A. Nyrop, Ph.D, said during a press briefing at the annual meeting of the American College of Rheumatology. "Some of the women with whom we spoke said: ‘My cardiologist told me to walk and my general practitioner told me to walk, but when my oncologist asked me to walk, I started walking.’ "
Dr. Nyrop, of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, and her associates studied 20 patients who were taking an aromatase inhibitor for stage I-III breast cancer and had self-reported joint pain. The walking program they used was the Arthritis Foundation’s Walk With Ease. The program recommends that participants walk 30 minutes per day at least 5 days per week.
"We wanted to be certain we were reaching these women with a message that would resonate with them and a program that they felt was safe, something that they could comfortably do," Dr. Nyrop said.
The researchers administered visual analog scales (VAS) for joint pain, stiffness, and fatigue, as well as Arthritic Self-Efficacy (ASE) scales for joint and pain symptoms. The mean age of study participants was 71 years, 85% were white, and their mean body mass index was 29 kg/m2.
After 6 weeks in the walking program, researchers noticed improvements from baseline in the VAS pain score (effect size = 0.15) and VAS fatigue score (effect size = 0.22); changes in the VAS stiffness score approached statistical significance (effect size = 0.56). "That’s promising," Dr. Nyrop said. Scores on the ASE scales also improved from baseline for pain and fatigue, but the changes did not reach significance.
Significant increases in walking were observed from baseline in terms of the number of times per week walked (mean increase of 1.9 times; effect size = 0.68), number of minutes per walk (mean increase of 8.3 minutes; effect size = 0.48), and total number of minutes walked per week (mean increase of 62.6 minutes; effect size = 0.53).
One study participant wrote: "I absolutely feel the connection between aromatase inhibitors and exercise. On days I don’t walk, I am stiff, but if I walk, I am not stiff. Keep moving; it really helps."
A larger, follow-up study with a randomized controlled design is underway with funding by the National Cancer Institute.
The study was funded by the University of North Carolina Institute on Aging. Dr. Nyrop said that she had no relevant financial conflicts to disclose.
AT THE ACR ANNUAL MEETING
Major finding: After 6 weeks in a low-impact walking program, patients experienced improvements from baseline on the visual analog scale (VAS) for pain (effect size = 0.15) and the VAS for fatigue (effect size = 0.22); changes in the VAS stiffness score approached statistical significance (effect size = 0.56).
Data source: A pilot study of 20 patients at the North Carolina Cancer Hospital in Chapel Hill who were taking an aromatase inhibitor for stage I-III breast cancer and had self-reported joint pain.
Disclosures: The study was funded by the University of North Carolina Institute on Aging. Dr. Nyrop said that she had no relevant financial conflicts to disclose.
Naltrexone, hyperbaric oxygen show promise for fibromyalgia
SAN DIEGO – Low-dose naltrexone and repeated visits to the hyperbaric oxygen chamber are two novel potential therapies for fibromyalgia that showed promise in separate studies presented at the annual meeting of the American College of Rheumatology.
The impetus for investigating these unconventional treatments lies in recognition that fibromyalgia is challenging to treat. The Food and Drug Administration–approved medications for this common condition – duloxetine (Cymbalta), pregabalin (Lyrica), and milnacipran (Savella) – often provide inadequate results.
Naltrexone is an opioid receptor antagonist indicated for the treatment of alcohol or opioid dependence. Dr. Daniel G. Arkfeld explained the therapeutic rationale for its use in fibromyalgia thusly: Fibromyalgia has been classified as a CNS sensitization syndrome mediated by proinflammatory cytokines, and naltrexone has been shown to suppress such centrally acting cytokines.
He presented a prospective, open-label, single-center, uncontrolled pilot study involving 25 patients with fibromyalgia diagnosed by ACR criteria. They were started on oral naltrexone at 3 mg at night, with titration up to 4.5 mg. Patients were permitted to continue on their FDA-approved medications for fibromyalgia, and 18 of the 25 did so. The other 7 patients were on naltrexone monotherapy for the study duration.
Twenty-two patients completed the 3-month study. Two dropped out because they deemed naltrexone to be ineffective and one patient quit because of diarrhea.
The primary study endpoint was change in the Revised Fibromyalgia Impact Questionnaire (FIQR) after 90 days on naltrexone. Overall, study participants improved their FIQR scores by an average of 19.5%. However, 11 of the 22 study completers displayed a more robust response, with an average 41% improvement in the metric, according to Dr. Arkfeld, a rheumatologist at the University of Southern California, Los Angeles.
"Naltrexone is dosed once daily and is inexpensive, making it a viable treatment in fibromyalgia," he concluded.
Controlled clinical trials are planned.
Separately, Dr. Shai Efrati presented a randomized, prospective, controlled clinical trial of hyperbaric oxygen therapy in 60 women with fibromyalgia of at least 2 years duration. The therapeutic rationale lies in an earlier randomized trial by Dr. Efrati and coworkers demonstrating that hyperbaric oxygen therapy induced late neuroplasticity in post-stroke patients (PLoS One 2013; 8:e53716).
Thirty fibromyalgia patients commenced an 8-week course of hyperbaric oxygen therapy consisting of five 90-minute sessions per week involving 100% oxygen at 2 atmospheres absolute. After an 8-week hiatus with no treatment, the other 30 patients embarked on the same protocol.
The baseline tender joint count was 17 out of a possible 18 in the first 30 patients; after completion of the 40 treatment sessions, the tender joint count dropped to 9. Similarly, in the second 30-patient cohort, the baseline tender joint count was 17. It remained at 17 at the end of the no-treatment period and dropped to 5 after the course of hyperbaric oxygen therapy. Scores on the FIQR also dropped significantly from baseline to post treatment in both cohorts, reported Dr. Efrati of Assaf Harofeh Medical Center, Zerifin, Israel.
Dr. Arkfeld and Dr. Efrati reported having no financial conflicts of interest regarding their studies, which were free of commercial sponsorship.
SAN DIEGO – Low-dose naltrexone and repeated visits to the hyperbaric oxygen chamber are two novel potential therapies for fibromyalgia that showed promise in separate studies presented at the annual meeting of the American College of Rheumatology.
The impetus for investigating these unconventional treatments lies in recognition that fibromyalgia is challenging to treat. The Food and Drug Administration–approved medications for this common condition – duloxetine (Cymbalta), pregabalin (Lyrica), and milnacipran (Savella) – often provide inadequate results.
Naltrexone is an opioid receptor antagonist indicated for the treatment of alcohol or opioid dependence. Dr. Daniel G. Arkfeld explained the therapeutic rationale for its use in fibromyalgia thusly: Fibromyalgia has been classified as a CNS sensitization syndrome mediated by proinflammatory cytokines, and naltrexone has been shown to suppress such centrally acting cytokines.
He presented a prospective, open-label, single-center, uncontrolled pilot study involving 25 patients with fibromyalgia diagnosed by ACR criteria. They were started on oral naltrexone at 3 mg at night, with titration up to 4.5 mg. Patients were permitted to continue on their FDA-approved medications for fibromyalgia, and 18 of the 25 did so. The other 7 patients were on naltrexone monotherapy for the study duration.
Twenty-two patients completed the 3-month study. Two dropped out because they deemed naltrexone to be ineffective and one patient quit because of diarrhea.
The primary study endpoint was change in the Revised Fibromyalgia Impact Questionnaire (FIQR) after 90 days on naltrexone. Overall, study participants improved their FIQR scores by an average of 19.5%. However, 11 of the 22 study completers displayed a more robust response, with an average 41% improvement in the metric, according to Dr. Arkfeld, a rheumatologist at the University of Southern California, Los Angeles.
"Naltrexone is dosed once daily and is inexpensive, making it a viable treatment in fibromyalgia," he concluded.
Controlled clinical trials are planned.
Separately, Dr. Shai Efrati presented a randomized, prospective, controlled clinical trial of hyperbaric oxygen therapy in 60 women with fibromyalgia of at least 2 years duration. The therapeutic rationale lies in an earlier randomized trial by Dr. Efrati and coworkers demonstrating that hyperbaric oxygen therapy induced late neuroplasticity in post-stroke patients (PLoS One 2013; 8:e53716).
Thirty fibromyalgia patients commenced an 8-week course of hyperbaric oxygen therapy consisting of five 90-minute sessions per week involving 100% oxygen at 2 atmospheres absolute. After an 8-week hiatus with no treatment, the other 30 patients embarked on the same protocol.
The baseline tender joint count was 17 out of a possible 18 in the first 30 patients; after completion of the 40 treatment sessions, the tender joint count dropped to 9. Similarly, in the second 30-patient cohort, the baseline tender joint count was 17. It remained at 17 at the end of the no-treatment period and dropped to 5 after the course of hyperbaric oxygen therapy. Scores on the FIQR also dropped significantly from baseline to post treatment in both cohorts, reported Dr. Efrati of Assaf Harofeh Medical Center, Zerifin, Israel.
Dr. Arkfeld and Dr. Efrati reported having no financial conflicts of interest regarding their studies, which were free of commercial sponsorship.
SAN DIEGO – Low-dose naltrexone and repeated visits to the hyperbaric oxygen chamber are two novel potential therapies for fibromyalgia that showed promise in separate studies presented at the annual meeting of the American College of Rheumatology.
The impetus for investigating these unconventional treatments lies in recognition that fibromyalgia is challenging to treat. The Food and Drug Administration–approved medications for this common condition – duloxetine (Cymbalta), pregabalin (Lyrica), and milnacipran (Savella) – often provide inadequate results.
Naltrexone is an opioid receptor antagonist indicated for the treatment of alcohol or opioid dependence. Dr. Daniel G. Arkfeld explained the therapeutic rationale for its use in fibromyalgia thusly: Fibromyalgia has been classified as a CNS sensitization syndrome mediated by proinflammatory cytokines, and naltrexone has been shown to suppress such centrally acting cytokines.
He presented a prospective, open-label, single-center, uncontrolled pilot study involving 25 patients with fibromyalgia diagnosed by ACR criteria. They were started on oral naltrexone at 3 mg at night, with titration up to 4.5 mg. Patients were permitted to continue on their FDA-approved medications for fibromyalgia, and 18 of the 25 did so. The other 7 patients were on naltrexone monotherapy for the study duration.
Twenty-two patients completed the 3-month study. Two dropped out because they deemed naltrexone to be ineffective and one patient quit because of diarrhea.
The primary study endpoint was change in the Revised Fibromyalgia Impact Questionnaire (FIQR) after 90 days on naltrexone. Overall, study participants improved their FIQR scores by an average of 19.5%. However, 11 of the 22 study completers displayed a more robust response, with an average 41% improvement in the metric, according to Dr. Arkfeld, a rheumatologist at the University of Southern California, Los Angeles.
"Naltrexone is dosed once daily and is inexpensive, making it a viable treatment in fibromyalgia," he concluded.
Controlled clinical trials are planned.
Separately, Dr. Shai Efrati presented a randomized, prospective, controlled clinical trial of hyperbaric oxygen therapy in 60 women with fibromyalgia of at least 2 years duration. The therapeutic rationale lies in an earlier randomized trial by Dr. Efrati and coworkers demonstrating that hyperbaric oxygen therapy induced late neuroplasticity in post-stroke patients (PLoS One 2013; 8:e53716).
Thirty fibromyalgia patients commenced an 8-week course of hyperbaric oxygen therapy consisting of five 90-minute sessions per week involving 100% oxygen at 2 atmospheres absolute. After an 8-week hiatus with no treatment, the other 30 patients embarked on the same protocol.
The baseline tender joint count was 17 out of a possible 18 in the first 30 patients; after completion of the 40 treatment sessions, the tender joint count dropped to 9. Similarly, in the second 30-patient cohort, the baseline tender joint count was 17. It remained at 17 at the end of the no-treatment period and dropped to 5 after the course of hyperbaric oxygen therapy. Scores on the FIQR also dropped significantly from baseline to post treatment in both cohorts, reported Dr. Efrati of Assaf Harofeh Medical Center, Zerifin, Israel.
Dr. Arkfeld and Dr. Efrati reported having no financial conflicts of interest regarding their studies, which were free of commercial sponsorship.
AT THE ACR ANNUAL MEETING
Major finding: Fibromyalgia patients experienced an average 19.5% reduction in Revised Fibromyalgia Impact Questionnaire scores from baseline after 3 months on low-dose naltrexone. Half of the patients were high-end responders, with an average 41% reduction in scores.
Data source: A prospective, open-label, single-center study involving 25 patients with fibromyalgia.
