Sharon Worcester

Dosing directions and measuring devices included with top-selling pediatric over-the-counter liquid medications were highly inconsistent as of November 2009, when the Food and Drug Administration issued voluntary industry guidelines in response to numerous reports of unintentional overdoses among children, according to a descriptive study of 200 such medications.

© Larry Allen/Fotolia.com

The study, conducted to provide baseline data for assessing the degree and pace of industry conformity with the new guidelines, showed that 146 of 148 medications (98.6%) that included measuring devices had one or more inconsistencies between the dosing directions and the markings on the device, Dr. H. Shonna Yin of New York University and colleagues reported online in the Nov. 30 issue of JAMA.

The inconsistencies included missing markings in 24% of the products, superfluous markings in 81% of the products, and inconsistencies between the product’s label and the measuring device in 89% of products.

Furthermore, 5.5% of the products used atypical units of measurement, such as cubic centimeters, drams, or fluid ounces; 71.5% used milliliters (although 97 products used a nonstandard abbreviation for milliliter); 77.5% used teaspoon units; and 18.5% used the tablespoon (JAMA 2010 Nov. 30[doi:10.1001/jama.2010.1797]).

Other potentially problematic findings included the lack of a leading zero in 12.5% of 40 products with a dose smaller than 1 presented in decimal format, the use of nonstandard fraction formats in 64.5% of 110 products that used fractions, and the lack of a statement that the measuring device should be used only with its associated product in 62% of the 148 medications that included a device.

The investigators evaluated 200 products representing 99% of the U.S. market of analgesic, cough/cold, allergy, and gastrointestinal OTC liquid products – including 58 private-label products – that contained dosing information for children under age 12 years. The medications were studied during the 52 weeks ending Oct. 30, 2009.

"Given the high prevalence of baseline inconsistencies, regulatory oversight may be helpful in accelerating adoption of the guidance recommendations," the investigators wrote, noting that several Institute of Medicine reports have identified variable and poor-quality drug labeling as a major cause of confusion among consumers – and therefore as a potential risk factor for unintentional misuse of products.

Indeed, many of the unintentional overdoses that prompted the FDA guidance in 2009 were attributed, at least in part, to products with inconsistent or confusing labels and measuring devices. The FDA recommendations state that:

• All OTC liquid medication products include a measuring device.

• Consistent abbreviations and units of measurement be used for a given product’s device.

• The devices bear only necessary markings and not hold significantly more medication than the largest prescribed dose.

• Abbreviations conform to standards and be defined.

• Decimals and fractions be used with care.

• Studies on accurate use of the medications by consumers be conducted.

More than half of all U.S. children are exposed to at least one medication in a given week – and more than half of those medications are OTC. Also at least one in three U.S. adults and at least one in four U.S. parents have limited health literacy and even worse numeracy. For these reasons, the findings support these recommendations and particularly underscore the need for standardized measuring devices with all nonprescription liquid products, consistency between dosing directions and markings on the measuring device, and standardization of measurement units, abbreviations, and numeric formats across products, Dr. Yin and associates said.

"Even frequently used terms like teaspoon and tablespoon may be misinterpreted," they wrote, noting that errors in understanding teaspoon vs. tablespoon have been found to contribute to threefold errors, and that the use of these terms endorses the use of kitchen spoons, which are known to be associated with measurement error.

More patient-centered research is needed to adequately address best practices under the FDA guidance, and to evaluate other aspects of product packaging and safe medication use, they said, concluding that since the FDA’s guidelines are voluntary, subsequent systematic product analyses may help monitor progress in terms of industry compliance – and assess whether additional regulatory oversight is needed to ensure safe and effective use of OTC medications.

This study was funded by a career development grant to Dr. Yin from the Robert Wood Johnson Physician Faculty Scholars Program. Dr. Yin also reported receiving funds from Pfizer and McKing Consulting Corp. Other authors on the study also said they received funding from Pfizer, McNeil Consumer Healthcare, Abbott, Johnson & Johnson, and/or McKing Consulting.

Dosing directions and measuring devices included with top-selling pediatric over-the-counter liquid medications were highly inconsistent as of November 2009, when the Food and Drug Administration issued voluntary industry guidelines in response to numerous reports of unintentional overdoses among children, according to a descriptive study of 200 such medications.

© Larry Allen/Fotolia.com

The study, conducted to provide baseline data for assessing the degree and pace of industry conformity with the new guidelines, showed that 146 of 148 medications (98.6%) that included measuring devices had one or more inconsistencies between the dosing directions and the markings on the device, Dr. H. Shonna Yin of New York University and colleagues reported online in the Nov. 30 issue of JAMA.

The inconsistencies included missing markings in 24% of the products, superfluous markings in 81% of the products, and inconsistencies between the product’s label and the measuring device in 89% of products.

Furthermore, 5.5% of the products used atypical units of measurement, such as cubic centimeters, drams, or fluid ounces; 71.5% used milliliters (although 97 products used a nonstandard abbreviation for milliliter); 77.5% used teaspoon units; and 18.5% used the tablespoon (JAMA 2010 Nov. 30[doi:10.1001/jama.2010.1797]).

Other potentially problematic findings included the lack of a leading zero in 12.5% of 40 products with a dose smaller than 1 presented in decimal format, the use of nonstandard fraction formats in 64.5% of 110 products that used fractions, and the lack of a statement that the measuring device should be used only with its associated product in 62% of the 148 medications that included a device.

The investigators evaluated 200 products representing 99% of the U.S. market of analgesic, cough/cold, allergy, and gastrointestinal OTC liquid products – including 58 private-label products – that contained dosing information for children under age 12 years. The medications were studied during the 52 weeks ending Oct. 30, 2009.

"Given the high prevalence of baseline inconsistencies, regulatory oversight may be helpful in accelerating adoption of the guidance recommendations," the investigators wrote, noting that several Institute of Medicine reports have identified variable and poor-quality drug labeling as a major cause of confusion among consumers – and therefore as a potential risk factor for unintentional misuse of products.

Indeed, many of the unintentional overdoses that prompted the FDA guidance in 2009 were attributed, at least in part, to products with inconsistent or confusing labels and measuring devices. The FDA recommendations state that:

• All OTC liquid medication products include a measuring device.

• Consistent abbreviations and units of measurement be used for a given product’s device.

• The devices bear only necessary markings and not hold significantly more medication than the largest prescribed dose.

• Abbreviations conform to standards and be defined.

• Decimals and fractions be used with care.

• Studies on accurate use of the medications by consumers be conducted.

More than half of all U.S. children are exposed to at least one medication in a given week – and more than half of those medications are OTC. Also at least one in three U.S. adults and at least one in four U.S. parents have limited health literacy and even worse numeracy. For these reasons, the findings support these recommendations and particularly underscore the need for standardized measuring devices with all nonprescription liquid products, consistency between dosing directions and markings on the measuring device, and standardization of measurement units, abbreviations, and numeric formats across products, Dr. Yin and associates said.

"Even frequently used terms like teaspoon and tablespoon may be misinterpreted," they wrote, noting that errors in understanding teaspoon vs. tablespoon have been found to contribute to threefold errors, and that the use of these terms endorses the use of kitchen spoons, which are known to be associated with measurement error.

More patient-centered research is needed to adequately address best practices under the FDA guidance, and to evaluate other aspects of product packaging and safe medication use, they said, concluding that since the FDA’s guidelines are voluntary, subsequent systematic product analyses may help monitor progress in terms of industry compliance – and assess whether additional regulatory oversight is needed to ensure safe and effective use of OTC medications.

This study was funded by a career development grant to Dr. Yin from the Robert Wood Johnson Physician Faculty Scholars Program. Dr. Yin also reported receiving funds from Pfizer and McKing Consulting Corp. Other authors on the study also said they received funding from Pfizer, McNeil Consumer Healthcare, Abbott, Johnson & Johnson, and/or McKing Consulting.

Dosing directions and measuring devices included with top-selling pediatric over-the-counter liquid medications were highly inconsistent as of November 2009, when the Food and Drug Administration issued voluntary industry guidelines in response to numerous reports of unintentional overdoses among children, according to a descriptive study of 200 such medications.

© Larry Allen/Fotolia.com

The study, conducted to provide baseline data for assessing the degree and pace of industry conformity with the new guidelines, showed that 146 of 148 medications (98.6%) that included measuring devices had one or more inconsistencies between the dosing directions and the markings on the device, Dr. H. Shonna Yin of New York University and colleagues reported online in the Nov. 30 issue of JAMA.

The inconsistencies included missing markings in 24% of the products, superfluous markings in 81% of the products, and inconsistencies between the product’s label and the measuring device in 89% of products.

Furthermore, 5.5% of the products used atypical units of measurement, such as cubic centimeters, drams, or fluid ounces; 71.5% used milliliters (although 97 products used a nonstandard abbreviation for milliliter); 77.5% used teaspoon units; and 18.5% used the tablespoon (JAMA 2010 Nov. 30[doi:10.1001/jama.2010.1797]).

Other potentially problematic findings included the lack of a leading zero in 12.5% of 40 products with a dose smaller than 1 presented in decimal format, the use of nonstandard fraction formats in 64.5% of 110 products that used fractions, and the lack of a statement that the measuring device should be used only with its associated product in 62% of the 148 medications that included a device.

The investigators evaluated 200 products representing 99% of the U.S. market of analgesic, cough/cold, allergy, and gastrointestinal OTC liquid products – including 58 private-label products – that contained dosing information for children under age 12 years. The medications were studied during the 52 weeks ending Oct. 30, 2009.

"Given the high prevalence of baseline inconsistencies, regulatory oversight may be helpful in accelerating adoption of the guidance recommendations," the investigators wrote, noting that several Institute of Medicine reports have identified variable and poor-quality drug labeling as a major cause of confusion among consumers – and therefore as a potential risk factor for unintentional misuse of products.

Indeed, many of the unintentional overdoses that prompted the FDA guidance in 2009 were attributed, at least in part, to products with inconsistent or confusing labels and measuring devices. The FDA recommendations state that:

• All OTC liquid medication products include a measuring device.

• Consistent abbreviations and units of measurement be used for a given product’s device.

• The devices bear only necessary markings and not hold significantly more medication than the largest prescribed dose.

• Abbreviations conform to standards and be defined.

• Decimals and fractions be used with care.

• Studies on accurate use of the medications by consumers be conducted.

More than half of all U.S. children are exposed to at least one medication in a given week – and more than half of those medications are OTC. Also at least one in three U.S. adults and at least one in four U.S. parents have limited health literacy and even worse numeracy. For these reasons, the findings support these recommendations and particularly underscore the need for standardized measuring devices with all nonprescription liquid products, consistency between dosing directions and markings on the measuring device, and standardization of measurement units, abbreviations, and numeric formats across products, Dr. Yin and associates said.

"Even frequently used terms like teaspoon and tablespoon may be misinterpreted," they wrote, noting that errors in understanding teaspoon vs. tablespoon have been found to contribute to threefold errors, and that the use of these terms endorses the use of kitchen spoons, which are known to be associated with measurement error.

More patient-centered research is needed to adequately address best practices under the FDA guidance, and to evaluate other aspects of product packaging and safe medication use, they said, concluding that since the FDA’s guidelines are voluntary, subsequent systematic product analyses may help monitor progress in terms of industry compliance – and assess whether additional regulatory oversight is needed to ensure safe and effective use of OTC medications.

This study was funded by a career development grant to Dr. Yin from the Robert Wood Johnson Physician Faculty Scholars Program. Dr. Yin also reported receiving funds from Pfizer and McKing Consulting Corp. Other authors on the study also said they received funding from Pfizer, McNeil Consumer Healthcare, Abbott, Johnson & Johnson, and/or McKing Consulting.

Active surveillance would be reasonable for managing low-risk prostate cancer in a 65-year-old man who has a preference for that approach over initial treatment, according to the findings of a decision analysis based on a simulation model.

In a hypothetical cohort of 65-year-old men with a new diagnosis of clinically localized, low-risk prostate cancer, the quality of life benefits and risks of active surveillance and three initial treatment strategies, including brachytherapy, intensity modulated radiation therapy (IMRT), and radical prostatectomy were compared. Active surveillance with IMRT in the event of disease progression was associated with the greatest quality-adjusted life expectancy (QALE), which was the main outcome measure, Dr. Julia H. Hayes of Dana-Farber Cancer Institute, Boston, and her colleagues found.

Active surveillance, which includes close monitoring with serial prostate-specific antigen measurements, digital rectal examinations, and biopsies with treatment at progression or by patient choice, was associated with 11.07 quality-adjusted life-years (QALYs), compared with 10.57 for brachytherapy, 10.51 for IMRT, and 10.23 for radical prostatectomy, the investigators report in the Dec. 1 issue of JAMA.

"The difference between the most and least effective initial treatment was 0.34 QALYs, or 4.1 months of QALE. In contrast, active surveillance provided 6.0 additional months of QALE, compared with brachytherapy, the most effective initial treatment," they wrote (JAMA 2010;304:2373-80).