Disclosures: The presenter reported having no financial conflicts with regard to the study, which was free of commercial support.
New international fibromyalgia guidelines indicate shifting focus
SAN DIEGO – The high degree of consistency among recent national fibromyalgia guidelines developed independently by multispecialty panels in Canada, Israel, and Germany suggests big changes are afoot in how this common and vexing syndrome is conceptualized and treated, according to Dr. Jacob N. Ablin.
"I hope to convey the feeling that there is somewhat of a paradigm change in the recommendations regarding treatment of fibromyalgia as expressed by these three guidelines. All three emphasize an individually tailored approach based upon the key symptoms and severity, with nonpharmacologic therapies as the major positive first choice for all. The emphasis is on the necessity of self-management strategies, which include aerobic exercise, cognitive-behavioral therapy, and multicomponent exercise and psychologic therapies," he said at the annual meeting of the American College of Rheumatology.
"Pharmacologic therapies were less enthusiastically recommended by all three groups. Contrary to popular perception, the drugs actually achieve only relatively modest effects. And all three groups caution about the side effects of drugs, which may mimic fibromyalgia symptoms," added Dr. Ablin of the Tel Aviv Sourasky Medical Center.
The three medications approved by the Food and Drug Administration for the treatment of fibromyalgia – pregabalin (Lyrica), duloxetine (Cymbalta), and milnacipran (Savella) – received only a weak grade C recommendation in the German guidelines (Schmerz 2012;26:287-90) because all three failed to achieve their primary endpoints in pivotal European clinical trials.
"While drug treatments absolutely continue to play a role in the management of fibromyalgia, the long-term safety and efficacy of nonpharmacologic treatments should be appreciated and stressed. Fibromyalgia is not rheumatoid arthritis: We don’t have true disease-modifying antirheumatic drugs for fibromyalgia. And until we do, pharmacologic treatment is a very useful adjunct, not an imperative. This is an important message for patients, who will probably need treatment for many years to come," Dr. Ablin explained.
The German and Israeli guidelines contain detailed recommendations for a variety of complementary and alternative medicine (CAM) practices, including Tai Chi, guided imagery, acupuncture, yoga, and spa therapy. In contrast, the Canadian guidelines (CMAJ 2013;185:E645-51) deem current evidence insufficient to support the use of CAM practices in fibromyalgia.
The German guidelines recommend a graded approach to treatment. Patients with mild fibromyalgia are to be managed by primary care physicians, with advice given to engage in physical exercise and social activities, with no additional treatment recommended and no specialist care. In moderate fibromyalgia, the treatment plan involves aerobic exercise, time-limited psychological therapy, and referral to a specialist, with drug therapy optional. Patients with severe fibromyalgia symptoms, as well as those with moderate fibromyalgia unresponsive to the earlier-stage interventions, are best managed in a specialized day clinic or inpatient service that emphasizes psychiatric treatment of mental comorbidities, according to the German guidelines. In Germany, insurance companies cover these more intensive services because of their proven track record in reducing occupational disability.
The Israeli approach is different in that it is not based upon the initial severity of fibromyalgia. In step 1, patients receive education about their disorder and the principles involved in its treatment. They also get an individualized aerobic exercise program and are referred for aquatic exercise. Amitriptyline at 10-25 mg at bedtime is prescribed, and a referral is to be made for cognitive-behavioral therapy.
Step 2 is based upon a reassessment 12 weeks after starting step 1. If the patient isn’t doing significantly better, consideration is given to substituting a serotonin-norepinephrine reuptake inhibitor for the amitriptyline, or adding a selective serotonin reuptake inhibitor to amitriptyline, along with prescribing pregabalin to improve sleep and reduce pain. Referral is made for spa therapy and yoga or another meditative movement practice.
As in the German guidelines, the Canadian guidelines also recommend that fibromyalgia diagnosis and care be centered in the primary care setting, with only selective referrals for specialist care.
Dr. Mary-Ann Fitzcharles, lead author of the new Canadian guidelines, said all three guidelines, developed independently on three continents, share in common the same broad clinical concept of fibromyalgia.
"We are all speaking with one voice with the same message: We accept that fibromyalgia is neither a distinct rheumatic nor mental disorder, but rather a cluster of symptoms spanning a broad range of medical disciplines. We’re saying that just focusing on pain is taking away from a large component of the suffering of many of these patients," according to Dr. Fitzcharles of McGill University, Montreal.
The Canadian and German guidelines advise dropping the tender point examination from the patient evaluation, replacing it with an examination for generalized soft tissue tenderness. The Israeli guidelines retain the tender point exam.
One audience member vigorously objected to eliminating the tender point examination.
"The trigger point exam has always been a way for physicians to assess whether the patient is believable. Without using a trigger point exam, I might as well just sign a blank check. How am I going to weed out those who have fibromyalgia from those who are faking and seeking disability status?" he asked.
Dr. Fitzcharles responded: "I think we all know that depending upon who is doing the trigger point exam and how hard you’re pressing, you can make positive trigger points or you can cool them down. So it really is a very inaccurate clinical assessment. However, I will concede that in taking away the security blanket of trigger points from this condition, we now have to think very hard about putting something back in its place for the average primary practitioner to use in the office," the rheumatologist said.
Just what that might be remains unclear, she said. "The conundrum of fibromyalgia is that we have no defining biomarker as yet," Dr. Fitzcharles noted.
She reported serving as a consultant to and/or receiving research funding from Purdue Pharma, Eli Lilly, Pfizer, and Valeant. Dr. Ablin is a consultant to Pfizer.
SAN DIEGO – The high degree of consistency among recent national fibromyalgia guidelines developed independently by multispecialty panels in Canada, Israel, and Germany suggests big changes are afoot in how this common and vexing syndrome is conceptualized and treated, according to Dr. Jacob N. Ablin.
"I hope to convey the feeling that there is somewhat of a paradigm change in the recommendations regarding treatment of fibromyalgia as expressed by these three guidelines. All three emphasize an individually tailored approach based upon the key symptoms and severity, with nonpharmacologic therapies as the major positive first choice for all. The emphasis is on the necessity of self-management strategies, which include aerobic exercise, cognitive-behavioral therapy, and multicomponent exercise and psychologic therapies," he said at the annual meeting of the American College of Rheumatology.
"Pharmacologic therapies were less enthusiastically recommended by all three groups. Contrary to popular perception, the drugs actually achieve only relatively modest effects. And all three groups caution about the side effects of drugs, which may mimic fibromyalgia symptoms," added Dr. Ablin of the Tel Aviv Sourasky Medical Center.
The three medications approved by the Food and Drug Administration for the treatment of fibromyalgia – pregabalin (Lyrica), duloxetine (Cymbalta), and milnacipran (Savella) – received only a weak grade C recommendation in the German guidelines (Schmerz 2012;26:287-90) because all three failed to achieve their primary endpoints in pivotal European clinical trials.
"While drug treatments absolutely continue to play a role in the management of fibromyalgia, the long-term safety and efficacy of nonpharmacologic treatments should be appreciated and stressed. Fibromyalgia is not rheumatoid arthritis: We don’t have true disease-modifying antirheumatic drugs for fibromyalgia. And until we do, pharmacologic treatment is a very useful adjunct, not an imperative. This is an important message for patients, who will probably need treatment for many years to come," Dr. Ablin explained.
The German and Israeli guidelines contain detailed recommendations for a variety of complementary and alternative medicine (CAM) practices, including Tai Chi, guided imagery, acupuncture, yoga, and spa therapy. In contrast, the Canadian guidelines (CMAJ 2013;185:E645-51) deem current evidence insufficient to support the use of CAM practices in fibromyalgia.
The German guidelines recommend a graded approach to treatment. Patients with mild fibromyalgia are to be managed by primary care physicians, with advice given to engage in physical exercise and social activities, with no additional treatment recommended and no specialist care. In moderate fibromyalgia, the treatment plan involves aerobic exercise, time-limited psychological therapy, and referral to a specialist, with drug therapy optional. Patients with severe fibromyalgia symptoms, as well as those with moderate fibromyalgia unresponsive to the earlier-stage interventions, are best managed in a specialized day clinic or inpatient service that emphasizes psychiatric treatment of mental comorbidities, according to the German guidelines. In Germany, insurance companies cover these more intensive services because of their proven track record in reducing occupational disability.
The Israeli approach is different in that it is not based upon the initial severity of fibromyalgia. In step 1, patients receive education about their disorder and the principles involved in its treatment. They also get an individualized aerobic exercise program and are referred for aquatic exercise. Amitriptyline at 10-25 mg at bedtime is prescribed, and a referral is to be made for cognitive-behavioral therapy.
Step 2 is based upon a reassessment 12 weeks after starting step 1. If the patient isn’t doing significantly better, consideration is given to substituting a serotonin-norepinephrine reuptake inhibitor for the amitriptyline, or adding a selective serotonin reuptake inhibitor to amitriptyline, along with prescribing pregabalin to improve sleep and reduce pain. Referral is made for spa therapy and yoga or another meditative movement practice.
As in the German guidelines, the Canadian guidelines also recommend that fibromyalgia diagnosis and care be centered in the primary care setting, with only selective referrals for specialist care.
Dr. Mary-Ann Fitzcharles, lead author of the new Canadian guidelines, said all three guidelines, developed independently on three continents, share in common the same broad clinical concept of fibromyalgia.
"We are all speaking with one voice with the same message: We accept that fibromyalgia is neither a distinct rheumatic nor mental disorder, but rather a cluster of symptoms spanning a broad range of medical disciplines. We’re saying that just focusing on pain is taking away from a large component of the suffering of many of these patients," according to Dr. Fitzcharles of McGill University, Montreal.
The Canadian and German guidelines advise dropping the tender point examination from the patient evaluation, replacing it with an examination for generalized soft tissue tenderness. The Israeli guidelines retain the tender point exam.
One audience member vigorously objected to eliminating the tender point examination.
"The trigger point exam has always been a way for physicians to assess whether the patient is believable. Without using a trigger point exam, I might as well just sign a blank check. How am I going to weed out those who have fibromyalgia from those who are faking and seeking disability status?" he asked.
Dr. Fitzcharles responded: "I think we all know that depending upon who is doing the trigger point exam and how hard you’re pressing, you can make positive trigger points or you can cool them down. So it really is a very inaccurate clinical assessment. However, I will concede that in taking away the security blanket of trigger points from this condition, we now have to think very hard about putting something back in its place for the average primary practitioner to use in the office," the rheumatologist said.
Just what that might be remains unclear, she said. "The conundrum of fibromyalgia is that we have no defining biomarker as yet," Dr. Fitzcharles noted.
She reported serving as a consultant to and/or receiving research funding from Purdue Pharma, Eli Lilly, Pfizer, and Valeant. Dr. Ablin is a consultant to Pfizer.
SAN DIEGO – The high degree of consistency among recent national fibromyalgia guidelines developed independently by multispecialty panels in Canada, Israel, and Germany suggests big changes are afoot in how this common and vexing syndrome is conceptualized and treated, according to Dr. Jacob N. Ablin.
"I hope to convey the feeling that there is somewhat of a paradigm change in the recommendations regarding treatment of fibromyalgia as expressed by these three guidelines. All three emphasize an individually tailored approach based upon the key symptoms and severity, with nonpharmacologic therapies as the major positive first choice for all. The emphasis is on the necessity of self-management strategies, which include aerobic exercise, cognitive-behavioral therapy, and multicomponent exercise and psychologic therapies," he said at the annual meeting of the American College of Rheumatology.
"Pharmacologic therapies were less enthusiastically recommended by all three groups. Contrary to popular perception, the drugs actually achieve only relatively modest effects. And all three groups caution about the side effects of drugs, which may mimic fibromyalgia symptoms," added Dr. Ablin of the Tel Aviv Sourasky Medical Center.
The three medications approved by the Food and Drug Administration for the treatment of fibromyalgia – pregabalin (Lyrica), duloxetine (Cymbalta), and milnacipran (Savella) – received only a weak grade C recommendation in the German guidelines (Schmerz 2012;26:287-90) because all three failed to achieve their primary endpoints in pivotal European clinical trials.
"While drug treatments absolutely continue to play a role in the management of fibromyalgia, the long-term safety and efficacy of nonpharmacologic treatments should be appreciated and stressed. Fibromyalgia is not rheumatoid arthritis: We don’t have true disease-modifying antirheumatic drugs for fibromyalgia. And until we do, pharmacologic treatment is a very useful adjunct, not an imperative. This is an important message for patients, who will probably need treatment for many years to come," Dr. Ablin explained.
The German and Israeli guidelines contain detailed recommendations for a variety of complementary and alternative medicine (CAM) practices, including Tai Chi, guided imagery, acupuncture, yoga, and spa therapy. In contrast, the Canadian guidelines (CMAJ 2013;185:E645-51) deem current evidence insufficient to support the use of CAM practices in fibromyalgia.
The German guidelines recommend a graded approach to treatment. Patients with mild fibromyalgia are to be managed by primary care physicians, with advice given to engage in physical exercise and social activities, with no additional treatment recommended and no specialist care. In moderate fibromyalgia, the treatment plan involves aerobic exercise, time-limited psychological therapy, and referral to a specialist, with drug therapy optional. Patients with severe fibromyalgia symptoms, as well as those with moderate fibromyalgia unresponsive to the earlier-stage interventions, are best managed in a specialized day clinic or inpatient service that emphasizes psychiatric treatment of mental comorbidities, according to the German guidelines. In Germany, insurance companies cover these more intensive services because of their proven track record in reducing occupational disability.
The Israeli approach is different in that it is not based upon the initial severity of fibromyalgia. In step 1, patients receive education about their disorder and the principles involved in its treatment. They also get an individualized aerobic exercise program and are referred for aquatic exercise. Amitriptyline at 10-25 mg at bedtime is prescribed, and a referral is to be made for cognitive-behavioral therapy.
Step 2 is based upon a reassessment 12 weeks after starting step 1. If the patient isn’t doing significantly better, consideration is given to substituting a serotonin-norepinephrine reuptake inhibitor for the amitriptyline, or adding a selective serotonin reuptake inhibitor to amitriptyline, along with prescribing pregabalin to improve sleep and reduce pain. Referral is made for spa therapy and yoga or another meditative movement practice.
As in the German guidelines, the Canadian guidelines also recommend that fibromyalgia diagnosis and care be centered in the primary care setting, with only selective referrals for specialist care.
Dr. Mary-Ann Fitzcharles, lead author of the new Canadian guidelines, said all three guidelines, developed independently on three continents, share in common the same broad clinical concept of fibromyalgia.
"We are all speaking with one voice with the same message: We accept that fibromyalgia is neither a distinct rheumatic nor mental disorder, but rather a cluster of symptoms spanning a broad range of medical disciplines. We’re saying that just focusing on pain is taking away from a large component of the suffering of many of these patients," according to Dr. Fitzcharles of McGill University, Montreal.
The Canadian and German guidelines advise dropping the tender point examination from the patient evaluation, replacing it with an examination for generalized soft tissue tenderness. The Israeli guidelines retain the tender point exam.
One audience member vigorously objected to eliminating the tender point examination.
"The trigger point exam has always been a way for physicians to assess whether the patient is believable. Without using a trigger point exam, I might as well just sign a blank check. How am I going to weed out those who have fibromyalgia from those who are faking and seeking disability status?" he asked.
Dr. Fitzcharles responded: "I think we all know that depending upon who is doing the trigger point exam and how hard you’re pressing, you can make positive trigger points or you can cool them down. So it really is a very inaccurate clinical assessment. However, I will concede that in taking away the security blanket of trigger points from this condition, we now have to think very hard about putting something back in its place for the average primary practitioner to use in the office," the rheumatologist said.
Just what that might be remains unclear, she said. "The conundrum of fibromyalgia is that we have no defining biomarker as yet," Dr. Fitzcharles noted.
She reported serving as a consultant to and/or receiving research funding from Purdue Pharma, Eli Lilly, Pfizer, and Valeant. Dr. Ablin is a consultant to Pfizer.
EXPERT ANALYSIS FROM THE ACR ANNUAL MEETING
Good news: ‘fibrofog’ doesn’t portend Alzheimer’s
SAN DIEGO – ‘Fibrofog’ – the cognitive dysfunction experienced by up to 80% of fibromyalgia patients – is not an early harbinger of Alzheimer’s disease, Dr. Robert S. Katz asserted at the annual meeting of the American College of Rheumatology.
The problems with memory, concentration, language, and thinking, collectively known as fibrofog, affect fibromyalgia patients in their 20s-50s. The onset is typically more sudden and dramatic than with classic forms of dementia. As fibrofog becomes chronic, many affected fibromyalgia patients – fearing the worst – worry they are on a road to Alzheimer’s disease in middle age.
Not so, according to Dr. Katz, professor of medicine at Rush Medical College, Chicago.
He presented a cross-sectional study involving two cohorts. One comprised 69 fibromyalgia patients with symptoms of cognitive dysfunction of 12 months duration or less. The other consisted of 39 fibromyalgia patients with fibrofog symptoms of 7-26 years duration. The long-duration group averaged 52.3 years of age, nearly 7 years older than the group with more recent onset of fibrofog. But the two groups were closely similar in terms of educational level, depression scores, and vocabulary scale scores.
The key study finding: No significant differences existed between the two groups on 13 of the 14 measures of neurocognitive function assessed in the study, including logical memory, paired associate, digit symbol, letter fluency, processing speed, and the Stroop word speed and color speed tests.
Indeed, the sole metric where the long-duration fibrofog patients fared significantly worse was the Trails A test, a measure of spatial scanning and cognitive sequencing. However, the two groups had closely similar scores on the Trails B.
Compared with standardized normative means that have been established for each of the 14 neurocognitive tests, the level of cognitive impairment in the fibromyalgia patients was markedly less than that seen in patients with Alzheimer’s disease. More specifically, measures of processing speed and episodic memory, which are significantly diminished in individuals with preclinical Alzheimer’s disease, were within normal range in both study groups. That’s reassuring. So is the fact that the cognitive deficits present in the shorter-duration group weren’t markedly more pronounced in the group troubled by cognitive problems for an additional 6-25 years. Thus, fibrofog does not appear to be a condition characterized by progressive cognitive decline, the rheumatologist observed.
Dr. Katz reported having no financial conflicts of interest with regard to this study.
SAN DIEGO – ‘Fibrofog’ – the cognitive dysfunction experienced by up to 80% of fibromyalgia patients – is not an early harbinger of Alzheimer’s disease, Dr. Robert S. Katz asserted at the annual meeting of the American College of Rheumatology.
The problems with memory, concentration, language, and thinking, collectively known as fibrofog, affect fibromyalgia patients in their 20s-50s. The onset is typically more sudden and dramatic than with classic forms of dementia. As fibrofog becomes chronic, many affected fibromyalgia patients – fearing the worst – worry they are on a road to Alzheimer’s disease in middle age.
Not so, according to Dr. Katz, professor of medicine at Rush Medical College, Chicago.
He presented a cross-sectional study involving two cohorts. One comprised 69 fibromyalgia patients with symptoms of cognitive dysfunction of 12 months duration or less. The other consisted of 39 fibromyalgia patients with fibrofog symptoms of 7-26 years duration. The long-duration group averaged 52.3 years of age, nearly 7 years older than the group with more recent onset of fibrofog. But the two groups were closely similar in terms of educational level, depression scores, and vocabulary scale scores.
The key study finding: No significant differences existed between the two groups on 13 of the 14 measures of neurocognitive function assessed in the study, including logical memory, paired associate, digit symbol, letter fluency, processing speed, and the Stroop word speed and color speed tests.
Indeed, the sole metric where the long-duration fibrofog patients fared significantly worse was the Trails A test, a measure of spatial scanning and cognitive sequencing. However, the two groups had closely similar scores on the Trails B.
Compared with standardized normative means that have been established for each of the 14 neurocognitive tests, the level of cognitive impairment in the fibromyalgia patients was markedly less than that seen in patients with Alzheimer’s disease. More specifically, measures of processing speed and episodic memory, which are significantly diminished in individuals with preclinical Alzheimer’s disease, were within normal range in both study groups. That’s reassuring. So is the fact that the cognitive deficits present in the shorter-duration group weren’t markedly more pronounced in the group troubled by cognitive problems for an additional 6-25 years. Thus, fibrofog does not appear to be a condition characterized by progressive cognitive decline, the rheumatologist observed.
Dr. Katz reported having no financial conflicts of interest with regard to this study.
SAN DIEGO – ‘Fibrofog’ – the cognitive dysfunction experienced by up to 80% of fibromyalgia patients – is not an early harbinger of Alzheimer’s disease, Dr. Robert S. Katz asserted at the annual meeting of the American College of Rheumatology.
The problems with memory, concentration, language, and thinking, collectively known as fibrofog, affect fibromyalgia patients in their 20s-50s. The onset is typically more sudden and dramatic than with classic forms of dementia. As fibrofog becomes chronic, many affected fibromyalgia patients – fearing the worst – worry they are on a road to Alzheimer’s disease in middle age.
Not so, according to Dr. Katz, professor of medicine at Rush Medical College, Chicago.
He presented a cross-sectional study involving two cohorts. One comprised 69 fibromyalgia patients with symptoms of cognitive dysfunction of 12 months duration or less. The other consisted of 39 fibromyalgia patients with fibrofog symptoms of 7-26 years duration. The long-duration group averaged 52.3 years of age, nearly 7 years older than the group with more recent onset of fibrofog. But the two groups were closely similar in terms of educational level, depression scores, and vocabulary scale scores.
The key study finding: No significant differences existed between the two groups on 13 of the 14 measures of neurocognitive function assessed in the study, including logical memory, paired associate, digit symbol, letter fluency, processing speed, and the Stroop word speed and color speed tests.
Indeed, the sole metric where the long-duration fibrofog patients fared significantly worse was the Trails A test, a measure of spatial scanning and cognitive sequencing. However, the two groups had closely similar scores on the Trails B.
Compared with standardized normative means that have been established for each of the 14 neurocognitive tests, the level of cognitive impairment in the fibromyalgia patients was markedly less than that seen in patients with Alzheimer’s disease. More specifically, measures of processing speed and episodic memory, which are significantly diminished in individuals with preclinical Alzheimer’s disease, were within normal range in both study groups. That’s reassuring. So is the fact that the cognitive deficits present in the shorter-duration group weren’t markedly more pronounced in the group troubled by cognitive problems for an additional 6-25 years. Thus, fibrofog does not appear to be a condition characterized by progressive cognitive decline, the rheumatologist observed.
Dr. Katz reported having no financial conflicts of interest with regard to this study.
AT THE ACR ANNUAL MEETING
Major finding: Fibromyalgia patients who had recent onset of the constellation of cognitive dysfunction complaints known as fibrofog did not score worse on 13 of 14 measures of neurocognitive function than did those with far longer duration of symptoms, suggesting this is not a progressive dementing process.
Data source: A cross-sectional study in which 69 fibromyalgia patients with fibrofog symptoms of 12 months or less and 39 others with cognitive symptoms of 7-26 years duration completed a battery of 14 measures of neurocognitive functioning.
Disclosures: The presenter reported having no financial conflicts of interest.
Maternal lupus doubled autism risk
SAN DIEGO – The risk of autism spectrum disorders is more than doubled among children born to mothers with systemic lupus erythematosus, according to the first-ever controlled study to address the question.
That being said, women with SLE can be reassured that despite this elevated relative risk, the absolute risk that their child will be diagnosed with an autism spectrum disorder (ASD) is low – less than 1 in 50 – Dr. Evelyne Vinet said at the annual meeting of the American College of Rheumatology.
The increased risk of ASD in children born to women with SLE documented in this large study was not mediated by in utero exposure to medications for SLE, including antimalarials, immunosuppressive agents, corticosteroids, and antidepressants. Use of those drugs in pregnancy wasn’t associated with any increased risk. In light of this, further research is warranted into a highly promising alternative hypothesis: that in utero exposure to SLE-related autoantibodies, such as anti-DNA and antiphospholipid antibodies, may play a causative role, said Dr. Vinet, a rheumatologist at McGill University, Montreal.
Children born to mothers with SLE also had an increased likelihood of being diagnosed with attention-deficit/hyperactivity disorder in this study. However, in contrast to the situation with ASD, the increased risk of ADHD appeared to result from exposure to medications in utero – specifically, antidepressants and possibly immunosuppressives – rather than to maternal SLE per se, she added.
Dr. Vinet presented an analysis of the OSLER (Offspring of Systemic Lupus Erythematosus Mothers Registry) database, the world’s largest cohort of children born to mothers with SLE. OSLER includes all women with a diagnosis of SLE hospitalized for childbirth in the province of Quebec since 1989. This study included 509 women who had 719 children after they had been diagnosed with SLE, as well as 5,824 controls matched for age and year of delivery along with their 8,493 children. The mean maternal age was 30.3 years. The children were followed out to a mean age of 9.1 years.