Inputs for the simulation model, including probabilities and utilities – the weights assigned to individuals’ preferences for a particular health state – were estimated from a systematic literature review. The base case assumption of relative risk of prostate cancer-specific death for initial treatment vs. active surveillance was a "conservative but reasonable" 0.83, but even at an assumed relative risk as low as 0.6, active surveillance remained associated with the highest QALE, they said.

However, although active surveillance was favored over initial treatment even at varied estimates of prostate cancer-specific death and progressive diseases during active surveillance, the result was "highly dependent on the utility individuals place on living under active surveillance compared with having been treated," the investigators said.

This indicates that the decision whether to pursue active surveillance must be individualized, taking into account patient preference, they said.

The findings are important, given that in 2009, 70% of the 192,000 men diagnosed with prostate cancer in the United States will have had clinically localized, low-risk disease, yet more than 90% will have undergone initial treatment, the investigators said, noting that the majority of treated men experience at least one adverse effect from treatment.

Up to 40% of men newly diagnosed with prostate cancer meet the criteria for active surveillance, but that approach is used infrequently.

"Barriers to its use have included concerns about long-term disease outcomes, the perception that most men will ultimately undergo treatment, and concerns about the quality of life of men who elect active surveillance," they wrote.

The findings of this study – though limited only to 65-year-old men and by the limitations inherent in the literature used to derive model inputs, suggest that active surveillance in patients with low-risk disease has the potential to mitigate overtreatment.

"However, the finding that the optimal strategy is sensitive to utility weights is evidence that the decision whether to pursue active surveillance must be individualized. Models that incorporate individual patient utilities should be developed to assist patients and their caregivers to estimate the risks and potential benefits of active surveillance before making this decision," the investigators concluded.

This study was supported by grants from the National Cancer Institute and the Department of Defense, and by a Young Investigator’s Award to Dr. Hayes from the Prostate Cancer Foundation. Blue Shield of California Foundation also supported the study through funding to the Institute for Clinical and Economic Review, with which some study authors are affiliated.

Active surveillance would be reasonable for managing low-risk prostate cancer in a 65-year-old man who has a preference for that approach over initial treatment, according to the findings of a decision analysis based on a simulation model.

In a hypothetical cohort of 65-year-old men with a new diagnosis of clinically localized, low-risk prostate cancer, the quality of life benefits and risks of active surveillance and three initial treatment strategies, including brachytherapy, intensity modulated radiation therapy (IMRT), and radical prostatectomy were compared. Active surveillance with IMRT in the event of disease progression was associated with the greatest quality-adjusted life expectancy (QALE), which was the main outcome measure, Dr. Julia H. Hayes of Dana-Farber Cancer Institute, Boston, and her colleagues found.

Active surveillance, which includes close monitoring with serial prostate-specific antigen measurements, digital rectal examinations, and biopsies with treatment at progression or by patient choice, was associated with 11.07 quality-adjusted life-years (QALYs), compared with 10.57 for brachytherapy, 10.51 for IMRT, and 10.23 for radical prostatectomy, the investigators report in the Dec. 1 issue of JAMA.

"The difference between the most and least effective initial treatment was 0.34 QALYs, or 4.1 months of QALE. In contrast, active surveillance provided 6.0 additional months of QALE, compared with brachytherapy, the most effective initial treatment," they wrote (JAMA 2010;304:2373-80).

Inputs for the simulation model, including probabilities and utilities – the weights assigned to individuals’ preferences for a particular health state – were estimated from a systematic literature review. The base case assumption of relative risk of prostate cancer-specific death for initial treatment vs. active surveillance was a "conservative but reasonable" 0.83, but even at an assumed relative risk as low as 0.6, active surveillance remained associated with the highest QALE, they said.

However, although active surveillance was favored over initial treatment even at varied estimates of prostate cancer-specific death and progressive diseases during active surveillance, the result was "highly dependent on the utility individuals place on living under active surveillance compared with having been treated," the investigators said.

This indicates that the decision whether to pursue active surveillance must be individualized, taking into account patient preference, they said.

The findings are important, given that in 2009, 70% of the 192,000 men diagnosed with prostate cancer in the United States will have had clinically localized, low-risk disease, yet more than 90% will have undergone initial treatment, the investigators said, noting that the majority of treated men experience at least one adverse effect from treatment.

Up to 40% of men newly diagnosed with prostate cancer meet the criteria for active surveillance, but that approach is used infrequently.

"Barriers to its use have included concerns about long-term disease outcomes, the perception that most men will ultimately undergo treatment, and concerns about the quality of life of men who elect active surveillance," they wrote.

The findings of this study – though limited only to 65-year-old men and by the limitations inherent in the literature used to derive model inputs, suggest that active surveillance in patients with low-risk disease has the potential to mitigate overtreatment.

"However, the finding that the optimal strategy is sensitive to utility weights is evidence that the decision whether to pursue active surveillance must be individualized. Models that incorporate individual patient utilities should be developed to assist patients and their caregivers to estimate the risks and potential benefits of active surveillance before making this decision," the investigators concluded.

This study was supported by grants from the National Cancer Institute and the Department of Defense, and by a Young Investigator’s Award to Dr. Hayes from the Prostate Cancer Foundation. Blue Shield of California Foundation also supported the study through funding to the Institute for Clinical and Economic Review, with which some study authors are affiliated.

Active surveillance would be reasonable for managing low-risk prostate cancer in a 65-year-old man who has a preference for that approach over initial treatment, according to the findings of a decision analysis based on a simulation model.

In a hypothetical cohort of 65-year-old men with a new diagnosis of clinically localized, low-risk prostate cancer, the quality of life benefits and risks of active surveillance and three initial treatment strategies, including brachytherapy, intensity modulated radiation therapy (IMRT), and radical prostatectomy were compared. Active surveillance with IMRT in the event of disease progression was associated with the greatest quality-adjusted life expectancy (QALE), which was the main outcome measure, Dr. Julia H. Hayes of Dana-Farber Cancer Institute, Boston, and her colleagues found.

Active surveillance, which includes close monitoring with serial prostate-specific antigen measurements, digital rectal examinations, and biopsies with treatment at progression or by patient choice, was associated with 11.07 quality-adjusted life-years (QALYs), compared with 10.57 for brachytherapy, 10.51 for IMRT, and 10.23 for radical prostatectomy, the investigators report in the Dec. 1 issue of JAMA.

"The difference between the most and least effective initial treatment was 0.34 QALYs, or 4.1 months of QALE. In contrast, active surveillance provided 6.0 additional months of QALE, compared with brachytherapy, the most effective initial treatment," they wrote (JAMA 2010;304:2373-80).

Inputs for the simulation model, including probabilities and utilities – the weights assigned to individuals’ preferences for a particular health state – were estimated from a systematic literature review. The base case assumption of relative risk of prostate cancer-specific death for initial treatment vs. active surveillance was a "conservative but reasonable" 0.83, but even at an assumed relative risk as low as 0.6, active surveillance remained associated with the highest QALE, they said.

However, although active surveillance was favored over initial treatment even at varied estimates of prostate cancer-specific death and progressive diseases during active surveillance, the result was "highly dependent on the utility individuals place on living under active surveillance compared with having been treated," the investigators said.

This indicates that the decision whether to pursue active surveillance must be individualized, taking into account patient preference, they said.

The findings are important, given that in 2009, 70% of the 192,000 men diagnosed with prostate cancer in the United States will have had clinically localized, low-risk disease, yet more than 90% will have undergone initial treatment, the investigators said, noting that the majority of treated men experience at least one adverse effect from treatment.

Up to 40% of men newly diagnosed with prostate cancer meet the criteria for active surveillance, but that approach is used infrequently.

"Barriers to its use have included concerns about long-term disease outcomes, the perception that most men will ultimately undergo treatment, and concerns about the quality of life of men who elect active surveillance," they wrote.

The findings of this study – though limited only to 65-year-old men and by the limitations inherent in the literature used to derive model inputs, suggest that active surveillance in patients with low-risk disease has the potential to mitigate overtreatment.

"However, the finding that the optimal strategy is sensitive to utility weights is evidence that the decision whether to pursue active surveillance must be individualized. Models that incorporate individual patient utilities should be developed to assist patients and their caregivers to estimate the risks and potential benefits of active surveillance before making this decision," the investigators concluded.

This study was supported by grants from the National Cancer Institute and the Department of Defense, and by a Young Investigator’s Award to Dr. Hayes from the Prostate Cancer Foundation. Blue Shield of California Foundation also supported the study through funding to the Institute for Clinical and Economic Review, with which some study authors are affiliated.

ATLANTA - The best available evidence suggests that exercise should be recommended as a nonpharmacologic treatment option for hip and knee osteoarthritis.

So says a technical panel of experts convened by the American College of Rheumatology to revise existing treatment recommendations on the nonpharmacologic treatment of hand, hip, and knee OA. The panel began work on the recommendations in 2008, and the proposed revisions – based on consensus of the panel – are now under review by the ACR.

The panel found "strong" evidence that aerobic land-based exercise, resistance land-based exercise, aquatic exercise, and weight loss for overweight patients can be helpful for reducing pain and improving physical function in hip and knee osteoarthritis, Carol Oatis, Ph.D., reported at the annual meeting of the American College of Rheumatology.

Photo (c)Elena Korenbaum/ iStockphoto.com

As such, the panel proposes to recommend these treatments, said Dr. Oatis, a physical therapist and professor of physical therapy at Arcadia University in Glenside, Pa., and a member of the technical expert panel.

This was the only time the panel deemed supporting evidence to be "strong." They did so based on the GRADE methodology used in developing the revised recommendations. GRADE (grades of recommendations, assessment, development, and evaluation) allows for rating of the available evidence as "strong," "weak," or "none." The GRADE working group developed the system for evaluating data supporting recommendation in health care in 2000.

Strong evidence is of high quality with a large gradient between benefits and risks, and little uncertainty or variability in values and preferences; weak evidence has moderate quality with a small gradient between benefits and risks, and moderate uncertainty or variability in values and preferences; and "none" means the evidence was of low or very low quality with no difference between benefits and risks.

The panel "recommends" modalities with strong evidence, "suggests" those with weak evidence, and provides "no guidance" for those in the "none" category.

Weak evidence of benefit in hip OA was found for manual therapy in combination with supervised exercise programs, therefore the panel suggests – but does not recommend – that this modality be considered for patients with hip OA, Dr. Oatis said.

No evidence was found either in support of or against balance exercises or tai chi, so the panel provided no guidance for these approaches, Dr. Oatis said.

The panel also considered the evidence for hand OA, and for various specific nonpharmacologic approaches to treating OA.

For hand OA, weak evidence was found for:

• Evaluating patients regarding activities of daily living.

• Providing instruction on joint protection techniques.

• Providing assistive devices as needed.

• Instructing patients regarding the use of thermal modalities.

• Using splints for the trapezio-metacarpal joint (CMC joint at the base of the thumb).

Thus, the panel "suggests" use of these modalities, said Catherine Backman, Ph.D., an occupational therapist and faculty member at the University of British Columbia, Vancouver, and a panel member.

When it comes to suggestions based on weak evidence, patient preference comes into play, because this generally means there is no evidence against – and there is some evidence in favor of – use of these modalities, Dr. Backman said.

"Clinicians may want to discuss [these modalities] with patients, and discuss the evidence with patients in relation to their values and preferences," she said.

No other recommendations or suggestions were made for hand OA.

As for specific treatment modalities, weak evidence was found for:

• Medial wedge shoe insoles for lateral compartment knee OA.

• Subtalar strapping and lateral wedge insoles for medial compartment knee OA.

• Medial patellar femoral taping.

Transcutaneous electrical nerve stimulation (TENS) for knee OA with chronic moderate-to-severe pain.

• Traditional Chinese acupuncture for knee OA with moderate to severe pain.

• Thermal modalities.

• Walking aids.

No evidence was found for or against valgus bracing for knee OA, or for lateral patellar-femoral taping, therefore the panel chose not to provide guidance on these, said G. Kelley Fitzgerald, Ph.D., a physical therapist and faculty member at the University of Pittsburgh, and a panel member.

The panel, which reviewed existing English-language studies and existing guidelines from the ACR and other organizations, based its evidence strength determinations on the quality of the evidence and the extent to which the evidence demonstrated pain relief and improved physical functionality.

The panel did not determine that any of the reviewed modalities should not be used.

"The lack of ‘do not do’ recommendations or suggestions means that there was no definitive evidence of harm or lack of efficacy for the interventions examined, Dr. Oatis explained.

These proposed revisions to the current ACR recommendations, which were last revised in 2000, with an update in 2005 following the withdrawal of rofecoxib from the market, are currently under review by the journal Arthritis Care and Research, and have been submitted to the ACR Committee on Quality of Care for review before they are sent the ACR board of directors for final approval, said Dr. Marc C. Hochberg, professor and head of the division of rheumatology and clinical immunology at the University of Maryland, Baltimore.

The ACR awarded the contract for the project to the University of Maryland with Dr. Hochberg as the principal investigator. He is also a member of the project steering committee.

"Hopefully, these will come to the point where the ACR board of directors will be satisfied, and we’ll have a publication in 2011," he said.