ASD was diagnosed in 1.4% of children born to mothers with SLE, compared with 0.6% of control children. The mean age at diagnosis of ASD was noticeably lower in the offspring of mothers with SLE: 3.8 years, compared with 5.7 years in the control children.
Women with SLE had higher rates of hypertension, asthma, and diabetes than did controls at the time of delivery. They also had higher rates of obstetric complications, including preterm birth, small for gestational age, and gestational diabetes. In a multivariate analysis adjusted for these variables, maternal SLE remained independently associated with a 2.3-fold increased risk of diagnosis of an ASD in offspring.
Complete and reliable records of prescription drug use during pregnancy were available only for the roughly 20% of mothers belonging to the provincial medication public assistance program. Of the 18 cases of ASD diagnosed in the children of 1,925 mothers covered by the program, only one occurred among the 155 offspring of SLE mothers; that child had been exposed to corticosteroids in utero. Of the 17 cases of ASD diagnosed in the control group, 16 had no exposures to the medications under scrutiny, and one involved in utero exposure to an anticonvulsant.
The OSLER database doesn’t include information about maternal autoantibody levels, but Dr. Vinet and her coinvestigators have made the collection of such data a top priority in light of recent studies in animal models of SLE by other investigators. Those studies showed that SLE-related autoantibodies, including n-methyl-d-aspartate receptor antibodies and antiphospholipid antibodies, as well as interleukin-6 and other cytokines, alter fetal brain development and induce behavioral anomalies suggestive of autism, such as withdrawal, in the mouse offspring.
In addition, French investigators recently reported that 3 of 36 children born to mothers with antiphospholipid syndrome developed ASD, although Dr. Vinet noted that this small but intriguing study lacked a control group (Semin. Arthritis Rheum. 2013 Aug. 1 [doi: 10.1016/j.semarthrit.2013.07.001]).
ADHD was diagnosed in 9.9% of the children of mothers with SLE in the OSLER database, compared with 6.1% of controls. It was diagnosed when the children were older: at a mean age of 12.5 years, compared with 7.8 years in the controls. In a multivariate analysis adjusted for in utero drug exposures, the association between ADHD and maternal SLE was no longer significant. However, in utero exposure to antidepressant medication, regardless of whether or not a mother had SLE, was associated with a hefty 3.7-fold increase in ADHD in the offspring. Because of the relatively small number of mothers on antidepressant medication, Dr. Vinet is now collaborating with investigators in other Canadian provinces having more comprehensive maternal medication exposure data to take a closer look at this tentative link between in utero drug exposure and ADHD.
This study of the OSLER database was funded by the Canadian Institutes of Health Research. Dr. Vinet reported having no financial conflicts.
SAN DIEGO – The risk of autism spectrum disorders is more than doubled among children born to mothers with systemic lupus erythematosus, according to the first-ever controlled study to address the question.
That being said, women with SLE can be reassured that despite this elevated relative risk, the absolute risk that their child will be diagnosed with an autism spectrum disorder (ASD) is low – less than 1 in 50 – Dr. Evelyne Vinet said at the annual meeting of the American College of Rheumatology.
The increased risk of ASD in children born to women with SLE documented in this large study was not mediated by in utero exposure to medications for SLE, including antimalarials, immunosuppressive agents, corticosteroids, and antidepressants. Use of those drugs in pregnancy wasn’t associated with any increased risk. In light of this, further research is warranted into a highly promising alternative hypothesis: that in utero exposure to SLE-related autoantibodies, such as anti-DNA and antiphospholipid antibodies, may play a causative role, said Dr. Vinet, a rheumatologist at McGill University, Montreal.
Children born to mothers with SLE also had an increased likelihood of being diagnosed with attention-deficit/hyperactivity disorder in this study. However, in contrast to the situation with ASD, the increased risk of ADHD appeared to result from exposure to medications in utero – specifically, antidepressants and possibly immunosuppressives – rather than to maternal SLE per se, she added.
Dr. Vinet presented an analysis of the OSLER (Offspring of Systemic Lupus Erythematosus Mothers Registry) database, the world’s largest cohort of children born to mothers with SLE. OSLER includes all women with a diagnosis of SLE hospitalized for childbirth in the province of Quebec since 1989. This study included 509 women who had 719 children after they had been diagnosed with SLE, as well as 5,824 controls matched for age and year of delivery along with their 8,493 children. The mean maternal age was 30.3 years. The children were followed out to a mean age of 9.1 years.
ASD was diagnosed in 1.4% of children born to mothers with SLE, compared with 0.6% of control children. The mean age at diagnosis of ASD was noticeably lower in the offspring of mothers with SLE: 3.8 years, compared with 5.7 years in the control children.
Women with SLE had higher rates of hypertension, asthma, and diabetes than did controls at the time of delivery. They also had higher rates of obstetric complications, including preterm birth, small for gestational age, and gestational diabetes. In a multivariate analysis adjusted for these variables, maternal SLE remained independently associated with a 2.3-fold increased risk of diagnosis of an ASD in offspring.
Complete and reliable records of prescription drug use during pregnancy were available only for the roughly 20% of mothers belonging to the provincial medication public assistance program. Of the 18 cases of ASD diagnosed in the children of 1,925 mothers covered by the program, only one occurred among the 155 offspring of SLE mothers; that child had been exposed to corticosteroids in utero. Of the 17 cases of ASD diagnosed in the control group, 16 had no exposures to the medications under scrutiny, and one involved in utero exposure to an anticonvulsant.
The OSLER database doesn’t include information about maternal autoantibody levels, but Dr. Vinet and her coinvestigators have made the collection of such data a top priority in light of recent studies in animal models of SLE by other investigators. Those studies showed that SLE-related autoantibodies, including n-methyl-d-aspartate receptor antibodies and antiphospholipid antibodies, as well as interleukin-6 and other cytokines, alter fetal brain development and induce behavioral anomalies suggestive of autism, such as withdrawal, in the mouse offspring.
In addition, French investigators recently reported that 3 of 36 children born to mothers with antiphospholipid syndrome developed ASD, although Dr. Vinet noted that this small but intriguing study lacked a control group (Semin. Arthritis Rheum. 2013 Aug. 1 [doi: 10.1016/j.semarthrit.2013.07.001]).
ADHD was diagnosed in 9.9% of the children of mothers with SLE in the OSLER database, compared with 6.1% of controls. It was diagnosed when the children were older: at a mean age of 12.5 years, compared with 7.8 years in the controls. In a multivariate analysis adjusted for in utero drug exposures, the association between ADHD and maternal SLE was no longer significant. However, in utero exposure to antidepressant medication, regardless of whether or not a mother had SLE, was associated with a hefty 3.7-fold increase in ADHD in the offspring. Because of the relatively small number of mothers on antidepressant medication, Dr. Vinet is now collaborating with investigators in other Canadian provinces having more comprehensive maternal medication exposure data to take a closer look at this tentative link between in utero drug exposure and ADHD.
This study of the OSLER database was funded by the Canadian Institutes of Health Research. Dr. Vinet reported having no financial conflicts.
SAN DIEGO – The risk of autism spectrum disorders is more than doubled among children born to mothers with systemic lupus erythematosus, according to the first-ever controlled study to address the question.
That being said, women with SLE can be reassured that despite this elevated relative risk, the absolute risk that their child will be diagnosed with an autism spectrum disorder (ASD) is low – less than 1 in 50 – Dr. Evelyne Vinet said at the annual meeting of the American College of Rheumatology.
The increased risk of ASD in children born to women with SLE documented in this large study was not mediated by in utero exposure to medications for SLE, including antimalarials, immunosuppressive agents, corticosteroids, and antidepressants. Use of those drugs in pregnancy wasn’t associated with any increased risk. In light of this, further research is warranted into a highly promising alternative hypothesis: that in utero exposure to SLE-related autoantibodies, such as anti-DNA and antiphospholipid antibodies, may play a causative role, said Dr. Vinet, a rheumatologist at McGill University, Montreal.
Children born to mothers with SLE also had an increased likelihood of being diagnosed with attention-deficit/hyperactivity disorder in this study. However, in contrast to the situation with ASD, the increased risk of ADHD appeared to result from exposure to medications in utero – specifically, antidepressants and possibly immunosuppressives – rather than to maternal SLE per se, she added.
Dr. Vinet presented an analysis of the OSLER (Offspring of Systemic Lupus Erythematosus Mothers Registry) database, the world’s largest cohort of children born to mothers with SLE. OSLER includes all women with a diagnosis of SLE hospitalized for childbirth in the province of Quebec since 1989. This study included 509 women who had 719 children after they had been diagnosed with SLE, as well as 5,824 controls matched for age and year of delivery along with their 8,493 children. The mean maternal age was 30.3 years. The children were followed out to a mean age of 9.1 years.
ASD was diagnosed in 1.4% of children born to mothers with SLE, compared with 0.6% of control children. The mean age at diagnosis of ASD was noticeably lower in the offspring of mothers with SLE: 3.8 years, compared with 5.7 years in the control children.
Women with SLE had higher rates of hypertension, asthma, and diabetes than did controls at the time of delivery. They also had higher rates of obstetric complications, including preterm birth, small for gestational age, and gestational diabetes. In a multivariate analysis adjusted for these variables, maternal SLE remained independently associated with a 2.3-fold increased risk of diagnosis of an ASD in offspring.
Complete and reliable records of prescription drug use during pregnancy were available only for the roughly 20% of mothers belonging to the provincial medication public assistance program. Of the 18 cases of ASD diagnosed in the children of 1,925 mothers covered by the program, only one occurred among the 155 offspring of SLE mothers; that child had been exposed to corticosteroids in utero. Of the 17 cases of ASD diagnosed in the control group, 16 had no exposures to the medications under scrutiny, and one involved in utero exposure to an anticonvulsant.
The OSLER database doesn’t include information about maternal autoantibody levels, but Dr. Vinet and her coinvestigators have made the collection of such data a top priority in light of recent studies in animal models of SLE by other investigators. Those studies showed that SLE-related autoantibodies, including n-methyl-d-aspartate receptor antibodies and antiphospholipid antibodies, as well as interleukin-6 and other cytokines, alter fetal brain development and induce behavioral anomalies suggestive of autism, such as withdrawal, in the mouse offspring.
In addition, French investigators recently reported that 3 of 36 children born to mothers with antiphospholipid syndrome developed ASD, although Dr. Vinet noted that this small but intriguing study lacked a control group (Semin. Arthritis Rheum. 2013 Aug. 1 [doi: 10.1016/j.semarthrit.2013.07.001]).
ADHD was diagnosed in 9.9% of the children of mothers with SLE in the OSLER database, compared with 6.1% of controls. It was diagnosed when the children were older: at a mean age of 12.5 years, compared with 7.8 years in the controls. In a multivariate analysis adjusted for in utero drug exposures, the association between ADHD and maternal SLE was no longer significant. However, in utero exposure to antidepressant medication, regardless of whether or not a mother had SLE, was associated with a hefty 3.7-fold increase in ADHD in the offspring. Because of the relatively small number of mothers on antidepressant medication, Dr. Vinet is now collaborating with investigators in other Canadian provinces having more comprehensive maternal medication exposure data to take a closer look at this tentative link between in utero drug exposure and ADHD.
This study of the OSLER database was funded by the Canadian Institutes of Health Research. Dr. Vinet reported having no financial conflicts.
AT THE ACR ANNUAL MEETING
Major finding: Children born to mothers with systemic lupus erythematosus had an adjusted 2.3-fold increased risk of being diagnosed with an autism spectrum disorder, compared with controls.
Data source: This study from the world’s largest cohort of children born to mothers with SLE included 509 affected mothers and their 719 children, as well as 5,824 matched control mothers and their 8,493 children.
Disclosures: This study of the OSLER database was funded by the Canadian Institutes of Health Research. Dr. Vinet reported having no financial conflicts.
Successful anti-TNF therapy may cancel excess coronary risk in RA
SAN DIEGO – Rheumatoid arthritis patients with a good response to tumor necrosis factor inhibitor therapy when assessed roughly 5 months into treatment had an acute coronary syndrome risk during the next 2 years that was no different than that of the matched general population in a large, Swedish national registry study.
"We could see that the risk of acute coronary syndrome in the TNF inhibitor–exposed population was doubled in the first year compared to the general population. But all this increased risk was carried by patients with a moderate or nonresponse to therapy. We saw no difference in risk between the general population and patients with a good response to treatment. My belief is that this benefit is not due to the TNF inhibitor as such, but rather it’s the control of inflammation that is crucial," Dr. Lotta Ljung said at the annual meeting of the American College of Rheumatology.
‘Good response’ was defined in this study via the EULAR response criteria: that is, a greater than 1.2-point improvement in the widely used Disease Activity Score 28 (DAS28) over baseline to a score of 3.2 or less at the 5-month evaluation.
Dr. Ljung, a senior consultant in rheumatology at Umea (Sweden) University Hospital, presented two analyses drawn from the Swedish Biologics Register, a national registry that captures 90% of all Swedes on biologic therapy for rheumatoid arthritis (RA). The study population included 7,704 RA patients with no history of ischemic heart disease when they started on their first TNF inhibitor during 2001-2010. They were matched by age, gender, and location to 23,112 RA patients who never took a biologic agent and to a second matched control group comprised of 38,520 individuals in the general population.
The crude incidence rate of acute coronary syndrome (ACS) in patients actively on TNF inhibitor therapy throughout follow-up was 5.7 events per 1,000 person-years, compared with 8.6 per 1,000 in biologic-naive RA patients and 3.3 per 1,000 in the matched general population.
In a fully adjusted Cox multivariate regression analysis factoring in socioeconomic variables, RA duration, joint surgery, and baseline atherosclerotic disease and other comorbid conditions, patients on anti-TNF therapy had a highly significant 27% reduction in ACS risk, compared with biologic-naive RA patients.
Nonetheless, patients on TNF inhibitor therapy remained at an adjusted 1.5-fold increased risk of ACS, compared with general population controls. However, this was significantly lower than the 2.3-fold elevated risk in biologic-naive RA patients.
In a separate analysis, the investigators took a closer look at the Swedish Biologics Register subgroup of the 4,931 RA patients on anti-TNF therapy for whom EULAR response data 5 months into treatment were available. Thirty-eight percent of these patients had a EULAR good response, 37% had a moderate response, and 25% had no response.
During 2 years of follow-up starting at the time of the EULAR response evaluation, the crude incidence rate of ACS among all TNF inhibitor–exposed RA patients, with close to 8,600 person-years of follow-up, was 6.9 cases per 1,000 person-years, compared with 3.4 per 1,000 among the matched general population controls. In an adjusted multivariate regression analysis, the ACS risk was 1.94-fold greater in moderate responders to anti-TNF therapy than in the general population and 2.53-fold greater in the nonresponders, but not significantly different between good responders and controls.
In addition, patients with an erythrocyte sedimentation rate (ESR) below 20 mm/hour at the time of their EULAR response evaluation had a subsequent 66% lower 1-year risk of ACS than did those with a higher ESR. And patients with a DAS28 remission at the 5-month evaluation – that is, a DAS28 below 2.6 – had a 79% lower ACS risk than did those with a DAS28 of 2.6 or above.
"This is dramatic," Dr. Ljung said in an interview. "I think it’s the first time we see a population in our RA cohorts that doesn’t have any proven cardiovascular risk increase compared with the general population. But it raises additional questions, of course, such as who are these patients who receive the good response: Is it due to factors related to their disease or background that gives them the opportunity to have the good response? We adjusted for a number of factors, but still ..."
She added that these studies contain two key take-home messages for rheumatologists: "I think the first thing for us to do is to treat our patients’ inflammation perfectly using traditional and biologic DMARDs. And the second thing is to be more aware of the traditional risk factors and start modifying those more aggressively for our patients."
The Swedish Biologics Register is funded by the Swedish Rheumatology Association, with support from half a dozen pharmaceutical companies. Dr. Ljung disclosed ties with AbbVie and Bristol-Myers Squibb.
SAN DIEGO – Rheumatoid arthritis patients with a good response to tumor necrosis factor inhibitor therapy when assessed roughly 5 months into treatment had an acute coronary syndrome risk during the next 2 years that was no different than that of the matched general population in a large, Swedish national registry study.
"We could see that the risk of acute coronary syndrome in the TNF inhibitor–exposed population was doubled in the first year compared to the general population. But all this increased risk was carried by patients with a moderate or nonresponse to therapy. We saw no difference in risk between the general population and patients with a good response to treatment. My belief is that this benefit is not due to the TNF inhibitor as such, but rather it’s the control of inflammation that is crucial," Dr. Lotta Ljung said at the annual meeting of the American College of Rheumatology.
‘Good response’ was defined in this study via the EULAR response criteria: that is, a greater than 1.2-point improvement in the widely used Disease Activity Score 28 (DAS28) over baseline to a score of 3.2 or less at the 5-month evaluation.
Dr. Ljung, a senior consultant in rheumatology at Umea (Sweden) University Hospital, presented two analyses drawn from the Swedish Biologics Register, a national registry that captures 90% of all Swedes on biologic therapy for rheumatoid arthritis (RA). The study population included 7,704 RA patients with no history of ischemic heart disease when they started on their first TNF inhibitor during 2001-2010. They were matched by age, gender, and location to 23,112 RA patients who never took a biologic agent and to a second matched control group comprised of 38,520 individuals in the general population.
The crude incidence rate of acute coronary syndrome (ACS) in patients actively on TNF inhibitor therapy throughout follow-up was 5.7 events per 1,000 person-years, compared with 8.6 per 1,000 in biologic-naive RA patients and 3.3 per 1,000 in the matched general population.
In a fully adjusted Cox multivariate regression analysis factoring in socioeconomic variables, RA duration, joint surgery, and baseline atherosclerotic disease and other comorbid conditions, patients on anti-TNF therapy had a highly significant 27% reduction in ACS risk, compared with biologic-naive RA patients.
Nonetheless, patients on TNF inhibitor therapy remained at an adjusted 1.5-fold increased risk of ACS, compared with general population controls. However, this was significantly lower than the 2.3-fold elevated risk in biologic-naive RA patients.
In a separate analysis, the investigators took a closer look at the Swedish Biologics Register subgroup of the 4,931 RA patients on anti-TNF therapy for whom EULAR response data 5 months into treatment were available. Thirty-eight percent of these patients had a EULAR good response, 37% had a moderate response, and 25% had no response.
During 2 years of follow-up starting at the time of the EULAR response evaluation, the crude incidence rate of ACS among all TNF inhibitor–exposed RA patients, with close to 8,600 person-years of follow-up, was 6.9 cases per 1,000 person-years, compared with 3.4 per 1,000 among the matched general population controls. In an adjusted multivariate regression analysis, the ACS risk was 1.94-fold greater in moderate responders to anti-TNF therapy than in the general population and 2.53-fold greater in the nonresponders, but not significantly different between good responders and controls.
In addition, patients with an erythrocyte sedimentation rate (ESR) below 20 mm/hour at the time of their EULAR response evaluation had a subsequent 66% lower 1-year risk of ACS than did those with a higher ESR. And patients with a DAS28 remission at the 5-month evaluation – that is, a DAS28 below 2.6 – had a 79% lower ACS risk than did those with a DAS28 of 2.6 or above.
"This is dramatic," Dr. Ljung said in an interview. "I think it’s the first time we see a population in our RA cohorts that doesn’t have any proven cardiovascular risk increase compared with the general population. But it raises additional questions, of course, such as who are these patients who receive the good response: Is it due to factors related to their disease or background that gives them the opportunity to have the good response? We adjusted for a number of factors, but still ..."
She added that these studies contain two key take-home messages for rheumatologists: "I think the first thing for us to do is to treat our patients’ inflammation perfectly using traditional and biologic DMARDs. And the second thing is to be more aware of the traditional risk factors and start modifying those more aggressively for our patients."
The Swedish Biologics Register is funded by the Swedish Rheumatology Association, with support from half a dozen pharmaceutical companies. Dr. Ljung disclosed ties with AbbVie and Bristol-Myers Squibb.
SAN DIEGO – Rheumatoid arthritis patients with a good response to tumor necrosis factor inhibitor therapy when assessed roughly 5 months into treatment had an acute coronary syndrome risk during the next 2 years that was no different than that of the matched general population in a large, Swedish national registry study.
"We could see that the risk of acute coronary syndrome in the TNF inhibitor–exposed population was doubled in the first year compared to the general population. But all this increased risk was carried by patients with a moderate or nonresponse to therapy. We saw no difference in risk between the general population and patients with a good response to treatment. My belief is that this benefit is not due to the TNF inhibitor as such, but rather it’s the control of inflammation that is crucial," Dr. Lotta Ljung said at the annual meeting of the American College of Rheumatology.
‘Good response’ was defined in this study via the EULAR response criteria: that is, a greater than 1.2-point improvement in the widely used Disease Activity Score 28 (DAS28) over baseline to a score of 3.2 or less at the 5-month evaluation.
Dr. Ljung, a senior consultant in rheumatology at Umea (Sweden) University Hospital, presented two analyses drawn from the Swedish Biologics Register, a national registry that captures 90% of all Swedes on biologic therapy for rheumatoid arthritis (RA). The study population included 7,704 RA patients with no history of ischemic heart disease when they started on their first TNF inhibitor during 2001-2010. They were matched by age, gender, and location to 23,112 RA patients who never took a biologic agent and to a second matched control group comprised of 38,520 individuals in the general population.
The crude incidence rate of acute coronary syndrome (ACS) in patients actively on TNF inhibitor therapy throughout follow-up was 5.7 events per 1,000 person-years, compared with 8.6 per 1,000 in biologic-naive RA patients and 3.3 per 1,000 in the matched general population.
In a fully adjusted Cox multivariate regression analysis factoring in socioeconomic variables, RA duration, joint surgery, and baseline atherosclerotic disease and other comorbid conditions, patients on anti-TNF therapy had a highly significant 27% reduction in ACS risk, compared with biologic-naive RA patients.
Nonetheless, patients on TNF inhibitor therapy remained at an adjusted 1.5-fold increased risk of ACS, compared with general population controls. However, this was significantly lower than the 2.3-fold elevated risk in biologic-naive RA patients.
In a separate analysis, the investigators took a closer look at the Swedish Biologics Register subgroup of the 4,931 RA patients on anti-TNF therapy for whom EULAR response data 5 months into treatment were available. Thirty-eight percent of these patients had a EULAR good response, 37% had a moderate response, and 25% had no response.
During 2 years of follow-up starting at the time of the EULAR response evaluation, the crude incidence rate of ACS among all TNF inhibitor–exposed RA patients, with close to 8,600 person-years of follow-up, was 6.9 cases per 1,000 person-years, compared with 3.4 per 1,000 among the matched general population controls. In an adjusted multivariate regression analysis, the ACS risk was 1.94-fold greater in moderate responders to anti-TNF therapy than in the general population and 2.53-fold greater in the nonresponders, but not significantly different between good responders and controls.
In addition, patients with an erythrocyte sedimentation rate (ESR) below 20 mm/hour at the time of their EULAR response evaluation had a subsequent 66% lower 1-year risk of ACS than did those with a higher ESR. And patients with a DAS28 remission at the 5-month evaluation – that is, a DAS28 below 2.6 – had a 79% lower ACS risk than did those with a DAS28 of 2.6 or above.
"This is dramatic," Dr. Ljung said in an interview. "I think it’s the first time we see a population in our RA cohorts that doesn’t have any proven cardiovascular risk increase compared with the general population. But it raises additional questions, of course, such as who are these patients who receive the good response: Is it due to factors related to their disease or background that gives them the opportunity to have the good response? We adjusted for a number of factors, but still ..."
She added that these studies contain two key take-home messages for rheumatologists: "I think the first thing for us to do is to treat our patients’ inflammation perfectly using traditional and biologic DMARDs. And the second thing is to be more aware of the traditional risk factors and start modifying those more aggressively for our patients."
The Swedish Biologics Register is funded by the Swedish Rheumatology Association, with support from half a dozen pharmaceutical companies. Dr. Ljung disclosed ties with AbbVie and Bristol-Myers Squibb.
AT THE ACR ANNUAL MEETING
Major finding: The acute coronary syndrome risk was 1.94-fold greater in rheumatoid arthritis patients with a moderate response to anti-TNF therapy than in the general population and 2.53-fold greater in those with no response, but not significantly different between controls and good responders (defined by the degree of improvement in the Disease Activity Score 28 when evaluated 5 months into treatment).