Dr. Hochberg disclosed that he has received research support from the National Institutes of Health, and has served as a consultant or on an advisory board or data safety monitoring board for numerous pharmaceutical companies. The other presenters had no disclosures.

ATLANTA - The best available evidence suggests that exercise should be recommended as a nonpharmacologic treatment option for hip and knee osteoarthritis.

So says a technical panel of experts convened by the American College of Rheumatology to revise existing treatment recommendations on the nonpharmacologic treatment of hand, hip, and knee OA. The panel began work on the recommendations in 2008, and the proposed revisions – based on consensus of the panel – are now under review by the ACR.

The panel found "strong" evidence that aerobic land-based exercise, resistance land-based exercise, aquatic exercise, and weight loss for overweight patients can be helpful for reducing pain and improving physical function in hip and knee osteoarthritis, Carol Oatis, Ph.D., reported at the annual meeting of the American College of Rheumatology.

Photo (c)Elena Korenbaum/ iStockphoto.com

As such, the panel proposes to recommend these treatments, said Dr. Oatis, a physical therapist and professor of physical therapy at Arcadia University in Glenside, Pa., and a member of the technical expert panel.

This was the only time the panel deemed supporting evidence to be "strong." They did so based on the GRADE methodology used in developing the revised recommendations. GRADE (grades of recommendations, assessment, development, and evaluation) allows for rating of the available evidence as "strong," "weak," or "none." The GRADE working group developed the system for evaluating data supporting recommendation in health care in 2000.

Strong evidence is of high quality with a large gradient between benefits and risks, and little uncertainty or variability in values and preferences; weak evidence has moderate quality with a small gradient between benefits and risks, and moderate uncertainty or variability in values and preferences; and "none" means the evidence was of low or very low quality with no difference between benefits and risks.

The panel "recommends" modalities with strong evidence, "suggests" those with weak evidence, and provides "no guidance" for those in the "none" category.

Weak evidence of benefit in hip OA was found for manual therapy in combination with supervised exercise programs, therefore the panel suggests – but does not recommend – that this modality be considered for patients with hip OA, Dr. Oatis said.

No evidence was found either in support of or against balance exercises or tai chi, so the panel provided no guidance for these approaches, Dr. Oatis said.

The panel also considered the evidence for hand OA, and for various specific nonpharmacologic approaches to treating OA.

For hand OA, weak evidence was found for:

• Evaluating patients regarding activities of daily living.

• Providing instruction on joint protection techniques.

• Providing assistive devices as needed.

• Instructing patients regarding the use of thermal modalities.

• Using splints for the trapezio-metacarpal joint (CMC joint at the base of the thumb).

Thus, the panel "suggests" use of these modalities, said Catherine Backman, Ph.D., an occupational therapist and faculty member at the University of British Columbia, Vancouver, and a panel member.

When it comes to suggestions based on weak evidence, patient preference comes into play, because this generally means there is no evidence against – and there is some evidence in favor of – use of these modalities, Dr. Backman said.

"Clinicians may want to discuss [these modalities] with patients, and discuss the evidence with patients in relation to their values and preferences," she said.

No other recommendations or suggestions were made for hand OA.

As for specific treatment modalities, weak evidence was found for:

• Medial wedge shoe insoles for lateral compartment knee OA.

• Subtalar strapping and lateral wedge insoles for medial compartment knee OA.

• Medial patellar femoral taping.

Transcutaneous electrical nerve stimulation (TENS) for knee OA with chronic moderate-to-severe pain.

• Traditional Chinese acupuncture for knee OA with moderate to severe pain.

• Thermal modalities.

• Walking aids.

No evidence was found for or against valgus bracing for knee OA, or for lateral patellar-femoral taping, therefore the panel chose not to provide guidance on these, said G. Kelley Fitzgerald, Ph.D., a physical therapist and faculty member at the University of Pittsburgh, and a panel member.

The panel, which reviewed existing English-language studies and existing guidelines from the ACR and other organizations, based its evidence strength determinations on the quality of the evidence and the extent to which the evidence demonstrated pain relief and improved physical functionality.

The panel did not determine that any of the reviewed modalities should not be used.

"The lack of ‘do not do’ recommendations or suggestions means that there was no definitive evidence of harm or lack of efficacy for the interventions examined, Dr. Oatis explained.

These proposed revisions to the current ACR recommendations, which were last revised in 2000, with an update in 2005 following the withdrawal of rofecoxib from the market, are currently under review by the journal Arthritis Care and Research, and have been submitted to the ACR Committee on Quality of Care for review before they are sent the ACR board of directors for final approval, said Dr. Marc C. Hochberg, professor and head of the division of rheumatology and clinical immunology at the University of Maryland, Baltimore.

The ACR awarded the contract for the project to the University of Maryland with Dr. Hochberg as the principal investigator. He is also a member of the project steering committee.

"Hopefully, these will come to the point where the ACR board of directors will be satisfied, and we’ll have a publication in 2011," he said.

Dr. Hochberg disclosed that he has received research support from the National Institutes of Health, and has served as a consultant or on an advisory board or data safety monitoring board for numerous pharmaceutical companies. The other presenters had no disclosures.

ATLANTA - The best available evidence suggests that exercise should be recommended as a nonpharmacologic treatment option for hip and knee osteoarthritis.

So says a technical panel of experts convened by the American College of Rheumatology to revise existing treatment recommendations on the nonpharmacologic treatment of hand, hip, and knee OA. The panel began work on the recommendations in 2008, and the proposed revisions – based on consensus of the panel – are now under review by the ACR.

The panel found "strong" evidence that aerobic land-based exercise, resistance land-based exercise, aquatic exercise, and weight loss for overweight patients can be helpful for reducing pain and improving physical function in hip and knee osteoarthritis, Carol Oatis, Ph.D., reported at the annual meeting of the American College of Rheumatology.

Photo (c)Elena Korenbaum/ iStockphoto.com

As such, the panel proposes to recommend these treatments, said Dr. Oatis, a physical therapist and professor of physical therapy at Arcadia University in Glenside, Pa., and a member of the technical expert panel.

This was the only time the panel deemed supporting evidence to be "strong." They did so based on the GRADE methodology used in developing the revised recommendations. GRADE (grades of recommendations, assessment, development, and evaluation) allows for rating of the available evidence as "strong," "weak," or "none." The GRADE working group developed the system for evaluating data supporting recommendation in health care in 2000.

Strong evidence is of high quality with a large gradient between benefits and risks, and little uncertainty or variability in values and preferences; weak evidence has moderate quality with a small gradient between benefits and risks, and moderate uncertainty or variability in values and preferences; and "none" means the evidence was of low or very low quality with no difference between benefits and risks.

The panel "recommends" modalities with strong evidence, "suggests" those with weak evidence, and provides "no guidance" for those in the "none" category.

Weak evidence of benefit in hip OA was found for manual therapy in combination with supervised exercise programs, therefore the panel suggests – but does not recommend – that this modality be considered for patients with hip OA, Dr. Oatis said.

No evidence was found either in support of or against balance exercises or tai chi, so the panel provided no guidance for these approaches, Dr. Oatis said.

The panel also considered the evidence for hand OA, and for various specific nonpharmacologic approaches to treating OA.

For hand OA, weak evidence was found for:

• Evaluating patients regarding activities of daily living.

• Providing instruction on joint protection techniques.

• Providing assistive devices as needed.

• Instructing patients regarding the use of thermal modalities.

• Using splints for the trapezio-metacarpal joint (CMC joint at the base of the thumb).

Thus, the panel "suggests" use of these modalities, said Catherine Backman, Ph.D., an occupational therapist and faculty member at the University of British Columbia, Vancouver, and a panel member.

When it comes to suggestions based on weak evidence, patient preference comes into play, because this generally means there is no evidence against – and there is some evidence in favor of – use of these modalities, Dr. Backman said.

"Clinicians may want to discuss [these modalities] with patients, and discuss the evidence with patients in relation to their values and preferences," she said.

No other recommendations or suggestions were made for hand OA.

As for specific treatment modalities, weak evidence was found for:

• Medial wedge shoe insoles for lateral compartment knee OA.

• Subtalar strapping and lateral wedge insoles for medial compartment knee OA.

• Medial patellar femoral taping.

Transcutaneous electrical nerve stimulation (TENS) for knee OA with chronic moderate-to-severe pain.

• Traditional Chinese acupuncture for knee OA with moderate to severe pain.

• Thermal modalities.

• Walking aids.

No evidence was found for or against valgus bracing for knee OA, or for lateral patellar-femoral taping, therefore the panel chose not to provide guidance on these, said G. Kelley Fitzgerald, Ph.D., a physical therapist and faculty member at the University of Pittsburgh, and a panel member.

The panel, which reviewed existing English-language studies and existing guidelines from the ACR and other organizations, based its evidence strength determinations on the quality of the evidence and the extent to which the evidence demonstrated pain relief and improved physical functionality.

The panel did not determine that any of the reviewed modalities should not be used.

"The lack of ‘do not do’ recommendations or suggestions means that there was no definitive evidence of harm or lack of efficacy for the interventions examined, Dr. Oatis explained.

These proposed revisions to the current ACR recommendations, which were last revised in 2000, with an update in 2005 following the withdrawal of rofecoxib from the market, are currently under review by the journal Arthritis Care and Research, and have been submitted to the ACR Committee on Quality of Care for review before they are sent the ACR board of directors for final approval, said Dr. Marc C. Hochberg, professor and head of the division of rheumatology and clinical immunology at the University of Maryland, Baltimore.

The ACR awarded the contract for the project to the University of Maryland with Dr. Hochberg as the principal investigator. He is also a member of the project steering committee.

"Hopefully, these will come to the point where the ACR board of directors will be satisfied, and we’ll have a publication in 2011," he said.

Dr. Hochberg disclosed that he has received research support from the National Institutes of Health, and has served as a consultant or on an advisory board or data safety monitoring board for numerous pharmaceutical companies. The other presenters had no disclosures.

ATLANTA – Canakinumab was safe, well tolerated, and highly effective in the long-term treatment of cryopyrin-associated periodic syndromes in pediatric patients in an open-label phase III extension study.

Treatment of cryopyrin-associated periodic syndromes (CAPS) in 47 patients, aged 3-17 years, who were enrolled in the study was associated with a rapid and sustained clinical and biochemical remission across varying disease severity phenotypes.

Five of the children had familial cold auto-inflammatory syndrome (FCAS), 23 had Muckle-Wells syndrome (MWS), and 18 had chronic infantile neurologic, cutaneous, and articular syndrome/neonatal-onset multisystem inflammatory disease (CINCA/NOMID). One patient was found to not have a CAPS disease phenotype, reported Dr. Jasmin B. Kuemmerle-Deschner at the annual meeting of the American College of Rheumatology.

Of the 47 patients, 38 had not previously been treated with the human interleukin-1 beta monoclonal antibody, and 9 were "rolled over" from earlier phase II or III studies. Of the 38 canakinumab-naive patients, 68% achieved a complete response based on physician global assessment of disease activity and skin assessment, plus normalization of C-reactive protein (CRP) and lowering of serum amyloid A (SAA) to less than 10 mg/L for both measures. More than 80% of the canakinumab-naive patients were relapse-free after a median of 290 days of exposure to treatment, and normal CRP and SAA levels were also maintained throughout the study period in the rollover patients, said Dr. Kuemmerle-Deschner, a pediatric rheumatologist at Universitaetsklinikum Tuebingen (Germany).

The response in the treatment-naive patients was rapid, with levels of CRP and SAA decreasing within 7 days from 14.8 to 2.5 mg/L, and from 40.6 to 7.4 mg/L, respectively, she noted.

Also of note was that 8 of the 11 patients who had an incomplete response within 7 days developed a complete response by 14 days, and the remaining patients – all of whom had the most severe disease phenotype (CINCA/NOMID) – had a partial response, she said.

All patients were treated with 150 mg (or 2 mg/kg for those weighing 40 kg or less) of subcutaneous canakinumab once every 8 weeks. Patients who did not have a complete response were allowed dose adjustments, including an additional dose of 300 mg or 4 mg/kg for those weighing 40 kg or less, or more frequent dosing. Dose adjustments were required in 17 patients, including all of the patients with NOMID; those patients required mean doses of 5.8 mg/kg, compared with 5.5 mg/kg in the MWS patients, and 2.7 mg/kg in the FCAS patients.

Adverse events were generally mild or moderate and transient, and they included abdominal pain, pyrexia, headache, nasopharyngitis, and rhinitis.

"It was remarkable that 92% of patients had no injections-site reaction, and only 8% patients reported mild reaction," Dr. Kuemmerle-Deschner said.

Serious adverse events occurred in six patients, and included nephrotic syndrome, bronchitis, pneumonia, and appendicitis, which occurred in one patient each, and tonsillitis, which occurred in two patients. Only one patient withdrew from the study because of an adverse event.

The findings of this study show that canakinumab, for which earlier phase II and III studies demonstrated high efficacy for treating CAPS, also has long-term safety, tolerability, and efficacy, Dr. Kuemmerle-Deschner said.

"Canakinumab led to rapid and sustained response in the majority of patients," she said, noting that importantly, children with severe CAPS phenotypes required dose adjustment and higher overall doses to sustain remission.