Data source: An observational study of 7,704 rheumatoid arthritis patients in the nationwide Swedish Biologics Register who started on a first tumor necrosis factor inhibitor during 2001-2010, together with 23,112 matched biologic-naive rheumatoid arthritis patients and 38,520 matched controls drawn from the general population.
Disclosures: The Swedish Biologics Register is funded by the Swedish Rheumatology Association, with support from half a dozen pharmaceutical companies. The presenter disclosed ties to AbbVie and Bristol-Myers Squibb.
Remission reinduction with rituximab a possibility for ANCA-associated vasculitis
SAN DIEGO – Retreatment of granulomatosis with polyangiitis or microscopic polyangiitis with rituximab may be safe and effective in reinducing remission, a prospective trial has shown.
"The vast majority of patients with ANCA [antineutrophil cytoplasmic antibody]–associated vasculitis are able to achieve disease remission initially," Dr. Eli Miloslavsky said at the annual meeting of the American College of Rheumatology. "However, there’s a high rate of flare, as frequent as 55% over the first 3 years. Therefore, it’s critical to determine the best remission agent in relapsing disease."
Dr. Miloslavsky presented data from 17 patients in the RAVE (Rituximab in ANCA–Associated Vasculitis) trial who received two courses of rituximab (RTX) and were followed for an average of 301 days. Patients with a severe flare were eligible to receive an open-label course of RTX between 6 and 18 months (375 mg/m2 once a week for 4 weeks). Severe flare was defined as having a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG) of greater than 3 or one major BVAS/WG item. Outcomes were complete remission (no disease activity and being off of steroids), complete response (no disease activity and taking 10 g of prednisone or less), remission (no disease activity regardless of the prednisone dose), limited flare (BVAS/WG of 3 or less), and severe flare (BVAS/WG of greater than 3 or one major disease activity item). At baseline, 82% of patients who received two courses of rituximab were proteinase 3 positive and 88% had granulomatosis with polyangiitis as the clinical diagnosis.
Of the 17 patients, 11 (65%) had relapsing disease at study entry. After receiving a second course of RTX, 15 patients (88%) achieved remission in an average of 2 months, 12 (71%) had at least a complete response in an average of 5 months, and 8 (47%) reached complete remission in an average of 6 months, reported Dr. Miloslavsky of the department of rheumatology at Massachusetts General Hospital, Boston.
At the 12-month time point, 13 patients (76%) had achieved complete responses and 8 (47%) had reached complete remission.
Four flares occurred during the study. "They were all limited and the time to flare was approximately 8 months after receiving RTX," he said.
Three severe adverse events occurred, including one death (a patient with diffuse alveolar hemorrhage who did not improve and died 7 weeks after the initial flare), one case of metastatic colon cancer, and one case of severe sinusitis.
Dr. Miloslavsky acknowledged certain limitations of the study, including the small sample size, the lack of a comparison group, the lack of long-term follow-up, and the limited generalizability to myeloperoxidase-ANCA–positive patients.
The trial was funded by the Immune Tolerance Network, which is supported by the National Institute of Allergy and Infectious Diseases. Partial funding was also derived from Genentech and Biogen Idec.
SAN DIEGO – Retreatment of granulomatosis with polyangiitis or microscopic polyangiitis with rituximab may be safe and effective in reinducing remission, a prospective trial has shown.
"The vast majority of patients with ANCA [antineutrophil cytoplasmic antibody]–associated vasculitis are able to achieve disease remission initially," Dr. Eli Miloslavsky said at the annual meeting of the American College of Rheumatology. "However, there’s a high rate of flare, as frequent as 55% over the first 3 years. Therefore, it’s critical to determine the best remission agent in relapsing disease."
Dr. Miloslavsky presented data from 17 patients in the RAVE (Rituximab in ANCA–Associated Vasculitis) trial who received two courses of rituximab (RTX) and were followed for an average of 301 days. Patients with a severe flare were eligible to receive an open-label course of RTX between 6 and 18 months (375 mg/m2 once a week for 4 weeks). Severe flare was defined as having a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG) of greater than 3 or one major BVAS/WG item. Outcomes were complete remission (no disease activity and being off of steroids), complete response (no disease activity and taking 10 g of prednisone or less), remission (no disease activity regardless of the prednisone dose), limited flare (BVAS/WG of 3 or less), and severe flare (BVAS/WG of greater than 3 or one major disease activity item). At baseline, 82% of patients who received two courses of rituximab were proteinase 3 positive and 88% had granulomatosis with polyangiitis as the clinical diagnosis.
Of the 17 patients, 11 (65%) had relapsing disease at study entry. After receiving a second course of RTX, 15 patients (88%) achieved remission in an average of 2 months, 12 (71%) had at least a complete response in an average of 5 months, and 8 (47%) reached complete remission in an average of 6 months, reported Dr. Miloslavsky of the department of rheumatology at Massachusetts General Hospital, Boston.
At the 12-month time point, 13 patients (76%) had achieved complete responses and 8 (47%) had reached complete remission.
Four flares occurred during the study. "They were all limited and the time to flare was approximately 8 months after receiving RTX," he said.
Three severe adverse events occurred, including one death (a patient with diffuse alveolar hemorrhage who did not improve and died 7 weeks after the initial flare), one case of metastatic colon cancer, and one case of severe sinusitis.
Dr. Miloslavsky acknowledged certain limitations of the study, including the small sample size, the lack of a comparison group, the lack of long-term follow-up, and the limited generalizability to myeloperoxidase-ANCA–positive patients.
The trial was funded by the Immune Tolerance Network, which is supported by the National Institute of Allergy and Infectious Diseases. Partial funding was also derived from Genentech and Biogen Idec.
SAN DIEGO – Retreatment of granulomatosis with polyangiitis or microscopic polyangiitis with rituximab may be safe and effective in reinducing remission, a prospective trial has shown.
"The vast majority of patients with ANCA [antineutrophil cytoplasmic antibody]–associated vasculitis are able to achieve disease remission initially," Dr. Eli Miloslavsky said at the annual meeting of the American College of Rheumatology. "However, there’s a high rate of flare, as frequent as 55% over the first 3 years. Therefore, it’s critical to determine the best remission agent in relapsing disease."
Dr. Miloslavsky presented data from 17 patients in the RAVE (Rituximab in ANCA–Associated Vasculitis) trial who received two courses of rituximab (RTX) and were followed for an average of 301 days. Patients with a severe flare were eligible to receive an open-label course of RTX between 6 and 18 months (375 mg/m2 once a week for 4 weeks). Severe flare was defined as having a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG) of greater than 3 or one major BVAS/WG item. Outcomes were complete remission (no disease activity and being off of steroids), complete response (no disease activity and taking 10 g of prednisone or less), remission (no disease activity regardless of the prednisone dose), limited flare (BVAS/WG of 3 or less), and severe flare (BVAS/WG of greater than 3 or one major disease activity item). At baseline, 82% of patients who received two courses of rituximab were proteinase 3 positive and 88% had granulomatosis with polyangiitis as the clinical diagnosis.
Of the 17 patients, 11 (65%) had relapsing disease at study entry. After receiving a second course of RTX, 15 patients (88%) achieved remission in an average of 2 months, 12 (71%) had at least a complete response in an average of 5 months, and 8 (47%) reached complete remission in an average of 6 months, reported Dr. Miloslavsky of the department of rheumatology at Massachusetts General Hospital, Boston.
At the 12-month time point, 13 patients (76%) had achieved complete responses and 8 (47%) had reached complete remission.
Four flares occurred during the study. "They were all limited and the time to flare was approximately 8 months after receiving RTX," he said.
Three severe adverse events occurred, including one death (a patient with diffuse alveolar hemorrhage who did not improve and died 7 weeks after the initial flare), one case of metastatic colon cancer, and one case of severe sinusitis.
Dr. Miloslavsky acknowledged certain limitations of the study, including the small sample size, the lack of a comparison group, the lack of long-term follow-up, and the limited generalizability to myeloperoxidase-ANCA–positive patients.
The trial was funded by the Immune Tolerance Network, which is supported by the National Institute of Allergy and Infectious Diseases. Partial funding was also derived from Genentech and Biogen Idec.
AT THE ACR ANNUAL MEETING
Major finding: Six months after receiving a second course of rituximab, 47% of patients achieved complete remission.
Data source: A study of17 patients in the rituximab in ANCA-associated vasculitis trial who received two courses of rituximab and were followed for an average of 301 days.
Disclosures: The trial was funded by the Immune Tolerance Network, which is supported by the National Institute of Allergy and Infectious Diseases. Partial funding was also derived from Genentech and Biogen Idec.
Gout cases jump sevenfold in half-century
SAN DIEGO – The number of Americans with gout has climbed sevenfold during the last 50 years, according to Dr. Eswar Krishnan.
The population burden of illness imposed by gout has risen both in men and women across all age groups, but most strikingly so in men older than 65 years, said Dr. Krishnan, director of clinical epidemiology in the division of immunology and rheumatology at Stanford (Calif.) University.
He turned to National Health and Nutrition Examination Survey (NHANES) data to gain a more precise picture of U.S. trends in gout prevalence over time than has previously been available. He accomplished this by comparing age- and sex-specific rates from the 1959-1962 and the 2009-2010 editions of the long-running Centers for Disease Control and Prevention–sponsored surveys.
The unadjusted population-based prevalence of self-reported gout jumped from 6 cases per 1,000 during 1959-1962 to 26 per 1,000 in 2009-2010. The estimated number of gout cases climbed from 1.1 million in 1960 to 8.1 million in 2010. Yet the proportion of gout patients who were women remained steady at 31% over time.
The mean age of Americans with gout rose over the half-century from 54 to 61 years among men and from 55 to 65 years among women, he reported at the annual meeting of the American College of Rheumatology.
Statistical analysis indicated that the increase in gout cases among women during the last 50 years could be accounted for entirely by the much-discussed societal growth in abdominal obesity. In contrast, the explanation for the increased prevalence of gout in men was multifactorial. The bulk of the increase was associated with an increased life span and the graying of America, coupled with higher rates of hypertension, diabetes, and abdominal obesity.
However, an immeasurable portion of the increase in gout during the past half-century is probably due to increased awareness of the disease among the U.S. population, Dr. Krishnan added.
NHANES is sponsored by the Centers for Disease Control and Prevention. Dr. Krishnan reported having received research grants from Takeda, which markets gout medication.
SAN DIEGO – The number of Americans with gout has climbed sevenfold during the last 50 years, according to Dr. Eswar Krishnan.
The population burden of illness imposed by gout has risen both in men and women across all age groups, but most strikingly so in men older than 65 years, said Dr. Krishnan, director of clinical epidemiology in the division of immunology and rheumatology at Stanford (Calif.) University.
He turned to National Health and Nutrition Examination Survey (NHANES) data to gain a more precise picture of U.S. trends in gout prevalence over time than has previously been available. He accomplished this by comparing age- and sex-specific rates from the 1959-1962 and the 2009-2010 editions of the long-running Centers for Disease Control and Prevention–sponsored surveys.
The unadjusted population-based prevalence of self-reported gout jumped from 6 cases per 1,000 during 1959-1962 to 26 per 1,000 in 2009-2010. The estimated number of gout cases climbed from 1.1 million in 1960 to 8.1 million in 2010. Yet the proportion of gout patients who were women remained steady at 31% over time.
The mean age of Americans with gout rose over the half-century from 54 to 61 years among men and from 55 to 65 years among women, he reported at the annual meeting of the American College of Rheumatology.
Statistical analysis indicated that the increase in gout cases among women during the last 50 years could be accounted for entirely by the much-discussed societal growth in abdominal obesity. In contrast, the explanation for the increased prevalence of gout in men was multifactorial. The bulk of the increase was associated with an increased life span and the graying of America, coupled with higher rates of hypertension, diabetes, and abdominal obesity.
However, an immeasurable portion of the increase in gout during the past half-century is probably due to increased awareness of the disease among the U.S. population, Dr. Krishnan added.
NHANES is sponsored by the Centers for Disease Control and Prevention. Dr. Krishnan reported having received research grants from Takeda, which markets gout medication.
SAN DIEGO – The number of Americans with gout has climbed sevenfold during the last 50 years, according to Dr. Eswar Krishnan.
The population burden of illness imposed by gout has risen both in men and women across all age groups, but most strikingly so in men older than 65 years, said Dr. Krishnan, director of clinical epidemiology in the division of immunology and rheumatology at Stanford (Calif.) University.