Dr. Kuemmerle-Deschner disclosed that she has received research grants and consulting fees from Novartis Pharmaceuticals, the maker of canakinumab (Ilaris).

ATLANTA – Canakinumab was safe, well tolerated, and highly effective in the long-term treatment of cryopyrin-associated periodic syndromes in pediatric patients in an open-label phase III extension study.

Treatment of cryopyrin-associated periodic syndromes (CAPS) in 47 patients, aged 3-17 years, who were enrolled in the study was associated with a rapid and sustained clinical and biochemical remission across varying disease severity phenotypes.

Five of the children had familial cold auto-inflammatory syndrome (FCAS), 23 had Muckle-Wells syndrome (MWS), and 18 had chronic infantile neurologic, cutaneous, and articular syndrome/neonatal-onset multisystem inflammatory disease (CINCA/NOMID). One patient was found to not have a CAPS disease phenotype, reported Dr. Jasmin B. Kuemmerle-Deschner at the annual meeting of the American College of Rheumatology.

Of the 47 patients, 38 had not previously been treated with the human interleukin-1 beta monoclonal antibody, and 9 were "rolled over" from earlier phase II or III studies. Of the 38 canakinumab-naive patients, 68% achieved a complete response based on physician global assessment of disease activity and skin assessment, plus normalization of C-reactive protein (CRP) and lowering of serum amyloid A (SAA) to less than 10 mg/L for both measures. More than 80% of the canakinumab-naive patients were relapse-free after a median of 290 days of exposure to treatment, and normal CRP and SAA levels were also maintained throughout the study period in the rollover patients, said Dr. Kuemmerle-Deschner, a pediatric rheumatologist at Universitaetsklinikum Tuebingen (Germany).

The response in the treatment-naive patients was rapid, with levels of CRP and SAA decreasing within 7 days from 14.8 to 2.5 mg/L, and from 40.6 to 7.4 mg/L, respectively, she noted.

Also of note was that 8 of the 11 patients who had an incomplete response within 7 days developed a complete response by 14 days, and the remaining patients – all of whom had the most severe disease phenotype (CINCA/NOMID) – had a partial response, she said.

All patients were treated with 150 mg (or 2 mg/kg for those weighing 40 kg or less) of subcutaneous canakinumab once every 8 weeks. Patients who did not have a complete response were allowed dose adjustments, including an additional dose of 300 mg or 4 mg/kg for those weighing 40 kg or less, or more frequent dosing. Dose adjustments were required in 17 patients, including all of the patients with NOMID; those patients required mean doses of 5.8 mg/kg, compared with 5.5 mg/kg in the MWS patients, and 2.7 mg/kg in the FCAS patients.

Adverse events were generally mild or moderate and transient, and they included abdominal pain, pyrexia, headache, nasopharyngitis, and rhinitis.

"It was remarkable that 92% of patients had no injections-site reaction, and only 8% patients reported mild reaction," Dr. Kuemmerle-Deschner said.

Serious adverse events occurred in six patients, and included nephrotic syndrome, bronchitis, pneumonia, and appendicitis, which occurred in one patient each, and tonsillitis, which occurred in two patients. Only one patient withdrew from the study because of an adverse event.

The findings of this study show that canakinumab, for which earlier phase II and III studies demonstrated high efficacy for treating CAPS, also has long-term safety, tolerability, and efficacy, Dr. Kuemmerle-Deschner said.

"Canakinumab led to rapid and sustained response in the majority of patients," she said, noting that importantly, children with severe CAPS phenotypes required dose adjustment and higher overall doses to sustain remission.

Dr. Kuemmerle-Deschner disclosed that she has received research grants and consulting fees from Novartis Pharmaceuticals, the maker of canakinumab (Ilaris).

ATLANTA – Canakinumab was safe, well tolerated, and highly effective in the long-term treatment of cryopyrin-associated periodic syndromes in pediatric patients in an open-label phase III extension study.

Treatment of cryopyrin-associated periodic syndromes (CAPS) in 47 patients, aged 3-17 years, who were enrolled in the study was associated with a rapid and sustained clinical and biochemical remission across varying disease severity phenotypes.

Five of the children had familial cold auto-inflammatory syndrome (FCAS), 23 had Muckle-Wells syndrome (MWS), and 18 had chronic infantile neurologic, cutaneous, and articular syndrome/neonatal-onset multisystem inflammatory disease (CINCA/NOMID). One patient was found to not have a CAPS disease phenotype, reported Dr. Jasmin B. Kuemmerle-Deschner at the annual meeting of the American College of Rheumatology.

Of the 47 patients, 38 had not previously been treated with the human interleukin-1 beta monoclonal antibody, and 9 were "rolled over" from earlier phase II or III studies. Of the 38 canakinumab-naive patients, 68% achieved a complete response based on physician global assessment of disease activity and skin assessment, plus normalization of C-reactive protein (CRP) and lowering of serum amyloid A (SAA) to less than 10 mg/L for both measures. More than 80% of the canakinumab-naive patients were relapse-free after a median of 290 days of exposure to treatment, and normal CRP and SAA levels were also maintained throughout the study period in the rollover patients, said Dr. Kuemmerle-Deschner, a pediatric rheumatologist at Universitaetsklinikum Tuebingen (Germany).

The response in the treatment-naive patients was rapid, with levels of CRP and SAA decreasing within 7 days from 14.8 to 2.5 mg/L, and from 40.6 to 7.4 mg/L, respectively, she noted.

Also of note was that 8 of the 11 patients who had an incomplete response within 7 days developed a complete response by 14 days, and the remaining patients – all of whom had the most severe disease phenotype (CINCA/NOMID) – had a partial response, she said.

All patients were treated with 150 mg (or 2 mg/kg for those weighing 40 kg or less) of subcutaneous canakinumab once every 8 weeks. Patients who did not have a complete response were allowed dose adjustments, including an additional dose of 300 mg or 4 mg/kg for those weighing 40 kg or less, or more frequent dosing. Dose adjustments were required in 17 patients, including all of the patients with NOMID; those patients required mean doses of 5.8 mg/kg, compared with 5.5 mg/kg in the MWS patients, and 2.7 mg/kg in the FCAS patients.

Adverse events were generally mild or moderate and transient, and they included abdominal pain, pyrexia, headache, nasopharyngitis, and rhinitis.

"It was remarkable that 92% of patients had no injections-site reaction, and only 8% patients reported mild reaction," Dr. Kuemmerle-Deschner said.

Serious adverse events occurred in six patients, and included nephrotic syndrome, bronchitis, pneumonia, and appendicitis, which occurred in one patient each, and tonsillitis, which occurred in two patients. Only one patient withdrew from the study because of an adverse event.

The findings of this study show that canakinumab, for which earlier phase II and III studies demonstrated high efficacy for treating CAPS, also has long-term safety, tolerability, and efficacy, Dr. Kuemmerle-Deschner said.

"Canakinumab led to rapid and sustained response in the majority of patients," she said, noting that importantly, children with severe CAPS phenotypes required dose adjustment and higher overall doses to sustain remission.

Dr. Kuemmerle-Deschner disclosed that she has received research grants and consulting fees from Novartis Pharmaceuticals, the maker of canakinumab (Ilaris).

ATLANTA – Canakinumab was safe, well tolerated, and highly effective in the long-term treatment of cryopyrin-associated periodic syndromes in pediatric patients in an open-label phase III extension study.

Treatment of cryopyrin-associated periodic syndromes (CAPS) in 47 patients, aged 3-17 years, who were enrolled in the study was associated with a rapid and sustained clinical and biochemical remission across varying disease severity phenotypes.

Five of the children had familial cold auto-inflammatory syndrome (FCAS), 23 had Muckle-Wells syndrome (MWS), and 18 had chronic infantile neurologic, cutaneous, and articular syndrome/neonatal-onset multisystem inflammatory disease (CINCA/NOMID). One patient was found to not have a CAPS disease phenotype, reported Dr. Jasmin B. Kuemmerle-Deschner at the annual meeting of the American College of Rheumatology.

Of the 47 patients, 38 had not previously been treated with the human interleukin-1 beta monoclonal antibody, and 9 were "rolled over" from earlier phase II or III studies. Of the 38 canakinumab-naive patients, 68% achieved a complete response based on physician global assessment of disease activity and skin assessment, plus normalization of C-reactive protein (CRP) and lowering of serum amyloid A (SAA) to less than 10 mg/L for both measures. More than 80% of the canakinumab-naive patients were relapse-free after a median of 290 days of exposure to treatment, and normal CRP and SAA levels were also maintained throughout the study period in the rollover patients, said Dr. Kuemmerle-Deschner, a pediatric rheumatologist at Universitaetsklinikum Tuebingen (Germany).

The response in the treatment-naive patients was rapid, with levels of CRP and SAA decreasing within 7 days from 14.8 to 2.5 mg/L, and from 40.6 to 7.4 mg/L, respectively, she noted.

Also of note was that 8 of the 11 patients who had an incomplete response within 7 days developed a complete response by 14 days, and the remaining patients – all of whom had the most severe disease phenotype (CINCA/NOMID) – had a partial response, she said.

All patients were treated with 150 mg (or 2 mg/kg for those weighing 40 kg or less) of subcutaneous canakinumab once every 8 weeks. Patients who did not have a complete response were allowed dose adjustments, including an additional dose of 300 mg or 4 mg/kg for those weighing 40 kg or less, or more frequent dosing. Dose adjustments were required in 17 patients, including all of the patients with NOMID; those patients required mean doses of 5.8 mg/kg, compared with 5.5 mg/kg in the MWS patients, and 2.7 mg/kg in the FCAS patients.

Adverse events were generally mild or moderate and transient, and they included abdominal pain, pyrexia, headache, nasopharyngitis, and rhinitis.

"It was remarkable that 92% of patients had no injections-site reaction, and only 8% patients reported mild reaction," Dr. Kuemmerle-Deschner said.

Serious adverse events occurred in six patients, and included nephrotic syndrome, bronchitis, pneumonia, and appendicitis, which occurred in one patient each, and tonsillitis, which occurred in two patients. Only one patient withdrew from the study because of an adverse event.

The findings of this study show that canakinumab, for which earlier phase II and III studies demonstrated high efficacy for treating CAPS, also has long-term safety, tolerability, and efficacy, Dr. Kuemmerle-Deschner said.

"Canakinumab led to rapid and sustained response in the majority of patients," she said, noting that importantly, children with severe CAPS phenotypes required dose adjustment and higher overall doses to sustain remission.

Dr. Kuemmerle-Deschner disclosed that she has received research grants and consulting fees from Novartis Pharmaceuticals, the maker of canakinumab (Ilaris).

ATLANTA – Canakinumab was safe, well tolerated, and highly effective in the long-term treatment of cryopyrin-associated periodic syndromes in pediatric patients in an open-label phase III extension study.

Treatment of cryopyrin-associated periodic syndromes (CAPS) in 47 patients, aged 3-17 years, who were enrolled in the study was associated with a rapid and sustained clinical and biochemical remission across varying disease severity phenotypes.

Five of the children had familial cold auto-inflammatory syndrome (FCAS), 23 had Muckle-Wells syndrome (MWS), and 18 had chronic infantile neurologic, cutaneous, and articular syndrome/neonatal-onset multisystem inflammatory disease (CINCA/NOMID). One patient was found to not have a CAPS disease phenotype, reported Dr. Jasmin B. Kuemmerle-Deschner at the annual meeting of the American College of Rheumatology.

Of the 47 patients, 38 had not previously been treated with the human interleukin-1 beta monoclonal antibody, and 9 were "rolled over" from earlier phase II or III studies. Of the 38 canakinumab-naive patients, 68% achieved a complete response based on physician global assessment of disease activity and skin assessment, plus normalization of C-reactive protein (CRP) and lowering of serum amyloid A (SAA) to less than 10 mg/L for both measures. More than 80% of the canakinumab-naive patients were relapse-free after a median of 290 days of exposure to treatment, and normal CRP and SAA levels were also maintained throughout the study period in the rollover patients, said Dr. Kuemmerle-Deschner, a pediatric rheumatologist at Universitaetsklinikum Tuebingen (Germany).

The response in the treatment-naive patients was rapid, with levels of CRP and SAA decreasing within 7 days from 14.8 to 2.5 mg/L, and from 40.6 to 7.4 mg/L, respectively, she noted.

Also of note was that 8 of the 11 patients who had an incomplete response within 7 days developed a complete response by 14 days, and the remaining patients – all of whom had the most severe disease phenotype (CINCA/NOMID) – had a partial response, she said.

All patients were treated with 150 mg (or 2 mg/kg for those weighing 40 kg or less) of subcutaneous canakinumab once every 8 weeks. Patients who did not have a complete response were allowed dose adjustments, including an additional dose of 300 mg or 4 mg/kg for those weighing 40 kg or less, or more frequent dosing. Dose adjustments were required in 17 patients, including all of the patients with NOMID; those patients required mean doses of 5.8 mg/kg, compared with 5.5 mg/kg in the MWS patients, and 2.7 mg/kg in the FCAS patients.

Adverse events were generally mild or moderate and transient, and they included abdominal pain, pyrexia, headache, nasopharyngitis, and rhinitis.

"It was remarkable that 92% of patients had no injections-site reaction, and only 8% patients reported mild reaction," Dr. Kuemmerle-Deschner said.

Serious adverse events occurred in six patients, and included nephrotic syndrome, bronchitis, pneumonia, and appendicitis, which occurred in one patient each, and tonsillitis, which occurred in two patients. Only one patient withdrew from the study because of an adverse event.

The findings of this study show that canakinumab, for which earlier phase II and III studies demonstrated high efficacy for treating CAPS, also has long-term safety, tolerability, and efficacy, Dr. Kuemmerle-Deschner said.

"Canakinumab led to rapid and sustained response in the majority of patients," she said, noting that importantly, children with severe CAPS phenotypes required dose adjustment and higher overall doses to sustain remission.

Dr. Kuemmerle-Deschner disclosed that she has received research grants and consulting fees from Novartis Pharmaceuticals, the maker of canakinumab (Ilaris).

ATLANTA – Canakinumab was safe, well tolerated, and highly effective in the long-term treatment of cryopyrin-associated periodic syndromes in pediatric patients in an open-label phase III extension study.

Treatment of cryopyrin-associated periodic syndromes (CAPS) in 47 patients, aged 3-17 years, who were enrolled in the study was associated with a rapid and sustained clinical and biochemical remission across varying disease severity phenotypes.

Five of the children had familial cold auto-inflammatory syndrome (FCAS), 23 had Muckle-Wells syndrome (MWS), and 18 had chronic infantile neurologic, cutaneous, and articular syndrome/neonatal-onset multisystem inflammatory disease (CINCA/NOMID). One patient was found to not have a CAPS disease phenotype, reported Dr. Jasmin B. Kuemmerle-Deschner at the annual meeting of the American College of Rheumatology.

Of the 47 patients, 38 had not previously been treated with the human interleukin-1 beta monoclonal antibody, and 9 were "rolled over" from earlier phase II or III studies. Of the 38 canakinumab-naive patients, 68% achieved a complete response based on physician global assessment of disease activity and skin assessment, plus normalization of C-reactive protein (CRP) and lowering of serum amyloid A (SAA) to less than 10 mg/L for both measures. More than 80% of the canakinumab-naive patients were relapse-free after a median of 290 days of exposure to treatment, and normal CRP and SAA levels were also maintained throughout the study period in the rollover patients, said Dr. Kuemmerle-Deschner, a pediatric rheumatologist at Universitaetsklinikum Tuebingen (Germany).

The response in the treatment-naive patients was rapid, with levels of CRP and SAA decreasing within 7 days from 14.8 to 2.5 mg/L, and from 40.6 to 7.4 mg/L, respectively, she noted.

Also of note was that 8 of the 11 patients who had an incomplete response within 7 days developed a complete response by 14 days, and the remaining patients – all of whom had the most severe disease phenotype (CINCA/NOMID) – had a partial response, she said.

All patients were treated with 150 mg (or 2 mg/kg for those weighing 40 kg or less) of subcutaneous canakinumab once every 8 weeks. Patients who did not have a complete response were allowed dose adjustments, including an additional dose of 300 mg or 4 mg/kg for those weighing 40 kg or less, or more frequent dosing. Dose adjustments were required in 17 patients, including all of the patients with NOMID; those patients required mean doses of 5.8 mg/kg, compared with 5.5 mg/kg in the MWS patients, and 2.7 mg/kg in the FCAS patients.

Adverse events were generally mild or moderate and transient, and they included abdominal pain, pyrexia, headache, nasopharyngitis, and rhinitis.

"It was remarkable that 92% of patients had no injections-site reaction, and only 8% patients reported mild reaction," Dr. Kuemmerle-Deschner said.

Serious adverse events occurred in six patients, and included nephrotic syndrome, bronchitis, pneumonia, and appendicitis, which occurred in one patient each, and tonsillitis, which occurred in two patients. Only one patient withdrew from the study because of an adverse event.

The findings of this study show that canakinumab, for which earlier phase II and III studies demonstrated high efficacy for treating CAPS, also has long-term safety, tolerability, and efficacy, Dr. Kuemmerle-Deschner said.

"Canakinumab led to rapid and sustained response in the majority of patients," she said, noting that importantly, children with severe CAPS phenotypes required dose adjustment and higher overall doses to sustain remission.

Dr. Kuemmerle-Deschner disclosed that she has received research grants and consulting fees from Novartis Pharmaceuticals, the maker of canakinumab (Ilaris).

ATLANTA – Canakinumab was safe, well tolerated, and highly effective in the long-term treatment of cryopyrin-associated periodic syndromes in pediatric patients in an open-label phase III extension study.

Treatment of cryopyrin-associated periodic syndromes (CAPS) in 47 patients, aged 3-17 years, who were enrolled in the study was associated with a rapid and sustained clinical and biochemical remission across varying disease severity phenotypes.

Five of the children had familial cold auto-inflammatory syndrome (FCAS), 23 had Muckle-Wells syndrome (MWS), and 18 had chronic infantile neurologic, cutaneous, and articular syndrome/neonatal-onset multisystem inflammatory disease (CINCA/NOMID). One patient was found to not have a CAPS disease phenotype, reported Dr. Jasmin B. Kuemmerle-Deschner at the annual meeting of the American College of Rheumatology.

Of the 47 patients, 38 had not previously been treated with the human interleukin-1 beta monoclonal antibody, and 9 were "rolled over" from earlier phase II or III studies. Of the 38 canakinumab-naive patients, 68% achieved a complete response based on physician global assessment of disease activity and skin assessment, plus normalization of C-reactive protein (CRP) and lowering of serum amyloid A (SAA) to less than 10 mg/L for both measures. More than 80% of the canakinumab-naive patients were relapse-free after a median of 290 days of exposure to treatment, and normal CRP and SAA levels were also maintained throughout the study period in the rollover patients, said Dr. Kuemmerle-Deschner, a pediatric rheumatologist at Universitaetsklinikum Tuebingen (Germany).

The response in the treatment-naive patients was rapid, with levels of CRP and SAA decreasing within 7 days from 14.8 to 2.5 mg/L, and from 40.6 to 7.4 mg/L, respectively, she noted.

Also of note was that 8 of the 11 patients who had an incomplete response within 7 days developed a complete response by 14 days, and the remaining patients – all of whom had the most severe disease phenotype (CINCA/NOMID) – had a partial response, she said.

All patients were treated with 150 mg (or 2 mg/kg for those weighing 40 kg or less) of subcutaneous canakinumab once every 8 weeks. Patients who did not have a complete response were allowed dose adjustments, including an additional dose of 300 mg or 4 mg/kg for those weighing 40 kg or less, or more frequent dosing. Dose adjustments were required in 17 patients, including all of the patients with NOMID; those patients required mean doses of 5.8 mg/kg, compared with 5.5 mg/kg in the MWS patients, and 2.7 mg/kg in the FCAS patients.

Adverse events were generally mild or moderate and transient, and they included abdominal pain, pyrexia, headache, nasopharyngitis, and rhinitis.

"It was remarkable that 92% of patients had no injections-site reaction, and only 8% patients reported mild reaction," Dr. Kuemmerle-Deschner said.

Serious adverse events occurred in six patients, and included nephrotic syndrome, bronchitis, pneumonia, and appendicitis, which occurred in one patient each, and tonsillitis, which occurred in two patients. Only one patient withdrew from the study because of an adverse event.

The findings of this study show that canakinumab, for which earlier phase II and III studies demonstrated high efficacy for treating CAPS, also has long-term safety, tolerability, and efficacy, Dr. Kuemmerle-Deschner said.

"Canakinumab led to rapid and sustained response in the majority of patients," she said, noting that importantly, children with severe CAPS phenotypes required dose adjustment and higher overall doses to sustain remission.

Dr. Kuemmerle-Deschner disclosed that she has received research grants and consulting fees from Novartis Pharmaceuticals, the maker of canakinumab (Ilaris).

ATLANTA – Canakinumab was safe, well tolerated, and highly effective in the long-term treatment of cryopyrin-associated periodic syndromes in pediatric patients in an open-label phase III extension study.

Treatment of cryopyrin-associated periodic syndromes (CAPS) in 47 patients, aged 3-17 years, who were enrolled in the study was associated with a rapid and sustained clinical and biochemical remission across varying disease severity phenotypes.

Five of the children had familial cold auto-inflammatory syndrome (FCAS), 23 had Muckle-Wells syndrome (MWS), and 18 had chronic infantile neurologic, cutaneous, and articular syndrome/neonatal-onset multisystem inflammatory disease (CINCA/NOMID). One patient was found to not have a CAPS disease phenotype, reported Dr. Jasmin B. Kuemmerle-Deschner at the annual meeting of the American College of Rheumatology.

Of the 47 patients, 38 had not previously been treated with the human interleukin-1 beta monoclonal antibody, and 9 were "rolled over" from earlier phase II or III studies. Of the 38 canakinumab-naive patients, 68% achieved a complete response based on physician global assessment of disease activity and skin assessment, plus normalization of C-reactive protein (CRP) and lowering of serum amyloid A (SAA) to less than 10 mg/L for both measures. More than 80% of the canakinumab-naive patients were relapse-free after a median of 290 days of exposure to treatment, and normal CRP and SAA levels were also maintained throughout the study period in the rollover patients, said Dr. Kuemmerle-Deschner, a pediatric rheumatologist at Universitaetsklinikum Tuebingen (Germany).

The response in the treatment-naive patients was rapid, with levels of CRP and SAA decreasing within 7 days from 14.8 to 2.5 mg/L, and from 40.6 to 7.4 mg/L, respectively, she noted.

Also of note was that 8 of the 11 patients who had an incomplete response within 7 days developed a complete response by 14 days, and the remaining patients – all of whom had the most severe disease phenotype (CINCA/NOMID) – had a partial response, she said.

All patients were treated with 150 mg (or 2 mg/kg for those weighing 40 kg or less) of subcutaneous canakinumab once every 8 weeks. Patients who did not have a complete response were allowed dose adjustments, including an additional dose of 300 mg or 4 mg/kg for those weighing 40 kg or less, or more frequent dosing. Dose adjustments were required in 17 patients, including all of the patients with NOMID; those patients required mean doses of 5.8 mg/kg, compared with 5.5 mg/kg in the MWS patients, and 2.7 mg/kg in the FCAS patients.

Adverse events were generally mild or moderate and transient, and they included abdominal pain, pyrexia, headache, nasopharyngitis, and rhinitis.

"It was remarkable that 92% of patients had no injections-site reaction, and only 8% patients reported mild reaction," Dr. Kuemmerle-Deschner said.

Serious adverse events occurred in six patients, and included nephrotic syndrome, bronchitis, pneumonia, and appendicitis, which occurred in one patient each, and tonsillitis, which occurred in two patients. Only one patient withdrew from the study because of an adverse event.

The findings of this study show that canakinumab, for which earlier phase II and III studies demonstrated high efficacy for treating CAPS, also has long-term safety, tolerability, and efficacy, Dr. Kuemmerle-Deschner said.

"Canakinumab led to rapid and sustained response in the majority of patients," she said, noting that importantly, children with severe CAPS phenotypes required dose adjustment and higher overall doses to sustain remission.

Dr. Kuemmerle-Deschner disclosed that she has received research grants and consulting fees from Novartis Pharmaceuticals, the maker of canakinumab (Ilaris).

ATLANTA – Canakinumab was safe, well tolerated, and highly effective in the long-term treatment of cryopyrin-associated periodic syndromes in pediatric patients in an open-label phase III extension study.

Treatment of cryopyrin-associated periodic syndromes (CAPS) in 47 patients, aged 3-17 years, who were enrolled in the study was associated with a rapid and sustained clinical and biochemical remission across varying disease severity phenotypes.

Five of the children had familial cold auto-inflammatory syndrome (FCAS), 23 had Muckle-Wells syndrome (MWS), and 18 had chronic infantile neurologic, cutaneous, and articular syndrome/neonatal-onset multisystem inflammatory disease (CINCA/NOMID). One patient was found to not have a CAPS disease phenotype, reported Dr. Jasmin B. Kuemmerle-Deschner at the annual meeting of the American College of Rheumatology.

Of the 47 patients, 38 had not previously been treated with the human interleukin-1 beta monoclonal antibody, and 9 were "rolled over" from earlier phase II or III studies. Of the 38 canakinumab-naive patients, 68% achieved a complete response based on physician global assessment of disease activity and skin assessment, plus normalization of C-reactive protein (CRP) and lowering of serum amyloid A (SAA) to less than 10 mg/L for both measures. More than 80% of the canakinumab-naive patients were relapse-free after a median of 290 days of exposure to treatment, and normal CRP and SAA levels were also maintained throughout the study period in the rollover patients, said Dr. Kuemmerle-Deschner, a pediatric rheumatologist at Universitaetsklinikum Tuebingen (Germany).