He turned to National Health and Nutrition Examination Survey (NHANES) data to gain a more precise picture of U.S. trends in gout prevalence over time than has previously been available. He accomplished this by comparing age- and sex-specific rates from the 1959-1962 and the 2009-2010 editions of the long-running Centers for Disease Control and Prevention–sponsored surveys.
The unadjusted population-based prevalence of self-reported gout jumped from 6 cases per 1,000 during 1959-1962 to 26 per 1,000 in 2009-2010. The estimated number of gout cases climbed from 1.1 million in 1960 to 8.1 million in 2010. Yet the proportion of gout patients who were women remained steady at 31% over time.
The mean age of Americans with gout rose over the half-century from 54 to 61 years among men and from 55 to 65 years among women, he reported at the annual meeting of the American College of Rheumatology.
Statistical analysis indicated that the increase in gout cases among women during the last 50 years could be accounted for entirely by the much-discussed societal growth in abdominal obesity. In contrast, the explanation for the increased prevalence of gout in men was multifactorial. The bulk of the increase was associated with an increased life span and the graying of America, coupled with higher rates of hypertension, diabetes, and abdominal obesity.
However, an immeasurable portion of the increase in gout during the past half-century is probably due to increased awareness of the disease among the U.S. population, Dr. Krishnan added.
NHANES is sponsored by the Centers for Disease Control and Prevention. Dr. Krishnan reported having received research grants from Takeda, which markets gout medication.
AT THE ACR ANNUAL MEETING
Major finding: The estimated number of Americans with gout in the United States increased more than sevenfold from 1.1 million in 1960 to 8.1 million in 2010.
Data source: The National Health and Nutrition Examination Survey is a program of periodic, large, government-funded, national cross-sectional surveys involving a representative sample of the U.S. population.
Disclosures: The National Health and Nutrition Examination Survey is sponsored by the Centers for Disease Control and Prevention. The presenter reported receiving research grants from Takeda, which markets gout medication.
Antimalarials prove protective against long-term lupus damage
SAN DIEGO – Potentially modifiable risk factors for future irreversible organ damage in lupus patients include hypertension, the use of corticosteroids, and higher levels of inflammation early on, according to findings from the SLICC (Systemic Lupus International Collaborating Clinics) Inception Cohort Study.
In addition, the study identified the use of antimalarial drugs as the one significant protective factor against steady accrual of irreversible organ damage in lupus patients.
"These findings help us pave the way to consider whether, firstly, one could use damage as a primary endpoint in future clinical trials in lupus – somewhat akin to how the erosion score is used in rheumatoid arthritis – and secondly, the results suggest particular interventions that might be important in reducing the risk of damage over time," Dr. Ian N. Bruce said at the annual meeting of the American College of Rheumatology.
The study also identified several fixed and unmodifiable risk factors for irreversible damage in lupus patients: older age at diagnosis, male gender, and being black or white Americans, added Dr. Bruce, professor of rheumatology at the University of Manchester (U.K.) and chair of the SLICC research group.
The SLICC Inception Cohort Study involves 1,722 patients at 31 centers in 11 countries in North America, Europe, and Asia who enrolled within 15 months after being formally diagnosed with systemic lupus erythematosus based upon the 1997 ACR criteria. They averaged 35 years of age and had an average of 4.25 comprehensive annual follow-up visits during the study period.
Irreversible organ damage was assessed using the SLICC/ACR Damage Index, or SDI. At baseline, 35% of patients had at least one item of damage as indicated by an SDI score of 1 or more. Over time, damage rates slowly and steadily increased such that by 6 years of follow-up 51% of participants had an SDI of at least 1.
In a multivariate analysis, patients with an SDI score of 1 at baseline had a highly significant 37% reduction in the risk of increasing their score during follow-up if they were taking antimalarials, compared with those not taking antimalarials.
On the other hand, patients with a baseline SDI of 1 were 61% more likely to experience an increase in their damage score during follow-up if they had hypertension and 43% more likely to do so if they were on corticosteroids than if they weren’t. Moreover, their risk of going from an SDI of 1 to a higher SDI indicative of mounting damage increased by 10% for every 3-point increase on the SLE Disease Activity Index (SLEDAI).
Patients with a baseline SDI of 0 were 64% more likely to progress to a score of 1 or more during follow-up if they were taking corticosteroids and 71% more likely to do so if they were hypertensive. Their risk also increased by 17% for each 3-point increase in SLEDAI. Men had a 48% greater risk of going from an SDI of 0 to 1 or more than women. Asians were 40% less likely to develop irreversible damage.
Each 1-point increase in SDI score was associated with a 46% increased risk of mortality, as well as with poorer health-related quality of life, especially as reflected in SF-36 physical component scores.
Session chair Dr. Roberto Caricchio of Temple University, Philadelphia, called the SLICC study "very important work."
"It teaches us to be aggressive up-front with our lupus patients, which we often aren’t. We tend to spare ourselves because it’s a chronic disease, and we know we’ll see these patients for the next 20 years, so we try to spare them from certain therapies," said Dr. Caricchio.
Dr. Bruce concurred. "I think a concerted effort to switch the disease off in almost a treat-to-target way, getting people into remission, may well be very important with regard to avoiding long-term damage. If we could do that without using steroids, that would be ideal," he commented.
"SLICC is interested in the fact that most clinical trials in lupus to date have taken a very small subsection of the population, those with high disease activity, and used a particular biologic agent or new molecule to show that it improved disease activity. But actually the majority of people with lupus – around 60% have low-grade, grumbling disease and are on low-dose steroids. And those are the ones who accumulate damage. I think we need to have a paradigm shift in how we do clinical trials in lupus and think about doing lupus trials against a damage endpoint," the rheumatologist continued.
Power calculations based upon the SLICC Inception Cohort Study suggest such trials could be relatively modest in size, he added.
SLICC receives financial support from GlaxoSmithKline, Bristol-Myers Squibb, and Human Genome Sciences. Dr. Bruce reported receiving research funding from GlaxoSmithKline, Bristol-Myers Squibb, Roche, and UCB.
SAN DIEGO – Potentially modifiable risk factors for future irreversible organ damage in lupus patients include hypertension, the use of corticosteroids, and higher levels of inflammation early on, according to findings from the SLICC (Systemic Lupus International Collaborating Clinics) Inception Cohort Study.
In addition, the study identified the use of antimalarial drugs as the one significant protective factor against steady accrual of irreversible organ damage in lupus patients.
"These findings help us pave the way to consider whether, firstly, one could use damage as a primary endpoint in future clinical trials in lupus – somewhat akin to how the erosion score is used in rheumatoid arthritis – and secondly, the results suggest particular interventions that might be important in reducing the risk of damage over time," Dr. Ian N. Bruce said at the annual meeting of the American College of Rheumatology.
The study also identified several fixed and unmodifiable risk factors for irreversible damage in lupus patients: older age at diagnosis, male gender, and being black or white Americans, added Dr. Bruce, professor of rheumatology at the University of Manchester (U.K.) and chair of the SLICC research group.
The SLICC Inception Cohort Study involves 1,722 patients at 31 centers in 11 countries in North America, Europe, and Asia who enrolled within 15 months after being formally diagnosed with systemic lupus erythematosus based upon the 1997 ACR criteria. They averaged 35 years of age and had an average of 4.25 comprehensive annual follow-up visits during the study period.
Irreversible organ damage was assessed using the SLICC/ACR Damage Index, or SDI. At baseline, 35% of patients had at least one item of damage as indicated by an SDI score of 1 or more. Over time, damage rates slowly and steadily increased such that by 6 years of follow-up 51% of participants had an SDI of at least 1.
In a multivariate analysis, patients with an SDI score of 1 at baseline had a highly significant 37% reduction in the risk of increasing their score during follow-up if they were taking antimalarials, compared with those not taking antimalarials.
On the other hand, patients with a baseline SDI of 1 were 61% more likely to experience an increase in their damage score during follow-up if they had hypertension and 43% more likely to do so if they were on corticosteroids than if they weren’t. Moreover, their risk of going from an SDI of 1 to a higher SDI indicative of mounting damage increased by 10% for every 3-point increase on the SLE Disease Activity Index (SLEDAI).
Patients with a baseline SDI of 0 were 64% more likely to progress to a score of 1 or more during follow-up if they were taking corticosteroids and 71% more likely to do so if they were hypertensive. Their risk also increased by 17% for each 3-point increase in SLEDAI. Men had a 48% greater risk of going from an SDI of 0 to 1 or more than women. Asians were 40% less likely to develop irreversible damage.
Each 1-point increase in SDI score was associated with a 46% increased risk of mortality, as well as with poorer health-related quality of life, especially as reflected in SF-36 physical component scores.
Session chair Dr. Roberto Caricchio of Temple University, Philadelphia, called the SLICC study "very important work."
"It teaches us to be aggressive up-front with our lupus patients, which we often aren’t. We tend to spare ourselves because it’s a chronic disease, and we know we’ll see these patients for the next 20 years, so we try to spare them from certain therapies," said Dr. Caricchio.
Dr. Bruce concurred. "I think a concerted effort to switch the disease off in almost a treat-to-target way, getting people into remission, may well be very important with regard to avoiding long-term damage. If we could do that without using steroids, that would be ideal," he commented.
"SLICC is interested in the fact that most clinical trials in lupus to date have taken a very small subsection of the population, those with high disease activity, and used a particular biologic agent or new molecule to show that it improved disease activity. But actually the majority of people with lupus – around 60% have low-grade, grumbling disease and are on low-dose steroids. And those are the ones who accumulate damage. I think we need to have a paradigm shift in how we do clinical trials in lupus and think about doing lupus trials against a damage endpoint," the rheumatologist continued.
Power calculations based upon the SLICC Inception Cohort Study suggest such trials could be relatively modest in size, he added.
SLICC receives financial support from GlaxoSmithKline, Bristol-Myers Squibb, and Human Genome Sciences. Dr. Bruce reported receiving research funding from GlaxoSmithKline, Bristol-Myers Squibb, Roche, and UCB.
SAN DIEGO – Potentially modifiable risk factors for future irreversible organ damage in lupus patients include hypertension, the use of corticosteroids, and higher levels of inflammation early on, according to findings from the SLICC (Systemic Lupus International Collaborating Clinics) Inception Cohort Study.
In addition, the study identified the use of antimalarial drugs as the one significant protective factor against steady accrual of irreversible organ damage in lupus patients.
"These findings help us pave the way to consider whether, firstly, one could use damage as a primary endpoint in future clinical trials in lupus – somewhat akin to how the erosion score is used in rheumatoid arthritis – and secondly, the results suggest particular interventions that might be important in reducing the risk of damage over time," Dr. Ian N. Bruce said at the annual meeting of the American College of Rheumatology.
The study also identified several fixed and unmodifiable risk factors for irreversible damage in lupus patients: older age at diagnosis, male gender, and being black or white Americans, added Dr. Bruce, professor of rheumatology at the University of Manchester (U.K.) and chair of the SLICC research group.
The SLICC Inception Cohort Study involves 1,722 patients at 31 centers in 11 countries in North America, Europe, and Asia who enrolled within 15 months after being formally diagnosed with systemic lupus erythematosus based upon the 1997 ACR criteria. They averaged 35 years of age and had an average of 4.25 comprehensive annual follow-up visits during the study period.
Irreversible organ damage was assessed using the SLICC/ACR Damage Index, or SDI. At baseline, 35% of patients had at least one item of damage as indicated by an SDI score of 1 or more. Over time, damage rates slowly and steadily increased such that by 6 years of follow-up 51% of participants had an SDI of at least 1.
In a multivariate analysis, patients with an SDI score of 1 at baseline had a highly significant 37% reduction in the risk of increasing their score during follow-up if they were taking antimalarials, compared with those not taking antimalarials.
On the other hand, patients with a baseline SDI of 1 were 61% more likely to experience an increase in their damage score during follow-up if they had hypertension and 43% more likely to do so if they were on corticosteroids than if they weren’t. Moreover, their risk of going from an SDI of 1 to a higher SDI indicative of mounting damage increased by 10% for every 3-point increase on the SLE Disease Activity Index (SLEDAI).
Patients with a baseline SDI of 0 were 64% more likely to progress to a score of 1 or more during follow-up if they were taking corticosteroids and 71% more likely to do so if they were hypertensive. Their risk also increased by 17% for each 3-point increase in SLEDAI. Men had a 48% greater risk of going from an SDI of 0 to 1 or more than women. Asians were 40% less likely to develop irreversible damage.
Each 1-point increase in SDI score was associated with a 46% increased risk of mortality, as well as with poorer health-related quality of life, especially as reflected in SF-36 physical component scores.