The response in the treatment-naive patients was rapid, with levels of CRP and SAA decreasing within 7 days from 14.8 to 2.5 mg/L, and from 40.6 to 7.4 mg/L, respectively, she noted.

Also of note was that 8 of the 11 patients who had an incomplete response within 7 days developed a complete response by 14 days, and the remaining patients – all of whom had the most severe disease phenotype (CINCA/NOMID) – had a partial response, she said.

All patients were treated with 150 mg (or 2 mg/kg for those weighing 40 kg or less) of subcutaneous canakinumab once every 8 weeks. Patients who did not have a complete response were allowed dose adjustments, including an additional dose of 300 mg or 4 mg/kg for those weighing 40 kg or less, or more frequent dosing. Dose adjustments were required in 17 patients, including all of the patients with NOMID; those patients required mean doses of 5.8 mg/kg, compared with 5.5 mg/kg in the MWS patients, and 2.7 mg/kg in the FCAS patients.

Adverse events were generally mild or moderate and transient, and they included abdominal pain, pyrexia, headache, nasopharyngitis, and rhinitis.

"It was remarkable that 92% of patients had no injections-site reaction, and only 8% patients reported mild reaction," Dr. Kuemmerle-Deschner said.

Serious adverse events occurred in six patients, and included nephrotic syndrome, bronchitis, pneumonia, and appendicitis, which occurred in one patient each, and tonsillitis, which occurred in two patients. Only one patient withdrew from the study because of an adverse event.

The findings of this study show that canakinumab, for which earlier phase II and III studies demonstrated high efficacy for treating CAPS, also has long-term safety, tolerability, and efficacy, Dr. Kuemmerle-Deschner said.

"Canakinumab led to rapid and sustained response in the majority of patients," she said, noting that importantly, children with severe CAPS phenotypes required dose adjustment and higher overall doses to sustain remission.

Dr. Kuemmerle-Deschner disclosed that she has received research grants and consulting fees from Novartis Pharmaceuticals, the maker of canakinumab (Ilaris).

ATLANTA – Methotrexate was an effective and well-tolerated treatment for juvenile localized scleroderma in a randomized, double-blind, placebo-controlled trial involving 70 patients with active disease.

At the end of the 12-month study, 31 of 46 patients randomized to receive methotrexate had responded to treatment and were flare-free, compared with 7 of 24 patients given placebo, Dr. Francesco Zulian reported at the annual meeting of the American College of Rheumatology.

Methotrexate patients received a weekly oral dose of 15 mg/m2 (maximum, 20 mg) for 12 months or until flare of disease. Patients in the placebo group received a placebo administered in the same fashion for 12 months or to flare. Patients in both groups received prednisone at a dose of 1 mg/kg per day, with a maximum dose of 50 mg, for 3 months. They were then tapered to 0 over 1 month. During the initial 3 months of the study, treatment response was comparable for the two groups. Differences in response rates began to emerge after that point, said Dr. Zulian of the University of Padua (Italy).

Patients' lesions were evaluated using a computerized scoring system, and changes were quantified using a skin score rate. Active lesions were monitored based on clinical examination and serial thermography. The mean skin score rates decreased significantly from 1.0 at baseline to 0.79 in the patients on methotrexate, but did not decrease in the patients given placebo. The mean target lesion temperature on thermography decreased by 44% in the methotrexate group and by 12% in the placebo group, a significant difference, he said.

Adverse events occurred in 26 of 46 patients in the methotrexate group, and in 11 of 24 in the placebo group. In the methotrexate group, adverse events included alopecia, nausea, headache, fatigue, hepatotoxicity, weight gain, and striae rubra. The only adverse events in the placebo group were weight gain and striae rubra.

Interestingly, weight gain of more than 5% of body weight occurred in 11% of the methotrexate patients and 42% of the placebo patients, Dr. Zulian said, noting that this may suggest there is some "biological or pathophysiological link" between prednisone and methotrexate that tempers this steroid-related side effect.

None of the side effects was severe enough to stop treatment, but there was a high drop-out rate – due to relapse or lack of response – in both groups; 31 of 46 patients in the methotrexate group, and 7 of 24 in the placebo group, completed the study. At the end of the 12-month study, 17 of 24 patients randomized to placebo had experienced a relapse, compared with 15 of 46 patients randomized to the methotrexate group.

Patients included in the study were aged 6-17 years with active localized scleroderma of linear, generalized, or deep subtypes with onset before age 16. The treatment and placebo groups were similar in regard to clinical and immunological features, as well as mean disease duration of about 2 years, and the absence of immunosuppressive treatment in the 6 months prior to enrollment.

Many treatments have been tried in patients with juvenile localized scleroderma, and methotrexate has emerged as one of the most frequently used drugs for this condition.

"The findings of this study show that a combination of methotrexate and prednisone is of benefit and is well tolerated as treatment for severe course juvenile localized scleroderma," Dr. Zulian said.

Prior studies have shown efficacy ranging from 74% to 93%, but the findings of those studies have been based mostly on clinical judgment, while the current study utilized more objective evaluation criteria, including thermography, and skin score rates calculated based on computerized skin scoring, he said.

"The inclusion of standardized objective parameters represents an innovative way to assess the disease and compare progression in future clinical trials," he added.

Dr. Zulian said he had no relevant financial disclosures.

ATLANTA – Methotrexate was an effective and well-tolerated treatment for juvenile localized scleroderma in a randomized, double-blind, placebo-controlled trial involving 70 patients with active disease.

At the end of the 12-month study, 31 of 46 patients randomized to receive methotrexate had responded to treatment and were flare-free, compared with 7 of 24 patients given placebo, Dr. Francesco Zulian reported at the annual meeting of the American College of Rheumatology.

Methotrexate patients received a weekly oral dose of 15 mg/m2 (maximum, 20 mg) for 12 months or until flare of disease. Patients in the placebo group received a placebo administered in the same fashion for 12 months or to flare. Patients in both groups received prednisone at a dose of 1 mg/kg per day, with a maximum dose of 50 mg, for 3 months. They were then tapered to 0 over 1 month. During the initial 3 months of the study, treatment response was comparable for the two groups. Differences in response rates began to emerge after that point, said Dr. Zulian of the University of Padua (Italy).

Patients' lesions were evaluated using a computerized scoring system, and changes were quantified using a skin score rate. Active lesions were monitored based on clinical examination and serial thermography. The mean skin score rates decreased significantly from 1.0 at baseline to 0.79 in the patients on methotrexate, but did not decrease in the patients given placebo. The mean target lesion temperature on thermography decreased by 44% in the methotrexate group and by 12% in the placebo group, a significant difference, he said.

Adverse events occurred in 26 of 46 patients in the methotrexate group, and in 11 of 24 in the placebo group. In the methotrexate group, adverse events included alopecia, nausea, headache, fatigue, hepatotoxicity, weight gain, and striae rubra. The only adverse events in the placebo group were weight gain and striae rubra.

Interestingly, weight gain of more than 5% of body weight occurred in 11% of the methotrexate patients and 42% of the placebo patients, Dr. Zulian said, noting that this may suggest there is some "biological or pathophysiological link" between prednisone and methotrexate that tempers this steroid-related side effect.

None of the side effects was severe enough to stop treatment, but there was a high drop-out rate – due to relapse or lack of response – in both groups; 31 of 46 patients in the methotrexate group, and 7 of 24 in the placebo group, completed the study. At the end of the 12-month study, 17 of 24 patients randomized to placebo had experienced a relapse, compared with 15 of 46 patients randomized to the methotrexate group.

Patients included in the study were aged 6-17 years with active localized scleroderma of linear, generalized, or deep subtypes with onset before age 16. The treatment and placebo groups were similar in regard to clinical and immunological features, as well as mean disease duration of about 2 years, and the absence of immunosuppressive treatment in the 6 months prior to enrollment.

Many treatments have been tried in patients with juvenile localized scleroderma, and methotrexate has emerged as one of the most frequently used drugs for this condition.

"The findings of this study show that a combination of methotrexate and prednisone is of benefit and is well tolerated as treatment for severe course juvenile localized scleroderma," Dr. Zulian said.

Prior studies have shown efficacy ranging from 74% to 93%, but the findings of those studies have been based mostly on clinical judgment, while the current study utilized more objective evaluation criteria, including thermography, and skin score rates calculated based on computerized skin scoring, he said.

"The inclusion of standardized objective parameters represents an innovative way to assess the disease and compare progression in future clinical trials," he added.

Dr. Zulian said he had no relevant financial disclosures.

ATLANTA – Methotrexate was an effective and well-tolerated treatment for juvenile localized scleroderma in a randomized, double-blind, placebo-controlled trial involving 70 patients with active disease.

At the end of the 12-month study, 31 of 46 patients randomized to receive methotrexate had responded to treatment and were flare-free, compared with 7 of 24 patients given placebo, Dr. Francesco Zulian reported at the annual meeting of the American College of Rheumatology.

Methotrexate patients received a weekly oral dose of 15 mg/m2 (maximum, 20 mg) for 12 months or until flare of disease. Patients in the placebo group received a placebo administered in the same fashion for 12 months or to flare. Patients in both groups received prednisone at a dose of 1 mg/kg per day, with a maximum dose of 50 mg, for 3 months. They were then tapered to 0 over 1 month. During the initial 3 months of the study, treatment response was comparable for the two groups. Differences in response rates began to emerge after that point, said Dr. Zulian of the University of Padua (Italy).

Patients' lesions were evaluated using a computerized scoring system, and changes were quantified using a skin score rate. Active lesions were monitored based on clinical examination and serial thermography. The mean skin score rates decreased significantly from 1.0 at baseline to 0.79 in the patients on methotrexate, but did not decrease in the patients given placebo. The mean target lesion temperature on thermography decreased by 44% in the methotrexate group and by 12% in the placebo group, a significant difference, he said.

Adverse events occurred in 26 of 46 patients in the methotrexate group, and in 11 of 24 in the placebo group. In the methotrexate group, adverse events included alopecia, nausea, headache, fatigue, hepatotoxicity, weight gain, and striae rubra. The only adverse events in the placebo group were weight gain and striae rubra.

Interestingly, weight gain of more than 5% of body weight occurred in 11% of the methotrexate patients and 42% of the placebo patients, Dr. Zulian said, noting that this may suggest there is some "biological or pathophysiological link" between prednisone and methotrexate that tempers this steroid-related side effect.

None of the side effects was severe enough to stop treatment, but there was a high drop-out rate – due to relapse or lack of response – in both groups; 31 of 46 patients in the methotrexate group, and 7 of 24 in the placebo group, completed the study. At the end of the 12-month study, 17 of 24 patients randomized to placebo had experienced a relapse, compared with 15 of 46 patients randomized to the methotrexate group.

Patients included in the study were aged 6-17 years with active localized scleroderma of linear, generalized, or deep subtypes with onset before age 16. The treatment and placebo groups were similar in regard to clinical and immunological features, as well as mean disease duration of about 2 years, and the absence of immunosuppressive treatment in the 6 months prior to enrollment.

Many treatments have been tried in patients with juvenile localized scleroderma, and methotrexate has emerged as one of the most frequently used drugs for this condition.

"The findings of this study show that a combination of methotrexate and prednisone is of benefit and is well tolerated as treatment for severe course juvenile localized scleroderma," Dr. Zulian said.

Prior studies have shown efficacy ranging from 74% to 93%, but the findings of those studies have been based mostly on clinical judgment, while the current study utilized more objective evaluation criteria, including thermography, and skin score rates calculated based on computerized skin scoring, he said.

"The inclusion of standardized objective parameters represents an innovative way to assess the disease and compare progression in future clinical trials," he added.

Dr. Zulian said he had no relevant financial disclosures.

ATLANTA – Methotrexate was an effective and well-tolerated treatment for juvenile localized scleroderma in a randomized, double-blind, placebo-controlled trial involving 70 patients with active disease.

At the end of the 12-month study, 31 of 46 patients randomized to receive methotrexate had responded to treatment and were flare-free, compared with 7 of 24 patients given placebo, Dr. Francesco Zulian reported at the annual meeting of the American College of Rheumatology.

Methotrexate patients received a weekly oral dose of 15 mg/m2 (maximum, 20 mg) for 12 months or until flare of disease. Patients in the placebo group received a placebo administered in the same fashion for 12 months or to flare. Patients in both groups received prednisone at a dose of 1 mg/kg per day, with a maximum dose of 50 mg, for 3 months. They were then tapered to 0 over 1 month. During the initial 3 months of the study, treatment response was comparable for the two groups. Differences in response rates began to emerge after that point, said Dr. Zulian of the University of Padua (Italy).

Patients’ lesions were evaluated using a computerized scoring system, and changes were quantified using a skin score rate. Active lesions were monitored based on clinical examination and serial thermography. The mean skin score rates decreased significantly from 1.0 at baseline to 0.79 in the patients on methotrexate, but did not decrease in the patients given placebo. The mean target lesion temperature on thermography decreased by 44% in the methotrexate group and by 12% in the placebo group, a significant difference, he said.

Adverse events occurred in 26 of 46 patients in the methotrexate group, and in 11 of 24 in the placebo group. In the methotrexate group, adverse events included alopecia, nausea, headache, fatigue, hepatotoxicity, weight gain, and striae rubra. The only adverse events in the placebo group were weight gain and striae rubra.

Interestingly, weight gain of more than 5% of body weight occurred in 11% of the methotrexate patients and 42% of the placebo patients, Dr. Zulian said, noting that this may suggest there is some "biological or pathophysiological link" between prednisone and methotrexate that tempers this steroid-related side effect.

None of the side effects was severe enough to stop treatment, but there was a high drop-out rate – due to relapse or lack of response – in both groups; 31 of 46 patients in the methotrexate group, and 7 of 24 in the placebo group, completed the study. At the end of the 12-month study, 17 of 24 patients randomized to placebo had experienced a relapse, compared with 15 of 46 patients randomized to the methotrexate group.

Patients included in the study were aged 6-17 years with active localized scleroderma of linear, generalized, or deep subtypes with onset before age 16. The treatment and placebo groups were similar in regard to clinical and immunological features, as well as mean disease duration of about 2 years, and the absence of immunosuppressive treatment in the 6 months prior to enrollment.

Many treatments have been tried in patients with juvenile localized scleroderma, and methotrexate has emerged as one of the most frequently used drugs for this condition.

"The findings of this study show that a combination of methotrexate and prednisone is of benefit and is well tolerated as treatment for severe course juvenile localized scleroderma," Dr. Zulian said.

Prior studies have shown efficacy ranging from 74% to 93%, but the findings of those studies have been based mostly on clinical judgment, while the current study utilized more objective evaluation criteria, including thermography, and skin score rates calculated based on computerized skin scoring, he said.

"The inclusion of standardized objective parameters represents an innovative way to assess the disease and compare progression in future clinical trials," he added.

Dr. Zulian said he had no relevant financial disclosures.

ATLANTA – Methotrexate was an effective and well-tolerated treatment for juvenile localized scleroderma in a randomized, double-blind, placebo-controlled trial involving 70 patients with active disease.

At the end of the 12-month study, 31 of 46 patients randomized to receive methotrexate had responded to treatment and were flare-free, compared with 7 of 24 patients given placebo, Dr. Francesco Zulian reported at the annual meeting of the American College of Rheumatology.

Methotrexate patients received a weekly oral dose of 15 mg/m2 (maximum, 20 mg) for 12 months or until flare of disease. Patients in the placebo group received a placebo administered in the same fashion for 12 months or to flare. Patients in both groups received prednisone at a dose of 1 mg/kg per day, with a maximum dose of 50 mg, for 3 months. They were then tapered to 0 over 1 month. During the initial 3 months of the study, treatment response was comparable for the two groups. Differences in response rates began to emerge after that point, said Dr. Zulian of the University of Padua (Italy).

Patients’ lesions were evaluated using a computerized scoring system, and changes were quantified using a skin score rate. Active lesions were monitored based on clinical examination and serial thermography. The mean skin score rates decreased significantly from 1.0 at baseline to 0.79 in the patients on methotrexate, but did not decrease in the patients given placebo. The mean target lesion temperature on thermography decreased by 44% in the methotrexate group and by 12% in the placebo group, a significant difference, he said.

Adverse events occurred in 26 of 46 patients in the methotrexate group, and in 11 of 24 in the placebo group. In the methotrexate group, adverse events included alopecia, nausea, headache, fatigue, hepatotoxicity, weight gain, and striae rubra. The only adverse events in the placebo group were weight gain and striae rubra.

Interestingly, weight gain of more than 5% of body weight occurred in 11% of the methotrexate patients and 42% of the placebo patients, Dr. Zulian said, noting that this may suggest there is some "biological or pathophysiological link" between prednisone and methotrexate that tempers this steroid-related side effect.

None of the side effects was severe enough to stop treatment, but there was a high drop-out rate – due to relapse or lack of response – in both groups; 31 of 46 patients in the methotrexate group, and 7 of 24 in the placebo group, completed the study. At the end of the 12-month study, 17 of 24 patients randomized to placebo had experienced a relapse, compared with 15 of 46 patients randomized to the methotrexate group.

Patients included in the study were aged 6-17 years with active localized scleroderma of linear, generalized, or deep subtypes with onset before age 16. The treatment and placebo groups were similar in regard to clinical and immunological features, as well as mean disease duration of about 2 years, and the absence of immunosuppressive treatment in the 6 months prior to enrollment.

Many treatments have been tried in patients with juvenile localized scleroderma, and methotrexate has emerged as one of the most frequently used drugs for this condition.

"The findings of this study show that a combination of methotrexate and prednisone is of benefit and is well tolerated as treatment for severe course juvenile localized scleroderma," Dr. Zulian said.

Prior studies have shown efficacy ranging from 74% to 93%, but the findings of those studies have been based mostly on clinical judgment, while the current study utilized more objective evaluation criteria, including thermography, and skin score rates calculated based on computerized skin scoring, he said.

"The inclusion of standardized objective parameters represents an innovative way to assess the disease and compare progression in future clinical trials," he added.

Dr. Zulian said he had no relevant financial disclosures.

ATLANTA – Methotrexate was an effective and well-tolerated treatment for juvenile localized scleroderma in a randomized, double-blind, placebo-controlled trial involving 70 patients with active disease.

At the end of the 12-month study, 31 of 46 patients randomized to receive methotrexate had responded to treatment and were flare-free, compared with 7 of 24 patients given placebo, Dr. Francesco Zulian reported at the annual meeting of the American College of Rheumatology.

Methotrexate patients received a weekly oral dose of 15 mg/m2 (maximum, 20 mg) for 12 months or until flare of disease. Patients in the placebo group received a placebo administered in the same fashion for 12 months or to flare. Patients in both groups received prednisone at a dose of 1 mg/kg per day, with a maximum dose of 50 mg, for 3 months. They were then tapered to 0 over 1 month. During the initial 3 months of the study, treatment response was comparable for the two groups. Differences in response rates began to emerge after that point, said Dr. Zulian of the University of Padua (Italy).

Patients’ lesions were evaluated using a computerized scoring system, and changes were quantified using a skin score rate. Active lesions were monitored based on clinical examination and serial thermography. The mean skin score rates decreased significantly from 1.0 at baseline to 0.79 in the patients on methotrexate, but did not decrease in the patients given placebo. The mean target lesion temperature on thermography decreased by 44% in the methotrexate group and by 12% in the placebo group, a significant difference, he said.

Adverse events occurred in 26 of 46 patients in the methotrexate group, and in 11 of 24 in the placebo group. In the methotrexate group, adverse events included alopecia, nausea, headache, fatigue, hepatotoxicity, weight gain, and striae rubra. The only adverse events in the placebo group were weight gain and striae rubra.

Interestingly, weight gain of more than 5% of body weight occurred in 11% of the methotrexate patients and 42% of the placebo patients, Dr. Zulian said, noting that this may suggest there is some "biological or pathophysiological link" between prednisone and methotrexate that tempers this steroid-related side effect.

None of the side effects was severe enough to stop treatment, but there was a high drop-out rate – due to relapse or lack of response – in both groups; 31 of 46 patients in the methotrexate group, and 7 of 24 in the placebo group, completed the study. At the end of the 12-month study, 17 of 24 patients randomized to placebo had experienced a relapse, compared with 15 of 46 patients randomized to the methotrexate group.

Patients included in the study were aged 6-17 years with active localized scleroderma of linear, generalized, or deep subtypes with onset before age 16. The treatment and placebo groups were similar in regard to clinical and immunological features, as well as mean disease duration of about 2 years, and the absence of immunosuppressive treatment in the 6 months prior to enrollment.

Many treatments have been tried in patients with juvenile localized scleroderma, and methotrexate has emerged as one of the most frequently used drugs for this condition.

"The findings of this study show that a combination of methotrexate and prednisone is of benefit and is well tolerated as treatment for severe course juvenile localized scleroderma," Dr. Zulian said.

Prior studies have shown efficacy ranging from 74% to 93%, but the findings of those studies have been based mostly on clinical judgment, while the current study utilized more objective evaluation criteria, including thermography, and skin score rates calculated based on computerized skin scoring, he said.

"The inclusion of standardized objective parameters represents an innovative way to assess the disease and compare progression in future clinical trials," he added.

Dr. Zulian said he had no relevant financial disclosures.

ATLANTA – Rheumatoid arthritis patients who switch from one tumor necrosis factor inhibitor to another during the course of their disease are not at increased risk for serious infections, according to an analysis of data from a large health claims database.

The unadjusted rates of first serious infection in 13,752 RA patients who received only one tumor necrosis factor (TNF) inhibitor between Jan. 1, 2001, and Dec. 21, 2007, and in 2,293 RA patients who switched at least once from one TNF inhibitor to another during that time period did not differ significantly in either a model that analyzed infection rates within 90 days of any health insurance claim for a TNF inhibitor (the index date), or in a model that analyzed infection rates at any time after the index date, Bao-Anh Nguyen-Khoa, D.Pharm, reported at the annual meeting of the American College of Rheumatology.

Rates of first serious infection in the 90-day model were 6.31 and 6.78/100 patient-years in the nonswitchers and switchers; rates in the ever-treated model were 8.45 and. 9.10/100 patient-years in the nonswitchers and switchers, he said.

Rates of first serious infection in both models declined significantly from the first year after the index date, to the second year after the index date and beyond. In the 90-day model, those rates declined from 8.59 to 2.66/100 patient-years in the nonswitchers, and from 8.72 to 2.64/100 patient-years in the switchers. In the ever-treated model, the rates declined from 10.15 to 4.18/100 patient-years in the nonswitchers, and from 10.11 to 4.44/100 patient-years in the switchers, said Dr. Nguyen-Khoa, a pharmacoepidemiology consultant in Arlington, Va.

After adjustment for age, sex, selected comorbidities, Charlson comorbidity score, hospitalizations, and other RA treatments, there still was no significant difference between the nonswitchers and switchers in the risk of serious infection for either attribution model (hazard ratio, 0.93 in the 90-day model, and hazard ratio, 0.94 in the ever-treated model).

Patients in the health insurance claims database used for this study were included if they had not been treated with other biologic agents, and if baseline data were available for at least 365 days of enrollment prior to the index date. Serious infections were defined as infections requiring intravenous antibiotic treatment or hospitalization.

Several prior studies have documented an increased risk of serious infections in patients using TNF inhibitors, with incident rates ranging from 3.6 to 10.5 cases per 100 patient-years, and with similar findings to the current study in regard to differences in infection rates in the first year compared with the second year. However, although switching anti-TNF agents is a common strategy in RA patients who experience adverse events or lack of efficacy, infection rates in patients who switch drugs have not been widely studied, Dr. Nguyen-Khoa said.

In the current study, he and his colleagues demonstrated that switching TNF inhibitors does not increase risk, and they also reported a reduced rate of serious infections in patients who survived into the second year – a finding that corresponded with the results of those earlier studies, he said.

This study was supported by Genentech and Biogen IDEC Inc. Dr. Nguyen-Khoa said he had no conflicts of interest.

ATLANTA – Rheumatoid arthritis patients who switch from one tumor necrosis factor inhibitor to another during the course of their disease are not at increased risk for serious infections, according to an analysis of data from a large health claims database.

The unadjusted rates of first serious infection in 13,752 RA patients who received only one tumor necrosis factor (TNF) inhibitor between Jan. 1, 2001, and Dec. 21, 2007, and in 2,293 RA patients who switched at least once from one TNF inhibitor to another during that time period did not differ significantly in either a model that analyzed infection rates within 90 days of any health insurance claim for a TNF inhibitor (the index date), or in a model that analyzed infection rates at any time after the index date, Bao-Anh Nguyen-Khoa, D.Pharm, reported at the annual meeting of the American College of Rheumatology.

Rates of first serious infection in the 90-day model were 6.31 and 6.78/100 patient-years in the nonswitchers and switchers; rates in the ever-treated model were 8.45 and. 9.10/100 patient-years in the nonswitchers and switchers, he said.

Rates of first serious infection in both models declined significantly from the first year after the index date, to the second year after the index date and beyond. In the 90-day model, those rates declined from 8.59 to 2.66/100 patient-years in the nonswitchers, and from 8.72 to 2.64/100 patient-years in the switchers. In the ever-treated model, the rates declined from 10.15 to 4.18/100 patient-years in the nonswitchers, and from 10.11 to 4.44/100 patient-years in the switchers, said Dr. Nguyen-Khoa, a pharmacoepidemiology consultant in Arlington, Va.

After adjustment for age, sex, selected comorbidities, Charlson comorbidity score, hospitalizations, and other RA treatments, there still was no significant difference between the nonswitchers and switchers in the risk of serious infection for either attribution model (hazard ratio, 0.93 in the 90-day model, and hazard ratio, 0.94 in the ever-treated model).

Patients in the health insurance claims database used for this study were included if they had not been treated with other biologic agents, and if baseline data were available for at least 365 days of enrollment prior to the index date. Serious infections were defined as infections requiring intravenous antibiotic treatment or hospitalization.