Session chair Dr. Roberto Caricchio of Temple University, Philadelphia, called the SLICC study "very important work."
"It teaches us to be aggressive up-front with our lupus patients, which we often aren’t. We tend to spare ourselves because it’s a chronic disease, and we know we’ll see these patients for the next 20 years, so we try to spare them from certain therapies," said Dr. Caricchio.
Dr. Bruce concurred. "I think a concerted effort to switch the disease off in almost a treat-to-target way, getting people into remission, may well be very important with regard to avoiding long-term damage. If we could do that without using steroids, that would be ideal," he commented.
"SLICC is interested in the fact that most clinical trials in lupus to date have taken a very small subsection of the population, those with high disease activity, and used a particular biologic agent or new molecule to show that it improved disease activity. But actually the majority of people with lupus – around 60% have low-grade, grumbling disease and are on low-dose steroids. And those are the ones who accumulate damage. I think we need to have a paradigm shift in how we do clinical trials in lupus and think about doing lupus trials against a damage endpoint," the rheumatologist continued.
Power calculations based upon the SLICC Inception Cohort Study suggest such trials could be relatively modest in size, he added.
SLICC receives financial support from GlaxoSmithKline, Bristol-Myers Squibb, and Human Genome Sciences. Dr. Bruce reported receiving research funding from GlaxoSmithKline, Bristol-Myers Squibb, Roche, and UCB.
AT THE ACR ANNUAL MEETING
Major finding: Patients with recently diagnosed SLE and no significant organ damage at baseline were 71% more likely to develop irreversible organ damage during follow-up if they were hypertensive and 64% more likely to do so if they were taking corticosteroids. Antimalarial drugs showed a protective effect against accrual of damage.
Data source: The Systemic Lupus International Collaborating Clinics Inception Cohort Study involves 1,722 patients at 31 centers in 11 countries, all recruited within 15 months after diagnosis.
Disclosures: The study group receives funding from GlaxoSmithKline, Bristol-Myers Squibb, and Human Genome Sciences. The presenter receives research grants from GlaxoSmithKline, Bristol-Myers Squibb, and several other pharmaceutical companies.
Minimally important differences defined for CDAI for rheumatoid arthritis
SAN DIEGO – The utility of the Clinical Disease Activity Index as a simple, practical tool to quantify rheumatoid arthritis activity in everyday practice has gotten a big boost as a result of formal determination of the absolute change in the index that constitutes a minimally important difference.
"Our hope and expectation is that these MIDs [minimally important differences] for absolute change in CDAI [Clinical Disease Activity Index] can be used to determine whether patients are improving, and to help manage the patients that we see in clinic in terms of what treatments might need to be altered," Dr. Jeffrey R. Curtis explained at the annual meeting of the American College of Rheumatology.
The Disease Activity Score 28 (DAS28) has a widely accepted MID of 1.2 units, making it highly useful in defining a patient’s magnitude of clinical improvement in clinical trial settings. For example, exceeding this MID early after going on tumor necrosis factor inhibitor therapy has been shown to predict high likelihood of low disease activity at 1 year (J. Rheumatol. 2012;39:1326-33). But the DAS28 is impractical except when a real-time measurement of acute phase reactants is available, which is often not the case in everyday practice. The CDAI could be a better option for clinicians who are willing to do a joint count. Until now, however, the MID for the CDAI in real-world settings has not been defined, noted Dr. Curtis of the University of Alabama, Birmingham.
He and his coinvestigators have rectified this situation. They accomplished this by analyzing data from the Canadian Early Arthritis Cohort (CATCH), a large observational cohort of patients with early rheumatoid arthritis. After exclusion of the 8% of CATCH participants with comorbid fibromyalgia, that left 1,191 patients with rheumatologist-diagnosed rheumatoid arthritis, a mean 5.8-month duration of symptoms at enrollment, and a baseline CDAI of 28.5.
The investigators compared changes in DAS28 and CDAI during a total of more than 3,200 pairs of rheumatology patient visits spaced at 3-month intervals during the first 12 months after enrollment.
Overall, the best discriminator between a DAS28 MID indicative of significant clinical improvement as opposed to no improvement or worsening was a CDAI cut point of 5 units. That is, an absolute reduction of more than 5 units on the CDAI correlated well with a DAS28 improvement of at least 1.2 units. Indeed, the area under the receiver operator curve using a CDAI cut point of 5 units was 0.87. But there’s more to the story than that, according to Dr. Curtis.
"If at all possible, it’s preferable to use more specific CDAI MID cut points conditional on where patients are starting in terms of disease activity. Patients need less of a change in order to say that they feel better if they’re already starting out doing pretty well, with low disease activity, than if they’re starting with high disease activity," the rheumatologist said.
The generally accepted CDAI threshold for low disease activity is a score below 10. Moderate disease activity is a score of 10-22, while high disease activity is a CDAI in excess of 22. Dr. Curtis and his coworkers determined that the MID for patients with low disease activity is an absolute difference greater than 2 units. For patients with moderately active disease, it’s greater than 6 units. And for those with high disease activity, an absolute reduction of greater than 11 units defines the MID.
The investigators also tested the utility of their CDAI cut points in comparison to changes in outcomes other than the DAS28, including patient self-reported pain and Health Assessment Questionnaire-Disability Index scores (see chart).
Dr. Curtis reported receiving grants from and serving as a consultant to Amgen and Pfizer, which sponsor the CATCH study. He also receives funding from other companies as well as the National Institutes of Health.
SAN DIEGO – The utility of the Clinical Disease Activity Index as a simple, practical tool to quantify rheumatoid arthritis activity in everyday practice has gotten a big boost as a result of formal determination of the absolute change in the index that constitutes a minimally important difference.
"Our hope and expectation is that these MIDs [minimally important differences] for absolute change in CDAI [Clinical Disease Activity Index] can be used to determine whether patients are improving, and to help manage the patients that we see in clinic in terms of what treatments might need to be altered," Dr. Jeffrey R. Curtis explained at the annual meeting of the American College of Rheumatology.
The Disease Activity Score 28 (DAS28) has a widely accepted MID of 1.2 units, making it highly useful in defining a patient’s magnitude of clinical improvement in clinical trial settings. For example, exceeding this MID early after going on tumor necrosis factor inhibitor therapy has been shown to predict high likelihood of low disease activity at 1 year (J. Rheumatol. 2012;39:1326-33). But the DAS28 is impractical except when a real-time measurement of acute phase reactants is available, which is often not the case in everyday practice. The CDAI could be a better option for clinicians who are willing to do a joint count. Until now, however, the MID for the CDAI in real-world settings has not been defined, noted Dr. Curtis of the University of Alabama, Birmingham.
He and his coinvestigators have rectified this situation. They accomplished this by analyzing data from the Canadian Early Arthritis Cohort (CATCH), a large observational cohort of patients with early rheumatoid arthritis. After exclusion of the 8% of CATCH participants with comorbid fibromyalgia, that left 1,191 patients with rheumatologist-diagnosed rheumatoid arthritis, a mean 5.8-month duration of symptoms at enrollment, and a baseline CDAI of 28.5.
The investigators compared changes in DAS28 and CDAI during a total of more than 3,200 pairs of rheumatology patient visits spaced at 3-month intervals during the first 12 months after enrollment.
Overall, the best discriminator between a DAS28 MID indicative of significant clinical improvement as opposed to no improvement or worsening was a CDAI cut point of 5 units. That is, an absolute reduction of more than 5 units on the CDAI correlated well with a DAS28 improvement of at least 1.2 units. Indeed, the area under the receiver operator curve using a CDAI cut point of 5 units was 0.87. But there’s more to the story than that, according to Dr. Curtis.
"If at all possible, it’s preferable to use more specific CDAI MID cut points conditional on where patients are starting in terms of disease activity. Patients need less of a change in order to say that they feel better if they’re already starting out doing pretty well, with low disease activity, than if they’re starting with high disease activity," the rheumatologist said.
The generally accepted CDAI threshold for low disease activity is a score below 10. Moderate disease activity is a score of 10-22, while high disease activity is a CDAI in excess of 22. Dr. Curtis and his coworkers determined that the MID for patients with low disease activity is an absolute difference greater than 2 units. For patients with moderately active disease, it’s greater than 6 units. And for those with high disease activity, an absolute reduction of greater than 11 units defines the MID.
The investigators also tested the utility of their CDAI cut points in comparison to changes in outcomes other than the DAS28, including patient self-reported pain and Health Assessment Questionnaire-Disability Index scores (see chart).
Dr. Curtis reported receiving grants from and serving as a consultant to Amgen and Pfizer, which sponsor the CATCH study. He also receives funding from other companies as well as the National Institutes of Health.
SAN DIEGO – The utility of the Clinical Disease Activity Index as a simple, practical tool to quantify rheumatoid arthritis activity in everyday practice has gotten a big boost as a result of formal determination of the absolute change in the index that constitutes a minimally important difference.
"Our hope and expectation is that these MIDs [minimally important differences] for absolute change in CDAI [Clinical Disease Activity Index] can be used to determine whether patients are improving, and to help manage the patients that we see in clinic in terms of what treatments might need to be altered," Dr. Jeffrey R. Curtis explained at the annual meeting of the American College of Rheumatology.
The Disease Activity Score 28 (DAS28) has a widely accepted MID of 1.2 units, making it highly useful in defining a patient’s magnitude of clinical improvement in clinical trial settings. For example, exceeding this MID early after going on tumor necrosis factor inhibitor therapy has been shown to predict high likelihood of low disease activity at 1 year (J. Rheumatol. 2012;39:1326-33). But the DAS28 is impractical except when a real-time measurement of acute phase reactants is available, which is often not the case in everyday practice. The CDAI could be a better option for clinicians who are willing to do a joint count. Until now, however, the MID for the CDAI in real-world settings has not been defined, noted Dr. Curtis of the University of Alabama, Birmingham.
He and his coinvestigators have rectified this situation. They accomplished this by analyzing data from the Canadian Early Arthritis Cohort (CATCH), a large observational cohort of patients with early rheumatoid arthritis. After exclusion of the 8% of CATCH participants with comorbid fibromyalgia, that left 1,191 patients with rheumatologist-diagnosed rheumatoid arthritis, a mean 5.8-month duration of symptoms at enrollment, and a baseline CDAI of 28.5.
The investigators compared changes in DAS28 and CDAI during a total of more than 3,200 pairs of rheumatology patient visits spaced at 3-month intervals during the first 12 months after enrollment.
Overall, the best discriminator between a DAS28 MID indicative of significant clinical improvement as opposed to no improvement or worsening was a CDAI cut point of 5 units. That is, an absolute reduction of more than 5 units on the CDAI correlated well with a DAS28 improvement of at least 1.2 units. Indeed, the area under the receiver operator curve using a CDAI cut point of 5 units was 0.87. But there’s more to the story than that, according to Dr. Curtis.
"If at all possible, it’s preferable to use more specific CDAI MID cut points conditional on where patients are starting in terms of disease activity. Patients need less of a change in order to say that they feel better if they’re already starting out doing pretty well, with low disease activity, than if they’re starting with high disease activity," the rheumatologist said.
The generally accepted CDAI threshold for low disease activity is a score below 10. Moderate disease activity is a score of 10-22, while high disease activity is a CDAI in excess of 22. Dr. Curtis and his coworkers determined that the MID for patients with low disease activity is an absolute difference greater than 2 units. For patients with moderately active disease, it’s greater than 6 units. And for those with high disease activity, an absolute reduction of greater than 11 units defines the MID.
The investigators also tested the utility of their CDAI cut points in comparison to changes in outcomes other than the DAS28, including patient self-reported pain and Health Assessment Questionnaire-Disability Index scores (see chart).
Dr. Curtis reported receiving grants from and serving as a consultant to Amgen and Pfizer, which sponsor the CATCH study. He also receives funding from other companies as well as the National Institutes of Health.
AT THE ACR ANNUAL MEETING
Major finding: The minimally important difference on the Clinical Disease Activity Index that defines clinically meaningful improvement in rheumatoid arthritis patients is an absolute reduction greater than 5 units.
Data source: This determination was made by correlating changes in the CDAI and the Disease Activity Score 28 in 1,191 patients with early rheumatoid arthritis in the CATCH cohort.
Disclosures: Dr. Curtis reported receiving grants from and serving as a consultant to Amgen and Pfizer, which sponsor the CATCH study. He also receives funding from other companies as well as the National Institutes of Health.