Several prior studies have documented an increased risk of serious infections in patients using TNF inhibitors, with incident rates ranging from 3.6 to 10.5 cases per 100 patient-years, and with similar findings to the current study in regard to differences in infection rates in the first year compared with the second year. However, although switching anti-TNF agents is a common strategy in RA patients who experience adverse events or lack of efficacy, infection rates in patients who switch drugs have not been widely studied, Dr. Nguyen-Khoa said.

In the current study, he and his colleagues demonstrated that switching TNF inhibitors does not increase risk, and they also reported a reduced rate of serious infections in patients who survived into the second year – a finding that corresponded with the results of those earlier studies, he said.

This study was supported by Genentech and Biogen IDEC Inc. Dr. Nguyen-Khoa said he had no conflicts of interest.

ATLANTA – Rheumatoid arthritis patients who switch from one tumor necrosis factor inhibitor to another during the course of their disease are not at increased risk for serious infections, according to an analysis of data from a large health claims database.

The unadjusted rates of first serious infection in 13,752 RA patients who received only one tumor necrosis factor (TNF) inhibitor between Jan. 1, 2001, and Dec. 21, 2007, and in 2,293 RA patients who switched at least once from one TNF inhibitor to another during that time period did not differ significantly in either a model that analyzed infection rates within 90 days of any health insurance claim for a TNF inhibitor (the index date), or in a model that analyzed infection rates at any time after the index date, Bao-Anh Nguyen-Khoa, D.Pharm, reported at the annual meeting of the American College of Rheumatology.

Rates of first serious infection in the 90-day model were 6.31 and 6.78/100 patient-years in the nonswitchers and switchers; rates in the ever-treated model were 8.45 and. 9.10/100 patient-years in the nonswitchers and switchers, he said.

Rates of first serious infection in both models declined significantly from the first year after the index date, to the second year after the index date and beyond. In the 90-day model, those rates declined from 8.59 to 2.66/100 patient-years in the nonswitchers, and from 8.72 to 2.64/100 patient-years in the switchers. In the ever-treated model, the rates declined from 10.15 to 4.18/100 patient-years in the nonswitchers, and from 10.11 to 4.44/100 patient-years in the switchers, said Dr. Nguyen-Khoa, a pharmacoepidemiology consultant in Arlington, Va.

After adjustment for age, sex, selected comorbidities, Charlson comorbidity score, hospitalizations, and other RA treatments, there still was no significant difference between the nonswitchers and switchers in the risk of serious infection for either attribution model (hazard ratio, 0.93 in the 90-day model, and hazard ratio, 0.94 in the ever-treated model).

Patients in the health insurance claims database used for this study were included if they had not been treated with other biologic agents, and if baseline data were available for at least 365 days of enrollment prior to the index date. Serious infections were defined as infections requiring intravenous antibiotic treatment or hospitalization.

Several prior studies have documented an increased risk of serious infections in patients using TNF inhibitors, with incident rates ranging from 3.6 to 10.5 cases per 100 patient-years, and with similar findings to the current study in regard to differences in infection rates in the first year compared with the second year. However, although switching anti-TNF agents is a common strategy in RA patients who experience adverse events or lack of efficacy, infection rates in patients who switch drugs have not been widely studied, Dr. Nguyen-Khoa said.

In the current study, he and his colleagues demonstrated that switching TNF inhibitors does not increase risk, and they also reported a reduced rate of serious infections in patients who survived into the second year – a finding that corresponded with the results of those earlier studies, he said.

This study was supported by Genentech and Biogen IDEC Inc. Dr. Nguyen-Khoa said he had no conflicts of interest.

ATLANTA – Renal dysfunction is independently associated with incident cardiovascular disease in patients with rheumatoid arthritis, according to findings from a prospective Dutch cohort study.

Of 353 RA patients who were part of the Cardiovascular Research and Rheumatoid Arthritis (CARRE) study and who were followed for at least 3 years, 23 developed a cardiovascular event. Serum creatinine levels and glomerular filtration rate (GFR) findings were unfavorable in the patients who had a cardiovascular event, compared with those who did not, Dr. Alper M. van Sijl reported at the annual meeting of the American College of Rheumatology.

Patients with a cardiovascular event had a mean serum creatinine level of 101, compared with 88 micromol/L in the unaffected group; GFR as measured using the Cockcroft-Gault (CG) formula was 63 vs. 80 mL/min, and GFR as measured using the Modification of Diet in Renal Disease (MDRD) formula was 59 vs. 78 mL/min, in the groups, respectively, said Dr. van Sijl of the Jan van Breemen Institute and VU Medical Center, Amsterdam.

Dr. van Sijl and his colleagues used logistic regression analysis to calculate whether incremental increases of 5 micromol/L in serum creatinine level, and incremental decreases of 5 mL/min in glomerular filtration rate as measured using both the CG and MDRD formulas were associated with incident cardiovascular disease. Indeed, all were significantly positively associated with incident cardiovascular disease (odds ratios of 1.13, 1.12, and 1.21, respectively).

"When adjusted for age, gender, body mass index, and prior cardiovascular disease, the association remains. And when adjusted additionally for traditional cardiovascular risk factors, the association becomes even stronger," he said, explaining that a decrease in GFR of 5 mL/min was associated with a 30%-35% increased risk of cardiovascular disease, independent of traditional cardiovascular risk factors.

By comparison, a prior cohort study showed that diabetes patients have about a 20% cardiovascular disease risk increase for every 5-mL/min decrease in GFR, he noted.

The findings of the current study suggest that renal dysfunction might be a "missing link" in the established, but only partially defined, connection between RA and cardiovascular disease, he said.

RA patients are known to have an increased risk of mortality, compared with the general population, and much of that risk has been shown to be attributable to cardiovascular disease. However, standard cardiovascular risk factors – particularly hypercholesterolemia, hypertension, and insulin resistance – explain only part of this association.

Furthermore, renal dysfunction has been shown to be associated with cardiovascular disease in the general population, although findings from landmark studies have shown that risk depends on coexisting hypertension, prior cardiovascular disease, and diabetes, Dr. van Sijl said.

Study findings have shown an association between renal dysfunction and RA. Renal dysfunction in the RA population has been attributed to extra-articular manifestations, NSAID use, and chronic inflammation. At least one study showed an association between renal function and prevalent cardiovascular disease in RA, he said.

Although the current findings do support the idea that decreased renal function can help identify RA patients at increased risk for future cardiovascular disease, further study is needed to determine whether chronic inflammation causes the decreases in GFR, and whether GFR can accurately predict cardiovascular disease occurrence in RA, he said.

"Also still unknown to us is whether possible residual confounding is still present in the form of newly discovered markers of both renal dysfunction and cardiovascular disease such as uric acid, endothelial dysfunction, and cumulative inflammatory burden," he said.

Dr. van Sijl said he had no disclosures to report.

ATLANTA – Renal dysfunction is independently associated with incident cardiovascular disease in patients with rheumatoid arthritis, according to findings from a prospective Dutch cohort study.

Of 353 RA patients who were part of the Cardiovascular Research and Rheumatoid Arthritis (CARRE) study and who were followed for at least 3 years, 23 developed a cardiovascular event. Serum creatinine levels and glomerular filtration rate (GFR) findings were unfavorable in the patients who had a cardiovascular event, compared with those who did not, Dr. Alper M. van Sijl reported at the annual meeting of the American College of Rheumatology.

Patients with a cardiovascular event had a mean serum creatinine level of 101, compared with 88 micromol/L in the unaffected group; GFR as measured using the Cockcroft-Gault (CG) formula was 63 vs. 80 mL/min, and GFR as measured using the Modification of Diet in Renal Disease (MDRD) formula was 59 vs. 78 mL/min, in the groups, respectively, said Dr. van Sijl of the Jan van Breemen Institute and VU Medical Center, Amsterdam.

Dr. van Sijl and his colleagues used logistic regression analysis to calculate whether incremental increases of 5 micromol/L in serum creatinine level, and incremental decreases of 5 mL/min in glomerular filtration rate as measured using both the CG and MDRD formulas were associated with incident cardiovascular disease. Indeed, all were significantly positively associated with incident cardiovascular disease (odds ratios of 1.13, 1.12, and 1.21, respectively).

"When adjusted for age, gender, body mass index, and prior cardiovascular disease, the association remains. And when adjusted additionally for traditional cardiovascular risk factors, the association becomes even stronger," he said, explaining that a decrease in GFR of 5 mL/min was associated with a 30%-35% increased risk of cardiovascular disease, independent of traditional cardiovascular risk factors.

By comparison, a prior cohort study showed that diabetes patients have about a 20% cardiovascular disease risk increase for every 5-mL/min decrease in GFR, he noted.

The findings of the current study suggest that renal dysfunction might be a "missing link" in the established, but only partially defined, connection between RA and cardiovascular disease, he said.

RA patients are known to have an increased risk of mortality, compared with the general population, and much of that risk has been shown to be attributable to cardiovascular disease. However, standard cardiovascular risk factors – particularly hypercholesterolemia, hypertension, and insulin resistance – explain only part of this association.

Furthermore, renal dysfunction has been shown to be associated with cardiovascular disease in the general population, although findings from landmark studies have shown that risk depends on coexisting hypertension, prior cardiovascular disease, and diabetes, Dr. van Sijl said.

Study findings have shown an association between renal dysfunction and RA. Renal dysfunction in the RA population has been attributed to extra-articular manifestations, NSAID use, and chronic inflammation. At least one study showed an association between renal function and prevalent cardiovascular disease in RA, he said.

Although the current findings do support the idea that decreased renal function can help identify RA patients at increased risk for future cardiovascular disease, further study is needed to determine whether chronic inflammation causes the decreases in GFR, and whether GFR can accurately predict cardiovascular disease occurrence in RA, he said.

"Also still unknown to us is whether possible residual confounding is still present in the form of newly discovered markers of both renal dysfunction and cardiovascular disease such as uric acid, endothelial dysfunction, and cumulative inflammatory burden," he said.

Dr. van Sijl said he had no disclosures to report.

ATLANTA – Renal dysfunction is independently associated with incident cardiovascular disease in patients with rheumatoid arthritis, according to findings from a prospective Dutch cohort study.

Of 353 RA patients who were part of the Cardiovascular Research and Rheumatoid Arthritis (CARRE) study and who were followed for at least 3 years, 23 developed a cardiovascular event. Serum creatinine levels and glomerular filtration rate (GFR) findings were unfavorable in the patients who had a cardiovascular event, compared with those who did not, Dr. Alper M. van Sijl reported at the annual meeting of the American College of Rheumatology.

Patients with a cardiovascular event had a mean serum creatinine level of 101, compared with 88 micromol/L in the unaffected group; GFR as measured using the Cockcroft-Gault (CG) formula was 63 vs. 80 mL/min, and GFR as measured using the Modification of Diet in Renal Disease (MDRD) formula was 59 vs. 78 mL/min, in the groups, respectively, said Dr. van Sijl of the Jan van Breemen Institute and VU Medical Center, Amsterdam.

Dr. van Sijl and his colleagues used logistic regression analysis to calculate whether incremental increases of 5 micromol/L in serum creatinine level, and incremental decreases of 5 mL/min in glomerular filtration rate as measured using both the CG and MDRD formulas were associated with incident cardiovascular disease. Indeed, all were significantly positively associated with incident cardiovascular disease (odds ratios of 1.13, 1.12, and 1.21, respectively).

"When adjusted for age, gender, body mass index, and prior cardiovascular disease, the association remains. And when adjusted additionally for traditional cardiovascular risk factors, the association becomes even stronger," he said, explaining that a decrease in GFR of 5 mL/min was associated with a 30%-35% increased risk of cardiovascular disease, independent of traditional cardiovascular risk factors.

By comparison, a prior cohort study showed that diabetes patients have about a 20% cardiovascular disease risk increase for every 5-mL/min decrease in GFR, he noted.

The findings of the current study suggest that renal dysfunction might be a "missing link" in the established, but only partially defined, connection between RA and cardiovascular disease, he said.

RA patients are known to have an increased risk of mortality, compared with the general population, and much of that risk has been shown to be attributable to cardiovascular disease. However, standard cardiovascular risk factors – particularly hypercholesterolemia, hypertension, and insulin resistance – explain only part of this association.

Furthermore, renal dysfunction has been shown to be associated with cardiovascular disease in the general population, although findings from landmark studies have shown that risk depends on coexisting hypertension, prior cardiovascular disease, and diabetes, Dr. van Sijl said.

Study findings have shown an association between renal dysfunction and RA. Renal dysfunction in the RA population has been attributed to extra-articular manifestations, NSAID use, and chronic inflammation. At least one study showed an association between renal function and prevalent cardiovascular disease in RA, he said.

Although the current findings do support the idea that decreased renal function can help identify RA patients at increased risk for future cardiovascular disease, further study is needed to determine whether chronic inflammation causes the decreases in GFR, and whether GFR can accurately predict cardiovascular disease occurrence in RA, he said.

"Also still unknown to us is whether possible residual confounding is still present in the form of newly discovered markers of both renal dysfunction and cardiovascular disease such as uric acid, endothelial dysfunction, and cumulative inflammatory burden," he said.

Dr. van Sijl said he had no disclosures to report.